gebhart/patrepeval huggingface dataset:
A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals (2010)

A protective vaccine against HIV-1 will likely require the elicitation of a broadly neutralizing antibody (bNAb) response. Although the development of an immunogen that elicits such antibodies remains elusive, a proportion of HIV-1 infected individuals evolve broadly neutralizing serum responses over time, demonstrating that the human immune system can recognize and generate NAbs to conserved epitopes on the virus. Understanding the specificities that mediate broad neutralization will provide insight into which epitopes should be targeted for immunogen design and aid in the isolation of broadly neutralizing monoclonal antibodies from these donors. Here, we have used a number of new and established technologies to map the bNAb specificities in the sera of 19 donors who exhibit among the most potent cross-clade serum neutralizing activities observed to date. The results suggest that broad and potent serum neutralization arises in most donors through a limited number of specificities (1-2 per donor). The major targets recognized are an epitope defined by the bNAbs PG9 and PG16 that is associated with conserved regions of the V1, V2 and V3 loops, an epitope overlapping the CD4 binding site and possibly the coreceptor binding site, an epitope sensitive to a loss of the glycan at N332 and distinct from that recognized by the bNAb 2G12 and an epitope sensitive to an I165A substitution. In approximately half of the donors, key N-linked glycans were critical for expression of the epitopes recognized by the bNAb specificities in the sera.
Scalable Grid Service Discovery based on UDDI (2005)

Efficient discovery of grid services is essential for the success of grid computing. The standardization of grids based on web services has resulted in the need for scalable web service discovery mechanisms to be deployed in grids Even though UDDI has been the de facto industry standard for web-services discovery, imposed requirements of tight-replication among registries and lack of autonomous control has severely hindered its widespread deployment and usage. With the advent of grid computing the scalability issue of UDDI will become a roadblock that will prevent its deployment in grids. In this paper we present our distributed web-service discovery architecture, called DUDE (Distributed UDDI Deployment Engine). DUDE leverages DHT (Distributed Hash Tables) as a rendezvous mechanism between multiple UDDI registries. DUDE enables consumers to query multiple registries, still at the same time allowing organizations to have autonomous control over their registries.. Based on preliminary prototype on PlanetLab, we believe that DUDE architecture can support effective distribution of UDDI registries thereby making UDDI more robust and also addressing its scaling issues. Furthermore, The DUDE architecture for scalable distribution can be applied beyond UDDI to any Grid Service Discovery mechanism.
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder (2020)

ClinicalTrials.gov Identifier: NCT03181529.
Mitochondrial G8363A mutation presenting as cerebellar ataxia and lipomas in an Italian family (1999)

We report an Italian family harboring the mitochondrial DNA (mtDNA) G8363A mutation in the tRNALys gene in association with various combinations of encephalopathy, ophthalmoparesis, and horse collar lipomas. These findings add to the complex relationship between mtDNA pathogenetic mutations and disease phenotype.

The proband (III-10), a 22-year-old man, developed normally until age 9 years, when he had progressive gait ataxia and dysarthria. Neurologic examination also showed progressive external ophthalmoparesis, dysphagia, myoclonic jerks, and bilateral hearing impairment. Venous lactic acid was elevated (5 mmol/L; normal <2.4 mmol/L). The maternal grandmother (I-1) reportedly had a late-onset gait disorder. Our proband’s mother (II-4) started to have gait and truncal ataxia at age 22. At age 60, neurologic examination revealed limited upper gaze, mild hearing impairment, and brisk tendon reflexes. Her serum lactate was 2.7 mmol/L. Similar clinical features were found in Patients II-5 and II-6, whose onset was in late adolescence. In addition, Patients II-4, II-5, and II-6 …
Relationship between bacteriophage T4 and T6 DNA topoisomerases. T6 39-protein subunit is equivalent to the combined T4 39- and 60-protein subunits. (1985)

T6 DNA topoisomerase has been purified from bacteriophage T6 infected Escherichia coli. Unlike the T4 DNA topoisomerase which has three subunits, it consists of two subunits of molecular weights 75,000 and 51,000. They are the products of T6 genes 39 and 52, respectively. The purified T6 enzyme can stimulate in vitro T6 DNA replication. It has an ATP-dependent DNA relaxation activity similar to the T4 enzyme. Either ATP or dATP can be used in both reactions. Using a Western blotting and radioimmuno-detection methods, we show that T6 39 subunit contains protein sequences specified by both the T4 39 and 60 genes. The 52-proteins of both phages appear to be identical. The T4 and T6 topoisomerase genes represent a naturally occurring example of gene separation or fusion.
High-frequency ferromagnetic resonance on ultrafine cobalt particles (1999)

We report on high-frequency (300--700 GHz) ferromagnetic resonance (HF-FMR) measurements on cobalt superparamagnetic particles with strong uniaxial effective anisotropy. We derive the dynamical susceptibility of the system on the basis of an independent-grain model by using a rectangular approach. Numerical simulations give typical line shapes depending on the anisotropy, the gyromagnetic ratio, and the damping constant. HF-FMR experiments have been performed on two systems of ultrafine cobalt particles of different sizes with a mean number of atoms per particles of $150\ifmmode\pm\else\textpm\fi{}20$ and $310\ifmmode\pm\else\textpm\fi{}20.$ In both systems, the magnetic anisotropy is found to be enhanced compared to the bulk value, and increases as the particle size decreases, in accordance with previous determinations from magnetization measurements. Although no size effect has been observed on the gyromagnetic ratio, the transverse relaxation time is two orders of magnitude smaller than the bulk value indicating strong damping effects, possibly originating from surface spin disorders.
Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective (2003)

The high cost and limited availability of factor concentrates make dosing of factor VIII (FVIII) or factor IX (FIX) a crucial issue in the prophylactic treatment of haemophilia. It has often been recommended that this treatment should aim to maintain a minimum plasma level of 1% of normal coagulation factor activity (FVIII:C or FIX:C). The dosage needed is commonly given as 25-40 U kg(-1) three times weekly for FVIII or twice weekly for FIX. However, these guidelines are valid only with several qualifications. First, the actual trough levels required may vary considerably between patients. The clinical severity of haemophilia may depend on more factors than the endogenous level of FVIII:C or FIX:C. Secondly, interindividual variations in dose requirements are also due to variance in the pharmacokinetics of the coagulation factors. Pharmacokinetic calculations are useful to design optimal dosing schedules to achieve required trough levels of FVIII:C or FIX:C. Moreover, tailoring of the dosing of FVIII or FIX according to their disposition in the individual patient can markedly improve the cost-effectiveness of prophylactic treatment. However, the usefulness of in vivo recovery as a guide for prophylactic dosing seems questionable. It should be clearly understood that maintaining a certain trough level of FVIII:C or FIX:C is not an end in itself. Clinical outcome, not the achieved trough level, determines whether a dosage is adequate. Chiefly for economic reasons, the minimum effective dosage of coagulation factor should be determined and used in every patient. The dose requirement should also be re-evaluated at appropriate times.
Effect of Danazol in Immune Thrombocytopenic Purpura (1987)

Danazol and vinblastine are effective in many patients with chronic immune thrombocytopenic purpura (ITP). To evaluate the mechanism of action of these drugs, we studied six consecutive patients with chronic ITP treated with danazol and one treated with vinblastine. All the patients responded clinically without a notable change in the level of platelet-associated IgG. Instead, the clinical response to therapy was associated with a decrease in the number of monocyte binding sites for monomeric IgG (Fc receptors). In one patient, clinical relapse was associated with a spontaneous 2.7-fold increase in the number of monocyte Fc (IgG) receptors, without a change in the level of platelet-associated immunoglobulin. A decrease in the number of monocyte Fc (IgG) receptors following vinblastine infusion was associated with a clinical remission. We conclude that the clinical course of ITP may be influenced by the expression of monocyte or macrophage Fc (IgG) receptors. Danazol and vinblastine may mediate their clinical effect, at least in part, by influencing the number of available Fc (IgG) receptors on phagocytic cells.
Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4 (2011)

Prx4 (peroxiredoxin 4) is the only peroxiredoxin located in the ER (endoplasmic reticulum) and a proposed scavenger for H2O2. In the present study, we solved crystal structures of human Prx4 in three different redox forms and characterized the reaction features of Prx4 with H2O2. Prx4 exhibits a toroid-shaped decamer constructed of five catalytic dimers. Structural analysis revealed conformational changes around helix α2 and the C-terminal reigon with a YF (Tyr-Phe) motif from the partner subunit, which are required for interchain disulfide formation between Cys87 and Cys208, a critical step of the catalysis. The structural explanation for the restricting role of the YF motif on the active site dynamics is provided in detail. Prx4 has a high reactivity with H2O2, but is susceptible to overoxidation and consequent inactivation by H2O2. Either deletion of the YF motif or dissociation into dimers decreased the susceptibility of Prx4 to overoxidation by increasing the flexibility of Cys87.
Regiospecific Synthesis of Benzo[b]fluorenones via Ring Contraction by Benzil-Benzilic Acid Rearrangement of Benz[a]anthracene-5,6-diones (2006)

A regiospecific route to benzo[b]fluorenones is described. The synthesis is based upon a one-pot, regiospecific benzannulation of 1,4-dipolar synthons with naphthoquinone monoketal and ring contraction of the generated benz[a]anthracene-5,6-diones through benzil-benzilic acid rearrangement.
Yeast Display Evolution of a Kinetically Efficient 13-Amino Acid Substrate for Lipoic Acid Ligase (2009)

Escherichia coli lipoic acid ligase (LplA) catalyzes ATP-dependent covalent ligation of lipoic acid onto specific lysine side chains of three acceptor proteins involved in oxidative metabolism. Our lab has shown that LplA and engineered mutants can ligate useful small-molecule probes such as alkyl azides ( Nat. Biotechnol. 2007 , 25 , 1483 - 1487 ) and photo-cross-linkers ( Angew. Chem., Int. Ed. 2008 , 47 , 7018 - 7021 ) in place of lipoic acid, facilitating imaging and proteomic studies. Both to further our understanding of lipoic acid metabolism, and to improve LplA's utility as a biotechnological platform, we have engineered a novel 13-amino acid peptide substrate for LplA. LplA's natural protein substrates have a conserved beta-hairpin structure, a conformation that is difficult to recapitulate in a peptide, and thus we performed in vitro evolution to engineer the LplA peptide substrate, called "LplA Acceptor Peptide" (LAP). A approximately 10(7) library of LAP variants was displayed on the surface of yeast cells, labeled by LplA with either lipoic acid or bromoalkanoic acid, and the most efficiently labeled LAP clones were isolated by fluorescence activated cell sorting. Four rounds of evolution followed by additional rational mutagenesis produced a "LAP2" sequence with a k(cat)/K(m) of 0.99 muM(-1) min(-1), >70-fold better than our previous rationally designed 22-amino acid LAP1 sequence (Nat. Biotechnol. 2007, 25, 1483-1487), and only 8-fold worse than the k(cat)/K(m) values of natural lipoate and biotin acceptor proteins. The kinetic improvement over LAP1 allowed us to rapidly label cell surface peptide-fused receptors with quantum dots.
Biosafety considerations associated with molecular farming in genetically modified plants. (2009)

The production in genetically modified plants of recombinant proteins for pharmaceutical or industrial use, also referred to as molecular deserves increasing interest due to its potential advantages. However, this type of application of genetic engineering also raises some biosafety concerns, in particular regarding aspects such as transgene spread in the environment or accidental contamination of the food and feed chains. This review presents the current state of the art of this sector, discusses some relevant regulatory issues and outlines important scientific aspects that should be considered during the safety assessment of genetically modified plants grown for this purpose. In particular, it addresses general strategies as well as specific potential containment measures that could be applied to limit the potential environmental and human health impacts linked to plant molecular farming.

	 

	Key words: Biopharming, biosafety, confinement, containment, genetically modified organism, plant molecular farming, plant-made industrials, plant-made pharmaceuticals.
Thermal Decomposition Chemistry of Poly(vinyl alcohol) (1995)

The fundamental condensed phase processes which lead to char formation during the fire-like pyrolysis of poly(vinyl alcohol), PVA, and PVA-containing maleimides were characterized using CP/MAS 13C NMR. In addition to evidence of the well known chain-stripping elimination of H2O and the chain-scission reactions, which occur during the pyrolysis of pure PVA, evidence is presented in support of cyclization and radical reaction pathways responsible for the conversion of unsaturated carbons into aliphatic carbons. Two general mechanisms; one described as a physical encapsulation, and the other a lowering of the average volatility of certain degradation products, are proposed for the primary modes of action of maleimides on the pyrolysis of PVA.
Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure (2009)

Oxidative stress and inflammation are constant features and major mediators of progression of chronic kidney disease (CKD). Nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against tissue injury by orchestrating antioxidant and detoxification responses to oxidative and electrophilic stress. While sources of oxidative stress and inflammation in the remnant kidney have been extensively characterized, the effect of CKD on Nrf2 activation and expression of its downstream gene products is unknown and was investigated. Subgroups of male Sprague-Dawley rats were subjected to 5/6 nephrectomy or sham operation and observed for 6 or 12 wk. Kidneys were then harvested, and Nrf2 activity and its downstream target gene products (antioxidant and phase II enzymes) were assessed. In addition, key factors involved in promoting inflammation and oxidative stress were studied. In confirmation of earlier studies, rats with chronic renal failure exhibited increased lipid peroxidation, glutathione depletion, NF-kappaB activation, mononuclear cell infiltration, and upregulation of monocyte chemoattractant protein-1, NAD(P)H oxidase, cyclooxygenase-2, and 12-lipoxygenase in the remnant kidney pointing to oxidative stress and inflammation. Despite severe oxidative stress and inflammation, remnant kidney tissue Nrf2 activity (nuclear translocation) was mildly reduced at 6 wk and markedly reduced at 12 wk, whereas the Nrf2 repressor Keap1 was upregulated and the products of Nrf2 target genes [catalase, superoxide dismutase, glutathione peroxidase, heme oxygenase-1, NAD(P)H quinone oxidoreductase, and glutamate-cysteine ligase] were reduced or unchanged at 6 wk and significantly diminished at 12 wk. Thus oxidative stress and inflammation in the remnant kidney are compounded by conspicuous impairment of Nrf2 activation and consequent downregulation of the antioxidant enzymes.
Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. (1978)

The tridecamer d(A-A-T-G-G-T-A-A-A-A-T-G-G), which is complementary to 13 nucleotides of the 3'- and 5'-reiterated terminal sequences of Rous sarcoma virus 35S RNA, was added to chick embryo fibroblast tissue cultures infected with Rous sarcoma virus. Inhibition of virus production resulted. The inference emerges that the tridecamer and its counterpart with blocked 3'- and 5'-hydroxyl termini enter the chick fibroblast cells, hybridize with the terminal reiterated sequences at the 3' and 5' ends of the 35S RNA, and interfere with one or more steps involved in viral production and cell transformation. Likely sites of action are (i) the circularization step of the proviral DNA intermediate, and (ii) the initiation of translation, the latter being described in the following communication [Stephenson, M. L. & Zamecnik, P. C. (1978) Proc. Natl. Acad. Sci. USA 75, 285--288].
Antimicrobial Peptides Protect Coho Salmon from Vibrio anguillarum Infections (2000)

Fish losses from infectious diseases are a significant problem in aquaculture worldwide. Therefore, we investigated the ability of cationic antimicrobial peptides to protect against infection caused by the fish pathogen Vibrio anguillarum. To identify effective peptides for fish, the MICs of certain antimicrobial peptides against fish pathogens were determined in vitro. Two of the most effective antimicrobial peptides, CEME, a cecropin-melittin hybrid peptide, and pleurocidin amide, a C-terminally amidated form of the natural flounder peptide, were selected for in vivo studies. A single intraperitoneal injection of CEME did not affect mortality rates in juvenile coho salmon infected with V. anguillarum, the causative agent of vibriosis. Therefore, the peptides were delivered continuously using miniosmotic pumps placed in the peritoneal cavity. Twelve days after pump implantation, the fish received intraperitoneal injections of V. anguillarum at a dose that would kill 50 to 90% of the population. Fish receiving 200 microg of CEME per day survived longer and had significantly lower accumulated mortalities (13%) than the control groups (50 to 58%). Fish receiving pleurocidin amide at 250 microg per day also survived longer and had significantly lower accumulated mortalities (5%) than the control groups (67 to 75%). This clearly shows the potential for antimicrobial peptides to protect fish against infections and indicates that the strategy of overexpressing the peptides in transgenic fish may provide a method of decreasing bacterial disease problems.
Genome-wide gene expression profiles of the developing mouse hippocampus (2001)

We have analyzed the developmental molecular programs of the mouse hippocampus, a cortical structure critical for learning and memory, by means of large-scale DNA microarray techniques. Of 11,000 genes and expressed sequence tags examined, 1,926 showed dynamic changes during hippocampal development from embryonic day 16 to postnatal day 30. Gene-cluster analysis was used to group these genes into 16 distinct clusters with striking patterns that appear to correlate with major developmental hallmarks and cellular events. These include genes involved in neuronal proliferation, differentiation, and synapse formation. A complete list of the transcriptional changes has been compiled into a comprehensive gene profile database (http://BrainGenomics.Princeton.edu), which should prove valuable in advancing our understanding of the molecular and genetic programs underlying both the development and the functions of the mammalian brain.
An Adenovirus Vector for Gene Transfer into Neurons and Glia in the Brain (1993)

The efficient introduction of genetic material into quiescent nerve cells is important in the study of brain function and for gene therapy of neurological disorders. A replication-deficient adenoviral vector that contained a reporter gene encoding beta-galactosidase infected rat nerve cells in vitro and in vivo. beta-Galactosidase was expressed in almost all sympathetic neurons and astrocytes in culture. After stereotactic inoculations into the rat hippocampus and the substantia nigra, beta-galactosidase activity was detected for 2 months. Infected cells were identified as microglial cells, astrocytes, or neurons with anatomical, morphological, and immunohistochemical criteria. No obvious cytopathic effect was observed.
Potential Cancer-Chemopreventive Activities of Wine Stilbenoids and Flavans Extracted From Grape (Vitis vinifera) Cell Cultures (2001)

Moderate consumption of wine is associated with a reduced risk of cancer. Grape plant cell cultures were used to purify 12 phenols: the stilbenoids trans-astringin, trans-piceid (2), trans-resveratroloside, trans-resveratrol, trans-piceatannol, cis-resveratroloside, cis-piceid, and cis-resveratrol; the flavans (+)-catechin, (-)-epicatechin, and epicatechin 3-O-gallate; and the flavan dimer procyanidin B2 3'-O-gallate. These compounds were evaluated for potential to inhibit cyclooxygenases and preneoplastic lesion formation in carcinogen-treated mouse mammary glands in organ culture. At 10 micrograms/ml, trans-astringin and trans-piceatannol inhibited development of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in mouse mammary glands with 68.8% and 76.9% inhibition, respectively, compared with untreated glands. The latter compound was the most potent of the 12 compounds tested in this assay, with the exception of trans-resveratrol (87.5% inhibition). In the cyclooxygenase (COX)-1 assay, trans isomers of the stilbenoids appear to be more active than cis isomers: trans-resveratrol [50% inhibitory concentration (IC50) = 14.9 microM, 96%] vs. cis-resveratrol (IC50 = 55.4 microM). In the COX-2 assay, among the compounds tested, only trans- and cis-resveratrol exhibited significant inhibitory activity (IC50 = 32.2 and 50.2 microM, respectively). This is the first report showing the potential cancer-chemopreventive activity of trans-astringin, a plant stilbenoid recently found in wine. trans-Astringin and its aglycone trans-piceatannol were active in the mouse mammary gland organ culture assay but did not exhibit activity in COX-1 and COX-2 assays. trans-Resveratrol was active in all three of the bioassays used in this investigation. These findings suggest that trans-astringin and trans-piceatannol may function as potential cancer-chemopreventive agents by a mechanism different from that of trans-resveratrol.
Wavelength-tunable silicon microring modulator (2010)

We present a wavelength-tunable, compact, high speed and low power silicon microring modulator. With a ring radius of 5 microm, we demonstrate a modulator with a high speed of 12.5 Gbps and a driving voltage of 3 V to achieve approximately 6 dB extinction ratio in high speed measurement. More importantly, tunability of the resonant wavelength is accomplished by means of a microheater on top of the ring, with an efficiency of 2.4 mW/nm (2.4 mW is needed to tune the resonant wavelength by 1 nm). This device aims to solve the narrow bandwidth problem of silicon microcavity modulators and increase the data bandwidth in optical interconnect systems.