gebhart/patrepeval huggingface dataset:
Helicobacter pylori, gastroduodenal disease, and recurrent abdominal pain in children (1995)

<h3>Objective.</h3> —To assess the evidence for a cause-and-effect relationship between<i>Helicobacter pylori</i>infection and antral gastritis, peptic ulcer disease, and recurrent abdominal pain in children. <h3>Data Sources.</h3> —A MEDLINE search from January 1983 through July 1994 was used to identify pertinent English-language publications.<i>Current Contents</i>and selected specialty journals were searched manually. Editorials, reviews, case reports, abstracts, and letters to the editor were excluded. <h3>Study Selection.</h3> —All studies in children (ie, 0 to 18 years) were included. <h3>Data Extraction.</h3> —Hill's criteria for causal inference were used to determine the strength of the evidence for a causal relationship. <h3>Data Synthesis.</h3> —In total, 45 studies (case series, cross-sectional surveys, and treatment trials) were retrieved. The rate ratio of antral gastritis in children with<i>H pylori</i>infection (compared with uninfected children) ranged from 1.9 to 71.0 (median, 4.6). The prevalence of<i>H pylori</i>infection in children with duodenal ulcer was high (range, 33% to 100%; median, 92%) compared with children with gastric ulcer (range, 11% to 75%; median, 25%). Prevalence rates of infection in children with recurrent abdominal pain were inconsistent (range, 0% to 81%; median, 22%), with lower rates in children meeting Apley's criteria (range, 0% to 9%; median, 6%). <h3>Conclusions.</h3> —There is strong evidence for an association between<i>H pylori</i>infection and antral gastritis and duodenal ulcer disease in children; however, data from randomized, double-blind, placebo-controlled treatment trials are required. There is weak evidence for an association with gastric ulcer and weak or no evidence for an association with recurrent abdominal pain. (<i>JAMA</i>. 1995;273:729-734)
Elevated-temperature-induced acceleration of PACT clearing process of mouse brain tissue (2017)

Tissue optical clearing technique shows a great potential for neural imaging with high resolution, especially for connectomics in brain. The passive clarity technique (PACT) is a relative simple clearing method based on incubation, which has a great advantage on tissue transparency, fluorescence preservation and immunostaining compatibility for imaging tissue blocks. However, this method suffers from long processing time. Previous studies indicated that increasing temperature can speed up the clearing. In this work, we aim to systematacially and quantitatively study this influence based on PACT with graded increase of temperatures. We investigated the process of optical clearing of brain tissue block at different temperatures, and found that elevated temperature could accelerate the clearing process and also had influence on the fluorescence intensity. By balancing the advantages with drawbacks, we conclude that 42-47 °C is an alternative temperature range for PACT, which can not only produce faster clearing process, but also retain the original advantages of PACT by preserving endogenous fluorescence well, achieving fine morphology maintenance and immunostaining compatibility.
Effect of fixation on the amplification of nucleic acids from paraffin-embedded material by the polymerase chain reaction. (1991)

Amplification of nucleic acids from paraffin-embedded material by the polymerase chain reaction (PCR) is increasingly being used to detect viral genomes and oncogene mutations. To determine the effect of fixation on the preservation of the nucleic acids, we fixed two randomly chosen fresh pathology specimens in formalin, B-5, Bouin's, Zenker's, ethanol, and Omnifix for 6, 24, 48, 72, and 168 hr (1 week), and then embedded the tissue in paraffin. Oligonucleotide primers specific for the cytoplasmic-beta-actin gene were chosen to span an intron such that amplification yielded a product of 250 BP for DNA and 154 BP for RNA. A single 6-microns section was cut from each paraffin block, deparaffinized, and then subjected to 30 rounds of amplification for either DNA or RNA. On amplifying DNA, consistent product was seen in the ethanol and Omnifix specimens up to 72 hr of fixation time, whereas variable product was seen with formalin or Zenker's fixation; all specimens fixed in Bouin's or B-5 were negative. On amplifying RNA, a product could be detected even after 1 week of fixation in ethanol or Omnifix, and after 48 hr in the formalin-fixed tissue. The Zenker's-fixed tissues gave variable results, and the Bouin's and B-5 tissues gave consistent results only after 6 hr of fixation. We therefore conclude that choice of fixative and fixation time are critical factors influencing the outcome of PCR amplification of nucleic acids from paraffin-embedded material.
Colony-Stimulating Factors and Host Defense (1989)

Colony-stimulating factors are growth factors responsible for the proliferation and the maturation of bone marrow stem cells to fully differentiated granulocytes and monocytes. In addition to their effects on hematopoiesis, some colony-stimulating factors prime mature cells for enhanced chemotaxis, phagocytosis, and killing in response to physiologic stimuli. The action of colony-stimulating factors is mediated by growth factor receptors on precursor and mature effector cells. The results of studies of granulocyte-macrophage colony-stimulating factors in patients with the acquired immunodeficiency syndrome (AIDS) suggest a possible therapeutic role for colony-stimulating factors in augmenting mechanism of host defense.
Impact of in vivo administration of interleukin 3 on proliferation, differentiation, and chemosensitivity of acute myeloid leukemia. (1995)

Early clinical trials of growth factor augmentation of induction chemotherapy for acute myeloid leukemia have yielded variable results. To test the hypothesis that this heterogeneity is a consequence of the pleiotropic effects of growth factors on leukemic cell biology, we measured the effects of in vivo interleukin 3 (IL-3) administration on leukemic cell proliferation and drug sensitivity. Thirty-four patients with acute myeloid leukemia with high-risk features or advanced myelodysplasia received IL-3 as a continuous infusion beginning 3 days prior to chemotherapy and continuing for the duration of intensive induction therapy. Bone marrow cells were studied prior to and after 3 days of IL-3 administration to assess changes in overall and leukemic progenitor cell [leukemia colony-forming unit (CFU-L)] proliferation, and progenitor cell sensitivity to 1-betad-arabinofuranosylcytosine. The median fold increase in overall leukemic cell proliferation in response to IL-3, assessed as expression of the nuclear antigen Ki67 in 28 patients, was 1.2. The median fold increase in percentage of cells in S phase (assessed in 29 patients) was 1.3. Despite the increase in overall cell proliferation in 70% of cases, CFU-L number increased in only 4 of 20 patients successfully studied (median day 4:day 1 ratio of CFU-L number, 0.6). While this suggests possible terminal differentiation of leukemic progenitor cells, expression of CD34, HLA-DR, c-kit, CD15, and CD14 were not consistently affected by the cytokine. 1-betad-Arabinofuranosylcytosine sensitivity of CFU-L increased significantly in 30% of cases, decreased in 30%, and was unchanged in 40%. Changes in overall cell proliferation (Ki67 expression) and CFU-L were independent predictors of change in 1-beta-d-arabinofuranosylcytosine sensitivity; increase in percentage of cells in S phase in response to IL-3 was correlated with attainment of complete remission. While these findings support the concept of cell cycle recruitment, IL-3 has marked pleiotropic effects on proliferation, differentiation, and survival of leukemic progenitors which make the clinical impact of in vivo cytokine administration for individual patients difficult to predict.
In vitro and in vivo comparison of hammerhead, hairpin, and hepatitis delta virus self-processing ribozyme cassettes. (1994)

Ribozyme expression cassettes were constructed which generate trimmed, trans-acting ribozymes from longer transcripts through the action of a downstream cis-acting ribozyme. This self-processing system produces small, well-defined trans-acting ribozymes with minimal, nonproductive, intramolecular structure. These cassettes also permit direct comparison of different ribozyme expression vectors without the need to compensate for different transcription initiation and termination sequences. Expression cassettes were created that contain a T7 promoter and that encode a single trans-acting ribozyme followed by either a hammerhead, hairpin, or hepatitis delta virus cis-acting ribozyme. All three ribozyme motifs function efficiently when transcribed in vitro, although slight differences are observed in the efficiency of self-processing for the different motifs. When transiently expressed in cultured mouse cells, the same specific cleavage products are observed. In addition, the relative efficiencies of in vitro self-processing between the three ribozyme constructs was maintained in vivo. Thus, the cellular milieu does not differentially alter the activity of the three ribozyme motifs. Detection of ribozyme-catalyzed RNA cleavage products from cultured cells is direct proof of ribozyme action in vivo.
Cardiovascular Tissue Engineering I. Perfusion Bioreactors: A Review (2006)

Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current status, unsolved problems, and challenges of bioreactor technology in cardiovascular tissue engineering and outlining future trends and developments.
Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis (2008)

The unfolded protein response (UPR) is a conserved adaptive reaction that increases cell survival under endoplasmic reticulum (ER) stress conditions. X-box-binding protein-1 (XBP-1) is a key transcriptional regulator of the UPR that activates genes involved in protein folding, secretion, and degradation to restore ER function. The occurrence of chronic ER stress has been extensively described in neurodegenerative conditions linked to protein misfolding and aggregation. However, the role of the UPR in the CNS has not been addressed directly. Here we describe the generation of a brain-specific XBP-1 conditional KO strain (XBP-1(Nes-/-)). XBP-1(Nes-/-) mice are viable and do not develop any spontaneous neurological dysfunction, although ER stress signaling in XBP-1(Nes-/-) primary neuronal cell cultures was impaired. To assess the function of XBP-1 in pathological conditions involving protein misfolding and ER stress, we infected XBP-1(Nes-/-) mice with murine prions. To our surprise, the activation of stress responses triggered by prion replication was not influenced by XBP-1 deficiency. Neither prion aggregation, neuronal loss, nor animal survival was affected. Hence, this most highly conserved arm of the UPR may not contribute to the occurrence or pathology of neurodegenerative conditions associated with prion protein misfolding despite predictions that such diseases are related to ER stress and irreversible neuronal damage.
Recovery of sulfur from sour acid gas: A review of the technology (2002)

Abstract The modified Claus process is the major technology for the recovery of elemental sulfur from H 2 S and SO 2 . A number of commercial technologies for the recovery of sulfur from acid gases are also highlighted here. A Claus tail‐gas clean‐up treatment is essential to give high sulfur recovery efficiency from sour acid gases. Generally, the existing tail‐gas clean‐up technologies can be classified into two groups: those that attain 99% overall sulfur recovery efficiency, and those that achieve 99.9% efficiency, including the sulfur recovered in the Claus unit. These processes are the Amoco's Cold Bed Adsorption (CBA), the SNPA/Lurgi Sulfreen, the IFP, the SCOT, the Beavon, and the Wellman‐Lord processes. The SCOT process is generally the most reliable and flexible technology. Process comparisons are also summarized in terms of the sulfur recovery efficiency, hazards and disadvantages, reliability and advantages, plant capacity and ecological impacts. Several changes and new trends are also highlighted here, such as the introduction of non‐permselective catalytic membrane reactors for the Claus reaction, and the in situ adsorption of water inside the Claus catalytic reactor. The successful utilization of H 2 S by converting it to sulfur and H 2 attains the triple objectives of waste minimization, resource utilization, and environmental pollution reduction. Photochemical and plasmochemical methods are still in the development stage. Application of electrochemical technology to H 2 S requires further development. Research for an optimum porous catalyst structure is ongoing for obtaining a relation of micropores and macropores which would provide effective conversion of H 2 S and SO 2 .
L- and P-selectins, but not CD49d (VLA-4) integrins, mediate monocyte initial attachment to TNF-α-activated vascular endothelium under flow in vitro (1996)

Monocyte adhesion to the vascular endothelium is a pivotal step during their egress to tissues at sites of inflammation and immune reactions, and during atherogenesis. In this study, an in vitro flow model and blocking mAb were used to define the role of adhesion molecules in monocyte interactions with activated HUVEC under flow conditions. By videomicroscopy, freely flowing monocytes abruptly halted (initial attachment) on 6-h TNF-alpha-activated HUVEC under flow via L- and P-selectin, whereas E-selectin was not involved. CD49d/CD29 integrin (VLA-4), which can mediate initial attachment of certain T cells to VCAM-1 under flow, did not support monocyte initial attachment. Once initially attached, a small number of monocytes began rolling at 9 microns/s through a mechanism involving L-selectin, as well as CD49d and CD11/CD18 integrins, while the remaining monocytes became firmly adherent, or released to the flow stream. Monocyte stable arrest and subsequent transendothelial migration occurred rapidly and efficiently through either CD49d or CD18 integrin adhesion pathways. Transendothelial passage was also dependent on PECAM-1 (CD31). These data reveal monocytes initially attach to activated endothelium via an L-selectin-dependent mechanism, with a smaller contribution from P-selectin and no contribution by CD49d. Subsequent monocyte rolling, arrest, and transmigration require overlapping functions between multiple members of the selectin, integrin, and Ig gene families.
Mip protein of Legionella pneumophila exhibits peptidyl‐prolyl‐cis/trans isomerase (PPIase) activity (1992)

Legionella pneumophila is an intracellular parasite which is able to survive and multiply in human monocytes and alveolar macrophages. The Mip (macrophage infectivity potentiator) protein has been shown to be an essential virulence factor. A search of translated nucleic acid data bases has shown that the Mip protein from strain Wadsworth possesses regions homologous to those found in the FK506-binding proteins (FKBPs) of several different eukaryotic organisms. FKBPs are able to bind to the immunosuppressant macrolide FK506 and possess peptidyl-prolyl cis/trans isomerase (PPIase) activity. The gene coding for the Mip protein was cloned from the chromosome of L. pneumophila strain Philadelphia I and sequenced. It was synthesized in Escherichia coli K-12 and after purification it exhibited PPIase activity catalysing the slow cis/trans isomerization of prolyl peptide bonds in oligopeptides. Mip is inhibited by FK506 and fully resistant to cyclosporin A, as was also found for the recently characterized FKBP-type PPIases of eukaryotes. However, the N-terminal extension of Mip and/or the substitutions of the variable amino acids in the C-terminal FKBP core leads to variations, when compared with eukaryotic FKBPs, in substrate specificity with the oligopeptide substrates of type Suc-Ala-Xaa-Pro-Phe-4-nitroanilide. Nevertheless, the Legionella Mip factor represents a bacterial gene product which shares some characteristics normally found in eukaryotic proteins. In view of the activity of PPIases in protein-folding reactions, such prokaryotic FKBP analogues may represent a new class of bacterial pathogenicity factors.
Practical, Lightweight Secure Inclusion of Third-Party Intellectual Property (2013)

The security of computing systems relies on trust in hardware. This trust can no longer be assumed due to vulnerabilities in hardware designs. Security methodologies have been proposed for mitigating these threats, offering a variety of security guarantees and wide variance in terms of design-time and runtime costs. From an engineering standpoint it is not clear which of the plethora of solutions should be applied or how they should be implemented. We develop an engineering process for the practical and lightweight inclusion of untrusted third-party hardware design components. We find that by combining previously proposed techniques, we are able to build a microcontroller that uses each design module as if it were untrusted third-party intellectual property. Our experience supports the surprising claim that implementing a chip with untrusted components is not significantly more difficult than implementing a regular one.
Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting (2017)

Pre-existing antibodies (Abs) to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%-80% at 4 weeks and 85%-93% at 8 weeks of treatment. The rapamycin plus prednisolone treatment resulted in significant decreases in the frequency of B cells, plasma cells, and IgG-secreting and AAV9-specific Ab-producing plasma cells in bone marrow. The rapamycin plus prednisolone treatment also significantly reduced frequencies of IgD<sup>-</sup>IgG<sup>+</sup> class-switched/FAS<sup>+</sup>CL7<sup>+</sup> germinal center B cells, and of activated CD4<sup>+</sup> T cells expressing PD1 and GL7, in spleen. These data suggest that rapamycin plus prednisolone has selective inhibitory effects on both T helper type 2 support of B cell activation in spleen and on bone marrow plasma cell survival, leading to effective AAV9 Abs depletion. This promising immunomodulation approach is highly translatable, and it poses minimal risk in the context of therapeutic benefits promised by gene therapy for severe monogenetic diseases, with a single or possibly a few treatments over a lifetime.
Micro-RNAs (2002)

Two small temporally regulated RNAs (stRNAs)* of approximately 22 nucleotides regulate timing of gene expression during development of the nematode C. elegans. This regulation occurs at a posttranscriptional, presumably translational, level and is distinct from RNA interference (RNAi). One of the two stRNAs, let-7, as well as its target gene, lin-41, are highly conserved even in humans, suggesting a wide employment of stRNA-mediated gene regulation. Recent reports indicate that these two stRNAs are indeed likely to represent only the tip of an iceberg with hundreds or more of additional micro-RNAs (miRNAs) existing in metazoans. miRNAs might thus be previously underestimated key participants in the field of gene regulation.
Biased Ostwald Ripening in Site-Selective Growth of Two-Dimensional Gold Clusters (2018)

Nucleation, growth, and ripening of nanoscale Au islands formed on the Au(111) substrate have been investigated using variable temperature scanning tunneling microscopy. The Au(111) surface consists of two types of naturally occurring dislocations. After deposition of Au atoms at 115 K, a single nanometer-sized Au island is formed at each dislocation. Thermal annealing to 180 K causes gross mass transport in which Au atoms systematically move from one type of dislocation to the other. This leads to the preferential ripening of Au islands at one of the two types of dislocations, a phenomenon that has not been observed for any other metals deposited in Au(111). With repeated deposition and thermal annealing cycles, we have succeeded in obtaining two types of clusters with very different sizes: large clusters at the bulged elbow site and small clusters at the pinched elbow site.
Regulation of T‐cell immunity by leucocyte immunoglobulin‐like receptors: innate immune receptors for self on antigen‐presenting cells (2009)

Following recognition of microbial patterns, innate immune receptors provide a rapid innate response and trigger antigen-presenting cell maturation to instruct adaptive immune responses. Here we discuss a family of innate immune receptors for self - the leucocyte immunoglobulin-like receptors (LILRs). These LILRs exert powerful inhibitory effects on antigen-presenting cell phenotype and subsequent T-cell responses, and may act to constrain the effects of Toll-like receptor signalling. Despite their broad ligand specificity, differing affinities of LILRs for individual complexes of peptide-major histocompatibility complex can determine the nature of their effect on downstream immune responses. Expression and function of LILRs may be skewed in certain conditions such as cancer or human immunodeficiency virus infection, particularly by ectopic expression of human leucocyte antigen-G, a high-affinity LILR ligand. We discuss the relevance of LILR-mediated immune regulation across a range of scenarios from autoimmunity to transplant medicine, infection and cancer.