gebhart/patrepeval huggingface dataset:
Imatinib Inhibits Proliferation of Ewing Tumor Cells Mediated by the Stem Cell Factor/KIT Receptor Pathway, and Sensitizes Cells to Vincristine and Doxorubicin-Induced Apoptosis (2004)

Abstract Purpose and Experimental Design: The stem cell factor/KIT receptor loop may represent a novel target for molecular-based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. Results: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. KIT expression was stronger in Ewing tumors showing EWS-FLI1 nontype 1 fusions. Despite absence of c-kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. Treatment with KIT tyrosine kinase inhibitor imatinib (0.5–20 μm) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC50, 12–15 μm). However, imatinib administered alone at doses close to IC50 for growth inhibition (10 μm) did not induce a significant increase in apoptosis. We then analyzed if blockade of KIT loop through imatinib (10 μm) was able to increase the antitumor in vitro effect of doxorubicin (DXR) and vincristine (VCR), drugs usually used in Ewing tumor treatment. Addition of imatinib decreased in 15–20 and 15–36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. Conclusions: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Inhibition of KIT increases sensitivity of these cells to DXR and VCR. This study supports a potential role for imatinib in the treatment of Ewing tumor.
Anesthetic Activity of Novel Water-Soluble 2β-Morpholinyl Steroids and Their Modulatory Effects at GABAAReceptors (1997)

(3 alpha,5 alpha)-3-Hydroxypregnan-20-ones and (3 alpha,5 alpha)-3-hydroxypregnane-11,20-diones bearing a 2 beta-morpholinyl substituent were synthesized, and the utility of these steroids as anesthetic agents was evaluated through determination of their potency and duration of hypnotic activity in mice after intravenous administration. Alkylation of the morpholinyl substituent or chlorination at C-21 afforded the novel amino steroids (2 beta,3 alpha,5 alpha)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)-pregnane-11,20-dione (19) and (2 beta,3 alpha,5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one (37) that were more potent and advantageously produced shorter sleep times than related compounds which were previously reported. Furthermore, salts of these and other amino steroids generally retained good aqueous solubility. In a radioligand binding assay the compounds inhibited the specific binding of [35S]-tert-butyl bicyclophosphorothionate to rat whole brain membranes, and in an electrophysiological assay they potentiated GABAA receptor-mediated currents recorded from voltage-clamped bovine chromaffin cells. These in vitro results are consistent with the anesthetic activity of the amino steroids being related to their modulatory effects at GABAA receptors.
Production of 3-Hydroxypropionaldehyde from Glycerol (1983)

3-Hydroxypropionaldehyde is a precursor to acrolein, which can be used as an intermediate for making acrylic acid and a variety of other useful industrial chemicals. Conversion of glycerol, a renewable resource, to 3-hydroxypropionaldehyde was attempted via action of glycerol dehydrase isolated from Lactobacillus sp. strain NRRL B-1720. This method, however, was unsatisfactory because enzyme activity was lost within 60 to 90 min after the reaction initiation. Fermentation of glycerol by whole cells of Klebsiella pneumoniae NRRL B-199 in the presence of optimal semicarbazide hydrochloride proved more effective. Using this technique, glycerol solutions of 30 g/liter yielded 3-hydroxypropionaldehyde solutions of 13.1 g/liter. Thus, a conversion efficiency equal to 55% of the theoretical maximum was realized.
Activin A Maintains Pluripotency of Human Embryonic Stem Cells in the Absence of Feeder Layers (2005)

To date, all human embryonic stem cells (hESCs) available for research require unidentified soluble factors secreted from feeder layers to maintain the undifferentiated state and pluripotency. Activation of STAT3 by leukemia inhibitory factor is required to maintain "stemness" in mouse embryonic stem cells, but not in hESCs, suggesting the existence of alternate signaling pathways for self-renewal and pluripotency in human cells. Here we show that activin A is secreted by mouse embryonic feeder layers (mEFs) and that culture medium enriched with activin A is capable of maintaining hESCs in the undifferentiated state for >20 passages without the need for feeder layers, conditioned medium from mEFs, or STAT3 activation. hESCs retained both normal karyotype and markers of undifferentiated cells, including Oct-4, nanog, and TRA-1-60 and remained pluripotent, as shown by the in vivo formation of teratomas.
Statistical characteristics of measured MIMO wireless channel data and comparison to conventional models (2002)

This paper presents measured data from a narrowband multiple-input multiple-output (MIMO) channel probe in an indoor office/laboratory environment. The system employs ten transmit and ten receive antennas and computes the 10 /spl times/ 10 narrowband channel matrix at 2.45 GHz every 80 milliseconds. We use the data to study the statistical behavior of the channel coefficients and the resulting channel capacity. We also demonstrate the ability of a simple statistically based physical model to accurately represent the channel behavior. The results of this model are compared to more conventional models that assume complex normal distributions of the channel matrix elements.
On image auto-annotation with latent space models (2003)

Image auto-annotation, i.e., the association of words to whole images, has attracted considerable attention. In particular, unsupervised, probabilistic latent variable models of text and image features have shown encouraging results, but their performance with respect to other approaches remains unknown. In this paper, we apply and compare two simple latent space models commonly used in text analysis, namely Latent Semantic Analysis (LSA) and Probabilistic LSA (PLSA). Annotation strategies for each model are discussed. Remarkably, we found that, on a 8000-image dataset, a classic LSA model defined on keywords and a very basic image representation performed as well as much more complex, state-of-the-art methods. Furthermore, non-probabilistic methods (LSA and direct image matching) outperformed PLSA on the same dataset.
Upgrading and Repairing PC's (1988)

a comprehensive resource for PC enthusiasts and professionals alike. Packed with the latest speeds and feeds, youll want to keep this book on-hand as an authoritative technology reference. Chris Angelini, Managing Editor, Toms Hardware For 20 years, Upgrading and Repairing PCs has been the industrys #1 guide to PC hardware: the single source for reliable, step-by-step information on identifying and fixing problems, adding hardware, optimizing performance, and building new PCs from scratch. Now, this 19th Edition has been completely updated to focus on todays technologies and todays maintenance challenges! From processors and motherboards, memory to storage, video to power, and networking to Internet connectivity, its all here: technical details, practical insights, and step-by-step solutions to difficult problems. Updates include new CPUs like the Intel Core i Series and AMDs Phenom family...solid state drives (SSDs) and hard disk drives...motherboard form factors, chipsets, power supplies, DDR3 memory, Windows 7 readiness, and a whole lot more! Your guide, Scott Mueller, has taught thousands in his legendary personal seminars and millions more through his books and videos. Nobody knows more about choosing, installing, troubleshooting, repairing, and maintaining PC hardware. Whether youre a professional technician, a small business owner who doesnt want to pay for service calls, or a home PC enthusiast, this is the one book you need! NEW IN THIS EDITION Intels and AMDs hottest new processors, including the Intel Core i Series and AMD Phenom family The latest PC system designs and form factors, including the new mini-ITX and DTX motherboard form factors State-of-the-art graphics cards, GPUs, and chipsets from NVIDIA and ATI/AMD Terabyte-class hard disks, solid state drives, and other data storage innovations Revamped coverage of building PCs from scratchfrom selecting and assembling hardware to BIOS Setup and troubleshooting ON THE DVD The DVD contains two hours of up-to-the minute, studio-quality how-to videosall playable on either your DVD player or computer! Youll find detailed presentations covering important PC components like processors, motherboards, chipsets, memory, hard disk drives, chassis, and power supplies, including tips that will help you select the best components when building or purchasing new systems as well as when upgrading or repairing existing ones. There is a complete step-by-step guide to building a new PC from scratch, including tips that will not only make the build process run smoothly, but will also help you build a system that has performance, durability, and will be easy to maintain, upgrade, and repair in the future. Thats not all: Youll also find the complete 16th Edition of this book, plus extensive technical reference material, a comprehensive PC glossary, and much more!
Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder (2016)

Apathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia.
A preliminary clinical and histopathological study of laser skin resurfacing using a frequency-doubled Nd:YAG laser after application of Chromofilm ® (1999)

Laser skin resurfacing using a 532-nm laser irradiation after application of a carbon film transfer is an effective method for skin resurfacing. With this new galenic approach (Chromofilm), the control of all parameters (thickness, chromophore concentration and distribution) can be achieved to predict the thermal injury obtained after laser irradiation.
Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154. (1999)

Clinical islet cell transplantation has resulted in insulin independence in a limited number of cases. Rejection, recurrence of autoimmunity, and impairment of normal islet function by conventional immunosuppressive drugs, e.g., steroids, tacrolimus, and cyclosporin A, may all contribute to islet allograft loss. Furthermore, intraportal infusion of allogeneic islets results in the activation of intrahepatic macrophages and endothelial cells, followed by production of proinflammatory mediators that can contribute to islet primary nonfunction. We reasoned that the beneficial effects of anti-CD154 treatment on autoimmunity, alloreactivity, and proinflammatory events mediated by macrophages and endothelial cells made it an ideal agent for the prevention of islet allograft failure. In this study, a nonhuman primate model (Papio hamadryas) was used to assess the effect of humanized anti-CD154 (hu5c8) on allogeneic islet engraftment and function. Nonimmunosuppressed and tacrolimus-treated recipients were insulin independent posttransplant, but rejected their islet allografts in 8 days. Engraftment and insulin independence were achieved in seven of seven baboon recipients of anti-CD154 induction therapy administered on days -1, 3, and 10 relative to the islet transplant. Three of three baboons treated with 20 mg/kg anti-CD154 induction therapy experienced delayed rejection episodes, first detected by elevations in postprandial blood glucose levels, on postoperative day (POD) 31 for one and on POD 58 for the other two. Re-treatment with three doses of anti-CD154 resulted in reversal of rejection in all three animals and in a return to normoglycemia and insulin independence in two of three baboons. It was possible to reverse multiple episodes of rejection with this approach. A loss of functional islet mass, as detected by reduced first-phase insulin release in response to intravenous glucose tolerance testing, was observed after each episode of rejection. One of two baboons treated with 10 mg/kg induction therapy became insulin independent post-transplant but rejected the islet graft on POD 10; the other animal experienced a reversible rejection episode on POD 58 and remained insulin independent and normoglycemic until POD 264. Two additional baboon recipients of allogeneic islets and donor bone marrow (infused on PODs 5 and 11) were treated with induction therapy (PODs -1, 3, 10), followed by initiation of monthly maintenance therapy (for a period of 6 months) on POD 28. Rejection-free graft survival and insulin independence was maintained for 114 and 238 days, with preservation of functional islet mass observed in the absence of rejection. Prevention and reversal of rejection, in the absence of the deleterious effects associated with the use of conventional immunosuppressive drugs, make anti-CD154 a unique agent for further study in islet cell transplantation.
Electrochemical Pretreatment of Thin Film Platinum Electrodes (1988)

Thin film noble metal electrodes and electrode arrays prepared by photolithographic process suffer from contamination of the surface by the traces of transition metals and their oxides which are used as adhesion promoters at the insulating substrates. This contamination is an ongoing process as the transition metals migrate continuously along the grain boundaries through the thin (1000–4000Å) layer of the noble metal. The transition metal oxide affects the electrochemical properties of the noble metal surface and also its electron work function. A simple electrochemical pretreatment has been developed which removes these contaminants from the surface and "anneals" the surface in such a way that acceptable electrochemical behavior identical with a thick noble metal electrode is obtained. It consists of electrochemical etching of the surface by pulsing it between 0 and +2V in solution containing 0.08M EDTA, 5.2% , and for 5–10 min. It is then followed by cycling of the applied potential between 0.4 and −0.4V in for 10 min. Surfaces prepared by this procedure have remained clean for a period of at least 24h.
Genomic Determinants of PI3K Pathway Inhibitor Response in Cancer (2012)

The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in cancer as a result of genetic (e.g., amplifications, mutations, deletions) and epigenetic (e.g., methylation, regulation by non-coding RNAs) aberrations targeting its key components. Several lines of evidence demonstrate that tumors from different anatomical sites depend on the continued activation of this pathway for the maintenance of their malignant phenotype. The PI3K pathway therefore is an attractive candidate for therapeutic intervention, and inhibitors targeting different components of this pathway are in various stages of clinical development. Burgeoning data suggest that the genomic features of a given tumor determine its response to targeted small molecule inhibitors. Importantly, alterations of different components of the PI3K pathway may result in distinct types of dependencies and response to specific therapeutic agents. In this review, we will focus on the genomic determinants of response to PI3K, dual PI3K/mechanistic target of rapamycin (mTOR), mTOR, and AKT inhibitors in cancer identified in preclinical models and clinical trials to date, and the development of molecular tools for the stratification of cancer patients.
The Metaphor Is the Key: Cryptography, the Clipper Chip, and the Constitution (1995)

Part I of this Article describes advances in encryption technology that are increasing personal privacy, particularly electronic privacy, but reducing the U.S. government's ability to wiretap telephones, read e-mail surreptitiously, and decrypt computer disks and other encrypted information. Specifically, Part I focuses on the Escrowed Encryption Standard (EES), to be implemented in the Clipper Chip and other similar devices. Part II examines the legal justifications and constitutional implications of the EES proposal. It argues that the EES proposal violates the spirit, although not the letter, of the Administrative Procedures Act and represents an abuse of the technical standard-setting process. Part III considers the constitutional implications of the more radical proposal that some commentators find implicit in the policies animating Clipper: requiring all users of strong encryption to register their ciphers' keys with the government. Part III concludes that although mandatory key escrow would infringe personal privacy, reduce associational freedoms, potentially chill speech, constitute a potentially unreasonable search, and might even require a form of self-incrimination, the constitutionality of mandatory key escrow legislation remains a distressingly close question under existing doctrines.Part IV addresses the cryptography controversy as an example of the law's occasionally awkward response to a new technology. Finally, the Technical Appendix discusses modern cryptographic systems, including the widely-used Data Encryption Standard (DES), and how they can (at least theoretically) be broken by attackers armed with large numbers of relatively modest computers. It also provides an introduction to public-key cryptosystems and to digital signatures, which could represent the most important commercial application of modern cryptographic techniques.
DCSO: Dynamic Combination of Detector Scores for Outlier Ensembles (2019)

Selecting and combining the outlier scores of different base detectors used within outlier ensembles can be quite challenging in the absence of ground truth. In this paper, an unsupervised outlier detector combination framework called DCSO is proposed, demonstrated and assessed for the dynamic selection of most competent base detectors, with an emphasis on data locality. The proposed DCSO framework first defines the local region of a test instance by its k nearest neighbors and then identifies the top-performing base detectors within the local region. Experimental results on ten benchmark datasets demonstrate that DCSO provides consistent performance improvement over existing static combination approaches in mining outlying objects. To facilitate interpretability and reliability of the proposed method, DCSO is analyzed using both theoretical frameworks and visualization techniques, and presented alongside empirical parameter setting instructions that can be used to improve the overall performance.
The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein (2003)

Pathological examinations, using a panel of tau and other antibodies, were performed on the brains from 55 consecutively acquired cases of frontotemporal lobar degeneration (FTLD). Clinically, these comprised 31 cases of frontotemporal dementia (FTD), 10 cases of motor neurone disease inclusion dementia (MNDID), seven cases of progressive aphasia (PA), four cases of semantic dementia (SD) and three cases of progressive apraxia (PAX). Tau pathology, in the form of neurofibrillary tangles (NFTs) and glial cell tangles, was present in six cases of FTD with parkinsonism linked to chromosome 17, five of these cases resulting from +16 splice-site mutation and one from +13 mutation in the tau gene. The insoluble tau proteins were comprised mostly of four-repeat (4-R) isoforms. Eight other cases of FTD, one of PA and all three cases of PAX showed tau-positive inclusions (Pick bodies) and swollen cells (Pick cells), characteristic of Pick's disease. In these cases, the insoluble tau proteins were present in most instances as three-repeat (3-R) tau isoforms, although two cases with a mixture of 3-R and 4-R isoforms were seen. One other case of FTD showed an unusual pathology characterized by massive extracellular deposition of tau protein, composed of 4-R tau isoforms, within white matter without neuronal or glial cell inclusions. However, 33 (60%) of 55 FTLD cases showed no tau pathology in the brain, except for the rare NFTs, composed of a mix of 3-R and 4-R isoforms, in some of the more elderly cases. Of these 33 cases, 13 had FTD, 10 had MNDID, six had PA and four had SD. The pathological changes present were those of a superficial cortical laminar microvacuolation with mild subpial and subcortical gliosis; the 10 MNDID cases had ubiquitin-positive inclusions in the cerebral cortex and hippocampus. These 33 nontau FTLD cases, along with five Alzheimer's disease (AD) and six Huntington's disease (HD) cases with severe pathology, showed a variable loss of soluble tau proteins, broadly comparable with the extent of neuronal loss from the cortex and loss of the intracortical perikaryal marker, NeuN, but unrelated to proteins within afferent projection fibres such as neurofilament and alpha-synuclein. Levels of tau mRNA were decreased in parallel in the tau-negative FTLD cases and in the severe AD and HD cases. Hence, the loss of tau from these 33 nontau FTLD cases is just one aspect of a neurodegenerative process that destroys many components of the nerve cell machinery and does not represent a specific disordering of the cell's ability to form tau proteins or incorporate these into microtubules.
Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis (2014)

Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. Subsequent to induction of collagen antibody-induced arthritis (CAIA), Hmgb1 mRNA and extranuclear protein levels were significantly increased in the lumbar spinal cord. Intrathecal (i.t.) injection of a neutralizing anti-HMGB1 monoclonal antibody or recombinant HMGB1 box A peptide (Abox), which each prevent extracellular HMGB1 activities, reversed CAIA-induced mechanical hypersensitivity. This occurred during ongoing joint inflammation as well as during the postinflammatory phase, indicating that spinal HMGB1 has an important function in nociception persisting beyond episodes of joint inflammation. Importantly, only HMGB1 in its partially oxidized isoform (disulfide HMGB1), which activates toll-like receptor 4 (TLR4), but not in its fully reduced or fully oxidized isoforms, evoked mechanical hypersensitivity upon i.t. injection. Interestingly, although both male and female mice developed mechanical hypersensitivity in response to i.t. HMGB1, female mice recovered faster. Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.