gebhart/patrepeval huggingface dataset:
Induction of Acrosomal Reaction in Sperm with lonophore A23187 and Calcium (1981)

The acrosome reaction was induced in ram, rabbit, and human sperm by incubating with the ionophore A23187 plus calcium ions, although the percentage of reacted sperm was different for each species: 90% in ram, 38% in rabbit, and 69% in man. Fusion of the outer acrosomal and plasma membranes of ram and rabbit sperm formed vesicles, but in human sperm only the outer acrosomal membrane was involved in vesiculation. Acrosin was lost from ram, rabbit, and human sperm after treatment with ionophore plus calcium. Ionophore alone induced the reaction in only 35% of ram sperm, 20% of human sperm, and 12% of rabbit sperm. On exposure to A23187 alone, the acrosome of unreacted rabbit sperm bulged and the acrosome and nuclear membrane of human sperm were often lifted away from the nucleus. The percentage of mammalian sperm undergoing the acrosome reaction in the presence of calcium alone, was very low.
MHC class I H-2Kd-restricted antigenic peptides: additional constraints for the binding motif (1993)

The previously defined binding motif of MHC class I H-2Kd-restricted antigenic peptides consists of a Y residue in position P2 and a hydrophobic residue with a large aliphatic side chain (L, I, or V) in position P9/P10 of optimal 9- or 10-mer peptides. We show now that the presence of a charged or a F residue in position P5 reduces the Kd-restricted competitor activity of several cytotoxic T lymphocyte (CTL) epitopes and model peptides, at a degree comparable to A substitutions for the P2 or the P9/P10 anchor residues. Various charged, polar, aromatic, and aliphatic amino acids were substituted for S256 in the CTL epitope Plasmodium berghei circumsporozoite (CS) 253-260 8-mer and in its CS 252-260 9-mer form, whereas a more restricted panel of substitutions was tested in the CTL epitopes influenza nucleoprotein 147-155 9-mer and HLA-CW3 170-179 10-mer. Analysis of all the Kd-restricted epitopes so far defined also revealed an uncharged residue at this position. These additional structural constraints present in the Kd binding motif may thus improve the prediction of new epitopes recognized by T cells in the context of this MHC molecule.
Self-Supervised Learning of Pretext-Invariant Representations (2020)

The goal of self-supervised learning from images is to construct image representations that are semantically meaningful via pretext tasks that do not require semantic annotations. Many pretext tasks lead to representations that are covariant with image transformations. We argue that, instead, semantic representations ought to be invariant under such transformations. Specifically, we develop Pretext-Invariant Representation Learning (PIRL, pronounced as `pearl') that learns invariant representations based on pretext tasks. We use PIRL with a commonly used pretext task that involves solving jigsaw puzzles. We find that PIRL substantially improves the semantic quality of the learned image representations. Our approach sets a new state-of-the-art in self-supervised learning from images on several popular benchmarks for self-supervised learning. Despite being unsupervised, PIRL outperforms supervised pre-training in learning image representations for object detection. Altogether, our results demonstrate the potential of self-supervised representations with good invariance properties.
Radio frequency energy for postharvest control of pests in dry nuts and legumes. (2009)

ith increasing globalization facilitated by World Trade Organization agreements and other treaties, the international trade in agricultural commodities has become an integral part of the global economy. The total value of world agricultural exports experienced an annual increase of 12.3 percent between 2003 and 2005, from $525 billion to $654 billion. Agricultural commodities are, however, natural carriers of exotic insect pests. These pests can cause major local economic losses when accidentally introduced to new areas without co-evolved natural enemies. To reduce the risk of introducing pests, importing countries or regions impose quarantine or phytosanitary requirements on the hosts of targeted pests. Methyl bromide (MeBr) is the most effective fumigant for pest control, but it is a highly toxic gas and listed as an ozone-depleting chemical along with chlorofluorocarbons (CFCs) under the Montreal Protocol of 1992. Developed countries were required to freeze production and importation of MeBr in 1994 at the 1991 levels and to reduce the use by 25 percent in 1999, 50 percent in 2001, 70 percent in 2003, and 100 percent in 2005. Developing countries were required to freeze consumption and production of MeBr by 2002, reduce it by 20 percent in 2005, and phase out by 2015. Annual exemptions are granted to companies in the United States and other developed countries to allow continued but limited use of MeBr in postharvest quarantine treatments. But it is expected that MeBr will become more expensive due to reduced production and uncertainty associated with the complicated annual approval process for those exemptions. Therefore, there is an urgent need to find environmentally friendly and effective alternatives.
Characterization of the coexisting multiple mechanisms of methotrexate resistance in mouse 3T6 R50 fibroblasts. (1992)

We have studied the discrepancy in the degree of methotrexate (MTX) resistance that exists between two clonal cell lines, mouse 3T6 R50 cells and Chinese hamster ovary B11 0.5 cells that overexpress comparable levels of dihydrofolate reductase, yet exhibit a 100-fold difference in MTX resistance while maintaining similar sensitivity to the lipophilic antifolates trimetrexate and piritrexim. These data suggested that R50 cells may possess additional mechanism(s) of antifolate resistance, such as MTX transport alteration. Flow cytometric analysis using fluorescein methotrexate revealed comparable levels of fluorescein MTX displacement with lipophilic antifolates in viable R50 and B11 0.5 cells, but marked insensitivity of R50 cells to MTX competition, thus suggesting a poor uptake of MTX into R50 cells. Analysis of the kinetic parameters of dihydrofolate reductase from R50 cells neither showed alterations in enzyme affinities for various antifolates nor in the Michaelis constant for folic acid and NADPH nor a change in the pH activity optimum. R50 cell-free extracts contained wild-type levels of folylpoly-gamma-glutamyl synthetase activity. However, following metabolic labeling with [3H]MTX, no MTX polyglutamates could be detected in R50 cells. We conclude that the high level of MTX resistance in R50 cells is multifactorial, including overexpression of dihydrofolate reductase, reduced MTX transport, and possibly altered formation of MTX polyglutamates. The potential interactions between the different modalities of MTX resistance in R50 cells are being discussed.
Bendamustine in Combination with Rituximab (BR) for Patients with Relapsed Chronic Lymphocytic Leukemia (CLL): A Multicentre Phase II Trial of the German CLL Study Group (GCLLSG). (2007)

Abstract Introduction: Bendamustine has shown considerable activity in monotherapy for solid and lymphoid malignancies including CLL and has been used for more than 30 years in anti-cancer treatment. In vitro and ex vivo studies have demonstrated synergistic pro-apoptotic effects of bendamustine and the CD20 antibody rituximab (BR) in primary B-CLL cells. Encouraging clinical results have been obtained using BR combination treatment in relapsed/refractory NHL or mantle cell lymphoma. The present phase II trial represents the first study assessing efficacy and toxicity of bendamustine in combination with rituximab in pts with relapsed/refractory B-CLL. Patients and Methods: Between March 2006 and June 2007 81 pts with relapsed/refractory B-CLL and a median number of 2 pretreatments were enrolled into this trial. Bendamustine was given at a dose of 70 mg/m2 on day 1 and 2, combined with 375mg/m2 rituximab for the first cycle and 500 mg/m2 for the second and subsequent cycles. BR treatment was administered every 28 days up to 6 courses. Blood samples were taken for molecular cytogenetics by fluorescence in situ hybridization (FISH), analysis of the IgVH mutational status and expression of ZAP70/CD38. Assessment of minimal residual disease (MRD) was evaluated in peripheral blood and bone marrow by 4-colour flow cytometry. Results: So far data of 31 pts (median age 66 years) with a total of 126 treatment cycles are available for analysis. There was notable toxicity with 48 reported CTC grade 3/4 adverse events, particularly myelosuppression and infections: grade 3/4 anemia occurred in 6.3.%, leukopenia/neutropenia in 10.8% and thrombocytopenia in 11.9% of all courses. 6 episodes of CTC grade 3/4 infections were documented: 1 sinusitis maxillaris, 1 FUO and 1 abscess, all of them being reversible after antibiotics. However, 3 pts died due to severe infections including 2 fatal pneumonias and 1 urosepsis. One pt died due to myocardial infarction. Regarding efficacy, 23 pts were evaluable for response: The overall response rate (ORR) was 65.2% with a CR rate of 13.0% (3 pts) and a PR rate of 52.2% (12 pts). No molecular remission was observed by 4-colour cytometry. Stable disease (SD) was achieved in 26.1% (6 pts) whereas 2 pts had progressive CLL (PD, 8.7%). Responses were observed in the majority of pts with genomic aberrations 11q deletion (ORR: 4/5) and trisomy 12 (ORR: 2/3), while none of the pts with 17p deletion (ORR: 0/4) was responsive (P=0.006). Conclusion: Bendamustine plus rituximab is an effective regimen in refractory/relapsed B-CLL. Major treatment toxicities were myelosuppression and infections. Updated data with respect to toxicity and efficacy based on the entire study population will be available for the Meeting.
Bandwidth allocation in wireless networks with guaranteed packet-loss performance (2000)

Providing quality-of-service (QoS) guarantees over wireless packet networks poses a host of technical challenges that are not present in wireline networks. One of the key issues is how to account for the characteristics of the time-varying wireless channel and for the impact of link-layer error control in the provisioning of packet-level QoS. We accommodate both aspects in analyzing the packet-loss performance over a wireless link. We consider the cases of a single and multiplexed traffic streams. The link capacity fluctuates according to a fluid version of Gilbert-Elliott channel model. Traffic sources are modeled as on-off fluid processes. For the single-stream case, we derive the exact packet-loss rate (PLR) due to buffer overflow at the sender side of the wireless link. We also obtain a closed-form approximation for the corresponding wireless effective bandwidth. In the case of multiplexed streams, we obtain a good approximation for the PLR using the Chernoff-dominant eigenvalue (CDE) approach. Our analysis is then used to study the optimal forward error correction code rate that guarantees a given PLR while minimizing the allocated bandwidth. Numerical results and simulations are used to verify the adequacy of our analysis and to study the impact of error control on the allocation of bandwidth for guaranteed packet-loss performance.
Commercial versus Native Surfactants (2000)

Despite their broad clinical use, there is no standardized comparative study on the functional, biochemical, and morphologic differences of the various commercial surfactants in relation to native surfactant. We investigated these parameters in Alveofact, Curosurf, Exosurf, and Survanta, and compared them with native bovine (NBS) and porcine (NPS) surfactant. For Curosurf and Alveofact the concentrations necessary for minimal surface tensions < 5 mN/m were six to 12 times higher (1.5 and 3 mg/ml, respectively) than with NPS and NBS. Exosurf and Survanta only reached 22 and 8 mN/m, respectively. Increasing calcium to nonphysiologic concentrations artificially improved the function of Alveofact and Curosurf, but it had little effect on Exosurf and Survanta. Impaired surface activity of commercial versus native surfactants corresponded with their lack in surfactant protein SP-A and decreased SP-B/C. The higher surface activity of Curosurf compared with Alveofact corresponded with its higher concentration of dipalmitoylphosphatidylcholine (DPPC). Despite their enrichment in DPPC Survanta and Exosurf exhibited poor surface activity because of low or absent SP-B/C. Ultrastructurally, Curosurf and Alveofact consisted mainly of lamellar and vesicular structures, which were also present in NPS and NBS. Exosurf contained crystalline structures only, whereas the DPPC-enriched Survanta contained separate lamellar/vesicular and crystalline structures. We conclude that in vitro surface activity of commercial surfactants is impaired compared with native surfactants at physiologic calcium concentrations. In the presence of SP-B/C, surface activity corresponds to the concentration of DPPC. Our data underscore the importance of a standardized protocol at physiologic calcium concentrations for the in vitro assessment of commercial surfactants.
Structure and function of eukaryotic proprotein processing enzymes of the subtilisin family of serine proteases. (1993)

Production of a broad spectrum of regulatory proteins in eukaryotes occurs via an intricate cascade of biosynthetic and secretory processes. Often these proteins initially are synthesized as parts of higher molecular weight, but inactive, precursor proteins. Specific endoproteolytic processing of these proproteins is required to generate the regulatory proteins in a mature and biologically active form. Such endoproteolysis generally occurs at cleavage sites consisting of particular sequence motifs of basic amino acids, often paired basic residues. This phenomenon, first observed almost 25 years ago, has intrigued scientists ever since then. Nevertheless, the responsible enzymes remained elusive for long. The first known eukaryotic enzyme with the exquisite cleavage specificity for paired basic amino acid residues was the prohormone processing enzyme kexin (EC 3.4.21.61), a subtilisin-like serine protease that is encoded by the KEX2 gene of yeast Saccharomyces cerevisiae. Recently, a number of kexin-like mammalian proprotein-processing enzymes were discovered. The enzyme furin, which is encoded by the fur gene, was the first and can be considered the prototype of a mammalian subclass of subtilisin-like serine proteases. It is predicted to contain a "prepro" domain, a subtilisin-like catalytic domain, a middle domain, a cysteine-rich region, a transmembrane anchor, and a cytoplasmic domain. Furin is expressed in a wide variety of tissues, perhaps even in all tissues. In all likelihood, it is the enzyme responsible for the proteolytic bioactivation of a wide variety of precursor proteins. Two other novel mammalian proprotein-processing enzymes are PC1 (also known as PC3) and PC2. Some of the protein domains of these enzymes resemble those in kexin and furin, however, there are also differences. The PC1/PC3 and PC2 enzymes exhibit a more restricted expression pattern than furin. It has been suggested that PC1/PC3 and PC2 are involved primarily in the processing of prohormones within the regulated secretory pathway of cells of endocrine and neural tissue. Recently, the coding sequences for two other candidate mammalian proprotein-processing enzymes were identified. They were called PACE4 and PC4. Like that of furin, the tissue distribution of PACE4 is widespread. PC4, however, may represent a candidate for a precursor-processing endoprotease that is specifically expressed in the testicular germ cells. Finally, DNA sequences encoding kexin- and furin-like candidate pro-protein-processing enzymes have been identified in Drosophila melanogaster, Dfur1 and Dfur2 genes; in Xenopus laevis, Xen-14 gene; and in Caenorhabditis elegans, bli-4 gene.(ABSTRACT TRUNCATED AT 400 WORDS)
Stimulation of human umbilical vein endothelial cell proliferation by A2‐adenosine and β2‐adrenoceptors (1995)

1. Adenosine is known to stimulate capillary outgrowth and endothelial cell proliferation, but the underlying mechanism has not been identified. In order to identify the receptor subtype involved, the effects of adenosine receptor agonists and antagonists on human umbilical vein endothelial cell (HUVEC) proliferation were investigated. 2. Raising intracellular adenosine levels by use of the adenosine transport inhibitor, 4-nitrobenzylthioinosine (NBMPR) did not affect cell growth. This observation suggests that stimulation of an extracellular adenosine receptor generates the mitogenic signal. 3. In the presence of adenosine deaminase (ADA), which was used to remove adenosine present in the culture medium, the adenosine receptor agonists N-ethylcarboxamidoadenosine (NECA, non-selective) and CGS21680 (A2A-receptor-selective) stimulated [3H]-thymidine incorporation with a half-maximum effect at about 10 nM, while N6-cyclopentyladenosine (CPA, A1-selective) was about 100 fold less potent. The adenosine receptor antagonist, xanthine amine congener (XAC) produced a concentration-dependent decrease in endothelial cell proliferation with a half-maximum effect at about 10 nM. Hence, stimulation of an endothelial A2A-adenosine receptor seems responsible for the mitogenic signal. 4. In the presence of ADA, isoprenaline is also able to stimulate [3H]-thymidine incorporation with a half maximal effect of about 3 nM, an effect, which is reversed by the highly beta 2-selective antagonist, ICI 118,551. In the absence of ADA, isoprenaline exerts only a minor stimulatory effect. Combination of A2A adenosine and beta 2-adrenoceptor agonists did not further enhance [3H]-thymidine incorporation when compared to the sole addition of each agonist. We therefore conclude that both receptors stimulate endothelial cell proliferation via a common signal transduction pathway. 5. Both receptors are coupled to stimulation of adenylyl cyclase via the stimulatory G protein G8.However, direct activation of downstream effectors in the cyclic AMP-signalling cascade (G8 with cholera toxin, adenylyl cyclase with forskolin, protein kinase A with 8Br-cyclic AMP) not only failed to mimic the action of receptor-activation, but even reduced cell proliferation.6. Similarly, pertussis toxin-treatment which inactivated the Gi 2 protein present in HUVEC and thus inhibited cell proliferation per se, did not impair the ability of A2A-receptor agonists to stimulate cell proliferation. This suggests that the A2A-adenosine and beta2-adrenoceptor-mediated stimulation of endothelial cell proliferation occurs via a mechanism that is independent of G8 and Gi.
Fibrin glue reduces seroma formation in the rat after mastectomy. (1992)

Fibrin glue is a biologic tissue adhesive that has been found to be useful in several areas of surgical treatment. Little has been written in the English literature, however, on its use in preventing postoperative fluid collections. We performed a prospective randomized trial to determine if fibrin glue could reduce postoperative fluid collections after mastectomy in a rat. Bilateral mastectomies and axillary lymph node dissections were performed upon 42 rats, one-half of which were treated with fibrin glue and one-half of which served as controls. The rats were sacrificed after seven days and inspected for quantity of fluid and adhesion formation. The mean plus or minus standard error of the mean fluid collections were 0.71 +/- 0.26 milliliter and 3.75 +/- 0.65 milliliter for the rats treated with fibrin glue and control rats, respectively. This was statistically significant (p < 0.0001). Seventeen of 21 rats treated with fibrin glue and four of 21 control rats were found to have fluid collections of less than 1 milliliter, again statistically significant (p = 0.00006). Furthermore, greater adhesion formation between the skin flap and chest wall was noted in the rats treated with fibrin glue. The results support the use of fibrin glue in clinical investigations to reduce postoperative fluid collections and also support the need to develop a standard reproducible method of producing fibrin glue or a commercial product free of transmissible disease.
Sequences in the 5′ and 3′ R Elements of Human Immunodeficiency Virus Type 1 Critical for Efficient Reverse Transcription (2000)

The genome of human immunodeficiency virus type 1 (HIV-1) contains two direct repeats (R) of 97 nucleotides at each end. These elements are of critical importance during the first-strand transfer of reverse transcription, during which the minus-strand strong-stop DNA (-sssDNA) is transferred from the 5' end to the 3' end of the genomic RNA. This transfer is critical for the synthesis of the full-length minus-strand cDNA. These repeats also contain a variety of other functional domains involved in many aspects of the viral life cycle. In this study, we have introduced a series of mutations into the 5', the 3', or both R sequences designed to avoid these other functional domains. Using a single-round infectivity assay, we determined the ability of these mutants to undergo the various steps of reverse transcription utilizing a semiquantitative PCR analysis. We find that mutations within the first 10 nucleotides of either the 5' or the 3' R sequence resulted in virions that were markedly defective for reverse transcription in infected cells. These mutations potentially introduce mismatches between the full-length -sssDNA and 3' acceptor R. Even mutations that would create relatively small mismatches, as little as 3 bp, resulted in inefficient reverse transcription. In contrast, virions containing identically mutated R elements were not defective for reverse transcription or infectivity. Using an endogenous reverse transcription assay with disrupted virus, we show that virions harboring the 5' or the 3' R mutations were not intrinsically defective for DNA synthesis. Similarly sized mismatches slightly further downstream in either the 5', the 3', or both R sequences were not detrimental to continued reverse transcription in infected cells. These data are consistent with the idea that certain mismatches within 10 nucleotides downstream of the U3-R junction in HIV-1 cause defects in the stability of the cDNA before or during the first-strand transfer of reverse transcription leading to the rapid disappearance of the -sssDNA in infected cells. These data also suggest that the great majority of first-strand transfers in HIV-1 occur after the copying of virtually the entire 5' R.
Antimycobacterial Agent Based on mRNA Encoding Human β-Defensin 2 Enables Primary Macrophages To Restrict Growth ofMycobacterium tuberculosis (2001)

Human macrophages are hosts for Mycobacterium tuberculosis, the causative agent of tuberculosis, which killed approximately 1.87 million people in 1997. Human alveolar macrophages do not express alpha- or beta-defensins, broad-spectrum antimicrobial peptides which are expressed in macrophages from other species more resistant to infection with M. tuberculosis. It has been previously reported that M. tuberculosis is susceptible to killing by defensins, which may explain the difference in resistance. Defensin peptides have been suggested as a possible therapeutic strategy for a variety of infectious diseases, but development has been hampered by difficulties in their large-scale production. Here we report the cellular synthesis of human beta-defensin 2 via highly efficient mRNA transfection of human macrophages. This enabled mycobactericidal and mycobacteristatic activity by the macrophages. Although human macrophages are difficult to transfect with plasmid vectors, these studies illustrate that primary macrophages are permissive for mRNA transfection, which enabled expression of a potentially therapeutic protein.