Miracle-dz/UniFAR-FTUs huggingface dataset:
Both transmembrane domains of SecG contribute to signal sequence recognition by the Escherichia coli protein export machinery

A chimeric protein containing the uncleaved signal sequence of plasminogen activators inhibitor‐2 (PAI2) fused to alkaline phosphatase (AP) interferes with Escherichia coli protein export and arrests growth. Suppressors of this toxicity include secG mutations that define the Thr‐41–Leu‐42–Phe‐43 (TLF) domain of SecG. These mutations slow down the export of PAI2‐AP. Another construct encoding a truncated PAI2 signal sequence (hB‐AP) is also toxic. Most suppressors exert their effect on both chimeric proteins. We describe here five secG suppressors that only suppress the toxicity of hB‐AP and selectively slow down its export. These mutations do not alter the TLF domain: three encode truncated SecG, whereas two introduce Arg residues in the transmembrane domains of SecG. The shortest truncated protein only contains 13 residues of SecG, suggesting that the mutation is equivalent to a null allele. Indeed, a secG disruption selectively suppresses the toxicity of hB‐AP. However, the missense mutations are not null alleles. They allow SecG binding to SecYE, although with reduced affinity. Furthermore, these mutated SecG are functional, as they facilitate the export of endogenous proteins. Thus, SecG participates in signal sequence recognition, and both transmembrane domains of SecG contribute to ensure normal signal sequence recognition by the translocase.
A systematic approach for ranking football players within an integrated DEA‐OWA framework

The ranking of players has always been an important input for key decisions in the football industry. This paper introduces a systematic methodology for ranking football players through objective performance factors within a framework that integrates data envelopment analysis and ordered weighted averaging operators. Players from European Premier League Football clubs are selected and ranked under a decision setting that involves the players' desirable and undesirable performance factors alongside the attitude of the decision maker. The robustness of the proposed methodology is evaluated using different levels of optimism of the decision maker.
Clinical characteristics of polycystic ovary syndrome in Indian women

Background: Polycystic ovary syndrome (PCOS) is common diagnosis in women presenting with infertility. All the dimensions of PCOS have not been completely explored. Many studies have tried to characterize the exact presentation of the disease. In this study we studied clinical features of PCOS in Indian women to characterize different phenotypes of this syndrome. Prevalence of acanthosis nigricans (AN) as surrogate marker of insulin resistance, obesity, hirsutism and hypothyroidism in PCOS women have been simultaneously studied. Materials and Methods: Present work is a non comparative cross-sectional open label study carried out over a period of 18 months in an endocrinology hospital in western Maharashtra, India. Results and Conclusion: Authors conclude that PCOS occurs both in obese and non-obese women; AN and hirsutism occur in equal proportion of patients. AN is correlated with obesity. Hormonal dysfunctions in PCOS manifested together or independently. PCOS women can be sub grouped based on clinical features suggestive of endocrinological malfunctions and can be investigated accordingly for selection of appropriate treatment modalities.
Improving combination antiretroviral therapy by targeting HIV-1 gene transcription

ABSTRACT Introduction: Combination Antiretroviral Therapy (cART) has not allowed the cure of HIV. The main obstacle to HIV eradication is the existence of quiescent reservoirs. Several other limitations of cART have been described, such as strict life-long treatment and high costs, restricting it to Western countries, as well as the development of multidrug resistance. Given these limitations and the impetus to find a cure, the development of new treatments is necessary. Areas covered: In this review, we discuss the current status of several efficient molecules able to suppress HIV gene transcription, including NF-kB and Tat inhibitors. We also assess the potential of new proteins belonging to the intriguing DING family, which have been reported to have potential anti-HIV-1 activity by inhibiting HIV gene transcription. Expert opinion: Targeting HIV-1 gene transcription is an alternative approach, which could overcome cART-related issues, such as the emergence of multidrug resistance. Improving cART will rely on the identification and characterization of new actors inhibiting HIV-1 transcription. Combining such efforts with the use of new technologies, the development of new models for preclinical studies, and improvement in drug delivery will considerably reduce drug toxicity and thus increase patient adherence.
Impact of intellectual capital on corporate performance: evidence from the Arab region

Purpose The purpose of this paper is twofold: first, to fill a gap in the intellectual capital (IC) literature by providing insights into the relationship between IC and corporate performance among Arab companies and second, to challenge the validity of the Value Added Intellectual Coefficient (VAIC) as a measure of IC’s contribution to performance. Design/methodology/approach The research sample included 100 publicly traded Arab companies selected by Forbes Middle East and ranked as top performers in terms of sales, profits, assets, and market value. The methodology included assessing the impact of IC components on company earnings, profitability, efficiency, and market performance for the period between 2011 and 2015. Research hypotheses were tested through the presentation of descriptive statistics, normality tests, correlation matrix, and multiple regression models. Findings The research yielded ambiguous results. Earnings and profitability were significantly affected by structural and physical capital; efficiency was determined primarily by physical capital; and market performance was mainly influenced by human capital. Research limitations/implications The main limitation of the research comes from disadvantages of VAIC as the measure of IC’s contributions to performance. Originality/value The paper fills a void in the study of IC and corporate performance among Arab companies.
Multi-objects recognition using unsupervised learning and classification

The objective of this paper is to develop a real-time unsupervised learning method to detect multi-objects. Variance and gradient variance, as main texture feature, are compressed based on PCA (Principal Component Analysis) to get initial classifications of clusters via K-means algorithm in the image frame. The cluster-kernel of each class, the nucleus as we defined, is figured out through shifting the sampling area in each cluster. Based on the nucleus, the policy of cell expansion as we designed is operated to merge different classes into one object which turns the work from feature level into object level. All potential objects and cells of the objects are detected and labeled in the frame. The descriptors of each object are employed as hypothesis for the next frames object-classification. Our results demonstrate that it is possible and fast to recognize multi-objects without and training model or labeled data. The process of learning could be operated with initial clustering and automatic updating with information of the new classification.
Attenuated frontal activation during a verbal fluency task in patients with schizophrenia.

OBJECTIVE Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in schizophrenic patients during a verbal fluency task. METHOD Five right-handed male schizophrenic patients and five volunteers matched on demographic variables and verbal fluency performance participated in the study. Echoplanar images were acquired over 5 minutes at 1.5 T while the subjects performed two tasks. The first involved paced silent generation of words beginning with an aurally presented cue letter. This task alternated with paced silent repetition of the aurally presented word "rest. " Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric hypothesis testing. Between-group differences in the mean power of experimental response were identified on a voxelwise basis by an analysis of covariance that controlled for between-group differences in stimulus-correlated motion. RESULTS The comparison group showed significant responses in the left prefrontal cortex, the insula bilaterally, the midline supplementary motor area, and the medial parietal cortex. Compared to those subjects, the schizophrenic subjects showed significantly reduced power of response in the left dorsal prefrontal cortex, the inferior frontal gyrus, and the insula but significantly increased power of response in the medial parietal cortex. In both groups frontal and parietal responses were negatively correlated. CONCLUSIONS Schizophrenic patients displayed attenuated power of response in several frontal regions during word generation but greater power of response in the medial parietal cortex during word repetition.
Five genes at the 3′ end of the Klebsiella pneumoniae pulC operon are required for pullulanase secretion

The nucleotide sequence of a 5082bp fragment of chromosomal DNA from Klebsiella pneumoniae strain UNF5023 is reported. The sequence includes the last four genes of an operon of genes specifically required for the secretion of the enzyme pullulanase. All four genes (puIL, puIM, puIN and puIO) are shown to be required for pullulanase secretion, as is a fifth gene (puIK) which extends beyond the 5′ end of the sequenced DNA. The products of the puIL, puIM, puIN and puIO genes (44kD, 18kD, 27kD and 24kD, respectively) are all predicted to have one or more hydrophobic domains typical of signal sequences and/or membrane anchors, and were all found mainly associated with the inner membranes of subfractionated cells in which the corresponding genes had been expressed from the bacteriophage T7 gene 10 promoter. The results of this study increase the number of genes which have been identified as required for pullulanase secretion to eight, in addition to genes coding for components of the general export pathway.
Cyclosporin A, but Not Tacrolimus, Inhibits the Biliary Excretion of Mycophenolic Acid Glucuronide Possibly Mediated by Multidrug Resistance-Associated Protein 2 in Rats

The onset of diarrhea after the administration of mycophenolate mofetil (MMF) is possibly associated with the biliary excretion of its metabolite, mycophenolic acid glucuronide (MPAG). This study was undertaken to clarify the mechanism underlying the biliary excretion of MPAG. Intravenously administered mycophenolic acid (MPA, 5 mg/kg) rapidly disappeared from plasma and was efficiently excreted as MPAG in the bile of Wistar (26% of dose) and Sprague-Dawley rats (21% of dose) over 1 h. On the other hand, in spite of the rapid disappearance of MPA from plasma, the biliary excretion of MPAG was very limited in Eisai hyperbilirubinemic rats (EHBRs), which display mutations in multidrug resistance-associated protein 2 (Mrp2)/canalicular multispecific organic anion transporter, and constituted only 0.5% of dose. Instead, high levels of MPA were noted in the plasma of EHBRs. Intravenous administration of CsA (5 mg/kg) to Wistar rats significantly lowered the biliary excretion of MPAG. However, intravenously administered tacrolimus (0.1 mg/kg) failed to produce such effect. In conclusion, it is suggested that there is an efficient MPAG transport mediated by Mrp2 on the bile canalicular membrane of rat hepatocytes and that the therapeutic range of CsA potentially interferes with Mrp2. However, the therapeutic range of tacrolimus does not inhibit the transporter. Thus, it should be noted that MMF coadministered with tacrolimus instead of CsA might increase the occurrence of diarrhea related to the biliary excretion of MPAG in transplant recipients.
Isolation and characterization of novel peroxisome biogenesis-defective Chinese hamster ovary cell mutants using green fluorescent protein.

We developed an improved method for isolation of peroxisome biogenesis-defective somatic animal cell mutants, using a combination of green fluorescent protein (GFP) expression and the 9-(1'-pyrene)nonanol/ultraviolet (P9OH/UV) selection method. We used TKaG1 and TKaG2 cells, the wild-type Chinese hamster ovary (CHO) cells, CHO-K1, that had been stably transfected with cDNAs each encoding rat Pex2p as well as GFP tagged at the C-terminus with peroxisome targeting signal type 1 (PTS1) or N-terminally PTS2-tagged GFP. P9OH/UV-resistant cell colonies were examined for intracellular location of GFP on unfixed cells, by fluorescence microscopy. Seven each of the mutant cell clones isolated from TKaG1 and TKaG2 showed cytosolic GFP-PTS1 and PTS2-GFP, respectively, indicating the defect in peroxisome assembly. By transfection of PEX2, PEX5, PEX6, and PEX12 cDNAs and cell fusion analysis between the CHO cell mutants, five different complementation groups (CGs) were identified. Two mutant clones, ZPG207 and ZPG208, belonged to novel CGs. Further CG analysis using fibroblasts from patients with peroxisome biogenesis disorders, including rhizomelic chondrodysplasia punctata (RCDP), revealed that ZPG208 belonged to none of human CGs. ZPG207 was classified into the same CG as RCDP. Taken together, ZPG208 is in a newly identified, the 12th, CG in peroxisome-deficient CHO mutants reported to date and represents a novel mammalian CG.
Multimodal treatment of advanced renal cancer in 2017

ABSTRACT Introduction: in the last decades, the treatment of renal cell carcinoma has become more complex due to the introduction of novel systemic agents and the improvement of the loco-regional therapies that prolong survival maintaining a good quality of life. Areas covered: in this review, we summarize the currently available local and systemic treatment options, their indications and their hypothetical role in the management of advanced renal cell carcinoma, highlighting the need of multimodality treatment paradigms within interdisciplinary decision-making. Expert commentary: in early disease, radical or partial nephrectomy remains the standard of care, but innovative ablation techniques, including radiofrequency ablation, microwave ablation, cryoablation and so on, may represent an alternative option of treatment for small renal lesions in unfit patients who cannot undergo surgery. In metastatic setting, it is imperative a multidisciplinary team approach to select patients for a cytoreductive nephrectomy, metastasectomy, and/or systemic treatment, aiming to the optimization of the treatment strategy.
Analysis on numbers and adaptive ranges of resonators for efficient resonant coupling wireless power transmission

Resonant coupling is the technology widely applied for efficient wireless power transfer in medium ranges. This paper applies reflected load theory to analyze the multi-coil system consisting of several resonators. Different number of resonators would change resistance reflected to primary side and influence power delivered to load. To optimize power transmission of system, this paper purposes a method to calculate critical coupling point. A practical 4-coil system was implemented for verification. Based on this method, optimal 71.10 % of efficiency can be obtained by adjusting coupling between coils. Further, shifting frequency of source could enhance efficiency over 40 % when the distance d23 is less than 2 cm.
Novel structure of the recA locus of Mycobacterium tuberculosis implies processing of the gene product

A fragment of Mycobacterium tuberculosis DNA containing recA-like sequences was identified by hybridization with the Escherichia coli recA gene and cloned. Although no expression was detected from its own promoter in E. coli, expression from a vector promoter partially complemented E. coli recA mutants for recombination, DNA repair, and mutagenesis, but not for induction of phage lambda. This clone produced a protein which cross-reacts with antisera raised against the E. coli RecA protein and was approximately the same size. However, the nucleotide sequence of the cloned fragment revealed the presence of an open reading frame for a protein about twice the size of other RecA proteins and the cloned product detected by Western blotting (immunoblotting). The predicted M. tuberculosis RecA protein sequence was homologous with RecA sequences from other bacteria, but this homology was not dispersed; rather it was localized to the first 254 and the last 96 amino acids, with the intervening 440 amino acids being unrelated. Furthermore, the junctions of homology were in register with the uninterrupted sequence of the E. coli RecA protein. Identical restriction fragments were found in the genomic DNAs of M. tuberculosis H37Rv and H37Ra and of M. bovis BCG. It is concluded that the ancestral recA gene of these species diversified via an insertional mutation of at least 1,320 bp of DNA. Possible processing mechanisms for synthesizing a normal-size RecA protein from this elongated sequence are discussed.
Variation in Alkaloid Production from Genetically Diverse Lolium Accessions Infected with Epichloë Species.

Widespread infection of Epichloë occultans in annual ryegrass in Australia suggests that infection provides its weedy host, Lolium rigidum, some ecological advantage. Initial studies determined the distribution and profiles of known Epichloë alkaloids (epoxy-janthitrems, ergovaline, lolines, lolitrem B, and peramine) in plant extracts using a combination of GC-FID and HPLC techniques utilizing a single accession of Australian L. rigidum. However, the lolines N-acetylnorloline (NANL) and N-formylloline (NFL) were the only alkaloids detected and were highly concentrated in the immature inflorescences of mature plants. Additional glasshouse studies subjected a wide range of Australian L. rigidum haplotypes and international annual Lolium accessions to a suite of analyses to determine alkaloid levels and profiles. Again, NFL and NANL were the key lolines produced, with NFL consistently predominating. Considerable variation in alkaloid production was found both within and between biotypes and accessions evaluated under identical conditions, at the same maturation stage and on the same tissue type. The pyrrolopyrazine alkaloid peramine was also present in 8 out of 17 Australian biotypes of L. rigidum and 7 out of 33 international accessions infected with Epichloë spp. ; the highest peramine concentrations were observed in seed extracts from L. rigidum collected from Australia. This study represents the first report of alkaloids from a geographically diverse collection of annual ryegrass germplasm infected with Epichloë spp. when grown under identical controlled conditions.
Bioresorbable scaffolds compared with everolimus-eluting stents for the treatment of chronic coronary total occlusion: clinical and angiographic results of a matched paired comparison

Objectives Data on bioresorbable vascular scaffolds for recanalization of chronic total occlusions (CTOs) are limited. We compared the bioresorbable scaffold Absorb with everolimus-eluting stents for the treatment of true CTO. Methods After recanalization of CTO, 15 lesions treated with the bioresorbable scaffold Absorb were matched with 15 lesions receiving everolimus-eluting stent (EES) (http://www.clinicaltrials.gov NCT02162082). Match criteria were presence of diabetes mellitus, total device length and maximal device diameter. Angiographic follow-up was scheduled after 9 months and clinical follow-up after 12 months. Dual antiplatelet therapy was administered for 12 months. Quantitative coronary analysis was carried out before and after implantation and at angiographic follow-up. All lesions were predilated. The Absorb scaffolds and drug-eluting stents were carefully placed and postdilatated with high-pressure balloons. Patients received dual antiplatelet therapy for 12 months. The baseline characteristics were similar between both the groups. The mean scaffold length was 81.7±29.1 versus 79.3±27.4 mm for the mean stent length (P=0.82). In-device late lumen loss at the 9-month follow-up was 0.38±0.47 versus 0.46±0.60 mm (P=0.69). The device-oriented composite endpoint was similar in both groups, with 6.7% in the Absorb-group versus 13.3% in the EES group because of target lesion revascularization (P=0.54). Conclusion In CTOs, the use of a bioresorbable scaffold Absorb after recanalization showed similar 9-month angiographic and 12-month clinical results compared with an EES with 12 months of dual antiplatelet therapy.
Serum Concentrations of Cardiac Troponin T in Sudden Death

Ischemic heart disease is the most common cause of sudden death of natural causes in most western countries. By autopsy, there may be no gross or histologic evidence of acute myocardial damage unless the patient survived for several hours following the event. Cardiac troponin in serum has become the recommended biochemical marker for myocardial injury in the clinical setting. We performed a prospective study on 102 autopsied subjects at the Central Hospital of Rogaland, Stavanger, Norway. Femoral blood was sampled for subsequent analysis of cardiac troponin T (cTnT). In the subjects with morphologic evidence of recent myocardial injury (n = 34), the mean serum cTnT level was 1.95 μg/L compared with 0.16 μg/L in the subjects with a noncardiac cause of death (n = 35) and 0.61 μg/L in the group with probable sudden cardiac death without morphologic signs of acute myocardial injury (n = 33). The observed differences in mean serum cTnT levels between the groups were statistically significant (P < 0.0001). These data suggest that elevated postmortem serum concentration of cTnT reflects ongoing myocardial damage and may support a diagnosis of cardiac-related death in cases associated with sparse or inconclusive morphologic findings postmortem.
The effectiveness of the controlled release of simvastatin from β‐TCP macrosphere in the treatment of OVX mice

Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side‐effects. Given the associated side‐effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta‐tricalcium phosphate (β‐TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β‐TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the r elease of simvastatin, an apatite coating was made around the β‐TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β‐TCP, β‐TCP with simvastatin, apatite‐coated β‐TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non‐implanted side (left) and showed that β‐TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite‐coated β‐TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release can be prolonged with an apatite coating to significantly promote relevant bone formation. Copyright © 2013 John Wiley & Sons, Ltd.