Miracle-dz/UniFAR-FTUs huggingface dataset:
Mycobacterium tuberculosis RpfE crystal structure reveals a positively charged catalytic cleft

Resuscitation promoting factor (Rpf) proteins, which hydrolyze the sugar chains in cell‐wall peptidoglycan (PG), play key roles in prokaryotic cell elongation, division, and escape from dormancy to vegetative growth. Like other bacteria, Mycobacterium tuberculosis (Mtb) expresses multiple Rpfs, none of which is individually essential. This redundancy has left unclear the distinct functions of the different Rpfs. To explore the distinguishing characteristics of the five Mtb Rpfs, we determined the crystal structure of the RpfE catalytic domain. The protein adopts the characteristic Rpf fold, but the catalytic cleft is narrower compared to Mtb RpfB. Also in contrast to RpfB, in which the substrate‐binding surfaces are negatively charged, the corresponding RpfE catalytic pocket and predicted peptide‐binding sites are more positively charged at neutral pH. The complete reversal of the electrostatic potential of the substrate‐binding site suggests that the different Rpfs function optimally at different pHs or most efficiently hydrolyze different micro‐domains of PG. These studies provide insights into the molecular determinants of the evolution of functional specialization in Rpfs.
Effect of dietary tetradecylthioacetic acid on colon cancer growth studied by dynamic contrast enhanced MRI

Purpose: To evaluate the effects of diets supplemented with the modified fatty acid tetradecylthioacetic acid (TTA) and fish protein hydrolysate (FPH) on tumor growth of the human colon cancer cell line SW620, and to investigate the properties of tumor vasculature by dynamic contrast-enhanced MRI in a human tumor xenograft. Experimental design: SW620 cells were grown in vitro in presence of TTA and palmitic acid and proliferation was measured by thymidine incorporation. The xenograft study in mice was performed with four distinct diets: (a) control diet; (b) diet with TTA; (c) diet with TTA and FPH; and (d) diet with FPH. SW620 cells were injected subcutaneously, and Dynamic Contrast Enhanced (DCE) MRI was performed on a Bruker BioSpec 7T system. The data was analyzed by two-compartment modeling of the contrast enhancement, initial area under the curve (IAUC) and by use of relative signal intensity (RSI) distributions. Results: The in vitro cell studies revealed that TTA reduced tumor cell proliferation as a function of both dose and time. The in vivo tumor growth was significantly reduced for the two groups fed TTA, as compared to the control group. The mean 10th percentile RSI, ve and IAUC for the TTA group were significant higher than for the control group Conclusions: This study confirms the growth inhibitory effects of TTA, both in vitro and in vivo, in a colon cancer model. The analysis of DCE MRI data showed that TTA influences the vascular properties of the tumor in addition to the growth.
Implant vendors and hospitals: Competing influences over product choice by orthopedic surgeons

Background: Vendors of hip and knee implants court orthopedic surgeons to adopt their products. Hospitals, which have to pay for these products, now court the same surgeons to help reduce the number of vendors and contain implant costs. Purposes: This study measures the surgeon's perceived alignment of interests with both vendors and hospitals and gauges surgeons' exposure and receptivity to hospital cost-containment efforts. Methodology/Approach: We surveyed all practicing orthopedists performing 12 or more implant procedures annually in Pennsylvania. The survey identified the surgeon's preferred vendor, tenure with that vendor, use of the vendor during residency training, receipt of financial payments from the vendor, alignment of interests with both vendor and hospital stakeholders, and exposure and receptivity to hospital cost-containment efforts. Findings: Surgeons have long-standing relationships with implant vendors, but only a small proportion receive financial payments. Surgeons align most closely with the vendor's sales representative and least closely with the hospital's purchasing manager. Paradoxically, surgeons support hospital efforts to limit the number of vendors but report that their own choice of vendor is not constrained. The major drivers of surgeons' alignment and stance toward cost containment are their tenure with and receipt of financial payments from the vendor. Practice Implications: Hospitals face a competitive disadvantage in capturing the attention of orthopedists, compared with implant vendors. The vendors' advantage stems from historical, financial, and service benefits offered to surgeons. Hospital executives now seek to offer comparable benefits to surgeons.
MMSE-Based Filtering in Presence of Non-Gaussian System and Measurement Noise

The problem of sequential Bayesian estimation in linear non-Gaussian problems is addressed. In the Gaussian sum filter (GSF), the non-Gaussian system noise, the measurement noise, and the posterior state densities are modeled by the Gaussian mixture model (GMM). The GSF is optimal under the minimum-mean-square error (MMSE) criterion, however it is impractical due to the exponential model order growth of the system probability density function (pdf). The proposed recursive estimator, named the Gaussian mixture Kalman filter (GMKF), combines the GSF and the model order reduction procedure. The posterior state density at each iteration is approximated by a lower order density. This model order reduction procedure minimizes the estimated Kullback-Leibler divergence (KLD) of the reduced order density from the original density at each step. The estimation performance of the proposed GMKF is compared with the interactive multiple modeling (IMM), particle filter (PF), Gaussian sum PF (GSPF), and the GSF with mixture reduction (MR) method via simulations. It is shown in several examples that the proposed GMKF outperforms the other tested algorithms in terms of estimation accuracy. The superior estimation performance of the GMKF is obtained at the expense of its computational complexity, which is higher than the IMM and the MR algorithms.
In utero exposure to alcohol alters reactivity of cerebral arterioles

Our goal was to examine whether in utero exposure to alcohol impaired reactivity of cerebral arterioles during development. We fed Sprague–Dawley dams a liquid diet with or without alcohol (3% ethanol) for the duration of pregnancy (21–23 days). Around 4–6 weeks after birth, we examined reactivity of cerebral arterioles to eNOS- (ADP) and nNOS-dependent (NMDA) agonists in the offspring. We found that in utero exposure to alcohol attenuated responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in rats exposed to alcohol in utero. L-NMMA reduced responses to agonists in control rats, but not in rats exposed to alcohol in utero. Treatment of dams with apocynin for the duration of pregnancy rescued the impairment in reactivity to ADP and NMDA in the offspring. Protein expression of NOX-2 and NOX-4 was increased in alcohol rats compared to control rats. We also found an increase in superoxide levels in the cortex of rats exposed to alcohol in utero. Our findings suggest that in utero exposure to alcohol impairs eNOS and nNOS reactivity of cerebral arterioles via a chronic increase in oxidative stress.
Leptin increases luteinizing hormone secretion of fasting female rats.

PURPOSE To investigate whether leptin acts directly on the anterior hypophysis by influencing gonadotropin secretion in vivo. MATERIALS AND METHODS Cycling female rats were catheterised for frequent blood sampling and were either fasted or allowed free access to food. Stereotactic lesion of the medial preoptic area (MPOA) of the hypothalamus was performed in order to eliminate gonadotropin releasing hormone (GnRH) production. Leptin was administered at a dose of one mg/kg i.v. and blood samples were taken just before leptin administration and then after 30, 60, 90, 120, and 180 minutes. Plasma gonadotropin levels were determined. With completion of sampling, the brains were removed and the localisation of the lesions was verified histologically. RESULTS Leptin at one mg/kg induced an increase in luteinizing hormone (LH) secretion in fasting rats, both in those with a lesion and those with intact medial preoptic area with a peak occurring 90 minutes after infusion. The augmenting effect was more prominent when the hypothalamus was intact. There was no effect in fed animals with or without lesion. Similarly, no effect was observed on follicle stimulating hormone (FSH) levels in any of the experimental groups. CONCLUSIONS Leptin acts directly on the hypophysis enhancing LH but not FSH secretion. Nutritional state influences leptin's effect on the hypothalamus and the hypophysis.
Optimal Power Allocation for Coordinated Transmission in Cognitive Radio Networks

Cognitive radio (CR) technology has been developed to solve the spectrum-underutilization problem. In CR networks, the CR users have opportunities to access the licensed spectrum bands assigned to the primary users (PUs). Since the PUs have priorities to use the bands, the CR users are not allowed to generate unacceptable interference to them. In this paper, we investigate power allocation schemes for source and relay nodes in CR with direct and relay link. We show that there is a significant benefit to the system rate by jointly distributing the transmitting power. Three schemes are considered, where particularly the scheme based on analogue network coding shows significant superior performance to other two classic schemes. The optimum power allocation is derived analytically. The proposed schemes are verified by the simulations which also show the impact of different positions of relay node and the primary user locations on power allocation solutions.
Primary auditory stream segregation and perception of order in rapid sequences of tones.

A recent finding of the inability of listeners to judge the order of three or four nonspeech sounds presented in a repetitive cycle is explained by the concept of stream segregation. Two experiments showed that at high presention rates of a short cycle of six tones (three high and three low), 5s invariably segregated the tone sequences into streams based on frequency and could perceive only those patterns relating elements of the same subjective stream.
Molecular cloning, expression and association study with reproductive traits of the duck LRP8 gene

Abstract 1. Two splice variants of duck LRP8 were identified, one containing 8 ligand-binding repeats (LRP8-1) and the other containing only 7 repeats (LRP8-2). The two transcripts share ~71–91% nucleic acid identity and ~65–94% amino acid identity with their counterparts in other species. A phylogenetic tree based on amino acid sequences shows that duck LRP8 proteins are closely related to those of chicken, turkey and zebra finch. 2. The semi-quantitative reverse transcription polymerase chain reaction (RT-PCR )analysis indicates that the two transcripts are expressed in all the examined tissues, and the LRP8-1 transcript is more highly expressed in hypothalamus, ovary and pituitary gland than in other detected tissues. 3. Six single nucleotide polymorphisms (SNPs) were identified in the coding region. Association analysis demonstrated that the c.528C > T genotypes were associated with egg production (EP) (EP210d, EP300d and EP360d), age at laying the first egg (AFE) and body weight at sexual maturity (BWSM). The c.1371A > G genotypes were associated with egg production (EP210d, EP300d and EP360d). 4. The haplotypes of c.528C > T and c.1371A > G were associated with EP (EP210d, EP300d and EP360d), yolk weight (YW), albumen weight (AW), egg weight (EW), BWSM and the first egg weight (FEW). 5. Duck LRP8 gene was associated with some reproductive traits and is an important candidate gene for the genetic selection of improved reproductive traits.
University of Groningen Therapeutic targeting and patient selection for cancers with homologous recombination defects

Introduction: DNA double-strand breaks (DSBs) are toxic DNA lesions that can be repaired by nonhomologous end-joining (NHEJ) or homologous recombination (HR). Mutations in HR genes elicit a predisposition to cancer; yet, they also result in increased sensitivity to certain DNA damaging agents and poly (ADP-ribose) polymerase (PARP) inhibitors. To optimally implement PARP inhibitor treatment, it is important that patients with HR-deficient tumors are adequately selected. Areas covered: Herein, the authors describe the HR pathway mechanistically and review the treatment of HR-deficient cancers, with a specific focus on PARP inhibition for BRCA1/2-mutated breast and ovarian cancer. In addition, mechanisms of acquired PARP inhibitor resistance are discussed. Furthermore, combination therapies with PARP inhibitors are reviewed, in the context of both HRdeficient and HR-proficient tumors and methods for proper patient selection are also discussed. Expert opinion: Currently, only patients with germline or somatic BRCA1/2 mutations are eligible for PARP inhibitor treatment and only a proportion of patients respond. Patients with HR-deficient tumors caused by other (epi)genetic events may also benefit from PARP inhibitor treatment. Ideally, selection of eligible patients for PARP inhibitor treatment include a functional HR read-out, in which cancer cells are interrogated for their ability to perform HR repair and maintain replication fork stability. ARTICLE HISTORY Received 18 January 2017 Accepted 19 April 2017
Effects of low- and moderate-intensity training in spinal cord-injured persons.

This study examined the applicability of exercise prescription guidelines established for the able-bodied to spinal cord-injured (SCI) persons. Two SCI groups performed wheelchair ergometry (WCE) 20 min three times per week for 8 wk. Low-intensity (LI, N = 6) and moderate-intensity (MI, N = 5) groups trained at 50-60% and 70-80% maximal heart rate reserve (HRR), respectively. The subjects completed an incremental discontinuous maximal WCE test to exhaustion pre- and post-training. A submaximal WCE test consisting of 4-min exercise stages at power outputs of 5, 10, and 15 W was also performed pre- and post-training. Blood samples were collected before and after training and analyzed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C). The TC/HDL-C ratio was calculated. Both groups exhibited no significant changes (P greater than 0.10) in VO2max, HRmax, POmax, lactate (La)max, and VO2 at 4 mmol [La]. No pre- to post-training differences were recorded in the LI group for submaximal VO2, HR, VE, La, and ratings of perceived exertion (RPE). The MI group had significantly lower (P less than or equal to 0.10) post-training submaximal HR, La, and RPE and no changes in VO2 or VE. Blood lipid levels remained unaltered in the LI group, while the MI group exhibited significant increases in HDL-C and decreases in TG, LDL-C, and the TC/HDL-C ratio. The maximal test data revealed that 8 wk of LI and MI wheelchair ergometry training did not improve VO2max in SCI persons. (ABSTRACT TRUNCATED AT 250 WORDS)
Ethanol effects on nitric oxide production in cerebral pial cultures.

BACKGROUND Although alcohol abusers are known to have higher incidences of hemorrhagic cerebrovascular diseases, it is not known whether these changes are associated with ethanol (EtOH) action on nitric oxide (NO) production in the cerebrovascular cells. The purpose of this study was to examine the effects of EtOH treatment on basal and cytokine-induced NO production in cortical pial cultures. METHODS Cell cultures for this study included murine primary pial vascular cells, primary glial cells and cortical neurons. These cells were exposed to cytokines or EtOH for 24 to 48 hr. The culture media were used for measurement of nitrite, as an indication for NO release, and lactate dehydrogenase (LDH), as an index of cell membrane integrity. In addition, immunocytochemical determinations were carried out to identify cell types and to assess inducible nitric oxide synthase (iNOS). RESULTS Exposure of primary pial vascular cultures to cytokines that consisted of interleukin-1 beta (IL-1 beta; 250 pg/mL) and interferon-gamma (IFNgamma; 2 ng/mL) or to EtOH (50 to 100 mM) for 24 to 48 hr significantly elevated NO production. NO production could be attenuated by N-nitro-L-arginine (N-arg), a nonspecific NOS inhibitor, or aminoguanidine (AG), an iNOS inhibitor. Increased iNOS immunoreactivity was observed in cytokines- or EtOH-treated pial cells. When pial cells were cocultured with cortical neurons, prolonged EtOH exposure led to a large increase in NO production as well as LDH release. However, this increase was not observed in pial culture alone or in mixed cortical culture. Nevertheless, inhibition of NO production with N-arg or AG did not alter the EtOH-induced LDH release in the pial cells cocultured with cortical neurons. CONCLUSION These results show that EtOH exposure led to increased production of NO in primary pial cell culture. In mixed culture that contained cortical neurons and pial cells, EtOH induced increase in NO as well as LDH release, which is an indication of loss of cell membrane integrity. However, EtOH-mediated LDH release in mixed cortical pial cultures was not a consequence of the increase in NO production by these cells. Studies that use mixed cortical-pial cultures may provide a unique in vitro system for examining the interactions among glial cells, neurons, and cerebrovascular cells.
Molecular Cytogenetic Characterization of Ciona intestinalis Chromosomes

Abstract The compact genome of the ascidian Ciona intestinalis has been sequenced. Chromosome karyotype and mapping of the genome sequence information on each of the 14 pairs of chromosomes are essential for genome-wide studies of gene expression and function in this basal chordate. Although the small chromosome size (most pairs measuring less than 2 μm) complicates accurate chromosome pairing based on morphology alone, the present results suggest that 20 chromosomes are metacentric and 8 are submetacentric or subtelocentric, and two pairs of large chromosomes (#1 and #2) were defined. The characterization of chromosomes by FISH and staining with propidium iodide indicated that 18S/28S ribosomal gene repeats are present in the short arms of three pairs of chromosomes and that the short arms of these pairs show remarkable size polymorphism. In addition, each chromosome was characterized molecular cytogenetically by mapping representative BAC clones with FISH. The present study is therefore a first step in expanding the karyotype analysis and entire physical mapping of the genome sequence of Ciona intestinalis.
Revisiting the Effective Rate of Protection in the Late Stages of Chinese Industrialisation

In this paper, we generalise conventional measures of the effective rate of protection by: (i) relaxing their small-country assumptions; (ii) taking into account multiple stages of production; and (iii) abstracting away from their assumptions on the time-invariance of the underlying technology using annual IO tables. We apply our new measure to China's structure of tariff protection from 1992 to 2010. When compared to conventional measures, we find its effective rates of protection to be smaller in magnitude and even negative in some sectors. The new measures are also related to industry characteristics in sensible ways, calling into question the applicability of conventional measures in the context of present-day China.
SEROLOGIC SURVEY FOR SELECTED VIRAL PATHOGENS IN FREE-RANGING ENDANGERED EUROPEAN MINK (MUSTELA LUTREOLA) AND OTHER MUSTELIDS FROM SOUTH-WESTERN FRANCE

To investigate the possible role of selected pathogens in the decline of endangered European mink (Mustela lutreola) populations and the potential for these pathogens to affect mink survival, a serologic survey was conducted using serum samples collected from March 1996 to March 2003 in eight departments of south-western France. In total, 481 free-ranging individuals of five mustelid species (including the European mink) were tested. Sympatric mustelids can serve as sentinels to determine the presence of antibodies to viruses in the study area that could potentially infect mink. Antibodies to Canine distemper virus (CDV) were detected in all species; 9% of 127 European mink, 20% of 210 polecats (Mustela putorius), 5% of 112 American mink (Mustela vison), 33% of 21 stone marten (Martes foina) and 5% of 20 pine marten (Martes martes). Antibody prevalence was significantly higher in stone marten and polecats, possibly because their ranges overlap more closely with that of domestic species than that of the other species tested. Antibodies to Canine adenovirus were detected in all species but the pine marten; antibody prevalence estimates ranging from 2% to 10%. Antibodies to canine parainfluenza virus were detected in 1% of European mink, 1% of American mink and 5% of tested polecats but were not detected in Martes species. Antibodies to Rabies virus (RV) were detected in three animals, possibly because of interspecies transmission of bat lyssaviruses as the sampling area is considered to be free of RV, or to a lack of test specificity, as antibody titers were low. The high antibody prevalence to potentially lethal CDV suggests that this pathogen could have significant effects on the free-ranging populations and has implications for the conservation efforts for the endangered European mink.
Closed Reduction of Fractured Anterior Wall of the Frontal Sinus Using Threaded K-Wires

Abstract Classic approach of the anterior wall of frontal sinus fracture involves bicoronal or direct forehead incisions. However, these methods have some disadvantages, for example, paresthesia, scarring, and even alopecia. The purpose of this study was to introduce the simple and effective method of reduction of the anterior wall of frontal sinus fracture with threaded K-wires. Thirteen patients with fracture of the anterior wall of the frontal sinus underwent our method from December 2005 to September 2011. The distance of threaded K-wires was measured by facial computed tomography, and those marks were made directly on the threaded K-wires with an aseptic pencil. Closed reduction with these K-wires was tried carefully until a tolerable level was attained with digital palpation. Facial computed tomography was performed the following day for comparison. On postoperative day 7, following disappearance of swelling, the patient and the doctor mutually evaluated the outcome; both were satisfied with the results. The postoperative course was uneventful, without any complications. Unlike other methods, this method can guarantee a short operating time, effective reduction, and inconspicuous scar.