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Background and Objectives: Overactive bladder and its hallmark symptom, urgency, are thought to be multifactorial in pathogenesis. Smoking is a particularly important risk factor to understand because it is modifiable; studies evaluating an association between smoking and urgency have been inconclusive. We therefore sought to rigorously assess the relationship between smoking and urgency in terms of both a temporal and quantitative pack year history of smoking while controlling for other possible confounding factors. Methods: Community‐based adult women were recruited using the ResearchMatch website to participate in an online survey of bladder health which included questions to assess urgency symptoms, medical comorbidities, and detailed smoking history. Smoking history was studied as the independent variable in three different formulations: smoking status (never vs. former vs. current), continuous pack year history, and categorical pack year history. The outcomes studied included urgency (any urgency in the past 7 days), moderate urgency (urgency at least half the time), and urgency urinary incontinence (UUI). Chi‐square tests were performed to detect associations between smoking and these outcomes, and multivariate regression was then performed to control for possible confounders and to help determine the comparative influence of temporality versus quantity of smoking history. Results: In 1720 women who completed the questionnaire, current smoking status was associated with a 23% increase in the risk of experiencing urgency (RR 1.23) and a 78% increase in the risk of experiencing moderate urgency (RR 1.78) relative to never smokers. The risk of experiencing UUI was 40% higher (RR 1.40). Lifetime pack year history was also significantly associated with urgency outcomes, although only in smokers/former smokers who had a 20+ pack year history (RR 1.15, 1.60, and 1.25 for urgency, moderate urgency, and UUI, respectively). The presence of former smoking history was not significantly associated with urgency outcomes, even when controlling for cumulative pack years. Conclusions: This analysis of a large cross‐sectional database of women suggests a strong, consistent link between current smoking status and urinary urgency and UUI. By contrast, no increased risk of urgency was attributed to former smoking status. Analysis of pack year history suggests a dose–response relationship wherein ≥ 20 pack years was significantly associated with a higher risk of all urgency outcomes. In models controlling for pack year history, the association of current smoking with urgency remained significant and former smoking remained nonsignificant. Taken together, this supports greater attention being given to the contribution of current smoking to urgency symptoms, and to the need for further longitudinal work to determine if smoking cessation can be a strategy to treat urgency. [ABSTRACT FROM AUTHOR]

Despite significant progress in solution‐processing of 2D materials, it remains challenging to reliably print high‐performance semiconducting channels that can be efficiently modulated in a field‐effect transistor (FET). Herein, electrochemically exfoliated MoS2 nanosheets are inkjet‐printed into ultrathin semiconducting channels, resulting in high on/off current ratios up to 103. The reported printing strategy is reliable and general for thin film channel fabrication even in the presence of the ubiquitous coffee‐ring effect. Statistical modeling analysis on the printed pattern profiles suggests that a spaced parallel printing approach can overcome the coffee‐ring effect during inkjet printing, resulting in uniform 2D flake percolation networks. The uniformity of the printed features allows the MoS2 channel to be hundreds of micrometers long, which easily accommodates the typical inkjet printing resolution of tens of micrometers, thereby enabling fully printed FETs. As a proof of concept, FET water sensors are demonstrated using printed MoS2 as the FET channel, and printed graphene as the electrodes and the sensing area. After functionalization of the sensing area, the printed water sensor shows a selective response to Pb2+ in water down to 2 ppb. This work paves the way for additive nanomanufacturing of FET‐based sensors and related devices using 2D nanomaterials. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. An increased risk for HEV infection has been reported in organ‐transplant recipients, mainly from Europe. Prospective data on HEV prevalence in the United States (U.S.) organ transplant population are limited. To determine the prevalence and factors associated with HEV infection among solid organ transplant‐recipients, we conducted a prospective, cross‐sectional, multicentre study among transplant‐recipients and age‐ and organ‐matched waitlist patients. Participants answered a risk‐exposure questionnaire and were tested for HEV‐RNA (in‐house PCR), HEV‐IgG, and IgM (ELISA, Wantai). Among 456 participants, 224 were transplant‐recipients, and 232 were waitlist patients. The mean age was 58 years, 35% female, and 74% White. HEV seroprevalence of the entire cohort was 20.2% and associated with older age (p < 0.0001) and organ transplantation (p = 0.02). The HEV seropositivity was significantly higher among transplant‐recipients compared with waitlist patients (24% vs. 16.4%, p = 0.042). Among transplant recipients, relative‐risk of being HEV seropositive increased with older age (RR = 3.4 [1.07–10.74] in patients >70 years compared with ≤50 years, p = 0.037); history of graft hepatitis (2.2 [1.27–3.72], p = 0.005); calcineurin inhibitor use (RR = 1.9 [1.03–3.34], p = 0.02); and kidney transplantation (2.4 [1.15–5.16], p = 0.02). HEV‐RNA, genotype 3 was detected in only two patients (0.4%), both transplant‐recipients. HEV seroprevalence was higher among transplant‐recipients than waitlist patients. HEV should be considered in transplant‐recipients presenting with graft hepatitis. Detection of HEV‐RNA was rare, suggesting that progression to chronic HEV infection is uncommon in transplant‐recipients in the U.S. [ABSTRACT FROM AUTHOR]

Background: Alcohol‐associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post‐LT opioid use (p‐LTOU) compared to non‐ALD patients. Methods: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post‐LT (>90 days), death within 90 days post‐LT, and re‐transplants were excluded. Results: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non‐ALD patients (P <.05). There was no difference in pre‐LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non‐ALD patients. Pre‐LT opioid use (OR = 11.7, P <.001), ALD (OR = 2.5, P =.01), and MELD score (OR =.95, P =.02) independently predicted 90‐day p‐LTOU. Conclusions: ALD, pre‐LT opioid use, and MELD score independently predict p‐LTOU. Special attention should be paid to identify post‐LT prolonged opioid use in ALD patients. [ABSTRACT FROM AUTHOR]

Memristive systems present a low‐power alternative to silicon‐based electronics for neuromorphic and in‐memory computation. 2D materials have been increasingly explored for memristive applications due to their novel biomimetic functions, ultrathin geometry for ultimate scaling limits, and potential for fabricating large‐area, flexible, and printed neuromorphic devices. While the switching mechanism in memristors based on single 2D nanosheets is similar to conventional oxide memristors, the switching mechanism in nanosheet composite films is complicated by the interplay of multiple physical processes and the inaccessibility of the active area in a two‐terminal vertical geometry. Here, the authors report thermally activated memristors fabricated from percolating networks of diverse solution‐processed 2D semiconductors including MoS2, ReS2, WS2, and InSe. The mechanisms underlying threshold switching and negative differential resistance are elucidated by designing large‐area lateral memristors that allow the direct observation of filament and dendrite formation using in situ spatially resolved optical, chemical, and thermal analyses. The high switching ratios (up to 103) that are achieved at low fields (≈4 kV cm−1) are explained by thermally assisted electrical discharge that preferentially occurs at the sharp edges of 2D nanosheets. Overall, this work establishes percolating networks of solution‐processed 2D semiconductors as a platform for neuromorphic architectures. [ABSTRACT FROM AUTHOR]

A mathematical model of a membrane with a thin, oriented, and selective MFI layer, which also includes contributions from defects, pore blockages, support layer, and external mass transfer, was formulated based on the Maxwell‐Stefan equations. It was validated using reported (Kim et al., Angew Chemie Int Ed, 2018, 57:480–485; Jeon et al., Nature, 2017, 543:690–694) para/ortho‐xylene separation data from five MFI membranes. The diffusivities of the xylenes were considered to be the same for all membranes, while the thickness and the density of defects and pore blockage were treated as unique properties of each membrane, and their contributions were estimated by fitting the model to the corresponding separation data. The effects of these properties and the role of permeate pressure on the separation performance were subsequently analyzed. The proposed modeling, parameter estimation, and analysis framework allow one to quantitatively interpret the variation of separation performance, to understand separation bottlenecks, and to provide guidance for designing membranes with desired performance. [ABSTRACT FROM AUTHOR]

Background: Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools. We hypothesized that saliva ncRNA levels would demonstrate comparable accuracy for identifyingmTBI asmeasures of symptom burden, neurocognition, and balance. Methods: This case-control study involved 538 individuals. Participants included 251 individuals with mTBI, enrolled ≤14 days postinjury, from 11 clinical sites. Saliva samples (n = 679) were collected at five time points (≤3, 4-7, 8-14, 15-30, and 31-60 days post-mTBI). Levels of ncRNAs (microRNAs, small nucleolar RNAs, and piwi-interacting RNAs) were quantified within each sample using RNA sequencing. The first sample from eachmTBI participant was compared to saliva samples from 287 controls. Samples were divided into testing (n = 430; mTBI = 201 and control = 239) and training sets (n = 108; mTBI = 50 and control = 58). The test set was used to identify ncRNA diagnostic candidates and create a diagnostic model. Model accuracy was assessed in the naïve test set. Results: A model utilizing seven ncRNA ratios, along with participant age and chronic headache status, differentiated mTBI and control participants with a cross-validated area under the curve (AUC) of .857 in the training set (95% CI, .816-.903) and .823 in the naïve test set. In a subset of participants (n = 321; mTBI = 176 and control = 145) assessed for symptom burden (Post-Concussion Symptom Scale), as well as neurocognition and balance (ClearEdge System), these clinical measures yielded cross-validated AUC of .835 (95% CI, .782-.880) and .853 (95% CI, .803-.899), respectively. A model employing symptom burden and four neurocognitive measures identified mTBI participants with similar AUC (.888; CI, .845-.925) as symptom burden and four ncRNAs (.932; 95% CI, .890-.965). Conclusion: Salivary ncRNA levels represent a noninvasive, biologic measure that can aid objective, accurate diagnosis of mTBI. [ABSTRACT FROM AUTHOR]

A low-temperature synthesis coupled with mild activation produces zeolite films exhibiting low dielectric constant (low- k) matching the theoretically predicted and experimentally measured values for single crystals. This synthesis and activation method allows for the fabrication of a device consisting of a b-oriented film of the pure-silica zeolite MFI (silicalite-1) supported on a gold-coated silicon wafer. The zeolite seeds are assembled by a manual assembly process and subjected to optimized secondary growth conditions that do not cause corrosion of the gold underlayer, while strongly promoting in-plane growth. The traditional calcination process is replaced with a nonthermal photochemical activation to ensure preservation of an intact gold layer. The dielectric constant ( k), obtained through measurement of electrical capacitance in a metal-insulator-metal configuration, highlights the ultralow k ≈ 1.7 of the synthetized films, which is among the lowest values reported for an MFI film. There is large improvement in elastic modulus of the film ( E ≈ 54 GPa) over previous reports, potentially allowing for integration into silicon wafer processing technology. [ABSTRACT FROM AUTHOR]

Nanoscale crystal growth control is crucial for tailoring two-dimensional (2D) zeolites (crystallites with thickness less than two unit cells) and thicker zeolite nanosheets for applications in separation membranes and as hierarchical catalysts. However, methods to control zeolite crystal growth with nanometer precision are still in their infancy. Herein, we report solution-based growth conditions leading to anisotropic epitaxial growth of 2D zeolites with rates as low as few nanometers per day. Contributions from misoriented surface nucleation and rotational intergrowths are eliminated. Growth monitoring at the single-unit-cell level reveals novel nanoscale crystal-growth phenomena associated with the lateral size and surface curvature of 2D zeolites. [ABSTRACT FROM AUTHOR]

This study presents a wind-solar photovoltaic based standalone hybrid energy system (HES) for an un-electrified village for central region of India - Madhya Pradesh. The inputs for the designing of HES are wind speed, solar radiation, temperature and the load demand which are variable with respect to time. In this study, hourly values of meteorological data and hourly load demand are considered over a year. For sizing and performance analysis of this standalone HES, ant colony optimisation technique has been used. The performance analysis of the system is done for the various parameters such as total cost of the system, power generated by various sources, state of charge of battery, contribution of various sources, continuity of supply to the load demand and unmet load. The obtained optimal configuration of the proposed HES is found to provide minimal energy cost with excellent performance and reduced unmet load. [ABSTRACT FROM AUTHOR]

Two-dimensional zeolite nanosheets that do not contain any organic structure-directing agents were prepared from a multilamellar MFI (ML-MFI) zeolite. ML-MFI was first exfoliated by melt compounding and then detemplated by treatment with a mixture of H2SO4 and H2O2 (piranha solution). The obtained OSDA-free MFI nanosheets disperse well in water and can be used for coating applications. Deposits made on porous polybenzimidazole (PBI) supports by simple filtration of these suspensions exhibit an n-butane/isobutane selectivity of 5.4, with an n-butane permeance of 3.5×10−7 mol m−2 s−1 Pa−1 (ca. 1000 GPU). [ABSTRACT FROM AUTHOR]

In the last few decades, considerable research has focused on the effects of trait interactions on job performance, but only a few studies have examined trait interaction effects on career commitment. This study investigates the interactive effects of conscientiousness and agreeableness on career commitment and its 3 facets of career identity, career resilience, and career planning in a sample of 254 employees in North India. Results suggest a partial interaction effect of conscientiousness and agreeableness on career commitment. Trait interactions were seen as significant predictors of career resilience in the Indian context. The authors discuss implications for research, theory, and practice. [ABSTRACT FROM AUTHOR]

Stable suspensions of zeolite nanosheets (3 nm thick MFI layers) were prepared in ethanol following acid treatment, which partially removed the associated organic structure-directing agent. Nanosheets from these suspensions could then be dispersed at the air-water interface and transferred to silicon wafers using Langmuir-Schaefer deposition. Using layer-by-layer deposition, control on coating thickness was demonstrated. In-plane X-ray diffraction (XRD) revealed that the deposited nanosheets contract upon calcination similar to bulk MFI crystals. Different methods for secondary growth resulted in preferentially oriented thin films of MFI, which had sub-12-nm thickness in certain cases. Upon calcination, there was no contraction detectable by in-plane XRD, indicating well-intergrown MFI films that are strongly attached to the substrate. [ABSTRACT FROM AUTHOR]

Background & Aims The long-term clinical outcomes in initial survivors with acute liver failure ( ALF) are not well known. The aim of this study was to provide an overview of the 2-year clinical outcomes among initial survivors and liver transplant ( LT) recipients that were alive 3 weeks after enrolment in the Acute Liver Failure Study Group ( ALFSG). Methods Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed. Results Two-year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen ( APAP) spontaneous survivors ( SS) (89.5%) and 200 non- APAP SS (75.5%) ( P < 0.0001). The causes of death were similar in the three groups but the time to death was significantly longer in the LT recipients ( P < 0.0001). Independent predictors of 2-year mortality in the APAP group were a high serum phosphate level and patient age (c-statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non- APAP group (c-statistic = 0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c-statistic = 0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level ( P < 0.05). Conclusions Two-year outcomes in initial survivors of ALF are generally good but non- APAP patients have a significantly lower survival which may relate to pre-existing medical comorbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow-up from ongoing psychiatric and substance abuse issues. [ABSTRACT FROM AUTHOR]

This study proposes an optimal sizing methodology for a solar photovoltaic (SPV) system considering lifetime cost requirements. The aim of the design is optimal sizing of SPV system, which is obtained by calculating SPV system output power at certain location, taking into account the calculated optimal number of SPV modules, optimal number of inverters, optimal tilt angle, for a given dimension of land. This design is aimed for minimising the annual cost of grid‐integrated SPV system over its life or years of operation. The cost function takes into account the capital cost of installation, operation and maintenance, for each component of the system and the cost of selling energy to the grid. The sizing optimisation has been formulated as a non‐linear, multi‐variable problem and the particle swarm optimisation algorithm has been tested using MATLAB platform for a particular location to swot up the feasibility of integrated system. The monthly averaged daily and hourly solar radiation data for a given location is calculated using empirical relations on MATLAB platform. Other inputs are specifications of commercially available devices and meteorological details of location. [ABSTRACT FROM AUTHOR]

Studies of IL-28 B genotype in patients with hepatitis C virus ( HCV) genotype 2/3 infection have yielded conflicting results. The aim of this meta-analysis was to obtain a pooled odds ratio ( OR) of the impact of IL-28 B genotype on achieving sustained virologic response ( SVR) in patients with HCV genotype 2/3 infection treated with peg IFN and ribavirin. A meta-analysis with a random effects model was performed, and study heterogeneity and publication bias were assessed. Forty-three percent of the Caucasians (11 studies) and 86% of Asians (five studies) had the favourable IL-28 B genotype. In Caucasians, the pooled OR of SVR with the favourable IL-28 B genotype was 1.36 (95% CI: 0.98-1.88, P = 0.07) in all patients and 1.55 (95% CI: 1.10-2.18, P = 0.01) in patients treated with peg IFN and ribavirin for ≥24 weeks. In Asians, the pooled OR of SVR in patients with the favourable IL-28 B genotype was 1.99 (95% CI: 0.94-4.25, P = 0.07). The favourable IL-28 B genotype was also significantly associated with rapid virologic response ( RVR) in both groups ( Caucasians: OR: 1.82, 95% CI: 1.12-2.96, P = 0.02; Asians: 2.39, 95% CI: 1.39-4.11, P = 0.002), as well as the likelihood of an SVR in a subgroup of 350 Caucasian patients without an RVR ( OR: 3.29, 95% CI: 1.67-6.51, P = 0.001). The favourable IL-28 B genotype is a statistically significant predictor of SVR and RVR in Caucasian patients treated with peg IFN and ribavirin for 24 weeks. In contrast, the favourable IL-28 B genotype is associated with RVR, but not SVR in Asian HCV genotype 2 patients. [ABSTRACT FROM AUTHOR]

Par-4 is a pro-apoptotic, tumor suppressor protein that induces apoptosis selectively in cancer cells. Endoplasmic reticulum-stress and higher levels of protein kinase A in tumor cells confer the coveted feature of cancer selective response to extracellular and intracellular Par-4, respectively. Recent studies have shown that systemic Par-4 confers resistance to tumor growth in mice, and that tumor-resistance is transferable by bone-marrow transplantation. Moreover, recombinant Par-4 inhibits the growth of tumors in mice. As systemic Par-4 induces apoptosis via cell surface GRP78, strategies that promote GRP78 trafficking to the cell surface are expected sensitize cancer cells to circulating levels of Par-4. This review illustrates the domains and mechanisms by which Par-4 orchestrates the apoptotic process in both cell culture models and in physiological settings. J. Cell. Physiol. 227: 3715-3721, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Tobacco use significantly increases the risk of developing cancer. Moreover, there is growing evidence that tobacco use decreases survival in cancer patients. Nicotine, a systemically available component of tobacco, is associated with tumor promotion and decreased apoptosis in cell culture; however, the role of nicotine on response to radiotherapy (RT) or chemoradiotherapy (CRT) in vivo has not been evaluated. Our study evaluated the effects of nicotine administration on cancer cell survival in cell culture and mouse models. Nicotine increased survival in two cell lines following RT in vitro. Nicotine administration in mice during fractionated RT or CRT increased xenograft regrowth as compared to RT or CRT alone. Nicotine increased hypoxia-inducible factor 1-alpha (HIF-1α) expression in tumor xenografts without altering expression of carbonic-anhydrase, a clinical marker of tumor hypoxia. The effects of nicotine on HIF-1α expression were transient, returning to baseline levels within 2-3 days after nicotine removal. Further mechanistic studies indicated that inhibition of phosphoinositide-3-kinase (PI3K) prevented nicotine-mediated increases in HIF-1α expression as well as the prosurvival effects of nicotine on RT. These findings imply that during tobacco use, nicotine may function as a systemic agent through acute and reversible regulation of HIF-1α expression and a decreased therapeutic response. [ABSTRACT FROM AUTHOR]

Background Polymorphisms in the IL-28 B region are a strong predictor of sustained virologic response ( SVR) in individual studies of HCV genotype 1 patients receiving peginterferon (peg IFN) and ribavirin. Aim To obtain a pooled odds ratio ( OR) of SVR in patients of varying race with the favourable IL-28 B genotype compared to those with the unfavourable genotype. Methods A literature search was conducted using online databases and a review of conference abstracts. A random effects meta-analysis was performed and study heterogeneity and publication bias were assessed. Results There were 21 individual studies of HCV genotype 1 patients of varying ethnicity treated with peg IFN and ribavirin. The pooled prevalence of the favourable IL-28 B genotype varied by race (73% vs. 41% vs. 13% in 2612 Asians, 3110 Caucasians and 452 African-Americans, respectively, P < 0.001). However, the strength of association of the IL-28 B genotype with SVR was similar in all three racial groups (Caucasians: odds ratio ( OR) 3.88, 2.75-5.49, African-Americans: OR 4.63, 2.52-8.50 and Asians OR 5.66, 3.99-8.02, all P < 0.001). The IL-28 B genotype was also associated with SVR in 263 HIV/ HCV co-infected Caucasians ( OR 5.49, 3.02-9.96, P < 0.001). Study quality score and anti-viral treatment regimen did not impact the strength of the association in patient subgroups nor in the pooled population. Conclusions IL-28 B genotype is significantly associated with SVR in HCV genotype 1 patients of varying race, as well as in HIV co-infected patients, receiving peg IFN and ribavirin. IL-28 B testing in conjunction with other pre-treatment parameters may prove useful in counselling HCV patients. [ABSTRACT FROM AUTHOR]

The article uses the case of Basmati to identify a number of problems concerning geographical indications, including the interface with trademarks and the issue of genericity. Attempts to enter and free-ride on Basmati's premium rice market include the use of trademarks and (RiceTec's US) patent. Reviewing these, the article notes the subject matter of geographical indications can be implicated by other forms of intellectual property, such as patents. The case of Basmati is all the more problematic because of its transborder reality for which no provisions exist in the Agreement on the Trade-Related Aspect of Intellectual Property Rights (TRIPS). The article outlines and discusses various institutional models for a joint registration of Basmati between India and Pakistan as a possible solution for the TRIPS requirement of “home protection” (compare article 24.9). [ABSTRACT FROM AUTHOR]

An introduction to the periodical is presented in which the editor discusses an article on concerns about the misappropriation and threat to the survival of holders of cultural expressions by Kamperman Sanders, the conceptualization of collective action, and possible institutional solution for transborder geographical indications.

In implementing its patent-related obligations to the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), India opted for the optional additional transitional provisions in article 65.4. This, delayed the introduction of product patents in exempt technologies, notably pharmaceuticals, until 1 January 2005. Ostensibly, this gave India the opportunity to exploit changing circumstances to and emergent views on TRIPS implementation, in particular exploring new interpretations to residual flexibility in TRIPS and any continuing legal ambiguity in TRIPS obligations. Here, the Panel Report in Canada: Patent Protection of Pharmaceutical Products is pertinent in having exhibited rare reticence in stepping back from defining the principle of non-discrimination in article 27.1 of TRIPS. In maintaining legal ambiguity, this reticence also provides space for law-making and regulatory diversity. The article reviews the three amendments to India's Patent Act 1970 and finds mixed use of residual flexibility and some evidence of efforts to explore legal ambiguity. Thus, despite a favourable climate to TRIPS implementation and an active transnational access to medicine campaign, legislators in India have demonstrated a degree of caution. The article concludes that this caution is best explained in terms of deepening ambivalence concerning intellectual property within the government and the changing economic interests of sections of Indian pharma. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is a common disease with a poorly understood etiology, and the methionine–choline-deficient (MCD) diet is a nutritional model of NASH. Quantitative trait loci (QTL) analysis is a standard method for chromosomal mapping of polygenic disease traits. The purpose of this study is to administer mice an MCD diet in order to determine the strain-specific susceptibility for developing steatohepatitis, and to apply a computational methodology of QTL analysis to identify associated chromosomal susceptibility loci. Methods: Inbred mice were fed an MCD diet and alanine aminotransferase (ALT), hepatic triglycerides, liver weight, and weight loss were measured as phenotypic markers of steatohepatitis. Results: A/J mice developed the highest ALT and hepatic triglyceride levels. Using linear regression analysis, gene loci affecting serum ALT levels were identified on four chromosomes, and four loci that affect liver weight were also identified. In contrast, no QTLs for hepatic triglycerides or body weight were identified. Of note, loci for ALT and liver weight co-localized to proximal segments of chromosomes 2 and 15, in regions previously identified as QTLs for liver fibrosis. Conclusions: These data indicate that experimental steatohepatitis is a polygenic disease with genes determining ALT, liver weight, and liver fibrosis. [ABSTRACT FROM AUTHOR]

Prostate apoptosis response-4 (Par-4) is a unique pro-apoptotic protein that selectively induces apoptosis in cancer cells. Moreover, Par-4 sensitizes cells to the action of diverse apoptotic stimuli and causes tumor regression. This review discusses the prominent structural and functional features of Par-4 and the multiple levels of regulation of its apoptotic function, all of which can be utilized to develop targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract: Synapses are often located at great distances from the cell body and so must be capable of transducing signals into both local and distant responses. Although progress has been made in understanding biochemical cascades involved in neuronal death during development of the nervous system and in various neurodegenerative disorders, it is not known whether such cascades function locally in synaptic compartments. Prostate apoptosis response-4 (Par-4) is a leucine zipper and death domaincontaining protein that plays a role in neuronal apoptosis. We now report that Par-4 levels are rapidly increased in cortical synaptosomes and in dendrites of hippocampal neurons in culture and in vivo, following exposure to apoptotic or excitotoxic insults. Par-4 expression is regulated at the translational level within synaptic compartments. Par-4 antisense treatment suppressed mitochondrial dysfunction and caspase activation in synaptosomes and prevented death of cultured hippocampal neurons following exposure to excitotoxic and apoptotic insults. Local translational regulation of death-related proteins in synaptic compartments may play a role in programmed cell death, adaptive remodeling of synapses, and neurodegenerative disorders. Key Words: Antisense oligodeoxynucleotide--Caspase-Hydroxynonenal--Mitochondrial transmembrane potential-Reactive oxygen species--Staurosporine--Protein translation. J. Neurochem. 72, 2312-2322 (1999) [ABSTRACT FROM AUTHOR]