gebhart/patrepeval huggingface dataset:
INTERFERON-GAMMA (IFN-GAMMA) PRODUCTION INVIVO IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (1992)

Experimental autoimmune uveoretinitis (EAU) is a well-characterized model of immune-mediated intraocular inflammation. The intraocular infiltrate in EAU consists predominantly of T lymphocytes. The in vivo production of interferon-gamma (IFN-gamma) by these T cells was investigated immunohistochemically and by in situ hybridization using a cDNA probe to rat IFN-gamma mRNA. Positive localization of IFN-gamma mRNA began simultaneously with disease onset and increased as the inflammatory tissue destruction progressed. The positive signal was seen on cells in the retina, uveal tract and extraocular region where collections of inflammatory cells contained many T lymphocytes. Numerous cells in these locations also stained positively immunohistochemically for IFN-gamma. These results indicate that the in vivo production of IFN-gamma within the eye could play a role in the immune regulation of intraocular inflammatory disease.
Potent inhibition of tubulin polymerisation and proliferation of paclitaxel-resistant 1A9PTX22 human ovarian cancer cells by albendazole. (2009)

Data from this study suggest that ABZ is effective in suppressing growth of PTX-resistant ovarian tumour cells.
Anthrax protective antigen forms oligomers during intoxication of mammalian cells. (1994)

The protective antigen component (PA) of anthrax toxin binds to receptors on target cells and conveys the toxin's edema factor (EF) and lethal factor (LF) components into the cytoplasm. PA (83 kDa) is processed by a cellular protease, yielding a 63-kDa fragment (PA63), which binds EF and/or LF. When exposed to acidic pH, PA63 inserts into membranes and forms ion-conductive channels. By electron microscopy, a significant fraction of purified PA63 was found to be in the form of a multi-subunit ring-shaped oligomer (outer diameter, 10.4 nm). The rings are heptameric, as judged by inspection and by rotational power spectra. Purified PA63 showed a high M(r) band, apparently corresponding to the oligomer, on SDS-polyacrylamide gels, and oligomer of similar size was formed in cells in a time-dependent manner after addition of full-length PA. Inhibitors of internalization and endosome acidification blocked conversion of cell-associated PA to a high molecular weight species, and medium at pH 5.0 induced oligomer formation in the presence or absence of the inhibitors. These results correlate PA63 oligomerization with conditions required for translocation of EF and LF across lipid bilayers, implying that the PA63 oligomer may function in translocation.
Acidic precursor revealed in human eosinophil granule major basic protein cDNA. (1988)

Eosinophil granule major basic protein (MBP), a potent toxin for helminths and various cell types, is a 13.8-kD single polypeptide rich in arginine with a calculated isoelectric point (pI) of 10.9. A cDNA for human MBP was isolated from a gamma GT10 HL-60 cDNA library. The nucleotide sequence of the MBP cDNA indicates that MBP is translated as a 25.2-kD preproprotein. The 9.9-kD pro-portion of proMBP is rich in glutamic and aspartic acids and has a calculated pI of 3.9, while proMBP itself has a calculated pI of 6.2. We suggest that MBP is translated as a nontoxic precursor that protects the eosinophil from damage while the protein is processed through the endoplasmic reticulum to its sequestered site in the granule core toxic MBP, and we present results from the literature suggesting that other cationic toxins, which damage cell membranes, may also be processed from nontoxic precursors containing distinct anionic and cationic regions.
Serum Dihydrotestosterone and Testosterone Concentrations in Human Immunodeficiency Virus‐Infected Men With and Without Weight Loss (1999)

Weight loss is an important determinant of disease outcome in human immunodeficiency virus (HIV)-infected men. Others have suggested that a defect in dihydrotestosterone (DHT) generation contributes to weight loss in HIV-infected men. To determine whether DHT levels correlate with weight loss independently of changes in testosterone levels, we prospectively measured serum total- and free-testosterone and DHT levels in 148 consecutive HIV-infected men and 42 healthy men. Thirty-one percent of HIV-infected men had serum testosterone levels less than 275 ng/dL, the lower limit of the normal male range; of these, 81% had normal or low LH and FSH levels (hypogonadotropic), and 19% had elevated LH and FSH levels (hypergonadotropic). Overall, serum testosterone, free-testosterone, and DHT levels were lower in HIV-infected men than in healthy men, but serum DHT-to-testosterone ratios were not significantly different between the two groups. Serum total- and free-testosterone levels were lower in HIV-infected men who had lost 5 lb or more of weight in the preceding 12 months than in those who had not lost any weight. Serum DHT levels and DHT-to-testosterone ratios did not differ between those who had lost weight and those who had not. Serum testosterone and free-testosterone levels, but not DHT levels, correlated with weight change and with Karnofsky performance status. We also performed a retrospective analysis of data from a previous study in which HIV-infected men with serum testosterone levels less than 400 ng/dL had been treated with placebo or testosterone patches designed to nominally release 5 mg testosterone over 24 hours. Serum testosterone-to-DHT ratios did not change after testosterone treatment. Changes in fat-free mass were correlated with changes in both serum testosterone (r = 0.42, P = 0.018) and DHT (r = 0.35, P = 0.049) levels. Serum total- testosterone and DHT levels were highly correlated with one another, and when the change in serum testosterone was taken into account, serum DHT levels no longer showed a significant correlation with change in fat-free mass. We conclude that DHT levels are lower in HIV-infected men than in healthy men but that neither DHT levels nor DHT-to-testosterone ratios correlate with weight loss. During testosterone treatment, serum DHT levels increase proportionately, but the increments in serum testosterone correlate with the change in fat-free mass. Our data do not support the hypothesis that a defect in DHT generation contributes to weight loss in HIV-infected men independently of changes in testosterone levels; it is possible that such a defect might exist in HIV-infected men with more severe weight loss.
Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in Human Fibroblasts (1999)

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by </=50% compared to young cells. We also provide new evidence that p21 may play a role in inactivation of the DNA replication factor proliferating cell nuclear antigen during early senescence. Finally, because p16 accumulates in parallel with the increases in senescence-associated beta-Gal activity and cell volume that characterize the senescent phenotype, we suggest that p16 upregulation may be part of a differentiation program that is turned on in senescent cells. Since p21 decreases after senescence is achieved, this upregulation of p16 may be essential for maintenance of the senescent-cell-cycle arrest.
.NET is coming [Microsoft Web services platform] (2001)

Discusses the emergence of Microsoft's .NET platform for XML based Web services. .NET has a central role in Microsoft's strategy to integrate the Internet, Web services, building block services, numerous tools for developers, and many other features. .NET has benefited from a several-billion-dollar investment in research. Microsoft's competitors haven't missed the message, as indicated by several recent announcements such as Sun's Open Net Environment. No one in this industry can be guaranteed to hold the lead for long, but Microsoft has the potential to stage a major coup. Whatever happens, .NET will affect nearly everyone involved in any kind of enterprise or Web development.
Active Site Modification of Factor VIIa Affects Interactions of the Protease Domain with Tissue Factor (1997)

In the initiation of coagulation, tissue factor (TF) allosterically activates the serine protease factor VIIa (VIIa) through specific interactions with protease domain residues. These interactions, and consequently affinity for TF, may be influenced by conformational changes in the protease domain that result from zymogen-enzyme transition or occupancy of the active site by tight binding inhibitors. In functional competition and direct binding analysis, we determined affinities for zymogen and enzyme species of wild-type VII and of mutants at protease domain residues that contact TF. We demonstrate that TF binding is not influenced by zymogen activation, indicating that the protease domain of zymogen and enzyme dock similarly with TF. In contrast, active site occupancy enhanced the affinity for TF by predominantly decreasing the dissociation rate of the TF.VIIa complex. Of the three interface residues studied, only Met306 played a major role in the inhibitor-induced increase in affinity. Met306 is also important for transmitting the allosteric changes from TF to the active site, resulting in enhanced catalysis. This study thus provides evidence for a bidirectional conformational interdependence of the interface residue Met306 and the active site of VIIa.
A cross-sectional assessment of health-related quality of life among type 2 diabetic patients in Pakistan (2015)

T2DM imposes a negative effect on HRQoL of the patients. Attention is needed to highlight determinants of HRQoL and to implement policies for better management of T2DM, particularly in early treatment phases where improving HRQoL is still possible.
Photoluminescence of Zn-implanted GaN (1974)

The photoluminescence spectrum of Zn-implanted GaN peaks at 2.87 eV at room temperature. The emission efficiency decreases linearly with the logarithm of the Zn concentration in the range 1–20×1018 Zn/cm3.
Successful treatment of refractory angioimmunoblastic T-cell lymphoma with thalidomide and dexamethasone. (2006)

Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized morphologically by lymphadenopathy with a polymorphic infiltrate, marked vascular and follicular dendritic cell proliferation. Patients usually present with advanced disease and the overall prognosis is poor. While intensive chemotherapy has been shown to induce complete remissions in 50-70% of patients, the majority of patients subsequently relapse. Herein we report the case of a 32 year old man with AITL who was refractory to conventional chemotherapy, but achieved a remarkable sustained response to treatment with thalidomide and dexamethasone. Thalidomide may be an effective therapeutic agent against AITL, and given the poor prognosis of AITL, prospective clinical studies with either thalidomide or one of the thalidomide analogues are warranted.
ExpressMatch: A System for Creating Ground-Truthed Datasets of Online Mathematical Expressions (2012)

In recognition domains, publicly available ground-truthed datasets are essential to perform effective performance evaluation and comparison of existing methods and systems. However, in the field of online handwritten mathematical expression recognition, datasets are quite scarce and their creation is one of the current challenging issues. In this paper, we present Express Match, a system designed to help creation and management of online mathematical expression datasets with ground-truth data. In this system, handwritten model expressions can be input and manually annotated with ground-truth data, transcriptions of these expressions can be automatically annotated by matching them to the respective models. Additional metadata can also be attached to each sample expression. To test the system, a dataset consisting of 56 model expressions and 910 sample expressions with a total of 20,010 symbols, written by 25 different writers, has been created. This dataset, as well as Express Match, will be made publicly available.
Acoustic radiation force on a sphere without restriction to axisymmetric fields (2013)

The analysis presented at the previous ASA meeting related to investigation of the acoustic radiation force on a sphere embedded in a soft elastic medium with shear modulus that is several orders of magnitude smaller than its bulk modulus. The acoustic field was assumed to be axisymmetric and the spherical scatterer to be located on the axis of the acoustic beam. When one of these conditions is violated the problem loses its symmetry. In this talk the acoustic radiation force is considered in the more general case of nonaxisymmetic fields. The calculation is performed in Lagrangian coordinates. All acoustic fields, incident as well as scattered, depend on all three spherical coordinates. The incident and scattered waves, which include both potential and solenoidal parts, are expanded with respect to spherical harmonics. An analytical expression for the acoustic radiation force derived in this investigation may contain as many spherical harmonics as needed. In limiting cases when the scatterer is in liquid and only two modes, monopole and dipole, remain in the scattered fields, the solution for the acoustic radiation force recovers the results reported by Gor'kov [Sov. Phys. Doklady 6, 773 (1962)]. [Work supported by NIH DK070618 and EB011603.]
P0513NECROINFLAMMATION VERSUS CRYSTAL CLOTS AS THERAPEUTIC TARGET IN CHOLESTEROL CRYSTAL EMBOLISM-RELATED KIDNEY INFARCT (2020)

Abstract Background and Aims Cholesterol crystal embolism (CCE) is usually a consequence of the rupture of atheromatous plaques in patients with advanced atherosclerosis. We hypothesized that necroinflammation contributes to CCE-related kidney injury/disease (AKI/AKD). Method Injection of cholesterol crystal (CC) into C56BL/6 WT mice kidney via the left kidney artery induced vascular obstruction, kidney infarction, and GFR loss (measured by transcutaneous monitoring of sinistrin clearance in awake and unrestricted mice). GFR recovered to baseline at 2 weeks despite persistent kidney injury and scarring, probably because the non-injected right kidney developed compensatory hypertrophy. To study the role of necroinflammation in this process, we injected CC to either Mlkl-/- mice or WT mice pre-treated with PBS, the necroptosis inhibitor Nec-1s or the NLRP3 inhibitor MCC950 30 min before CC injection. Results At 24h, Nec-1s, MCC950 treatment had significantly reduced infarct size, kidney injury, neutrophil infiltration, and vascular injury compared to PBS control group. Reduced infarct size, e.g. with Nec-1s persistented until day 14. CC injection into Mlkl-/- mice gave the same results. However, none of these interventions had an effect on GFR loss, i.e. AKI because they did not affect crystal clot formation in the arteria afferent to glomerular perfusion. In contrast, anticoagulant treatment prevented infarcts and GFR loss. Conclusion In this new model of unilateral CCE-induced AKI/AKD global kidney function recovers within 14 d, presumably due to adaptive responses in the contralateral kidney as the post-infarct tissue injury persists and leads to kidney atrophy. As both the NLRP3 inflammasome as well as necroptosis are involved in kidney infarct formation, we conclude on necroinflammation as the central mechanism of CCE-induced AKI/AKD. However, what defines AKI is renal function. We found that crystal clot formation is upstream of kidney infarction but independent of necroinflammation. We conclude, despite necroinflammation is central in kidney infarct formation, crystal clots are the better therapeutic target to prevent CCE-related AKI.
Genetic Instability of Live, Attenuated Human Immunodeficiency Virus Type 1 Vaccine Strains (1999)

Live, attenuated viruses have been the most successful vaccines in monkey models of human immunodeficiency virus type 1 (HIV-1) infection. However, there are several safety concerns about using such an anti-HIV vaccine in humans, including reversion of the vaccine strain to virulence and recombination with endogenous retroviral sequences to produce new infectious and potentially pathogenic viruses. Because testing in humans would inevitably carry a substantial risk, we set out to test the genetic stability of multiply deleted HIV constructs in perpetuated tissue culture infections. The Delta3 candidate vaccine strain of HIV-1 contains deletions in the viral long terminal repeat (LTR) promoter and the vpr and nef genes. This virus replicates with delayed kinetics, but a profound enhancement of virus replication was observed after approximately 2 months of culturing. Analysis of the revertant viral genome indicated that the three introduced deletions were maintained but a 39-nucleotide sequence was inserted in the LTR promoter region. This insert was formed by duplication of the region encoding three binding sites for the Sp1 transcription factor. The duplicated Sp1 region was demonstrated to increase the LTR promoter activity, and a concomitant increase in the virus replication rate was measured. In fact, duplication of the Sp1 sites increased the fitness of the Delta3 virus (Vpr/Nef/U3) to levels higher than that of the singly deleted DeltaVpr virus. These results indicate that deleted HIV-1 vaccine strains can evolve into fast-replicating variants by multiplication of remaining sequence motifs, and their safety is therefore not guaranteed. This insight may guide future efforts to develop more stable anti-HIV vaccines.
Pregnancy-Stimulated Neurogenesis in the Adult Female Forebrain Mediated by Prolactin (2003)

Neurogenesis occurs in the olfactory system of the adult brain throughout life, in both invertebrates and vertebrates, but its physiological regulation is not understood. We show that the production of neuronal progenitors is stimulated in the forebrain subventricular zone of female mice during pregnancy and that this effect is mediated by the hormone prolactin. The progenitors then migrate to produce new olfactory interneurons, a process likely to be important for maternal behavior, because olfactory discrimination is critical for recognition and rearing of offspring. Neurogenesis occurs even in females that mate with sterile males. These findings imply that forebrain olfactory neurogenesis may contribute to adaptive behaviors in mating and pregnancy.
The mechanisms of lethal action of arabinosyl cytosine (araC) and arabinosyl adenine (araA) (1977)

Certain D-arabinosyl nucleosides, notably arabinosyl cytosine (araC) and arabinosyl adenine (araA), are useful in the treatment of certain leukemias and some DNA virus infections, respectively. The compounds are lethal to animal cells and some bacteria. Despite extensive deamination, the parent nucleosides are transported within sensitive cells and phosphorylated to the mono-, di- and triphosphates. AraCTP and araATP are good specific competitive inhibitors of tumor cell of virus-induced DNA polymerases, competing with dCTP and dATP respectively. In addition to markedly inhibiting DNA synthesis, the aranucleotides enter newly formed DNA in internucleotide linkage. Sensitivity to the nucleosides appears to correlate with the relative ratio of formation of the triphosphate via a nucleoside kinase to degradation of the nucleoside via a nucleoside deaminase. Inhibition of the deaminase increases formation of the aranucleoside triphosphate in leukemic or virus-infected cells and markedly increases the toxicity of the nucleosides. Combinations of inhibitors of the deaminases and of the aranucleoside are being explored in clinical situations. In addition, the slow penetration of aranucleotides into cells has been observed and some of these 5'-phosphates are useful antiviral agents, e.g., against herpes virus in herpetic kiratitis.
Resource sharing for multi-party real-time communication (2002)

Approaches to supporting real-time communication allocate network resources either to individual connections, or to aggregates of connections. Resource sharing is a new approach that exploits known relationships between related connections to allow network resources to be shared between them without sacrificing well-defined guarantees. The authors present a fully distributed technique for using resource sharing to provide guaranteed performance communication in a heterogeneous internetwork. Results show that resource sharing leads to a large gain in the connection acceptance rate, and a significant reduction in the computational overhead associated with admission control. Thus, resource sharing is an important tool for providing real-time performance guarantees for large conferences.
Robust Antidepressant Effect Following Alternating Intravenous Racemic Ketamine and Electroconvulsive Therapy in Treatment-Resistant Depression (2017)

Bartova, Lucie MD; Weidenauer, Ana MD; Dold, Markus MD; Naderi-Heiden, Angela MD; Kasper, Siegfried MD; Willeit, Matthaeus MD; Praschak-Rieder, Nicole MD Author Information
GPU algorithms for radiosity and subsurface scattering (2003)

We capitalize on recent advances in modern programmable graphics hardware, originally designed to support advanced local illumination models for shading, to instead perform two different kinds of global illumination models for light transport. We first use the new floating-point texture map formats to find matrix radiosity solutions for light transport in a diffuse environment, and use this example to investigate the differences between GPU and CPU performance on matrix operations. We then examine multiple-scattering subsurface light transport, which can be modeled to resemble a single radiosity gathering step. We use a multiresolution meshed atlas to organize a hierarchy of precomputed subsurface links, and devise a three-pass GPU algorithm to render in real time the subsurface-scattered illumination of an object, with dynamic lighting and viewing.
p53 and Brain Tumors: From Gene Mutations to Gene Therapy (1998)

The p53 tumor suppressor gene (TP53) is the most frequently altered gene in human cancer and is also found mutated in several types of brain tumors. Loss of p53 function plays a central role in the development of cancer. The characterization of the biochemical pathways by which p53 alteration triggers tumorigenesis is the foundation for the design of novel therapeutic approaches. Investigations of the intracellular mechanisms at the origin of p53 tumor suppressive functions have shown that p53 is a transcription factor able to sense a variety of cellular insults and induce a dual response: cell growth arrest/senescence or apoptosis. Less well studied are p53's influences on extracellular events such as tumor angiogenesis, immunology and invasion. Here, we review these findings and specifically discuss their implications for brain tumor genesis, molecular diagnosis and prognosis. Of clinical importance are the findings that brain tumors with wild type (wt) or mutant p53 status may respond differently to radiation therapy and that novel therapeutic strategies using TP53 gene transfer or specifically targeting tumor cells with mutated p53 are being evaluated in clinical trials.