Miracle-dz/UniFAR-FTUs huggingface dataset:
ATM-dependent Phosphorylation of Human Rad9 Is Required for Ionizing Radiation-induced Checkpoint Activation*

ATM (ataxia-telangiectasia-mutated) is a Ser/Thr kinase involved in cell cycle checkpoints and DNA repair. Human Rad9 (hRad9) is the homologue of Schizosaccharomyces pombe Rad9 protein that plays a critical role in cell cycle checkpoint control. To examine the potential signaling pathway linking ATM and hRad9, we investigated the modification of hRad9 in response to DNA damage. Here we show that hRad9 protein is constitutively phosphorylated in undamaged cells and undergoes hyperphosphorylation upon treatment with ionizing radiation (IR), ultraviolet light (UV), and hydroxyurea (HU). Interestingly, hyperphosphorylation of hRad9 induced by IR is dependent on ATM. Ser272 of hRad9 is phosphorylated directly by ATM in vitro. Furthermore, hRad9 is phosphorylated on Ser272 in response to IR in vivo, and this modification is delayed in ATM-deficient cells. Expression of hRad9 S272A mutant protein in human lung fibroblast VA13 cells disturbs IR-induced G1/S checkpoint activation and increased cellular sensitivity to IR. Together, our results suggest that the ATM-mediated phosphorylation of hRad9 is required for IR-induced checkpoint activation.
Association study of brain‐derived neurotrophic factor in adults with a history of childhood onset mood disorder

Brain‐derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant‐like effects in animals. BDNF gene polymorphisms have been associated with bipolar disorder. We tested two genetic polymorphisms of BDNF for their association with childhood‐onset mood disorders (COMD) within the context of a case‐control design. Two BDNF polymorphisms, a dinucleotide repeat (GT)n, and a single nucleotide polymorphism (SNP) in the coding region, val66met, were genotyped in 99 adults with a history of COMD and matched psychiatrically healthy controls. A genomic control (GC) method was used to evaluate population substructure. Alleles at (GT)n were highly associated with COMD in this sample (χ2 = 17.8; d.f. = 5; P = 0.0032). The odds of carrying the 168 bp allele were 3.94 times greater for cases than controls (CI = 1.72–9.04). Alleles of val66met were not significantly associated with COMD. GC analysis suggested population substructure was not a confounder of association. Analysis of haplotypes, in which (GT)n was treated as a binary variable (long vs. short alleles), provided significant evidence that the haplotype val/short contributes to liability to COMD. The BDNF (GT)n marker and the val/short haplotype are associated with COMD in this sample, in accordance with the previously described neurotrophic hypothesis of depression and some previous studies of association for bipolar disorder and neuroticism. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience. wiley.com/jpages/0148‐7299:1/suppmat/index.html. © 2004 Wiley‐Liss, Inc.
Zeros and Poles of Linear Continuous-Time Periodic Systems: Definitions and Properties

The paper deals with definitions of zeros and poles and their features in finite-dimensional linear continuous-time periodic (FDLCP) systems under a harmonic framework. More precisely, system and transfer zeros and poles in the harmonic wave-to-wave sense are defined on what we call the regularized harmonic system operators and the harmonic transfer operators of FDLCP systems by means of regularized determinants; then their composition and properties related to system structures are examined via the Floquet theory and controllability/observability decompositions of FDLCP systems. The study shows that under mild assumptions, the harmonic transfer operators of FDLCP systems are analytic and meromorphic, on which zeros and poles are well-defined. Basic zero/pole relationships are established, which are similar to their linear time-invariant counterparts and in particular explicate some interesting harmonic wave-to-wave behaviors of FDLCP systems. The results are significant in analysis and synthesis of FDLCP systems when the harmonic approach is adopted.
Renal function changes and seasonal temperature in patients undergoing cardiac surgery

Some observations in humans and other mammalians suggest that serum creatinine (SC) and estimated glomerular filtration rate (eGFR) may change during the warm season. The objective of this study is to determine if temperature-dependent seasonal changes in levels of SC and eGFR are detectable in cardiac surgery patients, with associated changes in postoperative acute kidney injury (AKI) incidence. This is a single-center retrospective study based on the institutional database of cardiac surgery in the period 2000–2012. Sixteen-thousand and twenty-three consecutive adult patients undergoing cardiac surgery comprised the study population. Baseline and postoperative SC and eGFR values, and AKI rate according to the month when surgery was performed were measured. The month-related changes SC and eGFR, and AKI rate, were assessed in crude and adjusted models, and their association with the correspondent meteorological data registered at the time of surgery was tested. Patients operated in the six warmest months (May through October) had a significant (p < 0.001) higher value of baseline SC (1.17 ± 0.7 mg/dL) versus the six coldest months (1.12 ± 0.6 mg/dL), and a significantly (p = 0.031) higher value of peak postoperative SC (1.31 ± 0.85 mg/dL) versus the 6 coldest months (1.28 ± 0.89), with maximum values between July and August. A similar behaviour was found for eGFR. After adjustment for other confounders, the AKI rate was not significantly different in the warmest months, even if a trend towards a higher rate in August was observed (odds ratio 1.287, 95% confidence interval 0.96–1.74, p = 0.097). Baseline (p < 0.001) and peak postoperative (p = 0.0054) serum creatinine levels were significantly higher for increasing mean ambient temperature. Humidity and wind speed were negatively associated with pre- and postoperative eGFR. In conclusion, patients operated during the warmest season, have higher levels of SC and lower levels of eGFR, without a correspondent increase in the AKI rate. Different hypotheses underlying this pattern are generated by this study, including a dehydration status, concomitant anemia, and a higher transfusion rate.
Skin infection due to Geomyces pannorum var. pannorum

Geomyces pannorum var. pannorum is an ubiquitous saprophytic fungus frequently isolated from the soil and from air samples. It has rarely been reported as an animal or plant pathogen and it is an occasional aetiological agent of superficial infection of skin and nails in humans. Here, we report a case of superficial infection of the skin due to this fungus in a healthy man. The patient was treated orally with terbinafine 250 mg daily and topic bifonazole with complete resolution in 2 months.
Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer.

PURPOSE Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer. PATIENTS AND METHODS Twenty-two patients were treated in a dose-escalation trial with 100 microg, 500 microg, or 1,500 microg plasmid DNA, coadministered intradermally with 200 microg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment. RESULTS No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFN gamma-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054). CONCLUSION The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.
Identification of primitive faults in combinational and sequentialcircuits

This paper presents a method of primitive fault identification and test generation for combinational and nonscan sequential circuits. It uses the concept of sensitizing cubes to obtain input vectors that statically sensitize primitive faults in combinational circuits. The same technique is used to identify combinationally primitive faults in the next-state and output logic of sequential circuits. Such faults are primitive if and only if the fault effects on paths to state variable flip-flops can be propagated to a primary output (PO). Test sequences, including initializing sequences from a reset state and sequences that propagate fault effects from flip-flops to POs, are generated for primitive faults, wherever possible. The proposed method has been implemented and used to derive tests for primitive faults in the ISCAS'89 and MCNC'91 benchmark circuits. It was able to find all primitive faults and also obtain robust tests for a large fraction of them when the circuits were treated as combinational. When the same circuits were treated as nonscan sequential circuits, all primitive faults could not be found because fault propagation had to be limited to a relatively small number of time frames.
Lambda bacteriophage-mediated transduction of ColE1 deoxyribonucleic acid having a lambda bacteriophage-cohesive end site: selection of packageable-length deoxyribonucleic acid

An in vitro recombinant ColE1-cos lambda deoxyribonucleic acid (DNA) molecule, pKY96, has 70% of the length of lambda phage DNA. The process of lambda phage-mediated transduction of pKY96 generated a small amount of transducing phage particles containing ColE1-cos lambda DNA molecules of 80 or 101% of the length of lambda phage DNA, in addition to those containing original pKY96 DNA molecules. The newly isolated larger plasmid DNAs were transduced 100 times more efficiently than pKY96 DNA. Their structures were compared with that of a prototype pKY96 DNA, and the mechanism of the formation of these molecules is discussed.
FGF23 and primary hyperparathyroidism: is there a link?

INTRODUCTION Data regarding the role of FGF23 in primary hyperparathyroidism (PHPT) are scarce and discordant. Our study aimed at evaluating the prognostic impact of FGF23 upon the clinical and biochemical evolution of PHPT. MATERIALS AND METHODS 42 patients with ages between 30 - 80 years diagnosed with PHPT caused by a sporadic, solitary parathyroid adenoma and referred to surgery (minimally invasive parathyroidectomy) were prospectively included in the study. Serum levels of FGF23, PTH, 25(OH)D3, calcium, phosphate, total procollagen type 1 N-terminal propeptide and C-terminal telopeptide of type I collagen were determined at baseline (preoperatory), 1 day after surgery and, in 13 patients, also prospectively at 3, 6 and 12 months. Bone mineral density (BMD) was also evaluated before surgery in all patients and 12 months after surgery in the 13 followed up patients. RESULTS In the 42 PHPT patients with D hypovitaminosis (mean 25(OH)D3 levels of 16.2±1.5 ng/ml), preoperatory serum FGF23 concentration was within the normal range (75.55±3.39 pg/ml) and remained unchanged 1 day postoperatory (81.69 ± 4.67 pg/ml, p= non-significant). The 13 patients followed prospectively up to 12 months after surgery also showed unmodified FGF23 levels (80.9 ± 11.03 pg/ml, p=non-significant), despite PTH and calcium normalization and vitamin D replenishment. Preoperatory FGF23 negatively correlated to PTH (r = -0.37, p = 0.038), but not to 25(OH)D3, calcium, phosphate, bone mass or metabolism markers. CONCLUSIONS In PHPT, correlations between FGF23 and PTH seem rather an epiphenomenon. Therefore, we reckon that FGF23 evaluation and dynamics are not informative regarding PHPT severity.
Crystal structure of human recombinant ornithine aminotransferase.

Ornithine aminotransferase (OAT), a pyridoxal-5'-phosphate dependent enzyme, catalyses the transfer of the delta-amino group of L-ornithine to 2-oxoglutarate, producing L-glutamate-gamma-semialdehyde, which spontaneously cyclizes to pyrroline-5-carboxylate, and L-glutamate. The crystal structure determination of human recombinant OAT is described in this paper. As a first step, the structure was determined at low resolution (6 A) by molecular replacement using the refined structure of dialkylglycine decarboxylase as a search model. Crystallographic phases were then refined and extended in a step-wise fashion to 2.5 A by cyclic averaging of the electron density corresponding to the three monomers within the asymmetric unit. Interpretation of the resulting map was straightforward and refinement of the model resulted in an R-factor of 17.1% (Rfree=24.3%). The success of the procedure demonstrates the power of real-space molecular averaging even with only threefold redundancy. The alpha6-hexameric molecule is a trimer of intimate dimers with a monomer-monomer interface of 5500 A2 per subunit. The three dimers are related by an approximate 3-fold screw axis with a translational component of 18 A. The monomer fold is that of a typical representative of subgroup 2 aminotransferases and very similar to those described for dialkylglycine decarboxylase from Pseudomonas cepacia and glutamate-1-semialdehyde aminomutase from Synechococcus. It consists of a large domain that contributes most to the subunit interface, a C-terminal small domain most distant to the 2-fold axis and an N-terminal region that contains a helix, a loop and a three stranded beta-meander embracing a protrusion in the large domain of the second subunit of the dimer. The large domain contains the characteristic central seven-stranded beta-sheet (agfedbc) covered by eight helices in a typical alpha/beta fold. The cofactor pyridoxal-5'-phosphate is bound through a Schiff base to Lys292, located in the loop between strands f and g. The C-terminal domain includes a four-stranded antiparallel beta-sheet in contact with the large domain and three further helices at the far end of the subunit. The active sites of the dimer lie, about 25 A apart, at the subunit and domain interfaces. The conical entrances are on opposite sides of the dimer. In the active site, R180, E235 and R413 are probable substrate binding residues. Structure-based sequence comparisons with related transaminases in this work support that view. In patients suffering from gyrate atrophy, a recessive hereditary genetic disorder that can cause blindness in humans, ornithine aminotransferase activity is lacking. A large number of frameshift and point mutations in the ornithine aminotransferase gene have been identified in such patients. Possible effects of the various point mutations on the structural stability or the catalytic competence of the enzyme are discussed in light of the three-dimensional structure.
Activity of Tedizolid in Methicillin-Resistant Staphylococcus epidermidis Experimental Foreign Body-Associated Osteomyelitis

ABSTRACT We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia, and a stainless steel wire with a precolonized MRSE biofilm was implanted. Following a 1-week infection period, 92 rats received either no treatment (n = 17) or 14 days of intraperitoneal tedizolid (n = 15), tedizolid plus rifampin (n = 15), rifampin (n = 15), vancomycin plus rifampin (n = 15), or vancomycin (n = 15). Quantitative bone and wire cultures were performed after treatment completion and also 1 week after infection in a separate group of five rats. The median quantity of staphylococci in bone after the 1-week infection period was 4.89 log10 CFU/g bone (interquartile range, 3.83 to 5.33 log10 CFU/g bone); staphylococci were recovered from all associated wires. A median quantity of staphylococci of 3.70 log10 CFU/g bone was detected in bones of untreated control rats after 3 weeks. Quantities of staphylococci in bones of all treatment groups except the group receiving vancomycin alone (2.78 log10 CFU/g) were significantly lower than those for untreated controls, with no staphylococci being detected in the groups receiving rifampin monotherapy, tedizolid-plus-rifampin combination therapy, and vancomycin-plus-rifampin combination therapy. Quantities of staphylococci on wires from all treatment groups that included rifampin were significantly lower than those for untreated controls. No resistance to rifampin, tedizolid, or vancomycin was detected. Tedizolid combined with rifampin was active in a rat model of MRSE foreign body-associated osteomyelitis.
Polarization-Independent Plasmon-Induced Transparency in a Fourfold Symmetric Terahertz Metamaterial

Metamaterials that reveal fascinating and unique resonant properties allow for adequate control of electromagnetic waves at will. Recently, considerable studies have shown that the plasmon-induced transparency (PIT) effect can be realized by metamaterials via destructive interference between different resonance modes; however, most of them are sensitive to the polarization of incident wave. Here, we demonstrate a polarization-independent PIT metamaterial functioning in the terahertz regime. The proposed structure has a fourfold symmetry and exhibits a typical PIT behavior due to the coupling effect of four different modes, yielding polarization-independent characteristics.
Building a Bridge Between Journal Articles and Research Data: The PKP-Dataverse Integration Project

A growing number of funding agencies and international scholarly organizations are requesting that research data be made more openly available to help validate and advance scientific research. Thus, this is an opportune moment for research data repositories to partner with journal editors and publishers in order to simplify and improve data curation and publishing practices. One practical example of this type of cooperation is currently being facilitated by a two year (2012-2014) one million dollar Sloan Foundation grant, integrating two well-established open source systems: the Public Knowledge Project’s (PKP) Open Journal Systems (OJS), developed by Stanford University and Simon Fraser University; and Harvard University’s Dataverse Network web application, developed by the Institute for Quantitative Social Science (IQSS). To help make this interoperability possible, an OJS Dataverse plugin and Data Deposit API are being developed, which together will allow authors to submit their articles and datasets through an existing journal management interface, while the underlying data are seamlessly deposited into a research data repository, such as the Harvard Dataverse. This practice paper will provide an overview of the project, and a brief exploration of some of the specific challenges to and advantages of this integration.
PSSs design based on PMUs signals to enhance the stability of inter-area oscillations of interconnected power systems

Poorly damped or unstable mode of inter-area oscillations is undesirable as they result in inefficient operation of the power systems. Without proper remedial actions, these oscillations can result in power systems separation or major blackouts. Adequate damping of these oscillations is a pre-requisite for secure operation of power systems. An available solution to damp out these inter-area oscillations is the addition of power system stabilizers (PSSs) to the excitation systems of the generators. Although conventional PSSs exist on many generators, their effect is only on the damping of local oscillations and do not effectively damp out inter-area oscillations. In this paper a robust PSS based on PMU signals is proposed to ensure satisfactory damping of inter-area oscillations which result in enhancing system stability and maximizing power transfer capacity. The signal input to the proposed PSSs are detected and transmitted by the PMUs. Modal analysis and time-domain transient simulation results show that inter-area oscillation damping was improved effectively with the proposed PSSs.
Current progress on microRNAs‐based therapeutics in neurodegenerative diseases

MicroRNAs (miRNAs)‐based therapy has recently emerged as a promising strategy in the treatments of neurodegenerative diseases. Thus, in this review, the most recent and important challenges and advances on the development of miRNA therapeutics for brain targeting are discussed. In particular, this review highlights current knowledge and progress in the field of manufacturing, recovery, isolation, purification, and analysis of these therapeutic oligonucleotides. Finally, the available miRNA delivery systems are reviewed and an analysis is presented in what concerns to the current challenges that have to be addressed to ensure their specificity and efficacy. Overall, it is intended to provide a perspective on the future of miRNA‐based therapeutics, focusing the biotechnological approach to obtain miRNAs. WIREs RNA 2017, 8:e1409. doi: 10.1002/wrna.1409
Analogy, Cognitive Architecture and Universal Construction: A Tale of Two Systematicities

Cognitive science recognizes two kinds of systematicity: (1) as the property where certain cognitive capacities imply certain other related cognitive capacities (Fodor and Pylyshyn); and (2) as the principle that analogical mappings based on collections of connected relations are preferred over relations in isolation (Gentner). Whether these kinds of systematicity are two aspects of a deeper property of cognition is hitherto unknown. Here, it is shown that both derive from the formal, category-theoretic notion of universal construction. In conceptual/psychological terms, a universal construction is a form of optimization of cognitive resources: optimizing the re-utilization of common component processes for common task components. Systematic cognitive capacity and the capacity for analogy are hallmarks of human cognition, which suggests that universal constructions (in the category-theoretic sense) are a crucial component of human cognitive architecture.
The Anemia of Heart Failure

Anemia is common in congestive heart failure (CHF) and is associated with an increased mortality and morbidity. The most likely causes of anemia are chronic kidney disease (CKD) and excessive cytokine production, both of which can cause depression of erythropoietin (EPO) production and bone marrow activity. The cytokines also induce iron deficiency by both reducing gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes. Iron deficiency can cause thrombocytosis which might also contribute to cardiovascular complications in both CHF and CKD and is partially reversible with iron treatment. Thus attempts to control this anemia will have to consider both the use of erythropoiesis-stimulating agents (ESA), such as EPO, as well as oral and, probably more importantly, intravenous (IV) iron. The many studies on anemia in CHF patients treated with ESA and oral or IV iron, and even with IV iron without ESA have up to now shown a quite consistent positive effect on hospitalization, fatigue, shortness of breath, quality of life, exercise capacity, and β-natriuretic peptide reduction, in the absence of increased cardiovascular damage related to the therapy. Adequately powered long-term placebo-controlled studies of ESA and/or IV iron are currently being carried out and their results are eagerly awaited.