gebhart/patrepeval huggingface dataset:
Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation. (1993)

Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320-Lys322 has been identified as a key binding motif for the first component of complement, C1q, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specific residues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in gamma 4 is critical for determining the inability of that isotype to bind C1q and activate complement. Additionally, we provide further evidence that levels of C1q binding do not necessarily correlate with levels of complement activity, and that C1q binding alone is not sufficient for complement activation.
Preparation and properties of high quality crystalline silicon films grown by ECR plasma deposition (2002)

A process for growing high quality epitaxial silicon on heavily doped silicon (100) wafers at temperatures below 525/spl deg/C has been developed using a high vacuum electron cyclotron resonance (ECR) plasma deposition system. Plasma diagnostic work was done in order to optimize the growth conditions. The crystalline quality of our films has been verified using TEM, Raman and UV reflectance. Spreading resistance profiles (SRP) indicate that our undoped films are n-type with free carrier concentrations between 3/spl times/10/sup 16/ cm/sup -3/ and 3/spl times/10/sup 17/ cm/sup -3/. The junction between the heavily doped wafer and the undoped epi layer is shown to be abrupt. The mobilities of the carriers were measured using Hall measurements, and were found to be as high as in the best crystalline materials. This new technique may have significant applications for low cost Si solar cells.
Semantic Compositional Networks for Visual Captioning (2017)

A Semantic Compositional Network (SCN) is developed for image captioning, in which semantic concepts (i.e., tags) are detected from the image, and the probability of each tag is used to compose the parameters in a long short-term memory (LSTM) network. The SCN extends each weight matrix of the LSTM to an ensemble of tag-dependent weight matrices. The degree to which each member of the ensemble is used to generate an image caption is tied to the image-dependent probability of the corresponding tag. In addition to captioning images, we also extend the SCN to generate captions for video clips. We qualitatively analyze semantic composition in SCNs, and quantitatively evaluate the algorithm on three benchmark datasets: COCO, Flickr30k, and Youtube2Text. Experimental results show that the proposed method significantly outperforms prior state-of-the-art approaches, across multiple evaluation metrics.
Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway (2004)

Nonalcoholic fatty liver disease (NAFLD) is a serious health problem. Although NAFLD represents a form of lipotoxicity, its pathogenesis remains poorly understood. The aim of this study was to examine the cellular mechanisms involved in free fatty acid (FFA)-mediated hepatic lipotoxicity. FFA treatment of liver cells resulted in Bax translocation to lysosomes and lysosomal destabilization with release of cathepsin B (ctsb), a lysosomal cysteine protease, into the cytosol. This process was also partially dependent on ctsb. Lysosomal destabilization resulted in nuclear factor kappa B-dependent tumor necrosis factor alpha expression. Release of ctsb into the cytoplasm was also observed in humans with NAFLD and correlated with disease severity. In a dietary murine model of NAFLD, either genetic or pharmacological inactivation of ctsb protected against development of hepatic steatosis, liver injury, and insulin resistance with its associated "dysmetabolic syndrome." In conclusion, these data support a lipotoxic model of FFA-mediated lysosomal destabilization.
A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens (2011)

Bispecific antibodies based on full-length antibody structures are more optimal than fragment-based formats because they benefit from the favorable properties of the Fc region. However, the homodimeric nature of Fc effectively imposes bivalent binding on all current full-length bispecific antibodies, an attribute that can result in nonspecific activation of cross-linked receptors. We engineered a novel bispecific format, referred to as mAb-Fv, that utilizes a heterodimeric Fc region to enable monovalent co-engagement of a second target antigen in a full-length context. mAb-Fv constructs co-targeting CD16 and CD3 were expressed and purified as heterodimeric species, bound selectively to their co-target antigens, and mediated potent cytotoxic activity by NK cells and T cells, respectively. The capacity to co-engage distinct target antigens simultaneously with different valencies is an improved feature for bispecific antibodies with promising therapeutic implications.
The analysis of high explosives by liquid chromatography/electrospray ionization mass spectrometry: multiplexed detection of negative ion adducts (2004)

The negative ion electrospray ionization mass spectrometric (ESI-MS) detection of adducts of high explosives with chloride, formate, acetate, and nitrate was used to demonstrate the gas-phase interaction of neutral explosives with these anions. The relative intensities of the adduct species were determined to compare the competitive formation of the selected high explosives and anions. The relative stability of the adduct species varies, yielding preferential formation of certain anionic adducts with different high explosives. To exploit this effect, an isocratic high-performance liquid chromatography (HPLC)/ESI-MS method was developed and used for the simultaneous analysis of high explosives using two different techniques for the addition of the anionic additives; pre- and post-column. The results show that the pre-column approach provides similar results with improved selectivity for specific explosives. By detecting characteristic adduct species for each explosive, this method provides a qualitative and quantitative approach for the analysis and identification of high explosives.
ATPase Activity of p97/Valosin-containing Protein Is Regulated by Oxidative Modification of the Evolutionally Conserved Cysteine 522 Residue in Walker A Motif (2005)

Valosin-containing protein (p97/VCP) has been proposed as playing crucial roles in a variety of physiological and pathological processes such as cancer and neurodegeneration. We previously showed that VCP(K524A), an ATPase activity-negative VCP mutant, induced vacuolization, accumulation of ubiquitinated proteins, and cell death, phenotypes commonly observed in neurodegenerative disorders. However, any regulatory mechanism of its ATPase activity has not yet been clarified. Here, we show that oxidative stress readily inactivates VCP ATPase activity. With liquid chromatography/tandem mass spectrometry, we found that at least three cysteine residues were modified by oxidative stress. Of them, the 522nd cysteine (Cys-522) was identified as the site responsible for the oxidative inactivation of VCP. VCP(C522T), a single-amino acid substitution mutant from cysteine to threonine, conferred almost complete resistance to the oxidative inactivation. In response to oxidative stress, VCP strengthened the interaction with Npl4 and Ufd1, both of which are essential in endoplasmic reticulum-associated protein degradation. Cys-522 is located in the second ATP binding motif and is highly conserved in multicellular but not unicellular organisms. Cdc48p (yeast VCP) has threonine in the corresponding amino acid, and it showed resistance to the oxidative inactivation in vitro. Furthermore, a yeast mutant (delta cdc48 + cdc48[T532C]) was shown to be susceptible to oxidants-induced growth inhibition and cell death. These results clearly demonstrate that VCP ATPase activity is regulated by the oxidative modification of the Cys-522 residue. This regulatory mechanism may play a key role in the conversion of oxidative stress to endoplasmic reticulum stress response in multicellular organisms and also in the pathological process of various neurodegenerative disorders.
From lung images to lung models: A review (2008)

Automated 3D lung modeling involves analyzing 2D lung images and reconstructing a realistic 3D model of the lung. This paper presents a review of the existing works on automatic formation of 3D lung models from 2D lung images. A common framework for 3D lung modeling is proposed. It consists of eight components: image acquisition, image pre-processing, image segmentation, boundary creation, image recognition, image registration, 3D surface reconstruction, and 3D rendering and visualization. The algorithms used by the existing systems to implement these components are also reviewed.
A Novel Neutralizing Antibody Targeting Pregnancy-Associated Plasma Protein-A Inhibits Ovarian Cancer Growth and Ascites Accumulation in Patient Mouse Tumorgrafts (2015)

The majority of ovarian cancer patients acquire resistance to standard platinum chemotherapy and novel therapies to reduce tumor burden and ascites accumulation are needed. Pregnancy-associated plasma protein-A (PAPP-A) plays a key role in promoting insulin-like growth factor (IGF) pathway activity, which directly correlates to ovarian cancer cell transformation, growth, and invasiveness. Herein, we evaluate PAPP-A expression in tumors and ascites of women with ovarian cancer, and determine the antitumor efficacy of a neutralizing monoclonal PAPP-A antibody (mAb-PA) in ovarian cancer using primary patient ovarian tumorgrafts ("Ovatars"). PAPP-A mRNA expression in patient ovarian tumors correlated with poor outcome and was validated as a prognostic surrogate in Ovatar tumors. Following confirmation of mAb-PA bioavailability and target efficacy in vivo, the antitumor efficacy of mAb-PA in multiple Ovatar tumor models was examined and the response was found to depend on PAPP-A expression. Strikingly, the addition of mAb-PA to standard platinum chemotherapy effectively sensitized platinum-resistant Ovatar tumors. PAPP-A protein in ascites was also assessed in a large cohort of patients and very high levels were evident across the entire sample set. Therefore, we evaluated targeted PAPP-A inhibition as a novel approach to managing ovarian ascites, and found that mAb-PA inhibited the development, attenuated the progression, and induced the regression of Ovatar ascites. Together, these data indicate PAPP-A as a potential palliative and adjunct therapeutic target for women with ovarian cancer.
Toward Reliable Values of Electrochemical Stability Limits for Electrolytes (1999)

We scrutinized the conventional practice of measuring an electrolyte stability window. It is shown that misleading values might be generated by this practice. Thus, we recommend that to obtain a real stability window, the working electrode material should simulate the electrodes used in a real device. Further, in applications that have a high‐surface‐area electrode, a new quantification of a stability window is proposed. The electrochemical stability values of various nonaqueous electrolytes that are derived this way should reflect the actual operation limits of these electrolytes in real‐life devices. © 1999 The Electrochemical Society. All rights reserved.
Surface Loop 199–204 in Blood Coagulation Factor IX Is a Cofactor-dependent Site Involved in Macromolecular Substrate Interaction (1999)

In factor IX residues 199-204 encompass one of six surface loops bordering its substrate-binding groove. To investigate the contribution of this loop to human factor IX function, a series of chimeric factor IX variants was constructed, in which residues 199-204 were replaced by the corresponding sequence of factor VII, factor X, or prothrombin. The immunopurified and activated chimeras were indistinguishable from normal factor IXa in hydrolyzing a small synthetic substrate, indicating that this region is not involved in the interaction with substrate residues on the N-terminal side of the scissile bond. In contrast, replacement of loop 199-204 resulted in a 5-25-fold reduction in reactivity toward the macromolecular substrate factor X. This reduction was due to a combination of increased K(m) and reduced k(cat). In the presence of factor VIIIa the impaired reactivity toward factor X was largely restored for all factor IXa variants, resulting in a more pronounced stimulation by factor VIIIa compared with normal factor IXa (3 to 5 x 10(4)-fold versus 5 x 10(3)-fold). Inhibition by antithrombin was only slightly affected for the factor IXa variant with the prothrombin loop sequence, whereas factor IXa variants containing the analogous residues of factor VII or factor X were virtually insensitive to antithrombin inhibition. In the presence of heparin, however, all chimeric factor IXa variants formed complexes with antithrombin. Thus the cofactors heparin and factor VIIIa have in common that they both alleviate the deleterious effects of mutations in the factor IX loop 199-204. Collectively, our data demonstrate that loop 199-204 plays an important role in the interaction of factor IXa with macromolecular substrates.
Src family kinase activity is required for Kit-mediated mitogen-activated protein (MAP) kinase activation, however loss of functional retinoblastoma protein makes MAP kinase activation unnecessary for growth of small cell lung cancer cells. (2000)

Small cell lung cancer (SCLC) is characterized by multiple genetic alterations that include inactivation of the retinoblastoma protein (Rb), the establishment of several autocrine loops including that induced by coexpression of stem cell factor (SCF) and Kit, and the ectopic expression and activation of Src family kinases. Previous studies have shown that Lck associates with, and becomes activated by, Kit after SCF stimulation of SCLC cells. In the present study, we have demonstrated that PP1, a pharmacological inhibitor of Src kinases, blocked SCF-mediated activation of mitogen-activated protein (MAP) kinase, but it also inhibited Kit activation. However, MAP kinase activation was more sensitive than Kit activation to the effects of PP1. Overexpression of Lck reduced the sensitivity of MAP kinase activation to PP1 without altering the sensitivity of Kit activation, which suggested a role for Lck in SCF-mediated MAP kinase activation. Inducible expression of a dominant negative Lck inhibited MAP kinase activation in a dose-dependent manner, which confirmed that Src family kinase activity is required for SCF-induced MAP kinase activation. The growth of cells that expressed dominant negative Lck was unaffected, however, despite the inhibition of MAP kinase. Growth was also unaffected by the inhibition of the MAP kinase pathway using PD 98059, but sensitivity to the MAP/extracellular signal-regulated kinase kinase inhibitor could be partially restored by expression of wild-type Rb. Therefore, MAP kinase activation seems to be dispensable for the growth of SCLC only in the absence of Rb expression. These data suggest that the SCF/Kit autocrine loop, through activation of Lck and subsequently MAP kinase, and the mutational inactivation of Rb contribute to the loss of G1-S phase checkpoint regulation during the pathogenesis of SCLC. Furthermore, the data demonstrate that, in established SCLC cell lines, proliferative signal transduction initiated by Kit is mediated by pathways other than the classic MAP kinase pathway.
Personality and charismatic leadership (1992)

In this paper we review prior theory and empirical evidence relevant to the personality characteristics that differentiate charismatic leaders from noncharismatic leaders. We conclude from this review that charismatic leaders in present day complex organizations fit the stereotypical image of supportive, sensitive, nurturing, and considerate leaders such as Mahatma Gandhi or Nelson Mandela, rather than the traditional stereotype of aggressive, demanding, dominant and critical leaders such as Jim Jones or Field Marshall George Montgomery. We then present a review of research relevant to four traits that theoretically differentiate personalized (self-aggrandizing, non-egalitarian, and exploitive) charismatic leaders from socialized (collectively oriented, egalitarian, and nonexploitive) charismatic leaders. We conclude that the personality traits of the need for power, power inhibition, Machiavellianism, authoritarianism, narcissism, self esteem and locus of control are traits that are likely to differentiate personalized from socialized charismatic leaders.
Probabilistic latent semantic indexing (1999)

Probabilistic Latent Semantic Indexing is a novel approach to automated document indexing which is based on a statistical latent class model for factor analysis of count data. Fitted from a training corpus of text documents by a generalization of the Expectation Maximization algorithm, the utilized model is able to deal with domain speci c synonymy as well as with polysemous words. In contrast to standard Latent Semantic Indexing LSI by Singular Value Decomposition, the probabilistic variant has a solid statistical foundation and de nes a proper generative data model. Retrieval experiments on a number of test collections indicate substantial performance gains over direct term matching metho d s a s w ell as over LSI. In particular, the combination of models with di erent dimensionalities has proven to be advantageous.
Implications of technology scaling on leakage reduction techniques (2004)

The impact of technology scaling on three run-time leakage reduction techniques (Input Vector Control, Body Bias Control and Power Supply Gating) is evaluated by determining limits and benefits, in terms of the potential leakage reduction, performance penalty, and area and power overhead in 0.25um, 0.18um, and 0.07um technologies. HSPICE simulation results and estimations with various functional units and memory structures are presented to support a comprehensive analysis.
Effects of Abatacept in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis (2006)

Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.
The delta-opioid receptor: isolation of a cDNA by expression cloning and pharmacological characterization. (1992)

A random primed expression cDNA library was constructed from the RNA of NG 108-15 cells. Pools of plasmid DNA were transfected into COS cells, which were screened for their ability to bind 3H-labeled Tyr-D-Thr-Gly-Phe-Leu-Thr, a tritiated agonist for the delta-opioid receptor. A cDNA was isolated that encodes a 371-amino acid-residue protein presenting all the structural characteristics of receptors that interact with guanine nucleotide-binding proteins. Noticeable features are (i) the high hydrophobicity of the encoded protein, (ii) its low sequence similarity to both catecholamine receptors and peptide-binding receptors, although it presents the typical aspartate residue involved in catecholamine binding of the first group and the characteristic short third cytoplasmic loop of the second group. When expressed in COS cells, the receptor exhibits pharmacological properties similar to those of the native receptor: high-affinity binding sites for 3H-labeled Tyr-D-Thr-Gly-Phe-Leu-Thr (Kd = 1.4 nM), stereospecific binding sites for the - enantiomers of levorphanol and naloxone, and the selectivity profile of a delta receptor, as determined by competition experiments with a set of mu-, delta-, and kappa-opioid ligands.
Evaluating the Environmental Implications of Hydraulic Fracturing in Shale Gas Reservoirs (2009)

Abstract Exploration, drilling and production of shale gas plays such as the Barnett, Fayetteville, and Haynesville have transformed the unconventional gas industry. These and other existing and developing plays have had unimaginable economic impacts to many regions, created tens of thousands of jobs, and have generated royalty payments to a variety of state and local governments as well as many individuals. At the core of shale gas development are two key technologies: horizontal drilling and hydraulic fracturing. Techniques used to hydraulically fracture horizontal wells completed in shale reservoirs often require larger volumes of fracturing fluid than might be common for conventional, vertical well stimulations. The rapid development of shale gas across the country has created concerns on issues such as the use of infrastructure and environmental impacts. Specifically, the common practice of hydraulic fracturing of these shales has attracted critical interest regarding risks potentially posed to groundwater and surface water. This paper will present a summary and evaluation of the environmental implications of hydraulic fracturing in shale gas reservoirs, with examples from multiple basins. Introduction Natural gas production from tight shale formations, known as "shale gas", is one of the most rapidly expanding trends in onshore, domestic natural gas exploration and production. In some areas, development of shale gas resources is bringing drilling and production to regions of the country that has previously seen little to no oil and gas development activity. In plays like the Barnett Shale of Texas, development is occurring in urban and suburban areas where both operators and regulators are adapting to this new environment. Shales are the most abundant sedimentary rock in the Earth's crust and are present across the U.S. (Figure 1). Shales have been sources of natural gas in small but continuous volumes since the earliest years of gas development. The first producing gas well in the U.S. was completed in 1821 in Devonian-aged shale near the town of Fredonia, New York (Harper, 2008). Early sources of natural gas were shallow gas wells that were from dug wells and natural gas seeps (NY DEC, 1992). Shallow wells and seeps were capable of producing small amounts of natural gas which were used for illuminating city streets and households (Frantz and Jochen, 2005). These early gas wells played a key part in bringing illumination to the cities and towns of the eastern U.S. (Harper, 2008). In contrast, modern shale gas development has become a technological play, in which development is facilitated by the technological advances the oil and gas industry has made in hydraulic fracturing and horizontal drilling over the last two decades.
Exposure to Nonhuman Primates in Rural Cameroon (2004)

Exposure to nonhuman primates has led to the emergence of important diseases, including Ebola hemorrhagic fever, AIDS, and adult T-cell leukemia. To determine the extent of exposure to nonhuman primates, persons were examined in 17 remote villages in Cameroon that represented three habitats (savanna, gallery forest, and lowland forest). Questionnaire data were collected to assess whether persons kept wild animal pets; hunted and butchered wild game; had experienced bites, scratches, or injuries from live animals; or had been injured during hunting or butchering. While all villages had substantial exposure to nonhuman primates, higher rates of exposure were seen in lowland forest sites. The study demonstrates that exposure is not limited to small groups of hunters. A high percentage of rural villagers report exposure to nonhuman primate blood and body fluids and risk acquiring infectious diseases.