gebhart/patrepeval huggingface dataset:
Differentially Private Empirical Risk Minimization. (2011)

Privacy-preserving machine learning algorithms are crucial for the increasingly common setting in which personal data, such as medical or financial records, are analyzed. We provide general techniques to produce privacy-preserving approximations of classifiers learned via (regularized) empirical risk minimization (ERM). These algorithms are private under the ε-differential privacy definition due to Dwork et al. (2006). First we apply the output perturbation ideas of Dwork et al. (2006), to ERM classification. Then we propose a new method, objective perturbation, for privacy-preserving machine learning algorithm design. This method entails perturbing the objective function before optimizing over classifiers. If the loss and regularizer satisfy certain convexity and differentiability criteria, we prove theoretical results showing that our algorithms preserve privacy, and provide generalization bounds for linear and nonlinear kernels. We further present a privacy-preserving technique for tuning the parameters in general machine learning algorithms, thereby providing end-to-end privacy guarantees for the training process. We apply these results to produce privacy-preserving analogues of regularized logistic regression and support vector machines. We obtain encouraging results from evaluating their performance on real demographic and benchmark data sets. Our results show that both theoretically and empirically, objective perturbation is superior to the previous state-of-the-art, output perturbation, in managing the inherent tradeoff between privacy and learning performance.
The Structure of Phytochrome: A Picture Is Worth a Thousand Spectra (2005)

Sensing and responding to light is a central feature of plant biology that is critical for tuning plant metabolism to the light environment. To accomplish this vital task, plants use a number of different photosensory proteins that perceive different bands of the electromagnetic spectrum ([
The Crystal Structure ofPichia pastorisLysyl Oxidase (2003)

Pichia pastoris lysyl oxidase (PPLO) is unique among the structurally characterized copper amine oxidases in being able to oxidize the side chain of lysine residues in polypeptides. Remarkably, the yeast PPLO is nearly as effective in oxidizing a mammalian tropoelastin substrate as is a true mammalian lysyl oxidase isolated from bovine aorta. Thus, PPLO is functionally related to the copper-containing lysyl oxidases despite the lack of any significant sequence similarity with these enzymes. The structure of PPLO has been determined at 1.65 A resolution. PPLO is a homodimer in which each subunit contains a Type II copper atom and a topaquinone cofactor (TPQ) formed by the posttranslational modification of a tyrosine residue. While PPLO has tertiary and quaternary topologies similar to those found in other quinone-containing copper amine oxidases, its active site is substantially more exposed and accessible. The structural elements that are responsible for the accessibility of the active site are identified and discussed.
Erythropoietin gene therapy leads to autoimmune anemia in macaques (2003)

Gene therapy is being considered for the delivery of therapeutic proteins. We evaluated the delivery of the hormone erythropoietin (EPO) into cynomolgus macaques through intramuscularly administered adeno-associated virus (AAV) vectors. As expected, the animals developed supraphysiologic levels of EPO and polycythemia. However, severe anemia ensued in some animals because of an autoimmune response to endogenous and transgene derived EPO. This is the first example of gene therapy leading to inadvertent auto-immunity in primates.
JBIR-22, An Inhibitor for Protein−Protein Interaction of the Homodimer of Proteasome Assembly Factor 3 (2010)

Proteasome assembling chaperone (PAC) 3 acts as a homodimer and plays an important role in proteasome formation. We screened JBIR-22 (1) as an inhibitor for protein-protein interaction (PPI) of PAC3 homodimer from our natural product library using a protein fragment complementation assay (PCA) with monomeric Kusabira-Green fluorescent protein (mKG) in vitro and found that 1 exhibited potent inhibitory activity against PAC3 homodimerization. Compound 1 showed long-term cytotoxicity against the human cervical carcinoma cell line, HeLa. This is the first report of a PPI inhibitor for proteasome assembly factors.
An insect cell derived respiratory syncytial virus (RSV) F nanoparticle vaccine induces antigenic site II antibodies and protects against RSV challenge in cotton rats by active and passive immunization (2014)

Post-infectious immunity to respiratory syncytial virus (RSV) infection results in limited protection as evidenced by the high rate of infant hospitalization in the face of high titer, maternally derived RSV-specific antibodies. By contrast, RSV fusion (F) glycoprotein antigenic site II humanized monoclonal antibodies, palivizumab and motavizumab, have been shown to reduce RSV-related hospitalization in infants. Immunogenicity and efficacy studies were conducted in cotton rats comparing a recombinant RSV F nanoparticle vaccine with palivizumab and controlled with live RSV virus intranasal immunization and, formalin inactivated RSV vaccine. Active immunization with RSV F nanoparticle vaccine containing an alum adjuvant induced serum levels of palivizumab competing antibody (PCA) greater than passive administration of 15 mg/kg palivizumab (human prophylactic dose) in cotton rats and neutralized RSV-A and RSV-B viruses. Immunization prevented detectable RSV replication in the lungs and, unlike passive administration of palivizumab, in the nasal passage of challenged cotton rats. Histology of lung tissues following RSV challenge showed no enhanced disease in the vaccinated groups in contrast to formalin inactivated 'Lot 100' vaccine. Passive intramuscular administration of RSV F vaccine-induced immune sera one day prior to challenge of cotton rats reduced viral titers by 2 or more log10 virus per gram of lung and nasal tissue and at doses less than palivizumab. A recombinant RSV F nanoparticle vaccine protected lower and upper respiratory tract against both RSV A and B strain infection and induced polyclonal palivizumab competing antibodies similar to but potentially more broadly protective against RSV than palivizumab.
Pragmatic assessment of communication in dementia (PAC-D) (1996)

This study evaluates the pragmatic communicative abilities ofpatients with dementia, primarily of the Alzheimer's type. A special screening test andfour other tests were utilized along with video recordings of selected subjects' test performances. Results revealed significant correlation among scores of the various tests as well as some communication skills which appear to be robustfor progression of dementia.
Appearance of Water Channels in Xenopus Oocytes Expressing Red Cell CHIP28 Protein (1992)

Water rapidly crosses the plasma membrane of red blood cells (RBCs) and renal tubules through specialized channels. Although selective for water, the molecular structure of these channels is unknown. The CHIP28 protein is an abundant integral membrane protein in mammalian RBCs and renal proximal tubules and belongs to a family of membrane proteins with unknown functions. Oocytes from Xenopus laevis microinjected with in vitro-transcribed CHIP28 RNA exhibited increased osmotic water permeability; this was reversibly inhibited by mercuric chloride, a known inhibitor of water channels. Therefore it is likely that CHIP28 is a functional unit of membrane water channels.
Antimicrobial activity of methylene blue and toluidine blue O covalently bound to a modified silicone polymer surface (2009)

Methylene Blue or Toluidine Blue O were covalently bound to an activated silicone polymer by means of an amide condensation reaction. UV-visible absorption spectra confirmed that the dye was surface bound. The new polymers with covalently attached dye display significant bactericidal activity against Escherichia coli and Staphylococcus epidermidis with a 99.999% reduction in viable bacteria after four minutes exposure to a low power laser.
Changes in exploratory activity following stimulation of hippocampal 5‐HT1A and 5‐HT1B receptors in the rat (1995)

The object exploration task allows the measure of changes in locomotor and exploratory activities, habituation, and reaction to a spatial change and to novelty. The effects of intrahippocampal (dorsal CA1 field) microinjections of serotonin 1 receptor (5-HT1) agonists on these behavioral components were evaluated in the rat. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 5 micrograms/microliters) was used as a 5-HT1A agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93,129,16 micrograms/microliters) as a 5-HT1B agonist, and scopolamine (10 micrograms/microliters) as a muscarinic cholinergic antagonist. Scopolamine induced a long-lasting increase in locomotor activity and a lack of reaction to spatial change; both these results are in agreement with the known crucial influence of the septo-hippocampal cholinergic system in hippocampal functioning. Stimulation of 5-HT1A and 5-HT1B receptors induced a decrease in object exploration and habituation without affecting the retrieval of spatial information. But stimulation of hippocampal 5-HT1B receptors induced a selective change in the animal's emotional state, i.e., an initial decrease in locomotor activity and a neophobic reaction in response to a new object; such effects did not occur following stimulation of 5HT1A receptors. These results have to be considered in the light of the anxiogenic property of 5-HT1B agonists. On the whole, they support the hypothesis of the involvement of the serotonergic system, via 5HT1A and 5-HT1B receptors, in the modulation of hippocampal functions.
A demand for next-generation oncolytic adenoviruses. (2006)

Oncolytic viruses are a class of novel therapeutic agents used for the treatment of cancer that have the unique property of tumor-dependent self-perpetuation. Initial clinical trials have demonstrated that these agents are very safe and well tolerated. However, to date they have failed to demonstrate therapeutic benefit as monotherapies and as a consequence, next-generation oncolytic adenoviruses are now needed. This review discusses the approaches to deriving next-generation oncolytic adenoviruses together with potential preclinical test systems that might better predict their clinical outcome. Many of these approaches and test systems may be applicable to other viral systems being developed as oncolytic agents.
Oxygen-Rich Oxidase Enzyme Electrodes for Operation in Oxygen-Free Solutions (1998)

The oxygen dependence of oxidase enzyme electrodes is successfully addressed through the use of carbon paste biosensors with fluorocarbon pasting liquids. Due to the high oxygen solubility in perfluorocarbons, such pasting liquids provide an internal supply of oxygen, and efficient operation of first-generation oxidase electrodes under oxygen-deficit conditions. In particular, the use of poly(chlorotrifluorethylene) (Kel-F) oil results in an identical response up to 4 × 10-2 M glucose, in the presence and absence of oxygen. Such oxygen independence compares favorably with that reported for mediator or wired enzyme electrodes. The internal supply of oxygen of a Kel-F/carbon paste enzyme microelectrode is not depleted over a prolonged operation under oxygen-deficient conditions. The oxygen effect upon the kinetic parameters of the immobilized enzyme is examined for a variety of pasting liquids. Such attention to the oxygen demand addresses numerous practical biosensor applications, involving low or fluctuated levels of oxygen, including in-vivo monitoring of glucose.
T-Cell Proliferation Involving the CD28 Pathway Is Associated witH Cyclosporine-Resistant Interleukin 2 Gene Expression (1987)

CD28 is a homodimeric glycoprotein expressed on the surface of a major subset of human T cells that has recently been identified as a member of the immunoglobulin supergene family. The binding of monoclonal antibodies to the CD28 antigen on purified T cells does not result in proliferation; however, previous studies have shown that the combination of CD28 stimulation and protein kinase C activation by phorbol myristate acetate (PMA) results in T-cell proliferation that is independent of both accessory cells and activation of the T-cell receptor-CD3 complex. In the present study, effects of stimulation by anti-CD28 on cell cycle progression and on the interleukin 2 (IL-2) and IL-2 receptor system have been investigated on primary cultures of purified peripheral-blood CD28+ T cells. There was no measurable effect on cell size or on DNA synthesis after stimulation of resting (G0) cells by CD28 alone. After 3 h of activation of T cells by PMA alone, a slight (8%) increase in cell volume occurred that did not progress to DNA synthesis. In contrast, T-cell stimulation by CD28 in combination with PMA resulted in a progressive increase in cell volume in approximately 100% of cells at 12 to 14 h after stimulation. Northern blot (RNA blot) analysis revealed that CD28 stimulation alone failed to cause expression of the alpha chain of the IL-2 receptor or of IL-2 mRNA, and in accord with previous studies, stimulation by PMA alone resulted in the accumulation of IL-2 receptor transcripts but no detectable IL-2 mRNA. In contrast, T-cell stimulation by the combination of CD28 and PMA resulted in the appearance of IL-2 transcripts and enhanced expression of IL-2 receptor mRNA. Functional studies revealed that the proliferation induced by CD28 and PMA stimulation was entirely resistant to cyclosporine, in contrast to T-cell activation induced by the CD3-T-cell receptor complex. Cyclosporine was found not to affect the accumulation of IL-2 mRNA after CD28 plus PMA stimulation, although there was no detectable IL-2 mRNA after stimulation by CD3 in the presence of the drug. Furthermore, stimulation by CD28 in combination with immobilized CD3 antibodies caused a striking enhancement of IL-2 mRNA expression that was, in part, resistant to the effects of cyclosporine. These studies indicate that the CD28 molecule synergizes with protein kinase C activation to induce IL-2 gene expression and demonstrate that stimulation by the CD28 pathway can cause vigorous T-cell proliferation even in the presence of cyclosporine and that cyclosporine does not prevent transcription of 16-2 mRNA, as has been suggested previously. Moreover, these findings suggest that a potential role for the CD28 molecule in vivo may be to augment IL-2 production after stimulation of the CD3-T-cell receptor molecular complex and thereby to amplify an antigen-specific immune response. Finally, these results provide further evidence that the CD28 molecule triggers T-cell proliferation in a manner that differs biochemically from CD3-T-cell receptor-induced proliferation.
Changes of Chloride Channels in the Lacrimal Glands of a Rabbit Model of Sjögren Syndrome (2011)

Our data demonstrated significant changes of mRNA and protein expressions of NKCC1, CFTR, and ClC2γ in rabbits with IAD, suggesting that these changes may contribute to the altered lacrimal secretion, particularly Cl transport, in rabbits with IAD.
Alkaline CPD and the preservation of RBC 2,3‐DPG (2002)

Maintaining both 2,3-DPG and ATP requires both high pH and high concentrations of phosphate.
TNFα Is an Effective Therapeutic Target for Rheumatoid Arthritisa (1995)

Rheumatoid arthritis is the most common of a number of diseases in which inflammation and tissue destruction is driven by an autoimmune process. Current therapy is inadequate, and this has prompted major research efforts, both in academia and industry, to understand more about the pathogenesis, and hence provide the rationale for new therapeutic strategies. Here we review our studies of cytokine expression and regulation in rheumatoid joints, which has culminated in demonstrating that TNF alpha blockade, using a chimeric (human IgG1/K, mouse Fv) anti-TNF alpha antibody, cA2, markedly ameliorates arthritis. This defines a therapeutic target for rheumatoid arthritis.
Branched DNA amplification multimers for the sensitive, direct detection of human hepatitis viruses. (1991)

Branched oligonucleotides (bDNA) have been synthesized containing a unique primary segment and a set of identical secondary fragments covalently attached to the primary sequence through branch points. The primary sequence is designed to hybridize (directly or indirectly) to a target nucleic acid, such as hepatitis B virus (HBV) or hepatitis C virus (HCV) genomic DNA or RNA, respectively. The secondary fragments are used to direct the binding of multiple copies of a small oligonucleotide labelled with alkaline phosphatase. Assays for the presence of HBV and HCV based on the application of these branched amplification multimers have been devised. It is possible to detect as few as 1,000 hepatitis viral genomes directly.
Implicit interest indicators (2001)

Recommender systems provide personalized suggestions about items that users will find interesting. Typically, recommender systems require a user interface that can ``intelligently'' determine the interest of a user and use this information to make suggestions. The common solution, ``explicit ratings'', where users tell the system what they think about a piece of information, is well-understood and fairly precise. However, having to stop to enter explicit ratings can alter normal patterns of browsing and reading. A more ``intelligent'' method is to useimplicit ratings, where a rating is obtained by a method other than obtaining it directly from the user. These implicit interest indicators have obvious advantages, including removing the cost of the user rating, and that every user interaction with the system can contribute to an implicit rating.
Structural Instability of a Constitutively Active G Protein-coupled Receptor (1997)

Mutations in several domains can lead to agonist-independent, constitutive activation of G protein-coupled receptors. However, the nature of the structural and molecular changes that constitutively turn on a G protein-coupled receptor remains unknown. Here we show evidence that a constitutively activated mutant of the beta2 adrenergic receptor (CAM) is characterized by structural instability and an exaggerated conformational response to ligand binding. The structural instability of CAM could be demonstrated by a 4-fold increase in the rate of denaturation of purified receptor at 37 degrees C as compared with the wild type receptor. Spectroscopic analysis of purified CAM labeled with the conformationally sensitive and cysteine-reactive fluorophore, N,N'dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)ethylenediamine, further indicated that both agonist and antagonist elicit more profound structural changes in CAM than in the wild type protein. We propose that the mutation that confers constitutive activity to the beta2 adrenergic receptor removes some stabilizing conformational constraints, allowing CAM to more readily undergo transitions between the inactive and the active states and making the receptor more susceptible to denaturation.
Clinical trial design for adenoviral gene therapy products (2009)

Two adenoviral gene therapy products have now been approved for clinical use in China, and elsewhere at least four products are in phase III clinical trials. The adenovirus vector is the most commonly used vector for clinical gene therapy due to its high rate of gene transfer in vivo. However, the clinical efficacy of this vector has yet to be proven, despite over 300 clinical trials that have shown it to be well-tolerated and efficient in gene transfer. Recent studies in China have reported improved efficacy of an adenoviral gene therapy product in combination with radiotherapy and/or chemotherapy for the treatment of several types of cancer. There are now at least three phase III clinical trials for adenoviral cancer gene therapy that are ongoing in the U.S., and two of these call for combination therapy with either chemotherapy or radiation. In addition, in the European Union, one adenoviral gene therapy product for malignant glioma in combination with surgery showed a therapeutic benefit in the preliminary results of a phase III trial. This product, when applied as just one component of a multimodality approach, along with surgery, radiation and/or chemotherapy, holds some promise for proving the clinical efficacy of adenovirus vectors.
Efficient Synthesis of Tricyclic Benzobisoxazines by Silica Gel Catalysis (2007)

A new method for the synthesis of tricyclic benzobisoxazines, based upon silica gel-catalyzed formation of two 3,1-oxazine rings, is reported. The reversibility of the condensation reaction, forming an oxazine ring, allows for implementation of silica gel catalyzed ketone exchange in benzobisoxazine, thus enabling access to nonsymmetric derivatives of benzobisoxazines.
C‐terminal sequencing of peptides using electrospray ionization mass spectrometry (1992)

A low-flow reactor is described for the on-line monitoring of peptides digested with carboxypeptidase P by electrospray ionization. Two peptides were analyzed using this technique: glucagon (average MW 3482.8 Da), and apomyoglobin (average MW 16,951.5). Both peptides gave interpretable results. The first 19 amino acids of glucagon were successfully sequenced. Apomyoglobin yielded sequence information to the 30th amino acid with some gaps. At 300 nL/min, 50% of the first 30 amino acids were sequenced and at 1 microL/min, 67% of the first 30 amino acids were observed.
Interleukin-1A +4845(G> T) polymorphism is a factor predisposing to acne vulgaris (2010)

Acne vulgaris is a common chronic inflammatory skin disease of multifactorial origin. The aim of this study was to clarify whether known polymorphisms of the interleukin-1A (IL1A) and IL1RN genes play a role in the pathogenesis of acne vulgaris. A positive association was found between the minor T allele of the IL1A +4845(G>T) single nucleotide polymorphism (SNP) and acne, whereas no association was found with respect to any alleles of the variable number of tandem repeats (VNTR) polymorphism of the IL1RN gene. The severity of inflammatory acne symptoms correlated with the percentage of individuals carrying the homozygote T/T genotype. These results may help to elucidate the molecular events leading to the development of acne.
Novel 3′‐O‐Fluorescently Modified Nucleotides for Reversible Termination of DNA Synthesis (2009)

Serving a double purpose: 3′-O-fluorophore-labeled dTTPs were synthesized and used as reversible terminators of DNA polymerization. Successful incorporation of nucleotides with a bulky 3′-O-fluorophore and detection of fluorescence for base calling can potentially be used to improve sequencing-by-synthesis technology.