gebhart/patrepeval huggingface dataset:
Universal lab-on-a-chip platform for complex, perfused 3D cell cultures (2016)

The miniaturization, rapid prototyping and automation of lab-on-a-chip technology play nowadays a very important role. Lab-on-a-chip technology is successfully implemented not only for environmental analysis and medical diagnostics, but also as replacement of animals used for the testing of substances in the pharmaceutical and cosmetics industries. For that purpose the Fraunhofer IWS and partners developed a lab-on-a-chip platform for perfused cell-based assays in the last years, which includes different micropumps, valves, channels, reservoirs and customized cell culture modules. This technology is already implemented for the characterization of different human cell cultures and organoids, like skin, liver, endothelium, hair follicle and nephron. The advanced universal lab-on-a-chip platform for complex, perfused 3D cell cultures is divided into a multilayer basic chip with integrated micropump and application-specific 3D printed cell culture modules. Moreover a technology for surface modification of the printed cell culture modules by laser micro structuring and a complex and flexibly programmable controlling device based on an embedded Linux system was developed. A universal lab-on-a-chip platform with an optional oxygenator and a cell culture module for cubic scaffolds as well as first cell culture experiments within the cell culture device will be presented. The module is designed for direct interaction with robotic dispenser systems. This offers the opportunity to combine direct organ printing of cells and scaffolds with the microfluidic cell culture module. The characterization of the developed system was done by means of Micro-Particle Image Velocimetry (&mu;PIV) and an optical oxygen measuring system.
Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue (2009)

Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which resulted from a reduced lean body mass and preferential sparing of adipose tissue. Castration decreased gastrocnemius weight, but this atrophy was not associated with reduced basal muscle protein synthesis or differences in plasma IGF-I, insulin, or individual amino acids. However, oral leucine failed to normally stimulate muscle protein synthesis in castrated rats. In addition, castration-induced atrophy was associated with increased 3-methylhistidine excretion and in vitro-determined ubiquitin proteasome activity in skeletal muscle, changes that were associated with decreased atrogin-1 or MuRF1 mRNA expression. Castration decreased heart and kidney weight without reducing protein synthesis and did not alter either cardiac output or glomerular filtration. In contradistinction, the weight of the retroperitoneal fat depot was increased in castrated rats. This increase was associated with an elevated rate of basal protein synthesis, which was unresponsive to leucine stimulation. Castration also decreased whole body fat oxidation. Castration increased TNFα, IL-1α, IL-6, and NOS2 mRNA in fat but not muscle. In summary, the castration-induced muscle wasting results from an increased muscle protein breakdown and the inability of leucine to stimulate protein synthesis, whereas the expansion of the retroperitoneal fat depot appears mediated in part by an increased basal rate of protein synthesis-associated increased inflammatory cytokine expression.
DNAzymes Targeting the icl Gene Inhibit ICL Expression and Decrease Mycobacterium tuberculosis Survival in Macrophages (2005)

Latent infection with Mycobacterium tuberculosis presents a big obstacle for tuberculosis therapy. In this study, we investigated the effects of sequence-specific DNAzymes targeting the mRNA of isocitrate lyase (ICL), an enzyme playing a pivotal role in the metabolism of M. tuberculosis in the latent state, on the expression of ICL and survival of M. tuberculosis. In vitro studies showed that four of five designed DNAzymes, DZ1, DZ3, DZ4, and DZ5 could cleave icl mRNA efficiently and specifically. Treatment of virulent M. tuberculosis with 5microM DZ4 plus a subinhibitory concentration of isoniazid (INH) decreased ICL expression and the survival of M. tuberculosis in macrophages but had no obvious influence on the growth of M. tuberculosis in vitro. This study demonstrates that using INH to soften the cell wall of M. tuberculosis and help the entry of biomolecules is an efficient method of improving the uptake of DNAzymes. Silencing the icl gene by DNAzyme is a promising method to combat latent infection of tuberculosis.
The Characterization of a Bio-Assay of Erectile Function in a Rat Model (1991)

The investigation of biological phenomena in impotence using an animal system requires a determination of the erectile capabilities of the animal. Rats respond reliably to apomorphine by the exhibition of a phenomenon of erections and yawns. This property has been used to form the basis of a bio-assay of erectile integrity in the rat. We compared rats treated with placebo alone, sham operated rats, rats rendered surgically impotent and castrated rats with and without testosterone. Rats did not respond to placebo. The sham operated rats remained normal in all measured respects (2.66 erections/rat/30 minutes). Surgically impotent rats yawned normally but had no erections. Castrated rats did not have erections and had diminished yawning (3.21 yawns/rat/30 minutes vs. 7.7 for controls p less than .001) but responded normally after testosterone administration. The bio-assay is useful as a standard test of erectile function in the rat.
Glucagon-Like Peptide-1 (GLP-1) Receptors Expressed on Nerve Terminals in the Portal Vein Mediate the Effects of Endogenous GLP-1 on Glucose Tolerance in Rats (2007)

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that is secreted during meal absorption and is essential for normal glucose homeostasis. However, the relatively low plasma levels and rapid metabolism of GLP-1 raise questions as to whether direct endocrine action on target organs, such as islet cells, account for all of its effects on glucose tolerance. Recently, an alternative neural pathway initiated by sensors in the hepatic portal region has been proposed to mediate GLP-1 activity. We hypothesized that visceral afferent neurons in the portal bed express the GLP-1 receptor (GLP-1r) and regulate glucose tolerance. Consistent with this hypothesis, GLP-1r mRNA was present in the nodose ganglia, and nerve terminals innervating the portal vein contained the GLP-1r. Rats given an intraportal infusion of the GLP-1r antagonist, [des-His(1),Glu(9)] exendin-4, in a low dose, had glucose intolerance, with a 53% higher glucose excursion compared with a vehicle-infused control group. Infusion of [des-His(1),Glu(9)] exendin-4 at an identical rate into the jugular vein had no effect on glucose tolerance, demonstrating that this dose of GLP-1r antagonist did not affect blood glucose due to spillover into the systemic circulation. These studies demonstrate that GLP-1r are present on nerve terminals in the hepatic portal bed and that GLP-1 antagonism localized to this region impairs glucose tolerance. These data are consistent with an important component of neural mediation of GLP-1 action.
Nanobody Based Dual Specific CARs (2018)

Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.
Different Facets of Copy Number Changes: Permanent, Transient, and Adaptive (2016)

Chromosomal copy number changes are frequently associated with harmful consequences and are thought of as an underlying mechanism for the development of diseases. However, changes in copy number are observed during development and occur during normal biological processes. In this review, we highlight the causes and consequences of copy number changes in normal physiologic processes as well as cover their associations with cancer and acquired drug resistance. We discuss the permanent and transient nature of copy number gains and relate these observations to a new mechanism driving transient site-specific copy gains (TSSGs). Finally, we discuss implications of TSSGs in generating intratumoral heterogeneity and tumor evolution and how TSSGs can influence the therapeutic response in cancer.
In vivo antigen delivery by aSalmonella typhimurium type III secretion system for therapeutic cancer vaccines (2006)

Bacterial vectors may offer many advantages over other antigen delivery systems for cancer vaccines. We engineered a Salmonella typhimurium vaccine strain to deliver the NY-ESO-1 tumor antigen (S. typhimurium-NY-ESO-1) through a type III protein secretion system. The S. typhimurium-NY-ESO-1 construct elicited NY-ESO-1-specific CD8+ and CD4+ T cells from peripheral blood lymphocytes of cancer patients in vitro. Oral administration of S. typhimurium-NY-ESO-1 to mice resulted in the regression of established NY-ESO-1-expressing tumors. Intratumoral inoculation of S. typhimurium-NY-ESO-1 to NY-ESO-1-negative tumors resulted in delivery of antigen in vivo and led to tumor regression in the presence of preexisting NY-ESO-1-specific CD8+ T cells. Specific T cell responses against at least 2 unrelated tumor antigens not contained in the vaccine were observed, demonstrating epitope spreading. We propose that antigen delivery through the S. typhimurium type III secretion system is a promising novel strategy for cancer vaccine development.
Optimal control theory : an introduction (1970)

Optimal control theory is the science of maximizing the returns from and minimizing the costs of the operation of physical, social, and economic processes. Geared toward upper-level undergraduates, this text introduces three aspects of optimal control theory: dynamic programming, Pontryagin's minimum principle, and numerical techniques for trajectory optimization.Chapters 1 and 2 focus on describing systems and evaluating their performances. Chapter 3 deals with dynamic programming. The calculus of variations and Pontryagin's minimum principle are the subjects of chapters 4 and 5, and chapter
L1TD1 Is a Marker for Undifferentiated Human Embryonic Stem Cells (2011)

Taken together, our results suggest that L1TD1 is a downstream target of Nanog and represents a useful marker for identifying undifferentiated hESC.
A Study on Improving Luma-based Chroma Intra Prediction Method (2012)

In luma-based chroma intra prediction in an HEVC test model, chroma samples are predicted from down-sampled luma samples of the same block by a linear model relationship. We propose improving the prediction performance by applying horizontal filtering to luma samples which removes the horizontal aliasing effect. Experimental results using HM-3.0 had up to a 1.7% BD rate improvement of the chroma signals.
Characterization of the restriction site of a prokaryotic intron-encoded endonuclease. (1990)

The 1016-base-pair (bp) intron in the T4 bacteriophage thymidylate synthase gene (td) contains a 735-bp open reading frame that encodes a protein product with endonucleolytic activity. The endonuclease shows specificity for the intronless form of the td gene. Highly purified endonuclease cleaves the DNA of the intronless form of the td gene in vitro at 24 bp upstream of the exon 1-exon 2 junction, generating a 2-base staggered cut with 3'-hydroxyl overhangs. Although the endonuclease cleaves in exon 1, it requires some exon 2 sequence for recognition. The maximum recognition sequence lies in an 87-bp stretch, from 52 bp upstream to 35 bp downstream of the cleavage site, ending at 11 bp into exon 2. The td intron endonuclease appears involved in the conversion of the intronless form of td to intron-containing td gene in the T-even phages. A role for intron mobility is discussed.
The Purification of Poly(A)- Containing RNA by Affinity Chromatography (2003)

The vast majority of eukaryotic mRNA molecules contain tracts of poly(adenylic) acid, up to 250 bases in length, at the 3' end. This property is very useful from the point of view of mRNA extraction because it forms the basis of a convenient and simple affinity chromatography procedure (1). Under high salt conditions (0.3-0.5M NaCl or KCl), poly(A) will hybridize to oligo(dT)-cellulose or poly(U)-Sepharose. These commercially available materials consist of polymers of about 10-20 nucleotides, covalently bound to a carbohydrate support, and bind RNA containing a poly(A) tract as short as 20 residues. Ribosomal and transfer RNAs do not possess poly(A) sequences and will not bind (see Note 1).
Videotex: advancing to higher bandwidth (1988)

A description is given of a videotex communications system called Captain, (character and pattern telephone access information network), which has been providing commercial services since November 1984 to all major cities in Japan. HI-Captain, a full-color videotex system for local applications, and Super Captain, a video response system, are also described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Design, Synthesis, and Evaluation of an α-Helix Mimetic Library Targeting Protein−Protein Interactions (2009)

The design and solution-phase synthesis of an alpha-helix mimetic library as an integral component of a small-molecule library targeting protein-protein interactions are described. The iterative design, synthesis, and evaluation of the candidate alpha-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 x 20 x 20-mix), where the added subunits are designed to mimic all possible permutations of the naturally occurring i, i + 4, i + 7 amino acid side chains of an alpha-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead alpha-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an alpha-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.
Blood flow distribution and tissue allometry in channel catfish (1999)

Blood flow (as percentage of cardiac output) in fasted channel catfish acclimated to 21°C was directed primarily to white muscle (72%) followed by head kidney (5·7%), red muscle (5·5%), trunk kidney (3·1%), liver (2·2%), swim bladder (1·4%) and skin (1·1%). The stomach, intestines, pyloric caeca, gonads, brain, abdominal fat and spleen contained &lt;0·5% of blood flow. There was considerable interfish variation among blood flow distribution to visceral organs with substantial spatial heterogeneity of blood flow to white muscle. The spatial heterogeneity of flow to muscle prevented accurate estimation of total flow to this tissue based on the microsphere deposition of a few sub‐samples. Instead, a novel approach, based on the whole animal counting of the eviscerated carcass was used to measure blood flow to white muscle. The scaling relationships for tissue mass in catfish (63–1873 g) followed the allometric equation (aW b ) and tended to exhibit negative allometry, with organ weight decreasing in proportion to body weight. The b values for most tissues ranged between 0·83 and 1·0. The relative mass of the brain showed the greatest decline and with a b value of 0·32. The results, together with previous data on cardiac output, permitted calculation of organ blood flow rates in channel catfish. © 1999 The Fisheries Society of the British Isles
A fine-grained debugger for aspect-oriented programming (2012)

To increase modularity, aspect-oriented programming provides a mechanism based on implicit invocation: An aspect can influence runtime behavior of other modules without the need that these modules refer to the aspect. Recent studies show that a significant part of reported bugs in aspect-oriented programs are caused exactly by this implicitness. These bugs are difficult to detect because aspect-oriented source code elements and their locations are transformed or even lost after compilation. We investigate four dedicated fault models and identify ten tasks that a debugger should be able to perform for detecting aspect-orientation-specific faults. We show that existing debuggers are not powerful enough to support all identified tasks because the aspect-oriented abstractions are lost after compilation. This paper describes the design and implementation of a debugger for aspect-oriented languages using a dedicated intermediate representation preserving the abstraction level of aspect-oriented source code. We define a debugging model which is aware of aspect-oriented concepts. Based on the model, we implement a user interface with functionalities supporting the identified tasks, like visualizing pointcut evaluation and program composition.
Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism (2011)

ABSTRACT Gastrointestinal disturbance is frequently reported for individuals with autism. We used quantitative real-time PCR analysis to quantify fecal bacteria that could influence gastrointestinal health in children with and without autism. Lower relative abundances of Bifidobacteria species and the mucolytic bacterium Akkermansia muciniphila were found in children with autism, the latter suggesting mucus barrier changes.
Imaging membrane potential with voltage-sensitive dyes (2000)

Membrane potential can be measured optically using a variety of molecular probes. These measurements can be useful in studying function at the level of an individual cell, for determining how groups of neurons generate a behavior, and for studying the correlated behavior of populations of neurons. Examples of the three kinds of measurements are presented. The signals obtained from these measurements are generally small. Methodological considerations necessary to optimize the resulting signal-to-noise ratio are discussed.
Identification of OmpT as the Protease That Hydrolyzes the Antimicrobial Peptide Protamine before It Enters Growing Cells of Escherichia coli (1998)

The influence of extracytoplasmic proteases on the resistance of Escherichia coli to the antimicrobial peptide protamine was investigated by testing strains with deletions in the protease genes degP, ptr, and ompT. Only DeltaompT strains were hypersusceptible to protamine. This effect was abolished by plasmids carrying ompT. Both at low and at high Mg2+ concentrations, ompT+ strains cleared protamine from the medium within a few minutes. By contrast, at high Mg2+ concentrations, protamine remained present for at least 1 h in the medium of an ompT strain. These data indicate that OmpT is the protease that degrades protamine and that it exerts this function at the external face of the outer membrane.
Network Access to Multimedia Information (1994)

This report summarises the requirements of research and academic network users for network access to multimedia information.It does this by investigating some of the projects planned or currently underway in the community.Existing information systems such as Gopher, WAIS and World-Wide Web are examined from the point of view of multimedia support, and some interesting hypermedia systems emerging from the research community are also studied.Relevant existing and developing standards in this area are discussed.The report identifies the gaps between the capabilities of currentlydeployed systems and the user requirements, and proposes further work centred on the World-Wide Web system to rectify this.The report is in some places very detailed, so it is preceded by an extended summary, which outlines the findings of the report.
Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation (1996)

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic thymus has been reported previously. Here we show that Pax1 protein expression in thymic epithelial cells can be detected throughout thymic development and in the adult. Expression starts in the early endodermal epithelium lining the foregut region and includes the epithelium of the third pharyngeal pouch, a structure giving rise to part of the thymus epithelium. In early stages of thymus development a large proportion of thymus cells expresses Pax1. With increasing age, the proportion of Pax1-expressing cells is reduced and in the adult mouse only a small fraction of cortical thymic stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus epithelium is necessary for establishing the thymus microenvironment required for normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect not only the total size of the thymus but also the maturation of thymocytes. The number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+ immature and CD4+ mature thymocyte subsets. The expression levels of major thymocyte surface markers remains unchanged with the exception of Thy-1 which was found to be expressed at 3- to 4-fold higher levels.
Targeting PBK/TOPK decreases growth and survival of glioma initiating cells in vitro and attenuates tumor growth in vivo (2015)

Our study of identification and functional validation of PBK suggests that this candidate can be a promising molecular target for GBM treatment.
Dimethylamino-pyrazole und -pyrazolyliumsalze (1985)

Als neues stabiles Ringsystem mit 4π-Elektronen – formal somit antiaromatisch – kann das Kation im Pyrazolyliumsalz 1 angesehen werden. Es wurde aus dem entsprechenden 1-unsubstituierten Pyrazol durch Oxidation mit NO⊕BF hergestellt.