gebhart/patrepeval huggingface dataset:
Using function folding to improve silicon efficiency of reconfigurable arithmetic arrays (2005)

This work presents function folding, a design principle to improve the silicon efficiency of reconfigurable arithmetic (coarse-grain) arrays. Though highly parallel implementations of DSP algorithms have been demonstrated on these arrays, the overall silicon efficiency of current devices is limited by both the large numbers of ALUs required in the array and by the only moderate speeds which are achieved. The operating frequencies are mainly limited by the requirements of nonlocal routing connections. We present a novel approach to overcome these limitations: In function folding, a small number of distinct operators belonging to the same configuration are folded onto the same ALU, i.e. executed sequentially on one processing element. The ALU is controlled by a program repetitively executing the same instruction sequence. Data only required locally is stored in a local register file. This sequential approach uses the individual ALU resources more efficiently, while all processing elements of the array work in parallel as in current devices. Additionally, the ALUs and local registers can be clocked with a higher frequency than the (nonlocal) routing connections. Overall, a higher computational density than in current devices results.
FACIL: Fast and Accurate Genetic Code Inference and Logo (2011)

FACIL is available as a web-based service at http://www.cmbi.ru.nl/FACIL/ and as a stand-alone program.
Cell-mediated cleavage of Pseudomonas exotoxin between Arg279 and Gly280 generates the enzymatically active fragment which translocates to the cytosol. (1992)

Pseudomonas exotoxin (PE) is a three-domain toxin which is cleaved by a cellular protease within cells and then reduced to generate two prominent fragments (Ogata, M., Chaudhary, V. K., Pastan, I., and FitzGerald, D. J. (1990) J. Biol. Chem. 265, 20678-20685). The N-terminal fragment is 28 kDa in size and contains the binding domain. The 37-kDa C-terminal fragment, which translocates to the cytosol, contains the translocation domain and the ADP-ribosylation domain. Cleavage followed by reduction is essential for toxicity since mutant forms of the toxin that cannot be cleaved by cells are nontoxic. Previous results with these mutants suggest that cleavage occurred in an arginine-rich (arginine residues are at positions 274, 276, and 279) disulfide loop near the beginning of the translocation domain, but the exact site of cleavage was not determined. Since very few molecules of the 37-kDa fragment are generated within cells it was not possible to determine the site of cleavage by performing a conventional N-terminal sequence analysis of the 37-kDa fragment. Two experimental approaches were used to overcome this limitation. First, existing amino acids near the cleavage sites were replaced with methionine residues; this was followed by the addition of [35S]methionine-labeled versions of these toxins to cells. The pattern of radioactive toxin fragments recovered from the cells indicated that the toxin was cleaved either just before or just after Arg279. Second, [3H]leucine-labeled toxin was produced and added to the cells. Sequential Edman degradations were performed on the small amount of radioactive 37-kDa fragment that could be recovered from toxin-treated cells. A peak of radioactivity in the fifth fraction indicated that leucine was the 5th amino acid on the C-terminal side of the cleavage site. This result confirmed that cleavage was between Arg279 and Gly280.
Combination checkpoint immunotherapy and cytotoxic chemotherapy: Pembrolizumab (Pembro) plus either docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer. (2017)

398 Background: Metastatic urothelial cancer (mUC) is only modestly responsive to checkpoint inhibitor immunotherapy; e.g., the PDL1 inhibitor atezolizumab confers only a 16% tumor response rate (RR) in platinum-treated mUC. Chemotherapy is hypothesized to enhance tumoral neoantigen expression thus priming response to PD1-directed immunotherapy. Here we report results from the initial cohort of an investigator-initiated trial of Pembro plus either docetaxel or gemcitabine in platinum-treated mUC patients (pts). Methods: Primary endpoint was safety; secondary endpoints were overall RR and progression-free survival (PFS). Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemo (at least 1 platinum-based). Dose limiting toxicity (DLT) was any grade (Gr) 3+ non-heme toxicity, Gr3+ neutropenia w/ fever or infection, or Gr4 platelets (plts), or Gr3 plts with bleeding. In dose level (DL) 1, treatment consisted of Pembro 200 mg IV on D1 q3 weeks plus either docetaxel 75 mg/m2 on D1 (Arm 1) or gemcitabine 1000 mg/m2 on D1&amp;D8 (Arm 2). Results: Overall 12 pts were enrolled in DL1, six in each arm. Median age was 69 years (range 45-84), 8 (67%) male, &amp; 10 (83%) of white race. One pt in each arm had DLT: Gr3 hypophosphatemia in Arm 1, Gr3 diarrhea in Arm 2. Attributable Gr3+ toxicities were seen in 7 (54%). Most common Gr3+ AEs were anemia (5, 38%), fatigue (4, 31%), &amp; neutropenia (4, 31%). There were no treatment related deaths; 3 died from tumor progression (PD). As of 10/2016, 4 pts remain on active therapy. In total 4 pts had confirmed response (1 CR, 3 PR), 2 had stable disease (SD), and 6 had PD for an overall RR of 33% and Disease Control Rate (DCR) of 50%. Arm 1 had an overall RR of 50% (1CR, 2PR, 1SD) and DCR of 67%. Arm 2 had an overall RR of 17% (1PR, 1SD) and DCR of 33%. Median PFS (overall, Arm 1 &amp; 2) were 4.8, 5.7, and 3.7 months. Conclusions: Pembro 200 mg IV q3 weeks plus either full-dose docetaxel or gemcitabine is feasible in platinum-treated mUC pts. Encouraging anti-tumor activity for chemo-immunotherapy was seen in this ongoing study, particularly with Pembro+docetaxel. Further investigation of this approach is warranted. Clinical trial information: NCT02437370.
β-Secretase as a Therapeutic Target for Inhibitor Drugs (2002)

Recent identification of beta-scretasse being a membrane-associated aspartic protease has stimulated strong interest on this enzyme as a therapeutic target for Alzheimer s disease. Here we review the current understanding in the structure-function relationship as well as the status in the design of its inhibitors of this protease, memapsin 2 (BACE, ASP-2). The development in the basic tools, such as the preparation of recombinant memapsin 2, the assay method for kinetic measurements of inhibition, the determination of the subsite specificity and the crystal structure of memapsin 2 complexed to a tight-binding inhibitor, has made the structural based inhibitor design possible. More recent inhibitors, having Ki values in the nanomolar range and molecular size in low 700 Da, show some promise that clinically useful inhibitors of beta-scretasse may be attainable.
Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. (1991)

The roles of polypeptide growth factors in promoting wound healing and in directing the specificity and sequence of responses of different tissues in wounds are little understood. We investigated the influence of four growth factors on the rates of healing of a novel full thickness dermal ulcer placed on an avascular base in the rabbit ear. The wound model precludes significant wound contraction and requires new granulation tissue and epithelial cells for healing to originate centripetally. 5 micrograms (7-31 pmol/mm2) of platelet-derived growth factor-B chain (PDGF-BB), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) applied locally at the time of wounding resulted in a twofold increase in complete reepithelialization of treated wounds (PDGF-BB, P = 0.02 chi square analysis; bFGF, P = 0.04; EGF, P = 0.05); transforming growth factor (TGF)-beta 1 significantly inhibited reepithelialization (P = 0.05). Both PDGF-BB and TGF-beta 1 uniquely increased the depth and area of new granulation tissue (P less than 0.005), the influx of fibroblasts, and the deposition of new matrix into wounds. Explants from 7-d old PDGF-BB-treated wounds remained metabolically far more active than controls, incorporating 473% more [3H]thymidine into DNA (P = 0.05) and significantly more [3H]leucine and [3H]proline into collagenase-sensitive protein (P = 0.04). The results establish that polypeptide growth factors have significant and selective positive influences on healing of full thickness ulcers in the rabbit.
New Drugs in Development for the Treatment of Diabetes (2009)

In Brief A variety of new agents are in development for the treatment of type 1 or type 2 diabetes. In addition to new dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 analogs, thiazolidinediones, glinides, and new insulin formulations, there are also unique peroxisome proliferator-activated receptor agonists, selective sodium glucose cotransporter 2 inhibitors, and several other unique agents now in development.
Behavior of Glucosinolates in Pickling Cruciferous Vegetables (2006)

Crucifer species, which include widely consumed vegetables, contain glucosinolates as secondary metabolites. Cruciferous vegetables are consumed in Japan in salt-preserved or pickled form as well as cooked and raw fresh vegetables. In this study, changes in contents of glucosinolates during the pickling process were investigated. 4-Methylthio-3-butenyl glucosinolate, a major glucosinolate in the root of Japanese radish, daikon (Raphanus sativus L.), was detected in pickled products with a short maturation period but not in those with a long maturation period. As a model pickling experiment, fresh watercress (Nasturtium officinale) and blanched watercress were soaked in 3% NaCl solution for 7 days. The results showed that the ratio of indole glucosinolates to total glucosinolates increased during the pickling process, whereas total glucosinolates decreased. Myrosinase digestion of glucosinolates in nozawana (Brassica rapa L.) indicated that indole glucosinolates, especially 4-methoxyglucobrassicin, were relatively resistant to the enzyme. The effect of pickling on glucosinolate content and the possible mechanism are discussed in view of degradation by myrosinase and synthetic reaction in response to salt stress or compression during the pickling process.
Interactions between environmental variables determine immunity in the Indian meal moth Plodia interpunctella (2011)

1. Animals raised in good environmental conditions are expected to have more resources to invest in immunity than those raised in poor conditions. Variation in immune activity and parasite resistance in response to changes in environmental temperature, population density and food quality have been shown in many invertebrate species. 2. Almost all studies to date have examined the effects of individual variables in isolation. The aim of this study was to address whether environmental factors interact to produce synergistic effects on phenoloxidase (PO) activity and haemocyte count, both indicators of immune system activity. Temperature, food quality and density were varied in a fully factorial design for a total of eight treatment combinations. 3. Strong interactions between the three environmental variables led to the magnitude and in some cases the direction of the effect of most variables changing as the other environmental factors were altered. Overall, food quality had the most important and consistent influence, larvae raised on a good-quality diet having substantially higher PO activity in every case and substantially higher haemocyte counts in all treatments except unheated/low density. 4. When food quality was good, the larvae showed 'density-dependent prophylaxis': raising their investment in immunity when population density is high. When food quality was poor and the temperature low, however, those larvae raised at high densities invested less in immunity. 5. Increased temperature is often thought to lead to increased immune reactivity in ectotherms, but we found that the effect of temperature was strongly dependent on the values of other environmental variables. PO activity increased with temperature when larvae were raised on good food or when density was high, but when food was poor and density low, a higher temperature led to reduced PO activity. A higher temperature led to higher haemocyte counts when density was high and food quality was poor, but in all other cases, the effect of increased temperature was either close to zero or somewhat negative. 6. Although PO activity and haemocyte count were weakly correlated across the whole data set, there were a number of treatments where the two measures responded in different ways to environmental change. Overall, effect sizes for PO activity were substantially higher than those for haemocyte count, indicating that the different components of the immune system vary in their sensitivity to environmental change. 7. Predictions of the effect of environmental or population change on immunity and disease dynamics based on laboratory experiments that only investigate the effects of single variable are likely to be inaccurate or even entirely wrong.
Selective Catalytic Reduction for Treating the NOx Emissions from Lean-Burn Gasoline Engines: Durability Assessment (2008)

&lt;div class="htmlview paragraph"&gt;A laboratory study was performed to assess the potential of using selective catalytic reduction (SCR) with NH&lt;sub&gt;3&lt;/sub&gt; to treat the NO&lt;sub&gt;x&lt;/sub&gt; emissions from lean-burn gasoline engines. A primary concern was the potential for hot rich exhaust conditions on the vehicle, as such conditions could degrade the zeolite-based SCR catalysts being developed for automotive applications. Samples of an iron/zeolite formulation were aged for 34 hours behind samples of a three-way catalyst (TWC) on a pulse-flame combustion reactor using different A/F ratio schedules that exposed the catalysts to either continuously lean operation, mostly stoichiometric operation, or mostly rich operation. For each A/F ratio schedule, separate SCR samples were aged with inlet temperatures of 750°C, 800°C, or 850°C. The aged SCR samples were evaluated for NO&lt;sub&gt;x&lt;/sub&gt; conversion at 25K hr&lt;sup&gt;-1&lt;/sup&gt; during lean temperature ramps with 500 ppm NO and NH&lt;sub&gt;3&lt;/sub&gt;. After aging under mostly rich conditions at 750°C inlet, the Fe SCR catalyst provided a NO&lt;sub&gt;x&lt;/sub&gt; conversion of 94% at 500°C. After aging under mostly stoichiometric or continuously lean conditions at 800°C inlet, which is a reasonable maximum temperature for underfloor converters on some vehicles, the NO&lt;sub&gt;x&lt;/sub&gt; conversions at 500°C were 93% and 97%, respectively.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Samples of a copper/zeolite formulation were similarly aged with the different A/F ratio schedules at an inlet temperature of 800°C. When evaluated at 350°C, the Cu SCR samples provided peak NO&lt;sub&gt;x&lt;/sub&gt; conversions of approximately 95%, 100%, and 100% after aging under mostly rich conditions, mostly stoichiometric conditions, and continuously lean conditions, respectively. These results suggested that both SCR formulations have sufficient durability to be considered for potential use in controlling the NO&lt;sub&gt;x&lt;/sub&gt; emissions from lean-burn gasoline engines.&lt;/div&gt;
Identification and molecular cloning of a gene encoding a fibronectin‐binding protein (CadF) from Campylobacter jejuni (1997)

Campylobacter jejuni, a Gram-negative bacterium, is a common cause of gastrointestinal disease. By analogy with other enteric pathogens such as Salmonella and Shigella, the ability of C. jejuni to bind to host cells is thought to be essential in the pathogenesis of enteritis. Scanning electron microscopy of infected INT407 cells suggested that C. jejuni bound to a component of the extracellular matrix. Binding assays using immobilized extracellular matrix proteins and soluble fibronectin showed specific and saturable binding of fibronectin to C. jejuni. Ligand immunoblot assays using 125I-labelled fibronectin revealed specific binding to an outer membrane protein with an apparent molecular mass of 37 kDa. A rabbit antiserum, raised against the gel-purified protein, reacted with a 37 kDa protein in all C. jejuni isolates (n = 15) as tested by immunoblot analysis. Antibodies present in convalescent serum from C. jejuni-infected individuals also recognized a 37 kDa protein. The gene encoding the immunoreactive 37kDa protein was cloned and sequenced. Sequencing of overlapping DNA fragments revealed an open reading frame (ORF) that encodes a protein of 326 amino acids with a calculated molecular mass of 36872Da. The deduced amino acid sequence of the ORF exhibited 52% similarity and 28% identity to the root adhesin protein from Pseudomonas fluorescens. Isogenic C. jejuni mutants which lack the 37 kDa outer membrane protein, which we have termed CadF, displayed significantly reduced binding to fibronectin. Biotinylated fibronectin bound to a protein with an apparent molecular mass of 37 kDa in the outer membrane protein extracts from wild-type C. jejuni as judged by ligand-binding blots. These results indicate that the binding of C. jejuni to fibronectin is mediated by the 37 kDa outer membrane protein which is conserved among C. jejuni isolates.
History-Based Motion Vector Prediction in Versatile Video Coding (2019)

In this paper, History-based Motion Vector Prediction (HMVP) is presented for video coding. With the proposed method, a table of HMVP candidates is maintained and updated on-the-fly. After decoding one inter-coded block, the table is updated by appending the associated motion information to the table as a new HMVP candidate. A First-In-First-Out (FIFO) rule is applied to manage the table. The HMVP candidates could be added to the Advanced Motion Vector Prediction (AMVP) candidate list as additional motion vector predictors. And they could also be added to the merge candidate list as additional merge candidates. With the proposed method, the motion information of previously coded blocks even not adjacent to the current block can be utilized for more efficient motion vector prediction. Simulation results have validated the efficiency of HMVP, wherein up to 4% BD rate saving could be achieved. The proposed method has been adopted by the next generation video coding standard, named Versatile Video Coding (VVC) developed by Joint Video Exploration Team (JVET).
Concepts and Principles of O-Linked Glycosylation (1998)

The biosynthesis, structures, and functions of O-glycosylation, as a complex posttranslational event, is reviewed and compared for the various types of O-glycans. Mucin-type O-glycosylation is initiated by tissue-specific addition of a GalNAc-residue to a serine or a threonine of the fully folded protein. This event is dependent on the primary, secondary, and tertiary structure of the glycoprotein. Further elongation and termination by specific transferases is highly regulated. We also describe some of the physical and biological properties that O-glycosylation confers on the protein to which the sugars are attached. These include providing the basis for rigid conformations and for protein stability. Clustering of O-glycans in Ser/Thr(/Pro)-rich domains allows glycan determinants such as sialyl Lewis X to be presented as multivalent ligands, essential for functional recognition. An additional level of regulation, imposed by exon shuffling and alternative splicing of mRNA, results in the expression of proteins that differ only by the presence or absence of Ser/Thr(/Pro)-rich domains. These domains may serve as protease-resistant spacers in cell surface glycoproteins. Further biological roles for O-glycosylation discussed include the role of isolated mucin-type O-glycans in recognition events (e.g., during fertilization and in the immune response) and in the modulation of the activity of enzymes and signaling molecules. In some cases, the O-linked oligosaccharides are necessary for glycoprotein expression and processing. In contrast to the more common mucin-type O-glycosylation, some specific types of O-glycosylation, such as the O-linked attachment of fucose and glucose, are sequon dependent. The reversible attachment of O-linked GlcNAc to cytoplasmic and nuclear proteins is thought to play a regulatory role in protein function. The recent development of novel technologies for glycan analysis promises to yield new insights in the factors that determine site occupancy, structure-function relationship, and the contribution of O-linked sugars to physiological and pathological processes. These include diseases where one or more of the O-glycan processing enzymes are aberrantly regulated or deficient, such as HEMPAS and cancer.
Identification of Hepatitis G Virus Particles in Human Serum by E2-Specific Monoclonal Antibodies Generated by DNA Immunization (1998)

In order to elucidate the structure and morphology of hepatitis G virus (HGV), a recently isolated flavivirus, we generated a panel of eight monoclonal antibodies (MAbs) against the putative second envelope protein (E2) following DNA immunization. The MAbs were shown to be specific for four different epitopes on recombinant E2. MAb Mc6 was the only antibody able to detect the linear epitope LTGGFYEPL. In addition, Mc6 was able to immunoprecipitate viral particles in human blood samples as detected by reverse transcription-PCR amplification of HGV RNA. This precipitation could be competed by addition of saturating amounts of the linear peptide or abolished by addition of Nonidet P-40. We conclude that, albeit lacking the N-terminal sequence of a functional core protein, HGV builds classical viral particles displaying E2 envelope protein on their outer surfaces.
Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products (1991)

The proteins encoded by human immunodeficiency virus type 1 (HIV-1) can be divided into two temporally regulated classes. Early gene products are encoded by multiply spliced mRNA species and are expressed constitutively. In contrast, late proteins are encoded by a class of unspliced or singly spliced viral transcripts whose cytoplasmic expression is induced by the viral Rev trans activator. Here, we demonstrate that the viral Vif and Vpr proteins are encoded by singly spliced viral mRNAs whose expression is activated by Rev. This activation is shown to result from the reduced utilization of splice sites adjacent to or within the vif and vpr coding sequences. Vif and Vpr therefore belong to the class of late HIV-1 gene products.
Long-range organization of tandem arrays of alpha satellite DNA at the centromeres of human chromosomes: high-frequency array-length polymorphism and meiotic stability. (1989)

The long-range organization of arrays of alpha satellite DNA at the centromeres of human chromosomes was investigated by pulsed-field gel electrophoresis techniques. Both restriction-site and array-length polymorphisms were detected in multiple individuals and their meiotic segregation was observed in three-generation families. Such variation was detected in all of the alpha satellite arrays examined (chromosomes 1, 3, 7, 10, 11, 16, 17, X, and Y) and thus appears to be a general feature of human centromeric DNA. The length of individual centromeric arrays was found to range from an average of approximately 680 kilobases (kb) for the Y chromosome to approximately 3000 kb for chromosome 11. Furthermore, individual arrays appear to be meiotically stable, since no changes in fragment lengths were observed. In total, we analyzed 84 meiotic events involving approximately 191,000 kb of alpha satellite DNA from six autosomal centromeres without any evidence for recombination within an array. High-frequency array length variation and the potential to detect meiotic recombination within them allow direct comparisons of genetic and physical distances in the region of the centromeres of human chromosomes. The generation of primary consensus physical maps of alpha satellite arrays is a first step in the characterization of the centromeric DNA of human chromosomes.