gebhart/patrepeval huggingface dataset:
Tumor necrosis factor (cachectin) in the biology of septic shock syndrome. (1991)

The high mortality of septic shock syndrome has prompted extensive investigation into its pathogenesis. Tumor necrosis factor (TNF), a cytokine that is often over-produced during Gram-negative or Gram-positive infection, occupies a critical role in triggering this catastrophic illness. The net effects of TNF are dependent upon its concentration in certain vital tissues, and may be dissociated from the presence of the invading pathogens. Agents that inhibit TNF have been developed; these protect against shock and tissue injury and are currently being investigated in clinical trials of septic shock syndrome.
Homologous Recombination Conserves DNA Sequence Integrity Throughout the Cell Cycle in Embryonic Stem Cells (2010)

The maintenance of genomic integrity is crucial to embryonic stem cells (ESC) considering the potential for propagating undesirable mutations to the resulting somatic and germ cell lineages. Indeed, mouse ESC (mESC) exhibit a significantly lower mutation frequency compared to differentiated cells. This could be due to more effective elimination of genetically damaged cells via apoptosis, or especially robust, sequence-conserving DNA damage repair mechanisms such as homologous recombination (HR). We used fluorescence microscopy and 3-dimensional image analysis to compare mESC and differentiated cells, with regard to HR-mediated repair of spontaneous and X-ray-induced double-strand breaks (DSBs). Microscopic analysis of repair foci, flow cytometry, and functional assays of the major DSB repair pathways indicate that HR is greater in mESC compared to fibroblasts. Strikingly, HR appears to be the predominant pathway choice to repair induced or spontaneous DNA damage throughout the ESC cycle in contrast to fibroblasts, where it is restricted to replicated chromatin. This suggests that alternative templates, such as homologous chromosomes, are more frequently used to repair DSB in ESC. Relatively frequent HR utilizing homolog chromosome sequences preserves genome integrity in ESC and has distinctive and important genetic consequences to subsequent somatic and germ cell lineages.
Ganglioside GM2 on the K562 cell line is recognized as a target structure by human natural killer cells (1987)

Although human NK cells lyse a wide spectrum of target cells, the precise target structure recognized by NK cells has not yet been elucidated. In order to define a possible relationship between gangliosides on human target cells and susceptibility to NK lysis, 14 human leukemia and lymphoma cell lines were studied. A significant correlation was observed between the quantity of ganglioside GM2 on the target cells and sensitivity to NK lysis. In a single-cell binding assay purified GM2 specifically inhibited human NK cell binding to K562 target cells while other gangliosides did not inhibit binding. The competitive inhibition of NK cells by GM2 was restricted to the source of tissue from which GM2 was isolated. These results indicate that GM2 is a strong candidate as a target recognition structure for human NK cells.
Novel Endotoxin Adsorbing Materials, Polymyxin-Sepharose and Polyporous Polyethylene Membrane for Removal of Endotoxin from Dialysis Systems (1990)

In order to remove contaminated endotoxin from dialysis systems, we prepared and investigated two novel endotoxin adsorbing materials, Polymyxin-Sepharose (PxSeph) and polyporous polyethylene hollow fiber membrane (EHF). PxSeph was prepared by covalently immobilizing polymyxin B on Sepharose 4B beads by CNBr coupling method. It adsorbed various endotoxins with a high affinity constant and could effectively remove endotoxin from aqueous solution and human plasma. EHF also removed endotoxins from contaminated water by filtration through EHF modules, and its adsorption nature was demonstrated. Both PxSeph and EHF are stable in physiological conditions and proved to be useful adsorbents for removal of contaminated endotoxin from the hemodialysis systems.
Matrix Metalloproteinase Inhibitors: Current Status (1995)

Abstract: Due to the increasing evidence for the involvement of the matrix metalloproteinases (MMPs) in a variety of tissue degenerative disorders, such as arthritis and cancer, there is considerable interest in designing agents which inhibit their action, either collectively or selectively. Historically, MMP inhibitors have been designed using knowledge of the substrate cleavage sites of the enzymes, early collagenase inhibitors bearing similarity to the cleavage site of type-1 collagen. This review will describe the recent design of specific inhibitors of stromelysin and gelatinase based upon their own substrate preferences. The structure of these inhibitors will be rationalised in terms of the recently published crystal structures of the MMPs. The development of a new generation of peptide-based, yet orally active, inhibitors will be reviewed and their progress towards the clinic assessed. Recent advances in the discovery of non-peptide MMP inhibitors will also be described.
Electric Vehicle Development in Fiat (1991)

&lt;div class="htmlview paragraph"&gt;Within the strategical scope of energy conservation and improvement of human quality of life FIAT is since long time performing activities aimed at the technologies for electrically propelled vehicles for diversified applications.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The electricity as energy vector allows an application flexibility to different types of vehicles, full electrics hybrid and multimode vehicles which have been developed at prototypes level or small scale production.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The tactical process which has been followed is based on the three phases of:&lt;/div&gt; &lt;div class="htmlview paragraph"&gt; &lt;ul class="list disc"&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;technology research and development&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;demonstration programs and field trials&lt;/div&gt;&lt;/li&gt; &lt;li class="list-item"&gt;&lt;div class="htmlview paragraph"&gt;production.&lt;/div&gt;&lt;/li&gt; &lt;/ul&gt; &lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The experience achieved within several extensively tested prototypes and pilot service allowed to put in small series production light and medium delivery vans as well as minibuses, which are now in service in Rome and other italian cities.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;In 1990, the Panda Elettra has been put in commercialization as a first type of electric vehicle offered for private transport; this vehicle is based on technological solutions adequately and economically viable for the present state of the art.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The evolution process includes now further technological development in the field on board energy sources and drive system.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;As a first example of this new technologies, a solution with four “in wheel motor” has been developed and applied to a multimode hybrid bus.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The potential impact, features and issues are discussed for the new technologies which are presently under development.&lt;/div&gt;
Induction of a CD8+ cytotoxic T lymphocyte response to soluble antigen given together with a novel muramyl dipeptide adjuvant, N-acetyl-D-glucosaminyl-(beta 1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine (GMDP). (1995)

We have investigated the ability of the novel muramyl dipeptide, GMDP, to act as an adjuvant for the induction of ovalbumin (OVA)-specific, CD8+ cytotoxic T lymphocyte (CTL) responses. C57Bl/6 mice were twice immunized s.c. with 50 micrograms OVA emulsified with a squalane, L121 pluronic containing Tween-80 vehicle either with (STP-GMDP) or without (STP) GMDP. Splenic precursor CD8+ CTL activity against E.G7-OVA, but not against EL-4 parental targets was detected in STP-GMDP immunized mice after 5 days of in vitro re-stimulation with irradiated E.G7-OVA cells, while mice immunized with OVA in STP alone or OVA alone failed to demonstrate CTL activity. OVA emulsified in a microfluidized STP vehicle formulation without GMDP also elicited the E.G7-OVA precursor CTL. The ability of GMDP to induce a class I-restricted, CD8+ CTL response to a soluble protein antigen may have implications for the development of useful vaccines against viral pathogens or tumours against which CTL responses are desirable.
Smoking Induces Long-Lasting Effects through a Monoamine-Oxidase Epigenetic Regulation (2009)

This is one of the first reports that smoking induces an epigenetic modification. A better understanding of the epigenome may help to further elucidate the physiopathology and the development of new therapeutic approaches to tobacco addiction. The results could have a larger impact than cardiovascular damage, considering that MAO-dependent 5-HT catabolism is also involved in addiction, predisposition to cancer, behaviour and mental health.
Internet-Based Forestry Extension: Using It in the Classroom (2002)

The Internet Forestry Explorer is a Web site designed to present information about forest and watershed management. The target audience includes natural resource professionals, forest landowners, environmental education teachers, citizens of the featured forests and watersheds, and to a lesser extent anyone who is interested in learning more about their state’s natural resources. Components of the Web site include an interactive GIS that allows the creation of tailored maps, virtual “walking tours” where users can view photos, pages of forest management examples, and links to organizations and other pages of interest. One component was created as part of a three-university virtual forest project. Penn State chose a private, award-winning tree farm to discuss and highlight forest sustainability according to the Montreal Protocol. This site includes pages describing the 7 criteria and 67 indicators of the Montreal Protocol, as well as a walking tour of the tree farm. A survey was conducted to analyze the effectiveness of the Internet Forestry Explorer in educating target audiences. This presentation will discuss the technical construction of the Web site, the results of the survey, and how the site may be used in university classroom setting.
Myo-mechanical Analysis of Isolated Skeletal Muscle (2011)

To assess the in vivo effects of therapeutic interventions for the treatment of muscle disease, quantitative methods are needed that measure force generation and fatigability in treated muscle. We describe a detailed approach to evaluating myo-mechanical properties in freshly explanted hindlimb muscle from the mouse. We describe the atraumatic harvest of mouse extensor digitorum longus muscle, mounting the muscle in a muscle strip myograph (Model 820MS; Danish Myo Technology), and the measurement of maximal twitch and tetanic tension, contraction time, and half-relaxation time, using a square pulse stimulator (Model S48; Grass Technologies). Using these measurements, we demonstrate the calculation of specific twitch and tetanic tension normalized to muscle cross-sectional area, the twitch-to-tetanic tension ratio, the force-frequency relationship curve and the low frequency fatigue curve. This analysis provides a method for quantitative comparison between therapeutic interventions in mouse models of muscle disease, as well as comparison of the effects of genetic modification on muscle function.
Protein Adsorption on Alkanethiolate Self-Assembled Monolayers:  Nanoscale Surface Structural and Chemical Effects (2003)

We report a study of protein adsorption on controlled surfaces. Hydrophilic (carboxylic acid-terminated) and hydrophobic (methyl-terminated) self-assembled monolayers (SAMs) on Au(111) surfaces were prepared at different solution temperatures and characterized by low-current scanning tunneling microscopy (STM). Protein adsorption on these SAMs was investigated by surface plasmon resonance (SPR) sensors and tapping-mode atomic force microscopy (TM-AFM). Results show that both nanoscale surface chemical and structural properties of SAMs affect protein adsorption. Specifically, carboxylic acid-terminated SAMs formed at higher temperatures have more compact structures and generally promote protein adsorption, whereas the adsorbed amount of protein is similar on methyl-terminated SAMs regardless of solution temperatures at which SAMs are formed.
Wavelength-Division-Multiplexing Devices in Thin SOI: Advances and Prospects (2014)

Silicon photonics wavelength-division-multiplexing filters are important building blocks in >100 G transceivers and near future on-chip communications between many cores. This paper deals with four kinds of wavelength-division-multiplexing filters: they are, ring resonators, lattice-form filters, arrayed-waveguide gratings and planar Echelle gratings. Progress and technical challenges for these filter devices will be described.
A Versatile Periodate-Coupled Fluorogenic Assay for Hydrolytic Enzymes (2000)

Enzymes such as acylases, lipases, epoxide hydrolases, or phosphatases can be easily detected by fluorescence when they hydrolyze suitable precursors to produce the 1,2-diols 1 and 1,2-aminoalcohol 2 as products. Indeed, oxidation of 1 and 2 with sodium periodate and β-elimination of the intermediate aldehyde with bovine serum albumin yields umbelliferone, and results in a more than 20-fold increase in fluorescence at 460 nm (λex=360 nm). This simple assay is suitable for high-throughput screening.
Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor (1998)

Previous pharmacological studies have indicated the possible existence of functional interactions between mu-, delta- and kappa-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of delta- and kappa-opioid receptors in mice lacking the mu-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPgammaS binding and adenylyl cyclase inhibition showed that functional coupling of delta- and kappa-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[D-penicillamine2, D-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR -/- mice. delta-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR -/- mice. Analgesic and respiratory responses produced by the selective kappa-agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of delta- and kappa-receptor signaling properties in mice lacking mu-receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the kappa-agonist further suggest that the kappa-receptor mainly acts independently from the mu-receptor in vivo. Reduced delta-analgesia and the absence of delta-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between mu-receptors and central delta-receptors in specific neuronal pathways.
Increased translational fidelity caused by the antibiotic kasugamycin and ribosomal ambiguity in mutants harbouring the ksgA gene (1984)

The aminoglycoside kasugamycin, which has previously been shown to inhibit initiation of protein biosynthesis in vitro, also affects translational accuracy in vitro. This is deduced from the observation that the drug decreases the incorporation of histidine relative to alanine into the coat protein of phage MS2, the gene of which is devoid of histidine codons. The read-through of the MS2 coat cistron, due to frameshifts in vitro, is also suppressed by the antibiotic. In contrast, streptomycin enhances histidine incorporation and read-through in this system. The effects of kasugamycin take place at concentrations that do not inhibit coat protein biosynthesis. Kasugamycin-resistant mutants (ksgA) lacking dimethylation of two adjacent adenosines in 16 S ribosomal RNA, show an increased leakiness of nonsense and frameshift mutants (in the absence of antibiotic). They are therefore phenotypically similar to previously described ribosomal ambiguity mutants (ram).
Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis* (2000)

The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells. The purpose of this article is 3-fold: 1) to review the role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis; 2) to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis; and 3) to highlight the implications of bone cell birth and death for a better understanding of the mechanism of action and efficacy of present and future pharmacotherapeutic agents for osteoporosis.
Transcriptional Repression of Stat6-Dependent Interleukin-4-Induced Genes by BCL-6: Specific Regulation of Iɛ Transcription and Immunoglobulin E Switching (1999)

The BCL-6 proto-oncogene encodes a POZ/zinc-finger transcription factor that is expressed in B cells and a subset of CD4(+) T cells within germinal centers. Recent evidence suggests that BCL-6 can act as a sequence-specific repressor of transcription, but the target genes for this activity have not yet been identified. The binding site for BCL-6 shares striking homology to the sites that are the target sequence for the interleukin-4 (IL-4)-induced Stat6 (signal transducers and activators of transcription) signaling molecule. Electrophoretic mobility shift assays demonstrate that BCL-6 can bind, with different affinities, to several DNA elements recognized by Stat6. Expression of BCL-6 can repress the IL-4-dependent induction of immunoglobulin (Ig) germ line epsilon transcripts, but does not repress the IL-4 induction of CD23 transcripts. Consistent with the role of BCL-6 in modulating transcription from the germ line epsilon promoter, BCL-6(-/-) mice display an increased ability to class switch to IgE in response to IL-4 in vitro. These animals also exhibit a multiorgan inflammatory disease characterized by the presence of a large number of IgE(+) B cells. The apparent dysregulation of IgE production is abolished in BCL-6(-/-) Stat6(-/-) mice, indicating that BCL-6 regulation of Ig class switching is dependent upon Stat6 signaling. Thus, BCL-6 can modulate the transcription of selective Stat6-dependent IL-4 responses, including IgE class switching in B cells.
Accommodative response to blur* (1974)

By use of a blur-pseudostimulus technique and high-speed infrared optometric measurements, the singularity of blur as a stimulus to human accommodation was studied. Blur is not the sole stimulus; it is a necessary cue, but not a sufficient one. The accommodative system makes use of one or more available odd-error (error sign) cues, which are believed to supplement blur with requisite focusing information.
The Sec61 complex is essential for the insertion of proteins into the membrane of the endoplasmic reticulum (1995)

Cross-linking studies have implicated Sec61 alpha as the principal component adjacent to newly synthesised membrane proteins during insertion into the endoplasmic reticulum. Using proteoliposomes which have been reconstituted from purified components of the endoplasmic reticulum [Görlich, D and Rapoport, T.A., Cell 75 (1993) 615-630] we have found that the Sec61 complex, consisting of three subunits, is essential for the insertion of single-spanning membrane proteins. This is true for signal-anchor proteins of both orientations, and for proteins with a cleavable signal sequence. These results support the view that Sec61 alpha is a major component of the ER translocation site and promotes both the insertion of membrane proteins and the translocation of secretory proteins.
Mapping a cloned gene under sporulation control by inserttion of a drug resistance marker into the Bacillus subtilis chromosome (1980)

A segment of Bacillus subtilis deoxyribonucleic acid (DNA) previously cloned in Escherichia coli contains a gene (the 0.4-kilobase [kb] gene) whose transcription is activated at an early stage of spore development. To map the genetic location of the 0.4-kb gene, we constructed a hybrid plasmid that inserts a chloramphenicol resistance determinant into the B. subtilis chromosome by recombination at a site of homology between cloned B. subtilis DNA and the chromosome. This hybrid plasmid (p1949-2) was constructed from the E. coli plasmid pMB9, the B. sultilis chloramphenicol resistance plasmid pCM194 (whose replication function was inactivated), and B. subtilis DNA from the vicinity of the 0.4-kb gene. Transformation of B. subtilis cells to drug resistance by p1949-2 was dependent upon the B. subtilis RecE+ phenotype and resulted in specific and predictable changes in the pattern of endonuclease restriction sites in the 0.4-kb gene region of the chromosome. Chloramphenicol resistance in cells transformed by p1949-2 was mapped to the purA-cysA region of the B. subtilis chromosome, a region. In addition, DNA adjacent to the 0.4-kb gene was shown to contain the wild-type allele of genetic marker (tms-26) from that region.
Persistent Cytomegalovirus-Specific Memory Responses in the Lung Allograft and Blood following Primary Infection in Lung Transplant Recipients (2006)

Primary CMV infection in lung transplant recipients (LTRs) is associated with increased mortality. We studied 22 donor CMV-positive, recipient-negative (D(+)R(-)) LTRs for the development of posttransplant CMV-specific immunity. We found that 13 of 22 D(+)R(-) LTRs (59.1%) seroconverted (CMV IgG Ab(+)). Using pooled peptides of the immunodominant CMV Ags pp65 and IE1, we detected CMV-specific CD8(+)IFN-gamma(+) T cells in the PBMC of 90% of seroconverted individuals following primary infection by intracellular cytokine staining. In contrast, few seroconverters had detectable CMV-specific CD4(+)IFN-gamma(+) T cells during viral latency. However, the majority of IgG(+) LTRs demonstrated CMV-specific CD4(+) and CD8(+) T cell proliferative responses from PBMC, with CD4(+)IFN-gamma(+) T cells detectable upon re-expansion. Examination of lung allograft mononuclear cells obtained by bronchoalveolar lavage revealed both CMV-specific CD4(+) and CD8(+)IFN-gamma(+) T cells, including patients from whom CD4(+)IFN-gamma(+) T cells were simultaneously undetectable in the PBMC, suggesting differential effector memory populations between these compartments. Moreover, both responses in the PBMC and lung allograft were found to persist, despite substantial immunosuppression, long after primary infection. Clinical correlation in this cohort demonstrated that the acquisition of CMV immunity was associated with freedom from CMV disease (p < or = 0.009) and preservation of allograft function (p < or = 0.02) compared with those who failed to develop CMV immunity. Together, our data reveal immunologic heterogeneity in D(+)R(-) LTRs, with the development and persistence of primary CMV responses that may provide clinical benefit.