gebhart/patrepeval huggingface dataset:
Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer (2009)

IL-15 has potential as an immunotherapeutic agent for cancer treatment because it is a critical factor for the proliferation and activation of natural killer (NK) and CD8(+) T cells. Administration of anti-CD40 antibodies has shown anti-tumor effects in vivo through a variety of mechanisms. Furthermore, activation of CD40 led to increased expression of IL-15 receptor-alpha by dendritic cells, an action that is critical for trans-presentation of IL-15 to NK and CD8(+) T cells. In this study, we investigated the therapeutic efficacy of the combination regimen of murine IL-15 (mIL-15) with an agonistic anti-CD40 antibody (FGK4.5) in murine lung metastasis models involving CT26 and MC38, which are murine colon cancer cell lines syngeneic to BALB/c and C57BL/6 mice, respectively. Treatment with mIL-15 or the anti-CD40 antibody alone significantly prolonged survival of both CT26 and MC38 tumor-bearing mice compared with the mice in the PBS solution control group (P < 0.01). Furthermore, combination therapy with both mIL-15 and the anti-CD40 antibody provided greater therapeutic efficacy as demonstrated by prolonged survival of the mice compared with either mIL-15 or the anti-CD40 antibody-alone groups (P < 0.001). We found that NK cells isolated from the mice that received the combination regimen expressed increased levels of intracellular granzyme B and showed stronger cytotoxic activity on the target cells. The findings from this study provide the scientific basis for clinical trials using the combination regimen of IL-15 with an anti-CD40 antibody for the treatment of patients with cancer.
Conversion of cysteine to serine residues alters the activity, stability, and heparin dependence of acidic fibroblast growth factor. (1991)

Acidic fibroblast growth factor (aFGF) is a broad spectrum mitogen that is stabilized by complexation with heparin and heparan proteoglycans. The monomeric human protein contains 3 reduced cysteine residues of unknown function, the first 2 of which are conserved among all seven known fibroblast growth factors. The influence of these free sulfhydryl groups on the level, stability, and heparin dependence of the mitogenic activity at physiological temperature and pH is characterized using a complete set of site-directed mutants in which either any 1, 2, or all 3 of the cysteine residues are converted to serines. Mutants of aFGF in which either any 2 or all 3 cysteine residues are substituted by serines are more active, have longer activity half-lives, and are less heparin dependent than wild-type aFGF. In contrast, wild-type aFGF and the three mutants that each retain 2 cysteine residues inactivate more rapidly in the absence of heparin by a nonproteolytic mechanism but are markedly stabilized by heparin. This cysteine-mediated destabilization of aFGF not only diminishes its activity in the absence of heparin in tissue culture but also could functionally restrict its activity in vivo to the vicinity of mast cell-derived heparins and heparan proteoglycans associated with cell surfaces and basement membranes.
Studies related to antibody fragment (Fab) production in <i>Escherichia coli</i> W3110 fed‐batch fermentation processes using multiparameter flow cytometry (2008)

Microbiology is important to industry therefore rapid and statistically representative measurements of cell physiological state, proliferation, and viability are essential if informed decisions about fermentation bioprocess optimization or control are to be made, because process performance will depend largely on the number of metabolically active viable cells. Samples of recombinant Escherichia coli W3110, containing the gene for the D1.3 anti-lysozyme Fab fragment under the control of the lac-based expression system, were taken at various stages from fed-batch fermentation processes and stained with a mixture of bis-(1,3-dibutylbarbituric acid) trimethine oxonol and propidium iodide (PI/BOX). Where appropriate, measurements of dissolved oxygen tension (DOT), OD600nm and Fab concentration were made. Depending on time of induction the maximum amount of Fab accumulating in the supernatant varied quite markedly from 1 to 4 microg ml(-1) as did subsequent cell physiological state with respect to PI/BOX staining with a concomitant drop in maximum biomass concentration. Depending on point of induction a fourfold increase in Fab production could be achieved accompanied by a approximately 50% drop in maximum biomass concentration but with a higher proportion of viable cells as measured by multiparameter flow cytometry.
Reducing human effort and improving quality in peer code reviews using automatic static analysis and reviewer recommendation (2013)

Peer code review is a cost-effective software defect detection technique. Tool assisted code review is a form of peer code review, which can improve both quality and quantity of reviews. However, there is a significant amount of human effort involved even in tool based code reviews. Using static analysis tools, it is possible to reduce the human effort by automating the checks for coding standard violations and common defect patterns. Towards this goal, we propose a tool called Review Bot for the integration of automatic static analysis with the code review process. Review Bot uses output of multiple static analysis tools to publish reviews automatically. Through a user study, we show that integrating static analysis tools with code review process can improve the quality of code review. The developer feedback for a subset of comments from automatic reviews shows that the developers agree to fix 93% of all the automatically generated comments. There is only 14.71% of all the accepted comments which need improvements in terms of priority, comment message, etc. Another problem with tool assisted code review is the assignment of appropriate reviewers. Review Bot solves this problem by generating reviewer recommendations based on change history of source code lines. Our experimental results show that the recommendation accuracy is in the range of 60%-92%, which is significantly better than a comparable method based on file change history.
The expression and localization of β-endorphin and µ,δ-opioid receptors in synovial tissues in patient with rheumatoid arthritis and osteoarthritis (2003)

Abstract An examination of the localization and distribution of β-endorphin and opioid receptors in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemical staining, reverse transcription polymerase chain reaction (RT-PCR) analysis, and in situ hybridization were performed using synovial tissues obtained from RA and OA patients. Immunohistochemical staining showed that β-endorphin was strongly expressed in synovial lining cells and in a few lymphocytes and macrophages surrounding the vessels, whereas µ- and δ-opioid receptors were expressed in lymphocytes and macrophages. However, we detected the weak expression of these opioid peptides in synovial tissues of OA patients. RT-PCR analysis showed that preproopiomelanocortin (POMC) mRNA, a precursor of β-endorphin, was strongly expressed in synovial tissues of RA patients, but these PCR products of synovial tissues obtained from OA patients were weakly detected compared with those from RA patients. POMC mRNA was also expressed in synovial tissues in RA patients. In in situ hybridization, the expression of POMC mRNA was detected in macrophages, synovial lining cells, and fibroblasts in synovial tissues of RA patients as well as β-endorphin. In RA patients, β-endorphin and µ- and δ-opioid receptors are synthesized and located in synovial lining cells, lymphocytes, and macrophages surrounding the vessels in synovial tissues, and may play a role in the regulation and modulation of inflammation.
Modulation of associated ovarian carcinoma antigens by 5 cytokines used as single agents or in combination (1994)

Optimization of intraperitoneal radioimmunotherapy of ovarian cancer depends on increasing the antigenic expression of tumor cells. For this purpose, we studied the effect of 5 cytokines (IFN-alpha, IFN-beta, IFN-gamma, TNF-alpha and TGF-beta), used as single agents or in combination, on 4 ovarian cancer cell lines which present different antigenic profiles with the monoclonal antibodies (MAbs) tested (OC125, OVTL-3, MOv 18 and MOv 19). Analyses were performed by flow cytometry and the Scatchard technique in order to study antigenic modulation. The effect on proliferation was determined by cell counting. Expression of O3 antigen, recognized by the OVTL3 MAb, was increased up to 2.5 times after IFNs and TNF-alpha (used as single agent) on the 2 lines presenting low basal expression (SHIN-3 and IGROVI). The expression of CA125 antigen and the antigens recognized by MOv 18 and MOv 19 MAbs was not increased by any of the cytokines tested. The combination IFN-gamma+TNF-alpha was synergistic on cytotoxicity and enhanced O3 expression, providing 10 times as many sites per cell on the SHIN-3 line. For 3 other associations (IFN-alpha+IFN-gamma, IFN-beta+IFN-gamma and IFN-alpha+TNF-alpha), there was an additive effect on O3 expression and on cell cytotoxicity.
Defining dementia in old age (1998)

Dementia describes a condition characterized by loss of memory and skills, and a change in personality and behaviour caused by a variety of illnesses, the commonest and most well known being Alzheimer's disease. Practice nurses can be in the forefront of identifying dementia and arranging appropriate intervention.
The family of berberine bridge enzyme-like enzymes: A treasure-trove of oxidative reactions (2017)

Biological oxidations form the basis of life on earth by utilizing organic compounds as electron donors to drive the generation of metabolic energy carriers, such as ATP. Oxidative reactions are also important for the biosynthesis of complex compounds, i.e. natural products such as alkaloids that provide vital benefits for organisms in all kingdoms of life. The vitamin B<sub>2</sub>-derived cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) enable an astonishingly diverse array of oxidative reactions that is based on the versatility of the redox-active isoalloxazine ring. The family of FAD-linked oxidases can be divided into subgroups depending on specific sequence features in an otherwise very similar structural context. The sub-family of berberine bridge enzyme (BBE)-like enzymes has recently attracted a lot of attention due to the challenging chemistry catalyzed by its members and the unique and unusual bi-covalent attachment of the FAD cofactor. This family is the focus of the present review highlighting recent advancements into the structural and functional aspects of members from bacteria, fungi and plants. In view of the unprecedented reaction catalyzed by the family's namesake, BBE from the California poppy, recent studies have provided further insights into nature's treasure chest of oxidative reactions.
Transformation of a filamentous cyanobacterium by electroporation (1989)

The filamentous cyanobacterium Anabaena sp. strain M131 was transformed with the shuttle vector pRL6 by electroporation. Optimum conditions for electroporation required relatively high field strengths with short time constants. Restriction significantly lowered the efficiency of transformation. A plasmid containing a single unmodified AvaII restriction site transformed cells with about 100-fold-lower efficiency than did the same plasmid with a modified restriction site.
Fabrication of micro power source (MPS) using a micro direct methanol fuel cell (μDMFC) for the medical application (2002)

This paper presents the fabrication and test of a micro power source (MPS) using a micro direct methanol fuel cell (/spl mu/DMFC). Micro power sources are essential for cellular phones, portable electronics and MEMS devices to be miniaturized. The /spl mu/DMFC has a simple structure. The /spl mu/DMFC consists of one proton exchange membrane (PEM) and two silicon substrates with channels. The width and the depth of the micro channel are 250 /spl mu/m and 50 /spl mu/m, respectively. The dimension of one unit of /spl mu/DMFC is 16 mm/spl times/16 mm/spl times/1.2 mm. When fuel (methanol:water=1:1) is supplied to the fabricated cell, the measured output voltage is 100 mV at 25/spl deg/C and the atmospheric pressure.
Value-added Internet: a pragmatic TINA-based path to the Internet and PSTN integration (2002)

The paper deals with the issue of integrating the Internet with the PSTN in order to devise an architecture encompassing the advantages of both networks. Key TINA concepts like the Session Concept and the Service Architecture computational model are used to provide the glue for such an integration. The result is the enhancement of the Internet with real time packet delivery capability as well as advanced billing features that successfully exploit existing billing systems. A comparison with other approaches to quality of service over the Internet is provided. The prototype that is currently being developed within the SISTINA (Solutions for Integrated Services a la TINA) project to demonstrate the concepts outlined in the paper is described.
Effectiveness of Phages in Treating Experimental Escherichia coli Diarrhoea in Calves, Piglets and Lambs (1983)

A mixture of two phages, B44/1 and B44/2, protected calves against a potentially lethal oral infection with an O9:K30,99 enteropathogenic strain of Escherichia coli, called B44, when given before, but not after, the onset of diarrhoea; a mixture in which phage B44/3 was replaced by phage B44/3 was effective after the onset of diarrhoea. Calves that responded to phage treatment had much lower numbers of E. coli B44 in their alimentary tract than untreated calves. Usually, high numbers of phage B44/1 and rather lower numbers of phage B44/2 or B44/3 were present in the alimentary tract of these animals. At death, most calves that had not responded to treatment with phages B44/1 and B44/2 had high numbers of mutants of E. coli B44 resistant to phage B44/1 in their small intestine. Phage-treated calves that survived E. coli infection continued to excrete phage in their faeces, at least until the numbers of E. coli B44 also excreted were low. The phages survived longer than E. coli B44 in faecal samples taken from phage-treated calves and exposed to the atmosphere in an unheated animal house. Calves inoculated orally with faecal samples from phage-treated calves that contained sufficient E. coli B44 to cause a lethal infection remained healthy. A mixture of two phages, P433/1 and P433/2, and phage P433/1 alone cured diarrhoea in piglets caused by an O20:K101,987P strain of E. coli called P433. The numbers of the infecting bacteria and phages in the alimentary tract of the piglets resembled those in the calves. Another phage given to lambs 8 h after they were infected with an O8:K85,99 enteropathogenic strain of E. coli, called S13, reduced the numbers of these organisms in the alimentary tract and had an ameliorating effect on the course of the disease. No phage-resistant mutants of E. coli S13 were isolated from the lambs. The only mutants of E. coli B44 and P433 that emerged in the calves and piglets were K30- or K101- and resistant to phage B44/1 or P433/1 respectively; those tested were much less virulent than their parent strains.
Metabolic Approaches To Enhance Transdermal Drug Delivery. 1. Effect of Lipid Synthesis Inhibitors (1996)

The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following application of conventional, chemical penetration enhancers, cause a further boost in drug delivery, attributable to the ability of these agents to alter both permeability barrier homeostasis and thermodynamics. This biochemical/metabolic approach provides a novel means to enhance transdermal drug delivery in conjunction with the concurrent or prior use of chemical enhancers.
OPTIMIZING THE SCENARIO POSITIONS FOR ROBUST RADIATION THERAPY TREATMENT PLANNING (2012)

Complex external beam radiation therapy treatment plans are susceptible to errors. Robust optimization methods that take uncertainties into account during the optimization can alleviate the effects of the errors. For many robust methods, the possible error realizations are discretized into scenarios. The methods then aim at achieving high quality plans in all scenarios simultaneously. The choice of scenarios has high impact on the quality of the plans: when the optimization is aimed at high target coverage in scenarios that are incompatible with healthy tissue sparing in other scenarios, the plan quality in all scenarios may suffer. It can then be beneficial to reduce the range of errors the scenarios represent. To accomplish this, we propose a method that determines how large errors that can be accounted for in robust optimization of intensity-modulated photon and proton therapy. It does so by optimizing the scenario positions along predefined directions simultaneously with the direct machine parameter optimization, under constraints on target coverage and healthy tissue sparing. For both modalities, scenario position optimization was applied to a prostate case and a lung case. The optimization reduced the ranges of errors that were accounted for compared to the a priori ranges. The determined scenario positions were used in robust optimization with fixed scenarios. This resulted in plans that satisfied a substantially larger number of constraints in the determined scenarios and moreover a larger number of constraints in the a priori scenarios than the plans optimized with a priori scenario positions. 1.
Genetic Networks Controlling the Initiation of Sporulation and the Development of Genetic Competence in Bacillus subtilis (1995)

We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ...Read More
Efficient One-Pot Synthesis of 1-Aryl 1,2,3-Triazoles from Aryl Halides and Terminal Alkynes in the Presence of Sodium Azide (2005)

An efficient one-pot synthesis of 1-aryl 1,2,3-triazoles from aryl bromides/iodides and terminal alkynes in the presence of sodium azide is described. In the case of aryl iodides, the reactions proceeded at room temperature. The reactions normally gave high yields.
LOW-TEMPERATURE (&amp;lt;300ºC) LOW-STRESS SILICON CARBIDE SURFACE MICROMACHINING FABRICATION TECHNOLOGY (2008)

A low temperature (<300C), low-stress micro electromechanical systems fabrication process based on a silicon carbide structural layer is presented. A Hexoloy-SG target enables lowtemperature DC sputtering of amorphous silicon carbide. The process is designed for low-cost implementation and CMOS postintegration stemming from chemical and thermal compatibility. Process flow, deposition, etching, and stress control are discussed, and the electrical transfer characteristic of a fabricated resonator device is reported to demonstrate a process application.
Correlation between morphology of optic disc determined by Heidelberg Retina Tomograph II and visual function in eyes with open-angle glaucoma (2010)

The correlation between the HRT-II parameters and MDs was different for the four disc types. These findings suggest that a classification of optic disc morphology had a benefit for interpreting the measured values of HRT-II.
Prolonged but Delayed Postischemic Hypothermia: A Long-term Outcome Study in the Rat Middle Cerebral Artery Occlusion Model (2000)

Delayed but prolonged hypothermia persistently decreases cell death and functional deficits after global cerebral ischemia in rodents. Postischemic hypothermia also reduces infarction after middle cerebral artery occlusion (MCAO) in rat. Because initial neuroprotection is sometimes transient and may not subserve functional recovery, especially on demanding tasks, the authors examined whether postischemic cooling would persistently reduce infarction and forelimb reaching deficits after MCAO. Male spontaneously hypertensive rats were trained to retrieve food pellets in a staircase test that measures independent forelimb reaching ability. Later, rats underwent 90 minutes of normothermic MCAO, through a microclip, or sham operation. In some rats, prolonged cooling (33 degrees C for 24 hours and then 35 degrees C for 24 hours) began 2.5 hours after the onset of ischemia (60 minutes after the start of reperfusion; n = 17 with subsequently 1 death) or sham procedures (n = 4), whereas untreated sham (n = 4) and ischemic (n = 16 with subsequently 1 death) rats maintained normothermia. An indwelling abdominal probe continually measured core temperature, and an automated fan and water spray system was used to produce hypothermia. One month later rats were reassessed in the staircase test over five days and then killed. The contralateral limb impairment in food pellet retrieval was completely prevented by hypothermia (P = 0.0001). Hypothermia reduced an infarct volume of 67.5 mm3 after untreated ischemia to 35.8 mm3 (P < 0.0001). These findings of persistent benefit encourage the clinical assessment of hypothermia.