gebhart/patrepeval huggingface dataset:
Org 214007-0: A Novel Non-Steroidal Selective Glucocorticoid Receptor Modulator with Full Anti-Inflammatory Properties and Improved Therapeutic Index (2012)

Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects.
Failure Recovery in Cooperative Data Stream Analysis (2007)

We present a failure recovery framework for System S, a large-scale stream data analysis environment. It is intended to support multiple sites, which have their own local administration and goals. However, it is beneficial for these sites to cooperate with each other, especially in the presence of various failures. Our ultimate goal is to support automatic, timely failure recovery through cooperation among sites. We identify the unique challenges in the context of System S and present our initial design work. In particular, we consider a backup selection problem, specifying where to recover failed jobs, which we formulate as an optimization problem. We present an approximation algorithm together with empirical results obtained through simulations. Our numerical evaluations show that the proposed approximation algorithm is very efficient and effective compared to the optimal solutions. It exhibits a promising empirical performance ratio that is close to the theoretical limit of polynomial approximations of such a problem
Nonlinear technique for the enhancement of extremely high contrast images (2008)

An adaptive technique for image enhancement based on a specifically designed nonlinear function is presented in this paper. The enhancement technique constitutes three main processes-adaptive intensity enhancement, contrast adjustment, and color restoration. A sine function with an image dependent parameter is used to tune the intensity of each pixel in the luminance image. This process provides dynamic range compression by boosting the luminance of darker pixels while reducing the intensity of brighter pixels and maintaining local contrast. The normalized reflectance image is added to the enhanced image to preserve the details. The quality of the enhanced image is improved by applying a local contrast enhancement followed by a contrast stretch process. A basic linear color restoration process based on the chromatic information of the original image is employed to convert the enhanced intensity image back to a color image. The performance of the algorithm is compared with other state of the art enhancement techniques and evaluated using a statistical image quality evaluation method.
Synthesis of small cyclic peptides: An auxiliary approach to address the “difficult cyclization” problem (2006)

Cyclic peptides in general, and head-to-tail cyclic peptides in particular, comprise a large and important class of biologically active molecules. Whereas the synthesis of linear peptides generally proceeds well, head-to-tail cyclization is often troublesome, especially for small peptides of less than seven residues in length [1]. We are interested in developing chemical strategies that facilitate the assembly of libraries of small cyclic peptides [2]. In order to address the sequence-related inefficiency of small peptide cyclization we have aimed at utilizing auxiliary strategies that preorganize the Nand C-termini for head-to-tail cyclization. Here we describe a novel peptide cyclization auxiliary, 6-nitro-2hydroxybenzyl, which has enabled the formation of small cyclic peptides from ‘difficult’ linear precursors.
Prevention of bone marrow graft failure by an anti LFA-1 monoclonal antibody (1987)

Graft rejection is the major cause of failure of HLA mismatched bone marrow transplantation because of residual host immunity. we have proposed to use a monoclonal murine antibody specific for the LFA-1 molecule (25-3) to prevent graft failure in HLA mismatched bone marrow transplantation (BMT). The rationale for this approach is three fold: LFA-1 deficient patients (3/3) do not reject HLA mismatched BMT; anti LFA-1 blocka in vitro the induction of T cell responses and T/ non T cytotoxic functions; LFA-1 is not expressed by other cells than leucocytes. We have accordingly treated twenty two patients with inherited diseases and 8 with leikemia. The bone marrow was T cells depled by E rosetting of Campath antibody. The antibody was given at days -3, -1, +1, +3, +5 at dose of .1 mg/kg/d for the first 9 and then .2mg/kg/d from day -3 to +6. Engraftment occured in 23/30 patients as shown by at least HLA typing. Hematological recovery was rapid, GVH was limited. Side effects of antibody infusion included fever and possibly an increased incidence of early bacteral infection (sepsis, 1 death). Immunological reconstitution occured slowly leading in six cases to EBV-induced B cell poliferation (1 death and in two others to transient auto immune hemolytic anemia. There has been only one secondary graft rejection. Sisteen patients are alive 3 to 26 months post transplant with functional grafts. Although the number of patients treated is still low the absence of late rejection so far, gives hope for long term maintenance of the graft using anti LFA-1. Since the antibody is an IgG 1 unable to bind human complement, and since it is known to inhibit phagocytosis, there is a good suggestion that 25-3 act through functional blocking of host T and non T luymphocytes at both induction and effector levels.
Blockchained Post-Quantum Signatures. (2018)

Inspired by the blockchain architecture and existing Merkle tree based signature schemes, we propose BPQS, an extensible post-quantum (PQ) resistant digital signature scheme best suited to blockchain and distributed ledger technologies (DLTs). One of the unique characteristics of the protocol is that it can take advantage of application-specific chain/graph structures in order to decrease key generation, signing and verification costs as well as signature size. Compared to recent improvements in the field, BPQS outperforms existing hash-based algorithms when a key is reused for reasonable numbers of signatures, while it supports a fallback mechanism to allow for a practically unlimited number of signatures if required. We provide an open source implementation of the scheme and benchmark it.
ChemInform Abstract: DESULFURIZATION OF PENICILLINS (1983)

Abstract Penicillin‐Derivate (I) lassen sich durch kurzzeitiges Erhitzen mit Raney‐Nickel zu einem Gemisch der Verbindungen (II) und (III) ent‐ schwefeln.
Phosphoramidate Prodrugs of 2′-<i>C</i>-Methylcytidine for Therapy of Hepatitis C Virus Infection (2009)

The application of a phosphoramidate prodrug approach to 2'-C-methylcytidine (NM107), the first nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase, is reported. 2'-C-Methylcytidine, as its valyl ester prodrug (NM283), was efficacious in reducing the viral load in patients infected with HCV. Several of the phosphoramidates prepared demonstrated a 10- to 200-fold superior potency with respect to the parent nucleoside in the cell-based replicon assay. This is due to higher levels of 2'-C-methylcytidine triphosphate in the cells. These prodrugs are efficiently activated and converted to the triphosphate in hepatocytes of several species. Our SAR studies ultimately led to compounds that gave high levels of NTP in hamster and rat liver after subcutaneous dosing and that were devoid of the toxic phenol moiety usually found in ProTides.
Identification of cyano indenopyrazine derivatives as a novel series of potent ubiquitin-specific protease inhibitors (2007)

C220 Regulated protein turnover is primarily controlled by the ubiquitin-proteasome system. The only marketed drug related to the ubiquitin-proteasome system, bortezomib, is acting as a proteasome inhibitor and has been approved for the treatment of some hematological cancers. Targeting the upstream ubiquitin conjugation/deconjugation system carries out promises of therapeutics with increased specificity and selectivity. Ubiquitin-specific proteases (USP) are involved in the deubiquitination of specific target substrates regulating their stability, subcellular localization and/or activation status. USP represent a drugable target class due to their thiol-protease catalytic core which is amenable to pharmacological inhibition by small molecules.  A genome-wide RNAi screen of the catalytically active human USP in cancer-relevant cellular models and phenotypic assays identified USP7 and USP8 as promising cancer targets. Advanced HTS-compatible, HTRF-based screening assays using optimized USP substrates including various ubiquitin derivatives (ubiquitin precursor, branched ubiquitin chains) as well as specific, physiological substrates were developed to screen a chemically diverse library. Primary hits were run through a lead optimization program to improve potency, selectivity, cellular activity and pharmacokinetic profile. We report here the identification of a series of cyano indenopyrazine derivatives as novel and potent USP inhibitors. One of our lead compounds, HBX 41,108, was found to reversibly inhibit USP7 catalytic activity with an IC50 of 0.4 µM and to exhibit dose-dependent antiproliferative activity with sub-micromolar GI50. Reminiscent to RNAi-mediated USP7 silencing in cancer cells, HBX 41,108 stabilizes and activates p53 in a non-genotoxic manner, leading to cell growth inhibition and p53-dependent apoptosis as demonstrated using p53 wild-type and null isogenic cell lines. This compound also sensitizes colorectal carcinoma cells to the p53-dependent cytotoxic effect of 5-fluorouracil. A related compound displaying exquisite USP8 selectivity in vitro (HBX 90,659) exhibited antiproliferative and pro-apoptotic activities with sub-micromolar GI50 in different cancer cell lines and induced a marked increase in total cell protein ubiquitination, recapitulating the phenotypes observed in USP8 knock-down cells.  We report the development of unique, advanced ubiquitin-specific proteases screening assays and the identification of a novel chemical series of drug-like, small-molecule USP inhibitors. These will help further validate this novel class of molecular targets and may provide a structural basis for the development of new anticancer drugs.
Characteristics and Properties of Carboxylated Cellulose Nanocrystals Prepared from a Novel One‐Step Procedure (2010)

High quality cellulose nanocrystals are synthesized using a simple one-step procedure with ammonium persulfate. This versatile method processes a variety of cellulosic biomass without the need for pretreatments to remove non- cellulosic plant contents.
An Example of X-ray Nanochemistry: SERS Investigation of Polymerization Enhanced by Nanostructures under X-ray Irradiation (2012)

We demonstrated for the first time enhanced formation of polymers on nanostructures under X-ray irradiation. Surface enhanced Raman spectroscopy (SERS) using silver core–gold shell nanocoreshells (Ag@Au NCSs) as the SERS substrate was employed to quantify the amount of polymers on the surface. The yield of surface-grown polyaniline (PANI) from X-ray-irradiated aniline monomers in aqueous solution of the NCSs was 28 times that of aniline-mixed NCSs without X-rays or 400 times that with the monomers alone irradiated with X-rays. The enhancement was dose rate-dependent and is believed to originate from Ag/Au ionic species created from X-ray generated hydroxyl radicals (•OH) reacting with NCSs. The resulting Ag/Au ionic species on NCSs then initiate PANI formation from aniline molecules absorbed on the NCS surface. The results presented here help advance a new field of X-ray nanochemistry and may inspire applications requiring X-ray-triggered formation of polymers on nanomaterials.
Flame synthesis of nanostructured vanadium oxide based catalysts (1995)

Nanostructured V2O5-TiO2, V2O5-Al2O3, and V-P-O powders were synthesized in hydrogen-oxygen flames using a counterflow diffusion flame burner. This flame synthesis technique allows one to select a specific powder morphology or crystalline structure by selecting the appropriate flame temperature, precursor concentration ratio, and precursor. The operating conditions appropriate to produce vanadium oxide “monolayer” on TiO2 and Al2O3, VOPO4·2H2O, β-VOPO4, γ-VOPO4, σ-VOPO4, and (VO)2P2O7 are presented and discussed.
MicroRNA miR-425 is a negative regulator of atrial natriuretic peptide (2013)

Author(s): Arora, Pankaj; Wu, Connie; Bloch, Donald B; Davis-Dusenbury, Brandi N; Spagnolli, Ester; Hata, Akiko; Vandenwijngaert, Sara; Swinnen, Melissa; Janssens, Stefan; Buys, Emmanuel S; Bloch, Kenneth D; Newton-Cheh, Christopher; Wang, Thomas J
Adenoviral Vector-Mediated mRTVP-1 Gene Therapy for Prostate Cancer (2003)

We previously identified the mouse RTVP-1 (mRTVP-1; related to testes-specific, vespid, and pathogenesis proteins) gene as a direct target of p53 with proapoptotic activities in various cancer cell lines, including prostate cancer. To test the therapeutic potential of mRTVP-1 we constructed an adenoviral vector capable of efficient transduction and expression of mRTVP-1 (AdmRTVP-1) and used this vector in an orthotopic, metastatic mouse model of prostate cancer. A single intratumoral administration of AdmRTVP-1 gene therapy significantly reduced primary tumor wet weight compared with control Adbetagal-injected tumors at two time points after injection with two different vector doses (p < or = 0.01 at 7 and 14 days). Spontaneous metastasis to lung was also significantly reduced (p < or = 0.02). Evaluation of treated tumors revealed increased apoptosis and lower microvessel density counts. In a rat aortic ring sprouting assay, AdmRTVP-1 inhibited endothelial cell sprouting compared with Adbetagal, confirming its antiangiogenic activity. These therapeutic activities were associated with a significant increase in survival from 22.9 to 26.8 days (p = 0.003) in this aggressive model of prostate cancer. Interestingly, there were significant increases in the infiltration of tumor-associated macrophages, dendritic cells, and CD8+ T cells, which persisted at 14 days posttreatment in the AdmRTVP-1-treated tumors compared with Adbetagal control-treated tumors. In addition, significantly increased natural killer and cytotoxic T lymphocyte activities were demonstrated in the mice with AdmRTVP-1-treated tumors. The unique therapeutic properties of AdmRTVP-1 gene therapy demonstrated in this study provide new opportunities for gene and immunotherapy of prostate cancer and potentially other malignancies.
Comparison between norm constrained and robust Capon beamformers (2003)

The standard Capon beamformer (SCB) is known to have better resolution and much better interference rejection capability than the standard data-independent beamformer when the array steering vector is accurately known. However, the major problem of SCB is that it lacks robustness in the presence of array steering vector errors. In this paper, we will first provide a complete analysis of a norm constrained Capon beamformer (NCCB), which uses a norm constraint on the weight vector to improve the robustness against array steering vector errors and noise. Our analysis is thorough and sheds more light on the choice of the norm constraint than what was commonly known. We also briefly discuss our recently proposed robust Capon beamformer (RCB), which is obtained via extending the covariance matrix fitting approach to the case of uncertain steering vectors. Our RCB is based on a clear theoretical background and explicitly addresses the steering vector uncertainty problems. Both NCCB and RCB can be efficiently computed at a comparable cost with that of SCB. Performance comparisons of NCCB and RCB via a number of numerical examples are also presented.
Development of Melioidosis Subunit Vaccines Using an Enzymatically Inactive Burkholderia pseudomallei AhpC (2022)

Burkholderia pseudomallei, the causative agent of melioidosis, is a facultative intracellular, Gram-negative pathogen that is highly infectious via the respiratory route and can cause severe, debilitating, and often fatal diseases in humans and animals. At present, no licensed vaccines for immunization against this CDC Tier 1 select agent exist. Studies in our lab have previously demonstrated that subunit vaccine formulations consisting of a B. pseudomallei capsular polysaccharide (CPS)-based glycoconjugate (CPS-CRM197) combined with hemolysin-coregulated protein (Hcp1) provided C57BL/6 mice with high-level protection against an acute inhalational challenge of B. pseudomallei. In this study, we evaluated the immunogenicity and protective capacity of B. pseudomallei alkyl hydroperoxide reductase subunit C (AhpC) in combination with CPS-CRM197. AhpC is a peroxiredoxin involved in oxidative stress reduction and is a potential protective antigen. To facilitate our studies and maximize safety in animals, recombinant B. pseudomallei AhpC harboring an active site mutation (AhpC<sup>C57G</sup>) was expressed in Escherichia coli and purified using tandem nickel-cobalt affinity chromatography. Immunization of C57BL/6 mice with CPS-CRM197 combined with AhpC<sup>C57G</sup> stimulated high-titer IgG responses against the CPS component of the glycoconjugate as well as stimulated high-titer IgG and robust interferon gamma (IFN-γ)-, interleukin-5 (IL-5)-, and IL-17-secreting T cell responses against AhpC<sup>C57G</sup>. When challenged via an inhalational route with a high dose (~27 50% lethal doses [LD<sub>50</sub>s]) of B. pseudomallei, 70% of the immunized mice survived 35 days postchallenge. Collectively, our findings demonstrate that AhpC<sup>C57G</sup> is a potent activator of cellular and humoral immune responses and may be a promising candidate to include in future melioidosis subunit vaccines.
Hierarchical destination prediction based on GPS history (2013)

Understanding and predicting destination of a trip is a crucial component of location based services. Traditional destination prediction work mostly focus on mining mobility patterns from frequently been locations. However, location transition patterns are not regular enough to provide favorable predicting results. Meanwhile, it could only be used when a user has enough movements in a location. In this paper, we propose a hierarchical model which predict what to do first and where to go in next. We first demonstrate that activity transitions are more regular than location transitions. Then we employ a Hidden Markov Model (HMM) based predicting approach which takes user's activity transition into account. We introduce a supervised way to learn parameters for HMM. Experimental results show that hierarchical prediction scheme could improve accuracy of pre-destination. Hierarchical model could perform well in some situations that traditional methods are of poor accuracy.
Danazol therapy renders red cells resistant to osmotic lysis <sup>1</sup> (1989)

Danazol, an attenuated androgen, is useful in endometriosis, idiopathic thrombocytopenic purpura (ITP), and autoimmune hemolytic anemia (AIHA). However, its mechanism of action is unknown. We investigated the possibility that danazol affects cell membranes directly. Red cell osmotic fragility was studied in patients receiving danazol. A significant decrease in osmotic fragility was observed. Accompanying the change, peripheral blood smears showed many target cells and electron microscopy revealed extra folds in erythrocyte membranes. Twenty-two patients were studied prospectively before and after danazol. Osmotic fragility decreased significantly (P less than 0.001) in 1 month of therapy and progressed with further treatment. A rebound increase (P less than 0.01) was observed in 1 month after discontinuation of danazol among 16 patients. Incubation experiments showed that danazol-induced changes are not reversed with normal sera. Patient sera did not induce the changes in normal red cells. Danazol in vitro protected red cells from osmotic lysis at low concentrations but enhanced lysis at high concentrations. We suggest that danazol alters red cell membranes directly to increase their surface area, inducing target cell formation and increasing their resistance to osmotic lysis.
A comparison of the free fraction of serum prostate specific antigen in men with benign and cancerous prostates: the best case scenario (1996)

For total PSA 4 to 10 ng./ml., the sensitivity of approximately 15% free-to-total PSA for prostate cancer is high (94 to 95%) but 36 to 46% of men with BPH and a large gland will not be correctly identified. For PSA 2 to 4 ng./ml., no ratio of percent free-to-total PSA discriminated BPH from prostate cancer.
Adaptive Optics for Autofocusing Eyeglasses (2017)

Over 1 billion people worldwide including more than 100 million people in the United States of America alone suffer from an age-related eye condition known as presbyopia. Presbyopia is caused by a loss of focal accommodation of the crystalline lens inside the eye as the lens stiffens with age. A presbyopic person has reduced or very limited ability to focus on objects placed at different distances. The utilization of conventional fixed, uniform or graded power eyeglasses for presbyopia correction is generally unsatisfactory as fixed power eyepieces cannot provide any accommodation restoration. In this paper we will discuss an implementation of lightweight adaptive-optics auto-focusing eyeglasses that augment the accommodation range of vision thus partially or fully cancelling the accommodation loss caused by presbyopia and restoring normal vision function.
(Diphenylphosphino)-biheteroaryls: the first example of a new class of chiral atropisomeric chelating diphosphine ligands for transition metal catalysed stereoselective reactions (1995)

Ruthenium(II) dichloride complexes with (+)- and (–)-2,2′-bis(diphenylphosphino)-4,4′,6,6′-tetramethyl-3,3′-bibenzo[b]thiophene (1a), new chiral atropisomeric heterocyclic ligands, reduce α- and β-oxoesters to α- and β-hydroxyesters with an enantiomeric purity comparable, if not higher, to that reported for binap under the same experimental conditions.
Space Object Tracking Uncertainty Analysis with the URREF Ontology (2021)

Accurate and rapid space object behavioral tracking enables space protection and space domain awareness (SDA). Recent methods of artificial intelligence and machine learning (AI/ML) enhance space object behavior classification of evasive satellite behaviors detection within the Adaptive Markov Inference Game Optimization (AMIGO) tool. AMIGO integrates data fusion, stochastic modeling and, and AI/ML pattern classification. Numerical simulations demonstrate the advantage of using the Uncertainty Representation and Reasoning Evaluation Framework (URREF) for space ontological pattern of life assessment of veracity, precision, and recall when a resident space objects conducts a maneuver.