gebhart/patrepeval huggingface dataset:
Extension of the Analysis of the Time Structure Of Behavioral Acts (1989)

A parameter known as the K-function has previously been used to analyze the temporal structure of behavioral acts. In earlier work the study of these acts or of the joint relationship of separate acts has used a restricted list of activities whose definitions are difficult to explicate. In the present study this technique has been extended to a more extensive list of acts, each meaning of which is intuitively clear. As with the earlier work, the bootstrap method has been used to estimate the uncertainty in these measures, and the usefulness has been examined using data from studies of rats exposed to phenytoin or nitrous oxide.
Characterization and expression of the human <i>alpha</i>  <i>beta</i> T cell receptor by using a framework monoclonal antibody. (1987)

A monoclonal antibody (mAb) with framework reactivity against the T cell receptor (TCR) alpha beta complex is characterized. The mAb, beta Framework 1 (beta F1) is capable of immunoprecipitating the TCR alpha beta complex from 125I-labeled human T cell tumors, immunocompetent T cell clones, and peripheral blood lymphocytes (PBL). beta F1 recognizes the separated TCR beta subunit in Western blotting. Because it does not bind to the surface of viable T cells but does react with the plasma membrane form of the TCR after treatment with membrane solubilizing agents, the beta F1 mAb reacts with a "hidden" determinant on the TCR beta subunit. After solubilization with 70% ethanol, the TCR alpha beta complex is shown to exist on greater than 92% of T3+ human PBL, whereas 2 to 8% of T3+ PBL do not react with the mAb. The beta F1 mAb demonstrates the existence of differently glycosylated surface 125I-labeled TCR alpha-chains (alpha, alpha', alpha") in association with a common TCR beta-chain on the HPB-MLT T cell leukemia. Reactivity of the beta F1 mAb on thymus tissue sections is similar to that of anti-Leu-4 (anti-T3). The beta F1 mAb should prove useful as a research tool for both the immunochemical characterization and isolation of virtually any alpha beta T cell receptor, whether from individual T cell clones or polyclonal populations of T lymphocytes. Recognition of T cell receptors in histologic tissue sections suggests that the beta F1 mAb may be useful in the clinical diagnosis of T cell lineage neoplasms. In failing to recognize all T3+ lymphocytes, it allows the identification of novel populations of T3+ lymphocytes that may express non-alpha, non-beta T cell receptors.
Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor (2014)

Genetically modified T cells to recognize tumor-associated antigens by transgenic TCRs or chimeric antigen receptors (CAR) have been successfully applied in clinical trials. However, the disadvantages of either TCR mismatching or the requirement of a surface tumor antigen limit their wider applications in adoptive T cell therapy. A TCR-like chimeric receptor, specific for the melanoma-related gp100/HLA-A2 complex was created by joining a TCR-like antibody GPA7 with the endodomains of CD28 and CD3-ζ chain. This TCR-like CAR, GPA7-28z, was subsequently introduced into human T cells. Retargeted T cells expressing GPA7-28z could exhibit efficient cytotoxic activities against human melanoma cells in vitro in the context with HLA-A2. Furthermore, infusion of GPA7-28z-transduced T cells suppressed melanoma progression in a xenograft mouse model. Redirecting human T cells with TCR-like CARs would be a promising alternative approach to TCR-mediated therapy for melanoma patients, which is also feasible for targeting a variety of other tumor antigens.
Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. (1995)

Hepatocyte growth factor (scatter factor) and its receptor, the c-met proto-oncogene product (c-MET), have been implicated in embryogenesis, tissue reorganization, and tumor progression. Little is known, however, of the expression and functional significance of these molecules in prostatic cells and tissue. In this investigation, we assessed the expression of hepatocyte growth factor (HGF) and c-MET in prostatic tissues and cell lines and also determined the effect of purified recombinant HGF on cell proliferation and scattering of prostatic carcinoma cell lines. HGF was expressed by human prostatic stromal myofibroblasts in primary culture but not by three human prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3) as assessed by Northern blot analysis. HGF was also detected by reverse transcriptase-polymerase chain reaction in both benign and malignant tissues from radical prostatectomy specimens. c-MET transcripts were identified by Northern blot in two androgen-insensitive human prostatic carcinoma cell lines (DU 145 and PC-3) but not the androgen-sensitive LNCaP cell line. Additional evidence of linkage of androgen responsiveness and c-MET was provided by experiments in which androgen deprivation of normal rat prostates via castration produced a marked up-regulation of c-MET expression as determined by Northern blot and immunohistochemistry. c-MET protein was detected by immunohistochemical analysis in a substantial percentage (58 of 128 or 45%) of prostatic carcinomas and was found more often in metastatic growths of human prostatic carcinoma (15 of 20 patients) compared with primary tumors (43 of 108 patients; P < 0.005). Moreover, in Dunning R-3327 rat prostatic carcinoma cell lines, c-MET expression was highest in the androgen-insensitive subline with the highest metastatic capacity. Purified recombinant human HGF induced dose-dependent cellular proliferation and scattering in the DU 145 carcinoma cell line. These data indicate that HGF may function in the prostate gland as a paracrine growth factor, with synthesis by stromal cells and with biological target cells being the epithelial cells. Expression of the HGF receptor, c-MET, is up-regulated by androgen deprivation and c-MET appears to be preferentially expressed on androgen-insensitive, metastatic cells, suggesting a possible linkage of c-MET expression with prostatic carcinoma progression.
Control strategies for smart prosthetic hand technology: An overview (2008)

A chronological overview of the applications of control theory to prosthetic hand is presented. The overview focuses on hard computing or control techniques such as multivariable feedback, optimal, nonlinear, adaptive and robust and soft computing or control techniques such as artificial intelligence, neural networks, fuzzy logic, genetic algorithms and on the fusion of hard and soft control techniques. This overview is not intended to be an exhaustive survey on this topic and any omissions of other works is purely unintentional.
Immunopathogenesis of Pulmonary Tuberculosis (1993)

Antimicrobial therapy quickly eradicates susceptible bacilli, but the fight against drug-resistant disease must be waged entirely by host defenses. Knowledge of the two main types of immune response against tuberculosis and of how to manipulate those mechanisms--leading to precisely designed recombinant BCG vaccines--is essential to mounting an effective attack on the current epidemic.
Polymeric electrooptic 2×2 switch consisting of bifurcation optical active waveguides and a Mach-Zehnder interferometer (2001)

We interpret the modified bifurcation optically active waveguide switch structure for a polymeric electrooptic (EO) 2/spl times/2 switch. PEI-DR1, UFC150, and Resole HM2 were used as the core EO material, the lower clad material, and the upper clad material, respectively. We present the optical and electrical properties on this material system for high-performance devices. We fabricate the electrically and optically packaged polymeric EO 2/spl times/2 switch for high-speed optical communications. At an operating voltage of 8.5 V, the crosstalk of the cross-arm is -18.1 dB, and that of the straight arm is -18.5 dB. The measured optical loss is 14 dB at /spl lambda/=1.3 /spl mu/m. The 6-dB attenuation in radio-frequency transmission corresponds to about 17 GHz.
The Chemistry of Fluorescent Bodipy Dyes: Versatility Unsurpassed (2007)

The world of organic luminophores has been confined for a long time to fairly standard biological labeling applications and to certain analytical tests. Recently, however, the field has undergone a major change of direction, driven by the dual needs to develop novel organic electronic materials and to fuel the rapidly emerging nanotechnologies. Among the many diverse fluorescent molecules, the Bodipy family, first developed as luminescent tags and laser dyes, has become a cornerstone for these new applications. The near future looks extremely bright for "porphyrin's little sister".
Mechanism of Action and Structural Requirements of Constrained Peptide Inhibitors of RGS Proteins (2006)

Regulators of G-protein signaling (RGS) accelerate guanine triphosphate hydrolysis by Galpha-subunits and profoundly inhibit signaling by G protein-coupled receptors. The distinct expression patterns and pathophysiologic regulation of RGS proteins suggest that inhibitors may have therapeutic potential. We previously reported the design of a constrained peptide inhibitor of RGS4 (1: Ac-Val-Lys-[Cys-Thr-Gly-Ile-Cys]-Glu-NH2, S-S) based on the structure of the Galphai switch 1 region but its mechanism of action was not established. In the present study, we show that 1 inhibits RGS4 by mimicking and competing for binding with the switch 1 region of Galphai and that peptide 1 shows selectivity for RGS4 and RGS8 versus RGS7. Structure-activity relationships of analogs related to 1 are described that illustrate key features for RGS inhibition. Finally, we demonstrate activity of the methylene dithioether-bridged peptide inhibitor, 2, to modulate muscarinic receptor-regulated potassium currents in atrial myocytes. These data support the proposed mechanism of action of peptide RGS inhibitors, demonstrate their action in native cells, and provide a starting point for the design of RGS inhibitor drugs.
Abstract 4744: Structure-based development of covalent inhibitors of the activating and T790M gatekeeper mutant forms of the epidermal growth factor receptor (EGFR) leading to the discovery of AZD9291 (2014)

Abstract Small molecule inhibitors of the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase such as gefitinib and erlotinib have been employed successfully in the treatment of non-small cell lung cancer (NSCLC) patients harboring an activating mutation (EGFRm+). However, resistance to these inhibitors in the form of additional mutations such as T790M, (mutation of the gatekeeper residue), is recognized as a clinical issue. This presentation will describe the discovery and evolution of one of our novel chemical series, leading ultimately to the identification of AZD9291, an orally bioavailable, covalent EGFR inhibitor of both the resistance (NCI-H1975, cell phosphorylation IC50 &amp;lt;0.025 uM) and activating mutations (PC9, cell phosphorylation IC50&amp;lt;0.025 uM) that spares inhibition of the wild type form of the receptor (A431, cell phosphorylation IC50&amp;gt;0.5 uM). Wild type EGFR inhibition is believed to drive the observed dose limiting toxicities (such as skin rash and diarrhea) for these first generation therapies in the clinic. New data will be presented for the first time including a broader description of the medicinal chemistry program that led to the identification of AZD9291. We shall also present previously undisclosed work on the identification of additional distinct chemical series and an update of recent data from ongoing AZD9291 Phase I clinical studies in NSCLC patients. L858R/T790M Double Mutant (resistance) cell IC50 uMEGFRm+ Single Mutant (activating) cell IC50 uMEGFR Wild Type cell IC50 uMAqueous solubility, (salt) (pH=6.8, ug/mL)L858R/T790M Double Mutant efficacy (% TGI at 5mpk PO QD for 14 days)&amp;lt;0.025&amp;lt;0.025&amp;gt;0.5&amp;gt;490119 Citation Format: Richard A. Ward, Susan Ashton, Mark Anderton, Pete G. Ballard, Rob H. Bradbury, Sam Butterworth, Nicola Colclough, Darren A E Cross, M Ray V. Finlay, Heather L. McFarland, Martine Mellor, Mike J. Waring. Structure-based development of covalent inhibitors of the activating and T790M gatekeeper mutant forms of the epidermal growth factor receptor (EGFR) leading to the discovery of AZD9291. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4744. doi:10.1158/1538-7445.AM2014-4744
Hyperbranched glycoconjugated polymer from natural small molecule kanamycin as a safe and efficient gene vector (2011)

The exploration of safe and efficient polycationic gene vectors from natural small molecules such as kanamycin was proposed. Cationic hyperbranched glycoconjugated polymer was synthesized by the Michael-addition polymerization of kanamycin and N,N′-methylenebisacrylamide, and the resultant product was well characterized by FTIR, 1H NMR, 13C NMR, SEC-MALLS and ζ-potential analyses. The nitrogen content (7.3%) of this kanamycin-based hyperbranched glycoconjugated polymer was much lower than that (32.6%) of polyethylenimine (PEI) control. Moreover, this resultant polymer could be degraded in acidic conditions. Therefore, the hyperbranched glycoconjugated polymer showed low cytotoxicity, even lower than that of natural biomacromolecule chitosan. Due to the existence of various primary, secondary and tertiary amines in the polymer backbone, hyperbranched glycoconjugated polymer exhibited high buffering capacity and strong pDNA condensation ability. In vitro transfection showed that the luciferase expression of hyperbranched glycoconjugated polymer was about 4.4 × 108 RLU per mg protein, approximately 33-fold greater than that of chitosan transfection. These results demonstrate that the construction of highly branched polycations from natural small molecules provides a new opportunity for developing safe and efficient gene vectors.
Enzymatic synthesis of carbohydrate esters of fatty acid (I) esterification of sucrose, glucose, fructose and sorbitol (1984)

Abstract The authors attempted to synthesize carbohydrate esters of fatty acids enzymatically in order to overcome the problems associated with the chemical processes for the synthesis of commercial sucrose esters. The enzymes used were lipases from microorganisms belonging to Rhyzopus, Enterbacterium, Aspergillus, Pseudomonas, Chromobacterium, Candida, Mucor and Penicillium . Fatty acids (stearic, oleic and linoleic) and carbohydrates (sucrose, glucose, fructose and sorbitol) used for the reaction were obtained from commercial sources. The enzyme reaction was performed by mixing the enzyme and the substrates in the buffer solution and incubating at 40 C; after freeze‐drying the mixture, the products were extracted and subjected to thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). It was observed by TLC and HPLC that carbohydrate esters of fatty acid were produced by the enzyme reaction, and their structures were confirmed by infra red (IR) and nuclear magnetic resonance (NMR) spectrometries. The lipase from Candida cylindracea was the most enzyme active on the synthesis of carbohydrate esters. The optimum conditions for its activity were as follows: molar ratio of carbohydrate to fatty acid: 0.05mol/l : 0.2mol/l; amount of lipase: 4g/l; pH of the reaction mixture: 5.4 in phosphate buffer; reaction period: 72 hr.
Relapsing Clostridium difficile Enterocolitis Cured by Rectal Infusion of Normal Faeces (1984)

Repeated recurrence of Clostridium difficile-associated enterocolitis is uncommon but troublesome for the afflicted patient. The patient described here received vancomycin treatment several times but always had a relapse of C. difficile enterocolitis 2-3 weeks after discontinuation of treatment. She did not form serum antibodies to C. difficile cytotoxin (toxin B). Rectal infusion of enemas prepared from fresh faeces resulted in final cure.
Brokered collaborative infrastructure for CSCW (2002)

We demonstrate the advantages of a distributed collaborative system for CSCW and highlight the requirements of brokered support for such a system. We also demonstrate how we have augmented the infrastructure of a prototype CSCW environment called SHASTRA to accommodate brokered collaboration. Several applications and possible scenarios of CSCW with brokered cooperative system are also presented. We describe how brokers can be used to exploit plurality and commonality of tasks in a cooperative setting, improving performance for the entire system.
The α-Helical to β-Strand Transition in the Amino-terminal Fragment of the Amyloid β-Peptide Modulates Amyloid Formation (1995)

Amyloid-beta peptide (A beta) consists of a hydrophobic C-terminal domain (residues 29-42) that adopts beta-strand conformation and an N-terminal domain (amino acids 10-24) whose sequence permits the existence of a dynamic equilibrium between an alpha-helix and a beta-strand. In this paper we analyzed the effect of the alternate N-terminal conformations on amyloid fibril formation through the study of the analogous A beta peptides containing single amino acidic substitutions. The single mutation of valine 18 to alanine induces a significant increment of the alpha-helical content of A beta, determined by Fourier transform infrared spectroscopy and circular dichroism and dramatically diminishes fibrillogenesis, measured by turbidity, thioflavine T binding, Congo red staining, and electron microscopic examination. In hereditary Dutch cerebral hemorrhage with amyloidosis (a variant of Alzheimer's disease), the substitution of glutamine for glutamic acid at position 22 decreased the propensity of the A beta N-terminal domain to adopt an alpha-helical structure, with a concomitant increase in amyloid formation. We propose that A beta exists in an equilibrium between two species: one "able" and another "unable" to form amyloid, depending on the secondary structure adopted by the N-terminal domain. Thus, manipulation of the A beta secondary structure with therapeutical compounds that promote the alpha-helical conformation may provides a tool to control the amyloid deposition observed in Alzheimer's disease patients.
The movement and entrapment of petroleum fluids in the subsurface (1987)

This paper discusses the migration of petroleum from its formation in a source rock to its subsequent possible entrapment in a reservoir. The chemical and physical properties of petroleum gases and liquids are stressed, particularly their phase behaviour under subsurface conditions which is shown to be a very important factor in determining migration behaviour. Engineering correlations are presented for estimating the properties of petroleum fluids under geologically realistic conditions. The directions and magnitudes of the forces acting on migrating petroleum are deduced from the combined effects of buoyancy and water flow in compacting sediments. These forces are combined, using a fluid potential description. This procedure allows the direction of migration to be denned. The rate of migration is then estimated from the properties of the sediments involved, allowing a distinction to be made between ‘lateral’ and ‘vertical’ carrier beds. This simplified approach is suitable for rapid predictive calculations in petroleum exploration. It is compared with the more complex 3-D computer modelling approaches which are currently becoming available. Migration losses are related to the cumulative pore volume employed by the petroleum in establishing a migration pathway. The petroleum migration mechanism is shown to be predominantly by bulk flow, with a small diffusive contribution for light hydrocarbons over distances less than c. 100 m. The loss factors involved in secondary migration are estimated from field evidence. The mechanism of reservoir filling is presented as a logical extension to those described for migration. This, together with the inefficiency of in-reservoir mixing by diffusion or convection, is shown to tend to cause significant lateral compostional gradients in reservoirs over and above the gravitationally induced vertical gradients described by other workers.
Is blood glucose predictable from previous values? A solicitation for data. (1999)

An important question about blood glucose control in diabetes is, Can present and future blood glucose values be predicted from recent blood glucose history? If this is possible, new continuous blood glucose monitoring technologies under development may lead to qualitatively better therapeutic capabilities. Not only could continuous monitoring technologies alert a user when a hypoglycemic episode or other blood glucose excursion is underway, but measurements may also provide sufficient information to predict near-future blood glucose values. A predictive capability based only on recent blood glucose history would be advantageous because there would be no need to involve models of glucose and insulin distribution, with their inherent requirement for detailed accounting of vascular glucose loads and insulin availability. Published data analyzed here indicate that blood glucose dynamics are not random, and that blood glucose values can be predicted, at least for the near future, from frequently sampled previous values. Data useful in further exploring this concept are limited, however, and an appeal is made for collection of more.
Wave-breaking-free pulses in nonlinear-optical fibers (1993)

A qualitative as well as quantitative investigation is made of the conditions for avoiding wave breaking during pulse propagation in optical fibers. In particular, it is shown that pulses having a parabolic intensity variation are approximate wave-breaking-free solutions of the nonlinear Schrödinger equation in the high-intensity limit. A simple expression for the compression factor of a fiber-grating compressor based on parabolic pulses is also derived.
Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates. (1995)

Trial therapy for lymphoma with the radiolabeled chelate-antibody conjugate 67Cu-2IT-BAT-Lym-1 has been promising. It is desirable to deliver therapeutic doses of radiometal using a minimum amount of 2IT-BAT-Lym-1 to minimize the risks of adverse patient reaction and antigenic response to antibody. This is readily accomplished by increasing the number of metal-binding sites (i.e., chelating agents) conjugated per antibody, but the ability of the antibody to bind antigen and target tumor cells in vivo must not be impaired by the conjugation reaction. To determine the maximum chelator:antibody ratio (c/a) of 2IT-BAT-Lym-1 at which functional integrity is preserved, immunoconjugates with a c/a of 1.3-23 were prepared and examined by radioimmunoassay and competitive antigen binding versus lightly iodinated Lym-1. The biodistribution in tumored mice of conjugates with c/a of 2.1, 4.3, 8.4, and 11.4 also was examined. Conjugates with c/a up to 5 exhibited no loss of immunoreactivity, and conjugates with c/a up to 11 retained 75% or greater immunoreactivity relative to unmodified Lym-1. All conjugates examined competed less effectively than did unmodified Lym-1 for antigen binding, but the effect at c/a 5 was slight. Tumor uptake declined with increasing c/a, but the effect was insignificant at c/a 2.1 and 4.3. Conjugates of c/a 4-5 were found to be optimal for the preparation of radioimmunoconjugate of high specific activity with minimal, if any, loss of functional integrity.