gebhart/patrepeval huggingface dataset:
Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair (2003)

T helper 1 responses are typically proinflammatory, while Th2 responses have been considered regulatory. Interestingly, Th2 responses characterize a number of pulmonary diseases, many of which terminate in tissue remodeling and fibrosis. We developed a mouse model using Schistosoma mansoni eggs and cytokine-deficient mice to induce highly polarized Th1- or Th2-type inflammation in the lung. In this study, we examined the pathology and cytokine profiles in Th1- and Th2-polarized environments and used oligonucleotide microarray analysis to decipher the genes responsible for these effects. We further elaborated on the results using IL-10- and IL-13-deficient mice because these cytokines are believed to be the central regulators of Th2-associated pathology. We found that the Th1-polarized mice developed small granulomas with less fibrosis while expressing genes characteristic of tissue damage. Th2-polarized mice, in contrast, formed large granulomas with massive collagen deposition and up-regulated genes associated with wound healing, specifically, arginase, collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of MMP. In addition, several members of the chitinase-like family were up-regulated in the lung following egg challenge. We also developed a method of defining the net collagen deposition using the expression profiles of several collagen, MMP, and tissue inhibitors of MMP genes. We found that Th1-polarized mice did not elaborate collagens or MMPs and therefore did not have a significant capacity for repair in this model. Thus, Th1-mediated inflammation is characterized by tissue damage, while Th2 directs wound healing and fibrosis.
Multimarker Analysis of Circulating Tumor Cells in Peripheral Blood of Metastatic Breast Cancer Patients: A Step Forward in Personalized Medicine (2012)

AIM: To develop an immunomagnetic assay for the isolation of circulating tumor cells (CTCs) followed by the analysis of a multimarker panel, which will enable the characterization of these malignant cells with high accuracy. PATIENTS AND METHODS: Peripheral blood (PB) was collected from 32 metastatic breast cancer patients and 42 negative controls. The antibodies BM7 and VU1D9 were used for immunomagnetic tumor cell enrichment. A real-time reverse transcription-polymerase chain reaction (RT-PCR) approach for the markers KRT19, SCGB2A2, MUC1, EPCAM, BIRC5 and ERBB2 was used for CTC detection and characterization. RESULTS: THE POSITIVITY RATES FOR EACH MARKER WERE AS FOLLOWS: 46.9% for KRT19, 25.0% for SCGB2A2, 28.1% for MUC1, 28.1% for EPCAM, 21.9% for BIRC5, and 15.6% for ERBB2. After the creation of individualized cutoffs, the sensitivity and specificity of the combined marker gene panel increased to 56.3% and 100%, respectively. Interestingly, 27.0% of the HER2-negative tumor patients showed ERBB2 mRNA-positive CTCs. CONCLUSIONS: The described technique can be used to measure CTCs with great accuracy. The use of a multimarker panel for the characterization of CTCs may provide real-time information and be of great value in therapy monitoring.
Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis (2010)

Although the effects of commensal bacteria on intestinal immune development seem to be profound, it remains speculative whether the gut microbiota influences extraintestinal biological functions. Multiple sclerosis (MS) is a devastating autoimmune disease leading to progressive deterioration of neurological function. Although the cause of MS is unknown, microorganisms seem to be important for the onset and/or progression of disease. However, it is unclear how microbial colonization, either symbiotic or infectious, affects autoimmunity. Herein, we investigate a role for the microbiota during the induction of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Mice maintained under germ-free conditions develop significantly attenuated EAE compared with conventionally colonized mice. Germ-free animals, induced for EAE, produce lower levels of the proinflammatory cytokines IFN-γ and IL-17A in both the intestine and spinal cord but display a reciprocal increase in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). Mechanistically, we show that gut dendritic cells from germ-free animals are reduced in the ability to stimulate proinflammatory T cell responses. Intestinal colonization with segmented filamentous bacteria (SFB) is known to promote IL-17 production in the gut; here, we show that SFBs also induced IL-17A-producing CD4(+) T cells (Th17) in the CNS. Remarkably, germ-free animals harboring SFBs alone developed EAE, showing that gut bacteria can affect neurologic inflammation. These findings reveal that the intestinal microbiota profoundly impacts the balance between pro- and antiinflammatory immune responses during EAE and suggest that modulation of gut bacteria may provide therapeutic targets for extraintestinal inflammatory diseases such as MS.
Differences in Text Structure and Its Implications for Assessment of Struggling Readers (2006)

Abstract One source of potential difficulty for struggling readers is the variability of texts across grade levels. This article explores the use of automatic natural language processing techniques to identify dimensions of variation within a corpus of school-appropriate texts. Specifically, we asked: Are there identifiable dimensions of lexical and discourse/genre variation among these texts, and what are major differences among 3rd- to 6th-grade texts? At the lexical level, we identified sets of nonspecific lexical terms that appear to be used across wide sets of texts, another that appears to be more "academic" in nature, and a large number of topic specific sets. Additional analyses detected several dimensions of variation that were fairly similar to the dimensions detected in previous studies (e.g., Biber, 1988; Reppen, 2001), as well as several new dimensions. In comparing 3rd and 6th grade level texts, we observed a shift in the distribution of texts on several dimensions.
Conformational preferences of amino acids in globular proteins (1978)

In a previous paper [Levitt, M., and Greer, J. (1977), J. Mol. Biol. 114, 181--239], an objective compilation of the secondary-structure regions in more than 50 different globular proteins was produced automatically. In the present paper, these assignments of secondary structure are analyzed to give the frequency of occurrence of the 20 naturally occurring amino acids in alpha helix, beta sheet, and reverse-turn secondary structure. Nineteen of these amino acids have a weak but statistically signficant preference for only on type of secondary structure. These preferences correlate well with the chemical structure of the particular amino acids giving a more objective classification of the conformational properties of amino acids than available before.
Catalytic Asymmetric Michael Reactions of Acetaldehyde (2008)

Acetaldehyde, now a big contender: A silyl prolinol derivative was found to catalyze the first Michael addition of acetaldehyde with both aromatic and aliphatic nitroolefins in excellent enantioselectivities (see scheme, TMS=trimethylsilyl). The utility of the reaction is illustrated in the synthesis of three current pharmaceuticals and in the synthesis of an enantiopure 3-monosubstituted pyrrolidine.
Prospective Study Correlating Fibrinopeptide A, Troponin I, Myoglobin, and Myosin Light Chain Levels With Early and Late Ischemic Events in Consecutive Patients Presenting to the Emergency Department With Chest Pain (2000)

Elevated FPA and TnI correlated with cardiac events during the initial week in patients presenting to the Emergency Department with chest pain. FPA predicted adverse events and a shorter event-free survival at 6 months.
Efforts towards Expansion of the Genetic Alphabet: Pyridone and Methyl Pyridone Nucleobases (2006)

Getting on with it: A common problem with hydrophobic non-natural base pairs—the inefficient extension following such a base pair—is reduced by using the methylpyridone scaffold, which simultaneously limits another frequent problem of non-natural bases: mispairs with deoxyadenosine. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z601272_s.pdf 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.
Single-electron devices and their applications (1999)

The goal of this paper is to review in brief the basic physics of single-election devices, as well as their-current and prospective applications. These devices based on the controllable transfer of single electrons between small conducting "islands", have already enabled several important scientific experiments. Several other applications of analog single-election devices in unique scientific instrumentation and metrology seem quite feasible. On the other hand, the prospect of silicon transistors being replaced by single-electron devices in integrated digital circuits faces tough challenges and remains uncertain. Nevertheless, even if this replacement does not happen, single electronics will continue to play an important role by shedding light on the fundamental size limitations of new electronic devices. Moreover, recent research in this field has generated some by-product ideas which may revolutionize random-access-memory and digital-data-storage technologies.
Interoperability of peer-to-peer file sharing protocols (2002)

Peer-to-Peer (P2P) file sharing software has brought a hot discussion on P2P file sharing among all businesses. Freenet, Gnutella, and Napster are the three most popular P2P file sharing applications. They use three distinct protocols and these protocols come with different characteristics. In this paper, we discuss the protocols of these P2P file sharing applications, in terms of the methodologies used for peer registry, query and content sharing. In order to maximize the benefit of P2P file sharing application that is to facilitate file sharing among various P2P file sharing applications, we propose a framework to integrate various P2P file sharing protocols using P2P gateway in this paper.
Suppression and enhancement of in vitro lymphocyte reactivity by factors in rat submandibular gland extracts. (1985)

The addition of crude extracts from rat submandibular (SM) glands to murine spleen and lymph node cell cultures stimulated with concanavalin A (Con A) induced either suppression (at high concentrations) or further stimulation (at lower concentrations) or further stimulation (at lower concentrations) of proliferative activity. Gel filtration of the extracts revealed that suppressive activity was due to factors of molecular weight in the 50,000-96,000 range, while stimulation was due to factors in the 13,000-35,000 molecular weight range. The suppressor activity of the higher molecular weight fractions was not due to a reduction of cell viability or of the uptake of tritiated thymidine. This was demonstrated by the fact that the addition of IL-2 to the cultures completely reversed the suppressive effect. Further fractionation of the suppressive and of the stimulatory gel filtration fractions with the chromatofocusing technique led to the identification of a single fraction with suppressor activity and of multiple discrete fractions with stimulatory activity.
Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo (2018)

Photoacoustic (PA) computed tomography (PACT) benefits from genetically encoded probes with photochromic behavior, which dramatically increase detection sensitivity and specificity through photoswitching and differential imaging. Starting with a DrBphP bacterial phytochrome, we have engineered a near-infrared photochromic probe, DrBphP-PCM, which is superior to the full-length RpBphP1 phytochrome previously used in differential PACT. DrBphP-PCM has a smaller size, better folding, and higher photoswitching contrast. We have imaged both DrBphP-PCM and RpBphP1 simultaneously on the basis of their unique signal decay characteristics, using a reversibly switchable single-impulse panoramic PACT (RS-SIP-PACT) with a single wavelength excitation. The simple structural organization of DrBphP-PCM allows engineering a bimolecular PA complementation reporter, a split version of DrBphP-PCM, termed DrSplit. DrSplit enables PA detection of protein-protein interactions in deep-seated mouse tumors and livers, achieving 125-µm spatial resolution and 530-cell sensitivity in vivo. The combination of RS-SIP-PACT with DrBphP-PCM and DrSplit holds great potential for noninvasive multi-contrast deep-tissue functional imaging.
Dominant and diet-responsive groups of bacteria within the human colonic microbiota (2010)

The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resistant starch (RS) or non-starch polysaccharides (NSPs) and a reduced carbohydrate weight loss (WL) diet, over 10 weeks. Analysis of 16S rRNA sequences in stool samples of six volunteers detected 320 phylotypes (defined at >98% identity) of which 26, including 19 cultured species, each accounted for >1% of sequences. Although samples clustered more strongly by individual than by diet, time courses obtained by targeted qPCR revealed that 'blooms' in specific bacterial groups occurred rapidly after a dietary change. These were rapidly reversed by the subsequent diet. Relatives of Ruminococcus bromii (R-ruminococci) increased in most volunteers on the RS diet, accounting for a mean of 17% of total bacteria compared with 3.8% on the NSP diet, whereas the uncultured Oscillibacter group increased on the RS and WL diets. Relatives of Eubacterium rectale increased on RS (to mean 10.1%) but decreased, along with Collinsella aerofaciens, on WL. Inter-individual variation was marked, however, with >60% of RS remaining unfermented in two volunteers on the RS diet, compared to <4% in the other 12 volunteers; these two individuals also showed low numbers of R-ruminococci (<1%). Dietary non-digestible carbohydrate can produce marked changes in the gut microbiota, but these depend on the initial composition of an individual's gut microbiota.
Sympathetic discharges in the human supraorbital nerve and their relation to sudo‐ and vasomotor responses. (1990)

1. Sympathetic nerve activity occurring as bursts of multi-unit impulses was recorded with tungsten microelectrodes in the supraorbital nerve of awake healthy subjects. Within the fascicular innervation zone on the forehead, skin resistance was measured as an indicator of sweat gland activity, and skin blood flow was measured with laser-doppler flowmetry. 2. At room temperature, there was little or no background burst activity, but arousal stimuli or mental stress evoked bursts followed by a vasodilator response. Provided repeated arousal stimuli were delivered, individual bursts were followed by a decrease in skin resistance. 3. Body heating induced increasing background burst activity. After an initial period without associated electrodermal activity, there were decreases in skin resistance, which showed a positive linear correlation with the amplitude of the preceding burst. Individual bursts were followed by a vasodilator response with an average onset latency of 2.8 s and an average duration of 9.1 s, and rapid increases in blood flow coincided with a marked increase in burst activity. Arousal stimuli evoked bursts followed by both vasodilator and skin resistance responses. 4. During body cooling, there was no background burst activity, but signs of relatively weak, probably neurally mediated vasoconstriction were observed and arousal-evoked bursts were reduced or abolished, as were the associated vasodilator and skin resistance responses. 5. It is concluded that body heating induces active sympathetic vasodilatation in the skin of the human forehead, and that this is either sudomotor-mediated or caused by vasodilator fibres firing in synchrony with sudomotor fibres. A similar sympathetic mechanism probably underlies the vasodilator responses evoked by arousal stimuli and mental stress.
Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat (2013)

Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post-injury time points, as compared with sham-injured controls (P ≤ 0.05). Accumulation of β-amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post-injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase-3 co-labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post-injury (P ≤ 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI.
Simple, Short Peptide Derivatives of a Sulfonylindolecarboxamide (L-737,126) Active in Vitro against HIV-1 Wild Type and Variants Carrying Non-Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations (2004)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) active against NNRTI-resistant mutants were obtained by introducing two methyl groups at positions 3 and 5 of the benzenesulfonyl moiety of L-737,126 (1) and coupling one to three glycinamide/alaninamide units to its carboxyamide function. In cell-based assays, the new derivatives showed activities against HIV-1 wild type and NNRTI-resistant mutants [Y181C, K103N-Y181C, and triple mutant (K103R, V179D, P225H) highly resistant to efavirenz] superior to that of the parent indole derivative 1.
Activation of human prothrombin by porcine aortic endothelial cells???a potential barrier to pig to human xenotransplantation (1996)

A potential solution to the shortage of human organs for transplantation lies in the use of animal organs with the pig as the most likely donor. Perfusion of porcine organs with human blood, however, results in hyperacute rejection (xenograft reaction) which occurs within minutes to hours and is characterised by intravascular thrombosis. The pathogenesis of this xenograft reaction is attributed to xenoreactive natural antibodies (XNA) binding to epitopes on porcine endothelium activating complement with subsequent haemostatic activation. We have investigated whether there is direct activation of human coagulation by porcine endothelium in the absence of XNA and complement. Previous experiments demonstrated possible pathological activation of the common pathway, thus human prothrombin and factor X were added separately to porcine endothelium and monitored for activation. Human prothrombin was activated by porcine but not human endothelium. There was no activation of factor X. Hirudin inhibited prothrombin activation suggesting that a conformational change may occur in prothrombin on binding to porcine endothelium, such that its catalytic centre is exposed with subsequent autocatalytic cleavages. If this in vitro observation of direct prothrombin activation is translated to the in vivo situation then this phenomenon may pose a non-immunological obstacle to pig to human xenotransplantation.
Strategy for selecting and characterizing linker peptides for CBM9‐tagged fusion proteins expressed in Escherichia coli (2007)

The influence of linker design on fusion protein production and performance was evaluated when a family 9 carbohydrate-binding module (CBM9) serves as the affinity tag for recombinant proteins expressed in Escherichia coli. Two bioinformatic strategies for linker design were applied: the first identifies naturally occurring linkers within the proteome of the host organism, the second involves screening peptidases and their known specificities using the bioinformatics software MEROPS to design an artificial linker resistant to proteolysis within the host. Linkers designed using these strategies were compared against traditional poly-glycine linkers. Although widely used, glycine-rich linkers were found by tandem MS data to be susceptible to hydrolysis by E. coli peptidases. The natural (PT)(x)P and MEROPS-designed S(3)N(10) linkers were significantly more stable, indicating both strategies provide a useful approach to linker design. Factor X(a) processing of the fusion proteins depended strongly on linker chemistry, with poly(G) and S(3)N(10) linkers showing the fastest cleavage rates. Luminescence resonance energy transfer studies, used to measure average distance of separation between GFP and Tb(III) bound to a strong calcium-binding site of CBM9, revealed that, for a given linker chemistry, the separation distance increases with increasing linker length. This increase was particularly large for poly(G) linkers, suggesting that this linker chemistry adopts a hydrated, extended configuration that makes it particularly susceptible to proteolysis. Differential scanning calorimetry studies on the PT linker series showed that fusion of CBM9 to GFP did not alter the T(m) of GFP but did result in a destabilization, as seen by both a decrease in T(m) and DeltaH(cal), of CBM9. The degree of destabilization increased with decreasing length of the (PT)(x)P linker such that DeltaT(m) = -8.4 degrees C for the single P linker.