Miracle-dz/UniFAR-FTUs huggingface dataset:
A Branch Point of Streptomyces Sulfur Amino Acid Metabolism Controls the Production of Albomycin

ABSTRACT Albomycin (ABM), also known as grisein, is a sulfur-containing metabolite produced by Streptomyces griseus ATCC 700974. Genes predicted to be involved in the biosynthesis of ABM and ABM-like molecules are found in the genomes of other actinomycetes. ABM has potent antibacterial activity, and as a result, many attempts have been made to develop ABM into a drug since the last century. Although the productivity of S. griseus can be increased with random mutagenesis methods, understanding of Streptomyces sulfur amino acid (SAA) metabolism, which supplies a precursor for ABM biosynthesis, could lead to improved and stable production. We previously characterized the gene cluster (abm) in the genome-sequenced S. griseus strain and proposed that the sulfur atom of ABM is derived from either cysteine (Cys) or homocysteine (Hcy). The gene product, AbmD, appears to be an important link between primary and secondary sulfur metabolic pathways. Here, we show that propargylglycine or iron supplementation in growth media increased ABM production by significantly changing the relative concentrations of intracellular Cys and Hcy. An SAA metabolic network of S. griseus was constructed. Pathways toward increasing Hcy were shown to positively impact ABM production. The abmD gene and five genes that increased the Hcy/Cys ratio were assembled downstream of hrdBp promoter sequences and integrated into the chromosome for overexpression. The ABM titer of one engineered strain, SCAK3, in a chemically defined medium was consistently improved to levels ∼400% of the wild type. Finally, we analyzed the production and growth of SCAK3 in shake flasks for further process development.
Mitochondria as a source of mechanical signals in cardiomyocytes.

AIMS The myofibrillar and nuclear compartments in cardiomyocytes are known to be sensitive to extracellular mechanical stimuli. Recently, we have shown that alterations in the mitochondrial ionic balance in cells in situ are associated with considerably increased mitochondrial volume. Theoretically, this swelling of mitochondria could impose mechanical constraints on the myofibrils and nuclei in their vicinity. Thus, we studied whether modulation of mitochondrial volume in cardiomyocytes in situ has a mechanical effect on the myofibrillar and nuclear compartments. METHODS AND RESULTS We used the measurement of passive force developed by saponin-permeabilized mouse ventricular fibres as a sensor for compression of the myofibrils. Osmotic compression induced by dextran caused an increase in passive force. Similarly, mitochondrial swelling induced by drugs that alter ionic homeostasis (alamethicin and propranolol) markedly augmented passive force (confirmed by confocal microscopy). Diazoxide, a mitochondrial ATP-sensitive potassium channel opener known to cause moderate mitochondrial swelling, also increased passive force (by 28 +/- 5% at 10% stretch, P < 0.01). This effect was completely blocked by 5-hydroxydecanoate (5-HD), a putative specific inhibitor of these channels. Mitochondrial swelling induced by alamethicin and propranolol led to significant nuclear deformation, which was visualized by confocal microscopy. Furthermore, diazoxide decreased nuclear volume, calculated using three-dimensional reconstructed images, in a 5-HD-dependent manner by 12 +/- 2% (P < 0.05). This corresponds to an increase in intracellular pressure of 2.1 +/- 0.3 kPa. CONCLUSION This study is the first to demonstrate that mitochondria are able to generate internal pressure, which can mechanically affect the morphological and functional properties of intracellular organelles.
A Time Lower Bound for Multiple Nucleation on a Surface

Majumder, Reif and Sahu have presented a stochastic model of reversible, error-permitting, two-dimensional tile self-assembly, and showed that restricted classes of tile assembly systems achieved equilibrium in (expected) polynomial time. One open question they asked was how much computational power would be added if the model permitted multiple nucleation, i.e., independent groups of tiles growing before attaching to the original seed assembly. This paper provides a partial answer, by proving that if a tile assembly model uses only local binding rules, then it cannot use multiple nucleation on a surface to solve certain "simple" problems in constant time (time independent of the size of the surface). Moreover, this time bound applies to macroscale robotic systems that assemble in a three-dimensional grid, not just to tile assembly systems on a two-dimensional surface. The proof technique defines a new model of distributed computing that simulates tile (and robotic) self-assembly. Keywords: self-assembly, multiple nucleation, locally checkable labeling.
FermiKit: assembly-based variant calling for Illumina resequencing data

UNLABELLED FermiKit is a variant calling pipeline for Illumina whole-genome germline data. It de novo assembles short reads and then maps the assembly against a reference genome to call SNPs, short insertions/deletions and structural variations. FermiKit takes about one day to assemble 30-fold human whole-genome data on a modern 16-core server with 85 GB RAM at the peak, and calls variants in half an hour to an accuracy comparable to the current practice. FermiKit assembly is a reduced representation of raw data while retaining most of the original information. AVAILABILITY AND IMPLEMENTATION https://github.com/lh3/fermikit CONTACT hengli@broadinstitute.org.
Binding sites of VanRB and σ70 RNA polymerase in the vanB vancomycin resistance operon of Enterococcus faecium BM4524

The vanB operon of Enterococcus faecium BM4524 which confers inducible resistance to vancomycin is composed of the vanRBSB gene encoding a two‐component regulatory system and the vanYBWHBBXB resistance genes that are transcribed from promoters PRB and PYB respectively. In this study, primer extension revealed transcription start sites at 13 and 48 bp upstream from the start codon of vanRB and vanYB, respectively, that allowed identification of −10 and −35 promoter motifs. The VanRB protein was overproduced in Escherichia coli, purified and phosphorylated (VanRB‐P) non‐enzymically with acetylphosphate. VanRB‐P and VanRB specifically bound to PRB and PYB promoters. VanRB bound at a single site at position −32.5 upstream from the PRB transcriptional start site and at two sites at positions −33.5 and −55.5 upstream from that of PYB. The proximal VanRB binding site overlapped the −35 region of both promoters. VanRB was converted from a monomer to a dimer upon acetylphosphate treatment. VanRB‐P had higher affinity than VanRB for its targets and appeared more efficient than VanRB in promoting open complex formation with PRB and PYB. In the absence of regulator, E. coli RNA polymerase was able to interact with PRB but not with PYB. Phosphorylation of VanRB significantly increased promoter interaction with RNA polymerase and led to an extended and modified footprint. In vitro transcription assays showed that VanRB‐P activates PYB more strongly than PRB. Analysis of the protected regions revealed one copy of a 21 bp sequence in the PRB promoter and two copies in the PYB promoter which may serve as recognition sites for VanRB and VanRB‐P binding that are required for transcriptional activation and expression of vancomycin resistance.
The prevalence of infectious agents in patients with systemic sclerosis.

BACKGROUND/AIM Systemic sclerosis (SSc) is an autoimmune disease characterized by microvascular injury, excessive extracellular matrix deposition, and fibrosis in the skin and internal organs. Bacterial and viral infectious agents have been suspected to be contributing factors in the development and progression of the pathologic features of SSc. MATERIALS AND METHODS In this study, 30 SSc patients who were admitted to the rheumatology unit of the Konya Training and Research Hospital and 30 healthy controls were included. The presence of 9 different antibodies (IgM and IgG) against Helicobacter pylori, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and parvovirus B19 were investigated in sera samples obtained from the 60 participants using an enzyme-linked immunosorbent assay method. The characteristics of current and past infections with H. pylori, CMV, EBV, and parvovirus B19 were evaluated by determining the seropositivity of the tested bacterial and viral agents. RESULTS The prevalences of H. pylori, CMV, EBV, and parvovirus B19 were determined to be higher in patients with SSc than in the control group. CONCLUSION SSc is associated with a higher rate of certain infections, which deserves further investigation in order to assess the role of infections in disease etiology/pathogenesis.
Anxiety disorders are associated with increased plasma adrenomedullin level and left ventricular hypertrophy in patients with hypertension

Abstract Objective: To investigate the association between anxiety disorders and left ventricular hypertrophy in patients with essential hypertension. Methods: Left ventricular structure and function were assessed with echocardiography in 56 patients with essential hypertension and anxiety disorder (study group) and in 56 patients with hypertension only (control group). Serum adrenomedullin levels were also measured in these patients. Results: There was no statistically significant difference in the left ventricular ejection fraction between the study and the control group (54.21 ± 88.81% versus 56.01 ± 7.85%, p > 0.05). The left ventricular mass index (LVMI) in study group was higher than in control group (137.05 ± 9.42 versus 123.57 ± 7.01 g/m2, p = 0.001). The plasma levels of adrenomedullin in study group was higher than in control group (25.97 ± 5.48 versus 18.32 ± 6.97 ng/L, p = 0.001). Levels of plasma adrenomedullin were positively correlated with LVMI in the study (r = 0.734, p < 0.05) and control group (r = 0.592, p < 0.05). Conclusion: Anxiety disorders are associated with elevated plasma adrenomedullin levels and increased left ventricular hypertrophy in patients with essential hypertension. The clinical significance of these changes requires further investigation.
Different Influences of Hematocrit on the Results of Two Point-Of-Care Platelet Function Tests, the VerifyNow Assay and Multiple Electrode Platelet Aggregometry

Objective Previous studies have reported a considerable association between the VerifyNow (Accumetrics, San Diego, CA, USA) P2Y12 assay results and hematocrit. No reports, however, have described an association between the multiple electrode platelet aggregometry (MEA; Dynabyte, Munich, Germany) adenosine diphosphate (ADP) assay results and hematocrit. This study was conducted to evaluate the influence of hematocrit on the results of 2 different point-of-care platelet function tests. Methods A total of 462 consecutive patients who were undergoing percutaneous coronary intervention were enrolled. Platelet function was evaluated with both the VerifyNow P2Y12 and MEA ADP assays. Results Anemic patients (n = 152, 32.9%) demonstrated a significantly higher rate of cardiac death, myocardial infarction, and stroke (5.3% vs. 2.3%, p = 0.046) during the follow-up (median: 18.8 months). Although the VerifyNow P2Y12 assay results demonstrated a significant inverse correlation with hematocrit (r = −0.409, p<0.001), there was no such correlation between the MEA ADP assay results and hematocrit (r = 0.039, p = 0.401). In the multivariate analysis, anemia was an independent predictor of high on-treatment platelet reactivity, defined as a VerifyNow P2Y12 reaction unit level of ≥252.5 (odds ratio = 2.21, 95% confidence interval = 1.39–3.52; p = 0.001). Importantly, this association was independent of an intrinsic change in platelet reactivity as measured by the MEA ADP assay. Adjusting for the influence of hematocrit improved the strength of the correlation between the VerifyNow P2Y12 and MEA ADP assay results. Conclusions Hematocrit significantly influenced the VerifyNow P2Y12 assay results, a phenomenon that was presumably in-vitro. Hematocrit level should therefore be considered when interpreting results of the VerifyNow P2Y12 assay.
Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3-KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.
Microscopic analysis for decoupling principle of linear vector channel

This paper studies decoupling principle of a linear vector channel, which is an extension of CDMA and MIMO channels. We show that the scalar-channel characterization obtained via the decoupling principle is valid not only for collections of a large number of elements of input vector, as discussed in previous studies, but also for individual elements of input vector, i.e., the linear vector channel for individual elements of channel input vector is decomposed into a bank of independent scalar Gaussian channels in the large-system limit, where dimensions of channel input and output are both sent to infinity while their ratio fixed.
Cognitive ontologies for neuropsychiatric phenomics research

Now that genome-wide association studies (GWAS) are dominating the landscape of genetic research on neuropsychiatric syndromes, investigators are being faced with complexity on an unprecedented scale. It is now clear that phenomics, the systematic study of phenotypes on a genome-wide scale, comprises a rate-limiting step on the road to genomic discovery. To gain traction on the myriad paths leading from genomic variation to syndromal manifestations, informatics strategies must be deployed to navigate increasingly broad domains of knowledge and help researchers find the most important signals. The success of the Gene Ontology project suggests the potential benefits of developing schemata to represent higher levels of phenotypic expression. Challenges in cognitive ontology development include the lack of formal definitions of key concepts and relations among entities, the inconsistent use of terminology across investigators and time, and the fact that relations among cognitive concepts are not likely to be well represented by simple hierarchical “tree” structures. Because cognitive concept labels are labile, there is a need to represent empirical findings at the cognitive test indicator level. This level of description has greater consistency, and benefits from operational definitions of its concepts and relations to quantitative data. Considering cognitive test indicators as the foundation of cognitive ontologies carries several implications, including the likely utility of cognitive task taxonomies. The concept of cognitive “test speciation” is introduced to mark the evolution of paradigms sufficiently unique that their results cannot be “mated” productively with others in meta-analysis. Several projects have been initiated to develop cognitive ontologies at the Consortium for Neuropsychiatric Phenomics (www.phenomics.ucla.edu), in the hope that these ultimately will enable more effective collaboration, and facilitate connections of information about cognitive phenotypes to other levels of biological knowledge. Several free web applications are available already to support examination and visualisation of cognitive concepts in the literature (PubGraph, PubAtlas, PubBrain) and to aid collaborative development of cognitive ontologies (Phenowiki and the Cognitive Atlas). It is hoped that these tools will help formalise inference about cognitive concepts in behavioural and neuroimaging studies, and facilitate discovery of the genetic bases of both healthy cognition and cognitive disorders.
Empirical evaluation of optimized stacking configurations

Stacking is one of the most used techniques for combining classifiers and improves prediction accuracy. Early research in stacking showed that selecting the right classifiers, their parameters and the metaclassifiers was the main bottleneck for its use. Most of the research on this topic selects by hand the right combination of classifiers and their parameters. Instead of starting from these initial strong assumptions, our approach uses genetic algorithms to search for good stacking configurations. Since this can lead to overfitting, one of the goals of This work is to evaluate empirically the overall efficiency of the approach. A second goal is to compare our approach with current best stacking building techniques. The results show that our approach finds stacking configurations that, in the worst case, perform as well as the best techniques, with the advantage of not having to set up manually the structure of the stacking system.
Investigation of energy and mass - charging composition of a vacuum spark plasma at various pulse parameters and electrode arrangement

Vacuum spark plasmas with various pulse parameters were investigated. Two types of pulse generator were used to initiate the discharge. The pulse amplitude and duration were varied from 15 to 350 kV and from 100 to 400 ns, respectively. The electrode separation of the vacuum gap was varied from 2 to 15 mm. It has been found that the most probable energies of the ion flow species increase with gap spacing. Also, a dependence of the most probable energies of the ion flow species on ion charge has been revealed.
Numerical Investigation of Thermal Radiation and Viscous Effects on Entropy Generation in Forced Convection Blood Flow over an Axisymmetric Stretching Sheet

Numerical and analytical investigation of the effects of thermal radiation and viscous heating on a convective flow of a non-Newtonian, incompressible fluid in an axisymmetric stretching sheet with constant temperature wall is performed. The power law model of the blood is used for the non-Newtonian model of the fluid and the Rosseland model for the thermal radiative heat transfer in an absorbing medium and viscous heating are considered as the heat sources. The non-dimensional governing equations are transformed to similarity form and solved numerically. A parameter study on entropy generation in medium is presented based on the Second Law of Thermodynamics by considering various parameters such as the thermal radiation parameter, the Brinkman number, Prandtl number, Eckert number.
Prevalence of cervical human papillomavirus infection in healthy women is related to sexual behaviours and educational level: a cross-sectional study

This study reports the prevalence and risk factors of human papillomavirus (HPV) infection in healthy women in Singapore. Demography, education, sexual and reproductive history and cigarette smoking habits were obtained from a cross-sectional population of healthy women and girls aged above 12 years of age. Cervical or vaginal cytology samples were investigated for 37 known anogenital HPV subtypes using the linear array PCR method. Chi square statistics were used to test for associations of individual epidemiological factors with HPV infection. Independent risk factors were identified with binomial logistic regression analysis. Of 891 subjects, the prevalence of HPV infection was 9.31% (83/891 women) for any-type HPV and 5.05% (46/891 women) for the high-risk HPV (hrHPV). Of 30 HPV subtypes detected, the most prevalent genotypes in descending order of frequency were subtypes 51, 16, 52, 58 and 66 for hrHPV and subtypes 62, 61, 84, 72 and 53 for the low-risk HPV. This frequency distribution of HPV subtypes was different from reports from other countries within Asia. Forty-six virgins studied tested negative for HPV infection. Significant independent risk factors for any-type HPV infection were multiple sexual partners (adjusted OR 1.4) and low (≤6 years) educational level (adjusted OR 4.0). The distribution of HPV subtypes in healthy women varies between different countries within Asia. In Singapore, the prevalence of HPV infection was 9.31% and was related to penetrative sexual intercourse, multiple sexual partners and low educational level.
Clinical implications from drug–drug and drug–disease interactions in older people

This clinical review summarizes the evidence in relation to clinical outcomes from drug–drug and drug–disease interactions in older people. Exposure to drug–drug interactions is associated with increased risk of hospitalization‐related outcomes in older people. Drug–disease interactions have been linked with adverse drug interactions and adverse drug events in studies of older people. Although the prevalence of drug–drug and drug–disease interactions is common in older people, there are very limited empirical data on important clinical outcomes from drug–drug and drug–disease interactions. Clinical implications of interactions between drugs and geriatric syndromes such as frailty, falls, cognitive impairment, immobility and urinary incontinence should also be considered in older people.
NEUROANATOMICAL DIFFERENCES IN ADHD 1 Neuroanatomical Differences in Attention-Deficit / Hyperactivity Disorder : Influence of Stimulant Medication Administration

Attention-deficit/hyperactivity disorder (ADHD) is a common psychological disorder for which the preferred treatment is with stimulants (methylphenidate). With medication administration to young children becoming exceedingly common, it is important to investigate the neurodevelopment consequences of doing so. Much of the imaging literature that suggests neuroanatomical differences in ADHD patients has not considered the effects of lifetime medication administration in their samples. Animal studies have demonstrated that acute methylphenidate administration to juveniles causes significant brain structure changes. A multi-dimensional examination of the current literature assessing the structural differences in ADHD with respect to medication administration is the focus for this review. It is concluded that the current administration of methylphenidate to young ADHD patients should be reevaluated to incorporate the possibility for medication-induced neurodevelopment.
Energy bounds for fault-tolerant nanoscale designs

The problem of determining lower bounds for the energy cost of a given nanoscale design is addressed via a complexity theory-based approach. The paper provides a theoretical framework that is able to assess the trade-offs existing in nanoscale designs between the amount of redundancy needed for a given level of resilience to errors and the associated energy cost. Circuit size, logic depth and error resilience are analyzed and brought together in a theoretical framework that can be seamlessly integrated with automated synthesis tools and can guide the design process of nanoscale systems comprised of failure prone devices. The impact of redundancy addition on the switching energy and its relationship with leakage energy is modeled in detail. Results show that 99% error resilience is possible for fault-tolerant designs, but at the expense of at least 40% more energy if individual gates fail independently with probability of 1%.