Miracle-dz/UniFAR-FTUs huggingface dataset:
Podophyllum hexandrum ameliorates endosulfan-induced genotoxicity and mutagenicity in freshwater cyprinid fish crucian carp

Abstract Context: Medicinal plants continue to act as a repository for novel drug leads with novel mechanisms of action. Podophyllum hexandrum Royale (Berberideceae) treats diverse conditions in folk medicine. Objective: The antimutagenic potential of P. hexandrum was evaluated against endosulfan-induced clastogenicity in a piscine model by cytogenetic endpoints. Materials and methods: Podophyllum hexandrum rhizomes were subjected to successive solvent extraction. Fish were exposed to hexane, chloroform, ethyl acetate, methanol and aqueous extracts (15 mg/L each) of plant and endosulfan (0.05 mg/L) alone followed by their combination for antimutagenicity estimates. Chromosomal aberrations (CA) were made from kidney cells and micronuclei (MN) slides from peripheral blood erythrocytes at 48, 72 and 96 h. Antioxidant activity was analyzed by the DPPH assay. Phytochemical analyses were carried out using chromatographic and spectroscopic techniques. Results: Endosulfan induced significant (p < .05) MN, authenticated by scanning electron microscopy, and CA in a time-dependent manner. However, methanol and ethyl acetate extracts revealed ameliorating effects. The column eluted methanolic fraction-2 (ME-F2) showed highest reduction profile of 83 and 84% in CA and MN, followed in its extent (73 and 72%) by ethyl acetate fraction-4 (EE-F4). ME-F2 and EE-F4 showed three and six major peaks when analyzed by GC-MS. To explore possible mechanism of action, ME-F2 showed potent antioxidant potential and strong correlation (R2 = .900) with antimutagenic activity, whereas EE-F4 seemed to act through a different mechanism. Discussion and conclusion: This study confirms the antimutagenic potential of the subject plant with the identification of some novel compounds, justifying their use in folk medicine, and their corresponding benefit to mankind.
The phenotype of Arg555Trp mutation in a large Turkish family with corneal granular dystrophy.

PURPOSE A large Turkish family with 52 members, 26 of whom had Groenouw type 1 corneal granular dystrophy was evaluated by genetic linkage studies and mutation analyses. Phenotype- genotype correlations were also assessed. METHODS DNA from peripheral blood lymphocytes of 22 family members was used in establishing linkage to chromosome 5q31. Single-strand conformation polymorphism analysis was done to detect mutations in exons 4 and 12 of the human transforming growth factor -induced gene located on chromosome 5q31. Automated sequencing was performed on exon 12 of an affected patient. RESULTS Patients yonger than 15 years of age had typical linear, granular opacities whereas adults had coarser, deeper granular stromal deposits. These changes were not associated with recurrent erosions or significant visual disabilities. The family was linked to chromosome 5q31 and a DNA shift was observed on exon 12 of affected patients. CGG to TGG transition producing R555W mutation was found. CONCLUSIONS Segregation of Arg555Trp has been described as causing Groenouw type I corneal dystrophy of variable severity in patients of various ethnic backgrounds. In this large Turkish pedigree, the Arg555Trp mutation was associated with a mild phenotype that became clinically evident at five years of age but which remained asymptomatic in terms of corneal erosions. (Eur J Ophthalmol 2001; 11: 333-7).
Endometrial Glandular Dysplasia: A Newly Defined Precursor Lesion of Uterine Papillary Serous Carcinoma. Part I: Morphologic Features

Dysplastic epithelium frequently bridges the changes between normal epithelium and noninvasive carcinoma. However, such a dysplastic lesion has not been previously described in the development of uterine papillary serous carcinoma (UPSC) or between resting endometrium and serous endometrial intraepithelial carcinoma (EIC), which is composed of indisputably malignant noninvasive cancer cells. In this study, we hypothesize that there is a lesion bridging benign endometrium and serous EIC. Based on current understanding of carcinogenesis in general, the lesion should exhibit dysplastic features that are more atypical than “resting endometrium” but fall short of serous EIC. If the putative dysplastic endometrial lesion exists, it should be highly associated with UPSC rather than uterine endometrioid carcinoma (UEC). We examined the morphologic appearance of the endometrium from 32 uteri with UPSC, 16 with serous EIC, and 60 with UEC. The endometrial dysplastic lesions were identified and their pathologic features were characterized. Immunohistochemical staining with p53 and MIB-1 were performed in all sections containing endometrial dysplastic lesions, serous EICs, and benign areas. In addition, 25 postmenopausal endometrial biopsies including 6 benign resting endometria, 8 dysplastic lesions, and 11 serous EICs were also compared for the level of p53 overexpression and cellular proliferative activity. We found that endometrial dysplastic lesions do exist in the endometrial specimens we speculated and examined. We designate it as endometrial glandular dysplasia (EmGD). EmGD was present in 17 (53%) uteri with UPSC compared with 1 (1.7%) uterus removed for UEC (p = 0.001). EmGD was identified in 12 (75%) of 16 serous EIC uteri. Areas of both EmGD and serous EIC were found in 15 (47%) of the 32 UPSC uteri. Transitions from either EmGD to serous EIC or serous EIC to UPSC were present in 8 (25%) of the UPSC cases. No transitions from EmGD to UPSC were identified in any hysterectomy specimen. EmGD was frequently found in endometrial polyps. There was no statistically significant difference between EmGD in a polyp (48%) and EmGD in nonpolypoid endometrium (52%). The majority of EmGDs were multifocal and involved superficial endometrial glands. However, single glandular involvement and endometrial surface epithelial involvement were also seen. Immunohistochemically, EmGD lesions mostly showed intermediate scores/indices of p53 and MIB-1 in comparison with serous EIC and resting endometrium. EmGD is a morphologically distinct entity, which is commonly and specifically associated with uterine tumors with serous differentiation. EmGD may represent the earliest identifiable morphologic change in the development of UPSC. Characteristics of p53 and MIB-1 immunostains of EmGD may be of diagnostic usage in surgical pathology practice. Recognition of EmGD may provide an opportunity to improve the management of UPSC.
Brain PET measurement of PDE10A occupancy by TAK‐063, a new PDE10A inhibitor, using [11C]T‐773 in nonhuman primates

Because phosphodiesterase 10A (PDE10A) degrades both cyclic adenosine monophosphate and cyclic guanosine monophosphate and is distributed mainly in the striatum, PDE10A inhibitors have been considered to potentially be useful therapeutic agents for psychiatric and neurodegenerative diseases such as schizophrenia and Huntington's disease. We measured striatal PDE10A occupancy by TAK‐063, a newly developed compound with high affinity and selectivity for PDE10A, using PET with [11C]T‐773 in nonhuman primates. Two 123‐min dynamic PET measurements were performed on three female rhesus monkeys, once at baseline and again after intravenous administration of different doses of TAK‐063 (0.2–1.6 mg/kg). Total distribution volume (VT) was calculated with a two‐tissue compartment model using metabolite‐corrected plasma input. Although the in vitro autoradiography did not show high specific binding to [11C]T‐773 in the cerebellum, VT in the cerebellum decreased after TAK‐063 treatment. The specific binding to PDE10A (VS) was calculated as the difference of the VT between the target regions and the cerebellum. PDE10A occupancy was calculated as the percent change of VS. The average PDE10A occupancy of the caudate nucleus and putamen was 35.2% at 0.2 mg/kg and 83.2% at 1.6 mg/kg. In conclusion, this nonhuman primate PET study demonstrated that [11C]T‐773 is useful to estimate the PDE10A occupancy by TAK‐063 in the striatum although there is in vivo interaction of the uptake between [11C]T‐773 and TAK‐063 in the cerebellum. These results warrant further clinical occupancy study for TAK‐063. Synapse 70:253–263, 2016. © 2016 Wiley Periodicals, Inc.
Financing Technology-Based Small Firms in Europe: a review of the empirical evidence

This paper reviews the empirical evidence of the financial sources used by technology-based small firms (TBSFs) in Europe. We shed light on cross-country differences and similarities in the capital structures of TBSFs, in the organization and dynamics of the venture capital industries and high-tech stock markets, as well as in policy-making. We focus on the main European economies, i.e. France, Germany, Italy and the UK. The evidence of a pecking order among capital sources, the rather conservative investment behaviors of venture capital funds in all countries, and the differential performances of hi-tech stock markets cannot be accounted for by the market-based vs. bank-based taxonomy widely used in the research on financial systems.
TESTS OF THE MID-DOMAIN HYPOTHESIS: A REVIEW OF THE EVIDENCE

Geographic variation of species richness is strongly correlated with environmental gradients. However, random arrangement of species distributions within a bounded domain can also theoretically produce richness gradients without underlying environmental gradients. This mid-domain effect (MDE) could serve as the null hypothesis against which to test effects of environmental variables, or as a component of a multivariate explanation of species-richness patterns. Recent reviews have concluded that there is a substantial MDE signature in observed geographical patterns of richness, based on correlations between observed patterns of richness and the predictions of mid-domain models. However, the mid-domain hypothesis makes additional powerful predictions about how richness should vary through space, and about the slope of the relationship between predicted and observed richness. Very few studies have tested these more powerful MDE predictions. Here, we reexamine the published mid-domain literature for agreement between observed patterns of richness and MDE predictions. We find that 50 of 53 published studies of MDEs showed significant deviations from the predictions of mid-domain models. When observed richness is correlated with MDE predictions, there are nearly always strongly collinear environmental gradients (e.g., in the Americas, climatic favorability and MDE-predicted richness are both maximal in the middle). Interpolation in sparsely sampled data can also give rise to spurious, apparently strong, mid-domain effects (e.g., the classic study of the Madagascan rain forest). We conclude that observed broad-scale patterns of species richness are not consistent with the mid-domain hypothesis.
Mutation analysis in the HFE gene in patients with hereditary haemochromatosis in Saguenay–Lac‐Saint‐Jean (Quebec, Canada)

A mutation analysis of the HFE gene followed, when applicable, by sequencing was performed on 47 patients with hereditary haemochromatosis (HH) living in Saguenay–Lac‐Saint‐Jean. The C282Y and H63D mutations were present on 50% and 20·3% of the HH chromosomes respectively. These frequencies were very different from those found in other populations and could be, at least partially, the result of a founder effect. No new mutation was identified among the remaining 28·1% of the HH chromosomes. Five of the eight probands with no mutation in the HFE gene had a severe and early onset suggestive of juvenile haemochromatosis.
The expression and roles of Toll‐like receptors in the biology of the human neutrophil

Neutrophils are amongst the first immune cells to arrive at sites of infection, where they initiate antimicrobial and proinflammatory functions, which serve to contain infection. Sensing and defeating microbial infections are daunting tasks as a result of their molecular heterogeneity; however, Toll‐like receptors (TLRs) have emerged as key components of the innate‐immune system, activating multiple steps in the inflammatory reaction, eliminating invading pathogens, and coordinating systemic defenses. Activated neutrophils limit infection via the phagocytosis of pathogens and by releasing antimicrobial peptides and proinflammatory cytokines and generating reactive oxygen intermediates. Through the production of chemokines, they additionally recruit and activate other immune cells to aid the clearance of the microbes and infected cells and ultimately, mount an adaptive immune response. In acute inflammation, influx of neutrophils from the circulation leads to extremely high cell numbers within tissues, which is exacerbated by their delayed, constitutive apoptosis caused by local inflammatory mediators, potentially including TLR agonists. Neutrophil apoptosis and safe removal by phagocytic cells limit tissue damage caused by release of neutrophil cytotoxic granule contents. This review addresses what is currently known about the function of TLRs in the biology of the human neutrophil, including the regulation of TLR expression, their roles in cellular recruitment and activation, and their ability to delay apoptotic cell death.
AT&T at TREC-9

This year we come to TREC with a new retrieval system Tivra that we have implemented over the last year. Tivra is based on the vector space model, and is mainly designed to do large-scale web search with limited resources. We run Tivra on a cheap Linux box. It currently indexes around 14-15 gigabytes of web data per hour, and allows sub-second web searches for 2-3 word queries on a 700 MHz Pentium box. At the time of submissions Tivra was in its early development stages, and was not fully tested. However, we still submitted runs for both the web tracks { 10 gigabytes and 100 gigabytes. The results look quite reasonable for an untested version of the system. For the 10 gigabytes ad-hoc task, our results are above median for majority of the queries. This is specially notable given that we use only the title portion of the queries whereas the results pool contains results based on both long and short queries. Our results are among the top results in the 100 gigabytes task.
Trauma, mental representation, and the organization of memory for mother-referent material

Research on the effects of child maltreatment and exposure to community violence suggests that children who experience these types of traumatic events may be at risk for alterations and biases in attention and memory similar to those that have been observed in adults suffering from traumatic stress reactions. Along these lines, attachment theory posits that representational models of relationships also may act as moderators of similar cognitive biases by selectively guiding children's attention to and processing of interpersonal stimuli. Building upon the trauma and attachment literatures, the present investigation examined the links among trauma, representational models of caregivers, and children's memory for mother-relevant information using an incidental recall task in a sample of maltreated (n = 71) and nonmaltreated (n = 102) children between the ages of 8 and 13 years. Results were consistent with the hypothesis that experiences of trauma and representational models of caregivers are associated with differences in the way children process and retrieve information about positive and negative mother attribute words. In particular, experiences of trauma initially were associated with increased insecurity in children's representational models. Moreover, the interaction of traumatic experience and security of mental representation predicted children's recall for mother attribute words: victimized children with insecure models recalled the highest proportion of negative mother stimuli. Trauma and mental representation did not have a consistent effect on structurally encoded aspects of recall. Results were discussed in terms of the ways in which children who have experienced trauma process information about their worlds. The importance of assessing functioning in multiple developmental domains when studying memory also was discussed.
Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma.

PURPOSE Lenalidomide and bortezomib are active in relapsed and relapsed/refractory multiple myeloma (MM). In preclinical studies, lenalidomide sensitized MM cells to bortezomib and dexamethasone. This phase I, dose-escalation study (ie, NCT00153933) evaluated safety and determined the maximum-tolerated dose (MTD) of lenalidomide plus bortezomib in patients with relapsed or with relapsed and refractory MM. PATIENTS AND METHODS Patients received lenalidomide 5, 10, or 15 mg/d on days 1 through 14 and received bortezomib 1.0 or 1.3 mg/m(2) on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20mg or 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12) was added for progressive disease after two cycles. Primary end points were safety and MTD determination. RESULTS Thirty-eight patients were enrolled across six dose cohorts. The MTD was lenalidomide 15 mg/d plus bortezomib 1.0 mg/m(2). Dose-limiting toxicities (n = 1 for each) were grade 3 hyponatremia and herpes zoster reactivation and grade 4 neutropenia. The most common treatment-related, grades 3 to 4 toxicities included reversible neutropenia, thrombocytopenia, anemia, and leukopenia. Among 36 response-evaluable patients, 61% (90% CI, 46% to 75%) achieved minimal response or better. Among 18 patients who had dexamethasone added, 83% (90% CI, 62% to 95%) achieved stable disease or better. Median overall survival was 37 months. CONCLUSION Lenalidomide plus bortezomib was well tolerated and showed promising activity with durable responses in patients with relapsed and relapsed/refractory MM, including patients previously treated with lenalidomide, bortezomib, and/or thalidomide. The combination of lenalidomide, bortezomib, and dexamethasone is being investigated in a phase II study in this setting and in newly diagnosed MM.
Exposure to antiretroviral therapy and risk of cancer in HIV-infected persons

Objective:The incidence of certain non-AIDS-defining cancers (NADCs) in HIV patients has been reported to have increased in the combination antiretroviral therapy (ART) era. Studies are needed to directly evaluate the effect of ART use on cancer risk. Design:We followed 12 872 HIV-infected Kaiser Permanente members whose complete ART history was known for incident cancers between 1996 and 2008. Methods:Cancers, identified from Surveillance, Epidemiology, and End Results (SEER)-based cancer registries, were grouped as ADCs, infection-related NADCs, or infection-unrelated NADCs. We also evaluated the most common individual cancer types. Rate ratios for ART use (yes/no) and cumulative duration of any ART, protease inhibitor, and nonnucleotide reverse transcriptase inhibitor (NNRTI) therapy were obtained from Poisson models adjusting for demographics, pretreatment or recent CD4 cell count and HIV RNA levels, years known HIV-infected, prior antiretroviral use, HIV risk, smoking, alcohol/drug abuse, overweight/obesity, and calendar year. Results:The cohort experienced 32 368 person-years of ART, 21 249 person-years of protease inhibitor therapy, and 15 643 person-years of NNRTI therapy. The mean follow-up duration was 4.5 years. ADC rates decrease with increased duration of ART use [rate ratio per year = 0.61 (95% confidence interval 0.56–0.66)]; the effect was similar by therapy class. ART, protease inhibitor, or NNRTI therapy duration was not associated with infection-related or infection-unrelated NADC [rate ratio per year ART = 1.00 (0.91–1.11) and 0.96 (0.90–1.01), respectively], except a higher anal cancer risk with longer protease inhibitor therapy [rate ratio per year = 1.16 (1.02–1.31)]. Conclusion:No therapy class-specific effect was found for ADC. ART exposure was generally not associated with NADC risk, except for long-term use of protease inhibitor, which might be associated with increased anal cancer risk.
Comparison of an immunochromatographic card test with night blood smear examination for detection of Wuchereria bancrofti microfilaria carriers.

BACKGROUND At present, two diagnostic tests--Og4C3 ELISA and an immunochromatographic card test (ICT)--are available to detect circulating filarial antigens of Wuchereria bancrofti in serum/whole blood samples collected during the day. We aimed to assess the sensitivity of the new format card test 'NOW ICT Filariasis' in detecting microfilaria carriers of W. bancrofti in comparison with conventional microscopic techniques and Og4C3 ELISA. METHODS A total of 200 persons were selected from two villages following a quota sampling design (100 in each village). The required number of houses was selected using a systematic sampling procedure with a random start of the first household. Blood samples were taken from all the available persons in each selected house until the quota of 100 was reached. The new format ICT test, Og4C3 ELISA and night blood smear examination for microfilaria were carried out following standard procedures. RESULTS The sensitivity of the new format ICT test was 100% among microfilaria carriers (detected by both early and late readings). The kappa statistic measure of agreement between the two readings of all the samples (n =200) tested was 0.811 (p<0.05). The new format test also reported 25% of microfilaria-negative individuals as being positive for circulating filarial antigens. However, the diagnostic lines were not stable beyond 10 minutes (particularly in the case of amicrofilaraemic persons). Though there was an overall agreement between the results of ICT and Og4C3 tests (kappa =0.612; p< 0.05), the sensitivity of the Og4C3 test was lower than that of ICT. CONCLUSION The new format ICT test is highly sensitive in detecting microfilaria carriers in endemic communities. Improvement in the format to provide stable diagnostic lines, specificity of the format and cost of the test kit are to be considered before its large-scale use.
Equipping Ourselves in Tough times: Canada's Improved Business Investment Performance

After trailing the average performance of G7 countries for 15 years, Canada’s relative business investment performance stands out in a promising light for 2009 and 2010. Amid the recession, new capital spending on tools for workers, in the form of machinery, equipment or buildings, has held up better in Canada than in many other countries, and particularly the United States. Investment per worker in Canada for 2010 should surpass that in other G7 and OECD countries.
Web switching and international outsourcing: A matching approach

Formulating a model comprising transportation, uncertainty and price, we describe how Web procurement is likely to boost volumes of international services vs. materials inputs. Using panel data for over 2,000 firms, we find that Web procurement increases international services outsourcing by between 1.6 and 2.5 percent for the FE and D-in-D matching estimators. These values are comparable to those obtained by Bartel et al. (2005) using different methodologies and US aggregate data. Although no existing work has yet reported effects for international materials outsourcing we find that Web procurement decreases international materials outsourcing by between 2.2 and 3.7 percent.