gebhart/patrepeval huggingface dataset:
Selective Plating Underestimates Abundance and Shows Differential Recovery of Bifidobacterial Species from Human Feces (2003)

The aim of the present work was to compare the efficacies and levels of selectivity of different culture-dependent and -independent methods for analyzing bifidobacteria in human stool samples. The three different culture media used here significantly differed from each other, particularly with regard to the recovery of Bifidobacterium adolescentis. Bifidobacterium medium failed to recover B. adolescentis; Beerens medium recovered some B. adolescentis organisms (17% of total bifidobacteria), whereas tomato-Eugon medium recovered mainly B. adolescentis organisms (58% of total bifidobacteria). A culture-independent method that combines GC fractionation of bacterial community DNA and 16S rRNA sequencing indicated that B. adolescentis organisms accounted for 85% of all bifidobacteria. Methodological biases, such as those described in this paper, should be taken into account in interpreting earlier studies and designing future experiments.
Eldelumab [anti-interferon-γ-inducible protein-10 antibody] Induction Therapy for Active Crohn’s Disease: a Randomised, Double-blind, Placebo-controlled Phase IIa Study (2017)

No exposure-remission relationship was seen with eldelumab. Eldelumab induction treatment demonstrated trends towards clinical and endoscopic efficacy. Safety was consistent with that reported previously. ClinicalTrials.gov identifier: NCT01466374.
Expression of alpha v beta 3 integrin in patients with high and low grade glioma (2006)

226 Objective: The integrin alpha v beta 3 (αvβ3) has been appointed a key player in the angiogenesis of a large variety of solid tumors (e.g. melanoma, sarcoma) as well as malignant gliomas. Aim of our study was to assess the extent of αvβ3 expression by tumor as well as endothelial cells within gliomas compared to other solid tumors. Methods: Cryosectioned tumor biopsies of histopathologically confirmed high (n=25) and low (n=10) grade gliomas were immunostained with the monoclonal antibody LM609 for detection of αvβ3-expression. Microvascular density of the samples was determined by co-staining with endothelial cell specific markers (CD31, CD105). Moreover, Western blot analysis of consecutive cryosections was performed to investigate the relative vascularisation and integrin expression in these tumors. Results: Immunohistochemistry confirmed that high grade gliomas not only show a higher rate of αvβ3-positive proliferating endothelial cells but have a higher number of αvβ3-expressing tumor cells compared to low grade gliomas. Western blot analysis revealed that αvβ3-expression in malignant gliomas was higher as seen in low grade gliomas. Interestingly, all glial tumors showed less integrin expression and less αvβ3-positive endothelial cells compared to solid non-CNS tumors (melanomas, sarcomas). In return, the rate of integrin-positive tumor cells was higher in all gliomas compared to the peripheral tumors. Conclusion: Due to the relative strong expression of αvβ3 by glioma cells, the function of this integrin in gliomas can not be restricted to angiogenesis alone. Therefore, the effects of novel “antiangiogenic“ drugs targeting this integrin receptor might also exert effects on glioma cells and should be evaluated in this new context.
DFT Studies on the Mechanism of the Diboration of Aldehydes Catalyzed by Copper(I) Boryl Complexes (2008)

The detailed mechanism for the diboration of aldehydes catalyzed by (NHC)Cu(boryl) complexes (NHC = N-heterocyclic carbene) was studied with the aid of DFT by calculating the relevant intermediates and transition states. The results show that the catalyzed diboration occurs through aldehyde insertion into Cu-B to give a Cu-O-C(boryl) species followed by sigma-bond metathesis with a diboron reagent. It is the "electron-richness", that is, the nucleophilicity of the Cu-boryl bond, which gives rise to a small insertion barrier and determines the direction of insertion. The results of our calculations also explain the formation of the product, observed experimentally, from the stoichiometric reaction of (IPr)Cu-Bpin (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) with mesitylaldehyde. In the absence of a diboron reagent, the insertion intermediate having a Cu-O-C(boryl) linkage isomerizes to the thermodynamically preferred Cu-C-O(boryl) isomer via a boryl migration to the metal-bonded oxygen through an S(E)2-like transition state. We have also studied the catalyzed diboration of 2-pyridinecarboxaldehyde, which gives the unexpected reductive coupling product 1,2-di-2-pyridyl-1,2-bis(pinacolboroxy)ethane. The insertion intermediate, which contains a coordinated pyridyl group, isomerizes easily to a 1,2-dihydropyridine form, preventing its metathesis with a diboron reagent to give the expected diboration product as observed for other aldehyde substrates.
Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins (1997)

Limited endoproteolysis of inactive precursor proteins at sites marked by paired or multiple basic amino acids is a widespread process by which biologically active peptides and proteins are produced within the secretory pathway in eukaryotic cells. The identification of a novel family of endoproteases homologous with bacterial subtilisins and yeast Kex2p has accelerated progress in understanding the complex mechanisms underlying the production of the bioactive materials. Seven distinct proprotein convertases of this family (furin, PC2, PC1/PC3, PC4, PACE4, PC5/PC6, LPC/PC7/PC8/SPC7) have been identified in mammalian species, some having isoforms generated via alternative splicing. The family has been shown to be responsible for conversion of precursors of peptide hormones, neuropeptides, and many other proteins into their biologically active forms. Furin, the first proprotein convertase to be identified, has been most extensively studied. It has been shown to be expressed in all tissues and cell lines examined and to be mainly localized in the trans-Golgi network, although some proportion of the furin molecules cycle between this compartment and the cell surface. This endoprotease is capable of cleaving precursors of a wide variety of proteins, including growth factors, serum proteins, including proteases of the blood-clotting and complement systems, matrix metalloproteinases, receptors, viral-envelope glycoproteins and bacterial exotoxins, typically at sites marked by the consensus Arg-Xaa-(Lys/Arg)-Arg sequence. The present review covers the structure and function of mammalian subtilisin/Kex2p-like proprotein convertases, focusing on furin (EC 3.4.21.85).
Demonstration of direct involvement of cytokines in graft-versus-host reactions using an in vitro human skin explant model. (1991)

A human skin explant model was used to investigate the role of cytokines in graft-versus-host reactions (GVHR). Responder cells from HLA mismatched mixed lymphocyte cultures (MLC) produced GVHR (Grades I-III) in skin explant assays. Cell-free supernatants from these experiments also induced similar histopathological changes in the skin. The greatest degree of correlation between the GVHR observed with responder cells and the supernatant was shown with CD4 enriched MLC (p less than 0.001). Supernatants were assayed for tumour necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) and CD4 enriched MLC populations produced high levels of these cytokines. These results correlated with the grade of GVHR observed in skin explant assays. The GVHR produced by the supernatant alone could be inhibited by both anti-IFN gamma and anti-TNF alpha polyclonal antibodies. The results suggest that TNF alpha and IFN gamma are directly involved in tissue damage during graft-versus-host disease in allogeneic transplant in man.
Transgenic mice deficient in the LAR protein-tyrosine phosphatase exhibit profound defects in glucose homeostasis. (1998)

Protein-tyrosine phosphatases (PTPases) play an integral role in the regulation of cellular insulin action. LAR, a transmembrane PTPase expressed in insulin-sensitive tissues, acts as a negative regulator of insulin signaling in intact cell models. The physiological role of LAR was studied in mice in which LAR expression was eradicated by insertional mutagenesis. In the fasting state, adult male homozygous LAR (-/-) mice had significantly lower plasma levels of insulin and glucose, as well as a reduced rate of hepatic glucose production compared with wild-type controls, suggesting a heightened level of insulin sensitivity. In euglycemic clamp studies, the LAR (-/-) mice exhibited a significant resistance to insulin-stimulated glucose disposal and suppression of hepatic glucose output. Examination of hepatic insulin action demonstrated that the major alteration involved a 47% reduction in insulin-stimulated phosphatidylinositol 3'-kinase (PI 3-kinase) activity in the knockout mice, indicating a post-receptor signaling defect. Taken together with previous work on the cellular effects of LAR, the present results are consistent with a physiological role for LAR in the negative regulation of insulin action, with secondary abnormalities that contribute to the resistance to insulin-stimulated signaling in the knockout mice. Overall, these data provide further evidence for an important role for LAR in the regulation of insulin action and glucose homeostasis in intact animals.
Zoledronate Stimulates γδ T Cells in Prostate Cancer Patients (2009)

Androgen deprivation therapy is the mainstay of treatment for prostate cancer. Given its frequent failure, new therapy that reduces prostate cancer progression would be a breakthrough in treating this disease. Bisphosphonates are well-established agents for treating skeletal-related events (SREs) in prostate cancer patients with bone metastases. Exposure to bisphosphonates may not only reduce the incidence of SREs, but also have anticancer effects by modulating a patient's immunity. The purpose of this study was to examine the effect of zoledronate (ZOL) on gamma delta T cells, serum prostate-specific antigen (PSA) levels, and velocities. The effect of ZOL, with and without IL-2, on gamma delta T cell activation was examined in vitro. Furthermore, the activated state and the number of gamma delta T cells and changes in serum PSA levels were examined for patients who received ZOL infusion for the prevention of SREs. We found that ZOL activated gamma delta T cells, and the number of gamma delta T cell was increased when IL-2 was administered with ZOL in vitro. Comparisons before and after the first ZOL infusion revealed that gamma delta T cells in peripheral blood were activated by ZOL. Moreover, after the first ZOL treatment, reduction in serum PSA was observed in 3 of 11 patients, and reduction in PSA velocity was observed in 5 of 10 patients. Our findings indicate that ZOL stimulates gamma delta T cells in vivo and in vitro. This study provides further insight into the ability of gamma delta T cells to induce an antitumor immune response.
Laser generated ultrasound using directly coatedfibre optic patchcords (2000)

A novel technique is presented for laser generation of ultrasound using low power laser sources and fibre optic patchcords with coated end faces. Absorption of the laser pulse takes place in the coating on the end of the fibre, which in turn generates an ultrasonic stress wave by means of thermoelastic expansion. Results for laser generation of ultrasound in a glass plate are presented, alongside a comparison between ultrasonic generation by coated fibres and direct illumination in aluminium plates.
Exon identity crisis: disease-causing mutations that disrupt the splicing code (2014)

Cis-acting RNA elements control the accurate expression of human multi-exon protein coding genes. Single nucleotide variants altering the fidelity of this regulatory code and, consequently, pre-mRNA splicing are expected to contribute to the etiology of numerous human diseases.
Identification of a novel vertebrate homeobox gene expressed in haematopoietic cells (1992)

This paper describes the characterisation of a novel chicken homeobox gene, Prh, whose encoded homeodomain sequence differs significantly from those of other factors which have been described. As expected, a portion of the encoded protein, containing the homeodomain, is capable of sequence-specific DNA-binding. Outside the homeodomain, Prh, possesses an N-terminal region extremely rich in proline residues and a C-terminal acidic portion, either of which may function as transcription regulatory domains. Since, among the chicken tissues tested, its transcription is restricted to haematopoietic cells, lung and liver, it may function in tissue-specific patterns of gene regulation. Human and murine Prh homologues have also been identified; so it is likely that such genes are a general feature of vertebrate genomes.
Energy Management for Hypervisor-Based Virtual Machines (2007)

Current approaches to power management are based on operating systems with full knowledge of and full control over the underlying hardware; the distributed nature of multi-layered virtual machine environments renders such approaches insufficient. In this paper, we present a novel framework for energy management in modular, multi-layered operating system structures. The framework provides a unified model to partition and distribute energy, and mechanisms for energy-aware resource accounting and allocation. As a key property, the framework explicitly takes the recursive energy consumption into account, which is spent, e.g., in the virtualization layer or subsequent driver components. Our prototypical implementation targets hypervisor- based virtual machine systems and comprises two components: a host-level subsystem, which controls machine-wide energy constraints and enforces them among all guest OSes and service components, and, complementary, an energy-aware guest operating system, capable of fine-grained applicationspecific energy management. Guest level energy management thereby relies on effective virtualization of physical energy effects provided by the virtual machine monitor. Experiments with CPU and disk devices and an external data acquisition system demonstrate that our framework accurately controls and stipulates the power consumption of individual hardware devices, both for energy-aware and energyunaware guest operating systems.
The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. (1996)

In late 1994 and early 1995, Ebola (EBO) virus dramatically reemerged in Africa, causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these viruses and those of other EBO virus subtypes has shown that the virion glycoprotein (130 kDa) is encoded in two reading frames, which are linked by transcriptional editing. This editing results in the addition of an extra nontemplated adenosine within a run of seven adenosines near the middle of the coding region. The primary gene product is a smaller (50-70 kDa), nonstructural, secreted glycoprotein, which is produced in large amounts and has an unknown function. Phylogenetic analysis indicates that EBO virus subtypes are genetically diverse and that the recent Ivory Coast isolate represents a new (fourth) subtype of EBO virus. In contrast, the EBO virus isolate from the 1995 outbreak in Kikwit, Zaire, is virtually identical to the virus that caused a similar epidemic in Yambuku, Zaire, almost 20 years earlier. This genetic stability may indicate that EBO viruses have coevolved with their natural reservoirs and do not change appreciably in the wild.
The evolution of corneal and refractive surgery with the femtosecond laser (2015)

The use of femtosecond lasers has created an evolution in modern corneal and refractive surgery. With accuracy, safety, and repeatability, eye surgeons can utilize the femtosecond laser in almost all anterior refractive procedures; laser in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), penetrating keratoplasty (PKP), insertion of intracorneal ring segments, anterior and posterior lamellar keratoplasty (Deep anterior lamellar keratoplasty (DALK) and Descemet's stripping endothelial keratoplasty (DSEK)), insertion of corneal inlays and cataract surgery. As the technology matures, it will push surgical limits and open new avenues for ophthalmic intervention in areas not yet explored. As we witness the transition from femto-LASIK to femto-cataract surgery it becomes obvious that this innovation is here to stay. This article presents some of the most relevant advances of femtosecond lasers to modern corneal and refractive surgery.
Amplified genes in human gliomas. (1993)

The most common types of brain tumors in adults are collectively known as gliomas. The most common glioma is the most malignant, the glioblastoma. Double minute chromosomes, known to represent amplified genes, are found in 50% of glioblastomas. Four genes have been identified as being amplified in more than single cases of glioblastomas; MYCN, GLI, PDGFRA and EGFR. The first three have been reported in a few per cent of malignant gliomas, and EGFR in around 40% of glioblastomas. The latter two genes code for growth factor receptors. On amplification, the genes for these receptors frequently become rearranged, resulting in changes in the regions of their transcripts that code for the extra-cellular domains of these proteins. Such aberrant proteins may provide us with cell-surface, tumor-specific, epitopes. These findings provide simple examples of the impact the use of modern molecular biological techniques will have for our understanding and treatment of tumors in the future.
Increased Expression of Axl Tyrosine Kinase After Vascular Injury and Regulation by G Protein–Coupled Receptor Agonists in Rats (1998)

Axl is a receptor tyrosine kinase originally identified as a transforming gene product in human myeloid leukemia cells. Cultured rat vascular smooth muscle cells also express Axl, where it has been proposed that Axl may play a role in cell proliferation. In the current study, we tested the hypotheses that Axl expression would parallel neointima formation in balloon-injured rat carotid, and that Axl expression would be regulated by growth factors present at sites of vascular injury. Ribonuclease protection assay showed dynamic increases in Axl mRNA in vessels, with peak expression 7 and 14 days after injury. Immunohistochemical analysis confirmed these results and demonstrated that Axl protein expression was localized primarily to cells of the neointima after injury. Northern blot analysis indicated increased mRNA expression for the secreted Axl ligand, Gas6, in injured carotids, with a time course paralleling that of Axl upregulation. Axl and Gas6 expression were temporally correlated with neointima formation, suggesting a role for Axl signaling in this process. Other studies, performed in cultured rat vascular smooth muscle cells, revealed positive regulation of Axl mRNA expression by thrombin or angiotensin II but not by basic fibroblast growth factor, platelet-derived growth factor-BB, or transforming growth factor-ss1. Western blot analysis confirmed these results, showing that Axl protein expression was specifically increased by thrombin or angiotensin II. Our results implicate Axl as a potential mediator of vascular smooth muscle migration and proliferation caused by vascular injury and G protein-coupled receptor agonists.
T Cell Ig and Mucin Domain–Containing Protein 3 Is Recruited to the Immune Synapse, Disrupts Stable Synapse Formation, and Associates with Receptor Phosphatases (2013)

CD8(+) CTLs are adept at killing virally infected cells and cancer cells and releasing cytokines (e.g., IFN-γ) to aid this response. However, during cancer and chronic viral infections, such as with HIV, this CTL response is progressively impaired due to a process called T cell exhaustion. Previous work has shown that the glycoprotein T cell Ig and mucin domain-containing protein 3 (Tim-3) plays a functional role in establishing T cell exhaustion. Tim-3 is highly upregulated on virus and tumor Ag-specific CD8(+) T cells, and antagonizing Tim-3 helps restore function of CD8(+) T cells. However, very little is known of how Tim-3 signals in CTLs. In this study, we assessed the role of Tim-3 at the immunological synapse as well as its interaction with proximal TCR signaling molecules in primary human CD8(+) T cells. Tim-3 was found within CD8(+) T cell lipid rafts at the immunological synapse. Blocking Tim-3 resulted in a significantly greater number of stable synapses being formed between Tim-3(hi)CD8(+) T cells and target cells, suggesting that Tim-3 plays a functional role in synapse formation. Further, we confirmed that Tim-3 interacts with Lck, but not the phospho-active form of Lck. Finally, Tim-3 colocalizes with receptor phosphatases CD45 and CD148, an interaction that is enhanced in the presence of the Tim-3 ligand, galectin-9. Thus, Tim-3 interacts with multiple signaling molecules at the immunological synapse, and characterizing these interactions could aid in the development of therapeutics to restore Tim-3-mediated immune dysfunction.
Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver (2010)

shRNA overexpression from viral gene therapy vectors can trigger cytotoxicity leading to organ failure and lethality in mice and rats. This process likely involves saturation of endogenous cellular RNAi factors including exportin-5 (Xpo-5). Here, we have shown that Xpo-5 overexpression enhanced shRNA efficiency in the liver of adult mice but increased hepatotoxicity. We identified the 4 members of the human Argonaute (Ago) protein family as downstream factors involved in saturation of endogenous cellular RNAi, all of which were able to interact with shRNAs in cells and mice. In Ago/shRNA coexpression studies, Ago-2 (Slicer) was the primary rate-limiting determinant of both in vitro and in vivo RNAi efficacy, toxicity, and persistence. In adult mice, vector-based Ago-2/Xpo-5 coexpression enhanced U6-driven shRNA silencing of exogenous and endogenous hepatic targets, reduced hepatotoxicity, and extended RNAi stability by more than 3 months. Use of weaker RNA polymerase III promoters to minimize shRNA expression likewise alleviated in vivo toxicity and permitted greater than 95% persistent knockdown of hepatitis B virus and other transgenes in mouse liver for more than 1 year. Our studies substantiate that abundant small RNAs can overload the endogenous RNAi pathway and reveal possible strategies for reducing hepatotoxicity of short- and long-term clinical gene silencing in humans.
Relationship Between Offset Angle Alpha and Hip Chondral Injury in Femoroacetabular Impingement (2008)

Cam-type FAI, as measured by an increased offset angle alpha, was correlated with increased chondral damage, labral injury, and decreased range of motion.
Synthesis and properties of fluorescent 1,8-naphthalimide dyes for application in liquid crystal displays (2000)

A series of highly fluorescent 1,8-naphthalimide derivatives having an N-allylamino group at position 4 of the aromatic structure have been synthesised, and some of their properties for application in liquid crystal displays have been determined. The optical properties of the new substances are studied both in organic solvents and in the nematic liquid crystal ZLI 1840. The utility of the dyes for colouring liquid crystal displays of the "guest–host" type is discussed on the basis of their spectral properties (absorption and emission) and the effect that the dyes have upon the orientation order parameter 〈P2〉 and upon the phase-transition behaviour of the liquid crystal in surface-stabilised display cells.