gebhart/patrepeval huggingface dataset:
Identity of human epidermal growth factor (EGF) receptor with glycoprotein SA-7: evidence for differential phosphorylation of the two components of the EGF receptor from A431 cells. (1982)

A 165-kilodalton (kDal) surface glycoprotein encoded by human chromosome 7 (SA-7) had been characterized by using antisera raised against human chromosome 7-containing somatic cell hybrids. We now present evidence that SA-7 is the human receptor for epidermal growth factor (EGF) and that these antisera recognize human-specific determinants. The gene coding for the human EGF receptor is localized to the p12 to p22 region of chromosome 7. We have characterized the 145-kDal/165-kDal EGF receptor doublet of A431 cells after immunoprecipitation of radiolabeled cell extracts with these antisera. We find that a protein with endogenous kinase activity copurifies with the A431 receptor doublet and that both components of the doublet contain phosphotyrosine and phosphothreonine and the 165-kDal component contains phosphoserine as well. Further, although each component of the receptor doublet has an average pI of 7, both display charge heterogeneity and appear to have unique charge isomers. The relationship between the two components of the A431 EGF receptor is discussed.
A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene (2009)

Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea that FTO itself is involved in obesity. We show that a dominant point mutation in the mouse Fto gene results in reduced fat mass, increased energy expenditure, and unchanged physical activity. Exposure to a high-fat diet enhances lean mass and lowers fat mass relative to control mice. Biochemical studies suggest the mutation occurs in a structurally novel domain and modifies FTO function, possibly by altering its dimerisation state. Gene expression profiling revealed increased expression of some fat and carbohydrate metabolism genes and an improved inflammatory profile in white adipose tissue of mutant mice. These data provide direct functional evidence that FTO is a causal gene underlying obesity. Compared to the reported mouse FTO knockout, our model more accurately reflects the effect of human FTO variants; we observe a heterozygous as well as homozygous phenotype, a smaller difference in weight and adiposity, and our mice do not show perinatal lethality or an age-related reduction in size and length. Our model suggests that a search for human coding mutations in FTO may be informative and that inhibition of FTO activity is a possible target for the treatment of morbid obesity.
Line codes for digital subscriber lines (ISDN basic access) (1989)

The attributes of the several line codes considered for a North American standard for ISDN basic access are compared. Impairments that affect line code performance are examined, and their performance characteristics are discussed. An intuitive explanation of why the code performs as it does is attempted in each case. Some variations of the codes that were considered and that were intended to improve their performance are also discussed. The codes considered are bi-phase, modified duobinary, alternate mark inversion, 3B2T, 2B1Q and 4B3T.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Application of Microfluidic Devices to Proteomics Research (2002)

This report describes an integrated and modular microsystem providing rapid analyses of trace-level tryptic digests for proteomics applications. This microsystem includes an autosampler, a microfabricated device comprising a large channel (2.4 microl total volume), an array of separation channels, together with a low dead volume enabling the interface to nanoelectrospray mass spectrometry. The large channel of this microfluidic device provides a convenient platform to integrate C(18) reverse phase packing or other type of affinity media such as immobilized antibodies or immobilized metal affinity chromatography beads thus enabling affinity selection of target peptides prior to electrophoretic separation and mass spectrometry analyses on a quadrupole/time-of-flight instrument. Sequential injection, preconcentration, and separation of peptide standards and tryptic digests are achieved with a throughput of up to 12 samples/per h and a concentration detection limit of approximately 5 nM (25 fmol on chip). Replicate injections of peptide mixtures indicated that reproducibility of migration time was 1.2-1.8%, whereas relative standard deviation ranging from 9.2 to 11.8% are observed on peak heights. The application of this device for trace-level protein identification is demonstrated for two-dimensional gel spots obtained from extracts of human prostatic cancer cells (LNCap) using both peptide mass-fingerprint data base searching and on-line tandem mass spectrometry. Enrichment of target peptides prior to mass spectral analyses is achieved using c-myc-specific antibodies immobilized on protein G-Sepharose beads and facilitates the identification of antigenic peptides spiked at a level of 20 ng/ml in human plasma. Affinity selection is also demonstrated for gel-isolated protein bands where tryptic phosphopeptides are captured on immobilized metal affinity chromatography beads and subsequently separated and characterized on this microfluidic system.
Mechanical dissociation of human embryonic stem cell colonies by manual scraping after collagenase treatment is much more detrimental to cellular viability than is trypsinization with gentle pipetting (2007)

Because hESC (human embryonic stem cells) are 'social cells' that require co-operative interactions and intimate physical contact with each other, it is absolutely essential to dissociate hESC colonies into cellular clumps rather than into a single-cell suspension during serial passage. The present study compared two commonly used protocols for dissociating hESC colonies. The first protocol involved mild enzymatic treatment with collagenase type IV (1 mg/ml) for approx. 5-10 min, prior to mechanical dissociation into cellular clumps through manual scraping with a plastic pipette tip. The second protocol involved a short duration of exposure (2-3 min) to low concentrations of trypsin (0.05%), followed by gentle pipetting. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay was used to compare the recovery of viable cells after dissociating hESC colonies with these two protocols, before and after conventional freeze-thawing with 10% (v/v) DMSO. Besides undifferentiated hESC, the randomly differentiated fibroblastic progenies of hESC at various passages (P0-P4), together with an immortalized cell line (CRL-1486), were also utilized to compare the two protocols. The results demonstrated that the second protocol (trypsinization with gentle pipetting) is much less detrimental to cellular viability than is the first protocol (collagenase treatment with scratching). This in turn translated to higher freeze-thaw survival rates. It is hypothesized that scratching after collagenase treatment (first protocol) somehow induces physical damage to the cells, thereby leading to a lower recovery of viable cells, both before and after freeze-thawing.
A Thin Electromagnetic Absorber for Wide Incidence Angles and Both Polarizations (2009)

A design for planar electromagnetic absorbers is presented. The performance of this absorber is maintained over a wide incidence angles and for both TE and TM polarization. The absorber is composed of a high-impedance surface comprising an array of patches over a grounded lossy dielectric slab perforated with metallic vias (wire medium). The main contribution of the paper is to demonstrate and practically use the presence of an additional resonance when the plasma frequency of the wire medium in the dielectric substrate is close to the original resonance of the high-impedance surface. The presence of the vias between FSS and the ground plane is discussed both for the case of a high-permittivity absorber and for a low permittivity one, through the derivation of simple and efficient analytical expressions, specifically derived for the problem at hand. We show that the presence of the vias influences the oblique incidence TM absorption, and when properly designed, the insertion of the vias into the absorber structure results in a bandwidth enlargement and higher absorption performance.
The Theory of Thin Shell Structures 1888–1988 (1988)

This paper commemorates the publication in 1888 of A.E.H. Love's paper on thin elastic shells. It discusses Love's relationship with Rayleigh and others, and assesses the historical significance of the work.
Applying Chatbots to the Internet of Things: Opportunities and Architectural Elements (2016)

Internet of Things (IoT) is emerging as a significant technology in shaping the future by connecting physical devices or things with the web. It also presents various opportunities for the intersection of other technological trends which can allow it to become even more intelligent and efficient. In this paper, we focus our attention on the integration of Intelligent Conversational Software Agents or Chatbots with IoT. Prior literature has covered various applications, features, underlying technologies and known challenges of IoT. On the other hand, Chatbots are a relatively new concept, being widely adopted due to significant progress in the development of platforms and frameworks. The novelty of this paper lies in the specific integration of Chatbots in the IoT scenario. We analyzed the shortcomings of existing IoT systems and put forward ways to tackle them by incorporating chatbots. A general architecture is proposed for implementing such a system, as well as platforms and frameworks – both commercial and open source – which allow for the implementation of such systems. Identification of the newer challenges and possible future research directions with this new integration have also been addressed.
The nucleotide sequence of the Tn5271 3-chlorobenzoate 3,4-dioxygenase genes (cbaAB) unites the class IA oxygenases in a single lineage (1995)

The nucleotide sequence of the 3-chlorobenzoate 3,4-dioxygenase genes, designated cbaAB, from the transposon Tn5271 was determined. The function of the two sequenced open reading frames was evaluated by mutagenesis and expression in vivo to show that the cbaA and cbaB genes code for dioxygenase and reductase proteins, respectively. Comparison of the deduced amino acid sequences of the cbaAB genes with sequences for other oxygenases revealed a clearly defined lineage among the class IA oxygenases that shows several unique features. This lineage includes phthalate 4,5-dioxygenase (pht23), and based on the available NH3-terminal sequence of component A, also includes 4-sulphobenzoate 3,4-dioxygenase. Vanillate demethylase, encoded by the vanAB genes and formally a monooxygenase enzyme catalysing an oxidative demethylation, is also included in this lineage. The terminal chlorobenzoate dioxygenase (CbaA) component is characterized by a conserved Rieske-type [2Fe-2S]R ligand centre. The reductase component (CbaB) contains a plant-type ferredoxin [2Fe-2S]Fd, FMN-isoalloxazine and NAD-ribose-binding domains and the orientation of these domains is conserved in all known class IA reductases. These results support the hypothesis that alternative fusions of the electron transfer modules of the reductases arose early in the divergence of oxygenase systems. The over-riding evolutionary constraint acting on the divergence of the class IA oxygenases would appear to be the requirement for a carboxyl group para to the site of oxygen insertion into the aromatic ring.
ReasoNet: Learning to Stop Reading in Machine Comprehension (2016)

Teaching a computer to read and answer general questions pertaining to a document is a challenging yet unsolved problem. In this paper, we describe a novel neural network architecture called the Reasoning Network (ReasoNet) for machine comprehension tasks. ReasoNets make use of multiple turns to effectively exploit and then reason over the relation among queries, documents, and answers. Different from previous approaches using a fixed number of turns during inference, ReasoNets introduce a termination state to relax this constraint on the reasoning depth. With the use of reinforcement learning, ReasoNets can dynamically determine whether to continue the comprehension process after digesting intermediate results, or to terminate reading when it concludes that existing information is adequate to produce an answer. ReasoNets have achieved exceptional performance in machine comprehension datasets, including unstructured CNN and Daily Mail datasets, the Stanford SQuAD dataset, and a structured Graph Reachability dataset.
EdgeFlow: a technique for boundary detection and image segmentation (2000)

A novel boundary detection scheme based on "edge flow" is proposed in this paper. This scheme utilizes a predictive coding model to identify the direction of change in color and texture at each image location at a given scale, and constructs an edge flow vector. By propagating the edge flow vectors, the boundaries can be detected at image locations which encounter two opposite directions of flow in the stable state. A user defined image scale is the only significant control parameter that is needed by the algorithm. The scheme facilitates integration of color and texture into a single framework for boundary detection. Segmentation results on a large and diverse collections of natural images are provided, demonstrating the usefulness of this method to content based image retrieval.
Are Computer Focused Crimes Impacted by System Configurations? An Empirical Study (2012)

This paper describes an empirical study to assess whether computer focused crimes are impacted by system configurations. The study relies on data collected during 30 days on a farm of target computers of various configurations (disk space, memory size, and bandwidth). In addition, some target computers included a warning sign. Following a brute force attack on SSH, attackers randomly access one of these computer configurations and are allowed to use it for 30 days. We monitor network traffic and attackers' keystrokes to analyze the attack. This paper focuses specifically on the crime, i.e., the use of the computer to launch an attack towards an external target. We define various computer focused crime characteristics (i.e., whether the attack was destructive or not, whether the target was an opportunity or a choice, whether the attack was coordinated or not) and analyze whether the committed crime is significantly impacted by the system configuration.
Effects on Molecular Conformation and Anticoagulant Activities of 1,6-Anhydrosugars at the Reducing Terminal of Antithrombin-Binding Octasaccharides Isolated from Low-Molecular-Weight Heparin Enoxaparin (2010)

Terminal 1,6-anhydro-aminosugars (1,6-anAS) are typical structural moieties of enoxaparin, a low-molecular-weight heparin (LMWH) widely used for prevention and treatment of thrombotic disorders. In the enoxaparin manufacturing process, these modified amino sugars are formed during the β-eliminative cleavage of heparin. To investigate the effect of terminal anAS on antithrombin (AT) binding and on inhibition of factor Xa (FXa), two octasaccharides containing modified AT-binding pentasaccharide sequences were isolated from enoxaparin. The molecular conformation of the octasaccharides terminating with N-sulfo-1,6-anhydro-D-mannosamine and N-sulfo-1,6-anhydro-D-glucosamine, respectively, has been determined both in the absence and presence of AT by NMR experiments and docking simulations. Reduced overall contacts of the terminal anAS residues with the binding region of AT induce a decrease in affinity for AT as well as lower anti-FXa activity. The anti-FXa measured either in buffer or plasma milieu does not show any significant difference, suggesting that the inhibition of anti-FXa remains specific and biologically relevant.
Efficient Asymmetric Synthesis of N ‐ tert ‐Butoxycarbonyl α‐Aminoacids Using 4‐ tert ‐Butoxycarbonyl‐5,6‐Diphenylmorpholin‐2‐one: ( R )‐( N ‐ tert ‐Butoxycarbonyl)Allylglycine (2003)

Abstract (N‐tert‐Butoxycarbonyl)allylglycine 4‐tert‐Butyloxycarbonyl‐5,6‐diphenylmorpholin‐2‐one Allyl iodide 4‐tert‐Butoxycarbonyl‐5,6‐diphenyl‐3‐(1′prop‐2′‐enyl)morpholin‐2‐one Lithium bis(trimethylsilyl)amide
On-Line Monitoring of Cell Growth and Cytotoxicity Using Electric Cell-Substrate Impedance Sensing (ECIS) (2003)

An on-line and continuous technique based on electric cell-substrate impedance sensing (ECIS) was developed for measuring the concentration and time response function of fibroblastic V79 cells exposed to mercury chloride and 1,3,5-trinitrobenzene (TNB). Attachment, spreading and proliferation of V79 fibroblastic cells cultured on a microarray of small gold electrodes precoated with fibronectin were detected as resistance changes. The response function was derived to reflect the resistance change as a result of cell attachment, spreading, mitosis and cytotoxicity effect. Exposure of V79 cells to mercury chloride or TNB led to alterations in cell behavior, and therefore, chemical cytotoxicity was easily screened by measuring the response function of the attached and spread cells in the presence of inhibitor. The half inhibition concentration, the required concentration to achieve 50% inhibition, was obtained from the response function to provide information about cytotoxicity during the course of the assay. A simple mathematical model was developed to describe the responses of ECIS that were related to the attachment, spreading, and proliferation of V79 fibroblastic cells. The novel results of this paper are mainly characterized by the systematic study of several parameters including the cell number, detection limit, sensor sensitivity, and cytotoxicity, and they may motivate further research and study of ECIS sensors.
Polyplexes from Poly(aspartamide) Bearing 1,2-Diaminoethane Side Chains Induce pH-Selective, Endosomal Membrane Destabilization with Amplified Transfection and Negligible Cytotoxicity (2008)

Polyplexes assembled from poly(aspartamide) derivatives bearing 1,2-diaminoethane side chains, [PAsp(DET)] display amplified in vitro and in vivo transfection activity with minimal cytotoxicity. To elucidate the molecular mechanisms involved in this unique function of PAsp(DET) polyplexes, the physicochemical and biological properties of PAsp(DET) were thoroughly evaluated with a control bearing 1,3-diaminopropane side chains, PAsp(DPT). Between PAsp(DET) and PAsp(DPT) polyplexes, we observed negligible physicochemical differences in particle size and zeta-potential. However, the one methylene variation between 1,2-diaminoethane and 1,3-diaminopropane drastically altered the transfection profiles. In sharp contrast to the constantly high transfection efficacy of PAsp(DET) polyplexes, even in regions of excess polycation to plasmid DNA (pDNA) (high N/P ratio), PAsp(DPT) polyplexes showed a significant drop in the transfection efficacy at high N/P ratios due to the progressively increased cytotoxicity with N/P ratio. The high cytotoxicity of PAsp(DPT) was closely correlated to its strong destabilization effect on cellular membrane estimated by hemolysis, leakage assay of cytoplasmic enzyme (LDH assay), and confocal laser scanning microscopic observation. Interestingly, PAsp(DET) revealed minimal membrane destabilization at physiological pH, yet there was significant enhancement in the membrane destabilization at the acidic pH mimicking the late endosomal compartment (pH approximately 5). Apparently, the pH-selective membrane destabilization profile of PAsp(DET) corresponded to a protonation change in the flanking diamine unit, i.e., the monoprotonated gauche form at physiological pH and diprotonated anti form at acidic pH. These significant results suggest that the protonated charge state of 1,2-diaminoethane may play a substantial role in the endosomal disruption. Moreover, this novel approach for endosomal disruption neither perturbs the membranes of cytoplasmic vesicles nor organelles at physiological pH. Thus, PAsp(DET) polyplexes, residing in late endosomal or lysosomal states, smoothly exit into the cytoplasm for successful transfection without compromising cell viability.
Commercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodies (2004)

Abstract Stable therapeutic antibody dosage forms present production technology challenges, particularly when high‐concentration formulations are needed to meet the elevated dose requirements that are generally required for successful antibody therapy. Solid dosage forms, such as lyophilized powders, are generally more stable than liquid formulations. High‐concentration drug products can be achieved by reconstitution of the lyophilisate in a smaller volume than its initial (pre‐lyophilization) volume, but requires a significant vial overfill. High‐concentration liquid formulations are becoming feasible as new techniques and technologies become available. Analytical methods to detect subtle molecular variations have been developed to demonstrate manufacturing consistency. Some molecular heterogeneity is contributed by conserved sites, such as Asn297 glycosylation and the loss of heavy chain C‐terminal Lys residues. Characteristics that affect potency, stability, or immunogenicity must be elucidated for each therapeutic antibody. Drug Dev. Res. 61:137–154, 2004. © 2004 Wiley‐Liss, Inc.
FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma (2017)

On November 30, 2015, the FDA approved elotuzumab (Empliciti; Bristol-Myers Squibb) in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who received one to three prior therapies. FDA approval was based primarily on the results of a phase III, randomized, open-label, multicenter trial, CA204004, which evaluated elotuzumab in combination with lenalidomide and dexamethasone (E-Ld) compared with lenalidomide and dexamethasone (Ld) alone in patients with relapsed or refractory multiple myeloma. Coprimary endpoints were progression-free survival (PFS) and overall response rate (ORR). The key secondary endpoint was overall survival, but these data were not mature at the time of clinical database cutoff. The trial demonstrated a statistically significant improvement in PFS, with an estimated HR of 0.70 for E-Ld over Ld [95% confidence interval (CI), 0.57-0.85; <i>P</i> = 0.0004). Estimated median PFS was 19.4 months in the E-Ld arm and 14.9 months in the Ld arm. ORR was 75.8% in the E-Ld arm compared with 65.5% in the Ld arm. Serious adverse reactions were reported in 65% of patients in the E-Ld arm compared with 57% in the Ld arm. The FDA approved elotuzumab with the following warnings and precautions: infusion reactions, infections, second primary malignancies, hepatotoxicity, and interference with the determination of complete response. <i>Clin Cancer Res; 23(22); 6759-63. ©2017 AACR</i>.