gebhart/patrepeval huggingface dataset:
Genome-Wide Identification of Novel Genes Involved in Early Th1 and Th2 Cell Differentiation (2007)

Th cell subtypes, Th1 and Th2, are involved in the pathogenesis or progression of many immune-mediated diseases, such as type 1 diabetes and asthma, respectively. Defining the molecular networks and factors that direct Th1 and Th2 cell differentiation will help to understand the pathogenic mechanisms causing these diseases. Some of the key factors regulating this differentiation have been identified, however, they alone do not explain the process in detail. To identify novel factors directing the early differentiation, we have studied the transcriptomes of human Th1 and Th2 cells after 2, 6, and 48 h of polarization at the genome scale. Based on our current and previous studies, 288 genes or expressed sequence tags, representing approximately 1-1.5% of the human genome, are regulated in the process during the first 2 days. These transcriptional profiles revealed genes coding for components of certain pathways, such as RAS oncogene family and G protein-coupled receptor signaling, to be differentially regulated during the early Th1 and Th2 cell differentiation. Importantly, numerous novel genes with unknown functions were identified. By using short-hairpin RNA knockdown, we show that a subset of these genes is regulated by IL-4 through STAT6 signaling. Furthermore, we demonstrate that one of the IL-4 regulated genes, NDFIP2, promotes IFN-gamma production by the polarized human Th1 lymphocytes. Among the novel genes identified, there may be many factors that play a crucial role in the regulation of the differentiation process together with the previously known factors and are potential targets for developing therapeutics to modulate Th1 and Th2 responses.
Derivation of Human Embryonic Stem Cell Lines from Vitrified Human Embryos (2009)

Human embryonic stem cell lines are usually derived from human embryos that have become excess to clinical needs in assisted reproduction programs, whether because the couple in question has completed their family or because the embryo was found to be clinically unsuitable for transfer due to severe genetic condition (in case of pre-implantation genetic diagnosis, PGD). Culturing embryos to a blastocyst stage (5-6 days after IVF) before embryo transfer or cryopreservation instead of earlier commonly used 8-cell stage (3 days after IVF) calls for new methods for embryo cryopreservation and allows higher efficiencies for the actual stem cell derivation. Despite the vast advances in other fields of embryonic stem cell research, methods for derivation of new lines have not changed much over the years, mainly due to scarcity of embryos limiting experimentation. We describe here methods required to derive new embryonic stem cell lines starting from the initial cryopreservation of an embryo and finishing with a new cell line. We cover embryo cryopreservation and warming using a highly efficient vitrification method, the production of feeder cells and feeder plates, as well as embryo handling, plating and critical early passages, including earliest possible cryopreservation of putative stem cells using vitrification.
Video Microscopy of Dynamically Aggregated Paramagnetic Particle Chains in an Applied Rotating Magnetic Field (2003)

A rotating unidirectional magnetic field generated by a motor-mounted permanent magnet was used to dynamically aggregate paramagnetic particles from suspension to form chains. Video microscopy and image processing were used to analyze the data. Good synchronicity was observed between the chains and the field up to 8 Hz frequency. Chain growth is facilitated at very low rotational frequencies initially after starting from static conditions, after which the mean chain length decreases in response to increasing viscous drag forces. As the frequency is increased from low values, the mean chain length decreases initially rapidly and later more slowly at higher frequencies, thus resulting in two regimes: the fast and the slow decrease regimes. Typical structures such as linear chains and S-shaped chains are observed as well as unusual U-shaped structures. The formation of dynamic S-shaped structures can be predicted based on the flexibility of the chains and the principle of conservation of angular momentum. Formation of single-chain aggregates is observed in microwells that are up to 50 μm wide, whereas in larger microwells multichain formation was noticed. The motor-mounted permanent magnet arrangement has applications in the development of portable microchip biosensors. The arrangement proved sufficient and reliable in forming chains, which display behavior similar to that observed under more elaborate and controlled conditions.
Ab Initio Study of Adsorption and Decomposition of NH3 on Si(100)-(2×1) (2000)

We investigate the mechanism of NH3 adsorption and initial decomposition on the (2×1) reconstructed Si(100) surface using B3LYP density functional theory. The Si(100)-(2×1) surface is described using cluster approximation. Ammonia is found to adsorb on the “down” atom of the buckled silicon dimer with no activation barrier. We also find that only half of the surface silicon atoms are active sites for ammonia adsorption. Ammonia adsorption on the Si(100)-(2×1) is exothermic with an adsorption energy of 29 kcal/mol. Dissociation of the adsorbed ammonia to form NH2(a) and H(a) proceeds with a low activation energy of 5 kcal/mol below the NH3(g) and bare Si(100)-(2×1) energy. Our calculated recombination desorption energy of 51 kcal/mol is found to be in good agreement with the temperature-programmed desorption experimental result of 47 kcal/mol. Additionally, our calculated vibrational spectra of NH2(a) and H(a) agree within 2% of the experimental high-resolution electron energy loss spectra.
Mitigation strategies for pandemic influenza in the United States (2006)

Recent human deaths due to infection by highly pathogenic (H5N1) avian influenza A virus have raised the specter of a devastating pandemic like that of 1917-1918, should this avian virus evolve to become readily transmissible among humans. We introduce and use a large-scale stochastic simulation model to investigate the spread of a pandemic strain of influenza virus through the U.S. population of 281 million individuals for R(0) (the basic reproductive number) from 1.6 to 2.4. We model the impact that a variety of levels and combinations of influenza antiviral agents, vaccines, and modified social mobility (including school closure and travel restrictions) have on the timing and magnitude of this spread. Our simulations demonstrate that, in a highly mobile population, restricting travel after an outbreak is detected is likely to delay slightly the time course of the outbreak without impacting the eventual number ill. For R(0) < 1.9, our model suggests that the rapid production and distribution of vaccines, even if poorly matched to circulating strains, could significantly slow disease spread and limit the number ill to <10% of the population, particularly if children are preferentially vaccinated. Alternatively, the aggressive deployment of several million courses of influenza antiviral agents in a targeted prophylaxis strategy may contain a nascent outbreak with low R(0), provided adequate contact tracing and distribution capacities exist. For higher R(0), we predict that multiple strategies in combination (involving both social and medical interventions) will be required to achieve similar limits on illness rates.
Yersinia enterocolitica Promotes Deactivation of Macrophage Mitogen-activated Protein Kinases Extracellular Signal-regulated Kinase-1/2, p38, and c-Jun NH2-terminal Kinase (1997)

The enteropathogenic bacterium Yersinia enterocolitica counteracts host defense mechanisms by interfering with eukaryotic signal transduction pathways. In this study, we investigated the mechanism by which Y. enterocolitica prevents macrophage tumor necrosis factor-alpha (TNFalpha) production. Murine J774A.1 macrophages responded to Y. enterocolitica infection by rapid activation of mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK). However, after initial activation, the virulent Y. enterocolitica strain harboring the Y. enterocolitica virulence plasmid caused a substantial decrease in ERK1/2 and p38 tyrosine phosphorylation. Simultaneously, the virulent Y. enterocolitica strain gradually suppressed phosphorylation of the transcription factors Elk-1, activating transcription factor 2 (ATF2), and c-Jun, indicating time-dependent inhibition of ERK1/2, p38, and JNK kinase activities, respectively. Analysis of different Y. enterocolitica mutants revealed that (i) MAPK inactivation parallels the inhibition of TNFalpha release, (ii) the suppressor effect on TNFalpha production, which originates from the lack of TNFalpha mRNA, is distinct from the ability of Y. enterocolitica to resist phagocytosis and to prevent the oxidative burst, (iii) the tyrosine phosphatase YopH, encoded by the Y. enterocolitica virulence plasmid, is not involved in the decrease of ERK1/2 and p38 tyrosine phosphorylation or in the cytokine suppressive effect. Altogether, these results indicate that Y. enterocolitica possesses one or more virulence proteins that suppress TNFalpha production by inhibiting ERK1/2, p38, and JNK kinase activities.
3DFT MR angiography of carotid and basilar arteries. (1989)

Three-dimensional Fourier transform (3DFT) time-of-flight and two-dimensional Fourier transform (2DFT) projection phase-contrast MR angiography was performed in eight healthy volunteers and in 14 patients with known carotid artery or basilar artery occlusion, stenosis, or dissection. Comparative angiography was available in 13 cases (although in some cases the studies were separated by a number of months) and duplex sonography in one case. After localization of the carotid artery bifurcations by using 2DFT projection phase-contrast angiography, multiple 1.25-mm contiguous images were obtained with the 3DFT technique. In all cases, the lesions were identified on MR angiography. Because flow is detected in a manner that is independent of flow-induced phase shifts in the 3DFT time-of-flight technique, signal loss arising from complex flow and turbulence is minimized, yet the flow image remains sensitive to all velocity components of flow. Applications of this technique are ideal for relatively straight vessels where flow is laminar, but it can also be used to evaluate the carotid artery bifurcations where flow becomes complex.
Autoantibodies as potential biomarkers for breast cancer (2008)

Serum autoantibody profiling is a promising approach for early detection and diagnosis of breast cancer. Rather than one autoantibody, a panel of autoantibodies appears preferable to achieve superior accuracy. Further refinements will need to be made to further improve the accuracy. Once refined, the assay must be applied to a prospective patient population to demonstrate applicability.
Premature p34 cdc2 Activation Required for Apoptosis (1994)

Activation of the serine-threonine kinase p34cdc2 at an inappropriate time during the cell cycle leads to cell death that resembles apoptosis. Premature activation of p34cdc2 was shown to be required for apoptosis induced by a lymphocyte granule protease. The kinase was rapidly activated and tyrosine dephosphorylated at the initiation of apoptosis. DNA fragmentation and nuclear collapse could be prevented by blocking p34cdc2 activity with excess peptide substrate, or by inactivating p34cdc2 in a temperature-sensitive mutant. Premature p34cdc2 activation may be a general mechanism by which cells induced to undergo apoptosis initiate the disruption of the nucleus.
EphA2 Induction of Fibronectin Creates a Permissive Microenvironment for Malignant Cells (2004)

Normal and metastatic cells continuously exchange information with the surrounding tissue environment, and this communication governs many aspects of cell behavior. In particular, the physical placement or adhesions of cells within their environment are increasingly understood to facilitate this communication. Classically, cell-cell and cell-extracellular matrix adhesions have been viewed as separable events that are independently controlled. This simple view is changing, as evidence emerges of coordinated regulation of cellular adhesions. Here, we show that the EphA2 tyrosine kinase, which is overexpressed in many aggressive cancers, regulates a fine balance of cell-cell and cell-extracellular matrix adhesions in epithelial cells. EphA2 selectively inhibits cell-cell adhesions by increasing cell attachment and up-regulating the extracellular matrix protein fibronectin. We also show that fibronectin can contribute to important aspects of malignant character. Antibody-based targeting of EphA2 inhibits malignant cell growth by decreasing fibronectin and thereby inducing apoptotic death. Our findings strengthen a concept that cancer progression is regulated by a bidirectional communication between tumor cells and their surrounding microenvironment.
Three Rs for Vocal Skill Development in the Choral Rehearsal (1991)

Directors can hone students' vocal skills through an awareness of what it feels like to sing correctly. Gary B. Wilson uses respiration, relaxation, and registration to nurture young singers.
Gene probes for identification of the botulinal neurotoxin gene and specific identification of neurotoxin types B, E, and F (1993)

A polymerase chain reaction method was developed for the specific detection of the botulinum neurotoxin (BoNT) gene of Clostridium botulinum. Degenerate oligonucleotide primers, designed from the nucleotide sequence of the heavy chain of the BoNT gene, amplified a specific fragment of approximately 1.1 kb from strains of C. botulinum toxin types A, B, E, F, and G and neurotoxin-producing strains of Clostridium barati and Clostridium butyricum, but no fragment was obtained from nontoxigenic strains. The fragments amplified from several strains of C. botulinum types B, E, and F were cloned in Escherichia coli and their nucleotide sequences were determined. Sequences within this region were used to design oligonucleotide probes specific for BoNT type B (BoNT/B), BoNT/E, and BoNT/F genes. An additional probe was designed for the detection of the BoNT/F gene of C. barati, which differed in sequence from BoNT/F genes of both proteolytic and nonproteolytic strains of C. botulinum.
Cellular response to double‐stranded RNA (1991)

The study of double-stranded RNA (dsRNA) encompasses a variety of fields. Basic research in this area has contributed to a greater mechanistic understanding of gene induction, tumor cell growth arrest, the establishment of antiviral states, and immunomodulation. Because of the possible clinical value of these molecules, physicians are now exploring the use of synthetic dsRNA to treat patients with cancer, HIV-1 disease, and immune dysfunction. Continued studies of the mechanisms of action of dsRNA are likely to suggest an even wider scope of clinical applications.
The Hygiene Hypothesis of Atopic Disease–An Extended Version (2004)

The hygiene hypothesis of atopic disease suggests that environmental changes in the industrialized world have lead to reduced microbial contact at an early age and thus resulted in the growing epidemic of atopic eczema, allergic rhinoconjunctivitis, and asthma. The epidemiological findings have been combined with the Th1/Th2 paradigm of immune responsiveness to provide a coherent theory. Recent advances in epidemiology and immunology demonstrate, however, that the hygiene hypothesis may need to be extended in three respects. First, the importance of infections in causing immune deviance may be outweighed by other sources of microbial stimulation, perhaps most importantly by the indigenous intestinal microbiota. Second, immunomodulatory and suppressive immune responses complement the Th1/Th2 paradigm. Third, in addition to protection against atopy, protection against infectious, inflammatory, and autoimmune diseases may also depend upon healthy host-microbe interactions implicated in the hygiene hypothesis.
Public Health and Budget Impact of Probiotics on Common Respiratory Tract Infections: A Modelling Study (2015)

Public health and budget impact of probiotics are substantial, whether they reduce CRTI episodes frequency or duration. Noteworthy, the 2011-12 winter CRTI incidence was low and this analysis focused on the fraction of CRTI patients consulting a practitioner.
Mechanisms of IFN-gamma induction by natural killer cell stimulatory factor (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2 (1992)

We have investigated the molecular mechanisms regulating IFN-gamma production in human T lymphocytes stimulated by NK cell stimulatory factor (NKSF/IL-12). We show that NKSF synergizes with IL-2 and phorbol diesters inducing the accumulation of IFN-gamma mRNA in PHA-activated T cell blasts. NKSF regulates IFN-gamma mRNA expression in PHA blasts and the T leukemia cell line, TALL-103/2, at both the transcriptional and posttranscriptional levels. NKSF increases the transcriptional rate for IFN-gamma in both these cell types, as determined by nuclear run-on analysis. However, synergy between NKSF and IL-2 can be demonstrated only at the level of mRNA stability, and both cytokines are required to increase IFN-gamma mRNA half-life.
Direct detection of 0.1–20keV electrons with delta doped, fully depleted, high purity silicon p-i-n diode arrays (2006)

Direct detection of 0.1–20keV electrons is demonstrated using a boron delta doped high purity Si p-i-n diode array. Molecular beam epitaxy is used to grow a delta layer on the back surface of these fully depletable p-i-n diode arrays to form an electrode for detecting shallow-penetrating ionizing radiation. Device structure, processing, and characterization methods used for device testing and measurement of its response to electrons are discussed. Use of this detector for measuring the Si quantum yield over this wide energy range is also discussed.
Subunit structure of the erythropoietin receptor analyzed by 125I-Epo cross-linking in cells expressing wild-type or mutant receptors (1993)

To analyze the structure of the murine erythropoietin receptor (EpoR), wild-type or mutant EpoR cDNAs were expressed in cell lines, and the proteins that cross-linked with 125I-labeled erythropoietin (Epo) were analyzed by immunoprecipitation using an antibody against the intracellular region of the cloned EpoR. COS-7 cell transfectants expressing the wild-type EpoR showed two major cross-linked species of 145 and 110 Kd, both of which were recognized by the antibody against the cloned EpoR after denaturation under reducing conditions. Furthermore, a reduction in sizes of both cross-linked bands was observed in COS-7 transfectants expressing a mutant receptor with an internal deletion, thus indicating that both species contain the cloned EpoR. COS-7 cells expressing mutant receptors with carboxy-terminal deletions showed cross-linked bands corresponding to the smaller species of the two observed in cells expressing the wild-type receptor. In contrast to COS-7 cell transfectants, DA3 cells expressing wild-type or mutant EpoR cDNAs showed an additional cross-like species of 130 Kd. The size of this species was not altered by deletions in EpoR, showing that it did not contain EpoR. The 130-Kd cross-linked band, which would contain a 95-Kd protein, was also observed in a murine erythroleukemia cell line, D1B. These results suggest that Epo associates with a second component of 95 Kd, which is specifically expressed in hematopoietic cells.
Beta-peptides: twisting and turning. (1999)

Oligomers of beta-amino acids (beta-peptides), which are readily available by standard meth ods either in solution or on solid support, adopt a large variety of different secondary structures in solution and in the solid state. beta-Peptides 4, 5 and 10 fold into a helix with 3 residues per turn and 14-membered H-bonded rings (314 helix) that is left-handed for 5 and 10 and right-handed for 2 (due to the reversal of the chirality of the building blocks), as was clearly demonstrated by two-dimensional NMR-spectroscopy. This helix thermally is very stable in methanol solution upon heating. As shown by NMR- and CD-spectroscopy, it is partially populated even at 100 C (Figure 3). Another helix was dis covered for mixed beta-peptide 8 in methanol solution: it is characterized by 12- and 10- membered turns (Figure 4, left) and its central 10-membered turn has been found in the solid state of a geminally disubtituted beta-peptide (Figure 4, right). This central 10-membered turn was used as a scaffold to attach beta-amino acid residues that prefer a linear (non-helical) conformation (beta-peptide 21): a hairpin (pleated sheet-turn-pleated sheet) structure was determined in solution by NMR-spectroscopy (Figure 5). In contrast to this antiparallel pleated-sheet, a parallel pleated sheet was found for a beta-tripeptide in the solid state. For the first time it was possible to observe reversible peptide folding in MD simulations by studying beta-peptides (Figure 6) and to determine folding pathways and intermediates. beta-Peptides are a new class of promising peptidomimetics. They are resistant against the degradation by proteolytic enzymes such as pepsin, elastase, carboxypeptidase A, pro nase or proteasom 20S. A variety of beta-amino acids (27-34) was shown to be non- mutagenic by Ames tests and beta-peptides 47 and 48 reveal large elimination half-lives of 3 h (for 47) and 10 h (for 48) in the serum of rodents (Figure 7). Conjugates of alpha- and beta- peptides are efficient ligands for the HLA*B27 MHC Class I protein, a five fold increase of binding (2.0 microM for 55) compared to a natural peptidic ligand 51 was observed. Furthermore, beta-peptides are able to mimic natural a-peptidic hormones such as somatostatin. The cyclo-beta-tetrapeptide 57 binds to the five human somatostatin receptors in the micromolar range. In addition, several other non-natural oligomers such as beta-peptide nucleic acids (built from 58 and 59), beta-peptoids (60), oligomers of anthranilic acids and beta-sulfonamido peptides are discussed.
Analysis of Gene Expression in Parkinson's Disease: Possible Involvement of Neurotrophic Support and Axon Guidance in Dopaminergic Cell Death (2008)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. We have studied alterations in gene expression in the substantia nigra, the caudate nucleus and putamen of four PD patients and four matched controls using custom designed Agilent microarrays. To gain insight into changes in gene expression during early stages of dopaminergic neurodegeneration, we selectively investigated the relatively spared parts of the PD substantia nigra, and correlated gene expression changes with alterations in neuronal density. We identified changes in the expression of 287 transcripts in the substantia nigra, 16 transcripts in the caudate nucleus and four transcripts in the putamen. For selected transcripts, transcriptional alterations were confirmed with qPCR on a larger set of seven PD cases and seven matched controls. We detected concerted changes in functionally connected groups of genes. In the PD substantia nigra, we observed strong evidence for a reduction in neurotrophic support and alterations in axon guidance cues. As the changes occur in relatively spared parts of the PD substantia nigra, they suggest novel disease mechanisms involving neurotrophic support and axon guidance in early stages of cellular stress events, ultimately leading to dopaminergic cell death in PD.