Database Essay Example | Topics and Well Written Essays - 2000 words

Database - Essay Example In this scenario, IT managers face a lot of challenges in an attempt to bring real business intelligence within time and budget constraints. In the past, when the huge mainframe system empire clasped into a desktop era, IT businesses evolved as well. Additionally, the system storage capacity, processing power, specialized tools and decision-making information were distributed to clients who required freedom of corporate decision making. However, after few years, the pendulum started to shift and with the development of intranets and the Internet connected PC clients formed a networked society that valued information sharing. In this scenario, the IT businesses at the present must develop again. Nowadays they are forced to offer the central data repository and control that illustrate the mainframe era, in addition the rapid decision making and self-directed analysis that grows in the PC era (SAS, 2005), (Jiang et al., 2010) and (Lee & Noah, 1999). Carrefour, which is a France based co rporation, has decided to implement a new technology based solution for overall corporate marketing analysis and decision making. This report will present a detailed analysis of implementation of enterprise intelligence platform at Carrefour. OVERVIEW of Business Carrefour, which is a France based corporation, has decided to implement a new technology based solution for overall corporate marketing analysis and decision making. This report presents a detailed analysis of important aspects of the new enterprise intelligence platform establishment and investigates possible security and confidentiality related issues in customer data in business data warehouse. INTRODUCING NEW ENTERPRISE INTELLIGENCE PLATFORM The basic purpose of implementing enterprise intelligence platform at Carrefour business is to enhance the business productivity and performance through better operational technology solutions. Seeing that, an enterprise intelligence platform is a collection of manual or computer-s upported methods and tools that help manage a number of decision-making activities. In addition, in present day business structure, enterprise intelligence platforms are frequently recognized to be computerized administration information structures to facilitate business owners, decision-makers and executives to determine complicated business issues and challenges. In this scenario, a high-quality enterprise intelligence platform can be helpful for the business staff to carry out a broad range of jobs such as concept ranking, cash flow analysis, product performance development, multistage fore-casting and resource sharing investigation. Furthermore, in the past it was considered as a method or tool for huge corporations, but enterprise intelligence platform has now become equally important tool for small to large size businesses (ReferenceForBusiness, 2011), (Tang, 2006) and (Essaidi, 2010). Enterprise intelligence platform is a wide-ranging group of high-tech and advanced interacti ve computer systems and tools, mainly customizable systems, intended to support business data analysis and managerial decision making. In addition, enterprise intelligence framework is a member of a very large group which is known as management support systems. Furthermore, the main objective of implementing enterprise intelligence platform applications is to build an administrative structure in a more well-organized

Reasearch proprosal Coursework Example | Topics and Well Written Essays - 1000 words

Reasearch proprosal - Coursework Example The experimenter will read journals and check databases for previous research in this area. Case studies specific to Montserratian immigrants will be looked at. There will be looking in depth, at the areas these immigrants dominated and changes that has occurred overtime in these regions. Statistical evidence will be explored to determine the number of Montserratians residing in England in comparison to 1995 as a result of the volcanic eruption. A survey and semi-formal interviews will also be carried out with immigrants in order to test this hypothesis. On completion there should be an understanding if there is a profound change in the areas immigrants occupied. These changes could be political, social or economical. Census and crime statistics data will provide an adequate rationale to support the hypothesis. PROJECT DESCRIPTION Name, Class, School - 5/07/2011 Title: Caribbean Immigration to England following the 1995 Montserrat Volcano Eruption I. Introduction Considerable researc h has been conducted referencing environmental disasters and migration of people from danger zones to safer locations internationally. In 1995, the island of Montserrat experienced a devastating volcanic eruption. As T. H. Druitt and B. P. ... The methodology for this research will include quantitative approaches based in statistics from the UK Migration database as well as qualitative research drawn from interviews with Montserrat islanders. This case study should be of value for reference within the larger body of research related to migration patterns following natural disasters. II. The Statement of the Problem Research on the migration patterns that follow natural disasters is important for social planning, immigration management, humanitarian aid assessments, and to other aspects of governance internationally. The Montserrat volcano eruption resulted in a widespread displacement of people who were resettled both locally and internationally. In focusing on the statistical patterns related to this migration to the United Kingdom following the natural disaster, conclusions can be drawn as to how the lives of Montserrat Islanders have changed after losing their homes, the number who settled permanently in the UK, and the effect of these immigrants in the local economy. This can further be evaluated in the context of migration research following natural disasters. III. The Purpose of the Study The purpose of the study is to investigate immigration patterns from the island of Montserrat to the UK as a result of the 1995 volcanic eruption. The focus of this research is to explore spatial migration patterns specifically. The research question asks how mass migration affects the domestic economy in England positively and negatively, through economic production statistics, taxation, use of social resources, etc. The report references the wider research background of environmental

What Are The Uses Of Phenoxybenzamine Hydrochloride Biology Essay

What Are The Uses Of Phenoxybenzamine Hydrochloride Biology Essay Phenoxybenzamine Hydrochloride (RS)-benzyl(2-chloroethyl)1-methyl-2-phenoxyethylamine hydrochloride is a alpha-adrenoceptor blocker that covalently binds and irreversibly inhibits the activity of alpha-1 alpha -2 adrenoceptors.3,4 Phenoxybenzamine Hydrochloride is mainly used to treat episodes of high blood pressure and sweating related to phaeochromocytoma. Phaeochromocytoma is a rare catecholamine-secreting tumour of the adrenal medulla. Patients with phaeochromocytoma are usually hypertensive and suffer headache, palpitations, and excessive sweating.3 However it is rarely prescribed due to it unfavourable side effects. One of the side effects of Phenoxybenzamine is that block the ejaculation. Also some studies are under investigation to use Phenoxybenzamine as male contraceptive pills.11 , HCl Fig. 01 Molecular structure of (RS)-N-benzyl-N-(2-chloroethyl)-1- phenoxy-propan-2-amine Phenoxybenzamine hydrochloride is white, odourless, crystalline powder that is sparingly soluble in water; soluble in ethanol, chloroform, and propylene glycol; and insoluble in diethyl ether. Neutral and alkaline solutions are unstable; sensitive to oxidation and photo degradation.6,7,8 Molecular Weight9: 303.82638 [g/mol] Molecular Formula : C18H22ClNO MonoIsotopic Mass9: 303.138992 CAS-No. : 63-92-3 The stability studies for Phenoxybenzamine injection concentrate were carried out by Zeta Analytical Ltd. for their Clients. Also analytical method for related substance of Phenoxybenzamine Injection has been validated by them. During the stability studies, it has been found that some stability batches contain more than 0.1% of unknown impurities. Already there are three identified, process related impurities were reported in their clients analytical methods.10 Those three impurities A, B, and C are reported as shown below. 1. Impurity A: N-benzyl-N-(2-chloroethyl)-2-phenoxypropan-1-amine Fig. 02 Molecular structure of N-benzyl-N-(2-chloroethyl)-2- phenoxy-propan-1-amine 2. Impurity B: N-benzyl-N-(2, hydroxyethyl)-1-phenoxypropan-2-amine Fig. 03 Molecular structure of N-benzyl-N-(2-hydroxyethyl)-1-phenoxypropan-2-amine 3. Impurity C: N-(2-chloroethyl)-1-phenoxypropan-2-amine Fig. 04 Molecular structure a of N-(2-chloroethyl)-1-phenoxypropan-2-amine According to the International Conference on Harmonization1,2 (ICH) guidelines any component of a pharmaceutical product which is not the chemical entity of active substance or excipients, present at levels higher than 0.1% or 1 mg/day intake (whichever is lower) for a maximum daily dose of 2 g/day or less, need to be identified and qualified with appropriate toxicological studies. For a daily dose of greater than 2 g of drug substance, the identification threshold is 0.05%.1 ,2 Also British (BP), European (EP) and United states (USP) pharmacopeia texts refers the ICH criteria on impurity profiling for new drug substance and new drug products.5,6,7 Hyphenated techniques such as LC-MS and LC-NMR methods as an effective tool for characterization of impurities and degradation products in drug molecules. Therefore, Zeta Analytical proposed this project to perform LC-MS analysis on Phenoxybenzamine injection for structural elucidation of unknown impurity. This project involved method transferring (Tech transfer) from Zeta to Kingston University and developing a LC-MS compatible chromatographic method structural identifications of unknown impurity. Literature Study: There are no chromatographic methods have been reported in the literature describing the analysis of Phenoxybenzamine and its related substances using UV detection. The chromatographic Conditions mentioned in United States Pharmacopoeia (USP) monograph7 (refer Appendix) and Zetas method quiet similar apart from the detection wavelength, which is 268nm for USP and 220 nm for Zeta. Both methods are not compatible for LC/MS analysis. Because phosphate buffer is a one component that mobile phase consist in both methods. There are no reports available on the investigation using LC/MS/MS and isolation of related substances in Phenoxybenzamine active pharmaceutical ingredient (API). However, in order to analyse the sample in LC/MS and to get better chromatographic resolution the method has been modified for use in the present investigation. A synthesis route of Phenoxybenzamine has been mentioned in Vardanyan and Hruby,18 and slightly different route of synthesis for phenoxybenzaime related amines has been reported in Giardink et al.13 EXPERIMENTAL Material and Methods Chemicals used (all anal. Grade )were: Phenoxybenzamine Hydrochloride ( Sigma- Aldrich) , Impurity B (PBA) from med alchemy S.L Spain, HPLC grade Acetonitrile (Sigma- Aldrich), Potassium phosphate dibasic, Potassium phosphate monobasic, Ammonium formate, Ammonium Hydroxide, MilliQ grade water Samples Phenoxybenzamine injection concentrate ; Each 2 ml ampoule contains 100 mg Phenoxybenzamine Hydrochloride BP and excipients are absolute ethyl alcohol, hydrochloric acid AR and propylene glycol. Sample Preparation for HPLC and LC-MS Whole contents of ampoule was transferred to a 100mL volumetric flask and dissolved with 30 mL of acetonitrile. Then it was shacked for few minutes to mix well and added more acetonitrile to volume up the level of volumetric flask. HPLC analysis at Zeta Analytical Ltd. HPLC analysis was proceeded at these chromatographic condition : Column Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm. Mobile phase used : pH 7.5 20mM Phosphate buffer (Dissolved 2.4g of K2HPO4 in 1L of water and adjusted to pH 7.5 with KH2PO4) : Acetonitrile = 30% : 70% (Isocratic mode ) .Column temperature 25C , flow rate 0.9 cm3min-1 , detection at 220nm . HPLC system used at Zeta analytical Ltd : Pump , Auto sampler ,UV detector and thermostat are Agilent 1100 series with Agilent Chemstation for LC data system. HPLC analysis at School of chemistry and pharmacy, Kingston University: HPLC analysis was proceeded at these chromatographic condition : Column Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm. Mobile phase used : pH 7.5 20mM Phosphate buffer (Dissolved 2.4g of K2HPO4 in 1L of water and adjusted to pH 7.5 with KH2PO4) : Acetonitrile = 30% : 70% (Isocratic mode ) .Column temperature 25C , flow rate 0.9 cm3min-1 , detection at 220nm . HPLC system used at Kingston University: Pump , Auto sampler ,UV-VIS detector and thermostat are Perkin Elmer series 200 with Totalchrom v6.2 software. LC- MS analysis at School of chemistry and pharmacy, Kingston University: LC-MS analysis was proceeded at these chromatographic condition : Column Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm. Mobile phase used : pH 8.3 20mM Ammonium formate buffer (Dissolved 1.3g of NH4HCO2 in 1L of water and adjusted to pH 8.3 with NH4OH) : Aceotonitrile = 30% : 70% (Isocratic mode) .Column temperature 25C , flow rate 0.9 cm3min-1 , detection at 220nm . LC system : Pump , Auto sampler ,UV-VIS detector and thermostat are Perkin Elmer series 200 with Totalchrom v6.2 data system. Mass detetectors used : Two different mass detectors were employed : Waters Micromass LCT ESI-TOF-MS system with Mass Lynx 4.1 software Thermo TSQ Quantum Access system ( MSMS ) with Thermo Excalibur software RESULTS AND DICUSSION HPLC Analysis at Zeta Analytical Ltd. Initially the sample was analyzed in Agilent HPLC in Zeta Analytical Ltd. Based on the Zetas Analytical Method validation report for the related substance of Phenoxybenzamine HCl injection, the three identified impurities and one unidentified impurity were confirmed. Below the fig.05 (Appendix A-1) shows the peaks of Phenoxybenzamine and its impurities and the table 01 shows the retention time of those peaks. Fig. 05 HPLC chromatograms of Phenoxybenzamine HCl injections Table 01: Peaks and its retention time of Phenoxybenzamine (zeta) Peaks Retention Time / min Impurity C 5.2 Impurity B 7.3 Unidentified Impurity 8.6 Impurity A 18.2 Phenoxybenzamine 19.6 HPLC Analysis at Kingston University: (Method Transfer) The above results obtained at zeta were replicated again with Perkin-Elmer HPLC system in Kingston University. Same chromatographic condition was employed with same Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm column . The fig.06 below show chromatogram of Phenoxybenzamine HCl injection analysis repeated at Kingston University(Appendix A-2). The peaks were interested and its retention times are shown in the table 02 below. Fig.06 HPLC chromatogram of Phenoxybenzamine HCl Injection (Kingston) Table 02. Peaks and its retention time of Phenoxybenzamine (Kingston) Peaks Retention Time / min Impurity C 5.0 Impurity B 7.0 Unidentified Impurity 8.4 Impurity A 17.9 Phenoxybenzamine 19.5 LC-MS Analysis of Phenoxybenzamine Injection Concentrate: Phosphate buffers are not compatible for LC-MS due to their non volatile nature. Since it was necessary to replace the phosphate buffer to a volatile buffer. Mean while the chromatographic development should not be changed. The ammonium formate buffers are widely used in LC-MS analytical methods and has buffering pH range (8.2-10.2) close to the previous phosphate buffers used which is pH 7.5 . 20mM ammonium phosphate buffer was prepared adjusted the pH to 8.3. The HPLC analysis previously performed was repeated with mobile phase of Ammonium formate buffer : Acetonitrile =30: 70 instead of mobile phase of phosphate buffer : Acetonitrile = 30:70 . The isolation of peaks and the resolution obtained in previous analysis was replicated. Fig. 07 Show the HPLC chromatogram of replicated results with Ammonium formate buffer and the table 03 show retention time and its corresponding peaks. Fig.07 HPLC chromatogram of PBA Injection Sample ( Modified Mobile phase for LC-MS analysis) Table 03: Peaks and its retention time of Phenoxybenzamine (Ammonium formate as buffer)The samples were run on HPLC several times and constant chromatographic development was observed. Hence the sample fractions of unknown impurity was collected several time during HPLC run for LC-MS (accurate mass measurement) and LC-MS/MS (selective ion monitoring) analysis. Peaks Retention Time / min Impurity C 5.3 Impurity B 7.3 Unidentified Impurity 8.7 Impurity A 18.5 Phenoxybenzamine 19.8 Accurate mass measurement with Time of Flight (ToF) mass detector Feasibility of TOF mass detectors has made it to be used widely for measurement of accurate mass. Several unknown impurity sample fractions were analyzed for the accurate mass measurement on Waters micromass LCT ESI TOF-MS and obtained the average of the accurate mass value of unknown impurity. Ionization technique is Electron spray Ionization and mass analyzer is Time of Flight analyzer in this instrument. Results were taken on positive mode ( M + H + ). Hence mass of one proton must be deducted from the spectral mass value to obtain the exact mass value of unknown compound. H1 mass is considered to be 1.007 Da in the calculation below. Table 03: m/z value of Peaks observed its corresponding calculated monoisotopic mass M + H + / Da Mass of Unknown Compound / Da 344.215 343.208 344.216 343.209 344.216 343.209 344.219 343.212 344.211 343.204 344.209 343.202 344.215 343.208 344.214 343.207 344.215 343.208 344.213 343.206 344.215 343.208 344.22 343.213 344.213 343.206 344.221 343.214 344.223 343.216 The average molecular weight and standard deviation of results are found to be 343.2086667 and 0.003754363 respectively. Above results were subjected to statistical evaluation using Microsoft excel spread sheet. At 99% confidence level the molecular weight of the unknown impurity is found to be 343.2086667 0.002497. Determination of Elemental Composition of unknown impurity. Using Mass Lynx 4.1 MS data management software possible elemental composition was obtained for the molecular weight of 343.209 with 200.0 mDa tolerance . It was able to exclude a large amount elemental composition to narrow findings. That is elimination of Chlorine in the composition . Because the mass spectrum of unknown impurity does not show the isotopic pattern for chlorine. i.e. When one Chlorine atom is present in a molecule, that will show a n/n+2 ratio of 100/32.4 (35Cl/37Cl ratio of 100/32.4). 15,16 Hence only C,H,N and O elements were limited on search. Still hundreds of composition are left to be examined to find correct elemental composition . The second exclusion that is Nitrogen rule14 which was used to eliminate many of those composition. Since the unknown impurity molecular weight is odd number, we can eliminate all the composition with the even number of nitrogen in list. The following table shows considerable elemental composition left after above two exclusions . Table 04. Possible elemental composition and its Monoisotopic mass Elemental Composition Calculated Monoisotopic mass C12H25N9O3 343.2080 C16H29N3O5 343.2107 C23H25N3 343.2048 C21H29NO3 343.2147 C12H29N3O8 343.1955 C15H29N5O4 343.2220 C24H25NO 343.1936 The monoisotopic mass of main active compound is 303.14 and it contains 18 carbon on that molecule. Unknown impurity has the monoisotopic mass value 40 amu higher than the active compound. Therfore if it is been assumed that unknown impurity has more than 18 carbon on its molecule, only two elemental composition would be remained. i.e. C23H25N3 (343.2048) and C24H25NO (343.1936). LC -MS/MS (Tandem mass )Analysis of Phenoxybenzamine HCl Injection Concentrate Thermo TSQ Quantum Access LC-MS/MS was employed for the selective ion monitoring. The unknown impurity fractions , Phenoxybenzamine HCl standard (sigma ) and Impurity B standard were analysed. Analysis of Phenoxybenzamine HCl standard Parameter used: Parent mass: 304.4 Scan time: 0.5000 Collision energy: 16 Collision gas pressure: 1.1 Barr Spray Voltage: 4000 Scan Mode: Product Ion Scan Fig. 08 Product ion scan mass spectrum of Phenoxybenzamine Standard Peaks at m/z 63, 84, 91,107,120, 135 and 212 were observed. The base peak is observed at m/z 91 benzyl fragment . It is stabilized by the resonance form of benzene.17 The following figure illustrates the break downs and its corresponding mass units observed in the product ion scan spectrum. Fig. 09 Illustration of break downs of Phenoxybenzamine Apart from the peaks illustrated on above figure, the peaks at m/z 120 arise due to mass unit CH2NCH2CH2Cl + H+ . This is the middle portion after the mass unit at m/z 91 and 93 break apart from the whole Phenoxybenzamine molecule. i.e M + H+ the molecular ion is m/z 304, but 304 (91+93) = 120 . Analysis of Impurity B standard Parameter used: Parent mass: 286 Scan time: 0.5000 Collision energy: 16 Collision gas pressure: 1.1 Barr Spray Voltage: 4000 Scan Mode: Product Ion Scan Fig. 09 Product ion scan mass spectrum of Impurity B Standard Product Scan spectrum shows peaks at m/z 84, 91,102,107,135,178,194 and 285. The base peak is m/z 91and the molecular ion is m/z 286. The following figure illustrates the break downs and its corresponding mass units observed in the product ion scan spectrum. Fig. 09 Illustration of break downs of Impurity B As seen in the Phenoxybenzamine product ion scan spectrum the removal of mass units m/z 91 and 93 also is observed in this Impurity B spectrum. i.e . there is a peak arise at m/z 102 , this is due removal mass units m/z 91 and 93 from the molecular ion m/z 286. [286-(91+93)=102] Analysis of Unknown Impurity Parameter used: Parent mass: 286 Scan time: 0.5000 Collision energy: 16 Collision gas pressure: 1.1 Barr Spray Voltage: 4000 Scan Mode: Product Ion Scan Fig. 10 Product ion scan mass spectrum of Unknown Impurity Product ion Scan spectrum shows peaks at m/z 84,91,107,119,135,152,160,178,251,267 and 344 . Here the molecular ion peak and base peak are same at m/z 344. This mass spectrum shows quiet similar fragmentation pattern with Phenoxybenzamine and the impurity B were analysed before. Peaks at m/z 84, 91, 93, 107, and 135 are found in all three , Phenoxybenzamine , Impurity B and unknown impurity product ion scan spectrum. Also as studied previously in the spectrum of PBA and impurity B, the deduction of the mass units m/z 91 and 93 from the molecular ion (m/z 344) results a obvious sharp peak at m/z 160. From the facts studied above in product ion scan mass spectrum and accurate mass measurement for elemental composition using TOF -MS , It can be hypothesized a structure of the unknown impurity . The proposed structure for unknown impurity is shown below in figure. Fig. 11 The Molecular Structure proposed for unknown impurity, N-benzyl-N-[(E)-2-phenylethenyl] -1- phenoxy-propan-2-amine The proposed structure can be rationalized with the product ion mass spectrum of unknown impurity. Following fig.12 shows the break downs of the unknown impurity that correspond to the peaks observed on mass spectrum. Fig. 12 Illustration of break downs of Unknown Impurity Most of the impurities found in pharmaceutical compounds usually process-related compounds; they are most probably structurally similar to the synthesized target drugs. It is prominent to study the synthesis route of active pharmaceutical ingredient (API), when the unknown impurity of drugs substance is been identified. Unfortunately the original synthesis route followed by the API manufacturer of Phenoxybenzamine is not known. The prediction for synthesis route of Phenoxybenzamine with possibilities for arising of other 3 Identified process related impurities (A, B, and C) is shown in the following scheme below based on Giardink(1995).13 + (a) (ii) (iii) (iv) (b) (v) (c) (d) (vii) (vi) (a)Oxidation ;(b) 1-phenylmethanamine, HC1/EtOH,molecular sieves 4A, NaBH3CN; (c) Br(CH2)2OH, K2CO3, EtOH; (d) SOCI 2, HCI (g), Benzene (i)phenol; (2)2-methyl oxirane ;(3)1-phenoxypropan-2-ol;(4) 1-phenoxypropan-2-one; (5) N-benzyl-1-phenoxypropan-2-amine; (6) 2-[benzyl(1-phenoxypropan-2-yl)amino]ethanol;(7) N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine (Phenoxybenzamine) Scheme 1. Predicted synthesis route for Phenoxybenzamine Formation of Impurity A The reaction between phenol (i) and 2-methyl oxirane (ii) is SN2 nucleophilic substitution. Nucleophiles are more reactive to most substituted carbon of epoxides under acidic condition and least substituted carbon is favoured under basic condition.19 In this case carbon position 2 (fig.13) is favoured under basic condition and its form 1-phenoxypropan-2-ol ,which is the precursor molecule for PBA . Fig. 13 Structure of 2-methyl oxirane To very few extent the nucleophiles react at carbon position 3 will form 2-phenoxypropan-1-ol, which will lead to the formation of Impurity A along synthesis process of PBA. Fig.14 Structure of 2-phenoxypropan-1-ol Formation of Impurity B and Impurity C Impurity B, 2-[benzyl(1-phenoxypropan-2-yl)amino]ethanol is intermediate product during synthesis. Refer structure (vi) of scheme 01 . Impurity C, N-(2-chloroethyl)-1-phenoxypropan-2-amine formed due to chlorination of intermediate product 1-phenoxypropan-2-ol (refer structure (iii) of scheme 01). The unoxidised 1-phenoxypropan-2-ol left over is chlorinated by SOCI 2, HCI during last step of the synthesis. Refer (d) of the scheme. CONCLUSIONS Preliminary structural assignments for unknown impurity of Phenoxybenzamine Injection were made on the basis of mass spectral data. Initially the works started with transferring HPLC method from Zeta Lab to Kingston university and developing a LC-MS chromatographic method. Ammonium formate volatile buffer was replaced for phosphate buffer in HPLC method . Same chromatographic development was able to replicated with ammonium formate buffer. Accurate mass measurement was carried out on ESI-TOF LC-MS . Also this studies led to determine possible empirical formula . Then LC-MS/MS analysis was performed. The Product ion Scan mass spectral data are very vital information in final structural elucidation of unknown impurity. The structure deduced from MS/MS confirms the empirical formula C24H25NO that derived with LC-TOF-MS spectral data. Eventually the impurity identified in this this preliminary structural assignments , which eluted at retention time of 8.7 minute was predicted as N-benzyl-N-[(E)-2-phenylethenyl] -1- phenoxy-propan-2-amine . The proposed molecular structure for unknown impurity is shown in fig.11 . The formation of impurities A, B and C those had already identified by manufacture were described based on the predicted synthesis route for Phenoxybenzamine . The formation unknown impurity was not able to explained at this stage of this project since the reaction would have occurred found to be more complicated. This project work was wrapped up at this stage due to time limitation. Further to these preliminary structural assignments various spectroscopic studies such as LC-NMR and IR need to be carried out to complete the characterization of the unknown compound. Ultimately the proposed st ructure can be confirmed by synthesizing N-benzyl-N-[(E)-2-phenylethenyl] -1- phenoxy-propan-2-amine in future.

Cocaine :: essays research papers

Cocaine is a drug extracted from the leaves of the coca plant. It is a potent brain stimulant and one of the most powerfully addictive drugs. Cocaine is distributed on the street in two main forms: cocaine hydrochloride is a white crystalline powder that can be snorted or dissolved in water and injected; and "crack" is cocaine hydrochloride that has been processed with ammonia or sodium bicarbonate (baking soda) and water into a freebase cocaine. These chips, chunks, or rocks can be smoked. Cocaine may be used occasionally, daily, or in a variety of compulsive, repeated-use "binges". Regardless of how it is used, cocaine is highly addictive. Crack cocaine and injected cocaine reach the brain quickly and bring an intense and immediate high. Snorted cocaine produces a high more slowly. Cocaine can produce a surge in energy, a feeling of intense pleasure, and increased confidence. The effects of powder cocaine last about 20 minutes, while the effects of "crack" last about 12 minutes. Heavy use of cocaine may produce hallucinations, paranoia, aggression, insomnia, and depression. Cocaine's effects are short lived, and once the drug leaves the brain, the user experiences a "coke crash" that includes depression, irritability, and fatigue. Many people ask is cocaine addictive? Yes. Cocaine can take over your life and cause you to lose interest in everything else. Studies in monkeys have shown that animals will work very hard (press a bar over 10,000 times) for a single injection of cocaine, choose cocaine over food and water, and take cocaine even when this behavior is punished. Animals must have their access to cocaine limited in order not to take toxic or even lethal doses. People addicted to cocaine behave similarly. They will go to great lengths to get cocaine and continue to take it even when it hurts their school or job performance and their relationships with loved ones. Do users develop a tolerance to crack or cocaine? Yes. Users may find they need more and more of the drug to get high. What are the effects of cocaine use? Cocaine stimulates the central nervous system. It acts on the "pleasure centers" of the brain, producing heightened pleasure and increased confidence. Other immediate effects include dilated pupils and elevated blood pressure, heart rate, respiratory rate, and body temperature. The pleasurable effects of powder cocaine last about 20 minutes. Occasional use can cause a stuffy or runny nose, and chronic use can ulcerate the mucous membrane of the nose. Injecting cocaine with contaminated equipment can cause AIDS, hepatitis, and other diseases. Preparation of freebase cocaine, which involves the use of volatile solvents, can result in death or injury from fire or explosion.

A Game of Thrones Chapter Thirty-four

Catelyn My lady, you should have sent word of your coming,† Ser Donnel Waynwood told her as their horses climbed the pass. â€Å"We would have sent an escort. The high road is not as safe as it once was, for a party as small as yours.† â€Å"We learned that to our sorrow, Ser Donnel,† Catelyn said. Sometimes she felt as though her heart had turned to stone; six brave men had died to bring her this far, and she could not even find it in her to weep for them. Even their names were fading. â€Å"The clansmen harried us day and night. We lost three men in the first attack, and two more in the second, and Lannister's serving man died of a fever when his wounds festered. When we heard your men approaching, I thought us doomed for certain.† They had drawn up for a last desperate fight, blades in hand and backs to the rock. The dwarf had been whetting the edge of his axe and making some mordant jest when Bronn spotted the banner the riders carried before them, the moon-and-falcon of House Arryn, sky-blue and white. Catelyn had never seen a more welcome sight. â€Å"The clans have grown bolder since Lord Jon died,† Ser Donnel said. He was a stocky youth of twenty years, earnest and homely, with a wide nose and a shock of thick brown hair. â€Å"If it were up to me, I would take a hundred men into the mountains, root them out of their fastnesses, and teach them some sharp lessons, but your sister has forbidden it. She would not even permit her knights to fight in the Hand's tourney. She wants all our swords kept close to home, to defend the Vale . . . against what, no one is certain. Shadows, some say.† He looked at her anxiously, as if he had suddenly remembered who she was. â€Å"I hope I have not spoken out of turn, my lady. I meant no offense.† â€Å"Frank talk does not offend me, Ser Donnel.† Catelyn knew what her sister feared. Not shadows, Lannisters, she thought to herself, glancing back to where the dwarf rode beside Bronn. The two of them had grown thick as thieves since Chiggen had died. The little man was more cunning than she liked. When they had entered the mountains, he had been her captive, bound and helpless. What was he now? Her captive still, yet he rode along with a dirk through his belt and an axe strapped to his saddle, wearing the shadowskin cloak he'd won dicing with the singer and the chainmail hauberk he'd taken off Chiggen's corpse. Two score men flanked the dwarf and the rest of her ragged band, knights and men-at-arms in service to her sister Lysa and Jon Arryn's young son, and yet Tyrion betrayed no hint of fear. Could I be wrong? Catelyn wondered, not for the first time. Could he be innocent after all, of Bran and Jon Arryn and all the rest? And if he was, what did that make her? Six men ha d died to bring him here. Resolute, she pushed her doubts away. â€Å"When we reach your keep, I would take it kindly if you could send for Maester Colemon at once. Ser Rodrik is feverish from his wounds.† More than once she had feared the gallant old knight would not survive the journey. Toward the end he could scarcely sit his horse, and Bronn had urged her to leave him to his fate, but Catelyn would not hear of it. They had tied him in the saddle instead, and she had commanded Marillion the singer to watch over him. Ser Donnel hesitated before he answered. â€Å"The Lady Lysa has commanded the maester to remain at the Eyrie at all times, to care for Lord Robert,† he said. â€Å"We have a septon at the gate who tends to our wounded. He can see to your man's hurts.† Catelyn had more faith in a maester's learning than a septon's prayers. She was about to say as much when she saw the battlements ahead, long parapets built into the very stone of the mountains on either side of them. Where the pass shrank to a narrow defile scarce wide enough for four men to ride abreast, twin watchtowers clung to the rocky slopes, joined by a covered bridge of weathered grey stone that arched above the road. Silent faces watched from arrow slits in tower, battlements, and bridge. When they had climbed almost to the top, a knight rode out to meet them. His horse and his armor were grey, but his cloak was the rippling blue-and-red of Riverrun, and a shiny black fish, wrought in gold and obsidian, pinned its folds against his shoulder. â€Å"Who would pass the Bloody Gate?† he called. â€Å"Ser Donnel Waynwood, with the Lady Catelyn Stark and her companions,† the young knight answered. The Knight of the Gate lifted his visor. â€Å"I thought the lady looked familiar. You are far from home, little Cat.† â€Å"And you, Uncle,† she said, smiling despite all she had been through. Hearing that hoarse, smoky voice again took her back twenty years, to the days of her childhood. â€Å"My home is at my back,† he said gruffly. â€Å"Your home is in my heart,† Catelyn told him. â€Å"Take off your helm. I would look on your face again.† â€Å"The years have not improved it, I fear,† Brynden Tully said, but when he lifted off the helm, Catelyn saw that he lied. His features were lined and weathered, and time had stolen the auburn from his hair and left him only grey, but the smile was the same, and the bushy eyebrows fat as caterpillars, and the laughter in his deep blue eyes. â€Å"Did Lysa know you were coming?† â€Å"There was no time to send word ahead,† Catelyn told him. The others were coming up behind her. â€Å"I fear we ride before the storm, Uncle.† â€Å"May we enter the Vale?† Ser Donnel asked. The Waynwoods were ever ones for ceremony. â€Å"In the name of Robert Arryn, Lord of the Eyrie, Defender of the Vale, True Warden of the East, I bid you enter freely, and charge you to keep his peace,† Ser Brynden replied. â€Å"Come.† And so she rode behind him, beneath the shadow of the Bloody Gate where a dozen armies had dashed themselves to pieces in the Age of Heroes. On the far side of the stoneworks, the mountains opened up suddenly upon a vista of green fields, blue sky, and snowcapped mountains that took her breath away. The Vale of Arryn bathed in the morning light. It stretched before them to the misty cast, a tranquil land of rich black soil, wide slow-moving rivers, and hundreds of small lakes that shone like mirrors in the sun, protected on all sides by its sheltering peaks. Wheat and corn and barley grew high in its fields, and even in Highgarden the pumpkins were no larger nor the fruit any sweeter than here. They stood at the western end of the valley, where the high road crested the last pass and began its winding descent to the bottomlands two miles below. The Vale was narrow here, no more than a half day's ride across, and the northern mountains seemed so close that Catelyn could almost reach out and touch them. Looming over them all was the jagged peak called the Giant's Lance, a mountain that even mountains looked up to, its head lost in icy mists three and a half miles above the valley floor. Over its massive western shoulder flowed the ghost torrent of Alyssa's Tears. Even from this distance, Catelyn could make out the shining silv er thread, bright against the dark stone. When her uncle saw that she had stopped, he moved his horse closer and pointed. â€Å"It's there, beside Alyssa's Tears. All you can see from here is a flash of white every now and then, if you look hard and the sun hits the walls just right.† Seven towers, Ned had told her, like white daggers thrust into the belly of the sky, so high you can stand on the parapets and look down on the clouds. â€Å"How long a ride?† she asked. â€Å"We can be at the mountain by evenfall,† Uncle Brynden said, â€Å"but the climb will take another day.† Ser Rodrik Cassel spoke up from behind. â€Å"My lady,† he said, â€Å"I fear I can go no farther today.† His face sagged beneath his ragged, newgrown whiskers, and he looked so weary Catelyn feared he might fall off his horse. â€Å"Nor should you,† she said. â€Å"You have done all I could have asked of you, and a hundred times more. My uncle will see me the rest of the way to the Eyrie. Lannister must come with me, but there is no reason that you and the others should not rest here and recover your strength.† â€Å"We should be honored to have them to guest,† Ser Donnel said with the grave courtesy of the young. Beside Ser Rodrik, only Bronn, Ser Willis Wode, and Marillion the singer remained of the party that had ridden with her from the inn by the crossroads. â€Å"My lady,† Marillion said, riding forward. â€Å"I beg you allow me to accompany you to the Eyrie, to see the end of the tale as I saw its beginnings.† The boy sounded haggard, yet strangely determined; he had a fevered shine to his eyes. Catelyn had never asked the singer to ride with them; that choice he had made himself, and how he had come to survive the journey when so many braver men lay dead and unburied behind them, she could never say. Yet here he was, with a scruff of beard that made him look almost a man. Perhaps she owed him something for having come this far. â€Å"Very well,† she told him. â€Å"I'll come as well,† Bronn announced. She liked that less well. Without Bronn she would never have reached the Vale, she knew; the sellsword was as fierce a fighter as she had ever seen, and his sword had helped cut them through to safety. Yet for all that, Catelyn misliked the man. Courage he had, and strength, but there was no kindness in him, and little loyalty. And she had seen him riding beside Lannister far too often, talking in low voices and laughing at some private joke. She would have preferred to separate him from the dwarf here and now, but having agreed that Marillion might continue to the Eyrie, she could see no gracious way to deny that same right to Bronn. â€Å"As you wish,† she said, although she noted that he had not actually asked her permission. Ser Willis Wode remained with Ser Rodrik, a soft-spoken septon fussing over their wounds. Their horses were left behind as well, poor ragged things. Ser Donnel promised to send birds ahead to the Eyrie and the Gates of the Moon with the word of their coming. Fresh mounts were brought forth from the stables, surefooted mountain stock with shaggy coats, and within the hour they set forth once again. Catelyn rode beside her uncle as they began the descent to the valley floor. Behind came Bronn, Tyrion Lannister, Marillion, and six of Brynden's men. Not until they were a third of the way down the mountain path, well out of earshot of the others, did Brynden Tully turn to her and say, â€Å"So, child. Tell me about this storm of yours.† â€Å"I have not been a child in many years, Uncle,† Catelyn said, but she told him nonetheless. It took longer than she would have believed to tell it all, Lysa's letter and Bran's fall, the assassin's dagger and Littlefinger and her chance meeting with Tyrion Lannister in the crossroads inn. Her uncle listened silently, heavy brows shadowing his eyes as his frown grew deeper. Brynden Tully had always known how to listen . . . to anyone but her father. He was Lord Hoster's brother, younger by five years, but the two of them had been at war as far back as Catelyn could remember. During one of their louder quarrels, when Catelyn was eight, Lord Hoster had called Brynden â€Å"the black goat of the Tully flock.† Laughing, Brynden had pointed out that the sigil of their house was a leaping trout, so he ought to be a black fish rather than a black goat, and from that day forward he had taken it as his personal emblem. The war had not ended until the day she and Lysa had been wed. It was at their wedding feast that Brynden told his brother he was leaving Riverrun to serve Lysa and her new husband, the Lord of the Eyrie. Lord Hoster had not spoken his brother's name since, from what Edmure told her in his infrequent letters. Nonetheless, during all those years of Catelyn's girlhood, it had been Brynden the Blackfish to whom Lord Hoster's children had run with their tears and their tales, when Father was too busy and Mother too ill. Catelyn, Lysa, Edmure . . . and yes, even Petyr Baelish, their father's ward . . . he had listened to them all patiently, as he listened now, laughing at their triumphs and sympathizing with their childish misfortunes. When she was done, her uncle remained silent for a long time, as his horse negotiated the steep, rocky trail. â€Å"Your father must be told,† he said at last. â€Å"If the Lannisters should march, Winterfell is remote and the Vale walled up behind its mountains, but Riverrun lies right in their path.† â€Å"I'd had the same fear,† Catelyn admitted. â€Å"I shall ask Maester Colemon to send a bird when we reach the Eyrie.† She had other messages to send as well; the commands that Ned had given her for his bannermen, to ready the defenses of the north. â€Å"What is the mood in the Vale?† she asked. â€Å"Angry,† Brynden Tully admitted. â€Å"Lord Jon was much loved, and the insult was keenly felt when the king named Jaime Lannister to an office the Arryns had held for near three hundred years. Lysa has commanded us to call her son the True Warden of the East, but no one is fooled. Nor is your sister alone in wondering at the manner of the Hand's death. None dare say Jon was murdered, not openly, but suspicion casts a long shadow.† He gave Catelyn a look, his mouth tight. â€Å"And there is the boy.† â€Å"The boy? What of him?† She ducked her head as they passed under a low overhang of rock, and around a sharp turn. Her uncle's voice was troubled. â€Å"Lord Robert,† he sighed. â€Å"Six years old, sickly, and prone to weep if you take his dolls away. Jon Arryn's trueborn heir, by all the gods, yet there are some who say he is too weak to sit his father's seat, Nestor Royce has been high steward these past fourteen years, while Lord Jon served in King's Landing, and many whisper that he should rule until the boy comes of age. Others believe that Lysa must marry again, and soon. Already the suitors gather like crows on a battlefield. The Eyrie is full of them.† â€Å"I might have expected that,† Catelyn said. Small wonder there; Lysa was still young, and the kingdom of Mountain and Vale made a handsome wedding gift. â€Å"Will Lysa take another husband?† â€Å"She says yes, provided she finds a man who suits her,† Brynden Tully said, â€Å"but she has already rejected Lord Nestor and a dozen other suitable men. She swears that this time she will choose her lord husband.† â€Å"You of all people can scarce fault her for that.† Ser Brynden snorted. â€Å"Nor do I, but . . . it seems to me Lysa is only playing at courtship. She enjoys the sport, but I believe your sister intends to rule herself until her boy is old enough to be Lord of the Eyrie in truth as well as name.† â€Å"A woman can rule as wisely as a man,† Catelyn said. â€Å"The right woman can,† her uncle said with a sideways glance. â€Å"Make no mistake, Cat. Lysa is not you.† He hesitated a moment. â€Å"If truth be told, I fear you may not find your sister as helpful as you would like.† She was puzzled. â€Å"What do you mean?† â€Å"The Lysa who came back from King's Landing is not the same girl who went south when her husband was named Hand. Those years were hard for her. You must know. Lord Arryn was a dutiful husband, but their marriage was made from politics, not passion.† â€Å"As was my own.† â€Å"They began the same, but your ending has been happier than your sister's. Two babes stillborn, twice as many miscarriages, Lord Arryn's death . . . Catelyn, the gods gave Lysa only the one child, and he is all your sister lives for now, poor boy. Small wonder she fled rather than see him handed over to the Lannisters. Your sister is afraid, child, and the Lannisters are what she fears most. She ran to the Vale, stealing away from the Red Keep like a thief in the night, and all to snatch her son out of the lion's mouth . . . and now you have brought the lion to her door.† â€Å"In chains,† Catelyn said. A crevasse yawned on her right, falling away into darkness. She reined up her horse and picked her way along step by careful step. â€Å"Oh?† Her uncle glanced back, to where Tyrion Lannister was making his slow descent behind them. â€Å"I see an axe on his saddle, a dirk at his belt, and a sellsword that trails after him like a hungry shadow. Where are the chains, sweet one?† Catelyn shifted uneasily in her seat. â€Å"The dwarf is here, and not by choice. Chains or no, he is my prisoner. Lysa will want him to answer for his crimes no less than I. It was her own lord husband the Lannisters murdered, and her own letter that first warned us against them.† Brynden Blackfish gave her a weary smile. â€Å"I hope you are right, child,† he sighed, in tones that said she was wrong. The sun was well to the west by the time the slope began to flatten beneath the hooves of their horses. The road widened and grew straight, and for the first time Catelyn noticed wildflowers and grasses growing. Once they reached the valley floor, the going was faster and they made good time, cantering through verdant greenwoods and sleepy little hamlets, past orchards and golden wheat fields, splashing across a dozen sunlit streams. Her uncle sent a standard-bearer ahead of them, a double banner flying from his staff; the moon-and-falcon of House Arryn on high, and below it his own black fish. Farm wagons and merchants' carts and riders from lesser houses moved aside to let them pass. Even so, it was full dark before they reached the stout castle that stood at the foot of the Giant's Lance. Torches flickered atop its ramparts, and the horned moon danced upon the dark waters of its moat. The drawbridge was up and the portcullis down, but Catelyn saw lights burning in the gatehouse and spilling from the windows of the square towers beyond. â€Å"The Gates of the Moon,† her uncle said as the party drew rein. His standard-bearer rode to the edge of the moat to hail the men in the gatehouse. â€Å"Lord Nestor's seat. He should be expecting us. Look up.† Catelyn raised her eyes, up and up and up. At first all she saw was stone and trees, the looming mass of the great mountain shrouded in night, as black as a starless sky. Then she noticed the glow of distant fires well above them; a tower keep, built upon the steep side of the mountain, its lights like orange eyes staring down from above. Above that was another, higher and more distant, and still higher a third, no more than a flickering spark in the sky. And finally, up where the falcons soared, a flash of white in the moonlight. Vertigo washed over her as she stared upward at the pale towers, so far above. â€Å"The Eyrie,† she heard Marillion murmur, awed. The sharp voice of Tyrion Lannister broke in. â€Å"The Arryns must not be overfond of company. If you're planning to make us climb that mountain in the dark, I'd rather you kill me here.† â€Å"We'll spend the night here and make the ascent on the morrow,† Brynden told him. â€Å"I can scarcely wait,† the dwarf replied. â€Å"How do we get up there? I've no experience at riding goats.† â€Å"Mules,† Brynden said, smiling. â€Å"There are steps carved into the mountain,† Catelyn said. Ned had told her about them when he talked of his youth here with Robert Baratheon and Jon Arryn. Her uncle nodded. â€Å"It is too dark to see them, but the steps are there. Too steep and narrow for horses, but mules can manage them most of the way. The path is guarded by three waycastles, Stone and Snow and Sky. The mules will take us as far up as Sky.† Tyrion Lannister glanced up doubtfully. â€Å"And beyond that?† Brynden smiled. â€Å"Beyond that, the path is too steep even for mules. We ascend on foot the rest of the way. Or perchance you'd prefer to ride a basket. The Eyrie clings to the mountain directly above Sky, and in its cellars are six great winches with long iron chains to draw supplies up from below. If you prefer, my lord of Lannister, I can arrange for you to ride up with the bread and beer and apples.† The dwarf gave a bark of laughter. â€Å"Would that I were a pumpkin,† he said. â€Å"Alas, my lord father would no doubt be most chagrined if his son of Lannister went to his fate like a load of turnips. If you ascend on foot, I fear I must do the same. We Lannisters do have a certain pride.† â€Å"Pride?† Catelyn snapped. His mocking tone and easy manner made her angry. â€Å"Arrogance, some might call it. Arrogance and avarice and lust for power.† â€Å"My brother is undoubtedly arrogant,† Tyrion Lannister replied. â€Å"My father is the soul of avarice, and my sweet sister Cersei lusts for power with every waking breath. I, however, am innocent as a little lamb. Shall I bleat for you?† He grinned. The drawbridge came creaking down before she could reply, and they heard the sound of oiled chains as the portcullis was drawn up. Men-at-arms carried burning brands out to light their way, and her uncle led them across the moat. Lord Nestor Royce, High Steward of the Vale and Keeper of the Gates of the Moon, was waiting in the yard to greet them, surrounded by his knights. â€Å"Lady Stark,† he said, bowing. He was a massive, barrel-chested man, and his bow was clumsy. Catelyn dismounted to stand before him. â€Å"Lord Nestor,† she said. She knew the man only by reputation; Bronze Yohn's cousin, from a lesser branch of House Royce, yet still a formidable lord in his own right. â€Å"We have had a long and tiring journey. I would beg the hospitality of your roof tonight, if I might.† â€Å"My roof is yours, my lady,† Lord Nestor returned gruffly, â€Å"but your sister the Lady Lysa has sent down word from the Eyrie. She wishes to see you at once. The rest of your party will be housed here and sent up at first light.† Her uncle swung off his horse. â€Å"What madness is this?† he said bluntly. Brynden Tully had never been a man to blunt the edge of his words. â€Å"A night ascent, with the moon not even full? Even Lysa should know that's an invitation to a broken neck.† â€Å"The mules know the way, Ser Brynden.† A wiry girl of seventeen or eighteen years stepped up beside Lord Nestor. Her dark hair was cropped short and straight around her head, and she wore riding leathers and a light shirt of silvered ringmail. She bowed to Catelyn, more gracefully than her lord. â€Å"I promise you, my lady, no harm will come to you. It would be my honor to take you up. I've made the dark climb a hundred times. Mychel says my father must have been a goat.† She sounded so cocky that Catelyn had to smile. â€Å"Do you have a name, child?† â€Å"Mya Stone, if it please you, my lady,† the girl said. It did not please her; it was an effort for Catelyn to keep the smile on her face. Stone was a bastard's name in the Vale, as Snow was in the north, and Flowers in Highgarden; in each of the Seven Kingdoms, custom had fashioned a surname for children born with no names of their own. Catelyn had nothing against this girl, but suddenly she could not help but think of Ned's bastard on the Wall, and the thought made her angry and guilty, both at once. She struggled to find words for a reply. Lord Nestor filled the silence. â€Å"Mya's a clever girl, and if she vows she will bring you safely to the Lady Lysa, I believe her. She has not failed me yet.† â€Å"Then I put myself in your hands, Mya Stone,† Catelyn said. â€Å"Lord Nestor, I charge you to keep a close guard on my prisoner.† â€Å"And I charge you to bring the prisoner a cup of wine and a nicely crisped capon, before he dies of hunger,† Lannister said. â€Å"A girl would be pleasant as well, but I suppose that's too much to ask of you.† The sellsword Bronn laughed aloud. Lord Nestor ignored the banter. â€Å"As you say, my lady, so it will be done.† Only then did he look at the dwarf. â€Å"See our lord of Lannister to a tower cell, and bring him meat and mead.† Catelyn took her leave of her uncle and the others as Tyrion Lannister was led off, then followed the bastard girl through the castle. Two mules were waiting in the upper bailey, saddled and ready. Mya helped her mount one while a guardsman in a sky-blue cloak opened the narrow postern gate. Beyond was dense forest of pine and spruce, and the mountain like a black wall, but the steps were there, chiseled deep into the rock, ascending into the sky. â€Å"Some people find it easier if they close their eyes,† Mya said as she led the mules through the gate into the dark wood. â€Å"When they get frightened or dizzy, sometimes they hold on to the mule too tight. They don't like that.† â€Å"I was born a Tully and wed to a Stark,† Catelyn said. â€Å"I do not frighten easily. Do you plan to light a torch?† The steps were black as pitch. The girl made a face. â€Å"Torches just blind you. On a clear night like this, the moon and the stars are enough. Mychel says I have the eyes of the owl.† She mounted and urged her mule up the first step. Catelyn's animal followed of its own accord. â€Å"You mentioned Mychel before,† Catelyn said. The mules set the pace, slow but steady. She was perfectly content with that. â€Å"Mychel's my love,† Mya explained. â€Å"Mychel Redfort. He's squire to Ser Lyn Corbray. We're to wed as soon as he becomes a knight, next year or the year after.† She sounded so like Sansa, so happy and innocent with her dreams. Catelyn smiled, but the smile was tinged with sadness. The Redforts were an old name in the Vale, she knew, with the blood of the First Men in their veins. His love she might be, but no Redfort would ever wed a bastard. His family would arrange a more suitable match for him, to a Corbray or a Waynwood or a Royce, or perhaps a daughter of some greater house outside the Vale. If Mychel Redfort laid with this girl at all, it would be on the wrong side of the sheet. The ascent was easier than Catelyn had dared hope. The trees pressed close, leaning over the path to make a rustling green roof that shut out even the moon, so it seemed as though they were moving up a long black tunnel. But the mules were surefooted and tireless, and Mya Stone did indeed seem blessed with night-eyes. They plodded upward, winding their way back and forth across the face of the mountain as the steps twisted and turned. A thick layer of fallen needles carpeted the path, so the shoes of their mules made only the softest sound on the rock. The quiet soothed her, and the gentle rocking motion set Catelyn to swaying in her saddle. Before long she was fighting sleep. Perhaps she did doze for a moment, for suddenly a massive ironbound gate was looming before them. â€Å"Stone,† Mya announced cheerily, dismounting. Iron spikes were set along the tops of formidable stone walls, and two fat round towers overtopped the keep. The gate swung open at Mya's shout. Inside, the portly knight who commanded the waycastle greeted Mya by name and offered them skewers of charred meat and onions still hot from the spit. Catelyn had not realized how hungry she was. She ate standing in the yard, as stablehands moved their saddles to fresh mules. The hot juices ran down her chin and dripped onto her cloak, but she was too famished to care. Then it was up onto a new mule and out again into the starlight. The second part of the ascent seemed more treacherous to Catelyn. The trail was steeper, the steps more worn, and here and there littered with pebbles and broken stone. Mya had to dismount a half-dozen times to move fallen rocks from their path. â€Å"You don't want your mule to break a leg up here,† she said. Catelyn was forced to agree. She could feel the altitude more now. The trees were sparser up here, and the wind blew more vigorously, sharp gusts that tugged at her clothing and pushed her hair into her eyes. From time to time the steps doubled back on themselves, and she could see Stone below them, and the Gates of the Moon farther down, its torches no brighter than candles. Snow was smaller than Stone, a single fortified tower and a timber keep and stable hidden behind a low wall of unmortared rock. Yet it nestled against the Giant's Lance in such a way as to command the entire stone stair above the lower waycastle. An enemy intent on the Eyrie would have to fight his way from Stone step by step, while rocks and arrows rained down from Snow above. The commander, an anxious young knight with a pockmarked face, offered bread and cheese and the chance to warm themselves before his fire, but Mya declined. â€Å"We ought to keep going, my lady,† she said. â€Å"If it please you.† Catelyn nodded. Again they were given fresh mules. Hers was white. Mya smiled when she saw him. â€Å"Whitey's a good one, my lady. Sure of foot, even on ice, but you need to be careful. He'll kick if he doesn't like you.† The white mule seemed to like Catelyn; there was no kicking, thank the gods. There was no ice either, and she was grateful for that as well. â€Å"My mother says that hundreds of years ago, this was where the snow began,† Mya told her. â€Å"It was always white above here, and the ice never melted.† She shrugged. â€Å"I can't remember ever seeing snow this far down the mountain, but maybe it was that way once, in the olden times.† So young, Catelyn thought, trying to remember if she had ever been like that. The girl had lived half her life in summer, and that was all she knew. Winter is coming, child, she wanted to tell her. The words were on her lips; she almost said them. Perhaps she was becoming a Stark at last. Above Snow, the wind was a living thing, howling around them like a wolf in the waste, then falling off to nothing as if to lure them into complacency. The stars seemed brighter up here, so close that she could almost touch them, and the horned moon was huge in the clear black sky. As they climbed, Catelyn found it was better to look up than down. The steps were cracked and broken from centuries of freeze and thaw and the tread of countless mules, and even in the dark the heights put her heart in her throat. When they came to a high saddle between two spires of rock, Mya dismounted. â€Å"It's best to lead the mules over,† she said. â€Å"The wind can be a little scary here, my lady.† Catelyn climbed stiffly from the shadows and looked at the path ahead; twenty feet long and close to three feet wide, but with a precipitous drop to either side. She could hear the wind shrieking. Mya stepped lightly out, her mule following as calmly as if they were crossing a bailey. It was her turn. Yet no sooner had she taken her first step than fear caught Catelyn in its jaws. She could feel the emptiness, the vast black gulfs of air that yawned around her. She stopped, trembling, afraid to move. The wind screamed at her and wrenched at her cloak, trying to pull her over the edge. Catelyn edged her foot backward, the most timid of steps, but the mule was behind her, and she could not retreat. I am going to die here, she thought. She could feel cold sweat trickling down her back. â€Å"Lady Stark,† Mya called across the gulf. The girl sounded a thousand leagues away. â€Å"Are you well?† Catelyn Tully Stark swallowed what remained of her pride. â€Å"I . . . I cannot do this, child,† she called out. â€Å"Yes you can,† the bastard girl said. â€Å"I know you can. Look how wide the path is.† â€Å"I don't want to look.† The world seemed to be spinning around her, mountain and sky and mules, whirling like a child's top. Catelyn closed her eyes to steady her ragged breathing. â€Å"I'll come back for you,† Mya said. â€Å"Don't move, my lady.† Moving was about the last thing Catelyn was about to do. She listened to the skirling of the wind and the scuffling sound of leather on stone. Then Mya was there, taking her gently by the arm. â€Å"Keep your eyes closed if you like. Let go of the rope now, Whitey will take care of himself. Very good, my lady. I'll lead you over, it's easy, you'll see. Give me a step now. That's it, move your foot, just slide it forward. See. Now another. Easy. You could run across. Another one, go on. Yes.† And so, foot by foot, step by step, the bastard girl led Catelyn across, blind and trembling, while the white mule followed placidly behind them. The waycastle called Sky was no more than a high, crescent-shaped wall of unmortared stone raised against the side of the mountain, but even the topless towers of Valyria could not have looked more beautiful to Catelyn Stark. Here at last the snow crown began; Sky's weathered stones were rimed with frost, and long spears of ice hung from the slopes above. Dawn was breaking in the east as Mya Stone hallooed for the guards, and the gates opened before them. Inside the walls there was only a series of ramps and a great tumble of boulders and stones of all sizes. No doubt it would be the easiest thing in the world to begin an avalanche from here. A mouth yawned in the rock face in front of them. â€Å"The stables and barracks are in there,† Mya said. â€Å"The last part is inside the mountain. It can be a little dark, but at least you're out of the wind. This is as far as the mules can go. Past here, well, it's a sort of chimney, more like a stone ladder than proper steps, but it's not too bad. Another hour and we'll be there.† Catelyn looked up. Directly overhead, pale in the dawn light, she could see the foundations of the Eyrie. It could not be more than six hundred feet above them. From below it looked like a small white honeycomb. She remembered what her uncle had said of baskets and winches. â€Å"The Lannisters may have their pride,† she told Mya, â€Å"but the Tullys are born with better sense. I have ridden all day and the best part of a night. Tell them to lower a basket. I shall ride with the turnips.† The sun was well above the mountains by the time Catelyn Stark finally reached the Eyrie. A stocky, silver-haired man in a sky-blue cloak and hammered moon-and-falcon breastplate helped her from the basket; Ser Vardis Egen, captain of Jon Arryn's household guard. Beside him stood Maester Colemon, thin and nervous, with too little hair and too much neck. â€Å"Lady Stark,† Ser Vardis said, â€Å"the pleasure is as great as it is unanticipated.† Maester Colemon bobbed his head in agreement. â€Å"Indeed it is, my lady, indeed it is. I have sent word to your sister. She left orders to be awakened the instant you arrived.† â€Å"I hope she had a good night's rest,† Catelyn said with a certain bite in her tone that seemed to go unnoticed. The men escorted her from the winch room up a spiral stair. The Eyrie was a small castle by the standards of the great houses; seven slender white towers bunched as tightly as arrows in a quiver on a shoulder of the great mountain. It had no need of stables nor smithys nor kennels, but Ned said its granary was as large as Winterfell's, and its towers could house five hundred men. Yet it seemed strangely deserted to Catelyn as she passed through it, its pale stone halls echoing and empty. Lysa was waiting alone in her solar, still clad in her bed robes. Her long auburn hair tumbled unbound across bare white shoulders and down her back. A maid stood behind her, brushing out the night's tangles, but when Catelyn entered, her sister rose to her feet, smiling. â€Å"Cat,† she said. â€Å"Oh, Cat, how good it is to see you. My sweet sister.† She ran across the chamber and wrapped her sister in her arms. â€Å"How long it has been,† Lysa murmured against her. â€Å"Oh, how very very long.† It had been five years, in truth; five cruel years, for Lysa. They had taken their toll. Her sister was two years the younger, yet she looked older now. Shorter than Catelyn, Lysa had grown thick of body, pale and puffy of face. She had the blue eyes of the Tullys, but hers were pale and watery, never still. Her small mouth had turned petulant. As Catelyn held her, she remembered the slender, high-breasted girl who'd waited beside her that day in the sept at Riverrun. How lovely and full of hope she had been. All that remained of her sister's beauty was the great fall of thick auburn hair that cascaded to her waist. â€Å"You look well,† Catelyn lied, â€Å"but . . . tired.† Her sister broke the embrace. â€Å"Tired. Yes. Oh, yes.† She seemed to notice the others then; her maid, Maester Colemon, Ser Vardis. â€Å"Leave us,† she told them. â€Å"I wish to speak to my sister alone.† She held Catelyn's hand as they withdrew . . . . . . and dropped it the instant the door closed. Catelyn saw her face change. It was as if the sun had gone behind a cloud. â€Å"Have you taken leave of your senses?† Lysa snapped at her. â€Å"To bring him here, without a word of permission, without so much as a warning, to drag us into your quarrels with the Lannisters . . . â€Å" â€Å"My quarrels?† Catelyn could scarce believe what she was hearing. A great fire burned in the hearth, but there was no trace of warmth in Lysa's voice. â€Å"They were your quarrels first, sister. It was you who sent me that cursed letter, you who wrote that the Lannisters had murdered your husband.† â€Å"To warn you, so you could stay away from them! I never meant to fight them! Gods, Cat, do you know what you've done?† â€Å"Mother?† a small voice said. Lysa whirled, her heavy robe swirling around her. Robert Arryn, Lord of the Eyrie, stood in the doorway, clutching a ragged cloth doll and looking at them with large eyes. He was a painfully thin child, small for his age and sickly all his days, and from time to time he trembled. The shaking sickness, the maesters called it. â€Å"I heard voices.† Small wonder, Catelyn thought; Lysa had almost been shouting. Still, her sister looked daggers at her. â€Å"This is your aunt Catelyn, baby. My sister, Lady Stark. Do you remember?† The boy glanced at her blankly. â€Å"I think so,† he said, blinking, though he had been less than a year old the last time Catelyn had seen him. Lysa seated herself near the fire and said, â€Å"Come to Mother, my sweet one.† She straightened his bedclothes and fussed with his fine brown hair. â€Å"Isn't he beautiful? And strong too, don't you believe the things you hear. Jon knew. The seed is strong, he told me. His last words. He kept saying Robert's name, and he grabbed my arm so hard he left marks. Tell them, the seed is strong. His seed. He wanted everyone to know what a good strong boy my baby was going to be.† â€Å"Lysa,† Catelyn said, â€Å"if you're right about the Lannisters, all the more reason we must act quickly. We—† â€Å"Not in front of the baby,† Lysa said. â€Å"He has a delicate temper, don't you, sweet one?† â€Å"The boy is Lord of the Eyrie and Defender of the Vale,† Catelyn reminded her, â€Å"and these are no times for delicacy. Ned thinks it may come to war.† â€Å"Quiet!† Lysa snapped at her. â€Å"You're scaring the boy.† Little Robert took a quick peek over his shoulder at Catelyn and began to tremble. His doll fell to the rushes, and he pressed himself against his mother. â€Å"Don't be afraid, my sweet baby,† Lysa whispered. â€Å"Mother's here, nothing will hurt you.† She opened her robe and drew out a pale, heavy breast, tipped with red. The boy grabbed for it eagerly, buried his face against her chest, and began to suck. Lysa stroked his hair. Catelyn was at a loss for words. Jon Arryn's son, she thought incredulously. She remembered her own baby, three-year-old Rickon, half the age of this boy and five times as fierce. Small wonder the lords of the Vale were restive. For the first time she understood why the king had tried to take the child away from his mother to foster with the Lannisters . . . â€Å"We're safe here,† Lysa was saying. Whether to her or to the boy, Catelyn was not sure. â€Å"Don't be a fool,† Catelyn said, the anger rising in her. â€Å"No one is safe. If you think hiding here will make the Lannisters forget you, you are sadly mistaken.† Lysa covered her boy's ear with her hand. â€Å"Even if they could bring an army through the mountains and past the Bloody Gate, the Eyrie is impregnable. You saw for yourself. No enemy could ever reach us up here.† Catelyn wanted to slap her. Uncle Brynden had tried to warn her, she realized. â€Å"No castle is impregnable.† â€Å"This one is,† Lysa insisted. â€Å"Everyone says so. The only thing is, what am I to do with this Imp you have brought me?† â€Å"Is he a bad man?† the Lord of the Eyrie asked, his mother's breast popping from his mouth, the nipple wet and red. â€Å"A very bad man,† Lysa told him as she covered herself, â€Å"but Mother won't let him harm my little baby.† â€Å"Make him fly,† Robert said eagerly. Lysa stroked her son's hair. â€Å"Perhaps we will,† she murmured. â€Å"Perhaps that is just what we will do.†

The Role of HR Department in the Hiring of the New Employees

Before turning to the factors affecting the proper organization of a Human Resources department and its role in hiring new employees, briefly need to stress the organization of the department itself. National Hellenic Land and Property Register consist of HR Executive Manager, two HR generalists, one HR coordinator and one HR assistant.The binding function of human resource management to business strategy at the operational, administrative and strategic level, facilitating managers and line workers and the continuous monitoring of developments, both internal as well as external highlighting role of Human Resources into a modern enterprise, and demonstrate the importance of the department. Recruitment and selection of staff responsibilities are exclusively assigned to the Executive Manager of Human Resources.The manager is responsible for all actions relating to vacant or new job, promotions and personnel movements, and maintains the necessary number of employees by carrying out recru itment. The departures of employees and management mainly for reasons of retirement have resulted in the evacuation of jobs. Usually outgoing are people with enough experience in positions of responsibility. Thus the filling of these positions is usually done with internal recruitment. In particular, the HR manager is obliged to communicate in the form of circulars typically jobs that are to be met.The same procedure is followed in the event that created new jobs, but in which they can meet their employees with the knowledge and experience they possess. The various movements, promotions and retirements are leaving them uncovered jobs, responding mainly to simple tasks without supervision and accountability. To meet the specific positions, HR Department addresses recourse to external recruitment. As already mentioned, the decision to conduct large- scale recruitment is solely the responsibility of the manager.Usually in the medium term cared to cover positions internally (delay Promo tions – assignment of multiple tasks), while intakes are in the long periodic basis by conducting external competitions. The HR manager is responsible for the organization and conduct of these competitions, and for notification of job vacancies nationwide. Analyzing the recruitment process shows that there are some points that need improvement. First, the company needs to unblock the recruitment process from the logic of the periodic competitions.It is appropriate to be recruited annually, based programming needs already done the Human Resources Department. Even through â€Å"external recruitment should be extended tank pumping concerned, possibly by linking the company with the finance departments of Greek universities to attract people most concerned with the essential object of activity of the National Hellenic Land and Property Register, given that as the situation today , the attraction is rather randomâ€Å"(Petrakis, 2012) , however, and certainly without any necessa ry filters.The only case where it is applied successfully recruiting process as described scientifically by the Human Resources Administration, is recruiting qualified professional staff. The recruitment process has been upgraded to the extent that a separate sub-division within the Directorate of Human Resources. The HR generalists are primarily responsible for the execution of all actions that contribute to the proper staffing of various jobs. It operates on two levels, the original recruiting agents, and this selection of employees for staffing positions of responsibility.During the recruitment process, successful candidates go through specific stages of selection, and which lead to the final hiring decision or rejection. These stages are interviewing executive sub address selection, which mainly outlines the psychosocial profile of the candidate, a test of perception and intelligence, control and verification of references accompanying the application documents and medical exams . Noted at this point that successful candidate’s recruitment is rarely rejected at selection stages. These are more important for recording various characteristics of employees, and simply recorded and archived for future use.The selection plays a very important role in the process of promoting employees and staffing positions of responsibility. At this level, historical data have occasionally recorded, account together with the data obtained from a second selection process done at that time to candidates who meet the set criteria. The latter process involves a detailed interview with each candidate, where he is asked to describe the reasons is interested in a specific location, and design and analysis of annual performance evaluation sheetsâ€Å".  (McConnell, 2005)The final conclusions of this choice lead to the promotion decision or rejection of the official. The selection procedures used by the National Hellenic Land and Property Register judged as adequate and relati vely well designed. The tests and interviews are done by highly trained staff and have a high degree of reliability. It is useful to introduce assessment procedures of virtual projects, before taking up his new duties, in order to verify in practice if and when candidates for key positions are capable and experienced enough to cope with any difficulties.