Showing papers by "Rajesh Kumar published in 2004"

Global promotion of herbal medicine: India's opportunity

Abstract: MEDICINAL herbs are moving from fringe to mainstream use with a greater number of pe ople seeking remedies and health approaches free from side effects caused by sy nthetic chemicals. Recently, considerable attention has been paid to utilize eco-friendly and biofriendly plant-based products for the prevention and cure of different human diseases. Considering the adverse effects of sy nthetic drugs 1,2 , the Western population is looking for natural remedies which are safe and effective. It is documented that 80% of the worlds population has faith in traditional medicine, pa rticularly plant drugs for their primary healthcare. India is sitting on a gold mine of well -recorded and traditionally well-practised knowledge of herbal medicine. This country is perhaps the largest produc er of medicinal herbs and is rightly called the botanical garden of the world. There are very few medicinal herbs of commercial importance which are not found in this country. India off icially recognizes over 3000 plants for their m edicinal value. It is generally estimated that over 6000 plants in India are in use in traditional, folk and herbal medicine, repr esenting about 75% of the medicinal needs of the Third World countries 3 . Three of the ten most widely selling herbal medicines in the developed countries, namely preparations of Allium sativum, Aloe barbedensis and Panax sp. are available in India. There are about 7000 firms manufacturing traditional medicines with or without standardization. Medicinal herbs have been in use in one form or a nother, under indigenous systems of medicine like Ayurveda, Sidha and Unani. India, with its traditional background, needs to increase its share in the world ma rket. But unlike China, India has not been able to capita lize on this herbal wealth by promoting its use in the developed world, despite their renewed interest in herbal medicines. This can be achieved by judicious product identification based on diseases prevalent in the deve loped world for which no medicine or palliative the rapy is available. Such herbal medicines will find speedy access into those cou ntries. Undoubtedly, the plant kingdom still holds many species of plants containing su bstances of medicinal value which have yet to be discovered. India is a land of i mmense biodiversity in which two out of eighteen hot spots of the world are located. India is also one of the twelve mega biodiversity countries in the world. The total nu mber of plant species of all groups recorded from India is 45,000 (the total number may be even close to 60,000, as severa l parts of India are yet to be botanically e xplored). Of these, seed-bearing plants account for nearly 15,000 –18,000. India enjoys the benefits of varied climate, from alpine in the Himalaya to tropical wet in the south and arid in R ajasthan. Such climatic cond itions have given rise to rich and varied flora in the Indian subcont inent. In order to promote Indian herbal drugs, there is an urgent need to evaluate the therapeutic potentials of the drugs as per WHO guidelines 4 . Ironically, not many I ndian products are available in standardized form, which is the minimum requirement for introducing a product in the Western market.

Single nucleotide polymorphisms in breast cancer.

Abstract: A limited number of genes have been identified that explain heritable risks of breast cancer (BC). We searched for low-penetrant genes in an association study using two populations: 223 Finnish unselected patients and 172 Polish familial cases, both with locally collected healthy controls. Candidate genes included DNA repair genes, methylenetetrahydrofolate reductase (MTHFR) and cyclin D1 genes. The frequencies for single nucleotide polymorphisms (SNPs) were measured in the following genes: NBS1, XPC, XPD, XRCC1, XRCC3, MTHFR, and cyclin D1. Odds ratios (ORs) were calculated to the wild-type genotype. The positive findings in the Finnish series were repeated in the Polish series. Significant findings among Finns were associations to XPC exon 15, XPD exon 10 and XRCC3 exon 7, the latter of borderline significance. None of these results could be repeated in the Polish series. The XPC result among Finns was probably an artifact of the control group deviating from the Hardy-Weinberg Equilibrium (HWE). The attempt to repeat the result for the XPD polymorphism among Poles was probably not valid because the control group deviated from the HWE. We conclude that within statistical power of the present study, none of the tested polymorphisms associated with BC, with the probable exception of XPD.

Loss of Smad3 in acute T-cell lymphoblastic leukemia.

Abstract: Background The receptors for transforming growth factor β (TGF-β) and their signaling intermediates make up an important tumor-suppressor pathway. The role of one of these intermediates — Smad3 — i...

Tamoxifen in topical liposomes: development, characterization and in-vitro evaluation.

Abstract: Purpose: Tamoxifen, an anti-estrogen com- pound, has recently been figured as a useful agent in the treatment of certain skin specific disorders. This recent found application has generated an interest in its topical formulation in order to avoid the side effects associated with oral administration, while parenteral administration is restricted due to its limited aqueous solubility. Liposomal carriers, well known for their potential in topical drug delivery, have been chosen to help transport tamoxifen molecules in the skin layers. These vesicles are also expected to provide lipid enriched hydrating conditions to help retain the drug molecules within the dermal layers, at or near to the site of action. With this objective, tamoxifen loaded liposomal systems have been prepared and their topical performance has been compared with non-liposomal systems containing tamoxifen. Method: Multilamellar liposomes of tamoxifen were prepared by thin film hydration method. Various formulation (viz. lipid composition, drug-lipid ratio, amount and type of sur- face charge imparting agent etc.) and process parame- ters (hydration temperature, hydration time etc.) were studied to obtain liposomes with desired attributes. Prepared liposomes were characterized for morpholog- ical and micromeritic attributes, employing Malvern mastersizer and optical microscopy. Stability of the liposomes in terms of their drug holding capacity was assessed for a period of 5 weeks, on storage under defined conditions. Liposomal formulations of tamox- ifen were evaluated for in-vitro skin permeation, using mice skin. The results thus obtained were compared with that of aqueous solution and Carbopol gel, con- taining tamoxifen in equal amounts. Results: Opti- mized process and formulation parameters resulted in multilameller, homogenous population of liposomes in the size range of 1 to 13µm (mean vesicle diameter 5.3 µm), exhibiting normal size distribution. Maximum loading of tamoxifen was noted to be 57.5% (38.3 µg of drug per mg of lipids), for liposomes composed of hydrogenated phosphatidylcholine and cholesterol, employing 66.6 µg drug per mg of lipids during prepa- ration. Incorporation of dicetylphosphate or steary- lamine as charge imparting agent did not influence the vesicular entrapment of TAM in a favorable manner. Amongst different storage conditions, the liposomes stored at 2 to 8°C were found to be most stable, with only 5% drug loss over the storage period of 5 weeks. Significantly higher skin permeation of tamoxifen from liposomal formulations (flux values 63.67 µg/ cm 2 /h and 59.87 µg/cm 2 /h for liposomal suspension and liposomal gel) has been achieved, as compared to solution (21.65 µg/cm 2 /h) and Carbopol gel (24.55 µg/ cm 2 /h) containing tamoxifen. Higher magnitude of tamoxifen retention in the skin layers was noted with liposomal formulations vis-a-vis non-liposomal formu- lations of the drug. Conclusion: Tamoxifen molecules could be successfully entrapped in the liposomes with reasonable drug-loading and desired vesicle specific characters. Higher rate of drug transfer across the skin with liposomal formulations of tamoxifen, suggests that the drug in its lipo-solubilised state might have found facilitated entry into the tough barrier consist- ing of stratum corneum. The phospholipid enriched amphiphillic nature of the vesicles can be held respon- sible for modifying the properties of the keratinised layer. Integration of phospholipid molecules with the skin lipids might have served further, to help retain the drug molecules within the skin, thus leading to pro- longed presence of drug molecules at the receptor site. These findings have been seen to support the improved and localized drug action in the skin, thus providing a better option to deal with skin-cited problems.

Brain abscesses: etiologic categorization with in vivo proton MR spectroscopy.

Abstract: PURPOSE: To compare the metabolite patterns observed at in vivo proton magnetic resonance (MR) spectroscopy of brain abscesses in patients for whom bacteriologic information was obtained from cultures and to categorize the MR spectral patterns with respect to the underlying etiologic agents. MATERIALS AND METHODS: MR imaging and in vivo single-voxel proton MR spectroscopic data obtained from 75 patients with brain abscesses were retrospectively analyzed. Ex vivo spectroscopic experiments with the pus from 45 of these patients also were performed, and the data were further categorized on the basis of bacteriologic information. Quantification of various metabolites and metabolite ratios and statistical analyses of lactate and lactate/amino acid (AA) ratio levels were performed by using one-way analysis of variance. RESULTS: On the basis of in vivo proton MR spectroscopic and bacteriologic analysis findings, data were classified into three categories: Group 1 data showed resonances of lactate, AAs, and aceta...

Synthesis and spectral studies on mononuclear complexes of chromium(III) and manganese(II) with 12-membered tetradentate N 2 O 2 , N 2 S 2 and N 4 donor macrocyclic ligands

Abstract: Complexes of CrIII and MnII of general formula [Cr(L)X2] X and [Mn(L)X2] respectively were prepared from N2O2, N2S2 and N4 donor macrocyclic ligands. The complexes have been characterized by elemental analysis, molar conductance measurements, spectral methods (i.r, mass, 1H-n.m.r, electronic spectra and e.p.r.) and magnetic measurements. The macrocyclic ligands have three different donating atom cavities, one with two unsaturated nitrogens and the other two have saturated nitrogen, oxygen and sulphur atoms. The effect of different donor atoms on the spectra and ligand field parameters is discussed. All the complexes show magnetic moments corresponding to a high-spin configuration. On the basis of spectral studies a six coordinated octahedral geometry may be assigned to these complexes.

Cytogenetic markers, DNA single-strand breaks, urinary metabolites, and DNA repair rates in styrene-exposed lamination workers.

Abstract: The effect of occupational exposure to styrene on frequencies of chromosomal aberrations and binucleated cells with micronuclei and on single-strand break levels in peripheral blood lymphocytes was studied in 86 reinforced plastic workers and 42 control individuals (including 16 maintenance workers with intermittent, low-dose exposure). In these individuals, the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines were investigated. We assessed the exposure by measuring the concentrations of styrene in air and in blood and of mandelic acid, phenylglyoxylic acid, 4-vinyl phenol conjugates and regioisomeric phenyl hydroxyethyl mercapturic acids in urine. All these parameters correlated with one another. No clear relationship was found between the styrene exposure and the frequencies of chromosomal aberrations. Binucleated cells with micronuclei were moderately related to the parameters of styrene exposure. We found a negative correlation between all exposure parameters and single-strand breaks. The positive correlation between exposure parameters and DNA repair rates suggests that particular DNA repair pathways may be induced by styrene exposure.

Markers of individual susceptibility and DNA repair rate in workers exposed to xenobiotics in a tire plant

Abstract: Workers employed in tire plants are exposed to a variety of xenobiotics, such as 1,3-butadiene (BD), soots containing polycyclic aromatic hydrocarbons, and other organic chemicals (e.g., styrene). In the present study, we investigated markers of genotoxicity [chromosomal aberrations (CAs) and single-strand breaks (SSBs)] in a cohort of 110 tire plant workers engaged in jobs with different levels of xenobiotic exposure in relation to various polymorphisms in genes coding for biotransformation enzymes (CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, and GSTT1) and in genes involved in DNA repair (XPD exon 23, XPG exon 15, XPC exon 15, XRCC1 exon 10, and XRCC3 exon 7). In addition, the expression of CYP2E1, a gene playing a key role in BD metabolism, was determined by real-time PCR in peripheral blood lymphocytes, and the capacity of lymphocytes to repair gamma-ray-induced SSBs and to convert 8-oxoguanine in HeLa cell DNA into SSBs was assessed using in vitro assays. No positive associations were detected between the CA frequency or SSB induction and levels of workplace exposure; however, a nonsignificant twofold higher irradiation-specific DNA repair rate was found among highly exposed workers. In evaluations conducted with the markers of individual susceptibility, workers with low-EPHX1-activity genotypes exhibited a significantly higher CA frequency as compared to those with medium and high-EPHX1-activity genotypes (P = 0.050). CA frequencies were significantly lower in individuals homozygous for the XPD exon 23 variant allele in comparison to those with the wild-type CC genotype (P = 0.003). Interestingly, CAs were higher in individuals with higher CYP2E1 expression levels, but the association was nonsignificant (P = 0.097). The results from this study suggest the importance of evaluating markers of individual susceptibility, since they may modulate genotoxic effects induced by occupational exposure to xenobiotics.

Biliary microlithiasis in patients with idiopathic acute pancreatitis and unexplained biliary pain: response to therapy.

Abstract: Background and Aims: Microlithiasis has been suspected to cause acute pancreatitis and biliary pain. We studied the frequency of microlithiasis and response to treatment in recurrent idiopathic acute pancreatitis (RIAP) and unexplained biliary pain. Methods: Gallbladder bile was examined microscopically for cholesterol monohydrate crystals (CMC) and calcium bilirubinate granules (CBG) in patients with RAIP (n = 24; mean age 36 years, range 18–56 years; 14 men), unexplained biliary pain (n = 12; mean age 32 years, range 22–55 years; six men), gallstones (n = 22; mean age 40 years, range 30–58 years; 12 men) and patients without clinical or imaging evidence of gallstone disease (n = 12; mean age 32 years, range 14–54 years; six men). The presence of a single CMC or >25 CBG/slide was considered abnormal. Results: Bile microscopy was abnormal in 75% patients with RAIP (18/24; CMC in 10, CBG in six, CMC and CBG in two), 83.3% patients with unexplained biliary pain (10/12; CMC in seven, CBG in one, CMC and CBG in two) and 95.4% patients with gallstones (21/22; CMC in 12, CBG in one, CMC and CBG in eight). None of the controls without gallstone disease had CMC while three patients had low counts of CBG. Twenty-eight patients with RAIP and biliary pain having microlithiasis agreed to be treated with cholecystectomy (n = 2), endoscopic sphincterotomy (n = 21) or ursodeoxycholic acid (UDCA; n = 5). The 23 patients treated with cholecystectomy or sphincterotomy remained asymptomatic during follow up (mean 23 months, range 6–48 months). Four of five patients treated with UDCA remained asymptomatic for a follow-up period of 9, 10, 11 and 18 months, respectively. One patient who had refused cholecystectomy or sphincterotomy continued to experience pain at the same frequency as before during a follow-up period of 12 months. One patient, who was asymptomatic on UDCA for 9 months, agreed to undergo sphincterotomy and remained asymptomatic over a follow-up period of 14 months. Conclusions: Microlithiasis is a common cause for idiopathic acute pancreatitis and unexplained biliary pain. Lasting relief is obtained in most patients after treatment with UDCA, cholecystectomy or sphincterotomy.

Method and apparatus for placing sensors using 3D models

Abstract: Method and apparatus for dynamically placing sensors in a 3D model (101) is provided. Specifically, in one embodiment, the method selects a 3D model (101) and a sensor for placement into the 3D model (101). The method renders the sensor and the 3D model (101) in accordance with sensor parameters associated with the sensor and parameters desired by a user. In addition, the method determines whether an occlusion to the sensor is present.

Prevalence of anemia in adult rural population of north India.

Abstract: Objectives : To find the prevalence of anemia in adult males and non-pregnant females of rural north Indian population. Methods : During an epidemiological survey on hypertension in rural population of north India (n=2559), a random sample of 215 individuals underwent blood investigations including hemoglobin estimation. Results : The overall prevalence of anemia in 16-70 years of age group was 47.9% (n=215), being 50% (n=136) among females and 44.3% (n=78) among males. Low socioeconomic status, illiteracy and lower body mass index, were associated with higher prevalence of anemia. Conclusions : The finding of higher prevalence of anemia in adult males need further investigation and corroboration in other studies. The intervention for anemia should be directed on the community as a whole. ©

Diffuse bone marrow accumulation of FDG in a patient with chronic myeloid leukemia mimics hematopoietic cytokine-mediated FDG uptake on positron emission tomography.

Abstract: :It is well known that bone marrow stimulants such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause diffuse and increased FDG accumulation in bone marrow on positron emission tomography (PET) imaging. Therefore, diffuse

Method and apparatus for providing a scalable multi-camera distributed video processing and visualization surveillance system

Abstract: A scalable architecture for providing real-time multi-camera distributed video processing and visualization. An exemplary system comprises at least one video capture and storage system for capturing and storing a plurality of input videos, at least one vision based alarm system for detecting and reporting alarm situations or events, and at least one video rendering system (e.g., a video flashlight system) for displaying an alarm situation in a context that speeds up comprehension and response. One advantage of the present architecture is that these systems are all scalable, such that additional sensors (e.g., cameras, motion sensors, infrared sensors, chemical sensors, biological sensors, temperature sensors and like) can be added in large numbers without overwhelming the ability of security forces to comprehend the alarm situation.

Molecular heterogeneity among north Indian isolates of Group A Streptococcus.

Abstract: V . S A G A R , D . K . B A K S H I , S . N A N D I , N . K . G A N G U L Y , R . K U M A R A N D A . C H A K R A B O R T I . 2004. Aim: To monitor molecular heterogeneity among the clinical isolates of group A Streptococcus (GAS) from north India by Vir and emm typing. Methods and Results: GAS isolates, 31 from pharyngitis and nine from rheumatic fever (RF)/rheumatic heart disease (RHD) patients were differentiated into 16 Vir types (VT). These isolates were further discriminated into 23 emm types. Most of emm types were Vir type specific, except few (7AE5%), which revealed different Vir types within same emm type. The most prevalent emm type found was emm 49 (15%) followed by 7AE5% of emm 69, emm 71 and emm 75 which were different from emm type distribution reported from south India. Conclusions: Analysis of data revealed 40% heterogeneity by Vir typing and 57AE5% by emm typing among GAS isolates which is significant in view of small number of isolates studied. Significance of Impact of the Study: The molecular study for the first time demonstrates different emm types prevalent and circulating in northern region of India and such data may help in selection of types for vaccine development.

Induction of Defense Related Enzymes and Pathogenesis Related Proteins in Pseudomonas fluorescens-Treated Chickpea in Response to Infection by Fusarium oxysporum f. sp. ciceri

Abstract: Pseudomonas fluorescens 1–94 induced systemic resistance in chickpea against Fusarium wilt of chickpea caused by Fusarium oxysporum f. sp. ciceri by the synthesis and accumulation of phenolic compo...

Diffuse FDG uptake in the lungs in aspiration pneumonia on positron emission tomographic imaging

Abstract: The radiologic manifestations of aspiration pneumonia are protean and have been well-described. FDG PET has been used successfully in the evaluation of cancer. However, FDG is not a tumor-specific radiotracer. The authors present a case of aspiration pneumonia that demonstrated extensive and

Dielectric/metal sidewall diffusion barrier for Cu/porous ultralow-k interconnect technology

Abstract: With the acknowledged insufficiency of traditional Ta or TaN barriers, deposited by physical vapor deposition (PVD), in the Cu/porous ultralow-k intermetal dielectric integration, an amorphous hydrogenated SiC (a-SiC:H)/Ta bilayer sidewall diffusion barrier has been fabricated using 0.13 μm Cu/porous ultralow-k [Porous-SiLK (Proprietary product from Dow Chemical Corporation, USA), k∼2.2] single damascene process. The electrical tests show that the line-to-line leakage current and the electrical breakdown field (EBD) of samples with this a-SiC:H/Ta dielectric/metal bilayer structure are significantly improved compared to the conventional PVD multi-stacked Ta(N) sidewall barrier. This improvement is mostly due to surface roughness modification after the deposition of a-SiC:H film, which, in addition to being a good barrier to Cu diffusion, can effectively “seal” the weak points on the surface of porous low-k material that are responsible for the sidewall barrier failure.

Fabrication and characterization of polyvinyl-alcohol-based thin-film optical waveguides

Abstract: Polyvinyl alcohol (PVA)-based thin film optical waveguides are fabricated and characterized. Various waveguide parameters, namely, refractive index, propagation losses and depth, birefringence, and polarization conversion properties of dip-coated thin film optical waveguides are evaluated. The effective refractive index of PVA film is found to be between 1.506 and 1.531 for various concentrations. The propagation losses are 2.35 to 0.30 dB/cm for various thicknesses. The propagation loss reduces when the thickness of the film is increased. The low propagation losses, birefringence insensitivity, high transmission in the aged and annealed waveguides, control over film refractive index, the good adhesiveness of the film and good compatibility with substrate show that PVA-based waveguides are promising candidates for the optoelectronic field.

Epilepsy with focal cerebral calcification: role of magnetization transfer MR imaging.

Abstract: BACKGROUND: Some patients with focal cerebral calcification (FCC) have no seizure or a benign course of epilepsy, whilst others with a similar lesion have uncontrolled epilepsy. AIMS: To look for perilesional hyperintensity, presumed to be indicative of gliosis, around FCC on magnetization transfer (MT) MRI and to correlate seizure outcome with its presence. SETTING AND DESIGN: Case control study. MATERIAL AND METHODS: Fifty-one patients with epilepsy and 30 controls with single calcified cerebral lesion on CT were studied. Clinical and treatment details were noted. EEG and T1, T2, MT and contrast enhanced MRI were done. STATISTICAL ANALYSIS USED: Student's t test. RESULTS: On MT MRI, perilesional gliosis was seen around the focal calcified lesion in 17 (33.3%) patients. None of the controls had perilesional gliosis. The mean monthly seizure frequency was significantly higher in the 17 patients having perilesional gliosis (2.63+1.15) as compared to the 34 patients without it (0.59+0.63; P= 0.0014). Perilesional gliosis was seen in 8 out of 11 (72.7%) patients who were on 2 AEDs and in all 5 (100%) patients who were on 3 or more AEDs. It was present only in 4 (11.4%) out of 35 patients who were on one AED. CONCLUSION: Gliosis around a cerebral calcified lesion as seen on T1 weighted MT MRI indicates poor seizure control.

Association of outdoor air pollution with chronic respiratory morbidity in an industrial town in northern India.

Abstract: A cross-sectional study was performed in one industrial (study) and one non-industrial (reference) town in Punjab State, northern India. Ambient air quality samples were collected and analyzed each week for 2 yr. Subjects were 3,603 individuals <15 yr old who were interviewed and whose lung functions were measured spirometrically. Their biomarkers were categorized in terms of obstructive or restrictive defects. Levels of total suspended particulates, nitrogen oxides, sulfur oxides, carbon monoxide, and ozone were significantly higher in the study town than in the reference town. The prevalence of chronic respiratory symptoms (cough, phlegm, breathlessness, or wheezing) was 27.9 and 20.3% in the study and reference towns, respectively (p < 0.05). That of obstructive ventilatory defect was 24.9 and 11.8% (p < 0.05), respectively. Logistic regression analysis showed that residence in the study town was independently associated with chronic respiratory symptoms (odds ratio [OR] = 1.5; 95% confidence ...

Post-marketing surveillance of buprenorphine.

Abstract: Purpose This study was undertaken to evaluate the adverse consequences of recently introduced higher strength (0.4 and 2.0 mg per tablet) buprenorphine in Indian market. Buprenorphine, a partial opiate agonist and antagonist, is an emerging alternative to methadone as an agent for long-term treatment of opiate dependence. Methods The current investigation was conducted through a multi-centric post-marketing surveillance (PMS)study using a structured performa from patients receiving buprenorphine as routine therapy from de-addiction centres. Evaluation included subjective and objective assessments and recording of adverse events. Results Of the 5551 observations from ten centres, common subjective symptoms were generalised weakness (48.9%), sense of high (euphoria) (44.5%), muscle aches (39.5%) and relief from pain (37.2%). About 5% observations recorded systolic hypertension. Among 55 subjects where laboratory tests were conducted, 12 showed raised levels of AST ad 9 had elevated ALT. Twelve adverse events reported included seizure, epistaxis, panic attacks, constipation and dyspnoea. Significant relation was seen between duration of use and time since last dose, and total number of subjective symptoms reported. Conclusions Majority of the adverse effects could be understood as either effects related to intoxication or withdrawal from agonists. Copyright © 2004 John Wiley & Sons, Ltd.

Viable Agroforestry Models and their Economics in Yamunanagar District of Haryana and Haridwar District of Uttaranchal

Abstract: In India, natural forests are being conserved primarily for the environmental benefits. Serious efforts are also being done to plant large number of trees outside forest under social forestry programs to increase the tree cover and fulfill demand of various forest produce required by the people and forest based industries. Agricultural fields are one of the potential areas, where large scale planting of trees can be taken up along with the agricultural crops. Agroforestry models adopted by the farmers in Haryana and Uttaranchal states of India are highly lucrative, therefore, attracting farmers in a big way. NPV for different models on six years rotation varies from Rs. 26,626 to Rs. 72,705 ha -1 yr -1 whereas Benefit-Cost ratio and Internal Rate of Return vary from 2.35 to 3.73 and 94% to 389% respectively. Agroforestry has not only uplifted socioeconomic status of the farmers but also contributed towards overall development of the region.

Multiple document file tab channel

Abstract: Disclosed is a unique system and method that facilitates more efficient navigation and viewing of multiple open objects such as files, documents, pages, sheets, etc. The systems and methods make use of a navigation bar or tab channel. The tab channel can comprise a shifting region and optionally, a static region—the static region being positioned to the left of the shifting region. As files are opened, for example, the file name is appended to the left side of the tab channel. When another file is opened, it is appended to the left side of the tab channel, thus pushing the first file to the right. This proceeds so that the most relevant files are viewable in the tab channel. An on-screen menu is also maintained that includes all open files in an ordered manner. Thus, a file name no longer on the tab channel can be accessed from the menu—and then reinserted into the tab channel if viewing of its contents is desired.

P21-Activated Kinase 1: An Emerging Therapeutic Target

Abstract: The impressive amount of basic research data available on Pak1, the possibility that Pak1 is amplified or overexpressed in tumors and Pak1 ability to modulate motility and cell survival functions have generated considerable anticipation in the field of cancer research that strategies targeting Pak1 may lead to the design of target specific drugs. The identification of unique interacting proteins and the availability of the crystal structure of Pak1 provide an ideal environment to develop novel small molecules or peptides to interfere with Pak1 functions. To date no specific drug targeting Pak1 activity has been developed, althrough several companies are currently attempting to produce such drugs that inhibit Pak1 kinase activity. Similarly, althrough siRNA methods of blocking Pak1 expression is shown to work, the clinical application is still in the very early phases of development. Recent data have suggested that blocking of Pak1 upstream activators may also be benefecial by indirectly blocking Pak activity. Growth factor-induced activation of Pak1 can be inhibited by the PDGF-R-specific inhibitor AG1478 or by the EGF receptor specific inhibitors (Iressa), monoclonal antibody 225 or the HER2 blocker trastuzumab (Herceptin). Therefore these compounds may be clinically useful in regulating Pak activity in growth factor-regulated tumors [50]. Small peptide molecules blocking Pak1 interactions with its substrates could also be used to inhibit Pak1 functions. The feasibility of this approach was demonstrated using a small peptide that blocked the adaptor protein NCK from binding to Pak1 and thus interfered with angiogenesis [41], Because Pak1 promotes cell survival, and its expression is deregulated in tumors, inhibition of its functions could induce apoptosis in cancer cells. The difference in the levels of expression of the Pak1 between normal and cancer cells could provide a therapeutic opportunity to use drugs to selectively inhibit cancer cells. In addition, drugs causing Pak1 inhibition in combination with other commonly used chemotherapy drugs, may have synergistic effects. The ability of Pak1 to phosphorylate estrogen receptor [54] and induce expression of cyclin D1 [38], both of which activities are widely deregulated in breast cancer, suggests that pak1 inhibitors may be useful in managing or at least delaying hormonal resistance seen in breast cancer. Becasue Pak1 plays an important role in modulating cytoskeleton and because many pathogens use cytoskeleton to enter cells and translocate there, Pak inhibitors may have a therapeutic role in interfering with these pathogenic viral infections. Emerging studies unraveling the novel roles of Pak1 signaling and the possible clinical potential of targeting Pak1 will continue to stimulate efforts to develop Pak1 inhibitors or blockers.

Response of Generalized Thermoelastic Half-space with Voids to Mechanical and Thermal sources

Abstract: The dynamic response of a homogeneous, isotropic, generalized thermoelastic half-space with voids subjected to normal, tangential force and thermal source is investigated. The displacements, stresses, temperature distribution and change in volume fraction field so obtained in the physical domain are computed numerically and illustrated graphically. The numerical results of these quantities for magnesium crystal-like material are illustrated to depict the response of various sources in the Lord–Shulman (L–S) theory and Green–Lindsay (G–L) theory for an insulated boundary and temperature gradient boundary. Some particular cases have been deduced.