zahid khan

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Standardization of Herbal Medicines of Local Market by Different Analytical Methods

Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

OncoTargets and Therapy, 2016

Kirsten rat sarcoma (K-Ras) protein is a member of Ras family belonging to the small guanosine tr... more Kirsten rat sarcoma (K-Ras) protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphatebound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods: In the present study, we targeted the nucleotide-binding site in the "on" and "off" state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results: Interestingly, the designed compounds exhibit a binding preference for the "off" state over "on" state conformation of K-Ras protein. Moreover, the designed compounds' interactions are similar to guanosine diphosphate and, thus, could presumably act as a potential lead for K-Ras. The predicted drug-likeness properties of these compounds suggest that these compounds follow the Lipinski's rule of five and have tolerable absorption, distribution, metabolism, excretion and toxicity values. Conclusion: Thus, through the current study, we propose targeting only "off" state conformations as a promising strategy for the design of reversible inhibitors to pharmacologically inhibit distinct conformations of K-Ras protein.

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Endovascular repair of a mycotic thoracic aortic aneurysm in a patient with aortic coarctation

Journal of Vascular Surgery Cases, 2015

This report describes the management of a 28-year-old female patient who presented with septicemi... more This report describes the management of a 28-year-old female patient who presented with septicemia and mediastinal mass-effect secondary to a proximal mycotic aneurysm of the descending aorta. The patient had an infected bicuspid aortic valve, aortic coarctation, and a left vertebral artery arising directly from the aortic arch. Evidence of disseminated embolization affecting her posterior cerebral circulation, the left axillary, and the superior mesenteric arteries was noted. The patient had a considerably small aorta. An urgent thoracic endovascular aortic repair was performed successfully with a chimney stent to the left vertebral artery. The report discusses the planning and technique used in managing this complex case.

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Knowledge, Attitude and Practices Among Dental Students and House Officers Regarding Infection Control in Clinical Settings

International Journal of Pharmacy

ABSTRACT

Saphenous Vein Harvest: A Prospective Randomized Trial Single-Layer Versus Multiple-Layer Closure of Leg Wounds After Long

Education Level of Women and Watching of Cable Television

The objective of this study was to investigate the negative and positive effect of cable televisi... more The objective of this study was to investigate the negative and positive effect of cable television, importance of educated women, major purpose of viewing cable television and relationship between level of education of women and level of watching of cable television. Data was collected through a structured questioner from the educated women of district Swat. For presentation of data, frequency distribution was used and significance of the relationship was tested by Chai square test. The analysis showed that there is significant relationship between level of education of women and the level of watching cable television. Further major purpose of watching cable television was entertainment. The researcher suggested that, in making policy, PEMRA should keep in view the negative and positive impact of cable television, Also highly educated women were focus by PEMRA in their policies.

Association among Domestic Activities, Culture and Role of Educated Women and Cable Television in War Affected Area Swat

Journal of Mass Communication and Journalism, 2013

This study was conducted to assess the effects of watching cable television on some characteristi... more This study was conducted to assess the effects of watching cable television on some characteristics of women. Population of the study was the educated women between ages 18-30 of District Swat, Khyber Pathtunkhwa was selected. Purposive sampling method was used to select sample from the population. Total Eighty-nine respondents were selected from the population as a unit of analysis to investigate the effects. A structured questionnaire was used to collect the information from the respondents. Descriptive statistics was used to present the data through tables. The result was generalized to the population through chi-square test of association. The result analyzed, that the variables; domestic activities, culture and role of women were significantly associated to the exposure of cable television. Government and private companies have the responsibilities to promote the culture, domestic activities and role of women of Pashtun society by introducing special channel on cable television or frame programs on the existing channels.

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An Overview of Power Generation Technologies Suitable for Lunar Application

1st Space Exploration Conference: Continuing the Voyage of Discovery, 2005

An Overview of Power Generation Technologies Suitable for Lunar Application. Zahid A Khan, Alex Z... more

Low Power Implementation for Minimum Norm Sorting and Block Upper Tri-angularization of Matrices used in MIMO Wireless Systems

20th International Conference on VLSI Design held jointly with 6th International Conference on Embedded Systems (VLSID'07), 2007

Multiple Input-Multiple Output (MIMO) wireless technology involves highly complex vectors and mat... more Multiple Input-Multiple Output (MIMO) wireless technology involves highly complex vectors and matrix computations which are directly related to increased power and area consumption. This paper proposes an area and power efficient VLSI architecture that can serve the dual purpose of minimum norm sorting of rows as well as upper/lower block tri-angularization of matrices. The resources inside the architecture are shared among both operations and only primitive computations are used. Results indicate saving in silicon real estate as well as power consumption compared to previous architecture without degrading performance.

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Performance analysis of IEEE defined LDPC codes under various decoding algorithms and their implementation on a reconfigurable instruction cell architecture

2007 IEEE International SOC Conference, 2007

This paper builds a real time Programmable LDPC Decoder for decoding codes specified in IEEE 802.... more This paper builds a real time Programmable LDPC Decoder for decoding codes specified in IEEE 802.16 standard and discusses their performance under various decoding algorithms. Out of the decoding algorithms, the modified Min-Sum SPA is selected for implementation and optimization on a reconfigurable instruction cell architecture. Different general and architecture specific optimization techniques are applied to enhance the throughput. With the architecture, a throughput of 20 Mbps has been achieved.

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A New Pipelined Implementation for Minimum Norm Sorting used in Square Root Algorithm for MIMO-VBLAST Systems

2007 Design, Automation & Test in Europe Conference & Exhibition, 2007

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A real time programmable encoder for low density parity check code targeting a reconfigurable instruction cell architecture

2006 IEEE International Conference on Field Programmable Technology, 2006

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Homology Modeling of Hemagglutinin/Protease [HA/P (vibriolysin)] from Vibrio Cholerae: Sequence Comparision, Residue Interactions and Molecular Mechanism

The Protein Journal, 2007

Vibrio cholerae produces a zinc-containing and calcium-stabilized soluble hemagglutinin/protease,... more Vibrio cholerae produces a zinc-containing and calcium-stabilized soluble hemagglutinin/protease, which has been earlier shown to have the ability to cleave several physiologically important substrates including mucin, fibronectin and lactoferin. This study presents homology modeling of hemagglutinin/protease (vibriolysin) from Vibrio cholerae in the presence of inhibitor HPI [N-(1carboxy-3-phenylpropyl)-phenylalanyl-alpha-aspargine]. The 3D structure was predicted based on its sequence homology with Pseudomonas aeruginosa elastase (PAE). Comparison of the 3D structures of PAE and HA/P reveals a remarkable similarity having a conserved a + b domain. The inhibitor shows similar binding features as seen in other metalloproteases of M4 peptidase family. The study also highlights the key catalytic residues as well as the residues at the S 1 and S 0 1 binding sub-sites. The similarities between the two proteins provide support for the hypothesis that the two enzymes have similar three-dimensional structures and a common mechanism of action. The fact that both enzymes are secreted as zinc-containing proteases, led us to further hypothesize that they may play similar role in pathogenesis.

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Structural Bioinformatics of Vibrio cholerae Aminopeptidase A (PepA) Monomer

Protein & Peptide Letters, 2009

Aminopeptidase A (PepA) is a metalloexopeptidase found in Vibrio cholerae .It functions as a tran... more Aminopeptidase A (PepA) is a metalloexopeptidase found in Vibrio cholerae .It functions as a transcriptional repressor in regulatory cascade that controls virulence gene expression in V. cholerae. It is involved in protein degradation and in the metabolism of biologically active peptides. We proposed a 3D model of PepA based upon the crystal structure of PepA from Escherichia coli (E. coli) with an intention to evaluate the active site of the enzyme and to predict the properties of this enzyme, study of its 3D structure will help in understanding its role in DNA binding.

Purification of the photosynthetic reaction center from Heliobacterium modesticaldum

Photosynthesis Research, 2012

We have developed a purification protocol for photoactive reaction centers (HbRC) from Heliobacte... more We have developed a purification protocol for photoactive reaction centers (HbRC) from Heliobacterium modesticaldum. HbRCs were purified from solubilized membranes in two sequential chromatographic steps, resulting in the isolation of a fraction containing a single polypeptide, which was identified as PshA by LC-MS/MS of tryptic peptides. All polypeptides reported earlier as unknown proteins (in Heinnickel et al., Biochemistry 45:6756-6764, 2006; Romberger et al., Photosynth Res 104:293-303, 2010) are now identified by mass spectrometry to be the membrane-bound cytochrome c 553 and four different ABC-type transporters. The purified PshA homodimer binds the following pigments: 20 bacteriochlorophyll (BChl) g, two BChl g 0 , two 8 1-OH-Chl a F , and one 4,4 0-diaponeurosporene. It lacks the PshB polypeptide binding the F A and F B [4Fe-4S] clusters. It is active in charge separation and exhibits a trapping time of 23 ps, as judged by time-resolved fluorescence studies. The charge recombination rate of the P 800 ? F X state is 10-15 ms, as seen before. The purified HbRC core was able to reduce cyanobacterial flavodoxin in the light, exhibiting a K M of 10 lM and a k cat of 9.5 s-1 under near-saturating light. There are *1.6 menaquinones per HbRC in the purified complex. Illumination of frozen HbRC in the presence of dithionite can cause creation of a radical at g = 2.0046, but this is not a semiquinone. Furthermore, we show that highpurity HbRCs are very stable in anoxic conditions and even remain active in the presence of oxygen under low light.

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Analysis of Endogenous LRP6 Function Reveals a Novel Feedback Mechanism by Which Wnt Negatively Regulates Its Receptor

Molecular and Cellular Biology, 2007

The canonical Wnt pathway plays a crucial role in embryonic development, and its deregulation is ... more The canonical Wnt pathway plays a crucial role in embryonic development, and its deregulation is involved in human diseases. The LRP6 single-span transmembrane coreceptor is essential for transmission of canonical Wnt signaling. However, due to the lack of immunological reagents, our understanding of LRP6 structure and function has relied on studies involving its overexpression, and regulation of the endogenous receptor by the Wnt ligand has remained unexplored. Using a highly sensitive and specific antibody to LRP6, we demonstrate that the endogenous receptor is modified by N-glycosylation and is phosphorylated in response to Wnt stimulation in a sustained yet ligand-dependent manner. Moreover, following triggering by Wnt, endogenous LRP6 is internalized and recycled back to the cellular membrane within hours of the initial stimulus. Finally, we have identified a novel feedback mechanism by which Wnt, acting through β-catenin, negatively regulates LRP6 at the mRNA level. Together, ...

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Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial

The Lancet, 2012

Background In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol ... more Background In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the eff ects of this intervention on mortality in patients with ARDS. Methods We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO 2 /F I O 2) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86. Findings We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1•47, 95% CI 1•03-2•08). Interpretation Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be benefi cial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended.

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Posterior epidural migration of herniated lumbar disc fragment

Journal of Neurosurgery: Spine, 2011

Object Posterior epidural migration of a free disc fragment in the lumbar region is a very rare c... more Object Posterior epidural migration of a free disc fragment in the lumbar region is a very rare condition that has only been reported in isolated cases to date. Patients with this condition present with radiculopathy or major neurological deficits. Difficulties in diagnosis and the choice and timing of surgical treatment are important in these cases. In this clinical case series, features of cases with posterior epidural migration of free lumbar disc fragments accompanied by cauda equina syndrome are discussed. Methods Eight cases (0.27%) of posterior epidural migration of disc fragments were detected among 2880 patients surgically treated for lumbar disc herniation between 1995 and 2008. Seven of these patients had cauda equina syndrome. The mean duration of symptoms in the 8 cases was 4.2 days (range 1–10 days). The group included 6 men and 2 women, with a mean age of 48 years (range 34–72 years). The sequestered disc fragments were at the L3–4 level in 6 patients (75%) and the L4...

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Economic and Performance Evaluation of Heat Sink Options in Combined Cycle Applications

Journal of Engineering for Gas Turbines and Power, 2005

This paper is a guideline to selecting the most appropriate technology for the power plant heat s... more This paper is a guideline to selecting the most appropriate technology for the power plant heat sink based on water availability, site location, and wastewater disposal requirements. The paper discusses wet as well as dry cooling systems and evaluates the impact of the heat sink technology on the performance and cost of combined cycle power plants. Cogeneration applications and cycling plant operations are also considered. For each proposed option, the performance, relative costs, and noise issues will be presented.

Protection of Cells in Physiological Oxygen Tensions against DNA Damage-induced Apoptosis

Journal of Biological Chemistry, 2010

Oxygen availability has important effects on cell physiology. Although hyperoxic and hypoxic stre... more Oxygen availability has important effects on cell physiology. Although hyperoxic and hypoxic stresses have been well characterized, little is known about cellular functions in the oxygen levels commonly found in vivo. Here, we show that p53-dependent apoptosis in response to different DNA-damaging agents was reduced when normal and cancer cells were cultured at physiological oxygen tensions instead of the usual atmospheric levels. Different from what has been described in hypoxia, this was neither determined by decreases in p53 induction or its transactivation activity, nor by differences in the intracellular accumulation of reactive oxygen species. At these physiological oxygen levels, we found a constitutive activation of the ERK1/2 MAPK in all the models studied. Inhibition of this signaling pathway reversed the protective effect in some but not all cell lines. We conclude that a stress-independent constitutive activation of prosurvival pathways, including but probably not limited to MAPK, can protect cells in physiological oxygen tensions against genotoxic stress. Our results underscore the need of considering the impact of oxygen levels present in the tissue microenvironment when studying cell sensitivity to treatments such as chemotherapy and radiotherapy.

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