gebhart/patrepeval huggingface dataset:
Potent and selective inhibitors of the Met [hepatocyte growth factor/scatter factor (HGF/SF) receptor] tyrosine kinase block HGF/SF-induced tumor cell growth and invasion. (2003)

The hepatocyte growth factor/scatter factor (HGF/SF) receptor, Met, mediates various cellular responses on activation with its ligand, including proliferation, survival, motility, invasion, and tubular morphogenesis. Met expression is frequently up-regulated in sarcomas and carcinomas. Experimental evidence suggests that Met activation correlates with poor clinical outcome and the likelihood of metastasis. Therefore, inhibitors of Met tyrosine kinase may be useful for the treatment of a wide variety of cancers that have spread from the primary site. We have discovered potent and selective pyrrole-indolinone Met kinase inhibitors and characterized them for their ability to inhibit HGF/SF-induced cellular responses in vitro. These compounds inhibit HGF/SF-induced receptor phosphorylation in a dose-dependent manner. They also inhibit the HGF/SF-induced motility and invasion of epithelial and carcinoma cells. Therefore, these compounds represent a class of prototype small molecules that selectively inhibit the Met kinase and could lead to identification of compounds with potential therapeutic utility in treatment of cancers.
Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. (1986)

Previous studies demonstrated that endothelial cells participate actively in both anticoagulant and procoagulant reactions. Although anticoagulant mechanisms predominate on the surface of quiescent endothelial cells, perturbed endothelial cells can promote coagulation through the coordinated induction of procoagulant activity and suppression of anticoagulant mechanisms. Purified recombinant interleukin 1 was infused intravenously into rabbits and coagulant properties of the native aortic endothelium were subsequently studied. Interleukin 1 infusion resulted in a time- and dose-dependent induction of the procoagulant cofactor tissue factor, while concomitantly blocking the protein C anticoagulant pathway. Tissue factor activity increased greater than 10-fold by 3-5 hr after the infusion, while endothelial cell-dependent thrombin-mediated protein C activation decreased by 72% and assembly of functional activated protein C-protein S complex on the vessel surface was decreased by greater than 90%. Scanning electron microscopy of major arteries demonstrated fibrin strands closely associated with the luminal endothelial cell surface with a predilection for bifurcations. Interleukin 1, a mediator of the inflammatory response, can shift the balance of procoagulant and anticoagulant reactions on the endothelium unidirectionally favoring clot formation. The surface of perturbed endothelium can thus provide a template, facilitating the development of a prethrombotic state, and provides a model for the early stages of thrombosis.
The adsorption of biogenic amines on the surface of highly dispersed silica from aqueous solutions (2006)

The adsorption of some biogenic amines (histamine, tryptamine, and tyramine) on the surface of highly dispersed silica from aqueous solutions is studied as a function of pH and ionic strength. It is established that biogenic amines in a protonated form interact with dissociated silanol groups of SiO2 surface forming outer-sphere complexes. The constants of the formation of surface complexes are calculated.
Non-uniform access asynchronous register files (2004)

Register files of microprocessors have often been cited as performance bottlenecks and significant consumers of energy. The robust and modular nature of quasi-delay insensitive (QDI) design offers a toolchest of techniques for improving average-case performance and reducing energy consumption of register files, which cannot be leveraged as easily in synchronous designs. We focus on the design of an asynchronous register core, the heart of a register file. We describe the vertical pipelining transformation and describe the locking mechanism that maintains pipelined mutual exclusion among reads and writes to the same register. The primary contributions of this paper are: 1) detailed evaluation of the width-adaptive datapath (WAD) representation in register files, which leads to significant energy reduction by conditionally communicating higher significant bits of integers with little performance degradation, and 2) nesting the register core to create non-uniform banks to facilitate faster and lower energy accesses to more frequently used registers and slower accesses to less frequently used registers without increasing the interconnect requirement or control complexity. We present spice-simulated results for a wide variety of register files laid out in TSMC 0.18/spl mu/m technology.
Intelligent intraoral drug delivery microsystem (2006)

The authors report on the concept and development of an intelligent intraoral drug delivery microsystem, that provides an alternative approach for the treatment of addiction and chronic diseases. The drug delivery system (DDS) comprises a medication replacement reservoir, a medication release mechanism, a built-in intelligence, a remote control, microsensors, and microactuators. It is thus able to release the medication in a controlled manner according to the patient needs. The emphasis of this article is on the application of sensors and microfluidic components in a real microsystem and also showing some details of two system components, namely, the osmotic pump and the flow sensor. The motivation for the microfluidic approach, the concept of the DDS, the requirements for this specific application, and the arising problems will be presented and discussed. Regarding the sensors and actuators, the problems mainly concern size and power consumption. A major challenging aspect of microfluidic component development is to avoid clogging of small channels because of particles and recrystallization of saturated fluids.
Glycoprotein A34, a novel target for antibody-based cancer immunotherapy. (2006)

To identify novel, tissue-restricted cell surface proteins in cancer which can serve as targets for antibody-based diagnostics and therapeutics, a translated version of the expressed sequence tag database (tblastn) was mined for transcripts with similarity to the glycoprotein A33 (GPA33) colon cancer antigen. A novel human transcript, termed A34, was identified which encoded a putative cell surface protein, GPA34, which is approximately 30% identical to GPA33 and other members of the junctional adhesion molecule (JAM) family. Conventional end-point and quantitative real-time RT-PCR showed that A34 mRNA expression is highly tissue-restricted, as it is expressed predominantly in stomach and testis. A34 mRNA was also detected in 6/19 (31%) gastric cancers, 8/16 (50%) esophageal carcinomas, and 4/17 (23%) ovarian cancers, but not in lung, breast or colon carcinomas. A murine monoclonal antibody (mAb A34) was generated to the extracellular domain of the A34 protein and used to biochemically and immunohistochemically characterize the A34 antigenic system. The mAb A34 specifically recognized glycoproteins ranging in apparent size from 55-70 kDa, present in normal gastric mucosa and in COS-7 cells transfected with A34 cDNA. Of 31 different normal tissues examined by immunohistochemistry, GPA34 protein expression was detected primarily in normal stomach mucosa and testicular germ cells, and in the tumor cells of 5/17 (29%) gastric cancers, 7/11 (63%) esophageal cancers, and 2/21 (9%) ovarian cancers, in agreement with gene expression results. The A34 antigen and monoclonal antibody may be of considerable value for immunotherapy of different types of cancer.
Differential methylation of cell‐free circulating DNA among patients with pancreatic cancer versus chronic pancreatitis (2010)

: The current data suggested that, among patients with pancreatic disease, the methylation profiles of inflammatory disease and cancer are different and open a new venue for the development of biomarkers for differential diagnosis. Further investigation of diagnostic biomarkers for pancreatic cancer based on methylation in cell-free, circulating DNA appears to be warranted. Cancer 2010. (c) 2010 American Cancer Society.
Fast Anion-Exchange in Highly Luminescent Nanocrystals of Cesium Lead Halide Perovskites (CsPbX3, X = Cl, Br, I) (2015)

Postsynthetic chemical transformations of colloidal nanocrystals, such as ion-exchange reactions, provide an avenue to compositional fine-tuning or to otherwise inaccessible materials and morphologies. While cation-exchange is facile and commonplace, anion-exchange reactions have not received substantial deployment. Here we report fast, low-temperature, deliberately partial, or complete anion-exchange in highly luminescent semiconductor nanocrystals of cesium lead halide perovskites (CsPbX3, X = Cl, Br, I). By adjusting the halide ratios in the colloidal nanocrystal solution, the bright photoluminescence can be tuned over the entire visible spectral region (410-700 nm) while maintaining high quantum yields of 20-80% and narrow emission line widths of 10-40 nm (from blue to red). Furthermore, fast internanocrystal anion-exchange is demonstrated, leading to uniform CsPb(Cl/Br)3 or CsPb(Br/I)3 compositions simply by mixing CsPbCl3, CsPbBr3, and CsPbI3 nanocrystals in appropriate ratios.
Rubinstein–Taybi syndrome: clinical and molecular overview (2007)

Rubinstein-Taybi syndrome is characterised by mental retardation, growth retardation and a particular dysmorphology. The syndrome is rare, with a frequency of approximately one affected individual in 100,000 newborns. Mutations in two genes - CREBBP and EP300 - have been identified to cause the syndrome. These two genes show strong homology and encode histone acetyltransferases (HATs), which are transcriptional co-activators involved in many signalling pathways. Loss of HAT activity is sufficient to account for the phenomena seen in Rubinstein-Taybi patients. Although some mutations found in CREBBP are translocations, inversions and large deletions, most are point mutations or small deletions and insertions. Mutations in EP300 are comparatively rare. Extensive screening of patients has revealed mutations in CREBBP and EP300 in around 50% of cases. The cause of the syndrome in the remaining patients remains to be identified, but other genes could also be involved. Here, we describe the clinical presentation of Rubinstein-Taybi syndrome, review the mutation spectrum and discuss the current understanding of causative molecular mechanisms.
Preparation of well-defined protein conjugates using enzyme-assisted reverse proteolysis (1991)

A two-step approach to the production of well-defined protein conjugates is described. In the first step, a linker group, carbohydrazide, having unique reactivity (a hydrazide group) is attached specifically to the carboxyl terminus by using enzyme-catalyzed reverse proteolysis. Since the hydrazide group exists nowhere else on the protein, specificity is assured in a subsequent chemical reaction (formation of a hydrazone bond) of the modified protein with a molecule (chelator, drug, or polypeptide) carrying an aldehyde or keto group. The product is sufficiently stable at neutral pH, no reduction of the hydrazone bond being necessary for the hydrazones described. Protein modification is thus restricted to the carboxyl terminus and a homogeneous product results. With insulin as a model, conditions are described for producing such well-defined conjugates in good yields. The use of other linker groups besides carbohydrazide, and applications of these techniques to antibody fragments, are discussed.
Rational communicative behavior in anti-air defense (2002)

The authors' research addresses rational decision-making among anti-air units whose mission is to defend a specified territory from a number of attacking missiles. They present a decision-theoretic method that automated agents can use to select optimal communicative acts in this domain, given the characteristics of the threat situation. Since the communication bandwidth is usually limited in a battle field environment and disclosure of any information to hostile agents should be avoided, it is critical for a defending agent to be selective as to what messages should, or should not, be sent to other friendly agents. The work builds on their earlier work that uses the recursive modeling method (RMM) for coordination, and applies RMM to rational communication in the anti-air defense domain. They show how a defending automated agent can rank the values of alternative messages that could be communicated in a given defense situation. Further, they compare this ranking to communicative choices of human subjects under the same circumstances of the coordinated anti-air defense.
Impact of Cell-surface Antigen Expression on Target Engagement and Function of an Epidermal Growth Factor Receptor × c-MET Bispecific Antibody (2015)

The efficacy of engaging multiple drug targets using bispecific antibodies (BsAbs) is affected by the relative cell-surface protein levels of the respective targets. In this work, the receptor density values were correlated to the in vitro activity of a BsAb (JNJ-61186372) targeting epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET). Simultaneous binding of the BsAb to both receptors was confirmed in vitro. By using controlled Fab-arm exchange, a set of BsAbs targeting EGFR and c-MET was generated to establish an accurate receptor quantitation of a panel of lung and gastric cancer cell lines expressing heterogeneous levels of EGFR and c-MET. EGFR and c-MET receptor density levels were correlated to the respective gene expression levels as well as to the respective receptor phosphorylation inhibition values. We observed a bias in BsAb binding toward the more highly expressed of the two receptors, EGFR or c-MET, which resulted in the enhanced in vitro potency of JNJ-61186372 against the less highly expressed target. On the basis of these observations, we propose an avidity model of how JNJ-61186372 engages EGFR and c-MET with potentially broad implications for bispecific drug efficacy and design.
Loan delinquency in community lending organizations: Case studies of neighborworks organizations (1998)

Abstract This article reports on qualitative data gathered through interviews conducted in 1996 with key leadership and staff from 13 community lending organizations. Loan servicing and collection procedures within the organizations were examined. Findings suggest that several organizational factors of nonprofit lenders are related to their loan delinquency rates: social networks, business culture, funding sources, composition of the board and loan committees, staff structure, loan intake, and collection tools. The study also finds that the nonprofit sector's institutional environment and its partnership with the private sector in a mutually beneficial process influence the loan delinquency rate. More specifically, active participation of local bankers in NeighborWorks1 loan committees, diverse funding sources (from both the public and private sectors), and a diffusion of business practices through dense social networks are related to NeighborWorks’ loan servicing and collection policy and procedures. These factors in turn influence NeighborWorks’ rehabilitation loan delinquency rates.
Dissolution properties, solid-state transformation and polymorphic crystallization: progesterone case study (2013)

Progesterone is a natural steroid hormone and a poor soluble drug which presents two polymorphs (forms 1 and 2). Different methods to obtain form 2 were tested and a complete solid-state characterization of both polymorphs (forms 1 and 2) was conducted. X-ray powder diffraction, hot stage microscopy, Fourier transform infrared, dispersive Raman, (13)C solid-state nuclear magnetic resonance spectroscopy, thermal analysis, scanning electron microscopy techniques and intrinsic dissolution rates (IDR) were applied to investigate physical-chemical and dissolution properties of these two polymorphs. Form 2 was obtained from diluted solutions and from melting after cooling at room temperature. Form 1 was obtained from concentrated solutions and, a mixture of both polymorphs was crystallized from intermediate solutions. The crystal habit was not a distinctive characteristic of each polymorph. The effect of mechanical stress was evaluated in the metastable polymorph (form 2). We observed that grinding form 2 produced seeds of form 1 that induced the transformation of form 2 into form 1 at high temperature. The polymorphic quantification from XRD patterns of ground samples were carried out by the Rietveld method. After grinding and at room temperature conditions (∼25 °C), it was observed the transformation of 17% of form 2 into form 1 in 10 days.
Memory access optimisation for reconfigurable systems (2001)

Memory access optimisation for FPGA-based reconfigurable systems with a hierarchy of on-chip and off-chip (external) memory to speed up applications limited by memory access speed are discussed. Most of the techniques are also valid for dedicated embedded systems and system-on-a-chip (SoC) designs. The approach involves two kinds of optimisation: first, methods to reduce the number of accesses by caching repeatedly used values are considered. The notion of vector access equivalence is introduced to form the basis of techniques employing FPGA storage as shift registers for caching. Larger data sets can be stored, if possible, in FPGA on-chip RAMs; RAM inference, a technique to automatically extract small on-chip RAMs to reduce external memory accesses is presented. Secondly, the authors aim to minimise the time spent on accesses to bandwidth-limited external memory, by scheduling as many accesses in parallel as possible. They present a technique which optimally allocates program arrays to memory banks, thereby minimising the overall access time. It also determines the most effective addressing mode for memory which can be accessed using different bitwidths.
Toolkit support for developing and deploying sensor-based statistical models of human situations (2007)

Sensor based statistical models promise to support a variety of advances in human computer interaction, but building applications that use them is currently difficult and potential advances go unexplored. We present Subtle, a toolkit that removes some of the obstacles to developing and deploying applications using sensor based statistical models of human situations. Subtle provides an appropriate and extensible sensing library, continuous learning of personalized models, fully automated high level feature generation, and support for using learned models in deployed applications. By removing obstacles to developing and deploying sensor based statistical models, Subtle makes it easier to explore the design space surrounding sensor based statistical models of human situations. Subtle thus helps to move the focus of human computer interaction research onto applications and datasets, instead of the difficulties of developing and deploying sensor based statistical models.
Are hemostasis and thrombosis two sides of the same coin? (2006)

Factor XII (FXII), a clotting enzyme that can initiate coagulation in vitro, has long been considered dispensable for normal blood clotting in vivo because hereditary deficiencies in FXII are not associated with spontaneous or excessive bleeding. However, new studies show that mice lacking FXII are protected against arterial thrombosis (obstructive clot formation) and stroke. Thus, FXII could be a unique drug target that could be blocked to prevent thrombosis without the side effect of increased bleeding.
Anti-Inflammatory and Antimicrobial Roles of Secretory Leukocyte Protease Inhibitor (2005)

Human secretory leukocyte protease inhibitor (SLPI) is an 11.7-kDa cationic protein and a member of the innate immunity-associated proteins. It is a nonglycosylated, highly basic, acid-stable, cysteine-rich, 107-amino acid, single-chain polypeptide ([50][1]). The SLPI gene, along with the elafin
Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. (1985)

The asialoglycoprotein (ASGP) receptor isolated from human liver and from the human hepatoma cell line HepG2 migrates on NaDodSO4 gel electrophoresis as a single species of 45,000 daltons. Recently, we isolated a cDNA clone encoding this receptor (H1) from a HepG2 lambda gt11 library. From the same library, we have isolated and sequenced a clone encoding a second ASGP receptor, H2, with a protein sequence homology of 58% to H1. There are two subspecies of H2 that differ only by the presence of a five-amino acid insertion in the COOH-terminal extracytoplasmic domain. Comparison with the available sequences of the two rat ASGP receptors R1 and R2 indicates that H1 is more homologous to R1 than to H2, and H2 is more similar to R2 than to H1. Thus, the two receptor genes evolved before the separation of rat and man. As judged by RNA blot hybridization of HepG2 RNA using RNA transcribed in vitro from cDNA clones of the human receptors as standards, H1 and H2 mRNA are present in equimolar amounts, each 0.005-0.01% of the total mRNA. This finding raises the question of whether the three ASGP receptor proteins are functional as heterodimers or whether they might serve different functions in the cell.
Lymphocyte Proliferation Response to Baker’s Yeast in Crohn’s Disease (1994)

The etiology of Crohn's disease is still unknown. The present study served to test the hypothesis that baker's yeast (Saccharomyces cerevisiae) plays a role in Crohn's disease. Blood samples were obtained from 12 patients and 15 healthy controls. Peripheral blood leukocytes were isolated and incubated alone or with different concentrations of baker's yeast. After 3 days, the cultures were pulsed with tritiated thymidine. None of the lymphocyte cultures from healthy controls, including 3 bakers, proliferated in response to yeast. In striking contrast, all 9 patients with Crohn's disease in remission, on no medication, showed a threefold increase in their lymphocyte proliferation rate. Lymphocytes from 3 patients on 1.5 g of olsalazine maintenance therapy failed to respond. These results are consistent with previous findings that showed increased titers of IgG and IgA antibodies to baker's yeast in patients with Crohn's disease as compared to healthy controls. They confirm the suspicion that baker's yeast itself or a related antigen play a role in Crohn's disease and suggest that anti-inflammatory agents may act, in part, by inhibiting lymphocyte proliferation.
Gain adaptation of networked mobile robot to compensate QoS deterioration (2003)

The performance of a robot operated over a data network does not only depend on a control algorithm used, but also on network conditions. Providing network QoS (quality-of-service) to a networked robot system could significantly improve its system performances. However, the network QoS can degrade due to several factors, such as congestion and interference, and can affect the overall system performances. We propose a gain adaptation approach to compensate deteriorative changes in network QoS in order to maintain the performances of a robot system as much as possible. The approach is demonstrated by path tracking control of networked differential drive mobile robot over a QoS enabled network. The simulation results show that when the gain adaptation is applied, the robot can effectively tolerate network QoS deterioration, and increase the overall system robustness. The concept of gain adaptation can be easily extended to other network-based control applications.
Fundamental Aspects of Atomic Absorption Spectrometry (1987)

I. INTRODUCTION Modern atomic absorption spectrometry (AAS) only dates back to 1955 to the famous article by Walsh.1 He showed very clearly for the first time that the absorptivity k(λ0) at the absorption line center λ0 is the quantity that should be measured for analytical purposes