gebhart/patrepeval huggingface dataset:
Monoclonal antibodies in acute lymphoblastic leukemia (2015)

With modern intensive combination polychemotherapy, the complete response (CR) rate in adults with acute lymphoblastic leukemia (ALL) is 80% to 90%, and the cure rate is 40% to 50%. Hence, there is a need to develop effective salvage therapies and combine novel agents with standard effective chemotherapy. ALL leukemic cells express several surface antigens amenable to target therapies, including CD20, CD22, and CD19. Monoclonal antibodies target these leukemic surface antigens selectively and minimize off-target toxicity. When added to frontline chemotherapy, rituximab, an antibody directed against CD20, increases cure rates of adults with Burkitt leukemia from 40% to 80% and those with pre-B ALL from 35% to 50%. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has resulted in marrow CR rates of 55% and a median survival of 6 to 7 months when given to patients with refractory-relapsed ALL. Blinatumomab, a biallelic T cell engaging the CD3-CD19 monoclonal antibody, also resulted in overall response rates of 40% to 50% and a median survival of 6.5 months in a similar refractory-relapsed population. Other promising monoclonal antibodies targeting CD20 (ofatumumab and obinutuzumab) or CD19 or CD20 and bound to different cytotoxins or immunotoxins are under development. Combined modalities of chemotherapy and the novel monoclonal antibodies are under investigation.
Deoxyribonucleoside Kinases Activate Nucleoside Antibiotics in Severely Pathogenic Bacteria (2007)

Common bacterial pathogens are becoming progressively more resistant to traditional antibiotics, representing a major public-health crisis. Therefore, there is a need for a variety of antibiotics with alternative modes of action. In our study, several nucleoside analogs were tested against pathogenic staphylococci and streptococci. We show that pyrimidine-based nucleoside analogs, like 3'-azido-3'-deoxythymidine (AZT) and 2',2'-difluoro-2'deoxycytidine (gemcitabine), are specifically activated by the endogenous bacterial deoxyribonucleoside kinases, leading to cell death. Deoxyribonucleoside kinase-deficient Escherichia coli strains become highly susceptible to nucleoside analogs when they express recombinant kinases from Staphylococcus aureus or Streptococcus pyogenes. We further demonstrate that recombinant S. aureus deoxyadenosine kinase efficiently phosphorylates the anticancer drug gemcitabine in vitro and is therefore the key enzyme in the activation pathway. When adult mice were infected intraperitoneally with a fatal dose of S. pyogenes strain AP1 and afterwards received gemcitabine, they failed to develop a systemic infection. Nucleoside analogs may therefore represent a promising alternative for combating pathogenic bacteria.
An analysis of statistical models and features for reading difficulty prediction (2008)

A reading difficulty measure can be described as a function or model that maps a text to a numerical value corresponding to a difficulty or grade level. We describe a measure of readability that uses a combination of lexical features and grammatical features that are derived from subtrees of syntactic parses. We also tested statistical models for nominal, ordinal, and interval scales of measurement. The results indicate that a model for ordinal regression, such as the proportional odds model, using a combination of grammatical and lexical features is most effective at predicting reading difficulty.
PATTERN RECOGNITION APPLIED TO COUGH CATEGORIZATION (1967)

Abstract : The particular problem with which the research was concerned was the development of a technique to discriminate between coughs and other audible phenomena which originate in a hospital environment. Pattern recognition provided such a technique. Experimental data was available in the form of audio tape recordings. Implementation of a Bayes categorization decision requires knowledge of the underlying conditional joint probability density functions of the measures which typify the patterns to be recognized. An adaptive pattern classifier model was presented which circumvented the difficulty of estimating these functions. The model is generally applicable to the two-class case in which the patterns to be classified consist of sequential segments of data known to have originated from the same class. The model took the form of a layered machine. The first stage was a minimum distance classifier with respect to point sets while the second stage utilized the first stage binary valued outputs to implement a Bayes decision. The feature extraction and measure selection problems were examined experimentally. Feature calculation algorithms were developed which are generally applicable to time varying signals. The effectiveness of an algorithm for selection of a set of candidate measures was verified. Experimental results indicated that, for the particular data with which the research was concerned, an assumption of Markoff-1 dependency between sequential first stage decisions of the pattern classifier was warranted. A pattern classifier which was based on this assumption classified 97.9% of the patterns presented to its input correctly.
Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47 (2010)

Under normal physiological conditions, cellular homeostasis is partly regulated by a balance of pro- and anti-phagocytic signals. CD47, which prevents cancer cell phagocytosis by the innate immune system, is highly expressed on several human cancers including acute myeloid leukemia, non-Hodgkin's lymphoma, and bladder cancer. Blocking CD47 with a monoclonal antibody results in phagocytosis of cancer cells and leads to in vivo tumor elimination, yet normal cells remain mostly unaffected. Thus, we postulated that cancer cells must also display a potent pro-phagocytic signal. Here, we identified calreticulin as a pro-phagocytic signal that was highly expressed on the surface of several human cancers, but was minimally expressed on most normal cells. Increased CD47 expression correlated with high amounts of calreticulin on cancer cells and was necessary for protection from calreticulin-mediated phagocytosis. Blocking the interaction of target cell calreticulin with its receptor, low-density lipoprotein receptor-related protein, on phagocytic cells prevented anti-CD47 antibody-mediated phagocytosis. Furthermore, increased calreticulin expression was an adverse prognostic factor in diverse tumors including neuroblastoma, bladder cancer, and non-Hodgkin's lymphoma. These findings identify calreticulin as the dominant pro-phagocytic signal on several human cancers, provide an explanation for the selective targeting of tumor cells by anti-CD47 antibody, and highlight the balance between pro- and anti-phagocytic signals in the immune evasion of cancer.
Conserved role for autophagy in Rho1-mediated cortical remodeling and blood cell recruitment (2010)

Dynamic regulation of cell shape underlies many developmental and immune functions. Cortical remodeling is achieved under the central control of Rho GTPase pathways that modulate an exquisite balance in the dynamic assembly and disassembly of the cytoskeleton and focal adhesions. Macroautophagy (autophagy), associated with bulk cytoplasmic remodeling through lysosomal degradation, has clearly defined roles in cell survival and death. Moreover, it is becoming apparent that proteins, organelles, and pathogens can be targeted for autophagic clearance by selective mechanisms, although the extent and roles of such degradation are unclear. Here we report a conserved role for autophagy specifically in the cortical remodeling of Drosophila blood cells (hemocytes) and mouse macrophages. Continuous autophagy was required for integrin-mediated hemocyte spreading and Rho1-induced cell protrusions. Consequently, hemocytes disrupted for autophagy were impaired in their recruitment to epidermal wounds. Cell spreading required ref(2)P, the Drosophila p62 multiadaptor, implicating selective autophagy as a novel mechanism for modulating cortical dynamics. These results illuminate a specific and conserved role for autophagy as a regulatory mechanism for cortical remodeling, with implications for immune cell function.
10 beta-propynyl-substituted steroids. Mechanism-based enzyme-activated irreversible inhibitors of estrogen biosynthesis. (1981)

A series of 10 beta-propynyl-substituted steroids are reported as mechanism-based enzyme-activated irreversible inhibitors of the human placental aromatase which converts 4-androstene-3,17-dione to 1,3,5(10-estratrien-3-ol-17-one. Thus 10-propargylestr-4-ene-3,17-dione binds to the enzyme with an apparent Ki of 23 nM and causes time-dependent inactivation (pseudo-first order kinact = 1.11 X 10(-3) s-1). The 10-[(1S)-1-hydroxy-3-propynyl]estr-4-ene-3,17-dione analog of the known enzyme-generated intermediate, 4-androsten-19-ol-3,17-dione, behaved similarly and had an apparent Ki of 27 microM and a psuedo-first order kinact of 2.91 X 10(-3) s-1. The stereoisomeric 10-[(1R)-1-hydroxy-2-propynyl]estr-4-ene-3,17-dione did not cause time-dependent inactivation, but bound in a competitive manner with an apparent Ki of 2.5 microM. Finally, 10-(1-oxo-2-propynyl)-estr-4-ene-3,17-dione, the proposed enzyme-generated affinity label and analog of the second intermediate (3,17-dioxoandrost-4-en-19-al) in the enzymatic reaction, bound to the enzyme with an apparent Ki of 12 microM and caused time-dependent inactivation with a pseudo-first order kinact of 5.35 X 10(-4) s-1.
Soluble Guanylate Cyclase Stimulation on Cardiovascular Remodeling in Angiotensin II–Induced Hypertensive Rats (2006)

It is unknown whether long-term pharmacological stimulation of soluble guanylate cyclase (sGC), elevating intracellular cGMP levels, has a beneficial effect on hypertension. The purpose of this study is to investigate the effects of BAY41-2272, an orally available sGC stimulator, on cardiovascular remodeling in hypertensive rats. Eight-week-old male Wistar rats with hypertension induced by angiotensin II infused subcutaneously at 250 ng/kg per minute were treated orally with a low ([L] 2 mg/kg per day) or high ([H] 10 mg/kg per day) dose of BAY41-2272 for 14 days. BAY41-2272-H partially suppressed the rise in blood pressure and reduced the heart weight (4.20+/-0.34 versus 3.68+/-0.20 mg/g; P<0.01), whereas BAY41-2272-L had no effect. However, both doses decreased the angiotensin II-induced left ventricular accumulation of collagen in the perivascular area (L, -20%, P<0.05; H, -30%, P<0.01) and myocardial interstitium (L, -21%, P<0.05; H, -38%, P<0.01), reducing the number of activated fibroblasts surrounding coronary arteries (L, -74%; H, -79%; P<0.05). BAY41-2272 downregulated the angiotensin II-induced left ventricular gene expression of type 1 collagen (L, -41%, P<0.05; H, -49%, P<0.01) and transforming growth factor-beta1 (L, -49%, P<0.05; H, -65%, P<0.01). cGMP levels were elevated by BAY41-2272 not only in the left ventricle, but also in cultured cardiac fibroblasts, resulting in reduced thymidine incorporation into the cells. Thus, stimulation of sGC by BAY41-2272 attenuates fibrosis of the left ventricle in rats with angiotensin II-induced hypertension partly in a pressure-independent manner, suggesting an important role for sGC generating cGMP in inhibiting cardiovascular remodeling.
ERRATA: "THz DETECTION BY RESONANT 2-D PLASMONS IN FIELD EFFECT DEVICES" (2002)

We demonstrate resonant detection of terahertz radiation by two-dimensional plasma waves in two field effect devices: a commercial field effect transistor (FET) and a double quantum well field effect transistor with a periodic grating gate. In both devices, the standing 2-D plasmon is tuned to the frequency of the THz radiation by varying the gate bias. The double quantum well field effect transistors exhibits a rich photoconductive response corresponding to spatial harmonics of the standing 2-D plasmons under the metal part of the periodic gate.
Accelerating the Super-Resolution Convolutional Neural Network (2016)

As a successful deep model applied in image super-resolution (SR), the Super-Resolution Convolutional Neural Network (SRCNN) has demonstrated superior performance to the previous hand-crafted models either in speed and restoration quality. However, the high computational cost still hinders it from practical usage that demands real-time performance (24 fps). In this paper, we aim at accelerating the current SRCNN, and propose a compact hourglass-shape CNN structure for faster and better SR. We re-design the SRCNN structure mainly in three aspects. First, we introduce a deconvolution layer at the end of the network, then the mapping is learned directly from the original low-resolution image (without interpolation) to the high-resolution one. Second, we reformulate the mapping layer by shrinking the input feature dimension before mapping and expanding back afterwards. Third, we adopt smaller filter sizes but more mapping layers. The proposed model achieves a speed up of more than 40 times with even superior restoration quality. Further, we present the parameter settings that can achieve real-time performance on a generic CPU while still maintaining good performance. A corresponding transfer strategy is also proposed for fast training and testing across different upscaling factors.
Marijuana Compounds: A Non-Conventional Therapeutic Approach to Epilepsy in Children (2014)

Epilepsy in children is a complex disease, with a variety of distinct syndromes and many alternative treatment options. Even with a plethora of available treatment options, childhood epilepsies are commonly associated with seizures that are resistant to existing treatment methods. Treatment of pediatric epilepsy is challenging and requires more effective therapy to avoid short-term and long-term neurological disorders.
A rapid, sensitive and economical assessment of monoclonal antibody conformational stability by intrinsic tryptophan fluorescence spectroscopy (2008)

Steady-state intrinsic tryptophan fluorescence spectroscopy is used as a rapid, robust and economic way for screening the thermal protein conformational stability in various formulations used during the early biotechnology development phase. The most important parameters affecting protein stability in a liquid formulation, e. g. during the initial purification steps or preformulation development, are the pH of the solution, ionic strength, presence of excipients and combinations thereof. A well-defined protocol is presented for the investigation of the thermal conformational stability of proteins. This allows the determination of the denaturation temperature as a function of solution conditions. Using intrinsic tryptophan fluorescence spectroscopy for monitoring the denaturation and folding of proteins, it is crucial to understand the influence of different formulation parameters on the intrinsic fluorescence probes of proteins. Therefore, we have re-evaluated and re-assessed the influence of temperature, pH, ionic strength, buffer composition on the emission spectra of tryptophan, phenylalanine and tyrosine to correctly analyse and evaluate the data obtained from thermal-induced protein denaturation as a function of the solution parameters mentioned above. The results of this study are a prerequisite for using this method as a screening assay for analysing the conformational stability of proteins in solution. The data obtained from intrinsic protein fluorescence spectroscopy are compared to data derived from calorimetry. The advantage, challenges and applicability using intrinsic tryptophan fluorescence spectroscopy as a routine development method in pharmaceutical biotechnology are discussed.
Location of .gamma.-carboxyglutamyl residues in partially carboxylated prothrombin preparations (1988)

Prothrombin contains 10 gamma-carboxyglutamyl (Gla) residues in the N-terminal (fragment 1) domain of the protein. Following anticoagulant administration, a spectrum of undercarboxylated, physiologically less active forms of prothrombin is secreted into bovine or human plasma. The sites of undercarboxylation in these prothrombin species have now been investigated. Plasma containing a mixture of partially carboxylated forms of prothombin was obtained from a dicoumarol-treated bovine, and three pools of partially carboxylated (four, six, or eight Gla) species were purified by adsorption onto barium citrate and barium oxalate, ammonium sulfate fractionation, and chromatography. Fragment 1 obtained from these variants was equilibrated with 3H2O and heated in a dry state to decarboxylate Gla and incorporate 3H into the resulting Glu residues. This peptide was then sequenced by Edman degradation, and the specific radioactivity of PTH-Glu was determined for each potential Gla-containing site. Data obtained from normal prothrombin fragment 1 fit a linear model when the log of specific activity of PTH-Glu was plotted against the cycle number. Analysis of the 80% variant showed a decrease in carboxylation only in the last two Gla residues, while data obtained from the 60% variant indicated a general decrease in carboxylation from the most amino- to the more carboxyl-terminal Gla residues. In the 40% Gla variant, all but the most amino-terminal of the Gla residues appeared to be undercarboxylated. These data indicate that the gamma-carboxylation of glutamyl residues in prothrombin does not occur randomly but instead with preferential carboxylation of the most amino-terminal Gla residues. When carboxylation is limited, the impairment of carboxylation is more severe at the more carboxyl-terminal residues.
Chemical and structural dynamics of guanosine monophosphate synthetase (2006)

Glutamine amidotransferases catalyze the amination of a wide range of molecules using the amide nitrogen of glutamine to create ammonia. The enzyme family provides numerous examples for study of the regulation and interdomain communication in proteins with multiple catalytic activities. Guanosine monophosphate synthetase (GMPS) is a glutamine amidotransferase responsible for the last step in the guanosine branch of de novo purine biosynthesis, the amination of xanthosine monophosphate. In several amidotransferases, the intramolecular path of ammonia from glutamine to substrate is understood; however, the crystal structure of GMPS provided no details of the transfer process. Large-scale conformational changes in GMPS are necessary to allow efficient ammonia channeling to occur, and they are hypothesized to consist of global domain motions as well as the ordering of a long, conserved loop. Rapid kinetics studies were pursued to provide insight into the mechanism of the substrate-induced changes in this complex enzyme. Absorbance changes that occur upon mixing of GMPS with nucleotide substrates were established to be indicative of the formation of a reactive nucleotide intermediate. Subsequent mixing with glutamine was used to directly monitor the process of ammonia transfer to this intermediate. Nucleotide-induced changes in intrinsic tryptophan fluorescence provided the overall rate for the conformational changes upon substrate binding. A kinetic model for a single turnover event has been developed that highlights distinct chemical and conformational steps in the overall process. Structural information derived from both limited proteolysis and sedimentation velocity experiments support the hypothesis of nucleotide-induced loop- and domain-closure in the protein. These results were combined with information from sequence conservation and precedents from other glutamine amidotransferases to develop a structural model of GMPS in the closed, active state. The overall results provide a more complete kinetic and structural picture of GMPS function, from the binding of nucleotide substrates to the open enzyme, the ensuing chemical and conformational changes, and the final return to an open state with release of products. Finally, comparative analysis of the GMPS from different sources has further developed the distinctions in functional roles for dimeric and monomeric versions of protein.
Generating explanations of device behavior using compositional modeling and causal ordering (1993)

Generating explanations of device behavior is a long-standing goal of AI research in reasoning about physical systems. Much of the relevant work has concentrated on new methods for modeling and simulation, such as qualitative physics, or on sophisticated natural language generation, in which the device models are specially crafted for explanatory purposes. We show how two techniques from the modeling research---compositional modeling and causal ordering ---can be effectively combined to generate natural language explanations of device behavior from engineering models. The explanations offer three advances over the data displays produced by conventional simulation software: (1) causal interpretations of the data, (2) summaries at appropri ate levels of abstraction (physical mechanisms and component operating modes), and (3) query-driven, natural language summaries. Furthermore, combining the compositional modeling and causal ordering techniques allows models that are mo...
Characterization of Peptides Bound to the Class I MHC Molecule HLA-A2.1 by Mass Spectrometry (1992)

Antigens recognized by T cells are expressed as peptides bound to major histocompatibility complex (MHC) molecules. Microcapillary high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to fractionate and sequence subpicomolar amounts of peptides isolated from the MHC molecule HLA-A2.1. Of 200 different species quantitated, eight were sequenced and four were found in cellular proteins. All were nine residues long and shared a distinct structural motif. The sensitivity and speed of this approach should enhance the analysis of peptides from small quantities of virally infected and transformed cells as well as those associated with autoimmune disease states.
Thiazole-Based Synthesis of Formyl C-Glycosides (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThiazole-Based Synthesis of Formyl C-GlycosidesAlessandro Dondoni and Marie-Christine ScherrmannCite this: J. Org. Chem. 1994, 59, 21, 6404–6412Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://doi.org/10.1021/jo00100a050RIGHTS & PERMISSIONSArticle Views1161Altmetric-Citations112LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts