gebhart/patrepeval huggingface dataset:
Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition. (1994)

We reported previously that human interleukin-1 beta converting enzyme (ICE) is regulated by the CrmA serpin encoded by cowpox virus. We now report the mechanism and kinetics of this unusual inhibition of a cysteine proteinase by a member of the serpin superfamily previously thought to inhibit serine proteinase only. CrmA possesses several characteristics typical of a number of inhibitory serpins. It is conformationally unstable, unfolding around 3 M urea, and stable to denaturation in 8 M urea upon complex formation with ICE. CrmA rapidly inhibits ICE with an association rate constant (kon) of 1.7 x 10(7) M-1 s-1, forming a tight complex with an equilibrium constant for inhibition (Ki) of less than 4 x 10(-12) M. These data indicate that CrmA is a potent inhibitor of ICE, consistent with the dramatic effects of CrmA on modifying host responses to virus infection. The inhibition of ICE by CrmA is an example of a "cross-class" interaction, in which a serpin inhibits a non-serine proteinase. Since CrmA possesses characteristics shared by inhibitors of serine proteinases, we presume that ICE, though it is a cysteine proteinase, has a substrate binding geometry strikingly close to that of serine proteinases. We reason that it is the substrate binding geometry, not the catalytic mechanism of a proteinase, that dictates its reactivity with protein inhibitors.
The Google file system (2003)

article Share on The Google file system Authors: Sanjay Ghemawat Google GoogleView Profile , Howard Gobioff Google GoogleView Profile , Shun-Tak Leung Google GoogleView Profile Authors Info & Claims ACM SIGOPS Operating Systems ReviewVolume 37Issue 5December 2003 pp 29–43https://doi.org/10.1145/1165389.945450Online:19 October 2003Publication History 2,957citation60,150DownloadsMetricsTotal Citations2,957Total Downloads60,150Last 12 Months3,038Last 6 weeks280 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Cell-extracellular matrix interactions regulate neural differentiation of human embryonic stem cells (2008)

We defined laminin as a key ECM molecule to enhance neural progenitor generation, expansion and differentiation into neurons from hESCs. The cell-laminin interactions involve alpha6beta1 integrin receptors implicating a possible role of laminin/alpha6beta1 integrin signaling in directed neural differentiation of hESCs. Since laminin acts in concert with other ECM molecules in vivo, evaluating cellular responses to the composition of the ECM is essential to clarify further the role of cell-matrix interactions in neural derivation of hESCs.
A Porcine Burn Model (2003)

Not only are burns a leading cause of accidental death, but they also result in considerable morbidity and disfigurement leading to significant functional and social impairment. Fortunately, most burns are minor and relatively small. As a result, research efforts have largely focused on the local care of burn wounds. Because of moral and ethical considerations, the use of human skin for in vivo experiments is limited. Over the years researchers have used a variety of animal models as well as in vitro preparations to study cutaneous burns. We have developed and validated a porcine model for partial-thickness contact burns, using it to successfully evaluate a variety of therapeutic agents (). This chapter describes in detail the model for assessing burn therapies.
Feulgen DNA content and mitotic activity in proliferative breast disease. A comparison with ductal carcinoma in situ (1987)

Nuclear Feulgen DNA content was measured by cytophotometry and the number of mitoses per 40 high power fields was determined in hyperplastic and atypical hyperplastic lesions of fibrocystic disease in 18 patients, in ductal carcinoma in situ in 14 patients and in ductal carcinoma in situ associated with infiltrating carcinoma in 11 patients. These parameters were also investigated in the hyperplastic lesions accompanying ductal carcinoma in situ and ductal carcinoma in situ associated with infiltrating carcinoma. The nuclear Feulgen DNA content could not discriminate between atypical hyperplasia and ductal carcinoma in situ. Although differences in the mitotic count between hyperplastic and atypical breast lesions were not statistically significant, there was a statistically significant greater mitotic count in ductal carcinoma in situ alone or associated with infiltrating carcinoma. These findings suggest that the mitotic count is useful for the differential diagnosis between atypical hyperplasia and ductal carcinoma in situ. In addition, hyperplastic lesions associated with ductal carcinoma in situ, with or without infiltrating carcinoma, exhibited a statistically significant higher mitotic count than those in benign fibrocystic disease. Hyperplastic breast lesions exhibiting high mitotic counts may indicate the presence of a neighbouring ductal malignancy and suggest an increased proliferative activity in breast tissue in the neighbourhood of malignancy.
Modeling Lung Cancer Risk in Case-Control Studies Using a New Dose Metric of Smoking (2005)

Many approaches have been taken to adjust for smoking in modeling cancer risk. In case-control studies, these metrics are often used arbitrarily rather than being based on the properties of the metric in the context of the study. Depending on the underlying study design, hypotheses, and base population, different metrics may be deemed most appropriate. We present our approach to evaluating different smoking metrics. We examine the properties of a new metric, "logcig-years", that we initially derived from using a biological model of DNA adduct formation. We compare this metric to three other smoking metrics, namely pack-years, square-root pack-years, and a model in which smoking duration and intensity are separate variables. Our comparisons use generalized additive models and logistic regression to examine the relationship between the logit probability of cancer and each of the metrics, adjusting for other covariates. All models were fit using data from a lung cancer study of 1,275 cases and 1,269 controls that has focused on gene-smoking relationships. There was a very significant, linear relationship between logcig-years and the logit probability of lung cancer in this sample, without any need to adjust for smoking status. These properties together were not shared by the other metrics. In this sample, logcig-years captured more information about smoking that is important in lung cancer risk than the other metrics. In conclusion, we provide a general framework for evaluating different smoking metrics in studies where smoking is a critical variable.
Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines (2004)

The NOTCH ligand, JAG2, was found to be overexpressed in malignant plasma cells from multiple myeloma (MM) patients and cell lines but not in nonmalignant plasma cells from tonsils, bone marrow from healthy individuals, or patients with other malignancies. In addition, JAG2 overexpression was detected in 5 of 5 patients with monoclonal gammopathy of undetermined significance (MGUS), an early phase of myeloma disease progression. This overexpression appears to be a consequence of hypomethylation of the JAG2 promoter in malignant plasma cells. An in vitro coculture assay was used to demonstrate that JAG2 induced the secretion of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) in stromal cells. Further, the induction of IL-6 secretion was blocked in vitro by interference with anti-Notch-1 monoclonal antibodies raised against the binding sequence of Notch-1 with JAG2. Taken together, these results indicate that JAG2 overexpression may be an early event in the pathogenesis of multiple myeloma involving IL-6 production.
A video technique for phakometry of the human crystalline lens. (1992)

Accurate measurement of the dioptric power of the human crystalline lens is important in any study of ocular development and refractive error. Previous studies have used comparison ophthalmophakometry, measuring crystalline lens curvature and power from still flash photographs of Purkinje images I, III, and IV. This report presents a video-based technique for in vivo measurement of crystalline lens power suitable for use with children. The repeatability and validity of this video system were evaluated in comparison to a still photograph system through the measurement of anterior and posterior lens curvatures of 40 normal adults. The video system's repeatability (95% limits of agreement) was +/- 0.52 diopters for the anterior lens power, +/- 0.73 D for the posterior lens power, and +/- 0.88 D for the total lens power. The repeatability of the still flash photography system was +/- 0.78 D for the anterior, +/- 1.43 D for the posterior, and +/- 1.84 D for the lens power as a whole. An indirect method of calculating lens power using other ocular component measures gave a repeatability of +/- 1.78 D. The validity of the video system was improved by having the camera and the light source closer to the optic axis of the eye. The bias induced by having a more off-axis configuration (40 degrees separation between camera and light source) was a +0.10 D overestimation of surface power for the anterior and +0.73 D for the posterior lens surface power compared to a more coaxial arrangement (20 degrees between camera and light source). The use of video phakometry improved the repeatability and the validity of lens curvature measures relative to still flash photograph comparison ophthalmophakometry and to an indirect method of calculating lens power. This was achieved through the system's ability to analyze multiple frames, the use of a collimated light source, and the placement of the light source for the Purkinje images closer to the eye's optic axis.
New Insights on CO2−Methane Separation Using LTA Zeolites with Different Si/Al Ratios and a First Comparison with MOFs (2009)

LTA zeolites can be synthesized with tailored adsorption properties by controlling the Al content in the framework. In this work, we have demonstrated that it is possible to adjust the polarity of the zeolitic adsorbent to optimize its thermodynamic adsorption properties for the energetically relevant CO(2)/CH(4) separation process. The thermodynamic study has been made from the corresponding adsorption isotherms of the pure gases carried out at different pressures and temperatures, as well as breakthrough separation experiments of CO(2)/CH(4) mixtures and the results were compared to those reported on MOFs. The separation values obtained allow us to conclude that LTA zeolites offer unique possibilities for CH(4) upgrading from natural gas.
Export and intercellular transfer of DNA via membrane blebs of Neisseria gonorrhoeae (1989)

Naturally elaborated membrane bleb material is frequently observed in cultures of Neisseria gonorrhoeae. This material was purified and analyzed for protein, lipopolysaccharide, and nucleic acid content. The electrophoretic protein profiles of two bleb-rich fractions, called BI and BII, were distinct, with only BII containing lipopolysaccharide and outer membrane proteins I and III. Both fractions contained RNA, circular DNA, and linear DNA. Exogenous pancreatic DNase I appeared to hydrolyze all bleb-associated DNA in fraction BI and the linear DNA in fraction BII. The circular DNA molecules associated with fraction BII resisted digestion. Electron microscopy of the bleb fractions verified their DNA content. Fixing blebs with glutaraldehyde before mounting them for microscopy prevented release of internal DNA. Such fixation produced little change in the micrographs of BI; however, only traces of DNA were observed in fixed BII preparations. Incubation of wild-type gonococci in mixtures of DNase and blebs purified from antibiotic-resistant strains resulted in efficient exchange of penicillinase-specifying R plasmids. Recipients incorporated plasmids independently of endogenous and exogenous chromosomal streptomycin resistance markers. These in vitro results suggest that bleb formation by N. gonorrhoeae may serve to transfer plasmids intercellularly in vivo, perhaps constituting a previously unexplored genetic exchange mechanism in these bacteria.
Self-Assembled Lipid−Polymer Hybrid Nanoparticles: A Robust Drug Delivery Platform (2008)

We report the engineering of a novel lipid-polymer hybrid nanoparticle (NP) as a robust drug delivery platform, with high drug encapsulation yield, tunable and sustained drug release profile, excellent serum stability, and potential for differential targeting of cells or tissues. The NP comprises three distinct functional components: (i) a hydrophobic polymeric core where poorly water-soluble drugs can be encapsulated; (ii) a hydrophilic polymeric shell with antibiofouling properties to enhance NP stability and systemic circulation half-life; and (iii) a lipid monolayer at the interface of the core and the shell that acts as a molecular fence to promote drug retention inside the polymeric core, thereby enhancing drug encapsulation efficiency, increasing drug loading yield, and controlling drug release. The NP is prepared by self-assembly through a single-step nanoprecipitation method in a reproducible and predictable manner, making it potentially suitable for scale-up.
Identification and characterization of photomedins: novel olfactomedin-domain-containing proteins with chondroitin sulphate-E-binding activity (2005)

We screened more than 60000 RIKEN mouse cDNAs for novel ECM (extracellular matrix) proteins by extensive computational screening followed by recombinant expression and immunohistochemical characterization. We identified two novel olfactomedin-family proteins characterized by the presence of tandem CXCXCX9C motifs in the N-terminal region, a coiled-coil domain and an olfactomedin domain in the C-terminal region. These proteins, named photomedin-1 and photomedin-2, were secreted as disulphide-bonded dimers (photomedin-1) or oligomers/multimers (photomedin-2) with O-linked carbohydrate chains, although photomedin-1 was proteolytically processed in the middle of the molecule after secretion. In the retina, photomedin-1 was selectively expressed in the outer segment of photoreceptor cells and photomedin-2 was expressed in all retinal neurons. Among a panel of ECM components, including glycosaminoglycans, photomedins preferentially bound to chondroitin sulphate-E and heparin. These results, together, indicate that photomedins are novel olfactomedin-domain-containing extracellular proteins capable of binding to proteoglycans containing these glycosaminoglycan chains.
A new pixel circuit for active matrix organic light emitting diodes (2002)

We propose a new thin-film-transistor (TFT) pixel circuit for active-matrix organic light-emitting diode (AMOLED) composed of four TFTs and two capacitors. The simulation results, based on the device performances measured for an OLED and a poly-Si TFT, indicate that the proposed circuit has high immunity to the variation of poly-Si TFT characteristics.
Discriminative subvolume search for efficient action detection (2009)

Actions are spatio-temporal patterns which can be characterized by collections of spatio-temporal invariant features. Detection of actions is to find the re-occurrences (e.g. through pattern matching) of such spatio-temporal patterns. This paper addresses two critical issues in pattern matching-based action detection: (1) efficiency of pattern search in 3D videos and (2) tolerance of intra-pattern variations of actions. Our contributions are two-fold. First, we propose a discriminative pattern matching called naive-Bayes based mutual information maximization (NBMIM) for multi-class action categorization. It improves the state-of-the-art results on standard KTH dataset. Second, a novel search algorithm is proposed to locate the optimal subvolume in the 3D video space for efficient action detection. Our method is purely data-driven and does not rely on object detection, tracking or background subtraction. It can well handle the intra-pattern variations of actions such as scale and speed variations, and is insensitive to dynamic and clutter backgrounds and even partial occlusions. The experiments on versatile datasets including KTH and CMU action datasets demonstrate the effectiveness and efficiency of our method.
Discovery of 4-{4-[3-(Pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388):  A Potent, Selective, and Orally Active Transforming Growth Factor-β Type I Receptor Inhibitor (2006)

Inhibitors of transforming growth factor beta (TGF-beta) type I receptor (ALK5) offer a novel approach for the treatment of fibrotic diseases such as renal, hepatic, and pulmonary fibrosis. The optimization of a novel phenylpyridine pyrazole series (1a) led to the identification of potent, selective, and orally active ALK5 inhibitors. The cellular potency and pharmacokinetics profiles of these derivatives were improved and several compounds presented antifibrotic activity when orally administered to rats in an acute liver model of dimethylnitrosamine- (DMN-) induced expression of collagen IA1 mRNA, a major gene contributing to excessive extra cellular matrix deposit. One of the most potent ALK5 inhibitors identified in this chemical series, compound 13d (GW788388), reduced the expression of collagen IA1 by 80% at a dose of 1 mg/kg twice a day (b.i.d.). This compound significantly reduced the expression of collagen IA1 mRNA when administered orally at 10 mg/kg once a day (u.i.d.) in a model of puromycin aminonucleoside-induced renal fibrosis.
Interactive sound rendering (2009)

Extending the frontier of visual computing, sound rendering utilizes auditory display to communicate information to a user and offers an alternative means of visualization. By harnessing the sense of hearing, sound rendering can further enhance a user's experience in a multimodal virtual world. In addition to immersive environments, auditory displays can provide a natural and intuitive human-computer interface for many desktop applications. In this paper, we give a brief overview of recent work at UNC Chapel Hill on fast algorithms for sound synthesis and sound propagation. These include physically-based sound synthesis for rigid bodies and liquid sound generation, as well as numeric and geometric algorithms for sound propagation. We highlight their performance on different benchmarks and briefly discuss some problems for future research.
Inhibition of a protein‐protein interaction between INI1 and c‐Myc by small peptidomimetic molecules inspired by Helix‐1 of c‐Myc: identification of a new target of potential antineoplastic interest (2007)

c-Myc is a transcription modulator proto-oncogene. When overexpressed, it becomes an important contributor to the multi-hit process of malignant transformation. In two earlier papers in this journal (see refs. 19 , 20) we reported that retro-inverso peptidomimetic molecules inspired by the Helix-1 of c-Myc motif could be sequence-specific antiproliferative agents active in the low micromolar range. We also found that our peptides were not opening the four-alpha-helix Myc:Max bundle. Their antiproliferative activity in cancer cell lines needs the presence of side chains projecting outside of the bundle in the corresponding native H1 motif. This observation suggested interference with an external partner. In this study we investigated the INI1:Myc interaction. INI1 is a subunit of the SWI/SNF complex (component of the enhanceosome surrounding Myc:Max heterodimer). The INI1:Myc interaction was confirmed via pull down, ELISA, and fluorescence anisotropy assays. According to the length of INI1 fragments used, we calculated Kds ranging between 1.3x10(-6) and 4.8x10(-7) M. The three different techniques applied showed that the INI1:Myc interaction was also the target of our retro-inverso peptidomimetic molecules, which seem to bind specifically at INI1. A Myc binding, 21aa INI1 fragment (minimum interacting sequence), could inspire the synthesis of a new class of more selective c-Myc inhibitors.
Role of trypsin-like cleavage at arginine 192 in the enzymatic and cytotonic activities of Escherichia coli heat-labile enterotoxin (1994)

Previous studies of cholera toxin and Escherichia coli heat-labile enterotoxin have suggested that proteolytic cleavage plays an important role in the expression of ADP-ribosyltransferase activity and toxicity. Specifically, several studies have implicated a trypsin-like cleavage at arginine 192, which lies within an exposed region subtended by a disulfide bond in the intact A subunit, in toxicity. To investigate the role of this modification in the enzymatic and cytotonic properties of heat-labile enterotoxin, the response of purified, recombinant A subunit to tryptic activation and the effect of substituting arginine 192 with glycine on the activities of the holotoxin were examined. The recombinant A subunit of heat-labile enterotoxin exhibited significant levels of ADP-ribosyltransferase activity that were only nominally increased (approximately twofold) by prior limited trypsinolysis. The enzymatic activity also did not appear to be affected by auto-ADP-ribosylation that occurs during the high-level synthesis of the recombinant A subunit in E. coli. A mutant form of the holotoxin containing the arginine 192-to-glycine substitution exhibited levels of cytotonic activity for CHO cells that were similar to that of the untreated, wild-type holotoxin but exhibited a marked delay in the ability to increase intracellular levels of cyclic AMP in Caco-2 cells. The results indicate that trypsin-like cleavage of the A subunit of E. coli heat-labile enterotoxin at arginine 192 is not requisite to the expression of enzymatic activity by the A subunit and further reveal that this modification, although it enhances the biological and enzymatic activities of the toxin, is not absolutely required for the enterotoxin to elicit cytotonic effects.
Primary and Secondary Central Nervous System Vasculitis (2012)

Central nervous system vasculitis is an increasingly recognized inflammatory brain disease causing devastating neurological deficits and psychiatric manifestations in previously healthy children. Primary central nervous system vasculitis represents an isolated inflammatory attack targeting the cerebral vessels. In contrast, in children with secondary central nervous system vasculitis, an underlying condition can be identified. The spectrum of childhood primary and secondary central nervous system vasculitis is rapidly expanding, as is the differential diagnosis including nonvasculitic inflammatory brain diseases and noninflammatory vasculopathies. Early recognition, rapid diagnostic evaluation, and initiation of treatment have led to improved morbidity and mortality. This review focuses on clinical, laboratory, and neuroimaging characteristics of the distinct subtypes of primary childhood central nervous system vasculitis, reports the etiology of secondary central nervous system vasculitis, provides an overview of the differential diagnosis, and reviews the current approaches in treatment.