gebhart/patrepeval huggingface dataset:
Abstract B122: Human monoclonal antibodies to sialyl-Lewis-A with potent CDC and ADCC activity (2009)

Abstract The carbohydrate antigen sialyl-Lewis A (sLea) is widely expressed on epithelial tumors of the gastrointestinal tract, on breast cancer cells, and also on small cell lung cancer cells, but is expressed minimally or not at all on normal tissues. sLea serves as a ligand for epithelial leukocyte adhesion molecules and higher expression of sLea was observed in patients with greater node involvement. Since over-expression of sLea appears to be a key event in invasion and metastasis of many tumor cells and tumor cells expressing sLea are highly susceptible to antibody mediated lysis mechanisms, sLea presents an attractive molecular target for tumor therapy in a minimal disease setting. Here we report the discovery and initial characterization of fully human antibodies that were generated from blood lymphocytes from individuals immunized with sLea vaccine at MSKCC. Antibodies were identified by ELISA using sLea-HSA conjugates and binding to the native antigen was verified by FACS analysis on DMS-79 cells. Two antibodies were selected for further studies based on the apparent high affinity, which was estimated by Biacore at 0.14 nM for 5B1 (IgG/λ) and 0.04 nM for 7E3 (IgM/κ). These antibodies did not bind to sialyl-Lewis X, Lewis A and other related carbohydrates. Both antibodies have been expressed as fully functional human recombinant antibodies in CHO cells. Complement dependent cytotoxicity (CDC) against DMS-79 cells was approximately 60% and 70–90% for r5B1 and r7E3, respectively. Moreover, r5B1 antibodies showed approximately 50% ADCC of DMS-79 cells with human NK cells (at 5:1 ratio) and 80–90% ADCC with human peripheral blood mononuclear cells with two different blood donors (at 100:1 ratio). These results are very encouraging and we believe that further studies to scale up and test these antibodies in various tumor challenge models are warranted. Since sLea is widely expressed on human cancers, such antibodies could eventually find utility in approximately half of the new cancer cases occurring each year. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B122.
Sharpening image motion based on the spatio-temporal characteristics of human vision (2005)

Moving objects in films often appear normal or even sharper than they actually are, a phenomenon called motion sharpening. We sought to clarify which spatio-temporal frequency components of a moving image are sharpened when the pattern is moving. We applied various spatio-temporal filters to moving natural images and evaluated the perceived sharpness and smoothness of motion by comparing them to a stationary image. On each trial, subjects adjusted three parameters of the still image: overall luminance contrast, the slope of the amplitude function in the spatial frequency domain, and cut-off spatial frequency. We found the strongest motion sharpening when image frames were spatially band-reject filtered. In addition, spatially low-pass filtered movies induced stronger motion sharpening than spatially high-pass filtered movies. When temporal filters were applied, perceived sharpness became stronger when the movies were temporally low-pass filtered. A high-pass temporal filter drastically reduced the perceived quality of image motion. Our results demonstrate that the perceived contrast of higher spatial frequency components in moving images is enhanced by the interaction between different spatio-temporal frequency channels in the motion sharpening process. The results suggest that it is possible to compress and enhance moving images by removing higher spatio-temporal frequency information.
Identification of Vaccine Candidate Peptides in the NcSRS2 Surface Protein of<i>Neospora caninum</i>by Using CD4<sup>+</sup>Cytotoxic T Lymphocytes and Gamma Interferon-Secreting T Lymphocytes of Infected Holstein Cattle (2005)

Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-gamma) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Four experimentally infected cattle with six different major histocompatibility complex (MHC) class II haplotypes were the source of immune cells used to identify NcSRS2 peptides presented by Holstein MHC haplotypes. NcSRS2 peptides were mapped by using IFN-gamma secretion by rNcSRS2-stimulated, short-term T-lymphocyte cell lines, IFN-gamma enzyme-linked immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum-infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected ex vivo in peripheral blood by IFN-gamma ELISPOT and in vitro by measuring T-lymphocyte IFN-gamma production and cytotoxicity. An immunodominant region of NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from the four cattle. These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied MHC genotypes.
Oligo-2‘-deoxyribonucleotides Containing Uracil Modified at the 5-Position with Linkers Ending with Guanidinium Groups (2003)

We report here the synthesis and binding studies of oligo-2'-deoxyribonucleotides (ODNs) containing 2'-deoxyuridines, modified at the 5-position by linkers ending with either one or two guanidinium groups. Comparison was made with ODNs containing 2'-deoxyuridines modified at the 5-position with linkers ending with either two or one amino groups. One or two modified 2'-deoxyuridines were incorporated into pyrimidine strands, and their influence on the stability of duplex (with both DNA and RNA targets) and triplex structures was studied. The strongest stabilization was obtained with modified ODNs containing guanidinium groups. This result confirms that the reduction of the global negative charge number on one strand is an important parameter in the stability of duplex and triplex structures.
Canceling the ISI Due to Finite S/H Bandwidth in a Circular Buffer Forward Equalizer (2012)

In an analog discrete-time circular buffer forward equalizer (FE), finite bandwidth in the sample-and-hold (S/H) circuit can introduce significant intersymbol interference (ISI) that degrades the FE performance. This brief investigates the effect of the finite S/H bandwidth and presents two methods to equalize the ISI introduced by the finite S/H bandwidth. The first method uses a decision-feedback equalizer (DFE) that has nonuniform delays between its taps. The second method uses a DFE that has uniform delays between its taps, allows more time in the first DFE feedback loop, and requires fewer DFE taps at the expense of additional FE taps. Simulation results show that when the proposed methods equalize a 100-m CAT5 cable and a backplane channel, the signal-to-noise ratio improvement is at least 1 and 0.8 dB, respectively, for bit error rates <; 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> .
Theoretical method for full <i>ab initio</i> calculation of DNA/RNA–ligand interaction energy (2004)

In this paper, we further develop the molecular fractionation with conjugate caps (MFCC) scheme for quantum mechanical computation of DNA–ligand interaction energy. We study three oligonuclear acid interaction systems: dinucleotide dCG/water, trinucleotide dCGT/water, and a Watson–Crick paired DNA segment, dCGT/dGCA. Using the basic MFCC approach, the nucleotide chains are cut at each phosphate group and a pair of conjugate caps (concaps) are inserted. Five cap molecules have been tested among which the dimethyl phosphate anion is proposed to be the standard concap for application. For each system, one-dimensional interaction potential curves are computed using the MFCC method and the calculated interaction energies are found to be in excellent agreement with corresponding results obtained from the full system ab initio calculations. The current study extends the application of the MFCC method to ab initio calculations for DNA– or RNA–ligand interaction energies.
Synthesis and biological evaluation of benzo[a]phenazine derivatives as a dual inhibitor of topoisomerase I and II (2013)

Topoisomerases (Topo I and Topo II) are very important players in DNA replication, repair, and transcription, and are a promising class of antitumor target. In present study, a series of benzo[a]phenazine derivatives with alkylamino side chains at C-5 were designed, synthesized, and their biological activities were evaluated. Most of derivatives showed good antiproliferative activity with a range of IC50 values of 1-10 μM on the four cancer cell lines HeLa, A549, MCF-7, and HL-60. Topoisomerase-mediated DNA relaxation assay results showed that derivatives could effectively inhibit the activity of both Topo I and Topo II, and the structure-activity relationship studies indicated the importance of introducing an alkylamino side chain. Further mechanism studies revealed that the compounds could stabilize the Topo I-DNA cleavage complexes and inhibit the ATPase activity of hTopo II, indicating that they are a rare class of dual topoisomerase inhibitors by acting as Topo I poisons and Topo II catalytic inhibitors. Moreover, flow cytometric analysis and caspase-3/7 activation assay showed that this class of compounds could induce apoptosis of HL-60 cells.
CLEAR: Cumulative LEARning for One-Shot One-Class Image Recognition (2018)

This work addresses the novel problem of one-shot one-class classification. The goal is to estimate a classification decision boundary for a novel class based on a single image example. Our method exploits transfer learning to model the transformation from a representation of the input, extracted by a Convolutional Neural Network, to a classification decision boundary. We use a deep neural network to learn this transformation from a large labelled dataset of images and their associated class decision boundaries generated from ImageNet, and then apply the learned decision boundary to classify subsequent query images. We tested our approach on several benchmark datasets and significantly outperformed the baseline methods.
Parity vector compensation for FDI (1981)

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1982.
Effects of sulfur-containing gases on the performance of molten carbonate fuel cells (1981)

The effets of low-level (< 10 ppM) sulfur impurites as H/sub 2/S or COS in low-Btu fuel gas and as SO/sub 2/ in the oxidant gas were studied with 3-cm/sup 2/ molten carbonate fuel cells using standard components. Experiments were designed to study the cell performance responses to low-level sulfur excursions in fuel and/or oxidant that could occur during loss of cleanup capability of the sulfur removal subsytem. Results indicate that: (1) open circuit voltage (OCV) is not affected by low levels of sulfur, and all performance loss under current load occurs at the anode, even if sulfur is present as SO/sub 2/ in the oxidant; (2) for low-Btu fuel inlet compositions, a 10 mV loss per ppM H/sub 2/S at 160 mA/cm/sup 2/ can be expected, and higher performance losses will occur under anode outlet conditions (losses for COS were similar at 650/sup 0/C); (3) the anode performance loss resulting from H/sub 2/S is smaller at temperatures higher than the normal 650/sup 0/C operating temperature; (4) the performance loss resulting from SO/sub 2/ in the oxidant is more severe than that of the same level of H/sub 2/S in the fuel; and (5) performance losses are recovered after removal of sulfur from fuel or oxidant after exposures up to two weeks in duration.
The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum (1992)

In an effort to determine subunit compositions of in vivo GABAA receptors, the cellular localization of 13 subunit encoding mRNAs (alpha 1-alpha 6, beta 1-beta 3, gamma 2-gamma 3, delta) was determined in the rat olfactory bulb and cerebellum. Cerebellar granule cells expressed significant quantities of alpha 1, alpha 6, beta 2, beta 3, gamma 2, and delta mRNAs. They contained very much lower levels of alpha 4, beta 1, and gamma 3 mRNAs, and the alpha 2, alpha 3, alpha 5, and gamma 1 genes appeared to be silent. Purkinje cells contained only the alpha 1, beta 2, beta 3, and gamma 2 mRNAs. Putative Bergmann glial cells were found to contain the gamma 1 mRNA and possibly the alpha 2 mRNA. In the molecular layer, only the alpha 1, beta 2 and gamma 2 mRNAs were expressed in stellate/basket cells. The alpha 3 probe hybridized weakly to targets in the molecular layer. The inferior olivary nucleus contained significant quantities of alpha 2, alpha 4, and gamma 1 transcripts, with the alpha 1, alpha 3, beta 2, beta 3, and gamma 2 mRNAs also present. In the olfactory bulb, mitral cells were found to express the alpha 1, beta 1, beta 2, beta 3, and gamma 2 mRNAs strongly and the alpha 3 mRNA weakly. Tufted cells contained alpha 1, alpha 3, beta 2, beta 3, and gamma 2 mRNAs and, occasionally, the alpha 2 mRNA. In the internal granule cells the alpha 2, alpha 4, alpha 5, beta 3, and delta mRNAs were all present. Low levels of alpha 3, gamma 1, gamma 2, and gamma 3 mRNAs were also noted in these cells. Periglomerular cells expressed low levels of alpha 2, alpha 3, alpha 4, beta 2, beta 3, gamma 1, gamma 2, and gamma 3 mRNAs. No alpha 6 mRNA was present in the olfactory bulb. Correlations that are general ones from other brain regions are the colocalizations of alpha 1 beta 2, alpha 2 beta 3, and alpha 4 delta mRNAs. In both the olfactory bulb and cerebellum, alpha 1 beta 2 gamma 2 receptor cores are probably employed. The delta-subunit mRNA appears to codistribute with alpha-subunit mRNAs (alpha 4 and alpha 6) associated with GABAA subunits that fail to bind benzodiazepine agonists.
Molecular monolayers for conformal, nanoscale doping of InP nanopillar photovoltaics (2011)

Semiconductor nanopillar arrays with radially doped junctions have been widely proposed as an attractive device architecture for cost effective and high efficiency solar cells. A challenge in the fabrication of three-dimensional nanopillar devices is the need for highly abrupt and conformal junctions along the radial axes. Here, a sulfur monolayer doping scheme is implemented to achieve conformal ultrashallow junctions with sub-10 nm depths and a high electrically active dopant concentration of 1019–1020 cm−3 in arrays of InP nanopillars. The enabled solar cells exhibit a respectable conversion efficiency of 8.1% and a short circuit current density of 25 mA/cm3. The work demonstrates the utility of well-established surface chemistry for fabrication of nonplanar junctions for complex devices.
Specific binding of substance P aminoterminal heptapeptide [SP(1-7)] to mouse brain and spinal cord membranes (1990)

Aminoterminal fragments of substance P (SP) have been previously shown to produce effects distinct, and often opposite, from those produced by the C-terminal of SP. The present investigation was initiated to determine whether N-terminal fragments interact at binding sites distinct from the neurokinin-1 (NK-1) receptor where the C-terminal sequence of SP binds with high affinity, and distinct from mu-opiate receptors, where we have previously shown the N-terminal sequence of SP to interact. A tritium-labeled aminoterminal heptapeptide of SP, 3H-SP(1-7), was synthesized, purified, and used to characterize the binding of a variety of fragments of SP and opioids in the mouse brain and spinal cord membranes. Using the reduction of SP-induced caudally directed biting and scratching behaviors as an index of biological activity, 3H-SP(1-7) was shown to be equipotent to unlabeled SP(1-7). 3H-SP(1-7) was found to bind reversibly to a saturable population of sites. Scatchard analyses of concentration-dependent saturation of binding in the brain indicated a single population of noninteracting sites with a high affinity (Kd = 2.5 nM) and a low capacity (Bmax = 29.2 fmol/mg protein). Kinetic analyses indicated an apparent dissociation equilibrium constant of 2.1 nM. Two populations of binding sites were observed in the spinal cord, one with a very high affinity (Kd = 0.03 nM) and low capacity (Bmax = 0.87 fmol/mg protein), and the other with lower affinity (Kd = 5.4 nM) and intermediate capacity (Bmax = 19.6 fmol/mg protein). Specific agonists for NK-1, NK-2, and NK-3 and delta opioid receptors, carboxyterminal fragments of SP, and a variety of other peptides did not compete at the 3H-SP(1-7) binding sites, but structurally related N-terminal peptides and (D-Ala2, NMe-Phe4, Gly-ol)-enkephalin (DAMGO) were active in displacing the ligand. The binding site for 3H-SP(1-7) appeared to be a membrane-bound complex whose specific binding was dependent on the integrity of both proteins and phospholipids. These studies are the first to characterize the binding sites for the SP N-terminal partial sequence of SP that can be generated by metabolism in vivo. The expanding body of evidence for distinct biological activities of N-terminal metabolites of SP, together with the current characterization of N-terminal binding, strongly support the existence of an N-terminal-directed SP receptor. The characteristics of SP(1-7) binding sites are consistent with those expected for an SP N-terminal receptor.
Partially Separated Page Tables for Efficient Operating System Assisted Hierarchical Memory Management on Heterogeneous Architectures (2013)

Heterogeneous architectures, where a multicore processor is accompanied with a large number of simpler, but more power-efficient CPU cores optimized for parallel workloads, are receiving a lot of attention recently. At present, these co-processors, such as the Intel Xeon Phi product family, come with limited on-board memory, which requires partitioning computational problems manually into pieces that can fit into the device's RAM, as well as efficiently overlapping computation and communication. In this paper we propose an application transparent, operating system (OS)assisted hierarchical memory management system, where the OS orchestrates data movement between the host and the device and updates the process virtual memory address space accordingly. We identify the main scalability issues of frequent address space changes, such as the increasing price of TLB invalidations with the growing number of CPU cores, and propose partially separated page tables with address-range CPU masks to overcome the problem. With partially separated page tables each core maintains its own set of mappings of the computation area, enabling the OS to perform address space updates in a scalable manner, and involve a particular CPU core in TLB invalidation only if it is absolutely necessary. Furthermore, we propose dedicated data movement cores in order to efficiently overlap computation and communication. We provide experimental results on stencil computation, a common HPCkernel, and show that OS assisted memory management has the potential for scalable transparent data movement.
Development of DNA Vaccines against Hemolytic-Uremic Syndrome in a Murine Model (2003)

Shiga toxin type 2 (Stx2) produced by Escherichia coli O:157H7 can cause hemolytic-uremic syndrome in children, a disease for which there is neither a vaccine nor an effective treatment. This toxin consists of an enzymatically active A subunit and a pentameric B subunit responsible for the toxin binding to host cells, and also found to be immunogenic in rabbits. In this study we developed eukaryotic plasmids expressing the B subunit gene of Stx2 (pStx2B) and the B subunit plus the gene coding for the A subunit with an active-site deletion (pStx2 Delta A). Transfection of eukaryotic cells with these plasmids produced proteins of the expected molecular weight which reacted with specific monoclonal antibodies. Newborn and adult BALB/c mice immunized with two intramuscular injections of each plasmid, either alone or together with the same vector expressing the granulocyte and monocyte colony-stimulating factor (pGM-CSF), elicited a specific Th1-biased humoral response. The effect of pGM-CSF as an adjuvant plasmid was particularly notable in newborn mice and in pStx2B-vaccinated adult mice. Stx2-neutralizing activity, evaluated in vitro on VERO cell monolayers, correlated with in vivo protection. This is the first report using plasmids to induce a neutralizing humoral immune response against the Stx2.
Novel strategies for patients with chronic myeloproliferative disorders (2009)

Treating low-risk essential thrombocythemia and polycythemia vera patients presenting with leukocytosis or JAK2 V617F mutation in order to prevent thrombosis deserves a prospective validation. Pursuing clonal remission in polycythemia vera by interferon needs new evidence. Tipifarnib may be added to conventional therapeutic instruments for symptomatic primary myelofibrosis. The results of anti-JAK2-targeted therapies are encouraging as regards symptoms reduction but not clonal remission.
The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5′ splice site-like sequences (2009)

The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA(N(x))AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5' splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine "ladder." A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition.
Purification and characterization of TnsC, a Tn7 transposition protein that binds ATP and DNA (1992)

The bacterial transposon Tn7 encodes five transposition genes tnsABCDE. We report a simple and rapid procedure for the purification of TnsC protein. We show that purified TnsC is active in and required for Tn7 transposition in a cell-free recombination system. This finding demonstrates that TnsC participates directly in Tn7 transposition and explains the requirement for tnsC function in Tn7 transposition. We have found that TnsC binds adenine nucleotides and is thus a likely site of action of the essential ATP cofactor in Tn7 transposition. We also report that TnsC binds non-specifically to DNA in the presence of ATP or the generally non-hydrolyzable analogues AMP-PNP and ATP-gamma-S, and that TnsC displays little affinity for DNA in the presence of ADP. We speculate that TnsC plays a central role in the selection of target DNA during Tn7 transposition.