gebhart/patrepeval huggingface dataset:
Functional Genomic Analysis of Oligodendrocyte Differentiation (2006)

To better understand the molecular mechanisms governing oligodendrocyte (OL) differentiation, we have used gene profiling to quantitatively analyze gene expression in synchronously differentiating OLs generated from pure oligodendrocyte precursor cells in vitro. By comparing gene expression in these OLs to OLs generated in vivo, we discovered that the program of OL differentiation can progress normally in the absence of heterologous cell-cell interactions. In addition, we found that OL differentiation was unexpectedly prolonged and occurred in at least two sequential stages, each characterized by changes in distinct complements of transcription factors and myelin proteins. By disrupting the normal dynamic expression patterns of transcription factors regulated during OL differentiation, we demonstrated that these sequential stages of gene expression can be independently controlled. We also uncovered several genes previously uncharacterized in OLs that encode transmembrane, secreted, and cytoskeletal proteins that are as highly upregulated as myelin genes during OL differentiation. Last, by comparing genomic loci associated with inherited increased risk of multiple sclerosis (MS) to genes regulated during OL differentiation, we identified several new positional candidate genes that may contribute to MS susceptibility. These findings reveal a previously unexpected complexity to OL differentiation and suggest that an intrinsic program governs successive phases of OL differentiation as these cells extend and align their processes, ensheathe, and ultimately myelinate axons.
Serum susceptibility of Haemophilus somnus from bovine clinical cases and carriers (1985)

The serum susceptibility of 64 isolates of Haemophilus somnus from cattle was determined in a bactericidal assay with undiluted fresh or inactivated bovine serum with serial dilutions of bacterial suspension in RPMI 1640 medium. A total of 27 strains isolated from cattle with clinical disease (4 with thromboembolic meningoencephalitis, 13 with pneumonia, and 10 with reproductive failure) were compared with 35 strains from asymptomatic carriers (11 from the vagina and 24 from the prepuce). Essentially, all clinical isolates were serum resistant, whereas approximately 25% of preputial isolates were serum susceptible, as judged after 1 h of incubation in serum; a majority of vaginal isolates showed delayed serum susceptibility. Lysozyme played no role in serum killing, and the alternative complement pathway played only a minor role. Iron saturation, however, appeared to impart greater serum resistance to serum-susceptible strains from the vagina and prepuce. Perhaps the serum-susceptible strains from carriers would be useful vaccine candidates, but resistant strains from carriers may be pathogenic.
Successful Application of Joint Reflection/Refraction Tomographic Inversion in a Shallow Water Marine Environment (2013)

We show how refraction tomography (also called first arrival travel time tomography) helps to produce more accurate and detailed depth velocity models below a shallow seafloor. We do not use refractions by themselves to build a complete shallow velocity model. In our proposed workflow, refraction tomography complements standard reflection tomography and the priority remains with the reflections to guarantee stability of the solution and to avoid uncertainties associated with refracted or diving waves in complex media. We use wave equation modelling to calculate synthetic gathers and estimate the travel time mismatch between real and synthetic first arrivals. It leads to a robust workflow which can be easily introduced into production depth-velocity processing. We show how this joint reflection/refraction velocity inversion works using a real 1000sq.km 3D marine seismic dataset acquired in an area where the water depth varies from 20m to 1100m.
Peptidmimetica – maßgeschneiderte Enzyminhibitoren (1994)

Abstract Peptide und Proteine – die Übergänge zwischen diesen Verbindungsklassen sind fließend – sind in vielerlei Hinsicht essentielle Bestandteile von Organismen. Während den Proteinen vor allem biokatalytische Aufgaben sowie solche als wichtige Gewebebestandteile zukommen, haben die Peptide vor allem als Hormone, Neurotransmitter und Neuromodulatoren eine wichtige Funktion im Organismus. Schon seit langem bedient man sich in der medizinischen Chemie der Peptide und ihrer Analoga als Arzneimittel zur Therapie pathologischer Zustände, die zumeist durch eine Störung des Wechselspiels zwischen Botenstoffen oder Enzymsubstraten einerseits sowie ihren Adressaten – den Rezeptoren und Enzymen – andererseits gekennzeichnet sind. Die Entwicklung geht dabei aus biochemischen und biophysikalischen Gründen immer mehr in die Richtung chemischer “Trojanischer Pferde”, der Peptidmimetica. Dabei steigen die Erfolgsaussichten für die Wirksamkeit dieser Verbindungen in der Regel mit dem Ausmaß des Täuschungseffekts, d.h. proportional zur Wandlung eines Peptids zum Nichtpeptid. Rationales Design ist zu einem Schlagwort geworden, das gerade für die Konzeption von Peptidmimetica aktuelle Gültigkeit erlangt hat. Neue Computerprogramme leisten dabei eine unverzichtbare hilfreiche Arbeit. Bei allem Fortschritt ist man vom Endziel, dem De‐novo‐Design von Peptidmimetica, noch weit entfernt. Das rationale Design macht jedoch deutliche Fortschritte, und im Hinblick auf das Ganze kann man schon jetzt sagen: Der Peptidchemie insgesamt haben die Peptidmimetica bisher zu einem enormen Auftrieb verholfen. Das dürfte sich fortsetzen, so daß die Peptidchemie der Zukunft von einer Art symbiotischer Allianz aus Peptiden und Nichtpeptiden geprägt sein könnte.
Rapid and simultaneous typing of hemoglobin S, hemoglobin C, and seven Mediterranean beta-thalassemia mutations by covalent reverse dot-blot analysis: application to prenatal diagnosis in Sicily (1993)

The molecular lesions causing beta-thalassemia in Sicily can be subdivided into two groups. One that occurs at a 71% frequency and consists of the beta 39, IVS 1,110 and IVS 1,6 mutations and the other group at a 20% frequency comprising the -87, beta s, IVS 1,1 and IVS 2,745 mutations. The identification of all these mutations by polymerase chain reaction (PCR) and conventional dot-blot hybridization has been time consuming and expensive. In this article, we describe the implementation of the reverse dot-blot (RDB) hybridization as a rapid nonradioactive method for the identification of the nine most frequent molecular lesions in the beta-globin gene (-87, beta s, beta c, IVS 1,1, IVS 1,6, IVS 1,110, beta 39, IVS 2,1, IVS 2,745) in Sicily. Sixty prenatal diagnoses were performed by this RDB assay, each of which was confirmed by dot-blot/ASO hybridization; thus demonstrating the accuracy of the RDB. The main advantage of this assay is the rapid typing of an individual's DNA for many mutations in a single working day. Because the mutations in this assay are representative for the Mediterranean region, this mutational panel can also be extended to the screening of beta-thalassemia from other Mediterranean regions.
Magnetic resonance imaging of intracranial tumors: intra-patient comparison of gadoteridol and ferumoxytol (2010)

This study aims to compare gadoteridol with ferumoxytol for contrast-enhanced and perfusion-weighted (PW) MRI of intracranial tumors. The final analysis included 26 patients, who underwent 3 consecutive days of 3T MRI. Day 1 consisted of anatomical pre- and postcontrast images, and PW MRI was acquired using gadoteridol (0.1 mmol/kg). On Day 2, the same MRI sequences were obtained with ferumoxytol (510 mg) and on Day 3, the anatomical images were repeated to detect delayed ferumoxytol-induced signal changes. The T₁-weighted images were evaluated qualitatively and quantitatively for enhancement volume and signal intensity (SI) changes; PW data were used to estimate the relative cerebral blood volume (rCBV). All 26 lesions showed 24-hour T₁-weighted ferumoxytol enhancement; 16 also had T₂-weighted hypointensities. In 6 patients, ferumoxytol-induced signal changes were noted in areas with no gadoteridol enhancement. Significantly greater (P< .0001) SI changes were seen with gadoteridol, and qualitative analyses (lesion border delineation, internal morphology, contrast enhancement) also showed significant preferences (P= .0121; P = .0015; P < .0001, respectively) for this agent. There was no significant difference in lesion enhancement volumes between contrast materials. The ferumoxytol-rCBV values were significantly higher (P = .0016) compared with the gadoteridol-rCBV values. In conclusion, ferumoxytol provides important information about tumor biology that complements gadoteridol imaging. The rCBV measurements indicate areas of tumor undergoing rapid growth, whereas the 24-hour scans mark the presence of inflammatory cells. Both of these functions provide useful information about tumor response to treatment. We suggest that dynamic and anatomical imaging with ferumoxytol warrant further assessment in brain tumor therapy.
Anti‐angiogenic perfluorocarbon nanoparticles for diagnosis and treatment of atherosclerosis (2009)

Complementary developments in nanotechnology, genomics, proteomics, molecular biology and imaging offer the potential for early, accurate diagnosis. Molecularly-targeted diagnostic imaging agents will allow noninvasive phenotypic characterization of pathologies and, therefore, tailored treatment close to the onset. For atherosclerosis, this includes anti-angiogenic therapy with specifically-targeted drug delivery systems to arrest the development of plaques before they impinge upon the lumen. Additionally, monitoring the application and effects of this targeted therapy in a serial fashion will be important. This review covers the specific application of alpha(nu)beta(3)-targeted anti-angiogenic perfluorocarbon nanoparticles in (1) the detection of molecular markers for atherosclerosis, (2) the immediate verification of drug delivery with image-based prediction of therapy outcomes, and (3) the serial, noninvasive observation of therapeutic efficacy.
Dendritic-cell infection by human cytomegalovirus is restricted to strains carrying functional UL131–128 genes and mediates efficient viral antigen presentation to CD8+ T cells (2005)

Human cytomegalovirus (HCMV) genetic determinants of endothelial-cell tropism and virus transfer to leukocytes (both polymorphonuclear and monocyte) have been recently identified in the UL131-128 genes. Here it is documented that the same genetic determinants of HCMV are responsible for monocyte-derived dendritic-cell (DC) tropism, i.e. all endotheliotropic and leukotropic strains of HCMV are also DC-tropic (or dendrotropic). In fact, all recent clinical HCMV isolates and deletion mutants sparing the UL131-128 locus as well as the endotheliotropic revertants AD169 and Towne were able to productively infect DC following co-culture with infected endothelial cells. On the contrary, the same clinical isolates extensively propagated in human fibroblasts, the UL131-128 deletion mutants and the reference laboratory strains were not. Peak extracellular virus titres in DC were reached 4-7 days post-infection (p.i.). Viral proteins pp65 and p72 were detected 1-3 h p.i., involving the great majority of DC 24 h p.i., while gB was abundantly detected 96 h p.i., when a cytopathic effect first appeared. Infection of DC with cell-free virus released into the medium could only be achieved with HCMV strains extensively adapted to growth in endothelial cells, reaching the peak titres 10 days p.i. DC infected for 24 h with cell-free virus and incubated for 16 h with autologous peripheral blood mononuclear cells were found to act as a potent stimulator of both HCMV-specific CD4+- and CD8+-mediated immune responses, as determined by cytokine flow cytometry. DC incubated with inactivated crude whole viral antigen preparations were only capable of eliciting a significant CD4+-mediated immune response.
Remote Radio‐Frequency Controlled Nanoliter Chemistry and Chemical Delivery on Substrates (2007)

A matter of control: Metallic, self-assembled nanoliter containers have been prepared that can be remotely guided in any chosen spatial trajectory by a magnetic field, as well as remotely triggered by radio-frequency electromagnetic fields to release chemical reactants (see picture). The containers were utilized to facilitate, on demand, spatially localized microfabrication in a capillary and non-invasive chemical delivery to living cells. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z604414_s.html or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Chimeric animal and plant viruses expressing epitopes of outer membrane protein F as a combined vaccine against Pseudomonas aeruginosa lung infection (2000)

Outer membrane protein F of Pseudomonas aeruginosa has vaccine efficacy against infection by P. aeruginosa as demonstrated in a variety of animal models. Through the use of synthetic peptides, three surface-exposed epitopes have been identified. These are called peptides 9 (aa 261–274 in the mature F protein, TDAYNQKLSERRAN), 10 (aa 305–318, NATAEGRAINRRVE), and 18 (aa 282–295, NEYGVEGGRVNAVG). Both the peptide 9 and 10 epitopes are protective when administered as a vaccine. In order to develop a vaccine that is suitable for use in humans, including infants with cystic fibrosis, the use of viral vector systems to present the protective epitopes has been investigated. An 11-amino acid portion of epitope 10 (AEGRAINRRVE) was successfully inserted into the antigenic B site of the hemagglutinin on the surface of influenza virus. This chimeric influenza virus protects against challenge with P. aeruginosa in the mouse model of chronic pulmonary infection. Attempts to derive a chimeric influenza virus carrying epitope 9 have been unsuccessful. A chimeric plant virus, cowpea mosaic virus (CPMV), with epitopes 18 and 10 expressed in tandem on the large coat protein subunit (CPMV-PAE5) was found to elicit antibodies that reacted exclusively with the 10 epitope and not with epitope 18. Use of this chimeric virus as a vaccine afforded protection against challenge with P. aeruginosa in the mouse model of chronic pulmonary infection. Chimeric CPMVs with a single peptide containing epitopes 9 and 18 expressed on either of the coat proteins are in the process of being evaluated. Epitope 9 was successfully expressed on the coat protein of tobacco mosaic virus (TMV), and this chimeric virus is protective when used as a vaccine in the mouse model of chronic pulmonary infection. However, initial attempts to express epitope 10 on the coat protein of TMV have been unsuccessful. Efforts are continuing to construct chimeric viruses that express both the 9 and 10 epitopes in the same virus vector system. Ideally, the use of a vaccine containing two epitopes of protein F is desirable in order to greatly reduce the likelihood of selecting a variant of P. aeruginosa that escapes protective antibodies in immunized humans via a mutation in a single epitope within protein F. When the chimeric influenza virus containing epitope 10 and the chimeric TMV containing epitope 9 were given together as a combined vaccine, the immunized mice produced antibodies directed toward both epitopes 9 and 10. The combined vaccine afforded protection against challenge with P. aeruginosa in the chronic pulmonary infection model at approximately the same level of efficacy as provided by the individual chimeric virus vaccines. These results prove in principle that a combined chimeric viral vaccine presenting both epitopes 9 and 10 of protein F has vaccine potential warranting continued development into a vaccine for use in humans.
Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells (1992)

We have analyzed the effects of NK cell stimulatory factor/IL-12, on proliferation of PBL and their subsets. IL-12 synergizes with lectins and phorbol diesters to induce proliferation of CD4+ and CD8+ peripheral blood T lymphocytes. In the case of phorbol-diester-induced proliferation, the effect of IL-12 is in part mediated by induced IL-2 production, as suggested by the observation that IL-12 enhances IL-2 production in these cultures and that anti-IL-2 antibodies inhibit proliferation. IL-12 synergizes also with anti-CD3 antibodies and with allogeneic stimulation in MLC in inducing T cell proliferation. IL-12 alone is mitogenic for preactivated T and NK lymphoblasts. This mitogenic effect is observed with similar doses of IL-12 on NK lymphoblasts as well as on CD4+ and CD8+ TCR-alpha beta+ and on TCR-gamma delta+ lymphoblasts. On TCR-alpha beta+ T lymphocytes the effect of IL-12 is always additive to that of IL-2 over a wide dose range. The same effect is observed on highly activated, actively proliferating NK cells. However, on NK and TCR-gamma delta+ lymphoblasts reverting to a resting state after stimulation and on a TCR-gamma delta+ acute leukemia-derived T cell line, IL-12 inhibits significantly the proliferation induced by moderate to high doses (10 to 100 U/ml) of IL-2. This inhibitory effect is, at least in part, indirect, and depends on IL-12-induced production of TNF. Neutralizing anti-TNF antibodies, but not anti-IFN-gamma and anti-transforming growth factor antibodies, restore by more than 70% the inhibition of proliferation induced by IL-12 in these cultures. However, TNF alone cannot mimic the inhibitory effect of IL-12 on the IL-2-induced proliferation of NK and TCR-gamma delta+ lymphoblasts, suggesting the involvement of additional mechanisms. The relevance of these findings for the biology of lymphocyte subsets mediating MHC nonrestricted cytotoxicity is discussed.
Evaluation of [ 11 C]‐choline positron‐emission/computed tomography in patients with increasing prostate‐specific antigen levels after primary treatment for prostate cancer (2007)

[(11)C]-choline PET/CT seems to be useful for re-staging prostate cancer after curative therapy and with increasing PSA levels; this was verified by histological examination. We recommend this method at PSA levels of <2.5 ng/mL.
The Need For Formal Verification In Hardware Design And What Formal Verification Has Not Done For Me Lately (2005)

The problem of verifying that the design of an integrated circuit will perform the tasks required by its specification is currently a perplexing one for circuit designers. Unfortunately, formal verification techniques in general, and theorem proving techniques in particular, have not been able to alleviate this problem. This paper briefly outlines the verification tasks required in a circuit design and identify those verification tasks for which formal approaches may be most beneficial.
Bacterial contamination of inanimate surfaces and equipment in the intensive care unit (2015)

Intensive care unit (ICU)-acquired infections are a challenging health problem worldwide, especially when caused by multidrug-resistant (MDR) pathogens. In ICUs, inanimate surfaces and equipment (e.g., bedrails, stethoscopes, medical charts, ultrasound machine) may be contaminated by bacteria, including MDR isolates. Cross-transmission of microorganisms from inanimate surfaces may have a significant role for ICU-acquired colonization and infections. Contamination may result from healthcare workers' hands or by direct patient shedding of bacteria which are able to survive up to several months on dry surfaces. A higher environmental contamination has been reported around infected patients than around patients who are only colonized and, in this last group, a correlation has been observed between frequency of environmental contamination and culture-positive body sites. Healthcare workers not only contaminate their hands after direct patient contact but also after touching inanimate surfaces and equipment in the patient zone (the patient and his/her immediate surroundings). Inadequate hand hygiene before and after entering a patient zone may result in cross-transmission of pathogens and patient colonization or infection. A number of equipment items and commonly used objects in ICU carry bacteria which, in most cases, show the same antibiotic susceptibility profiles of those isolated from patients. The aim of this review is to provide an updated evidence about contamination of inanimate surfaces and equipment in ICU in light of the concept of patient zone and the possible implications for bacterial pathogen cross-transmission to critically ill patients.
The structure of the sinus wall of the lymph node relative to its endocytic properties and transmural cell passage (1980)

The internal structure of cells lining the lymphatic sinus of the lymph node includes the presence of large bristle-coated vesicles, transfer tubules, and vesicular organelles for the uptake and intracellular disposition of endocytosed material. The lining cells of the sinuses phagocytose particulate material from the lymph in the same manner as the sinusoidal endothelium of the bone marrow takes up particulates from the blood and, thus, are similar in this respect to the endothelial lining of the bone marrow sinusoids. Transmission and scanning electron microscopic examination of the lymphatic sinus wall in rat lymph nodes show that the walls of the lymphatic sinuses are continuous and do not have permanent apertures allowing free communication between the extrasinusoidal and intrasinusoidal compartments in the lymph node. Migrating lymphocytes cross the lymphatic sinus wall intracellularly, i.e., through the body of the lining cell, by making a temporary migration pore, which closes after the cell has reached the lumen of the sinus. In addition there are sporadic aggregations of macrophages in transmural positions. The direction of their movement is unknown.
Rapid Co-Optimization of Processing and Circuit Design to Overcome Carbon Nanotube Variations (2015)

Carbon nanotube field-effect transistors (CNFETs) are promising candidates for building energy-efficient digital systems at highly scaled technology nodes. However, carbon nanotubes (CNTs) are inherently subject to variations that reduce circuit yield, increase susceptibility to noise, and severely degrade their anticipated energy and speed benefits. Joint exploration and optimization of CNT processing options and CNFET circuit design are required to overcome this outstanding challenge. Unfortunately, existing approaches for such exploration and optimization are computationally expensive, and mostly rely on trial-and-error-based ad hoc techniques. In this paper, we present a framework that quickly evaluates the impact of CNT variations on circuit delay and noise margin, and systematically explores the large space of CNT processing options to derive optimized CNT processing and CNFET circuit design guidelines. We demonstrate that our framework: 1) runs over 100× faster than existing approaches and 2) accurately identifies the most important CNT processing parameters, together with CNFET circuit design parameters (e.g., for CNFET sizing and standard cell layouts), to minimize the impact of CNT variations on CNFET circuit speed with ≤5% energy cost, while simultaneously meeting circuit-level noise margin and yield constraints.
Simultaneous three-dimensional myocardial T1 and T2 mapping in one breath hold with 3D-QALAS (2014)

The 3D-QALAS method has demonstrated good accuracy and intra-scan variability both in-vitro and in-vivo. It allows rapid acquisition and provides quantitative information of both T1 and T2 relaxation times in the same scan with full coverage of the left ventricle, enabling clinical application in a broader spectrum of cardiac disorders.