gebhart/patrepeval huggingface dataset:
Fragmentation of Proteins in Cartilage Treated with Interleukin-1 (2007)

Degradation of bovine nasal cartilage induced by interleukin-1 (IL-1) was used to study catabolic events in the tissue over 16 days. Culture medium was fractionated by two-dimensional electrophoresis (isoelectric focusing and SDS-PAGE). Identification of components by peptide mass fingerprinting revealed released fragments representing the NC4 domain of the type IX collagen alpha1 chain at days 12 and 16. A novel peptide antibody against a near N-terminal epitope of the NC4 domain confirmed the finding and indicated the presence of one of the fragments already at day 9. Mass spectrometric analysis of the two most abundant fragments revealed that the smallest one contained almost the entire NC4 domain cleaved between arginine 258 and isoleucine 259 in the sequence -ETCNELPAR258-COOH NH2-ITP-. A larger fragment contained the NC4 domain and the major part of the COL3 domain with a cleavage site between glycine 400 and threonine 401 in COL3 (-RGPPGPPGPPGPSG400-COOH NH2-TIG-). The presence of multiple collagen alpha1 (IX) N-terminal sequences demonstrates that the released molecules were cleaved at sites very close to the original N terminus either prior to or due to IL-1 treatment. Matrix metalloproteinase 13 (MMP-13) is active and cleaves fibromodulin in the time interval studied. Cartilage explants treated with MMP-13 were shown to release collagen alpha1 (IX) fragments with the same sizes and with the same cleavage sites as those obtained upon IL-1 treatment. These data describe cleavage by an MMP-13 activity toward non-collagenous and triple helix domains. These potentially important degradation events precede the major loss of type II collagen.
An engineered scorpion toxin analogue with improved Kv1.3 selectivity displays reduced conformational flexibility (2015)

The voltage-gated Kv1.3 K(+) channel plays a key role in the activation of T lymphocytes. Kv1.3 blockers selectively suppress immune responses mediated by effector memory T cells, which indicates the great potential of selective Kv1.3 inhibitors in the therapy of certain autoimmune diseases. Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin is a high affinity blocker of Kv1.3, but also blocks Kv1.2 with similar potency. We designed and produced three AnTx variants: ([F32T]-AnTx, [N17A]-AnTx, [N17A/F32T]-AnTx) using solid-phase synthesis with the goal of improving the selectivity of the toxin for Kv1.3 over Kv1.2 while keeping the high affinity for Kv1.3. We used the patch-clamp technique to determine the blocking potency of the synthetic toxins on hKv1.3, mKv1.1, hKv1.2 and hKCa3.1 channels. Of the three variants [N17A/F32T]-AnTx maintained the high affinity of the natural peptide for Kv1.3 but became more than 16000-fold selective over Kv1.2. NMR data and molecular dynamics simulations suggest that the more rigid structure with restricted conformational space of the double substituted toxin compared to the flexible wild-type one is an important determinant of toxin selectivity. Our results provide the foundation for the possibility of the production and future therapeutic application of additional, even more selective toxins targeting various ion channels.
Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis (2016)

<b>Purpose:</b> Characterization of colorectal cancer transcriptome by high-throughput techniques has enabled the discovery of several differentially expressed genes involving previously unreported miRNA abnormalities. Here, we followed a systematic approach on a global scale to identify miRNAs as clinical outcome predictors and further validated them in the clinical and experimental setting.<b>Experimental Design:</b> Genome-wide miRNA sequencing data of 228 colorectal cancer patients from The Cancer Genome Atlas dataset were analyzed as a screening cohort to identify miRNAs significantly associated with survival according to stringent prespecified criteria. A panel of six miRNAs was further validated for their prognostic utility in a large independent validation cohort (<i>n</i> = 332). <i>In situ</i> hybridization and functional experiments in a panel of colorectal cancer cell lines and xenografts further clarified the role of clinical relevant miRNAs.<b>Results:</b> Six miRNAs (miR-92b-3p, miR-188-3p, miR-221-5p, miR-331-3p, miR-425-3p, and miR-497-5p) were identified as strong predictors of survival in the screening cohort. High miR-188-3p expression proves to be an independent prognostic factor [screening cohort: HR = 4.137; 95% confidence interval (CI), 1.568-10.917; <i>P</i> = 0.004; validation cohort: HR = 1.538; 95% CI, 1.107-2.137; <i>P</i> = 0.010, respectively]. Forced miR-188-3p expression increased migratory behavior of colorectal cancer cells <i>in vitro</i> and metastases formation <i>in vivo</i> (<i>P</i> < 0.05). The promigratory role of miR-188-3p is mediated by direct interaction with MLLT4, a novel identified player involved in colorectal cancer cell migration.<b>Conclusions:</b> miR-188-3p is a novel independent prognostic factor in colorectal cancer patients, which can be partly explained by its effect on MLLT4 expression and migration of cancer cells. <i>Clin Cancer Res; 23(5); 1323-33. ©2016 AACR</i>.
Creatine Phosphate, Not ATP, Is Required for 3′ End Cleavage of Mammalian Pre-mRNA in Vitro (1997)

The poly(A) tail of a mammalian mRNA is generated by endonucleolytic cleavage and poly(A) addition. Previous studies conducted with nuclear extracts suggested an ATP requirement for the cleavage step. We have reexamined the cofactor requirement, initially with the SV40 late pre-mRNA, which requires for cleavage four protein factors, cleavage and polyadenylation specificity factor, cleavage stimulation factor, cleavage factor I, and cleavage factor II. Using highly purified preparations of these factors, which lacked detectable creatine phosphokinase and ATPase activities, creatine phosphate (CP) was, surprisingly, found to be sufficient to promote efficient cleavage. Although other phosphate compounds substituted poorly or not at all for CP, another phosphoguanidine, arginine phosphate, was fully functional. Notably, ATP was neither necessary nor sufficient, and could in fact inhibit the reaction. Treatment of the purified factors with hexokinase plus glucose (to deplete any contaminating ATP) was without effect, as was addition of EDTA. Using 32P-labeled CP, we found that neither hydrolysis of CP nor phosphate transfer from CP occurred during the cleavage reaction. CP also allowed cleavage of the adenovirus 2 L3 pre-mRNA. However, in this case, ATP both enhanced the reaction and influenced the precise site of cleavage, perhaps reflecting the requirement of poly(A) polymerase for cleavage of this RNA. These results indicate that ATP is not essential for 3' pre-mRNA cleavage and that CP or a related compound can function as a necessary cofactor.
2.0 W CW, diffraction-limited operation of a monolithically integrated master oscillator power amplifier (1993)

The authors fabricated a monolithically integrated master oscillator power amplifier, M-MOPA, with a flared power amplifier region which radiates in a single diffraction limited lobe to an output power in excess of 2 W CW. The radiation pattern is stable with increasing drive current. The spectral output of the M-MOPA is a single longitudinal mode with a side-mode suppression ratio greater than 25 dB.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Network Coded TCP (CTCP) Performance over Satellite Networks (2013)

We show preliminary results for the performance of Network Coded TCP (CTCP) over large latency networks. While CTCP performs very well in networks with relatively short RTT, the slow-start mechanism currently employed does not adequately fill the available bandwidth when the RTT is large. Regardless, we show that CTCP still outperforms current TCP variants (i.e., Cubic TCP and Hybla TCP) for high packet loss rates (e.g., >2.5%). We then explore the possibility of a modified congestion control mechanism based off of H-TCP that opens the congestion window quickly to overcome the challenges of large latency networks. Preliminary results are provided that show the combination of network coding with an appropriate congestion control algorithm can provide gains on the order of 20 times that of existing TCP variants. Finally, we provide a discussion of the future work needed to increase CTCP's performance in these networks.
Deep unsupervised multi-view detection of video game stream highlights (2018)

We consider the problem of automatic highlight-detection in video game streams. Currently, the vast majority of highlight-detection systems for games are triggered by the occurrence of hard-coded game events (e.g., score change, end-game), while most advanced tools and techniques are based on detection of highlights via visual analysis of game footage. We argue that in the context of game streaming, events that may constitute highlights are not only dependent on game footage, but also on social signals that are conveyed by the streamer during the play session (e.g., when interacting with viewers, or when commenting and reacting to the game). In this light, we present a multi-view unsupervised deep learning methodology for novelty-based highlight detection. The method jointly analyses both game footage and social signals such as the players facial expressions and speech, and shows promising results for generating highlights on streams of popular games such as Player Unknown's Battlegrounds.
cDNA microarray analysis of endothelial cells subjected to cyclic mechanical strain: importance of motion control (2005)

Microarrays were utilized to determine gene expression of vascular endothelial cells (ECs) subjected to mechanical stretch for insight into the role of strain in vascular pathophysiology. Over 4,000 genes were screened for expression changes resulting from cyclic strain (10%, 1 Hz) of human umbilical vein ECs for 6 and 24 h. Comparison of t-statistics and adjusted P values identified genes having significantly different expression between strained and static cells but not between strained and motion control. Relative to static, 6 h of cyclic stretch upregulated two genes and downregulated two genes, whereas 24 h of cyclic stretch upregulated eight genes but downregulated no genes. However, incorporating the motion control revealed that fluid agitation over the cells, rather than strain, is the primary regulator of differential expression. Furthermore, no gene exceeded a threefold change when comparing cyclic strain to either static or motion control. Quantitative real-time polymerase chain reaction confirmed the dominance of fluid agitation in gene regulation with the exception of heat shock protein 10 at 24 h and plasminogen activator inhibitor 1 at 6 h. Taken together, the small number of differentially expressed genes and their low fold expression levels indicate that cyclic strain is a weak inducer of gene regulation in ECs. However, many of the differentially expressed genes possess antioxidant properties, suggesting that oxidative mechanisms direct EC adaptation to cyclic stretch.
Sol–gel transition of poly(3-hexylthiophene) revealed by capillary measurements: phase behaviors, gelation kinetics and the formation mechanism (2011)

π-Conjugated organogels of poly(3-hexylthiophene) (P3HT) are prepared via the addition of a marginal solvent, anisole, into solutions of P3HT. We initiate a novel and facile route to determine the gelation threshold of P3HT nanowire dispersions by capillary measurements. The effects of the P3HT concentration (c), anisole volume fraction (φ) and temperature (T) on the phase behaviors are discussed. A thermodynamic c–φ phase diagram is constructed, in which the P3HT dispersion is divided into four regions: solution, sol, sol–gel blend and gel. The concentration and solvent dependent sol–gel transition kinetics shows that the gelation process could be accelerated via increasing c and φ. The gelation temperature gives an exponential relationship with the concentration of P3HT and the anisole volume fraction. Morphological studies reveal the formation process and the topological structure of the P3HT microgel clusters. Based on the above results, a three-stage physical scenario for the sol–gel transition of P3HT dispersions is proposed.
The interaction of antibody/dna immune complexes with complement (1987)

In 28 serum and plasma samples from patients with systemic lupus erythematosus, we examined the importance of antibody class with respect to complement-mediated binding to human red blood cells (RBC) of antibody/DNA immune complexes (IC) prepared with anti-DNA antibodies. We used both 3H-double-stranded DNA and 3H-single-stranded DNA (ssDNA). Generally, double-stranded DNA IC showed considerably higher binding than did ssDNA IC in the RBC binding assay. Further analysis indicated that although ssDNA IC fix complement, it is necessary that these IC contain IgM anti-DNA antibodies in order for them to bind to RBC. The results suggest that the mechanisms of clearance and pathogenic potential of these IC may depend upon both the DNA conformation and antibody class. In particular, complement-fixing IC which contain IgG anti-DNA antibodies and ssDNA may not be cleared via the erythrocyte clearance mechanism, and therefore, could be more likely to deposit in certain tissues and initiate inflammatory reactions.
Activated Protein C Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production by Inhibiting Activation of both Nuclear Factor-κB and Activator Protein-1 in Human Monocytes (2002)

Activated protein C (APC), an important natural anticoagulant, inhibits tumor necrosis factor-alpha (TNF-alpha) production and attenuates various deleterious events induced by lipopolysaccharide (LPS), contributing thereby to a significant reduction of mortality in patients with severe sepsis. In this study, we investigated the mechanism(s) by which APC inhibits TNF-alpha production by LPS-stimulated human monocytes in vitro. Although APC inhibited LPS-induced TNF-alpha production in a concentration-dependent fashion, diisopropyl fluorophosphate-treated APC, an active-site-blocked APC, had no effect. APC inhibited both the binding of nuclear factor-kappa B (NF-kappa B) to target sites and the degradation of I kappa B alpha. APC also inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways. These observations strongly suggest that APC inhibited LPS-induced TNF-alpha production by inhibiting the activation of both NF-kappa B and AP-1 and that the inhibitory activity of APC might depend on its serine protease activity. These results would at least partly explain the mechanism(s) by which APC reduces the tissue injury seen in animal models of sepsis and in patients with sepsis.
Biological Fabrication of Photoluminescent Nanocomb Structures by Metabolic Incorporation of Germanium into the Biosilica of the Diatom Nitzschia frustulum (2008)

Diatoms are single-celled algae that make microscale silica shells or “frustules” with intricate nanoscale features such as two-dimensional pore arrays. In this study, the metabolic insertion of low levels of germanium into the frustule biosilica of the pennate diatom Nitzschia frustulum by a two-stage cultivation process induced the formation of frustules which strongly resembled double-sided nanocomb structures. The final product from the two-stage cultivation process contained 0.41 wt % Ge in biosilica and consisted of an equal mixture of parent frustule valves possessing a normal two-dimensional array of 200 nm pores and daughter valves possessing the nanocomb structure. The nanocomb structures had overall length of 8 μm, rib width of 200 nm, rib length of 500 nm, and slit width of 100 nm. Each slit of the nanocomb was most likely formed by a directed morphology change of a row of 200 nm pores to a single open slit following Ge incorporation into the developing frustule during the final cell division. The frustules possessed blue photoluminescence at peak wavelengths between 450 and 480 nm, which was attributed to contributions from nanostructured biosilica in both the parent valves and in the nanocomb daughter valves. This is the first reported study of using a cell culture system to biologically fabricate a photoluminescent nanocomb structure.
A Study of Apoptosis in Normal and Pathologic Nervous Tissue After In situ End-Labeling of DNA Strand Breaks (1994)

Programmed cell death (PCD) via apoptosis is characterized by nuclear pyknosis and fragmentation, and biochemically by oligonucleosomal cleavage of DNA. Apoptosis occurs in the developing nervous system, whereas its role in neurodegenerative diseases is still debated. Recognition of apoptotic cells has recently been facilitated by in situ end-labeling (ISEL) techniques which identify DNA strand breaks through incorporation of labeled nucleotides. We have applied two ISEL assays to physiological and pathological conditions affecting the nervous system in which PCD is likely to occur. Terminal transferase assay was more sensitive than DNA polymerase assay and allowed the recognition of a larger number of cells than conventional histology. Apoptotic cells were readily found in the developing spinal cord and dorsal root ganglia. Medulloblastomas, gliomas, brain lymphomas and metastases showed abundant apoptotic cells either isolated or grouped in small foci. Labeling was also found in cells without a clearcut apoptotic morphology. Apoptotic cells were not found in Alzheimer's disease, amyotrophic lateral sclerosis and human and mouse prionic encephalopathies. Our results show that ISEL is a useful technique for demonstrating apoptotic cells in nervous tissue during development and in brain tumors. Lack of staining in neurodegenerative diseases suggests that other types of PCD might be involved.
Stretching in the Rehabilitation of Low-Back Pain Patients (1992)

The major objective of this investigation was to study the effectiveness of the physical conditioning program used at the University of Miami Comprehensive Pain and Rehabilitation Center in restoring certain elements of the functional abilities of individuals suffering from chronic low-back pain and to evaluate the effectiveness of using a systematically applied, aggressive stretching maneuver as an add-on therapy in the treatment of chronic low-back pain patients. The effect(s) of the proposed stretching maneuver was evaluated. Twenty-eight chronic low-back pain patients were randomly assigned to one of two groups. The control group underwent a multimodal rehabilitation program, and the experimental group underwent the same rehabilitation program in addition to the systematic stretching maneuver under investigation. The results obtained showed that patients undergoing the multimodal rehabilitation program with and without the proposed systematic stretching maneuver showed a significant improvement in their functional abilities as seen from the significant increase in the static strength of the back extensors, with corresponding significant increase in back muscle myoelectric signals. Also, a significant decrease in their pain level was reported after 2 weeks of continuous treatment. The use of the systematic stretching maneuver enhanced the functional gains of chronic low-back pain patients compared to the control group.
The energy-integral criterion of transient stability limits of power systems (1958)

Methods have been devised, in the study of second-order non-linear differential equations, for identifying the nature of the phase-plane trajectories, without having to find the solutions to the equations. These methods are applied to determine the transient stability limits for a power system with two machines and are shown to be equivalent to establishing the energy integrals of the system. Formulae are derived for the critical switching time taking resistance into account. The methods are then generalized for multi-machine systems both with and without an infinite busbar, and the energy integrals are given. The application of these integrals, in conjunction with step-by-step integration, to find the critical switching time for a fault is described. An example of a three-machine system solved by the conventional and by the new methods is given.
<i>In vitro</i> effect of low concentrations of oltipraz on the antioxidant defence of mouse hepatocytes and <i>Schistosoma mansoni</i> worms (2004)

The direct effects of oltipraz (OPZ) on mouse hepatocytes and Schistosoma mansoni worms are studied in vitro at a concentration range of 5–25 µmol/L following one- and three-hour incubations. Oxidative stress is reflected by increases in malondialdehyde (MDA), representing the end products of lipid peroxidation, and depletion of glutathione (GSH), representing protective thiol groups. Activities of glutathione peroxidase isoenzymes, GST and GR as components of antioxidative defence are also determined. The opposite effects of low concentrations of OPZ on mammalian hepatocytes and S. mansoni worms were confirmed. In incubation with S. mansoni, addition of OPZ resulted in significantly increased production of MDA, together with depletion of GSH, both of which were time- and OPZ concentration-dependent. In incubation with mouse hepatocytes, however, there was little change in MDA concentrations, and a gradual increase in GSH levels, both of which were time- and concentration-dependent. Addition of OPZ to the incubation media also affected the activities of antioxidant enzymes. Although total GPx activity increased in both mammalian hepatocyte and S. mansoni experiments, the opposite was noted with the selenium-dependent isoenzyme. While there was a gradual increase in sGPx in hepatocytes, there was a timeand concentration-dependent inhibition in the worm isoenzyme. Contrasting results were also obtained with GR. While increased activity was obtained with the enzyme from mouse hepatocytes, the worm enzyme was inhibited, especially at the upper end of the OPZ concentration range and also following longer periods of incubation. The increase in GST activity followed the same qualitative pattern in both hepatocytes and schistosomes. Therefore, OPZ given in doses that maintain a serum concentration in the range 5–25 µmol/L induces biochemical changes in mouse hepatocytes that could be utilised for chemo-preventive purposes and prevention of oxidative damage. However, progressive oxidative damage to S. mansoni worms occurred despite some protective biochemical changes.