Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific detection of Stachybotrys chartarum in pure culture using quantitative polymerase chain reaction.

Research was conducted with laboratory cultures to establish a protocol for the rapid detection and quantitation of the toxigenic fungus Stachybotrys chartarum by means of polymerase chain reaction (PCR). Sequences for the 18 S rRNA gene of S. chartarum were obtained from GenBank and compared against all other available sequences on-line with the Basic Local Alignment Search Tool (BLAST). Two sets of TaqMan primers and one fluorescently labelled probe were designed and tested for selectivity, specificity and sensitivity of detection. A fluorogenic nuclease assay in conjunction with a sequence detector were used for the amplification and quantitation of S. chartarum. The primers designed amplified all S. chartarum isolates tested and did not amplify DNA extracted from other Stachybotrys species or 15 other fungal genera. The primer set selected had a sensitivity of <23 template copies. Many S. chartarum samples were initially negative after PCR amplification. Incorporation of an internal positive control in the PCR reaction demonstrated the presence of inhibitors in these samples. PCR inhibitors were removed by dilution or further purification of the DNA samples. The results of this research report on a quantitative PCR (QPCR) method for detection and quantitation of S. chartarum and demonstrate the presence of PCR inhibitors in some S. chartarum isolates.
A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder.

OBJECTIVE SLI381 (Adderall XR) is a 2-component extended-release capsule formulation of Adderall designed to produce a therapeutic effect that lasts throughout the day with 1 morning dose. The primary objective of this study was to assess the efficacy and safety of SLI381 compared with placebo in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a naturalistic school and home setting. A secondary objective was to assess the diurnal variation in responses based on morning and afternoon assessments. METHODS A multicenter, randomized, double-blind, parallel-group, placebo-controlled trial was conducted at 47 sites. After a 1-week washout of any previous stimulant medication, patients were randomized to receive single-daily morning doses of placebo or SLI381 10 mg, 20 mg, or 30 mg for 3 weeks. Participants aged 6 to 12 years inclusive who satisfied Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria diagnosis of ADHD were included. The primary efficacy parameter was the Conners Global Index Scale for Teachers. Secondary efficacy parameters included the Conners Global Index Scale for Parents, the Clinical Global Impressions Scale for improvement, and the Parent Global Assessment for improvement. Safety was assessed by recording adverse events, laboratory tests, and vital signs at each visit during the study. Physical examinations and electrocardiograms were performed at the screening and the end of the study. RESULTS Five hundred eighty-four children were randomized, 563 were included in the intent-to-treat population, and 509 completed the entire study. Intention-to-treat analysis of Conners Global Index Scale for Teachers and Conners Global Index Scale for Parents scores revealed significant improvement in morning, afternoon, and late afternoon behavior for all active treatment groups versus placebo. All active treatment groups showed significant dose-related improvement in behavior from baseline. Both the Clinical Global Impressions Scale for improvement and Parent Global Assessment for improvement showed all doses of SLI381 to be superior to placebo at treatment end and both confirmed the dose-response relationship between improvement and the SLI381 dose. The incidence of spontaneously reported adverse events was low and similar for active treatments and placebo. CONCLUSIONS SLI381 produced consistent, dose-related improvements on all measures of efficacy. The extended-release nature of the SLI381 formulation was shown by continued, significant improvement in afternoon assessments by teachers and afternoon and late afternoon assessments by parents. The time course and therapeutic effects of SLI381 suggests that this medication is an efficacious once-daily treatment for children with ADHD.
A low-power scan-path architecture

In this paper, we propose a scan cell architecture that decreases power consumption and the total consumed energy. In the method, which is based on data compression, the test vector (TV) set is divided into two repeated and unrepeated partitions. The repeated part, which is common among some of the TVs, is not changed during the new scan path where the new TV will be filled. Therefore, every time that a new TV is applied to the circuit, only the cells of the scan-path which are not repeated are altered and other cells retain their values. As a result, the TV is applied to the CUT in a fewer number of clock cycles. In addition, the values of some scan cells remain unchanged leading to a lower switching activity in the scan-path during test mode. Besides, by latching the inputs of the CUT, the proposed scan chain architecture avoids transitioning of TVs into the circuit inputs at the time of shifting. This also saves system power during the test mode. Our architecture has been applied to ISCAS89 circuits. Simulation results reveal up to 66% reduction in the test power consumption when compared to the conventional scan-path architecture.
Mutation in the AChR ion channel gate underlies a fast channel congenital myasthenic syndrome

Background: Most congenital myasthenic syndromes (CMS) have postsynaptic defects from mutations within the muscle acetylcholine receptor (AChR). Mutations underlying the slow channel syndrome cause a “gain of function” and usually show dominant inheritance, whereas mutations underlying AChR deficiency or the fast channel syndrome cause a “loss of function” and show recessive inheritance. Objective: To characterize the disease mechanism underlying an apparently dominantly inherited CMS that responds to IV edrophonium. Methods: DNA from CMS patients was analyzed for mutations by single-strand conformation polymorphism analysis, DNA sequence analysis, and restriction endonuclease digestion. Functional analysis of mutations was by α-bungarotoxin binding studies and by patch clamp analysis of mutant AChR expressed in human embryonic kidney cells. Results: Analysis of muscle biopsies from father and son in an affected kinship showed normal endplate morphology and AChR number but severely reduced miniature endplate potentials. DNA analysis revealed that each harbors a single missense mutation in the AChR α-subunit gene, αF256L. Expression studies demonstrate this mutation underlies a fast channel phenotype with fewer and shorter ion channel activations. The major effect of αF256L, located within the M2 transmembrane domain, is on channel gating, both reducing the opening and increasing the closure rate. Conclusions: Mutation αF256L results in fast channel kinetics. Expression studies suggest a dominant-negative effect within the AChR pentamer, severely compromising receptor function.
Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes

G protein-coupled receptor (GPCR) kinases (GRKs) are critical regulators of cellular signaling and function. In cardiomyocytes, GRK2 and GRK5 are two GRKs important for myocardial regulation, and both have been shown to be up-regulated in the dysfunctional heart. We report that increased levels and activity of GRK5 in failing myocardium may have unique significance due to its nuclear localization, a property not shared by GRK2. We find that transgenic mice with elevated cardiac GRK5 levels have exaggerated hypertrophy and early heart failure compared with control mice after pressure overload. This pathology is not present in cardiac GRK2-overexpressing mice or in mice with overexpression of a mutant GRK5 that is excluded from the nucleus. Nuclear accumulation of GRK5 is enhanced in myocytes after aortic banding in vivo and in vitro in myocytes after increased Gαq activity, the trigger for pressure-overload hypertrophy. GRK5 enhances activation of MEF2 in concert with Gq signals, demonstrating that nuclear localized GRK5 regulates gene transcription via a pathway critically linked to myocardial hypertrophy. Mechanistically, we show that this is due to GRK5 acting, in a non-GPCR manner, as a class II histone deacetylase (HDAC) kinase because it can associate with and phosphorylate the myocyte enhancer factor-2 repressor, HDAC5. Moreover, significant HDAC activity can be found with GRK5 in the heart. Our data show that GRK5 is a nuclear HDAC kinase that plays a key role in maladaptive cardiac hypertrophy apparently independent of any action directly on GPCRs.
Characterization of cis‐acting prgQ mutants: evidence for two distinct repression mechanisms by Qa RNA and PrgX protein in pheromone‐inducible enterococcal plasmid pCF10

The pCF10‐encoded negative regulators PrgX and Qa (prgQ antisense) RNA inhibit pCF10 transfer by blocking prgQ transcription extension past a potential transcription terminator sequence IRS1. To identify potential target sites for negative regulation, we isolated and analysed 13 cis‐acting mutations in the prgXQ region. Determination of the 3′ end of Qa RNA showed that eight mutations mapped in the region encoding Qa RNA. Four mutations were in the Qa promoter region and one was in IRS1. Three mutations in Qa greatly reduced the intracellular level of this RNA but did not affect that of PrgX. However, both Qa RNA and PrgX protein were reduced in three Qa promoter region mutants and the expression of prgQ transcripts extending 3′ from IRS1 became constitutive. Qa RNA could mediate its negative regulatory activity in the absence of PrgX, and this activity was not abolished by cCF10, the peptide pheromone that induces pCF10 transfer. RNA analysis showed that Qa RNA abolished transcription readthrough. Based on the experimental data as well as computer analysis of predicted secondary structures of prgQ mRNA in the presence or absence of Qa, we concluded that Qa RNA is a pheromone‐insensitive effector of prgQ mRNA termination or degradation at IRS1. In cells lacking a Qa target sequence, expression of PrgX repressed transcription from the prgQ promoter, and this repression was relieved by addition of exogenous cCF10. Thus, even though the synthesis of these negative regulators is coupled, they each act independently on separate targets to regulate expression of conjugation functions.
Tinnitus: the dark side of the auditory cortex plasticity

Music has increasingly been used as a tool for investigation of human cognition and its underlying brain mechanisms. However, music can be used also for neurorehabilitation. Chronic tinnitus is a symptom with high prevalence, especially in industrialized countries. There is evidence that the tinnitus perception is related to unfavorable cortical plastic changes. Maladaptive auditory cortex reorganization may contribute to the generation and maintenance of tinnitus. Because cortical organization can be modified by behavioral training, potentially via reversing maladaptive auditory cortex reorganization, we attempted to reduce tinnitus loudness by exposing chronic tinnitus patients to self‐chosen, enjoyable music that was modified (“notched”) to contain no energy in the frequency range surrounding the individual tinnitus frequency and thus attracting lateral inhibition to the brain area generating tinnitus. On this basis, we have developed and evaluated a customized music training strategy that appears capable of both reducing cortical tinnitus‐related neuronal activity and alleviating subjective tinnitus perception.
Continuous infusion carboplatin on a 21-day schedule: a phase I and pharmacokinetic study.

A phase I study with continuous infusion carboplatin for 21 days every 6 weeks using a venous access port and portable pump was performed over a dose range of 12 to 32 mg/m2/d, with increments of 2 mg/m2/d. Forty-four patients received 107 courses (median, two; range, one to nine). World Health Organization (WHO) grade III/IV leukopenia and thrombocytopenia occurred in one of seven patients at 30 mg/m2/d, and in two of six and four of six patients at 32 mg/m2/d. Cumulative platelet depression was found at dose levels of 28 mg/m2/d or more. Median glomerular filtration rate (GFR) and effective renal plasma flow, monitored by radioisotope clearances at doses greater than or equal to 20 mg/m2/d, decreased 8.2% (P less than .05) and 10.9% (P less than .01) after two courses. There was a relationship (r = .50, P less than .0002) between the percentage of platelet depression and GFR. No other toxicity was observed. Of the 17 patients who were evaluable, one complete response and four partial responses were observed. In addition, six patients had stable disease. Pharmacokinetic analysis of total and ultrafiltrable platinum (UFPt) was performed by atomic absorption spectrophotometry. Steady-state plasma levels for UFPt were reached after 8 hours. These levels could be detected from the 20 mg/m2/d dose. During steady state, carboplatin dose and UFPt plasma levels were not correlated, but steady-state UFPt and GFR (r = -.27, P less than .05) were. Twenty-four percent of total platinum (Pt) was present as UFPt during steady state (x = 160 +/- 10 micrograms/L). Total body clearance of UFPt exceeded GFR 2.2 times. Mean area under the curve (AUC) for UFPt during continuous infusion was 4,921.8 +/- 301.72 mg.min/L. For total Pt, steady-state plasma levels were not reached; total Pt plasma levels increased between day 7 and day 21 (P less than .0001). There was a significant relation between total Pt serum levels day 7, 14, and 21 and the drug dose administered. Immunohistochemical analysis of DNA-bound Pt in leukocytes showed a linear increase from day 7 to day 14 to day 21 (r = .97) between DNA-bound Pt and duration of infusion in individual patients. The maximum-tolerable dose of carboplatin is 30 mg/m2/d for 21 days (total dose 630 mg/m2) and is recommended for phase II studies.
Dynamic Contour Tonometry in Keratoconus and Postkeratoplasty Eyes

Purpose: To compare the performance of dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in measuring intraocular pressure in eyes with irregular corneas. Methods: GAT and DCT measures were taken in 30 keratoconus and 29 postkeratoplasty eyes of 35 patients after pachymetry and corneal topography. Regression and correlation analyses were performed between both tonometry methods and between tonometry methods and corneal parameters. Bland-Altman plots were constructed. Results: DCT values were significantly higher than GAT values in both study groups: +4.1 ± 2.3 mm Hg (mean ± SD) in keratoconus and +3.1 ± 2.5 mm Hg after keratoplasty. In contrast to DCT, GAT values were significantly higher in postkeratoplasty eyes than in keratoconus. The correlation between the 2 tonometry methods was moderate in keratoconus (Kendall correlation coefficient, τ = 0.34) as well in postkeratoplasty eyes (τ = 0.66). The ±1.96 SD span of the DCT-GAT differences showed a considerable range: −0.42 to +8.70 mm Hg in keratoconus and −1.87 to +7.98 mm Hg in postkeratoplasty eyes. In the keratoconus group, neither DCT nor GAT correlated significantly with any of the corneal parameters. In the postkeratoplasty group, both DCT and GAT measures showed a moderate positive correlation with corneal steepness, but only DCT had a significant negative correlation with the central corneal thickness (τ = −0.33). Conclusions: DCT measured significantly higher intraocular pressures than GAT in keratoconus and postkeratoplasty eyes. DCT and GAT measures varied considerably, and DCT was not less dependent on biomechanical properties of irregular corneas than GAT.
Effectiveness of a community health worker cardiovascular risk reduction program in public health and health care settings.

OBJECTIVES We evaluated whether a program to prevent coronary heart disease (CHD) with community health workers (CHWs) would improve CHD risk in public health and health care settings. METHODS The CHWs provided point-of-service screening, education, and care coordination to residents in 34 primarily rural Colorado counties. The CHWs utilized motivational interviewing and navigated those at risk for CHD into medical care and lifestyle resources. A software application generated a real-time 10-year Framingham Risk Score (FRS) and guideline-based health recommendations while supporting longitudinal caseload tracking. We used multiple linear regression analysis to determine factors associated with changes in FRS. RESULTS From 2010 to 2011, among 4743 participants at risk for CHD, 53.5% received medical or lifestyle referrals and 698 were retested 3 or more months after screening. We observed statistically significant improvements in diet, weight, blood pressure, lipids, and FRS with the greatest effects among those with uncontrolled risk factors. Successful phone interaction by the CHW led to lower FRS at retests (P = .04). CONCLUSIONS A CHW-based program within public health and health care settings improved CHD risk. Further exploration of factors related to improved outcomes is needed.
Acute effects of static and dynamic stretching on leg flexor and extensor isokinetic strength in elite women athletes

The aim of this study was to explore the effects of static and dynamic stretching of the leg flexors and extensors on concentric and eccentric peak torque (PT) and electromyography (EMG) amplitude of the leg extensors and flexors in women athletes. Ten elite women athletes completed the following intervention protocol in a randomized order on separate days: (a) non‐stretching (control), (b) static stretching, and (c) dynamic stretching. Stretched muscles were the quadriceps and hamstring muscles. Before and after the stretching or control intervention, concentric and eccentric isokinetic PT and EMG activity of the leg extensors and flexors were measured at 60 and 180°/s. Concentric and eccentric quadriceps and hamstring muscle strength at both test speeds displayed a significant decrease following static stretching (P<0.01–0.001). In contrast, a significant increase was observed after dynamic stretching for these strength parameters (P<0.05–0.001). Parallel to this, normalized EMG amplitude parameters exhibited significant decreases following static (P<0.05–0.001) and significant increases following dynamic stretching (P<0.05–0.001) during quadriceps and hamstring muscle actions at both concentric and eccentric testing modes. Our findings suggest that dynamic stretching, as opposed to static or no stretching, may be an effective technique for enhancing muscle performance during the pre‐competition warm‐up routine in elite women athletes.
PlayTheCityRE: A visual storytelling system that transforms recorded film memories into visual history

Within social media we find many stories that tell us the world that is around us. Unfortunately, we tend to forget what happened in the past and the young generations are losing a cultural heritage passed down for generations. In the attempt of preserving memories and of intercepting the attention of the new generations, in this paper we propose PlayTheCityRE, a location-based storytelling system that merges private film memories shot from 1940 to 1989 (e.g., 8mm, super8mm) with modern communication technologies to tell the story of our past while walking in city streets. The system is provided with a mobile application that allows people to explore an unusual city through the eyes of amateur film sequences (now historic) and to select different routes that will bring them in the same city places where they were filmed. By merging film memories with modern technologies, our system engages different audiences in specific ways and on multiple levels, allowing them to walk through history. Therefore, our storytelling system may help fostering historical consciousness within our society.
p53 sumoylation: Mechanistic insights from reconstitution studies

Sumoylation represents a cascade of enzymatic reactions mediated by SUMO-activating enzyme (SAE1/SAE2 heterodimer), SUMO-conjugating enzyme Ubc9, and SUMO E3 ligases that include five protein inhibitors of activated STATs (PIAS1, PIAS3, PIASy, PIASxa, and PIASxb), and culminates in the formation of an isopeptide bond between the C-terminal glycine of a small ubiquitin-related modifier (SUMO) and the lysine residue of a protein substrate. Conjugation of a SUMO moiety, ranging from 92 (for SUMO-2) to 97 (for SUMO-1) amino acids, not only increases the molecular size but also alters the property and function of the modified protein. Although sumoylation has been observed with many cellular proteins and the majority of transcription factors including the p53 tumor suppressor, this covalent modification is normally detectable only in a small population, often less than 5%, of a given substrate in vivo. This low abundance of SUMO-modified proteins, due to the presence of sentrin/SUMO-specific proteases (SENPs) that actively cleave the reversible SUMO linkage, has posed a challenge to define the biological effect of SUMO in living cells. Nevertheless, the recent development of reconstituted modification and chromatin-dependent transcription assays has provided unique insights into the molecular action of SUMO in modifying protein function. The availability of these reconstitution systems has unraveled the interplay between sumoylation and acetylation in regulating the DNA binding and transcriptional activity of p53 tetramers and further allow the identification of transcriptional corepressors, such as mSin3A, CoREST1/LSD1 and Mi-2/NuRD, implicated in SUMO-dependent gene silencing events.
The effect of sucralose on flavor sweetness in electronic cigarettes varies between delivery devices

The appeal of sweet electronic cigarette flavors makes it important to identify the chemical compounds that contribute to their sweetness. While volatile chemicals that produce sweet aromas have been identified in e-liquids, there are no published reports of sugars or artificial sweeteners in commercial e-liquids. However, the sweetener sucralose is marketed as an e-liquid additive to commercial flavors. The primary aims of the study were to determine if sucralose is delivered in sufficient concentration in the inhaled aerosol to enhance flavor sweetness, and whether the amount delivered depends on the e-liquid delivery system. Thirty-two adult smokers rated flavor intensity, sweetness, harshness and liking/disliking for 4 commercial flavors with and without sucralose (1%) using 2 e-cigarette delivery systems (cartridge and tank). Participants alternately vaped normally or with the nose pinched closed to block perception of volatile flavor components via olfaction. LC/MS was used to measure the concentration of sucralose in the e-liquid aerosols using a device that mimicked vaping. Sweetness and flavor intensity were perceived much more strongly when olfaction was permitted. The contribution of sucralose to sweetness was significant only for the cartridge system, and the chemical analysis showed that the concentration of sucralose in the aerosol was higher when the cartridge was used. Together these findings indicate that future regulation of sweet flavor additives should focus first on the volatile constituents of e-liquids with the recognition that artificial sweeteners may also contribute to flavor sweetness depending upon e-cigarette design.