gebhart/patrepeval huggingface dataset:
Parallel Genomic Sequence-Searching on an Ad-Hoc Grid: Experiences, Lessons Learned, and Implications (2006)

The Basic local alignment search tool (BLAST) allows bioinformaticists to characterize an unknown sequence by comparing it against a database of known sequences. The similarity between sequences enables biologists to detect evolutionary relationships and infer biological properties of the unknown sequence. mpiBLAST, our parallel BLAST, decreases the search time of a 300 KB query on the current NT database from over two full days to under 10 minutes on a 128-processor cluster and allows larger query files to be compared. Consequently, we propose to compare the largest query available, the entire NT database, against the largest database available, the entire NT database. The result of this comparison can provide critical information to the biology community, including insightful evolutionary, structural, and functional relationships between every sequence and family in the NT database. Preliminary projections indicated that to complete the task in a reasonable length of time required more processors than were available to us at a single site. Hence, we assembled GreenGene, an ad-hoc grid that was constructed "on the fly" from donated computational, network, and storage resources during last year's SC|05. GreenGene consisted of 3048 processors from machines that were distributed across the United States. This paper presents a case study of mpiBLAST on GreenGene - specifically, a pre-run characterization of the computation, the hardware and software architectural design, experimental results, and future directions
Relative Immunogenicity of PorA Subtypes in a Multivalent Neisseria meningitidis Vaccine Is Not Dependent on Presentation Form (2003)

The hexavalent meningococcal vaccine HexaMen, containing six PorAs on two vesicles, was tested in clinical studies. Although fourfold increases in serum bactericidal activity (SBA) titers against all of the PorAs were observed, there were significant differences between PorA-specific SBA titers. SBA titers were mainly directed against one PorA from each vesicle, P1.5-2,10 and P1.5-1,2-2, and were lower against the other PorAs, especially P1.7-2,4 and P1.19,15-1. We investigated whether these differences were due to immunological interference that resulted in competition between the three PorAs on the same vesicle or whether they were caused by a difference in the immunogenicities of the separate PorAs. Therefore, mice were immunized either with HexaMen, with six monovalent outer membrane vesicles (OMVs) representing the same six PorAs simultaneously (HexaMix), or with only one of the monovalent OMVs. The immunoglobulin G and SBA titers after HexaMen immunization in mice resembled the results obtained in clinical studies. Although immunization with HexaMix gave higher titers than immunization with HexaMen for some PorAs, the pattern of high and low titers was the same. Similar differences in immunogenicity between subtypes were seen after monovalent immunization when interference was eliminated as a cause of the differences. Monovalent immunization resulted in higher titers for P1.5-1,2-2 and P1.7,16 than immunization with HexaMen. However, no significant differences were found for the weakly immunogenic PorAs, P1.7-2,4 and P1.19,15-1. Since immunization with the six PorAs in the trivalent presentation form (HexaMen) and in the mixture of monovalent vesicles (HexaMix) resulted in the same pattern of high and low titers, we concluded that the differences between the PorA-specific responses are due to differences in the immunogenicities of the various PorAs and not due to interference that results in competition between different PorAs.
Expression of macrophage‐selective markers in human and rodent adipocytes (2005)

CD14, CD68 and/or mouse F4/80 or human epidermal growth factor module-containing mucin-like receptor 1 (EMR1) are widely used as macrophage-specific markers. Since macrophages infiltrate several tissues during inflammatory processes, CD14, CD68 and EMR1-F4/80 have been employed to discriminate between tissue-containing macrophages, like adipose tissue (AT), and other cells. Using real-time PCR experiments, we show that isolated adipocytes from humans and mice AT express high levels of CD14 and CD68 mRNA, whereas EMR1-F4/80 is mainly present in the macrophage-containing stroma-vascular fraction. Furthermore, fibroblasts-like cells (adipoblasts), preadipocytes and adipocytes from the murine cell lines, 3T3-F442A and BFC-1, express CD14 and CD68 mRNA and protein as determined by fluorescence-activated cell sorter, but not F4/80 which, as expected, is strongly expressed in the macrophage cell line RAW264.7. These results reinforce the view that EMR1-F4/80 is the best macrophage marker to date and show that CD14 and CD68 are not macrophage-specific proteins.
P2X7Receptor Expression after Ischemia in the Cerebral Cortex of Rats (2004)

Large amounts of adenosine 5'-triphosphate (ATP) released from cellular sources under pathological conditions such as ischemia may activate purinoceptors of the P2X and P2Y types. In the present study, the expression of the P2X7 receptor-subtype in the brain cortex of spontaneously hypertensive rats was investigated using a permanent focal cerebral ischemia model. Immunocytochemistry with antibodies raised against the intracellular C-terminus of the P2X7 receptor showed a time-dependent upregulation of labeled cells in the peri-infarct region after right middle cerebral artery occlusion (MCAO) in comparison to controls. Double immunofluorescence visualized with confooal laser scanning microscopy indicated the localization of the P2X7 receptor after ischemia on microglial cells (after 1 and 4 days), on tubulin betaIII-labeled neurons (after 4 and 7 days), and on glial fibrillary acidic protein (GFAP)-positive astrocytes (after 4 days). In the following experiments, changes occurring 4 days after MCAO were investigated in detail. Western blot analysis of the cortical tissue around the area of necrosis indicated an increase in the P2X7 receptor protein. Immunoelectron microscopy revealed the receptor localization on synapses (presynaptically), on dendrites, as well as on the nuclear membrane of neurons (postsynaptically) and glial cells. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling in combination with P2X7 receptor immunocytochemistry indicated a co-expression on the apoptotic cells. Active caspase 3 was especially observed on GFAP-positive astrocytes. In conclusion, the present data demonstrate a postischemic, time-dependent upregulation of the P2X7 receptor-subtype on neurons and glial cells and suggest a role for this receptor in the pathophysiology of cerebral ischemia in vivo.
RNA interference in human cells is restricted to the cytoplasm (2002)

RNA interference (RNAi) is an evolutionarily conserved eukaryotic adaptive response that leads to the specific degradation of target mRNA species in response to cellular exposure to homologous double-stranded RNA molecules. Here, we have analyzed the subcellular location at which RNA degradation occurs in human cells exposed to double-stranded short interfering RNAs. To unequivocally determine whether a given mRNA is subject to degradation in the cytoplasm, the nucleus, or both, we have used the retroviral Rev/RRE system to control whether target mRNAs remain sequestered in the nucleus or are exported to the cytoplasm. In the absence of export, we found that the nuclear level of the RRE-containing target mRNA was not affected by activation of RNAi. In contrast, when nuclear export was induced by expression of Rev, cytoplasmic target mRNAs were effectively and specifically degraded by RNAi. Curiously, when the target mRNA molecule was undergoing active export from the nucleus, induction of RNAi also resulted in a reproducible approximately twofold drop in the level of target mRNA present In the nuclear RNA fraction. As this same mRNA was entirely resistant to RNAi when sequestered in the nucleus, this result suggests that RNAi is able to induce degradation of target mRNAs not only in the cytoplasm but also during the process of nuclear mRNA export. Truly nucleoplasmic mRNAs or pre-mRNAs are, in contrast, resistant to RNAi.
Oxo-Bridged Bimetallic Group 4 Complexes Bearing Amine-Bis(benzotriazole phenolate) Derivatives as Bifunctional Catalysts for Ring-Opening Polymerization of Lactide and Copolymerization of Carbon Dioxide with Cyclohexene Oxide (2014)

We report the synthesis, crystal structure, and catalytic studies for ring-opening polymerization (ROP) of group 4 metal alkoxides based on amine-BiBTP derivatives (amine-BiBTP = amine-bis(benzotriazole phenolate)). Dinuclear group 4 metal alkoxides [{(amine-BiBTP)Mt(OiPr)}2(μ-O)] (4–7, Mt = Ti, Zr, Hf) resulted from treatment of amine-BiBTP-H2 as the ligand precursor with 1.0 molar equiv of metal precursor (Ti(OiPr)4, Zr(OiPr)4(iPrOH), or Hf(OiPr)4(iPrOH)), followed by the addition of H2O (0.5 equiv) in good yields. The solid-state structure of 4–7 reveals a bimetallic BiBTP-ligated metal(IV) alkoxide with an oxo ligand chelating two metal atoms, and the bonding mode of the metal-O(μ-oxo)-metal moiety assumes a linear type. Catalysis of lactide polymerization and carbon dioxide/cyclohexene oxide copolymerization of oxo-bridged bimetallic metal complexes was systematically examined. Zirconium alkoxide 6 shows an effective catalyst in the ROP of lactide with “living” and “immortal” fashions, yielding poly(lactide)s with the predicted molecular weights and narrow polydispersity indices (PDIs <1.25) as well as an isotactic-enriched predominance (Pm up to 0.71). Bimetallic BiBTP-featuring Zr complex 6 was also able to couple carbon dioxide and cyclohexene oxide to give poly(cyclohexene carbonate-co-cyclohexene oxide), having a high copolymer selectivity and good carbonate-linkage contents under the optimal conditions. This is a successful example of catalysis for both processes using one well-defined zirconium(IV) alkoxide complex as a bifunctional catalyst.
Synthesis and Biological Evaluation of Disulfide‐Linked HPMA Copolymer‐Mesochlorin e6 Conjugates (2008)

Novel polymeric delivery systems for the photosensitizer mesochlorin e6 (Mce6) were synthesized to overcome problems of systemic toxicity. A disulfide bond was included to allow for quick release of Mce6 from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone once internalized in tumor tissue. The synthesized conjugates demonstrated a time-dependent reductive cleavage with an accompanying increase in the quantum yield of singlet oxygen generation on exposure to DTT. Quicker release kinetics and a higher cytotoxicity in SKOV-3 human ovarian carcinoma cells were obtained as compared to polymer conjugate with a proteolytically cleavable GFLG spacer. These novel conjugates hold promise as clinically relevant drug delivery systems for photodynamic therapy of cancer.
Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase. A novel serine/threonine protein kinase that defines a second subfamily of mixed lineage kinases. (1994)

Molecular cloning using a degenerate oligonucleotide-based polymerase chain reaction was undertaken to test the possibility that novel, developmentally regulated protein kinases are expressed in the embryonic mouse kidney. Several receptor tyrosine kinase and serine/threonine kinase cDNA clones were identified. One of these, designated DLK, represented a novel gene product whose 3.6-kilobase transcript was expressed in a tissue-specific and developmentally regulated fashion. Several clones encoding the entire open reading frame were isolated and sequenced. The identified open reading frame encodes an 888-amino acid polypeptide that defines a new subfamily within the mixed lineage protein kinase family. Sequence analysis revealed: 1) a kinase catalytic domain most characteristic of serine/threonine kinases but hybrid between members of the family of microtubule-associated protein kinase kinase kinases and the fibroblast growth factor receptor family; 2) two putative alpha-helical leucine zipper motifs separated by a 25-amino acid charged intermediate segment but lacking an NH2-terminal basic domain; and 3) COOH-terminal and NH2-terminal proline-rich domains suggestive of src homology 3 (SH3) domain binding regions. Rabbit polyclonal immune sera generated against a carboxyl-terminal bacterial fusion protein recognized a protein with an apparent molecular mass of 130 kDa in COS 7 cells that were transiently transfected with a full-length DLK cDNA expression vector. Moreover, COS 7 cells transiently transfected with an epitope-tagged DLK expression vector expressed protein with an apparent molecular mass of 130 kDa that became autophosphorylated on serine and threonine in an in vitro kinase assay.
H2xMnxSn3‐xS6 (x = 0.11–0.25): A Novel Reusable Sorbent for Highly Specific Mercury Capture Under Extreme pH Conditions (2009)

Abstract The H 2x Mn x Sn 3‐x S 6 (x = 0.11–0.25) is a new solid acid with a layered hydrogen metal sulfide (LHMS). It derives from K 2x Mn x Sn 3–x S 6 (x = 0.5–0.95) (KMS‐1) upon treating it with highly acidic solutions. We demonstrate that LHMS‐1 has enormous affinity for the very soft metal ions such as Hg 2+ and Ag + which occurs via a rapid ion exchange process. The tremendous affinity of LHMS‐1 for Hg 2+ is reflected in very high distribution coefficient K d Hg values (&gt;10 6 mL g −1 ). The large affinity and selectivity of LHMS‐1 for Hg 2+ persists in a very wide pH range (from less than zero to nine) and even in the presence of highly concentrated HCl and HNO 3 acids. LHMS‐1 is significantly more selective for Hg 2+ and Ag + than for the less soft cations Pb 2+ and Cd 2+ . The Hg 2+ ions are immobilized in octahedral sites between the sulfide layers of the materials via Hg–S bonds as suggested by pair distribution function (PDF) analysis. LHMS‐1 could decrease trace concentrations of Hg 2+ (e.g. &lt;100 ppb) to well below the acceptable limits for the drinking water in less than two min. Hg‐laden LHMS‐1 shows a remarkable hydrothermal stability and resistance in 6 M HCl solutions. LHMS‐1 could be regenerated by treating Hg‐loaded samples with 12 M HCl and re‐used without loss of its initial exchange capacity.
Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer β-amyloid peptides (1999)

The excessive generation and accumulation of 40- and 42-aa beta-amyloid peptides (Abeta40/Abeta42) in selectively vulnerable brain regions is a major neuropathological feature of Alzheimer's disease. Abeta, derived by proteolytic cleavage from the beta-amyloid precursor protein (betaAPP), is normally secreted. However, recent evidence suggests that significant levels of Abeta also may remain inside cells. Here, we have investigated the subcellular compartments within which distinct amyloid species are generated and the compartments from which they are secreted. Three experimental approaches were used: (i) immunofluorescence performed in intact cortical neurons; (ii) sucrose gradient fractionation performed with mouse neuroblastoma cells stably expressing wild-type betaAPP695 (N2a695); and (iii) cell-free reconstitution of Abeta generation and trafficking from N2a695 cells. These studies demonstrate that: (i) Abeta40 (Abeta1-40 plus Abetax-40, where x is an NH2-terminal truncation) is generated exclusively within the trans-Golgi Network (TGN) and packaged into post-TGN secretory vesicles; (ii) Abetax-42 is made and retained within the endoplasmic reticulum in an insoluble state; (iii) Abeta42 (Abeta1-42 plus Abetax-42) is made in the TGN and packaged into secretory vesicles; and (iv) the amyloid peptides formed in the TGN consist of two pools (a soluble population extractable with detergents and a detergent-insoluble form). The identification of the organelles in which distinct forms of Abeta are generated and from which they are secreted should facilitate the identification of the proteolytic enzymes responsible for their formation.
Management of asthma in adults: current therapy and future directions (2003)

Asthma is increasing in prevalence worldwide and results in significant use of healthcare resources. Although most patients with asthma can be adequately treated with inhaled corticosteroids, an important number of patients require additional therapy and an increasing number of options are available. A further minority of patients develop severe persistent asthma which remains difficult to manage despite current pharmacological therapies. This review discusses the various treatment options currently available for each stage of asthma severity, highlights some of the limitations of current management, and outlines directions which may improve the management of asthma in the future.
Synthesis, Characteristics and Bioactivities of Novel Isosteviol Derivatives (2019)

a a a a * ,a,d * ,e ( a 116029) ( b 116600) ( c 133002) ( d 116029) ( e 116044)
Leptin depolarizes rat hypothalamic paraventricular nucleus neurons (1998)

Leptin, the protein product of the ob/ob gene, is thought to have a central site of action, presumably within the hypothalamus, through which it regulates feeding behavior. THe paraventricular nucleus (PVN) is one structure that has been implicated in regulating feeding behavior. Using patch-clamp recording techniques, this study examines the direct membrane effects of leptin on neurons in a coronal PVN slice. Bath application of the physiologically active leptin fragment (amino acids 22-56) elicited dose-related depolarizations in 82% of the type I cells tested (n = 17) and 67% of the type II cells tested (n = 9). By contrast, the physiologically inactive leptin fragment (amino acids 57-92) had no discernible effect on membrane potential (n = 7). The effects of this peptide were unaffected following synaptic isolation of the cells by bath application of the sodium channel blocker tetrodotoxin (n = 5). Voltage clamp recordings in six cells demonstrated that leptin increased a nonspecific cation conductance with a reversal potential near -30 mV. These findings suggest that neurons in PVN may play an important role in the central neuronal circuitry involved in the physiological response to leptin.
Crystallization of the gastric H,K-ATPase. (1986)

Crystalline arrays of the gastric H,K-ATPase were obtained in membrane preparations from hog and rabbit gastric mucosa. The lattice was formed rapidly in a medium containing K+, vanadate, Mg2+, and dimethyl sulfoxide at pH 6.0-6.9 in imidazole buffer from 4 to 22 degrees C. The crystal lattice exhibited P2 symmetry, and the unit cell dimension (a = 5.6, b = 11, and c = 10 nm) could accommodate 2 polypeptides of mass 116-129 kDa. In addition, the isolated preparation contained previously undescribed long cylindrical structures 16 nm thick. These structures consisted of a central core 6-7 nm wide from which particles spaced 5.5 nm apart protruded symmetrically.
A dimer as a building block in assembling RNA. A hexamer that gears bacterial virus phi29 DNA-translocating machinery. (2000)

Six RNA (pRNA) molecules form a hexamer, via hand-in-hand interaction, to gear bacterial virus phi29 DNA translocation machinery. Here we report the pathway and the conditions for the hexamer formation. Stable pRNA dimers and trimers were assembled in solution, isolated from native gels, and separated by sedimentation, providing a model system for the study of RNA dimers and trimers in a protein-free environment. Cryo-atomic force microscopy revealed that monomers displayed a check mark outline, dimers exhibited an elongated shape, and trimers formed a triangle. Dimerization of pRNA was promoted by a variety of cations including spermidine, whereas procapsid binding and DNA packaging required specific divalent cations, including Mg(2+), Ca(2+), and Mn(2+). Both the tandem and fused pRNA dimers with complementary loops designed to form even-numbered rings were active in DNA packaging, whereas those without complementary loops were inactive. We conclude that dimers are the building blocks of the hexamer, and the pathway of building a hexamer is: dimer --> tetramer --> hexamer. The Hill coefficient of 2.5 suggests that there are three binding sites with cooperative binding on the surface of the procapsid. The two interacting loops played a key role in recruiting the incoming dimer, whereas the procapsid served as the foundation for hexamer assembly.
Face Synthesis with Landmark Points from Generative Adversarial Networks and Inverse Latent Space Mapping (2018)

Facial landmarks refer to the localization of fundamental facial points on face images. There have been a tremendous amount of attempts to detect these points from facial images however, there has never been an attempt to synthesize a random face and generate its corresponding facial landmarks. This paper presents a framework for augmenting a dataset in a latent Z-space and applied to the regression problem of generating a corresponding set of landmarks from a 2D facial dataset. The BEGAN framework has been used to train a face generator from CelebA database. The inverse of the generator is implemented using an Adam optimizer to generate the latent vector corresponding to each facial image, and a lightweight deep neural network is trained to map latent Z-space vectors to the landmark space. Initial results are promising and provide a generic methodology to augment annotated image datasets with additional intermediate samples.
Increased Antibody Affinity Confers Broad In Vitro Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus (2012)

Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (K(D)) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection.