Miracle-dz/UniFAR-FTUs huggingface dataset:
Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy

SUMMARY The global tuberculosis (TB) control effort is focused on interrupting transmission of the causative agent, Mycobacterium tuberculosis, through chemotherapeutic intervention in active infectious disease. The insufficiency of this approach is manifest in the inexorable annual increase in TB infection and mortality rates and the emergence of multidrug-resistant isolates. Critically, the limited efficacy of the current frontline anti-TB drug combination suggests that heterogeneity of host and bacillary physiologies might impair drug activity. This review explores the possibility that strategies enabling adaptation of M. tuberculosis to hostile in vivo conditions might contribute to the subversion of anti-TB chemotherapy. In particular, evidence that infecting bacilli are exposed to environmental and host immune-mediated DNA-damaging insults suggests a role for error-prone DNA repair synthesis in the generation of chromosomally encoded antibiotic resistance mutations. The failure of frontline anti-TB drugs to sterilize a population of susceptible bacilli is independent of genetic resistance, however, and instead implies the operation of alternative tolerance mechanisms. Specifically, it is proposed that the emergence of persister subpopulations might depend on the switch to an altered metabolic state mediated by the stringent response alarmone, (p)ppGpp, possibly involving some or all of the many toxin-antitoxin modules identified in the M. tuberculosis genome.
Characterization and modeling of on-chip spiral inductors for Si RFICs

The paper presents a complete characterization of on-chip inductors fabricated in BiCMOS technology. First, a study of the scaling effect of inductance on geometry and structure parameters is presented to provide a clear guideline on inductor scaling with suitable quality factors. The substrate noise analysis and noise reduction techniques are then investigated. It is shown that floating well can improve both quality factor and noise elimination by itself under 3 GHz and together with a guard ring above 3 GHz. Finally, for accurate circuit simulations, a new inductor model is developed for predicting the skin effect and eddy effect and associated quality factor and inductance.
Stein Variational Gradient Descent: A General Purpose Bayesian Inference Algorithm

We propose a general purpose variational inference algorithm that forms a natural counterpart of gradient descent for optimization. Our method iteratively transports a set of particles to match the target distribution, by applying a form of functional gradient descent that minimizes the KL divergence. Empirical studies are performed on various real world models and datasets, on which our method is competitive with existing state-of-the-art methods. The derivation of our method is based on a new theoretical result that connects the derivative of KL divergence under smooth transforms with Stein's identity and a recently proposed kernelized Stein discrepancy, which is of independent interest.
De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly

Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm. DOI: http://dx.doi. org/10.7554/eLife.10586. 001
MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction

Microtubule-associated protein 2 (MAP2) is a major component of cross-bridges between microtubules in dendrites, and is known to stabilize microtubules. MAP2 also has a binding domain for the regulatory subunit II of cAMP-dependent protein kinase (PKA). We found that there is reduction in microtubule density in dendrites and a reduction of dendritic length in MAP2-deficient mice. Moreover, there is a significant reduction of various subunits of PKA in dendrites and total amounts of various PKA subunits in hippocampal tissue and cultured neurons. In MAP2-deficient cultured neurons, the induction rate of phosphorylated CREB after forskolin stimulation was much lower than in wild-type neurons. Therefore, MAP2 is an anchoring protein of PKA in dendrites, whose loss leads to reduced amount of dendritic and total PKA and reduced activation of CREB.
miRNA Expression Profiling of the Murine TH-MYCN Neuroblastoma Model Reveals Similarities with Human Tumors and Identifies Novel Candidate MiRNAs

Background MicroRNAs are small molecules which regulate gene expression post-transcriptionally and aberrant expression of several miRNAs is associated with neuroblastoma, a childhood cancer arising from precursor cells of the sympathetic nervous system. Amplification of the MYCN transcription factor characterizes the most clinically aggressive subtype of this disease, and although alteration of p53 signaling is not commonly found in primary tumors, deregulation of proteins involved in this pathway frequently arise in recurrent disease after pharmacological treatment. TH-MYCN is a well-characterized transgenic model of MYCN-driven neuroblastoma which recapitulates many clinicopathologic features of the human disease. Here, we evaluate the dysregulation of miRNAs in tumors from TH-MYCN mice that are either wild-type (TH-MYCN) or deficient (TH-MYCN/p53ERTAM) for the p53 tumor suppressor gene. Principal Findings We analyzed the expression of 591 miRNAs in control (adrenal) and neuroblastoma tumor tissues derived from either TH-MYCN or TH-MYCN/p53ERTAM mice, respectively wild-type or deficient in p53. Comparing miRNA expression in tumor and control samples, we identified 159 differentially expressed miRNAs. Using data previously obtained from human neuroblastoma samples, we performed a comparison of miRNA expression between murine and human tumors to assess the concordance between murine and human expression data. Notably, the miR-17-5p-92 oncogenic polycistronic cluster, which is over-expressed in human MYCN amplified tumors, was over-expressed in mouse tumors. Moreover, analyzing miRNAs expression in a mouse model (TH-MYCN/p53ERTAM) possessing a transgenic p53 allele that drives the expression of an inactive protein, we identified miR-125b-3p and miR-676 as directly or indirectly regulated by the level of functional p53. Significance Our study represents the first miRNA profiling of an important mouse model of neuroblastoma. Similarities and differences in miRNAs expression between human and murine neuroblastoma were identified, providing important insight into the efficacy of this mouse model for assessing miRNA involvement in neuroblastoma and their potential effectiveness as therapeutic targets.
COGNITIVE FUNCTIONING IN LESCH‐NYHAN SYNDROME

The present study represents the first effort to assess systematically the cognitive functioning of a population of individuals with Lesch‐Nyhan syndrome using standardized psychometric instruments. Seven residents from a special hospital setting participated. They ranged in age from 10 years 1 month to 22 years 3 months (mean 13 years 7 months). Using the Stanford‐Binet Intelligence Scale: IV, scores in each of the four domains assessed by this battery (Verbal Reasoning, Abstract/Visual Reasoning. Quantitative and Short‐Term Memory), as well as the general composite score, ranged from moderately mentally retarded to low average. Areas of weakness included attention, the manipulation of complex visual images, the comprehension of complex or lengthy speech, mathematical ability, and multi‐step reasoning.
Verapamil treatment of intractable ventricular arrhythmias after cardiopulmonary bypass.

Life-threatening ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, are commonly treated with intravenous lidocaine, procainamide, or DC countershock. There is, however, growing appreciation of the role calcium-dependent ionic currents may play in the genesis and perpetration of such arrhythmias when they occur in the setting of the acutely ischemic myocardium (1). Recently, verapamil was reported to have successfully converted intractible ventricular arrhythmias that occurred during cardiac surgery in four patients with marked cardiac hypertrophy (2). Two of those patients were having procedures for the relief of severe obstructive hypertrophic cardiomyopathy, one for a complex congenital heart lesion, and one was having aortic valve replacement for severe aortic stenosis and regurgitation caused by a congenital unicuspid valve. We now describe a case of a patient with good ventricular function undergoing coronary artery bypass surgery in which verapamil was used to terminate ventricular arrhythmias that were refractory to traditional therapeutic measures and that prevented termination of cardiopulmonary bypass. Continued arrhythmia suppression was provided by an intravenous infusion of verapamil.
A single-cell pedigree analysis of alternative stochastic lymphocyte fates

In contrast to most stimulated lymphocytes, B cells exposed to Toll-like receptor 9 ligands are nonself-adherent, allowing individual cells and families to be followed in vitro for up to 5 days. These B cells undergo phases typical of an adaptive response, dividing up to 6 times before losing the impetus for further growth and division and eventually dying by apoptosis. Using long-term microscopic imaging, accurate histories of individual lymphocyte fates were collected. Quantitative analysis of family relationships revealed that times to divide of siblings were strongly related but these correlations were progressively lost through consecutive divisions. A weaker, but significant, correlation was also found for death times among siblings. Division cessation is characterized by a loss of cell growth and the division in which this occurs is strongly inherited from the original founder cell and is related to the size this cell reaches before its first division. Thus, simple division-based dilution of factors synthesized during the first division may control the maximum division reached by stimulated cells. The stochastic distributions of times to divide, times to die, and divisions reached are also measured. Together, these results highlight the internal cellular mechanisms that control immune responses and provide a foundation for the development of new mathematical models that are correct at both single-cell and population levels.
Evaluation of the effects of the anti-retroviral drug regimen (zidovudine + lamivudine + nevirapine) on CD4 count, body weight, and Hb% of the HIV patients-a retrospective study

The main objective of study is to evaluate the effectiveness of triple drug therapy Zidovudine + lamivudine + nevirapine on cd 4 counts, weight and Hb% for the duration of 6 months. In this retrospective study, data was collected from the anti-retroviral therapy (ART) centre where 315 subjects infected with HIV received ZIDOVUDINE + LAMIVUDINE + NEVIRAPINE. Baseline and after 6 months of therapy; CD4 count, weight and Hb% were recorded and compared. Records with incomplete data were excluded. Statistical analysis was done using paired ‘t’ test for body weight , Hb% and CD4 count.It was found that after 6 months of treatment, both CD4 count and body weight improved significantly(p value: 0.001). Whereas in case of haemoglobin %, even after the treatment period, no significant changes were observed in Hb % (p value: 0.227). It was concluded that ZLN regimen for treatment in HIV patient is efficacious in improving both CD4 count and body weight and not Hb%.
Aerosol optical depth over the Tibetan Plateau and its relation to aerosols over the Taklimakan Desert

The Multiangle Imaging SpectroRadiometer (MISR) aerosol optical depths (AODs) over the Tibetan Plateau (TP) are compared with ground‐based remote sensing data. The result shows that 27 out of 32 MISR AODs fall within the expected uncertainty, i.e., 0.05 or 20% × AOD. The mean bias and the root mean square error between ground and satellite AODs are 0.01 and 0.03, respectively. The 7‐year MISR AOD data are used to study seasonal and inter‐annual variations of AOD over the TP. The results show distinct seasonal variation, with seasonal AOD being 0.27, 0.25, 0.13 and 0.11 from spring to winter. AOD over the TP is closely related to that over the Taklimakan desert in summer; however poor correlation is observed in spring. Higher AOD in spring and summer over the TP merits further study, including its causes and implications for climate and environment.
Numerical simulation on improvement of a Savonius vertical axis water turbine performance to advancing blade side with a circular cylinder diameter variations

The use of fossil fuel will generate particulate gas in the atmosphere and forming the greenhouse effect. One of the ways to reducing greenhouse effect is used renewable energy as hydropower without generating particulate gas impacted in human life. The present study uses hydropower as the renewable energy by using a Savonius turbine. The main objective investigates the performance of Savonius water turbine numerically due to the installation of a circular cylinder beside of the advancing blade with circular cylinder diameter variations. The method used is numerically toward Savonius turbine disturbed a circular cylinder. The numerical simulation using two-dimensional (2D) analysis of Computational Fluid Dynamics (CFD) simulation by using ANSYS 17.0-Fluent and sliding Mesh technique used is to solve the incompressible Unsteady Reynolds Averaged Navier-Stokes (URANS) equations. The turbulence model uses Realizable k-epsilon (RKE) and transport equation uses the finite volume discretization method with the second-order upwind scheme and the SIMPLE algorithm. Firstly, the numerical model has been validated by the published experimental data toward the torque coefficient by using air fluid at Reynolds of 4.32. 105. Then the fluid is changed the water fluid at the same Reynolds. The circular cylinder diameter relative to the turbine diameter (ds/D) is varied of 0.1, 0.3, 0.5, 0.7 and 0.9 at X/D of 0.5 and Y/D of 0.7 kept constant with TSR of 0.5, 0.7, 0.9, 1.1 and 1.3. The numerical simulation uses the transient and two dimensional (2D) simulations. The results show that the increase of disturbance diameter (ds/D) will improve the performance of the conventional Savonius turbine and the maximum power coefficient increase about 18.04% at ds/D of 0.7 with TSR of 0.7.
A WCDMA/WLAN digital polar transmitter with low-noise ADPLL, wide-band PM/AM modulator and linearized PA in 65nm CMOS

A single-chip digital polar transmitter integrates an all-digital synthesizer, a PM/AM modulator, and a linearized power amplifier for WCDMA/WLAN. The 1.7~2.5GHz LO signal is generated from an ADPLL together with a ÷1.5 divider to eliminate DCO pulling. A 2-segment ΣΔ phase modulator enhances the PM bandwidth up to 200MHz, and a digital polar amplifier employs AM-replica linearization to eliminate predistortion. The TX measures EVM 4% for a 20MHz-bandwidth 64-QAM while providing a peak output power of 22.1dBm with bit-to-RF efficiency 27.6%.
The Toxicity of Amyloid β Oligomers

In this review, we elucidate the mechanisms of Aβ oligomer toxicity which may contribute to Alzheimer’s disease (AD). In particular, we discuss on the interaction of Aβ oligomers with the membrane through the process of adsorption and insertion. Such interaction gives rises to phase transitions in the sub-structures of the Aβ peptide from α-helical to β-sheet structure. By means of a coarse-grained model, we exhibit the tendency of β-sheet structures to aggregate, thus providing further insights to the process of membrane induced aggregation. We show that the aggregated oligomer causes membrane invagination, which is a precursor to the formation of pore structures and ion channels. Other pathological progressions to AD due to Aβ oligomers are also covered, such as their interaction with the membrane receptors, and their direct versus indirect effects on oxidative stress and intraneuronal accumulation. We further illustrate that the molecule curcumin is a potential Aβ toxicity inhibitor as a β-sheet breaker by having a high propensity to interact with certain Aβ residues without binding to them. The comprehensive understanding gained from these current researches on the various toxicity mechanisms show promises in the provision of better therapeutics and treatment strategies in the near future.
Scale effects in species distribution models: implications for conservation planning under climate change

Predictions of future species' ranges under climate change are needed for conservation planning, for which species distribution models (SDMs) are widely used. However, global climate model-based (GCM) output grids can bias the area identified as suitable when these are used as SDM predictor variables, because GCM outputs, typically at least 50×50 km, are biologically coarse. We tested the assumption that species ranges can be equally well portrayed in SDMs operating on base data of different grid sizes by comparing SDM performance statistics and area selected by four SDMs run at seven grid sizes, for nine species of contrasting range size. Area selected was disproportionately larger for SDMs run on larger grid sizes, indicating a cut-off point above which model results were less reliable. Up to 2.89 times more species range area was selected by SDMs operating on grids above 50×50 km, compared to SDMs operating at 1 km2. Spatial congruence between areas selected as range also diverged as grid size increased, particularly for species with ranges between 20 000 and 90 000 km2. These results indicate the need for caution when using such data to plan future protected areas, because an overly large predicted range could lead to inappropriate reserve location selection.
Temporal stability of gait in Parkinson's disease.

BACKGROUND AND PURPOSE. Evaluation of physical therapy for gait disorders in patients with Parkinson's disease (PD) requires an under-standing of how the patients' medication cycle affects function. Four experiments were conducted to investigate stability of gait variables. METHODS AND RESULTS. In experiment 1, 15 subjects with idiopathic PD and 15 subjects without PD performed two sets of gait trials spaced 30 minutes apart, with the initial trial conducted with the subjects at a peak dose of medication. Strong correlations, as determined by intraclass correlation coefficients (ICC[2,1]), occurred between repeat measures of speed (ICC = .92), cadence (ICC = .92), stride length (ICC = .94), and time spent in double support (DS) (ICC = .93). In experiment 2, 16 subjects with PD were tested at the same time on two consecutive days. There was good repeatability for speed (ICC = .88), cadence (ICC = .85), stride length (ICC = .84), and DS (ICC = .80). When we assessed the repeatability of measurements taken at peak dose and at end of dose, there were low correlations for speed (ICC = -.54), cadence (ICC = -.07), stride length (ICC = -.35), and DS (ICC = -.38). In a final experiment on 16 subjects with PD, we used time-series analysis to examine the stability of measurements taken every 15 minutes for 2 1/2 hours. Slopes of regression models, standard deviations, and residual autocorrelations were negligible, indicating that the measurements were stable. CONCLUSION AND DISCUSSION. The parkinsonian gait pattern is reproducible across either brief time intervals or 24 hours when peak medication prevails. At the end of dose, however, marked changes in gait occur, apparently related to depletion of medication.
Latency-associated Peptide of Transforming Growth Factor-β1 Is Not Subject to Physiological Mannose Phosphorylation*

Background: Previous reports indicate latent TGF-β1 activation is mediated by mannose phosphorylation of its N-glycans. Results: Minimal mannose phosphorylation was detected on secreted TGF-β1, and its activation in corneal fibroblasts is not Man-6-P-dependent. Conclusion: Latent TGF-β1 is not subject to physiological mannose phosphorylation. Significance: Because free Man-6-P reduces scarring by inhibiting TGF-β1 activation, further investigation into molecular mechanisms explaining this phenomenon is warranted. Latent TGF-β1 was one of the first non-lysosomal glycoproteins reported to bear mannose 6-phosphate (Man-6-P) residues on its N-glycans. Prior studies have suggested that this sugar modification regulates the activation of latent TGF-β1 by allowing it to bind cell surface-localized Man-6-P receptors. Man-6-P has also been proposed as an anti-scarring therapy based on its ability to directly block the activation of latent TGF-β1. A complete understanding of the physiological relevance of latent TGF-β1 mannose phosphorylation, however, is still lacking. Here we investigate the degree of mannose phosphorylation on secreted latent TGF-β1 and examine its Man-6-P-dependent activation in primary human corneal stromal fibroblasts. Contrary to earlier reports, minimal to no Man-6-P modification was found on secreted and cell-associated latent TGF-β1 produced from multiple primary and transformed cell types. Results showed that the inability to detect Man-6-P residues was not due to masking by the latent TGF-β1-binding protein (LTBP). Moreover, the efficient processing of glycans on latent TGF-β1 to complex type structures was consistent with the lack of mannose phosphorylation during biosynthesis. We further demonstrated that the conversion of corneal stromal fibroblast to myofibroblasts, a well known TGF-β1-dependent process, was not altered by Man-6-P addition when latent forms of this growth factor were present. Collectively, these findings indicate that Man-6-P-dependent effects on latent TGF-β1 activation are not mediated by direct modification of its latency-associated peptide.
The Relation Between Family Adversity and Social Anxiety Among Adolescents in Taiwan: Effects of Family Function and Self-Esteem

Abstract This study aimed to examine the relationship between three indicators of family adversity (domestic violence, family substance use, and broken parental marriage) and the severity of social anxiety among adolescents in Taiwan, as well as the mediating effects of perceived family function and self-esteem on that relationship, using structural equation modeling (SEM). A total of 5607 adolescents completed the social anxiety subscale of the Multidimensional Anxiety Scale for Children; the Family APGAR Index; the Rosenberg Self-Esteem Scale; and a questionnaire for domestic violence, family substance use, and broken parental marriage. The relation between family adversity and social anxiety, as well as the mediating effects of family function and self-esteem, was examined using SEM. SEM analysis revealed that all three indicators of family adversity reduced the level of family function, that decreased family function compromised the level of self-esteem, and that a low level of self-esteem further increased the severity of social anxiety. The results indicated that, along with intervening to change family adversity, evaluating and improving adolescents’ self-esteem and family function are also important clinical issues when helping adolescents reduce their social anxiety.