gebhart/patrepeval huggingface dataset:
Ph+ acute lymphoblastic leukemia resistant to the tyrosine kinase inhibitor STI571 has a unique BCR-ABL gene mutation (2002)

The tyrosine kinase inhibitor STI571 is a promising agent for the treatment of advanced Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL), but resistance develops rapidly in most patients after an initial response. To identify mechanisms of resistance to STI571, 30 complementary DNAs (including 9 matched samples) obtained from the bone marrow of individuals with Ph(+) ALL were analyzed by direct sequencing of a 714-base pair region of ABL encoding for the adenosine triphosphate (ATP)-binding site and the kinase activation loop. A single point mutation was found at nucleotide 1127 (GI6382056) resulting in Glu255Lys. This mutation occurred in 6 of 9 patients (67%) following their treatment with STI571 but not in the samples from patients before beginning treatment with STI571. Glu255Lys is within the motif important for forming the pocket of the ATP-binding site in ABL and it is highly conserved across species. In conclusion, Ph(+) ALL samples resistant to STI571 have a unique mutation Glu255Lys of BCR-ABL.
Helmet: A resistance drift resilient architecture for multi-level cell phase change memory system (2011)

Phase change memory (PCM) is emerging as a promising solution for future memory systems and disk caches. As a type of resistive memory, PCM relies on the electrical resistance of Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Sb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Te <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> (GST) to represent stored information. With the adoption of multi-level programming PCM devices, unwanted resistance drift is becoming an increasing reliability concern in future high-density, multi-level cell PCM systems. To address this issue without incurring a significant storage and performance overhead in ECC, conventional design employs a conservative approach, which increases the resistance margin between two adjacent states to combat resistance drift. In this paper, we show that the wider margin adversely impacts the low-power benefit of PCM by incurring up to 2.3X power overhead and causes up to 100X lifetime reduction, thereby exacerbating the wear-out issue. To tolerate resistance drift, we proposed Helmet, a multi-level cell phase change memory architecture that can cost-effectively reduce the readout error rate due to drift. Therefore, we can relax the requirement on margin size, while preserving the readout reliability of the conservative approach, and consequently minimize the power and endurance overhead due to drift. Simulation results show that our techniques are able to decrease the error rate by an average of 87%. Alternatively, for satisfying the same reliability target, our schemes can achieve 28% power savings and a 15X endurance enhancement due to the reduced margin size when compared to the conservative approach.
Restoring a functional β‐cell mass in diabetes (2008)

Type 1 and type 2 diabetes have often been presented as disease forms that profoundly differ in the presence and pathogenic significance of a reduced beta-cell mass. We review evidence indicating that the beta-cell mass in type 1 diabetes is usually not decreased by at least 90% at clinical onset, and remains often detectable for years after diagnosis at age above 15 years. Clinical and experimental evidence also exists for a reduced beta-cell mass in type 2 diabetes where it can be the cause for and/or the consequence of dysregulated beta-cell functions. With beta-cell mass defined as number of beta-cells, these views face the limitation of insufficient data and methods for human organs. Because beta-cells can occur under different phenotypes that vary with age and with environmental conditions, we propose to use the term functional beta-cell mass as an assessment of a beta-cell population by the number of beta-cells and their phenotype or functional state. Assays exist to measure functional beta-cell mass in isolated preparations. We selected a glucose-clamp test to evaluate functional beta-cell mass in type 1 patients at clinical onset and in type 1 recipients following intraportal islet cell transplantation. Comparison of the data with those in non-diabetic controls helps targeting and monitoring of therapeutic interventions.
Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells (2015)

HIV reservoirs and production of viral antigens are not eliminated in chronically infected participants treated with combination antiretroviral therapy (cART). Novel therapeutic strategies aiming at viral reservoir elimination are needed to address chronic immune dysfunction and non-AIDS morbidities that exist despite effective cART. The HIV envelope protein (Env) is emerging as a highly specific viral target for therapeutic elimination of the persistent HIV-infected reservoirs via antibody-mediated cell killing. Dual-Affinity Re-Targeting (DART) molecules exhibit a distinct mechanism of action via binding the cell surface target antigen and simultaneously engaging CD3 on cytotoxic T lymphocytes (CTLs). We designed and evaluated Env-specific DARTs (HIVxCD3 DARTs) derived from known antibodies recognizing diverse Env epitopes with or without broadly neutralizing activity. HIVxCD3 DARTs derived from PGT121, PGT145, A32, and 7B2, but not VRC01 or 10E8 antibodies, mediated potent CTL-dependent killing of quiescent primary CD4 T cells infected with diverse HIV isolates. Similar killing activity was also observed with DARTs structurally modified for in vivo half-life extension. In an ex vivo model using cells isolated from HIV-infected participants on cART, combinations of the most potent HIVxCD3 DARTs reduced HIV expression both in quiescent and activated peripheral blood mononuclear cell cultures isolated from HIV-infected participants on suppressive cART. Importantly, HIVxCD3 DARTs did not induce cell-to-cell virus spread in resting or activated CD4 T cell cultures. Collectively, these results provide support for further development of HIVxCD3 DARTs as a promising therapeutic strategy for targeting HIV reservoirs.
A COMPARATIVE STUDY OF MODIFIED BIELSCHOWSKY, BODIAN AND THIOFLAVIN S STAINS ON ALZHEIMER'S NEUROFIBRILLARY TANGLES (1986)

Serial sections of the brains of two cases with Alzheimer's disease were stained with the standard Bodian, modified Bielschowsky (reformed Gros-Schultze's modification) and thioflavin S methods. The numbers of demonstrated Alzheimer's neurofibrillary tangles (NFTs) were different between the two silver stains: from 15 to 75% more NFTs were shown and more distinctly with the modified Bielschowsky stain than with the Bodian stain. Many of the NFTs in both cases were of eosinophilic and less argentophilic type. Although the NFTs were not counted, the thioflavin S stain seemed to have no apparent advantage over the modified Bielschowsky stain in the demonstration of NFTs.
Effect of dexmedetomidine on postoperative cognitive dysfunction and inflammation in patients after general anaesthesia (2019)

Perioperative dexmedetomidine treatment is associated with significantly reduced incidence of POCD and inflammation and better neurocognitive function postoperatively in comparison with both saline controls and comparator anaesthetics.
Lipopolyplex for Therapeutic Gene Delivery and Its Application for the Treatment of Parkinson’s Disease (2016)

Lipopolyplex is a core-shell structure composed of nucleic acid, polycation and lipid. As a non-viral gene delivery vector, lipopolyplex combining the advantages of polyplex and lipoplex has shown superior colloidal stability, reduced cytotoxicity, extremely high gene transfection efficiency. Following intravenous administration, there are many strategies based on lipopolyplex to overcome the complex biological barriers in systemic gene delivery including condensation of nucleic acids into nanoparticles, long circulation, cell targeting, endosomal escape, release to cytoplasm and entry into cell nucleus. Parkinson's disease (PD) is the second most common neurodegenerative disorder and severely influences the patients' life quality. Current gene therapy clinical trials for PD employing viral vectors didn't achieve satisfactory efficacy. However, lipopolyplex may become a promising alternative approach owing to its stability in blood, ability to cross the blood-brain barrier (BBB) and specific targeting to diseased brain cells.
Homodimeric and Heterodimeric Bis(amino thiol) Oxometal Complexes with Rhenium(V) and Technetium(V). Control of Heterodimeric Complex Formation and an Approach to Metal Complexes that Mimic Steroid Hormones (1994)

We have investigated the possibility of preparing complexes of rhenium and technetium whose shape resembles that of ligands for steroid receptors. The general structure of N2S2 complexes of oxorhenium(V) and oxotechnetium(V) is such that they could replace the BC ring system of steroid, thereby generating a metal complex system with considerable size and shape similarity to a steroid. Such a metal-integrated steroid-shaped complex can be constructed as a heterodimer of two different amino thiols; complexes of rhenium and technetium with such heterodimeric bis-bidentate structure have not been systematically studied. In this investigation, we have shown that complexes of this nature form readily when appropriate metal precursors are combined with a mixture of amino thiols. In the systems we have studied, heterodimeric complex formation is preferred over homodimeric complex formation, and in one system where we were able to obtain an X-ray crystal structure, this oxorhenium heterodimer had the desired trans geometry. These rhenium and technetium-99m complexes are reasonably stable toward ligand exchange; they can be readily purified by chromatography under appropriate conditions, and the one technetium-99m complex studied in vivo shows some persistence in blood and gives good initial uptake in several tissues. The convenient and selective formation of such bis-bidentate heterodimeric complexes suggests that the development of metal-integrated complexes that resemble ligands for receptors may be possible.
The Preference Functions Method for Predicting Protein Helical Turns with Membrane Propensity (1998)

The prediction of secondary structure conformation of membrane-buried segments of integral membrane proteins is done in this work by using the method of preference functions (Juretić et al. In Theoretical and Computational Chemistry; Párkányi, C., Ed.; Elsevier Science: Amsterdam, 1998; Vol 5, Chapter 13, p 405). The method is here extended by predicting sequence location, hydrophobic moments, and transmembrane orientation of helical segments. Independent evaluation of the method with ubiquinol-cytochrome c reductase subunits is performed before some already known details of the crystal structure of that respiratory complex are released. Tests with potassium channels revealed that their characteristic super-secondary structure in the pore region can be recognized by performing the analysis with preference functions and with hydrophobic moment threshold functions.
Molecular and antigenic heterogeneity of the rat leukocyte‐common antigen from thymocytes and T and B lymphocytes (1985)

The molecular forms and antigenic heterogeneity of the leukocyte-common antigen (L-CA) of rat lymphocytes have been analyzed. Thymocytes show one main band at 180 kDa, T cells four bands at 180, 190, 200 and 220 kDa and B cells one broad band at about 240 kDa. T helper and T cytotoxic cell subsets show the same four bands with some differences in the proportion of each. Four mouse monoclonal antibodies (MRC OX-1, 28, 29 and 30) reacted with all molecular forms of L-CA and fell into two sets that were noncompetitive in binding to L-CA (MRC OX-1, 28, 29 vs. OX-30). The antigenic determinants seen by all these antibodies were lost when L-CA was reduced and alkylated. Three antibodies (MRC OX-22, 31 and 32) reacted selectively with B cells, T cytotoxic cells and about 2/3 of T helper cells. OX-22 and OX-31 competed for binding but were noncompetitive with OX-32. All these antibodies bound to a subfraction of the 190, 200 and 220-kDa forms of T cell L-CA but not at all to the 180-kDa form of T cells or thymocytes. One antibody bound to B cells only (MRC OX-33) and precipitated a subfraction of B cell L-CA. With all the antibodies that did not label thymocytes the antigenic determinants survived reduction and alkylation. Subsequent proteolysis with trypsin then destroyed all determinants except the one reacting with MRC OX-22 antibody. In this case tryptic peptides retained full antigenic activity which was, however, destroyed by further proteolysis with pronase.
Antimicrobial Resistance of Major Foodborne Pathogens from Major Meat Products (2010)

The bacterial contamination of raw and processed meat products with resistant pathogens was studied. The raw samples included sheep (40), goat (40), pork (120), beef (80), and chicken (19) meat, and the processed samples included turkey filets (33), salami (8), readymade mincemeat (16), stuffing (22), and roast-beef (50). The samples were collected from retail shops in Northwestern Greece over a period of 3 years. The isolated pathogens were evaluated for susceptibilities to 19 antimicrobial agents used in humans. Out of 428 samples, 157 strains of Escherichia coli, 25 of Yersinia enterocolitica, 57 of Staphylococcus aureus, 57 of Enterococcus spp., 4 of Salmonella spp., and 3 of Campylobacter jejuni were isolated. Among the isolates 14.6% of the E. coli, 10.5% of S. aureus, 4% of Y. enterocolitica, 25% of Salmonella spp., and 42.1% of Enterococcus spp. were susceptible to antibiotics. E. coli from chicken exhibited high rates of resistance to ciprofloxacin (62.5%) followed by lamb/goat (10.9%), pork (15.7%), and beef (27.9%) meat. Resistance to nitrofurantoin dominated in the lamb/goat isolates (60%). Resistance to tetracycline predominated in pork (68.2%) and chicken (62.5%), and resistance to aminoglycosides dominated in lamb/goat meat isolates. S. aureus resistance to clindamycin predominated in lamb/goat isolates (50%), whereas resistance to ciprofloxacin predominated in the pork strains, but no resistance to methicillin was observed. Of the enterococci isolates 21.1% were resistant to vancomycin. High resistance to ampicillin (96%) was observed in Y. enterocolitica and all of the C. jejuni isolates were resistant to ampicillin, cephalothin, and cefuroxime. These results indicate that meat can be a source of resistant bacteria, which could potentially be spread to the community through the food chain.
Wavelength stable uncooled fibre grating semiconductorlaser for use in an alloptical WDM access network (1996)

The use of angled facet semiconductor laser chips in fibre grating lasers (FGL) is shown to dramatically improve device characteristics over conventional normal facet FGLs. This improvement in performance allows the laser to be operated with no temperature control at 155 Mbit/s and makes it feasible for it to be used as a wavelength stable, uncooled source in a WDM optical access network.
Simultaneous in-Situ Monitoring of Parallel Polymerization Reactions Using Light Scattering; A New Tool for High-Throughput Screening (2004)

A recently introduced technique, simultaneous multiple sample light scattering (SMSLS), was used to monitor parallel polymerization reactions in situ. SMSLS is designed for real-time, high-throughput screening and provides a time-dependent light scattering signature for each reaction, which contains both qualitative and semiquantitative information. Qualitatively, the signature immediately indicates whether the reaction occurs or not, whether there is an initial lag period, and how long the reaction takes until it stops. The signature also provides estimates of the reaction rate and weight average molecular mass M(w), and its shape can help identify mechanistic aspects, for example, controlled versus free radical polymerization, presence of impurities, etc. The method is inherently adapted to small sample volumes and requires no special sample preparation or postpolymerization characterization. The demonstration here involved the free radical polymerization of acrylamide under varying conditions and should be readily applicable to a wide variety of other reactions. Results were cross-checked with multi-detector gel permeation chromatography.
Cryptosporidium parvum in calves: kinetics and immunoblot analysis of specific serum and local antibody responses (immunoglobulin A [IgA], IgG, and IgM) after natural and experimental infections (1992)

Fecal and serum anti-Cryptosporidium parvum immunoglobulin A (IgA), IgM, and IgG were monitored by an enzyme-linked immunosorbent assay after experimental and natural infection of calves with C. parvum. Although all experimentally infected calves showed high levels of colostral antibodies in the feces, they acquired C. parvum infection. Three of five animals died. Calves which acquired natural infection showed only diarrhea. Levels of colostral coproantibodies dropped quickly. Experimental infection was followed by a rise in local anti-C. parvum IgM levels from day 5 postinfection (p.i.). IgM peaked at day 14 p.i. and then disappeared quickly. Anti-C. parvum IgA levels rose between days 7 and 14 p.i. and decreased slowly. Rising levels of coproantibodies coincided with falling oocyst output. Fecal anti-C. parvum IgG levels rose slightly during oocyst output, and IgG disappeared 3 weeks p.i. Similar kinetics were established in naturally infected calves. Although fecal anti-C. parvum IgA levels declined slowly, reinfections were established 5, 7, and 14 weeks after the primary contact. Serum anti-C. parvum IgG levels rose during maximal oocyst excretion, whereas serum anti-C. parvum IgA levels peaked later than did local IgA levels. Challenge reinfection of naturally infected calves at day 112 was not followed by clinical signs or oocyst output or by a secondary antibody response. Sequential Western immunoblotting with fecal extracts revealed up to 32 different parasite antigens. Convalescent-phase sera recognized up to 23 antigens. Fecal IgA reacted intensely with antigens with relative molecular weights (M(r)) of approximately 11,000 and 15,000. These antigens were not recognized by convalescent-phase serum IgG. Both local IgA and serum IgG also showed strong reactions with 23,000- and 44,000-M(r) antigens and with several antigens of between 66,200 and 200,000 M(r). Most bands remained detectable for at least 16 weeks p.i.
Crystal Structure of the Cowpox Virus-Encoded NKG2D Ligand OMCP (2012)

ABSTRACT The NKG2D receptor is expressed on the surface of NK, T, and macrophage lineage cells and plays an important role in antiviral and antitumor immunity. To evade NKG2D recognition, herpesviruses block the expression of NKG2D ligands on the surface of infected cells using a diverse repertoire of sabotage methods. Cowpox and monkeypox viruses have taken an alternate approach by encoding a soluble NKG2D ligand, the orthopoxvirus major histocompatibility complex (MHC) class I-like protein (OMCP), which can block NKG2D-mediated cytotoxicity. This approach has the advantage of targeting a single conserved receptor instead of numerous host ligands that exhibit significant sequence diversity. Here, we show that OMCP binds the NKG2D homodimer as a monomer and competitively blocks host ligand engagement. We have also determined the 2.25-Å-resolution crystal structure of OMCP from the cowpox virus Brighton Red strain, revealing a truncated MHC class I-like platform domain consisting of a beta sheet flanked with two antiparallel alpha helices. OMCP is generally similar in structure to known host NKG2D ligands but has notable variations in regions typically used to engage NKG2D. Additionally, the determinants responsible for the 14-fold-higher affinity of OMCP for human than for murine NKG2D were mapped to a single loop in the NKG2D ligand-binding pocket.
TBK1 inhibitors: a review of patent literature (2011 – 2014) (2015)

The role of TBK1 in various diseases has prompted the further investigation of significant targets. Although research on TBK1 inhibitors has increased over the last few years, only a few inhibitors of this kinase have been identified. In addition, almost all of the chemical inhibitors are modified from different scaffolds and/or chemotypes of pyrimidine. Specifically, compound BX795 is the representative one, which was first patented as a potent TBK1 inhibitor. Even though some compounds have displayed interesting potential inhibition and selectivity of TBK1 in vitro and in in vivo trials, the development of more efficient and selective TBK1 inhibitors is still required.
Content-based image retrieval (2005)

The last decade has witnessed great interest in research on content-based image retrieval. This has paved the way for a large number of new techniques and systems, and a growing interest in associated fields to support such systems. Likewise, digital imagery has expanded its horizon in many directions, resulting in an explosion in the volume of image data required to be organized. In this paper, we discuss some of the key contributions in the current decade related to image retrieval and automated image annotation, spanning 120 references. We also discuss some of the key challenges involved in the adaptation of existing image retrieval techniques to build useful systems that can handle real-world data. We conclude with a study on the trends in volume and impact of publications in the field with respect to venues/journals and sub-topics.
Necessary and sufficient conditions for deadlock-free operation in flexible manufacturing systems using a colored Petri net model (1999)

Concurrent competition for finite resources by multiple parts in flexible manufacturing systems (FMS) results in deadlock. This is an important issue to be addressed in the operation of the system. A Petri net model, called colored resource-oriented Petri net (CROPN), is developed in this paper. The concurrent resource contention and the important characteristics of the production processes necessary for deadlock control are well modeled by this model. Based on the developed model, necessary and sufficient conditions and an efficient control law are presented for deadlock-free operation in FMS. This control law is a policy of dynamic resource allocation. It determines when a resource can be allocated to which job to avoid deadlock. This control law allows as many active parts as possible to be in the system, while deadlock is totally avoided. This control law is easy to implement and can be embedded into the real-time scheduler. A simple example is used to illustrate the application of the approach.
Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. (1978)

Alveolar macrophages have been shown to bind glycoproteins and synthetic glycoconjugates (neoglycorpoteins) that have mannose, N-acetylglucosamine, or glucose in the exposed, nonreducing position. Galactose-terminal glycoproteins are not bound. Binding of radiolabeled ligands to cells is nearly completely impaired by the presence of an excess of yeast mannan. Binding is temperature sensitive and proceeds optimally at pH 7.0. Prior treatment of the cells with trypsin severely decreases their capacity to bind ligands. An inhibition assay has been developed, using radioiodinated glucose-albumin conjugate, agalacto-orosomucoid, beta-glucuronidase, and RNase B as ligands. Various glycoproteins have been shown to be effective inhibitors of ligand binding including horseradish peroxidase, agalacto-orosomucoid, beta-glucuronidase, ovalbumin, agalacto-fetuin, and RNase B. RNase A and asialo-fetuin are ineffective as antagonists. The results suggest the presence of a cell surface receptor on alveolar macrophages that binds glycoproteins having terminal sugars with the mannose or glucose configuration.