gebhart/patrepeval huggingface dataset:
A Factor VIII Neutralizing Monoclonal Antibody and a Human Inhibitor Alloantibody Recognizing Epitopes in the C2 Domain Inhibit Factor VIII Binding to von Willebrand Factor and to Phosphatidylserine (1993)

A neutralizing monoclonal antibody, NMC-VIII/5, recognizing the 72 kDa thrombin-proteolytic fragment of factor VIII light chain was obtained. Binding of the antibody to immobilized factor VIII (FVIII) was completely blocked by a light chain-specific human alloantibody, TK, which inhibits FVIII activity. Immunoblotting analysis with a panel of recombinant protein fragments of the C2 domain deleted from the amino-terminal or the carboxy-terminal ends demonstrated binding of NMC-VIII/5 to an epitope located between amino acid residues 2170 and 2327. On the other hand, the epitope of the inhibitor alloantibody, TK, was localized to 64 amino acid residues from 2248 to 2312 using the same recombinant fragments. NMC-VIII/5 and TK inhibited FVIII binding to immobilized von Willebrand factor (vWF). The IC50 of NMC-VIII/5 for the inhibition of binding to vWF was 0.23 micrograms/ml for IgG and 0.2 micrograms/ml for F(ab)'2. This concentration was 100-fold lower than that of a monoclonal antibody NMC-VIII/10 which recognizes the amino acid residues 1675 to 1684 within the amino-terminal portion of the light chain. The IC50 of TK was 11 micrograms/ml by IgG and 6.3 micrograms/ml by F(ab)'2. Furthermore, NMC-VIII/5 and TK also inhibited FVIII binding to immobilized phosphatidylserine. The IC50 for inhibition of phospholipid binding of NMC-VIII/5 and TK (anti-FVIII inhibitor titer of 300 Bethesda units/mg of IgG) was 10 micrograms/ml.
A novel peptide delivery system involving peptidase activated prodrugs as antimicrobial agents. Synthesis and biological activity of peptidyl derivatives of 5-fluorouracil (1984)

As an approach to the development of antimicrobial agents, a novel peptide carrier system was designed, based on the chemical instability of alpha-substituted glycine analogues, with the explicit intent of actively transporting therapeutically useful compounds into microbial cells. Peptides containing 5-fluorouracil (5-FU) linked to the peptide backbone were selected to test the feasibility of this new delivery system. These peptide conjugates were designed such that they would be substrates for both the microbial peptide permeases and peptidases. After entry into cells, enzymatic hydrolysis of the peptide generates an unstable alpha-(5-FU)-glycine that spontaneously decomposes to release 5-FU. The 5-FU-peptide conjugates were tested for antifungal (Candida albicans) and antibacterial (Escherichia coli) activity and were found to have antimicrobial activities comparable to free 5-FU. Noninhibitory peptides antagonized the antimicrobial activities of the 5-FU-peptide conjugates but not of free 5-FU, a result consistent with peptide transport mediated entry of the peptide conjugates into cells. Further support for this conclusion was provided by the finding that biological activities were dependent upon peptide stereochemistry.
Design and Synthesis of Poly ADP-ribose Polymerase-1 Inhibitors. 2. Biological Evaluation of Aza-5[H]-phenanthridin-6-ones as Potent, Aqueous-Soluble Compounds for the Treatment of Ischemic Injuries (2003)

A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors of poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency of the unsubstituted aza-5[H]-phenanthridin-6-ones (i.e., benzonaphthyridones) was dependent on the position of the nitrogen atom within the core structure. The A ring nitrogen analogues (7-, 8-, and 10-aza-5[H]-phenanthridin-6-ones) were an order of magnitude less potent than C ring nitrogen analogues (1-, 2-, 3-, and 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- and 2-aza-5[H]-phenanthridin-6-one prompted structure−activity relationships to be established for several 2- and 3-substituted 1-aza-5[H]-phenanthridin-6-ones. The 2-substituted 1-aza-5[H]-phenanthridin-6-ones were designed to improve the solubility and pharmacokinetic profiles for this series of PARP-1 inhibitors. Most importantly, three compounds from this series demonstrated statistically significant protective effects in rat models of stroke and heart ischemia.
Two novel mutations in the ATP2A2 gene in Chinese patients with Darier disease (2009)

Auteur(s) : Jia Huo, XiaoPeng Wang, YingYing Dong, JiaWen Wu, XiaoLi Li, Yan Liu, SengXiang Xiao Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, R.P. China Darier disease (DD; OMIM 124200) is a rare autosomal dominant hereditary skin disorder characterized by warty papules and plaques on the seborrheic areas of the skin. The cause of DD is defects in the ATP2A2 gene on chromosome 12q23-24.1 [1]. This gene encodes the sarco/endoplasmic [...]
Variation of peak temperature with heating rate in differential thermal analysis (1956)

In differe ntial thermal analys is, the temp erat ure at whi ch th e maxi mum de nection is obse rved varies with h eating rate for certain ty pes of r eactio ns. An ex press ion ca n be d eri ved r elating this variat ion with t h e kin etics of t lw r eaction . By ma kin g a !lumber of d ir-J'erential t her mal patterns at dir-J'er ent h eating rates, t he kinetic eOJl stants can be obtai ned diree Uy from t h e differential t h ermal data.
Remote surface enhanced Raman spectroscopy imaging via a nanostructured optical fiber bundle (2009)

Remote surface enhanced Raman spectroscopy (SERS) imaging of an adsorbed monolayer was demonstrated through a nanostructured array of conical tips inscribed onto the distal face of a 30 cm optical fiber bundle. Despite intense Raman signal from the germanium oxide doped fibers, the Raman signal of an adsorbed monolayer of a reference compound (benzene thiol) was detected in the fingerprint region. This opens up the possibility of local remote imaging through an optical fiber that embeds a SERS active platform.
Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression (2007)

Zinc is an essential trace element and catalytic/structural component used by many metalloenzymes and transcription factors. Recent studies indicate a possible correlation of zinc levels with the cancer risk; however, the exact role of zinc and zinc transporters in cancer progression is unknown. We have observed that a zinc transporter, ZIP4 (SLC39A4), was substantially overexpressed in 16 of 17 (94%) clinical pancreatic adenocarcinoma specimens compared with the surrounding normal tissues, and ZIP4 mRNA expression was significantly higher in human pancreatic cancer cells than human pancreatic ductal epithelium (HPDE) cells. This indicates that aberrant ZIP4 up-regulation may contribute to the pancreatic cancer pathogenesis and progression. We studied the effects of ZIP4 overexpression in pancreatic cancer cell proliferation in vitro and pancreatic cancer progression in vivo. We found that forced expression of ZIP4 increased intracellular zinc levels, increased cell proliferation by 2-fold in vitro, and significantly increased tumor volume by 13-fold in the nude mice model with s.c. xenograft compared with the control cells. In the orthotopic nude mice model, overexpression of ZIP4 not only increased the primary tumor weight (7.2-fold), it also increased the peritoneal dissemination and ascites incidence. Moreover, increased cell proliferation and higher zinc content were also observed in the tumor tissues that overexpressed ZIP4. These data reveal an important outcome of aberrant ZIP4 expression in contributing to pancreatic cancer pathogenesis and progression. It may suggest a therapeutic strategy whereby ZIP4 is targeted to control pancreatic cancer growth.
Switching directly to prasugrel from clopidogrel results in greater inhibition of platelet aggregation in aspirin-treated subjects (2008)

Prasugrel, a novel P2Y(12) antagonist, achieves faster onset and greater inhibition of platelet aggregation than clopidogrel 300 and 600 mg loading doses (LD). We studied the safety, time course, and level of platelet inhibition when switching directly from clopidogrel 75 mg maintenance dose (MD) to a prasugrel 60 mg LD/10 mg MD or 10 mg MD regimen. Healthy subjects (n = 39) on aspirin (81 mg/d) received a clopidogrel 600 mg LD followed by 10 days of clopidogrel MD (75 mg/d). Subjects were then randomized without a washout period to prasugrel 60 mg LD (n = 16) followed by 10 days of prasugrel MD (10 mg/d) or to prasugrel MD (10 mg/d, n = 19) for 11 days. Maximal platelet aggregation (MPA) to 20 microM ADP was measured by turbidimetric aggregometry. In subjects on clopidogrel 75 mg MD, mean MPA decreased from 39 to 12% by 30 minutes, and to 5% by 1 hour after a prasugrel 60 mg LD (p < 0.001 for both) and from 37 to 28% (p < 0.001) by 1 hour after a prasugrel 10 mg MD. During prasugrel MD, a new pharmacodynamic steady state MPA of approximately 24% (p < 0.01 vs. clopidogrel MD) occurred within four to five days of switching from clopidogrel. Changing from clopidogrel to prasugrel did not increase bleeding episodes or other adverse events. Switching directly from clopidogrel MD to either prasugrel LD or MD was well tolerated and resulted in significantly greater levels of platelet inhibition than a clopidogrel 75 mg MD.
Principles in the biomodulation of cytotoxic drugs by interferons. (1992)

The interferons (IFNs) were identified as novel, endogenous antiviral agents in 1957. Shortly thereafter, antiproliferative and immunostimulatory activities were identified for these compounds. Based on these observations, partially purified IFNs entered clinical trials in the 1970s and recombinant IFNs in 1980. IFNs have demonstrated important clinical activity in hairy cell leukemia, melanoma, renal cell carcinoma, and Kaposi's sarcoma as monotherapy. Shortly after their introduction into clinical trials, however, preclinical studies demonstrated synergistic interactions between IFNs and cytotoxic drugs. Numerous preclinical trials have demonstrated a broad spectrum of interactions between IFNs and at least 20 cytotoxic agents both in vitro and in vivo. Early clinical trials suggest a benefit to combinations of fluorouracil and recombinant interferon alfa in refractory gastrointestinal malignancies. Combinations of IFNs and cytotoxic agents deserve further investigations; however, different principles apply for combining IFNs with cytotoxic drugs than for the design of combination chemotherapy regimens.
Strongly red-fluorescent novel donor–π-bridge–acceptor–π-bridge–donor (D–π–A–π–D) type 2,1,3-benzothiadiazoles with enhanced two-photon absorption cross-sections (2004)

Novel donor-pi-bridge-acceptor-pi-bridge-donor (D-pi-A-pi-D) type 2,1,3-benzothiadiazole fluorescent dyes connected to the N,N-diarylamino terminus via various type pi-conjugate spacers exhibits large two-photon absorption cross-sections and high fluorescent quantum yields in orange-red color.
Liposome‐stabilized oil‐in‐water emulsions as adjuvants: Increased emulsion stability promotes induction of cytotoxic T lymphocytes against an HIV envelope antigen (2004)

Protective or therapeutic immunity against HIV infection is currently believed to require both antibody and CTL responses against the envelope protein. In the present study, the adjuvant activity of a unique oil‐in‐water emulsion, in which liposomes containing lipid A (LA) and encapsulated antigen served as the emulsifying agent, was examined in mice using oligomeric gp140 (ogp140) derived from the HIV‐1 envelope as the antigen. Emulsions rendered either highly stable or unstable by altering the ratio of liposomes to oil were used to examine the effect of stability of the emulsion on adjuvant activity. Stable and unstable emulsions had similar potencies for inducing both IgG antibodies to ogp140 and antigen‐specific T‐lymphocyte proliferation. Stable emulsions, but not unstable emulsions, induced antigen‐specific CTL responses, possibly because of the depot effect of the stable emulsions. Furthermore, stable emulsions induced lower IgG2a/IgG1 ratios than the unstable emulsions. We conclude that stable liposomal oil‐in‐water emulsions provide an effective means of obtaining both antibody and CTL responses against an HIV envelope antigen.
An Analytical Model of Reactive Diffusion for Transient Electronics (2013)

Abstract Transient electronics is a class of technology that involves components which physically disappear, in whole or in part, at prescribed rates and at programmed times. Enabled devices include medical monitors that fully resorb when implanted into the human body (“bio‐resorbable”) to avoid long‐term adverse effects, or environmental monitors that dissolve when exposed to water (“eco‐resorbable”) to eliminate the need for collection and recovery. Analytical models for dissolution of the constituent materials represent important design tools for transient electronic systems that are configured to disappear in water or biofluids. Here, solutions for reactive‐diffusion are presented in single‐ and double‐layered structures, in which the remaining thicknesses and electrical resistances are obtained analytically. The dissolution time and rate are defined in terms of the reaction constants and diffusivities of the materials, the thicknesses of the layer, and other properties of materials and solution. These models agree well with the experiments for single layers of Mg and SiO 2 , and double layers of Mg/MgO. The underlying physical constants extracted from analysis fall within a broad range previously reported in other studies; these constants can be extremely sensitive to the morphologies of the materials, temperature, and the PH value, concentration, and properties of the surrounding liquid.
APOBEC-Mediated Editing of Viral RNA (2004)

Retroviral DNA can be subjected to cytosine-to-uracil editing through the action of members of the APOBEC family of cytidine deaminases. Here we demonstrate that APOBEC-mediated cytidine deamination of human immunodeficiency virus (HIV) virion RNA can also occur. We speculate that the natural substrates of the APOBEC enzymes may extend to RNA viruses that do not replicate through DNA intermediates. Thus, cytosine-to-uracil editing may contribute to the sequence diversification of many viruses.
Curing HIV: Pharmacologic Approaches to Target HIV-1 Latency (2011)

HIV-1 infection persists even after years of antiretroviral therapy (ART). Although ART can halt viral replication and thereby reduce viremia to clinically undetectable levels, proviral latency established within the host genome remains largely unaffected by ART and can replenish systemic infection following interruption of therapy. Pharmacologic strategies, which not only target viral replication but also deplete proviral infection, are required for successful clearance of HIV-1 infection. This review highlights the current understanding of molecular mechanisms that establish and maintain HIV-1 latency in its major reservoir, the resting memory CD4(+) T cell. We also identify the molecular targets that might be exploited to induce HIV-1 expression, remove epigenetic restrictions, or enhance effective transcription. Finally, we discuss the potential pharmacologic approaches toward targeting viral persistence in different cellular and anatomical reservoirs to achieve a cure of HIV-1 infection.
THE REX GENE OF BACTERIOPHAGE λ IS REALLY TWO GENES (1982)

Complementation tests among previously isolated rex- mutants of bacteriophage lambda reveal that the mutants comprise two complementation groups, designated rexA and rexB. Because rexB- mutants complement prm- mutants, but rexA- mutants do not, it appears that the rexA gene is coordinately controlled with the cI (repressor) gene under the direction of PRM promoter, but that some other promoter is capable of directing the expression of rexB.
The Sample Complexity of Exploration in the Multi-Armed Bandit Problem (2004)

We consider the multi-armed bandit problem under the PAC (probably approximately correct) model. It was shown by Even-Dar et al. (2002) that given n arms, a total of O((n/e2)log(1/δ)) trials suffices in order to find an e-optimal arm with probability at least 1-δ. We establish a matching lower bound on the expected number of trials under any sampling policy. We furthermore generalize the lower bound, and show an explicit dependence on the (unknown) statistics of the arms. We also provide a similar bound within a Bayesian setting. The case where the statistics of the arms are known but the identities of the arms are not, is also discussed. For this case, we provide a lower bound of Θ((1/e2)(n+log(1/δ))) on the expected number of trials, as well as a sampling policy with a matching upper bound. If instead of the expected number of trials, we consider the maximum (over all sample paths) number of trials, we establish a matching upper and lower bound of the form Θ((n/e2)log(1/δ)). Finally, we derive lower bounds on the expected regret, in the spirit of Lai and Robbins.
Organogel‐based Thin Films for Self‐Cleaning on Various Surfaces (2013)

Self-cleaning on various surfaces is obtained using the facile approach of modifying the surface with a thin organogel film. The film not only absorbs oil but also holds it in a crosslinked network, which endows the material with excellent self-cleaning properties. This facile method can be applied to various common engineering metals.
Classification criteria for psoriatic arthritis: Development of new criteria from a large international study (2006)

The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria.
Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes (2007)

CXC chemokine ligand 10 (CXCL10) plays a pivotal role in the self-perpetuation of the inflammatory processes in patients with autoimmune thyroid disease. Treatment with methimazole (MMI) reduces serum CXCL10 in patients with Graves' disease. In isolated human thyrocytes, tumor necrosis factor (TNF)alpha demonstrates a potent synergistic effect on interferon (IFN)gamma-induced CXCL10 secretion. We investigated the mechanism underlying the synergism between IFNgamma and TNFalpha and the effect of MMI on CXCL10 secretion in human thyrocytes. A peroxisome proliferator-activated receptor gamma agonist, rosiglitazone (RGZ), a known inhibitor of T helper 1 (Th1)-mediated responses, was also studied for comparison. Experiments were carried out in human thyrocytes isolated from internodular parenchyma of thyroid tissues derived from patients who had undergone surgery for multinodular goiter. ELISA was used to measure CXCL10 levels in culture supernatant. Flow cytometry was used to assess IFNgamma membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-kappaB (NF-kappaB). In human thyrocytes, the synergistic effect of TNFalpha with IFNgamma on CXCL10 secretion is due to the upregulation of IFNgamma receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNFalpha-induced upregulation of the IFNgamma receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-kappaB translocation, without affecting IFNgamma receptor. MMI and RGZ targeted thyrocytes with the same pharmacological potency, likely acting throughout different mechanisms. Targeting T helper 1-mediated autoimmune thyroid disease with drugs that impair different intracellular pathways could be a novel pharmacological tool.
Synthesis of (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid, a potent broad spectrum β-lactamase inhibitor, from 6-aminopenicillanic acid (1994)

(5R)-(Z)-6-(1-Methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34(BRL 42715) has been prepared from 6-aminopenicillanic acid 4(6-APA) by a short, stereoselective and efficient route via the novel intermediate, p-methoxybenzyl (5R, 6S)-6-bromopenem-3-carboxylate 17.Elaboration of 6-APA 4 to the azetidinone disulfide 10 by established methodology, followed by reductive formylation provided the crystalline C-4 formylthio-azetidinone derivative 29. Cyclization of the oxalimide 28, obtained by ozonolysis of the formylthio derivative 29, to the crystalline 6α-bromopenem ester 17 was effected by way of the phosphite-mediated carbonyl–carbonyl coupling reaction.Sequential treatment of bromopenem 17 with lithium diphenylamide, 1-methyl-1,2,3-triazole-4-carbaldehyde, and acetic anhydride gave a diastereoisomeric mixture of acylated bromohydrins 32; reductive elimination of this mixture afforded a separable mixture of (Z)- and (E)-triazolylmethylene penem esters, 33 and 35 respectively. Lewis acid-mediated deprotection of ester 33 provided (5R)(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34(BRL 42715) as a crystalline sodium salt monohydrate.The 6-heterocyclylmethylene penems, represented by BRL 42715, are potent inhibitors of bacterial β-lactamases and their combination with an appropriate penicillin or cephalosporin results in good synergistic activity against a broad range of β-lactamase-producing bacteria.
Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-γ (2006)

Mesenchymal stem cells (MSCs) are mostly found around the vasculature system of the adult bone marrow (BM). They function as immune suppressors, express MHC-II, are phagocytic, and support T-cell cytotoxicity. We hypothesize that these contradictory properties of MSCs are important for BM homeostasis and occur partly through antigen presentation (antigen-presenting cells [APCs]) within a narrow window. Indeed, we have verified APC functions of MSCs to recall antigens, Candida albicans and Tetanus toxoid. The target cells have been identified to be CD4(+) T cells. APC assays with IFNgamma-knockdown MSCs and with anti-IFNgamma receptor confirmed that MHC-II expression requires autocrine stimulation by IFNgamma. During APC functions, as IFNgamma levels become elevated, there was a concomitant decrease in MHC-II on MSCs. This observation was correlated with flow cytometry studies showing a gradual decrease in MHC-II expression as IFNgamma levels were increased. The reduced levels of MHC-II correlated with losses in their allogeneic potential, as indicated in mixed lymphocyte reaction. In summary, endogenous and low levels of IFNgamma are required for MHC-II expression on MSCs, and for APC functions. APC functions occur during a narrow window before IFNgamma levels are increased. The study has implications for BM protection against infection and exacerbated inflammatory responses.
A Neuromorphic Depth-From-Motion Vision Model With STDP Adaptation (2006)

We propose a simplified depth-from-motion vision model based on leaky integrate-and-fire (LIF) neurons for edge detection and two-dimensional depth recovery. In the model, every LIF neuron is able to detect the irradiance edges passing through its receptive field in an optical flow field, and respond to the detection by firing a spike when the neuron's firing criterion is satisfied. If a neuron fires a spike, the time-of-travel of the spike-associated edge is transferred as the prediction information to the next synapse-linked neuron to determine its state. Correlations between input spikes and their timing thus encode depth in the visual field. The adaptation of synapses mediated by spike-timing-dependent plasticity is used to improve the algorithm's robustness against inaccuracy caused by spurious edge propagation. The algorithm is characterized on both artificial and real image sequences. The implementation of the algorithm in analog very large scale integrated (aVLSI) circuitry is also discussed.