Miracle-dz/UniFAR-FTUs huggingface dataset:
Polymorphic Internal Transcribed Spacer Region 1 DNA Sequences Identify Medically Important Yeasts

ABSTRACT Species-specific polymorphisms in the noncoding internal transcribed spacer 2 (ITS2) region of the rRNA operon provide accurate identification of clinically significant yeasts. In this study, we tested the hypothesis that ITS1 noncoding regions contain diagnostically useful alleles. The length of ITS1 region PCR products amplified from 40 species (106 clinical strains, 5 reference strains, and 30 type strains) was rapidly determined with single-base precision by automated capillary electrophoresis. Polymorphisms in the PCR product length permitted 19 species to be distinguished by ITS1 alone, compared with 16 species distinguished by using only ITS2. However, combination of both ITS alleles permitted identification of 30 species (98% of clinical isolates). The remaining 10 species with PCR products of similar sizes contained unique ITS alleles distinguishable by restriction enzyme analysis. DNA sequence analysis of amplified ITS1 region DNA from 79 isolates revealed species-specific ITS1 alleles for each of the 40 pathogenic species examined. This provided identification of unusual clinical isolates, and 53 diagnostic ITS1 sequences were deposited in GenBank. Phylogenetic analyses based on ITS sequences showed a similar overall topology to 26S rRNA gene-based trees. However, different species with identical 26S sequences contained distinct ITS alleles that provided species identification with strong statistical support. Together, these data indicate that the analysis of ITS polymorphisms can reliably identify 40 species of clinically significant yeasts and that the capacity for identifying potentially new pathogenic species by using this database holds significant promise.
Gene Mutations as Emerging Biomarkers and Therapeutic Targets for Relapsed Acute Myeloid Leukemia

It is believed that there are key differences in the genomic profile between adult and childhood acute myeloid leukemia (AML). Relapse is the significant contributor of mortality in patients with AML and remains as the leading cause of cancer death among children, posing great challenges in the treatment of AML. The knowledge about the genomic lesions in childhood AML is still premature as most genomic events defined in children were derived from adult cohorts. However, the emerging technologies of next generation sequencing have narrowed the gap of knowledge in the biology of AML by the detection of gene mutations for each sub-type which have led to the improvement in terms of prognostication as well as the use of targeted therapies. In this review, we describe the recent understanding of the genomic landscape including the prevalence of mutation, prognostic impact, and targeted therapies that will provide an insight into the pathogenesis of AML relapse in both adult and childhood cases.
An Application of Deterrence Theory to Software Piracy

Although the research on software piracy is growing, criminologists have not examined the role of deterrence in software piracy. Using data collected from 382 undergraduate students attending a southeastern university, this study examined the role of deterrence in reducing instances of software piracy using a factorial design. The findings from the analysis showed that certainty and not severity was important in reducing software piracy. The study also found that contemporary parts of deterrence theory (i
Greedy scheduling of cellular self-replication leads to optimal doubling times with a log-Frechet distribution

Significance In production scheduling, a temporal assignment of tasks to their respective processing units is sought, such that precedence and resource constraint are satisfied and an optimization goal is minimized. So how is bacterial self-replication scheduled? Scarcity of resources creates a hard-to-solve scheduling problem in the worst case. Here, we show that proper loading of metabolic and catalytic reservoirs results in optimal scheduling, provided that the catalytic processing units are “greedy,” i.e., do not idle if they can perform a task. The distribution of doubling times of optimally scheduled self-replication has a universal form—the log-Frechet distribution. Recent measurements of doubling times of Escherichia coli in different media well fit this distribution, suggesting that E. coli optimally scheduled its replication in these experiments. Bacterial self-replication is a complex process composed of many de novo synthesis steps catalyzed by a myriad of molecular processing units, e.g., the transcription–translation machinery, metabolic enzymes, and the replisome. Successful completion of all production tasks requires a schedule—a temporal assignment of each of the production tasks to its respective processing units that respects ordering and resource constraints. Most intracellular growth processes are well characterized. However, the manner in which they are coordinated under the control of a scheduling policy is not well understood. When fast replication is favored, a schedule that minimizes the completion time is desirable. However, if resources are scarce, it is typically computationally hard to find such a schedule, in the worst case. Here, we show that optimal scheduling naturally emerges in cellular self-replication. Optimal doubling time is obtained by maintaining a sufficiently large inventory of intermediate metabolites and processing units required for self-replication and additionally requiring that these processing units be “greedy,” i.e., not idle if they can perform a production task. We calculate the distribution of doubling times of such optimally scheduled self-replicating factories, and find it has a universal form—log-Frechet, not sensitive to many microscopic details. Analyzing two recent datasets of Escherichia coli growing in a stationary medium, we find excellent agreement between the observed doubling-time distribution and the predicted universal distribution, suggesting E. coli is optimally scheduling its replication. Greedy scheduling appears as a simple generic route to optimal scheduling when speed is the optimization criterion. Other criteria such as efficiency require more elaborate scheduling policies and tighter regulation.
A novel dead time compensation method

Dead time that is utilized to prevent the phase shortage of inverter bridges causes serious output waveform distortion in PWM VSI and the consequent torque ripple on motor shaft. In this paper, the effect of dead time is investigated. A low cost current direction detecting circuit with high precision is presented. Based on that, a novel compensation method to suppress this output distortion is proposed. Finally the effectiveness of the method is verified by experiments together with other two types of marketing product of inverter in comparison.
Signal Transduction Pathways in Modulation of Ciliary Beat Frequency by Methacholine

The release of endogenous neurotransmitters plays an important role in the airway mucosal defense system. We studied the in vitro effect of methacholine, a β-methyl ester of acetylcholine, on the ciliary beat frequency (CBF) of human adenoid explants and its mechanism of action. Tissue explants were cultured at 35°C and covered with 1.0 mL of culture medium: minimum essential Eagle's medium (MEM) containing L-arginine (1.2 × 10−3 mol/L). Methacholine was added to the cultured tissue at concentrations of 10−10, 10−8, and 10−6 mol/L. The CBF was determined by phase contrast microscopy and microphotometry. Methacholine increased CBF in a dose-dependent manner with a maximum increase of 23.0% ± 1.8% (p <.001). Atropine (10−6 mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p <.0007). The role of endogenous prostaglandins in methacholine-induced ciliostimulation was determined by treating specimens with a cyclooxygenase inhibitor (diclofenac sodium). Diclofenac (10−6 mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p <.0007). To determine if nitric oxide (NO) acts as an intermediary in ciliostimulation by methacholine, endogenous NO production was inhibited by treating specimens with an L-arginine analog, NG-nitro-L-arginine methyl ester (L-NAME), prior to addition of methacholine. L-NAME (10−6 mol/L) inhibited the effects of methacholine in L-arginine-free MEM (p <.008), and this inhibition was reversed by L-arginine (10−3 mol/L). To further examine the actions of NO in methacholine-induced ciliostimulation, a cyclic guanosine 3′5′-monophosphate (cGMP) kinase inhibitor (KT-5823) was used, prior to the addition of methacholine. KT-5823 (10−6 mol/L) significantly inhibited the effects of methacholine (p <.0001). Ciliostimulation by methacholine in human upper airway mucosa involves both prostaglandin and NO second messengers and activation of a cGMP-dependent kinase.
Protocol for a mixed studies systematic review on the implementation of the recovery approach in adult mental health services

Introduction Recovery is integral to mental health planning in G-8 countries including Canada. A recovery-oriented approach to care aims to promote personal empowerment, illness self-management and a life beyond services for people with serious mental illness (SMI), while reducing the financial burden associated with mental illness. Although there is a growing body of literature on recovery, no synthesis of research on the implementation of recovery into mental health services exists. Objectives The objective is to conduct a mixed studies systematic review on the operationalisation of recovery into mental health services for adults with SMI. It will inform the transformation of Canadian services to a recovery orientation, but may be applicable to other countries. Methods and analysis Seven databases including PubMed, Ovid Medline, Ovid Embase, Ovid PsycInfo, CINAHL, the Cochrane Library and Scopus will be searched for peer-reviewed empirical studies published from 1998 to December 2016. Systematic reviews and studies using quantitative, qualitative and mixed methodologies will be included. Secondary searches will be conducted in reference lists of all selected full text articles. Handsearches will also be performed in the tables of contents of three recovery-focused journals for the last 5 years. International experts in the field will be contacted for comments and advice. Data extraction will include identification and methodological synthesis of each study; definition of recovery; information on recovery implementation; facilitators and barriers and study outcomes. A quality assessment will be conducted on each study. The data will be synthesised and a stepwise thematic analysis performed. Ethics and dissemination Ethics approval is not required for this knowledge synthesis. Findings will be disseminated through knowledge translation activities including: (1) a 1-day symposium; (2) presentations in national and international conferences and to local stakeholders; (3) publications in peer-reviewed journals; (4) posts on the organisational websites.
Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis

The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the “natural infection”.
Association between interleukin-6 and carotid atherosclerosis in hemodialysis patients.

BACKGROUND Interleukin-6 (IL-6) is associated with cardiovascular complications in general subjects. Although blood IL-6 is greatly elevated in hemodialysis (HD) patients, the role of IL-6 in the advance of atherosclerosis remains to be determined. METHODS We conducted a cross-sectional study to investigate the relationship between circulating IL-6 and carotid atherosclerotic changes in 156 HD patients (age 58 +/- 1 years; time on HD treatment 13 +/- 1 years; 97 males and 59 females). Serum IL-6, IgG and IgA titers of Chlamydia pneumoniae antibodies, the intima-media thickness (IMT) and the cross-sectional intima-media area (IMarea) of the carotid arteries were measured by ultrasonography in each patient. RESULTS Serum IL-6 levels were significantly higher in HD patients (2.04 +/- 0.16 pg/mL) compared to normal age-matched control subjects (0.31 +/- 0.06 pg/mL, N = 24). Circulating log IL-6 levels were positively correlated with IMT (r = 0.278, P < 0.01) and IMarea (r = 0.344, P < 0.01), respectively. A stepwise multiple regression analysis revealed that IL-6 became significant predictors for IMT and IMarea but not for aortic wall calcification at L2/3 vertebrae. Serum log IL-6 was significantly correlated with IgG (r = 0.277, P < 0.01) and IgA titers of anti-Chlamydia antibodies (r = 0.192, P < 0.02). Serum IgA anti-Chlamydia titers were also correlated with the maximal diameter of carotid plaque (r = 0.293, P < 0.04). CONCLUSIONS These findings suggested that IL-6 is associated with the severity of carotid atherosclerosis in HD patients. Persistent chronic chlamydial infection may be related, in part, to the advance of carotid plaque enlargement in dialysis patients.
Human cutaneous reactive hyperaemia: role of BKCa channels and sensory nerves

Reactive hyperaemia is the increase in blood flow following arterial occlusion. The exact mechanisms mediating this response in skin are not fully understood. The purpose of this study was to investigate the individual and combined contributions of (1) sensory nerves and large‐conductance calcium activated potassium (BKCa) channels, and (2) nitric oxide (NO) and prostanoids to cutaneous reactive hyperaemia. Laser‐Doppler flowmetry was used to measure skin blood flow in a total of 18 subjects. Peak blood flow (BF) was defined as the highest blood flow value after release of the pressure cuff. Total hyperaemic response was calculated by taking the area under the curve (AUC) of the hyperaemic response minus baseline. Infusates were perfused through forearm skin using microdialysis in four sites. In the sensory nerve/BKCa protocol: (1) EMLA® cream (EMLA, applied topically to skin surface), (2) tetraethylammonium (TEA), (3) EMLA®+ TEA (Combo), and (4) Ringer solution (Control). In the prostanoid/NO protocol: (1) ketorolac (Keto), (2) NG‐nitro‐l‐arginine methyl ester (l‐NAME), (3) Keto +l‐NAME (Combo), and (4) Ringer solution (Control). CVC was calculated as flux/mean arterial pressure and normalized to maximal flow. Hyperaemic responses in Control (1389 ± 794%CVCmax s) were significantly greater compared to TEA, EMLA and Combo sites (TEA, 630 ± 512, P= 0.003; EMLA, 421 ± 216, P < 0.001; Combo, 201 ± 200, P < 0.001%CVCmax s). Furthermore, AUC in Combo (Keto +l‐NAME) site was significantly greater than Control (4109 ± 2777 versus 1295 ± 368%CVCmax s). These data suggest (1) sensory nerves and BKCa channels play major roles in the EDHF component of reactive hyperaemia and appear to work partly independent of each other, and (2) the COX pathway does not appear to have a vasodilatory role in cutaneous reactive hyperaemia.
SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS CHORIOCAPILLARIS ALTERATIONS IN EYES WITH NASCENT GEOGRAPHIC ATROPHY AND DRUSEN-ASSOCIATED GEOGRAPHIC ATROPHY

Purpose: To investigate choriocapillaris (CC) alteration in patients with nascent geographic atrophy (nGA) and/or drusen-associated geographic atrophy (DAGA) using swept-source optical coherence tomography angiography (OCTA). Methods: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric swept-source optical coherence tomography angiography over 6 mm × 6 mm fields of view in patients with nGA and/or DAGA. The resulting optical coherence tomography (OCT) and OCTA data were analyzed using a combination of en face and cross-sectional techniques. Variable interscan time analysis (VISTA) was used to differentiate CC flow impairment from complete CC atrophy. Results: A total of 7 eyes from 6 patients (mean age: 73.8 ± 5.7 years) were scanned. Seven areas of nGA and three areas of DAGA were identified. Analysis of cross-sectional OCT and OCTA images identified focal alterations of the CC underlying all seven areas of nGA and all three areas of DAGA. En face OCTA analysis of the CC revealed diffuse CC alterations in all eyes. Variable interscan time analysis processing suggested that the observed CC flow alterations predominantly corresponded to flow impairment rather than complete CC atrophy. Conclusion: The OCTA imaging of the CC revealed focal CC flow impairment associated with areas of nGA and DAGA, as well as diffuse CC flow impairment throughout the imaged field. En face OCT analysis should prove useful for understanding the pathogenesis of nGA and DAGA and for identifying the formation of nGA and DAGA as endpoints in therapeutic trials.
Plaque vulnerability at non-culprit lesions in obese patients with coronary artery disease: Frequency-domain optical coherence tomography analysis

Background Obesity is associated with adverse atherosclerotic cardiovascular events. While various metabolic abnormalities associated with obesity promote plaque formation, the morphological phenotype of atherosclerotic plaque has not been well characterized in the setting of obesity. Frequency-domain optical coherence tomography (FD-OCT) enables in vivo visualization of plaque microstructures associated with vulnerability. We characterized plaque microstructures in obese patients. Methods FD-OCT imaging was performed in 308 patients with coronary artery disease undergoing percutaneous coronary intervention. Patients were stratified according to the presence or absence of obesity (body mass index > 30 kg/m2). Plaques in obese (n = 129) and non-obese (n = 179) patients were compared with regard to clinical characteristics and FD-OCT-derived features of plaque vulnerability. Results Obese patients were more likely to be younger (p = 0.01), female (p = 0.01) and have a history of hypertension (p = 0.01). Higher levels of triglyceride (p < 0.0001) and glucose (p = 0.02), whereas a lower level of high-density lipoprotein cholesterol (HDL-C) (p = 0.02) was observed in obese patients. FD-OCT imaging demonstrated thinner fibrous caps (85.3 ± 31.1 vs 110.1 ± 32.4 µm, p = 0.01) and a higher prevalence of thin-cap fibroatheroma (28.8 vs 14.3%, p = 0.01) in obese patients, which remained significant after controlling for differences in clinical characteristics. Achieving a low-density lipoprotein cholesterol (LDL-C) level < 1.8 mmol/l was associated with thicker fibrous caps in obese patients, but only to the level observed in non-obese patients with suboptimal lipid control. Conclusions Obese patients harbor more vulnerable plaques in association with atherogenic risk factors. The limited benefit of lipid control suggests the need to adopt novel anti-atherosclerotic strategies in higher-risk patients.
Regulation of Sindbis virus RNA replication: uncleaved P123 and nsP4 function in minus-strand RNA synthesis, whereas cleaved products from P123 are required for efficient plus-strand RNA synthesis

Nonstructural proteins of Sindbis virus, nsP1, nsP2, nsP3, and nsP4, as well as intermediate polyproteins, are produced from two precursor polyproteins, P123 and P1234, by a proteolytic enzyme encoded in the C-terminal half of nsP2. We studied the requirements for and the functions of the intermediate and mature processing products for Sindbis virus RNA synthesis by using site-directed mutants which have a defect(s) in processing the 1/2, 2/3, or 3/4 cleavage sites either singly or in various combinations. A mutant defective in cleaving both the 1/2 and 2/3 sites, which makes only uncleavable P123 and mature nsP4 as final products, produced 10(-3) as much virus as did the wild-type virus after 10 h at 30 degrees C and was nonviable at 40 degrees C. A mutant defective in processing the 2/3 site, which makes nsP1, nsP4, and P23 as well as precursor P123, grew 10(-1) as efficiently as wild-type virus at 30 degrees C and 10(-3) as efficiently at 40 degrees C. Early minus-strand RNA synthesis by these mutants was as efficient as that by wild-type virus, whereas plus-strand RNA synthesis was substantially decreased compared with that by wild-type virus. A mutant defective in processing the 3/4 site was nonviable at either 30 or 40 degrees C. The 3/4 site mutant could be complemented by the mutant unable to cleave either the 1/2 or 2/3 site, which can provide mature nsP4. We interpret these results to signify that (i) mature nsP4 is required for RNA replication, (ii) nsP4 and uncleaved P123 function in minus-strand RNA synthesis, and (iii) cleavage of P123 is required for efficient plus-strand RNA synthesis. We propose that Sindbis virus RNA replication is regulated by differential proteolysis of P123. Early in infection, nsP4 and uncleaved P123 form transient minus-strand RNA replication complexes which vanish upon cleavage of P123. Later in infection, an elevated level of viral proteinase activity eliminates de novo synthesis of P123, and no further synthesis of minus-strand RNA is possible. In contrast, nsP4 and cleavage products from P123 form plus-strand RNA replication complexes which are stable and remain active throughout the infection cycle.