gebhart/patrepeval huggingface dataset:
Poly(ADP-ribose) Binds to Specific Domains in DNA Damage Checkpoint Proteins (2000)

Poly(ADP-ribose) is formed in possibly all multicellular organisms by a familiy of poly(ADP-ribose) polymerases (PARPs). PARP-1, the best understood and until recently the only known member of this family, is a DNA damage signal protein catalyzing its automodification with multiple, variably sized ADP-ribose polymers that may contain up to 200 residues and several branching points. Through these polymers, PARP-1 can interact noncovalently with other proteins and alter their functions. Here we report the discovery of a poly(ADP-ribose)-binding sequence motif in several important DNA damage checkpoint proteins. The 20-amino acid motif contains two conserved regions: (i) a cluster rich in basic amino acids and (ii) a pattern of hydrophobic amino acids interspersed with basic residues. Using a combination of alanine scanning, polymer blot analysis, and photoaffinity labeling, we have identified poly(ADP-ribose)-binding sites in the following proteins: p53, p21(CIP1/WAF1), xeroderma pigmentosum group A complementing protein, MSH6, DNA ligase III, XRCC1, DNA polymerase epsilon, DNA-PK(CS), Ku70, NF-kappaB, inducible nitric-oxide synthase, caspase-activated DNase, and telomerase. The poly(ADP-ribose)-binding motif was found to overlap with five important functional domains responsible for (i) protein-protein interactions, (ii) DNA binding, (iii) nuclear localization, (iv) nuclear export, and (v) protein degradation. Thus, PARPs may target specific signal network proteins via poly(ADP-ribose) and regulate their domain functions.
Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 bind to a single leucine-rich motif of TrkB (1995)

TrkB is a member of the Trk family of neurotrophin receptors. Its extracellular domain exhibits the same modular structure found in its homologs, TrkA and TrkC, consisting of an N-terminal LRM3 cassette and two immunoglobulin-like modules (Ig2 domain) adjacent to the membrane. The LRM3 cassette comprises two cysteine-rich clusters framing a tandem array of three leucine-rich motifs (LRMs). On the basis of the recent identification of a nerve growth factor (NGF) binding site within TrkA, the ability of the different structural entities within the extracellular domain of TrkB to bind the various neurotrophins was determined by using a recombinant receptor approach. Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) bound to the LRM3 cassette of TrkB, whereas NGF did not. These binding characteristics evidently reflect in vivo specificities. A more precise mapping of the region(s) responsible for binding BDNF, NT-3, and NT-4 identified the second leucine-rich motif of TrkB as a functional unit capable of binding all three neurotrophins. The affinities and kinetics that this short stretch of amino acids exhibited with respect to the different neurotrophins were clearly akin to those observed for cells ectopically expressing TrkB receptors. With 24 amino acids determining the affinities and kinetics of the interactions with three different partners, the leucine-rich motif is strongly established as one of the most potent and flexible protein--protein interaction motifs.
3D Direct Human-Computer Interface Paradigm Based on Free Hand Tracking (2014)

Directed at some of the difficult problems and key problems in building uniform human computer interaction model under the single channel or free gesture input,a new tracking and interacting method for three-dimensional(3D)gesture based on a two-level behavioral model is put forward in this paper.First of all,the two-level behavioral model is built upon which a 3D human-computer interface paradigm is designed.The main contributions of this paper are as follows.(1)The two-level behavioral model for a basic gesture database is built;(2)capture interaction intention of users with token-ring,so as to form the interaction model for choosing an object from multiples;(3)replace objects with proxies to solve complexity and diversity for 3D hand model to grasp objects with different shapes and sizes.The proposed algorithm has been tested on several virtual assembling platforms.Experimental results with real video data show the efficiency and effectiveness of the new approach.This research also provides us a natural,direct,convenient and harmonious human-computer interaction paradigm.
Administration of Ascorbic Acid and an Aldose Reductase Inhibitor (Tolrestat) in Diabetes: Effect on Urinary Albumin Excretion (1998)

The important role of ascorbic acid (AA) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor, tolrestat, on AA metabolism and urinary albumin excretion in diabetes. Blood and urine samples were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subjects who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA1c, plasma lipids, urinary albumin, and total glycosaminoglycan excretion were measured at all time points, and heparan sulphate (glycosaminoglycan) was measured at 0 and 12 months. The same parameters, as well as urinary AA excretion, were determined at 0 and 3 months for 16 diabetes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excretion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but did not change the other parameters measured. Tolrestat lowered plasma AA (Wilcoxon's signed-rank test, p < 0.05), but did not change AER or the other parameters measured. The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism. Unlike the rat model of diabetes, inhibition of aldose reductase did not normalize plasma AA or AER in humans. In fact, tolrestat reduced the plasma AA concentration, a phenomenon which may be due to increased utilization of AA. Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications.
Death receptor 5 mediated-apoptosis contributes to cholestatic liver disease (2008)

Chronic cholestasis often results in premature death from liver failure with fibrosis; however, the molecular mechanisms contributing to biliary cirrhosis are not demonstrated. In this article, we show that the death signal mediated by TNF-related apoptosis-inducing ligand (TRAIL) receptor 2/death receptor 5 (DR5) may be a key regulator of cholestatic liver injury. Agonistic anti-DR5 monoclonal antibody treatment triggered cholangiocyte apoptosis, and subsequently induced cholangitis and cholestatic liver injury in a mouse strain-specific manner. TRAIL- or DR5-deficient mice were relatively resistant to common bile duct ligation-induced cholestasis, and common bile duct ligation augmented DR5 expression on cholangiocytes, sensitizing mice to DR5-mediated cholangitis. Notably, anti-DR5 monoclonal antibody-induced cholangitis exhibited the typical histological appearance, reminiscent of human primary sclerosing cholangitis. Human cholangiocytes constitutively expressed DR5, and TRAIL expression and apoptosis were significantly elevated in cholangiocytes of human primary sclerosing cholangitis and primary biliary cirrhosis patients. Thus, TRAIL/DR5-mediated apoptosis may substantially contribute to chronic cholestatic disease, particularly primary sclerosing cholangitis.
Peroxisome Proliferator-activated Receptor α Activators Improve Insulin Sensitivity and Reduce Adiposity (2000)

Fibrates and glitazones are two classes of drugs currently used in the treatment of dyslipidemia and insulin resistance (IR), respectively. Whereas glitazones are insulin sensitizers acting via activation of the peroxisome proliferator-activated receptor (PPAR) gamma subtype, fibrates exert their lipid-lowering activity via PPARalpha. To determine whether PPARalpha activators also improve insulin sensitivity, we measured the capacity of three PPARalpha-selective agonists, fenofibrate, ciprofibrate, and the new compound GW9578, in two rodent models of high fat diet-induced (C57BL/6 mice) or genetic (obese Zucker rats) IR. At doses yielding serum concentrations shown to activate selectively PPARalpha, these compounds markedly lowered hyperinsulinemia and, when present, hyperglycemia in both animal models. This effect relied on the improvement of insulin action on glucose utilization, as indicated by a lower insulin peak in response to intraperitoneal glucose in ciprofibrate-treated IR obese Zucker rats. In addition, fenofibrate treatment prevented high fat diet-induced increase of body weight and adipose tissue mass without influencing caloric intake. The specificity for PPARalpha activation in vivo was demonstrated by marked alterations in the expression of PPARalpha target genes, whereas PPARgamma target gene mRNA levels did not change in treated animals. These results indicate that compounds with a selective PPARalpha activation profile reduce insulin resistance without having adverse effects on body weight and adipose tissue mass in animal models of IR.
Bone Morphogenetic Protein 2 Induces Dental Follicle Cells to Differentiate Toward a Cementoblast/Osteoblast Phenotype (2002)

When triggered appropriately, dental follicle cells are considered to be able to differentiate toward a cementoblast/osteoblast phenotype. However, factors and mechanisms regulating follicle cell differentiation remain undefined. This study focused on determining the ability of bone morphogenetic protein (BMP) 2 to promote the differentiation of follicle cells and periodontal ligament (PDL) cells along a cementoblast/ osteoblast pathway. Follicle cells and PDL cells were isolated from the first molar region of CD-1 mice and immortalized with SV40. Both cell types expressed BMP-4 and BMP receptors (BMPR) IA and II, but only follicle cells expressed BMP-2 mRNA. Cells were exposed to recombinant human BMP (rhBMP)-2 (0-100 ng/ml) and Northern blots were used to determine the expression of mineral-associated markers. BMP-2, in a dose- and time-dependent manner, induced cementoblast/osteoblast differentiation of follicle cells, as reflected by enhanced core binding factor alpha (Cbfal), bone sialoprotein (BSP), and osteocalcin (OCN) mRNA expression and enhanced mineral formation. U0126, a specific inhibitor of MEK-1/2 members of the MAPK family, abolished BMP-2-mediated expression of BSP and OCN. In contrast, exposure of PDL cells to BMP-2 resulted in modest expression of OCN and minimal promotion of mineralization. These results suggest that BMP-2 triggers follicle cells to differentiate toward a cementoblast/osteoblast phenotype and that the MAPK pathway is involved.
Conducting polymers: Efficient thermoelectric materials (2011)

Abstract This review highlights the recent progress made in the area of thermoelectric (TE) applications of conducting polymers and related composites. Several examples of such materials and their TE properties are discussed. TE properties of new poly(2,7‐carbazole) derivatives are highlighted. References are also made to carbon nanotube/polymer composites and their improved electrical and TE performance. Studies on polymer/inorganic materials composites have also taken a step forward and have shown very promising TE properties. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011
A Glycine-Dependent Riboswitch That Uses Cooperative Binding to Control Gene Expression (2004)

We identified a previously unknown riboswitch class in bacteria that is selectively triggered by glycine. A representative of these glycine-sensing RNAs from Bacillus subtilis operates as a rare genetic on switch for the gcvT operon, which codes for proteins that form the glycine cleavage system. Most glycine riboswitches integrate two ligand-binding domains that function cooperatively to more closely approximate a two-state genetic switch. This advanced form of riboswitch may have evolved to ensure that excess glycine is efficiently used to provide carbon flux through the citric acid cycle and maintain adequate amounts of the amino acid for protein synthesis. Thus, riboswitches perform key regulatory roles and exhibit complex performance characteristics that previously had been observed only with protein factors.
Secondary conformational conversion is involved in glycosaminoglycans‐mediated cellular uptake of the cationic cell‐penetrating peptide PACAP (2014)

Glycosaminoglycans (GAGs) contribute to the cellular uptake of cationic cell-penetrating peptides (CPPs). However, molecular details about the contributions of GAGs in CPP internalization remain unclear. In this study, we examined the cellular uptake mechanism of the arginine-rich CPP pituitary adenylate-cyclase-activating polypeptide (PACAP). We observed that the uptake efficacy of PACAP is dependent on the expression of cell surface GAGs. As the binding of PACAP to sulfated GAGs induced a random coil-to-α-helix conformational conversion, we investigated the role of the helical formation in PACAP internalization. Whereas this secondary structure was not crucial for efficient internalization in GAGs-deficient cells, PACAP α-helix was essential for GAGs-dependent uptake.
Piezoelectric 3–3 composites (1982)

Abstract Piezoelectric composites of PZT and polymers were prepared by mixing tiny plastic spheres with PZT powder in an organic binder and firing the mixture to give a ceramic skeleton. After cooling, the skeleton was back-filled with polymer and poled. Dielectric and piezoelectric properties were measured on samples ranging from 30 to 70 volume % PZT, and compared with a rectangular skeleton model for 3–3 composites. Composites containing 50% PZT-50% silicone rubber appear especially useful for hydrophone applications with dhgh products a hundred times larger than PZT.
Voting experts: An unsupervised algorithm for segmenting sequences (2007)

We describe a statistical signature of chunks and an algorithm for finding chunks. While there is no formal definition of chunks, they may be reliably identified as configurations with low internal entropy or unpredictability and high entropy at thei
Electrochemical Sensors for Monitoring Hydrogen in Steel (1994)

Information obtained from two amperometric sensors and from a potentiometric sensor for monitoring hydrogen (H) in steel in contact with corrosive solutions saturated with hydrogen sulfide (H2S) at ambient temperature was compared. The apparent diffusion coefficient (Dapp) for H in the steel as determined by experiments using the amperometric sensors was shown to be independent of H concentration in the steel (cH). Experiments with the potentiometric sensor indicated Dapp values increased with increasing cH. The calculated H concentration at the surface of the steel in contact with the corrosive medium (chi), as obtained from the two amperometric sensors, showed poor agreement. The equivalent pressure of H in the steel (pH2eq), as calculated from the voltage measurement of the potentiometric sensor, was strongly dependent on pH of the corrosive solution.
Noncovalent Tripeptidyl Benzyl- and Cyclohexyl-Amine Inhibitors of the Cysteine Protease Caspase-1 (2010)

Potent and noncovalent inhibitors of caspase-1 were produced by incorporating a secondary amine (reduced amide) isostere in place of the conventional electrophile (e.g., aldehyde) that normally confers high potency to cysteine protease inhibitors. Benzyl- or cyclohexylamines produced potent, reversible, and competitive inhibitors that were selective for caspase-1 (e.g., K(i) = 47 nM) over caspases 3 and 8 with minimal cytotoxicity. Unlike most cysteine protease inhibitors, these compounds do not react covalently and indiscriminately with thiols.
Large-Scale Adeno-Associated Viral Vector Production Using a Herpesvirus-Based System Enables Manufacturing for Clinical Studies (2009)

The ability of recombinant adeno-associated viral (rAAV) vectors to exhibit minimal immunogenicity and little to no toxicity or inflammation while eliciting robust, multiyear gene expression in vivo are only a few of the salient features that make them ideally suited for many gene therapy applications. A major hurdle for the use of rAAV in sizeable research and clinical applications is the lack of efficient and versatile large-scale production systems. Continued progression toward flexible, scalable production techniques is a prerequisite to support human clinical evaluation of these novel biotherapeutics. This review examines the current state of large-scale production methods that employ the herpes simplex virus type 1 (HSV) platform to produce rAAV vectors for gene delivery. Improvements have substantially advanced the HSV/AAV hybrid method for large-scale rAAV manufacture, facilitating the generation of highly potent, clinical-grade purity rAAV vector stocks. At least one human clinical trial employing rAAV generated via rHSV helper-assisted replication is poised to commence, highlighting the advances and relevance of this production method.
Analysis of Naphthenic Acids and Derivatization Agents Using Two-Dimensional Gas Chromatography and Mass Spectrometry: Impact on Flow Assurance Predictions (2010)

In this work, a sensitivity study was conducted on naphthenic acid derivatization agents. Four silylation chemistries and one methylation chemical were initially evaluated on 10 model naphthenic acids using gas chromatography. An experimental design procedure was setup to look at a number of effects, including contact time, catalyst presence, and reagent concentration. Overall, the silylation agents resulted in higher derivatization yields compared to the methylation agent. Moreover, the silylation agents did not show major evidence of selective derivatization as a function of the naphthenic acid structure. A silylation agent [(N,O-bis-(trimethylsilyl)trifluoroacetamide (BSTFA)] was then used to test commercial naphthenic acid mixtures with two-dimensional gas chromatography coupled to time-of-flight mass spectrometry using the electron-impact source (GC×GC−TOFMS). The results enabled identification of many different naphthenic acid species. To test the derivatization agents on realistic samples, naphthenic acid extracts obtained from two crude oils of flow assurance significance were separated with a liquid-phase extraction procedure. The naphthenic acids were then treated with a silylation agent (BSTFA) and a methylation agent (BF3/methanol). The derivatized naphthenic acids together with the non-derivatized naphthenic acids from both crude oils were further examined using medium-resolution time-of-flight mass spectrometry with an electrospray source (TOFMS). Differences were observed in the TOFMS spectra for the naphthenic acid extracts. Extracts that did not contain ARN naphthenic acid species did not show major differences between non-derivatized and derivatized spectra in the negative mode. Extracts that contained ARN did show differences between derivatized and non-derivatized samples in the negative mode. Use of BSTFA resulted in enhanced signals for ARN, particularly the second ionization. Use of BF3/methanol resulted in a poor ARN response compared to the non-derivatized spectra. ARN species were also observed in the positive mode after treatment with both BSTFA and BF3/methanol, but signals were very poor. Moreover, use of BF3/methanol resulted in poor solubility of the naphthenic acid extracts from the crude oil containing ARN species. No solubility issues were observed with the use of BSTFA. Overall, the results point to the shortcomings of the application of methylation chemicals as derivatization agents, particularly for naphthenic acids extracted from crude oil samples containing high-molecular-weight acids of flow assurance significance (e.g., ARN species).
Automation and Optimization of Protein Expression and Purification on a Novel Robotic Platform (2006)

This article describes a novel robotic system for protein expression and purification. This area has traditionally proved a bottleneck in pharmaceutical discovery owing to the difficulty and unpredictability of outcome in evaluating multiple sets of expression conditions that will yield biologically active protein in sufficient quantity to meet the demands of discovery teams. This position has been exacerbated by the requirement of structural biology groups to have access to 100 mg scale quantities of pure protein for early and complex structural studies. The Piccolo robotic system described here was able to perform multiple parallel induction, expression, and single stage protein purification of a target protein (6-His tagged β-galactosidase) using a model E. coli expression system. The Piccolo system monitored E. coli cell growth automatically and rescheduled tasks dynamically based on individual instances of cell growth within purpose built 24-well bioreactor units termed culture vessel blocks. On completion of protein expression, the system performed cell lysis and purification of the expressed β-galactosidase through Ni-NTA histidine affinity chromatography. We show that alterations in the induction and expression conditions used resulted in changes in the yield of expressed β-galactosidase. In addition to the E. coli studies described here, the system is also applicable for other bacterial species and for eukaryotic cell culture applications. The Piccolo robotic system has the capacity to allow exploration of hundreds of different combinations of expression variables within a working week thereby allowing rapid identification of optimal conditions for expressing the biologically active protein of interest. This strategy confers a significant increase in the parallel processing capability of protein expression groups and goes a long way to addressing the current protein expression bottleneck.
Evil humors take their toll as innate immunity makes gouty joints TREM‐ble (2006)

Acute gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular tophaceous deposits of monosodium urate monohydrate (MSU) crystals. Full-blown acute gouty arthritis is dependent on the influx into the joint space of neutrophils, a cell type normally absent from this locus. Hence, the clinical term “gout,” classically described in the 5th century BC by Hippocrates, was derived in a remarkably prescient manner from the Latin word “gutta,” which literally means “drop.” Specifically, gout was named to reflect the notion of “evil humors” aberrantly seeping into affected joints. Recent advances have revealed the uncanny link between this ancient disease and innate immune inflammatory responses that are phylogenetically primeval. Innate immunity provides a first line of defense against infection via primitive responses that are nonspecific and broad in spectrum (1). Unlike adaptive immune responses, stereotypic innate immune “early induced” responses do not directly induce immunologic memory or lasting protective immunity, consistent in acute gout with the recurrent paroxysmal nature of the disease and the primary role in pathogenesis of “professional phagocytes.” Central to rapid innate immune inflammatory and killing responses is the remarkable capacity of all eukaryotic organisms to recognize the same constituents of microbes (termed pathogenassociated molecular patterns [PAMPs]). Seminal identification of Toll and Toll-like receptors (TLRs) that recognize PAMPs in Drosophila indicates that human innate immune mechanisms for discrimination of nonself PAMPs such as lipopolysaccharide (LPS) and peptidoglycan from self are phylogenetically primordial. The majority of encounters with microorganisms expressing PAMPs do not result in disease, but breaching of tissue barriers by pathogens can stimulate innate immune alternative complement pathway activation, the expression of chemokines and certain other inflammatory cytokines, and uptake of the pathogen by resident and recruited professional phagocytes in a rapid effort to eliminate the noxious agent.