Miracle-dz/UniFAR-FTUs huggingface dataset:
Potentiation of the P2X3 ATP receptor by PAR‐2 in rat dorsal root ganglia neurons, through protein kinase‐dependent mechanisms, contributes to inflammatory pain

Proinflammatory agents trypsin and mast cell tryptase cleave and activate protease‐activated receptor‐2 (PAR‐2), which is expressed on sensory nerves and causes neurogenic inflammation. P2X3 is a subtype of the ionotropic receptors for adenosine 5′‐triphosphate (ATP), and is mainly localized on nociceptors. Here, we show that a functional interaction of the PAR‐2 and P2X3 in primary sensory neurons could contribute to inflammatory pain. PAR‐2 activation increased the P2X3 currents evoked by α, β, methylene ATP in dorsal root ganglia (DRG) neurons. Application of inhibitors of either protein kinase C (PKC) or protein kinase A (PKA) suppressed this potentiation. Consistent with this, a PKC or PKA activator mimicked the PAR‐2‐mediated potentiation of P2X3 currents. In the in vitro phosphorylation experiments, application of a PAR‐2 agonist failed to establish phosphorylation of the P2X3 either on the serine or the threonine site. In contrast, application of a PAR‐2 agonist induced trafficking of the P2X3 from the cytoplasm to the plasma membrane. These findings indicate that PAR‐2 agonists may potentiate the P2X3, and the mechanism of this potentiation is likely to be a result of translocation, but not phosphorylation. The functional interaction between P2X3 and PAR‐2 was also confirmed by detection of the α, β, methylene‐ATP‐evoked extracellular signal‐regulated kinases (ERK) activation, a marker of neuronal signal transduction in DRG neurons, and pain behavior. These results demonstrate a functional interaction of the protease signal with the ATP signal, and a novel mechanism through which protease released in response to tissue inflammation might trigger the sensation to pain through P2X3 activation.
Transurethral Procedures for Lower Urinary Tract Symptoms Resulting From Benign Prostatic Enlargement: A Quality and Meta-Analysis

Purpose Thanks to advancements in surgical techniques and instruments, many surgical modalities have been developed to replace transurethral resection of the prostate (TURP). However, TURP remains the gold standard for the surgical treatment of benign prostatic hyperplasia (BPH). We conducted a meta-analysis on the efficacy and safety of minimally invasive surgical therapies for BPH compared with TURP. Methods This meta-analysis used a Medline search assessing the period from 1997 to 2011. A total of 784 randomized controlled trials were identified in an electronic search. Among the 784 articles, 36 randomized controlled trials that provided the highest level of evidence (level 1b) were included in the meta-analysis. We also conducted a quality analysis of selected articles. Results Only 2 articles (5.56%) were assessed as having a low risk of bias by use of the Cochrane collaboration risk of bias tool. On the other hand, by use of the Jadad scale, there were 26 high-quality articles (72.22%). Furthermore, 28 articles (77.78%) were assessed as high-quality articles by use of the van Tulder scale. Holmium laser enucleation of the prostate (HoLEP) showed the highest reduction of the International Prostate Symptom Score compared with TURP (P<0.0001). Bipolar TURP, bipolar transurethral vaporization of the prostate, HoLEP, and open prostatectomy showed superior outcome in postvoid residual urine volume and maximum flow rate. The intraoperative complications of the minimally invasive surgeries had no statistically significant inferior outcomes compared with TURP. Also, there were no statistically significant differences in any of the modalities compared with TURP. Conclusions The selection of an appropriate surgical modality for BPH should be assessed by fully understanding each patient's clinical conditions.
Capacity forecast model for control and dummy wafers

Tool capacity planning is a frequent task in semiconductor wafer fabrication plants. Various control and dummy wafers (C/D wafers) used to enhance product quality and process stability become increasingly important to fab performance. The capacity required to fabricate complex C/D wafers must be taken into consideration in the tool investment plan. Inaccurate capacity forecast of C/D wafers results in tool investment surplus or shortage. This paper describes a successful methodology to establish capacity forecast model for C/D wafers. The proposed model presents the solution to be explored effectively and has demonstrated a capability superior to the current planning method in wafer fabrication plants
A frequency doubling two-path phased-array FMCW radar transceiver in 65nm CMOS

This paper presented a frequency doubling two-path phased-array FMCW radar transceiver in 65nm CMOS process. The FMCW signal is generated by a fractional-N PLL. The frequency doubling scheme can lower down the frequency of the PLL, reduce the required phase shifting range of phase shifter and the design complexity of the LO distributed network. The FMCW chirp bandwidth is 1.93 GHz from 76.92 to 78.85 GHz, while the root-mean-square frequency error is 674 kHz. The transmitting power is 12.9~13.2 dBm. The receive conversion gain is programmable from 47.8 dB to 100.7 dB. The two-path receiver noise figure is 10 dB and 6.6 dB at 400 kHz and 3.3 MHz IF frequencies, respectively. The transceiver consumes 343 mW power.
Induced Deletion of the N-Cadherin Gene in the Heart Leads to Dissolution of the Intercalated Disc Structure

The structural integrity of the heart is maintained by the end-to-end connection between the myocytes called the intercalated disc. The intercalated disc contains different junctional complexes that enable the myocardium to function as a syncytium. One of the junctional complexes, the zonula adherens or adherens junction, consists of the cell adhesion molecule, N-cadherin, which mediates strong homophilic cell–cell adhesion via linkage to the actin cytoskeleton. To determine the function of N-cadherin in the working myocardium, we generated a conditional knockout containing loxP sites flanking exon 1 of the N-cadherin (Cdh2) gene. Using a cardiac-specific tamoxifen-inducible Cre transgene, N-cadherin was deleted in the adult myocardium. Loss of N-cadherin resulted in disassembly of the intercalated disc structure, including adherens junctions and desmosomes. The mutant mice exhibited modest dilated cardiomyopathy and impaired cardiac function, with most animals dying within two months after tamoxifen administration. Decreased sarcomere length and increased Z-line thickness were observed in the mutant hearts consistent with loss of muscle tension because N-cadherin was no longer available to anchor myofibrils at the plasma membrane. Ambulatory electrocardiogram monitoring captured the abrupt onset of spontaneous ventricular tachycardia, confirming that the deaths were arrhythmic in nature. A significant decrease in the gap junction protein, connexin 43, was observed in the N-cadherin–depleted hearts. This animal model provides the first demonstration of the hierarchical relationship of the structural components of the intercalated disc in the working myocardium, thus establishing N-cadherin’s paramount importance in maintaining the structural integrity of the heart.
2 ( Not ) Executing a measurement tool

Conducting sound measurement studies of the global Internet is inherently difficult. The collected data significantly depends on vantage point(s), sampling strategies, security policies, or measurement populations – and conclusions drawn from the data can be sensitive to these biases. Crowdsourcing is a promising approach to address these challenges, although the epistemological implications have not yet received substantial attention by the research community. We share our findings from leveraging Amazon’s Mechanical Turk (MTurk) system for three distinct network measurement tasks. We describe our failure to outsource to MTurk an execution of a security measurement tool, our subsequent successful integration of a simple yet meaningful measurement within a HIT, and finally the successful use of MTurk to quickly provide focused small sample sets that could not be obtained easily via alternate means. Finally, we discuss the implications of our experiences for other crowdsourced measurement research. CCS Concepts •Networks → Network measurement;
Coordinate synthesis and turnover of heat shock proteins in Borrelia burgdorferi: degradation of DnaK during recovery from heat shock

The synthesis and turnover of heat shock proteins (Hsps) by Borrelia burgdorferi, the Lyme disease spirochete, was investigated by radiolabeling of whole spirochetes and spheroplasts, comparison of one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and use of immunochemistry. The approximately 72-kDa DnaK homolog and three additional Hsps of 39, 27, and 21 kDa increased in amount by 3- to 15-fold between 2 and 6 h following temperature upshift from 28 to 39 degrees C. Temperature downshift experiments following the transfer of spirochetes from 40 to 28 degrees C showed that within 15 to 30 min, synthesis of most of the major Hsps returned to levels seen in spirochetes statically maintained at the lower temperature. Spheroplasts of B. burgdorferi produced by treatment with EDTA and lysozyme were radiolabeled, and specific Hsps were localized to either the cytoplasm or membrane fraction. Further analysis by two-dimensional electrophoresis demonstrated three constitutively expressed DnaK isoforms with pIs near 5.5. A pattern suggestive of DnaK degradation was observed following recovery from heat shock but not in spirochetes maintained entirely at a low temperature. Some of these putative degradation products were recognized by monoclonal antibodies directed against the B. burgdorferi DnaK protein. These data suggest that following a period of peak synthesis, DnaK is actively degraded as the spirochete reestablishes its metabolic thermometer. These findings provide a new interpretation of previous work suggesting that 10 to 15 B. burgdorferi polypeptides, including DnaK have a common epitope.
HIV seroconversion in Swedish haemophiliacs: Relation to type and dosage of factor concentrate

Human immunodeficiency virus (HIV) seroconversion among 40 Swedish haemophilia A patients has been investigated by retrospective sera testing. 22/40 patients had developed HIV antibodies before 1983, i.e., when heat‐treatment of American factor concentrates was introduced. All patients had received American and Swedish factor concentrates, thus no case of seroconversion was seen among patients treated exclusively with non‐heat‐treated Swedish concentrates. Of 79 patients with severe or moderate haemophilia, all of whom had received both American and Swedish concentrates, the 36 seropositives were compared with the 43 seronegatives. The total number of units received did not differ between the two groups, though the seropositive group had received significantly more American concentrate. Two batches of concentrate were proved to have been infected. 29 seropositive and 13 seronegative patients had been treated with at least one of these batches. As expected, and unlike most of the seronegative patients, patients in the seropositive group generally had abnormal lymphocyte subsets.
A fluorescence-based one-step assay for serum non-transferrin-bound iron.

We introduce a method for monitoring non-transferrin-bound iron (NTBI), a labile and potentially toxic form of serum iron associated with imbalanced iron metabolism. The assay employs fluorescein-labeled apotransferrin (Fl-aTf), which undergoes fluorescence quenching upon binding iron. It has the advantages of simplicity, high sensitivity, and detection of those forms of NTBI that persist in sera with low transferrin saturations. Since NTBI is not readily available for detection, it is mobilized by 10 mM oxalate. Endogenous serum apotransferrin, capable of binding oxalate-mobilized NTBI, is blocked by 0.1 mM gallium(III). This metal, like iron, binds to Fl-aTf, but it neither quenches its fluorescence nor interferes with quenching by iron. Serum and reagent containing oxalate, Ga(Cl)(3), and Fl-aTf are mixed in multiwell plates and fluorescence is determined after 1 h in a microplate reader. To compensate for artifactual fluorescence changes caused by serum color, parallel samples are prepared with excess unlabeled apotransferrin, which scavenges all iron in the sample. Sera from eight hemochromatosis patients were tested for NTBI by the present assay and by an established alternative method, with qualitatively similar results. A potential application of the test is for screening large numbers of samples from patients at risk of developing NTBI.
Ball Milling Pretreatment of Bagasse for Ethanol Production by Enzymatic Saccharification and Fermentation

Enzymatic saccharification (Hydrolysis) is one of the technologies to hydrolyze lignocellulosic biomass. In this study, Bangladeshi bagasse is used as feedstock for enzymatic saccharification and ethanol fermentation. Cutter mill and Mechano-chemical treatment (Ball mill) are used for pretreatment. The main objective of this study is to investigate the effect of substrate concentration, pretreatment time and enzyme concentration to enzymatic hydrolysis and ethanol fermentation. The yield of glucose from cellulose is decreased with increasing substrate concentration from 5% to 15%, but the total amount of glucose is increased with increasing substrate concentration. Sample with long pretreatment time hydrolysis easily. Ball milling pretreatment of 1 hour is the most effective on enzymatic hydrolysis which gives better sugar yield than others. Enzyme loading has significant effect on enzymatic hydrolysis. Yeast Saccharomyces cerevisiae was used to converts C6 sugar into ethanol and incubated at 30C for 96 hours. Almost all fermentable sugar converted into ethanol within 24 hours.
Crystal Structure of PriB, a Primosomal DNA Replication Protein of Escherichia coli*

PriB is one of the Escherichia coli φX-type primosome proteins that are required for assembly of the primosome, a mobile multi-enzyme complex responsible for the initiation of DNA replication. Here we report the crystal structure of the E. coli PriB at 2.1 Å resolution by multi-wavelength anomalous diffraction using a mercury derivative. The polypeptide chain of PriB is structurally similar to that of single-stranded DNA-binding protein (SSB). However, the biological unit of PriB is a dimer, not a homotetramer like SSB. Electrophoretic mobility shift assays demonstrated that PriB binds single-stranded DNA and single-stranded RNA with comparable affinity. We also show that PriB binds single-stranded DNA with certain base preferences. Based on the PriB structural information and biochemical studies, we propose that the potential tetramer formation surface and several other regions of PriB may participate in protein-protein interaction during DNA replication. These findings may illuminate the role of PriB in φX-type primosome assembly.
Draft Genome Sequence of Bacillus farraginis R-6540T (DSM 16013), a Spore-Forming Bacterium Isolated at Dairy Farms

ABSTRACT Bacillus farraginis R-6540T is a Gram-positive, aerobic, and spore-forming bacterium with very high intrinsic heat resistance. Here, we report the 5.32-Mb draft genome sequence of B. farraginis R-6540T, which is the first genome sequence of this species and will promote its fundamental research.
Conformation spaces of proteins

We report a simple method for measuring the accessible conformational space explored by an ensemble of protein structures. The method is useful for diverse ensembles derived from molecular dynamics trajectories, molecular modeling, and molecular structure determinations. It can be used to examine a wide range of time scales. The central tactic we use, which has been previously employed, is to replace the true mechanical degrees of freedom of a molecular system with the conformationally effective degrees of freedom as measured by the root‐mean squared cartesian distances among all pairs of conformations. Each protein conformation is treated as a point in a high dimensional euclidean space. In this article, we model this space in a novel way by representing it as an N‐dimensional hypercube, describable with only two parameters: the number of dimensions and the edge length. To validate this approach, we provide a number of elementary test cases and then use the N‐cube method for measuring the size and shape of conformational space covered by molecular dynamics trajectories spanning 10 orders of magnitude in time. These calculations were performed on a small protein, the villin headpiece subdomain, exploring both the native state and the misfolded/folding regime. Distinct features include single, vibrationally averaged, substate minima on the 0.1–1‐ps time scale, thermally averaged conformational states that persist for 1–100 ps and transitions between these local minima on nanosecond time scales. Large‐scale refolding modes appear to become uncorrelated on the microsecond time scale. Associated length scales for these events are 0.2 Å for the vibrational minima; 0.5 Å for the conformational minima; and 1–2 Å for the nanosecond events. We find that the conformational space that is dynamically accessible during folding of villin has enough volume for ∼109 minima of the variety that persist for picoseconds. Molecular dynamics trajectories of the native protein and experimentally derived solution ensembles suggest the native state to be composed of ∼102 of these thermally accessible minima. Thus, based on random exploration of accessible folding space alone, protein folding for a small protein is predicted to be a milliseconds time scale event. This time can be compared with the experimental folding time for villin of 10–100 μs. One possible explanation for the 10–100‐fold discrepancy is that the slope of the “folding funnel” increases the rate 1–2 orders of magnitude above random exploration of substates. Proteins 2001;42:495–511. © 2001 Wiley‐Liss, Inc.
Knowledge Reuse for Innovation

This study was conducted to better understand the knowledge reuse process when radical innovation (e.g., experiments to prepare for human exploration of Mars) is expected. The research involved detailing the knowledge reuse process in six case studies varying in degree of innovation. Across the six cases, a six-stage reuse-for-innovation process was identified consisting of three major actions: reconceptualize the problem and approach, including deciding to search for others' ideas to reuse; search-and-evaluate others' ideas to reuse; and develop the selected idea. Findings include (1) the need for an insurmountable gap in performance to stimulate the decision to reuse others' knowledge; (2) the critical importance of an adapter to bridge the idea source and recipient; (3) three layers of search-and-evaluate activities in which the first layer of scanning to find ideas to reuse and the last layer of detailed analysis of ideas are bridged by a layer of brief evaluations of ideas assessing the presence (or absence) of targeted information about each idea; and (4) the differential use of metaknowledge about each idea to facilitate proceeding through each search-and-evaluate layer. In addition, reusers in the more (versus less) innovative cases redefined problems at the outset in nontraditional ways using analogies and extensions, rather than accepting the preexisting problem definition; used a substantially broader search strategy with a greater variety of search methods; and worked more closely with adapters during the latter stages of the reuse process.
Protective effects of a free radical scavenger, MCI‐186, on high‐glucose–induced dysfunction of human dermal microvascular endothelial cells

Functional damage to microvascular endothelial cells by hyperglycemia is thought to be one of the critical risk factors in the impaired wound healing seen with diabetes mellitus. It is also thought that free radical stress plays a significant role in this endothelial cell dysfunction. In the present study, the effect of a free radical scavenger, MCI 186, on the endothelial cell dysfunction of cultured cells induced by high‐glucose conditions was studied. Human dermal microvascular endothelial cells were cultured with high‐glucose medium (50 mM) with or without MCI‐18 6 (10 μM) for 7 days. Fifty mM mannitol was used as an osmotic control in this study. After this treatment, cell proliferation, activation of mitogen‐activated protein kinase (MAPK), the level of apoptosis, and caspase‐3 activation induced by removal of growth factors or tumor necrosis factor‐α treatment were studied. High‐glucose conditions significantly decreased cell proliferation and increased apoptosis levels with the activation of caspase‐3 induced by growth factor removal. The high‐glucose condition significantly activated MAPK. MCI‐186 treatment improved cellular proliferation and reduced apoptosis and caspase‐3 activation induced by high‐glucose conditions. MCI‐186 also inhibited the activation of MAPK. On the other hand, MCI‐186 did not alter the level of apoptosis and caspase‐3 activation induced by TNF‐α treatment. In conclusion, we suggest that MCI‐186 may be beneficial for improving the endothelial cell dysfunction induced by hyperglycemia.
Human skeletal muscle cell differentiation is associated with changes in myogenic markers and enhanced insulin-mediated MAPK and PKB phosphorylation.

AIM We hypothesized that myogenic differentiation of HSMC would yield a more insulin responsive phenotype. METHODS We assessed expression of several proteins involved in insulin action or myogenesis during differentiation of primary human skeletal muscle cultures (HSMC). RESULTS Differentiation increased creatine kinase activity and expression of desmin and myocyte enhancer factor (MEF)2C. No change in expression was observed for big mitogen-activated protein kinase (BMK1/ERK5), MEF2A, insulin receptor (IR), hexokinase II, and IR substrates 1 and 2, while expression of glycogen synthase, extracellular signal-regulated kinase 1 and 2 (ERK1/2 MAP kinase) and the insulin responsive aminopeptidase increased after differentiation. In contrast to protein kinase B (PKB)a, expression of (PKB)b increased, with differentiation. Both basal and insulin-stimulated PI 3-kinase activity increased with differentiation. Insulin-mediated phosphorylation of PKB and ERK1/2 MAP kinase increased after differentiation. CONCLUSION Components of the insulin-signalling machinery are expressed in myoblast and myotube HSMC; however, insulin responsiveness to PKB and ERK MAP kinase phosphorylation increases with differentiation.
An Evaluation of Affect and Binge Eating

The affect regulation model of binge eating suggests that binge eating occurs because it provides momentary relief from negative affect. The purpose of this study was to evaluate change in affect during binge eating to evaluate the merits of this model. Participants were young adult women from a midwestern university. Binge eaters recorded their level of pleasantness using the affect grid at 2-minute intervals before, during, and after binge eating episodes and regular meals. Controls recorded in a similar manner during meals. The results showed a different pattern of affect for binge eaters during binge eating episodes and normal meals and for binge eaters and controls at normal meals. The results support the affect regulation model of binge eating and suggest that binge eating is negatively reinforced because it produces momentary relief from negative affect.