gebhart/patrepeval huggingface dataset:
A Flexible Synthetic Approach to Phosphatidylglycerols (2017)

We report a 5‐step sequence for the synthesis of phosphatidylglycerols (PG) bearing different or identical chains at positions sn ‐1 and sn ‐2 starting from phenyl dichlorophosphate and using ( S )‐glycidol as the chiral source. Overall, this new approach is more convergent that the previously reported syntheses as the PG derivatives are constructed around the phosphorus center. Hence, this method is more convenient for the incorporation of expensive or complex acyl chains at the sn ‐2 position.
Deformable Convolutional Networks (2017)

Convolutional neural networks (CNNs) are inherently limited to model geometric transformations due to the fixed geometric structures in their building modules. In this work, we introduce two new modules to enhance the transformation modeling capability of CNNs, namely, deformable convolution and deformable RoI pooling. Both are based on the idea of augmenting the spatial sampling locations in the modules with additional offsets and learning the offsets from the target tasks, without additional supervision. The new modules can readily replace their plain counterparts in existing CNNs and can be easily trained end-to-end by standard back-propagation, giving rise to deformable convolutional networks. Extensive experiments validate the performance of our approach. For the first time, we show that learning dense spatial transformation in deep CNNs is effective for sophisticated vision tasks such as object detection and semantic segmentation. The code is released at https://github.com/msracver/Deformable-ConvNets.
Genome modifications in plant cells by custom‐made restriction enzymes (2012)

Genome editing, i.e. the ability to mutagenize, insert, delete and replace sequences, in living cells is a powerful and highly desirable method that could potentially revolutionize plant basic research and applied biotechnology. Indeed, various research groups from academia and industry are in a race to devise methods and develop tools that will enable not only site-specific mutagenesis but also controlled foreign DNA integration and replacement of native and transgene sequences by foreign DNA, in living plant cells. In recent years, much of the progress seen in gene targeting in plant cells has been attributed to the development of zinc finger nucleases and other novel restriction enzymes for use as molecular DNA scissors. The induction of double-strand breaks at specific genomic locations by zinc finger nucleases and other novel restriction enzymes results in a wide variety of genetic changes, which range from gene addition to the replacement, deletion and site-specific mutagenesis of endogenous and heterologous genes in living plant cells. In this review, we discuss the principles and tools for restriction enzyme-mediated gene targeting in plant cells, as well as their current and prospective use for gene targeting in model and crop plants.
New Base Pairing Motifs. The Synthesis and Thermal Stability of Oligodeoxynucleotides Containing Imidazopyridopyrimidine Nucleosides with the Ability to Form Four Hydrogen Bonds (2003)

The synthesis and thermal stability of oligodeoxynucleotides (ODNs) containing imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleosides 1-4 (N(N), O(O), N(O), and O(N), respectively) with the aim of developing two sets of new base pairing motifs consisting of four hydrogen bonds (H-bonds) is described. The proposed four tricyclic nucleosides 1-4 were synthesized through the Stille coupling reaction of a 5-iodoimidazole nucleoside with an appropriate 5-stannylpyrimidine derivative, followed by an intramolecular cyclization. These nucleosides were incorporated into ODNs to investigate the H-bonding ability. When one molecule of the tricyclic nucleosides was incorporated into the center of each ODN (ODN I and II, each 17mer), no apparent specificity of base pairing was observed, and all duplexes were less stable than the duplexes containing natural G:C and A:T pairs. On the other hand, when three molecules of the tricyclic nucleosides were consecutively incorporated into the center of each ODN (ODN III and IV, each 17mer), thermal and thermodynamic stabilization of the duplexes due to the specific base pairings was observed. The melting temperature (T(m)) of the duplex containing the N(O):O(N) pairs showed the highest T(m) of 84.0 degrees C, which was 18.2 and 23.5 degrees C higher than that of the duplexes containing G:C and A:T pairs, respectively. This result implies that N(O)and O(N) form base pairs with four H-bonds when they are incorporated into ODNs. The duplex containing N(O):O(N) pairs was markedly stabilized by the assistance of the stacking ability of the imidazopyridopyrimidine bases. Thus, we developed a thermally stable new base pairing motif, which should be useful for the stabilization and regulation of a variety of DNA structures.
Recognition of minor histocompatibility antigens on lymphocytic and myeloid leukemic cells by cytotoxic T-cell clones (1994)

Clinical studies indicated an enhanced antileukemic effect of allogeneic bone marrow transplantation (BMT), as compared with autologous BMT. After allogeneic HLA-identical BMT, donor-derived cytotoxic T lymphocytes (CTLs) directed at minor histocompatibility (mH) antigens on the recipients, tissues can be shown. To evaluate the antileukemic reactivity of mH antigen-specific CTLs, we analyzed the expression of mH antigens on circulating lymphocytic and myeloid leukemic cells. We show that the defined mH specificities HA-1 through HA-5 and H-Y are present on leukemic cells, indicating that mH antigen-specific CTLs are capable of HLA class I-restricted antigen-specific lysis of leukemic cells. Compared with interleukin-2-stimulated normal lymphocytes, leukemic cells of lymphocytic origin are less susceptible to T-cell-mediated cytotoxicity by the HA-2 mH antigen-specific CTL and the anti-HLA-A2 CTL clone. A possible explanation for this phenomenon is impaired expression of the LFA-1 adhesion molecule. Our study suggests that mH antigen-specific HLA class I-restricted CD8+ CTLs may be involved in the graft-versus-leukemia reactivity after allogeneic BMT.
HRTF Measurements of a KEMAR Dummy-Head Microphone (1994)

An extensive set of head-related transfer function (HRTF 1 ) measurements of a KEMAR dummy head microphone has recently been completed. The measurements consist of the left and right ear impulse responses from a Realistic Optimus Pro 7 loudspeaker mounted 1.4 meters from the KEMAR. Maximum length (ML) pseudo-random binary sequences were used to obtain the impulse responses at a sampling rate of 44.1 kHz. In total, 710 different positions were sampled at elevations from-40 degrees to +90 degrees. Also measured were the impulse response of the speaker in free field and several headphones placed on the KEMAR. This data is being made available to the research community on the Internet via anonymous FTP and the World Wide Web. 1 Measurement technique Measurements were made using a Macintosh Quadra computer equipped with an Audiomedia II DSP card, which has 16-bit stereo A/D and D/A converters that operate at a 44.1 kHz sampling rate. One of the audio output channels was sent to an amplif...
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis (1983)

Four persons developed marked parkinsonism after using an illicit drug intravenously. Analysis of the substance injected by two of these patients revealed primarily 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) with trace amounts of 1-methyl-4-phenyl-4-propionoxy-piperidine (MPPP). On the basis of the striking parkinsonian features observed in our patients, and additional pathological data from one previously reported case, it is proposed that this chemical selectively damages cells in the substantia nigra.
The Nonreceptor Protein-Tyrosine Kinase CSK Complexes Directly with the GTPase-Activating Protein-Associated p62 Protein in Cells Expressing v-Src or Activated c-Src (1995)

CSK is a predominantly cytosolic protein-tyrosine kinase (PTK) that negatively regulates Src family PTKs by phosphorylation of a conserved tyrosine near their C termini. Little is known about how CSK itself is regulated. On the basis of immunofluorescence studies, a model has been proposed that when c-Src is activated, it is redistributed to podosomes, in which substrates become phosphorylated, creating binding sites for CSK. CSK is recruited to these sites of c-Src activation via its SH2 and SH3 domains and is then in a position to downregulate c-Src activity (B. W. Howell and J. A. Cooper, Mol. Cell. Biol. 14:5402-5411, 1994). To identify phosphotyrosine (P.Tyr)-containing proteins that may mediate translocation of CSK due to c-Src activation, we have examined the whole spectrum of P.Tyr-containing proteins that associate with CSK in v-Src NIH 3T3 cells by anti-P.Tyr immunoblotting. Nine P.Tyr-containing proteins coimmunoprecipitated with CSK from v-Src NIH 3T3 cells. One of these, an approximately 62-kDa protein, also associated with CSK in NIH 3T3 cells treated with vanadate prior to lysis and in NIH 3T3 cells expressing an activated c-Src mutant. This 62-kDa protein was shown to be identical to the GTPase-activating protein (GAP)-associated p62 (GAP-A.p62) protein. The interaction between CSK and GAP-A.p62 could be reconstituted in vitro with glutathione S-transferase fusion proteins containing full-length CSK or the CSK SH2 domain. Furthermore, our data show that CSK interacts directly with GAP.A-p62 and that the complex between the two proteins is localized in subcellular membrane or cytoskeletal fractions. Our results suggest that GAP-A.p62 may function as a docking protein and may mediate translocation of proteins, including GAP and CSK, to membrane or cytoskeletal regions upon c-Src activation.
Mapping of QTL for Seed Size and Shape Traits in Common Bean (2000)

Our objective was to identify quantitative trait loci (QTL) for seed weight, length, and height segregating in a recombinant inbred line population derived from the common bean ( Phaseolus vulgaris L.) cross `PC-50' × XAN-159. The parents and progeny were grown in two separate greenhouse experiments in Nebraska, and in field plots in the Dominican Republic and Wisconsin. Data analysis was done for individual environments separately and on the mean over all environments. A simple linear regression analysis of all data indicated that most QTL appeared to be detected in the mean environment. Based on these results, composite interval mapping (CIM) analysis was applied to the means over environments. For seed weight, strong evidence was indicated for five QTL on common bean linkage groups (LGs) 3, 4, 6, 7, and 8. Multiple regression analysis (MRA) indicated that these QTL explained 44% of the phenotypic variation for the trait. Weaker evidence was found for three additional candidate QTL on bean LGs 4, 5, and 8. All eight markers associated with these QTL were significant in a MRA where the full model explained 63% of the variation among seed weight means. For seed length, CIM results indicated strong evidence for three QTL on LG 8 and one on LG 2. Three additional putative QTL were detected on LGs 3, 4, and 11. The markers associated with the three seed length QTL on LG 8, and the QTL on LGs 2 and 11 were significant in a MRA with the full model explaining 48% of the variation among seed length means. For seed height, three QTL on LGs 4, 6, and 11 explained 36% of the phenotypic variation for trait means. Four of the seven QTL for seed length and two of three QTL for seed height also appeared to correspond to QTL for seed weight. Four QTL for common bacterial blight resistance [ Xanthomonas campestris pv. phaseoli (Smith Dye)] and for smaller seed size were associated on LGs 6, 7, and 8. The implications of these findings for breeders is discussed.
Analysis of protective immune responses to the glycoprotein H-glycoprotein L complex of herpes simplex virus type 1 (1993)

A recombinant vaccinia virus expressing both glycoprotein H (gH) and glycoprotein L (gL) of herpes simplex virus type 1 (HSV-1) was used to examine the protective response to gH-gL in immunized mice and to compare these responses with those induced by the highly protective immunogen, glycoprotein D (gD). Weak levels of HSV-1-specific neutralizing antibody were obtained in response to the gH-gL complex, virus clearance from the site of challenge was marginally enhanced compared to that observed following immunization with gH alone, and gH-gL was found to protect mice against acute infection in the ganglia, although not as efficiently as gD.
Psychosocial Stress Elevates Blood Pressure Via an Opioid Dependent Mechanism in Normotensive Rats (1991)

Stress is an important risk factor in cardiovascular diseases, including hypertension. Endogenous opioids are known to be elevated in stress and in various models of hypertension with differing etiologies. Blockade of endogenous opioids with naloxone has been demonstrated to attenuate or reverse the elevation in blood pressure in both renovascular and spontaneous hypertension. In the current study, increased blood pressure was induced using a model of psychosocial stress. During the first week of stress, systolic blood pressure rose rapidly to reach a level that was sustained throughout the remaining period of stress. Chronic infusion of the opiate antagonist, naloxone, both prevented and completely reversed the elevated blood pressure due to psychosocial stress. These data demonstrate that elevated endogenous opioids are important factors in cardiovascular regulation and are likely to influence both the development and maintenance of stress-induced hypertension.
Overview of systematic reviews on the health-related effects of government tobacco control policies (2015)

When designing and implementing tobacco control programs, governments should prioritize smoking bans and price increases of tobacco products followed by other interventions. Additional studies are needed on the various factors that can influence a policy's effectiveness and feasibility such as cost, local context, political barriers and implementation strategies.
A Combination Strategy to Inhibit Pim‐1: Synergism between Noncompetitive and ATP‐Competitive Inhibitors (2013)

Pim-1 is a serine/threonine kinase critically involved in the initiation and progression of various types of cancer, especially leukemia, lymphomas and solid tumors such as prostate, pancreas and colon, and is considered a potential drug target against these malignancies. In an effort to discover new potent Pim-1 inhibitors, a previously identified ATP-competitive indolyl-pyrrolone scaffold was expanded to derive structure-activity relationship data. A virtual screening campaign was also performed, which led to the discovery of additional ATP-competitive inhibitors as well as a series of 2-aminothiazole derivatives, which are noncompetitive with respect to both ATP and peptide substrate. This mechanism of action, which resembles allosteric inhibition, has not previously been characterized for Pim-1. Notably, further evaluation of the 2-aminothiazoles indicated a synergistic inhibitory effect in enzymatic assays when tested in combination with ATP-competitive inhibitors. A synergistic effect in the inhibition of cell proliferation by ATP-competitive and ATP-noncompetitive compounds was also observed in prostate cancer cell lines (PC3), where all Pim-1 inhibitors tested in showed synergism with the known anticancer agent, paclitaxel. These results further establish Pim-1 as a target in cancer therapy, and highlight the potential of these agents for use as adjuvant agents in the treatment of cancer diseases in which Pim-1 is associated with chemotherapeutic resistance.
Immune responses in congenic mice to multiple antigen peptides based on defined epitopes from the malaria antigen Pf332 (1996)

Repeat sequences from the Plasmodium falciparum blood stage antigen Pf332 frequently comprise the pentapeptide VTEEI, an epitope recognized by certain parasite neutralizing antibodies. This B-cell epitope was assembled in an octavalent multiple antigen peptide (MAP) system either as trimers (VTEEI)3 (MAP1) or as an integral part of a naturally occurring Pf332 undecamer repeat sequence SVTEEIAEEDK (MAP2). Characteristics of the immunogenicity of these subunit constructs were evaluated in H-2 congenic mice. MAP1 generated antibody responses in mice of the H-2d, H-2k and H-2q haplotypes, but not in H-2b or H-2s mice, whereas MAP2 only induced antibodies in mice of H-2k haplotype. When analysing T-cell responses induced by the MAP, lymph node cells from responder strains primed in vivo with MAP1 proliferated in response to restimulation with both MAP1 and the peptide (VTEEI)3. MAP2, however, did not induce a detectable T-cell proliferation. Additionally, the lack of antibody response to MAP1 in H-2b mice could be circumvented by combining the MAP1 peptide and a H-2b-restricted T-cell epitope in a diepitope MAP construct. Despite the fact that the motif VTEEI has not been identified in Pf332 sequences in the form of a trimer, MAP1 did induce Pf332 protein-reactive antibodies. Assembly of multimers of short defined epitopes in MAP constitutes an interesting approach for the design of polyvalent subunit immunogens.
The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing -(1 -pentynyl)-2′-deoxyuridine (1994)

Combinatorial libraries of nucleic acids are developing into novel sources for lead compounds in drug development. In order to diversify the pool of ss DNA sequences, we have used a modified nucleotide, 5-(1-pentynyl)-2'-deoxyuridine, in place of thymidine in a random nucleic acid library and screened this library against human thrombin. Previously, we described this screening method to identify a novel structural inhibitor (an aptamer) of the coagulation protease thrombin (Bock, L. et. al. (1992) Nature 355 564-566). Using the modified nucleic acid library, we have now isolated a second pool of thrombin inhibitors with strikingly different sequence composition compared to the selection using natural bases. This second class of aptamers is dependent on the presence of the modified nucleotide for protein binding and clotting inhibition. Our method represents a potential strategy to enhance the diversity of libraries for in vitro selection, and thereby increasing the utility of this technique in the identification of molecules with novel biochemical properties.
Alkaline Phosphatase Mono- and Diesterase Reactions:  Comparative Transition State Analysis (2006)

Enzyme-catalyzed phosphoryl transfer reactions have frequently been suggested to proceed through transition states that are altered from their solution counterparts. Previous work with Escherichia coli alkaline phosphatase (AP), however, suggests that this enzyme catalyzes the hydrolysis of phosphate monoesters through a loose, dissociative transition state, similar to that in solution. AP also exhibits catalytic promiscuity, with a low level of phosphodiesterase activity, despite the tighter, more associative transition state for phosphate diester hydrolysis in solution. Because AP is evolutionarily optimized for phosphate monoester hydrolysis, it is possible that the active site environment alters the transition state for diester hydrolysis to be looser in its bonding to the incoming and outgoing groups. To test this possibility, we have measured the nonenzymatic and AP-catalyzed rate of reaction for a series of substituted methyl phenyl phosphate diesters. The values of beta(lg) and additional data suggest that the transition state for AP-catalyzed phosphate diester hydrolysis is indistinguishable from that in solution. Instead of altering transition state structure, AP catalyzes phosphoryl transfer reactions by recognizing and stabilizing transition states similar to those in aqueous solution. The AP active site therefore has the ability to recognize different transition states, a property that could assist in the evolutionary optimization of promiscuous activities.
Minor-Groove Recognition of Double-Stranded RNA by the Double-Stranded RNA-Binding Domain from the RNA-Activated Protein Kinase PKR (1996)

The human double-stranded RNA- (dsRNA) activated protein kinase (PKR) has a dsRNA-binding domain (dsRBD) that contains two tandem copies of the dsRNA-binding motif (dsRBM). The minimal-length polypeptide required to bind dsRNA contains both dsRBMs, as determined by mobility-shift and filter-binding assays. Mobility-shift experiments indicate binding requires a minimum of 16 base pairs of dsRNA, while a minimal-length site for saturation of longer RNAs is 11 base pairs. Bulge defects in the helix disfavor binding, and single-stranded tails do not strongly influence the dsRNA length requirement. These polypeptides do not bind an RNA-DNA hybrid duplex or dsDNA as judged by either mobility-shift or competition experiments, suggesting 2'-OH contacts on both strands of the duplex stabilize binding. Related experiments on chimeric duplexes in which specific sets of 2'-OHs are substituted with 2'-H or 2'-OCH3 reveal that the 2'-OHs required for binding are located along the entire 11 basepair site. These results are supported by Fe(II) EDTA footprinting experiments that show protein-dependent protection of the minor groove of dsRNA. The dependence of dsRNA-protein binding on salt concentration suggests that only one ionic contact is made between the protein and dsRNA phosphate backbone and that at physiological salt concentrations 90% of the free energy of binding is nonelectrostatic. Thus, the specificity of PKR for dsRNA over RNA-DNA hybrids and dsDNA is largely due to molecular recognition of a network of 2'-OHs involving both strands of dsRNA and present along the entire 11 base-pair site.
Actin gene expression visualized in chicken muscle tissue culture by using in situ hybridization with a biotinated nucleotide analog. (1982)

The chicken muscle tissue culture system has been used for visualizing actin gene expression after in situ hybridization. Cell differentiation is morphologically distinguishable in this system as the myoblasts fuse into myotubes. This differentiation involves the production of large amounts of actin required for myofibrils. The presence of actin mRNA has been observed in cells preserved with ethanol and paraformaldehyde by hybridizing a recombinant plasmid into which a biotinated analog of dUTP was incorporated by nick-translation. The biotin was then detected by using an anti-biotin antibody and a rhodamine-conjugated second antibody. Alternatively, avidin conjugated to rhodamine or avidin complexed to biotinated peroxidase has been used for mRNA detection. The procedure described preserved morphological detail yet is compatible with hybridization conditions and reveals the disposition of actin mRNA during gene expression.