Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of Bacteroides succinogenes and measurement of the main digestive parameters in the rumen of gnotoxenic lambs.

We attempted to determine the degree of diversification of the microflora that allow the establishment of Bacteroides succinogenes S85 in the rumen of gnotoxenic lambs. Four lambs (group I) received an inoculum orally, composed of 182 noncellulolytic bacterial strains (inoculum 1) previously isolated from the rumen of conventional young lambs. Two lambs (group II) were inoculated with 32 strains (inoculum 2) selected among the 182 strains of inoculum 1. Two lambs (group III) received an inoculum (inoculum 3) composed of 106 noncellulolytic bacterial strains previously isolated from the rumen of meroxenic lambs. Two lambs (group IV) were inoculated with 16 strains (inoculum 4) chosen among the 106 strains of inoculum 3. All lambs were inoculated from birth except two lambs of group I, which were inoculated from 1 month of age. Each lamb then received orally a pure culture of B. succinogenes. This strain became established more easily in the rumen of lambs that had received complex inocula (group I). Its population reached a level close to that generally observed in conventional lambs (10(7)-10(8) bacteria.mL-1). In contrast, B. succinogenes became established in only one lamb of group II, but bacterial numbers varied considerably. In group III, repeated inoculations were necessary to obtain its definitive establishment (10(7)-10(8) bacteria.mL-1 after weaning). In spite of several inoculations, this cellulolytic species failed to establish in the rumen of lambs of group IV, which had received the less complex inoculum. The volatile fatty acid levels were very different from one lamb group to another. The more complex the inoculum administered to the animals, the higher the concentration. (ABSTRACT TRUNCATED AT 250 WORDS)
Exploring the phenomenon of company-specific production systems: one-best-way or own-best-way?

This explorative study investigates the phenomenon of the company-specific production system (XPS). It has been a strong and recent trend across many manufacturing industries to develop and deploy such a corporate improvement programme. Five propositions regarding the uniqueness of XPSs are derived from universalistic versus contingent perspectives on improvement programmes. The main XPS principles of 30 renowned multinationals are analysed for similarities and differences. In conclusion, XPSs largely represent variants of the same in content. They represent an own-best-way approach to the one-best-way paradigm. Even though a tight relationship to the Toyota Production System (TPS) and lean production is established, the findings raise a red flag that XPSs might suffer under a too rigid, path-dependent development process from what has become an overly technical understanding of the TPS. This study also questions whether modern manufacturers have sufficiently integrated other essential elements of modern operations such as the use of ERP, automation and real-time response technologies in their XPSs. These findings have direct implications for practitioners and provide interesting opportunities for further research.
ATR inhibition rewires cellular signaling networks induced by replication stress

The slowing down or stalling of replication forks is commonly known as replication stress and arises from multiple causes such as DNA lesions, nucleotide depletion, RNA‐DNA hybrids, and oncogene activation. The ataxia telangiectasia and Rad3‐related kinase (ATR) plays an essential role in the cellular response to replication stress and inhibition of ATR has emerged as therapeutic strategy for the treatment of cancers that exhibit high levels of replication stress. However, the cellular signaling induced by replication stress and the substrate spectrum of ATR has not been systematically investigated. In this study, we employed quantitative MS‐based proteomics to define the cellular signaling after nucleotide depletion‐induced replication stress and replication fork collapse following ATR inhibition. We demonstrate that replication stress results in increased phosphorylation of a subset of proteins, many of which are involved in RNA splicing and transcription and have previously not been associated with the cellular replication stress response. Furthermore, our data reveal the ATR‐dependent phosphorylation following replication stress and discover novel putative ATR target sites on MCM6, TOPBP1, RAD51AP1, and PSMD4. We establish that ATR inhibition rewires cellular signaling networks induced by replication stress and leads to the activation of the ATM‐driven double‐strand break repair signaling.
Long‐term outcomes and predictors in pediatric liver retransplantation

Historically, 9–29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed. Kaplan–Meier estimates were used to depict patient and graft survival. Predictors of survival were analyzed using a series of Cox proportional hazards models. Predictors were analyzed separately for patients who had “early” (≤30 days after primary transplant) and “late” retransplants. Eighty‐four patients underwent retransplant at a median time of 241 days. Sixty percent had late retransplants. At one, five, and 10 yr, actuarial patient and graft survival were 73%/71%, 66%/63%, and 58%/53%, respectively. Since 2002, patient and graft survival improved to 86%/86% at one yr and 93%/87% at five yr. While operative complications were a common cause of death after earlier retransplants, since 2002, infection has been the only cause of death. Significant morbidities at five‐yr follow‐up include renal dysfunction (15%), diabetes (13%), hypertension (26%), chronic rejection (7%), and PTLD (2%). Current survival after pediatric liver retransplantation has improved significantly, but long‐term immunosuppressant morbidity remains an opportunity for improvement.
Response to Succinylcholine in Patients Carrying the K-Variant of the Butyrylcholinesterase Gene

BACKGROUND:Succinylcholine is usually metabolized quickly by the butyrylcholinesterase enzyme (BChE) but genetic variants of BChE may prolong the duration of action. The Kalow (K) variant is the most common mutation in the butyrylcholinesterase gene (BCHE), being present in 25% of Caucasians. The significance of the K-variant for the duration of action of succinylcholine has not been well studied. Our hypothesis was that the duration of action of succinylcholine would be prolonged in patients heterozygous for the K-variant genotype compared with the normal genotype (wild-type). METHODS:We included 70 adult surgical patients who received succinylcholine 1 mg/kg for rapid sequence induction. Neuromuscular monitoring was performed using ulnar nerve stimulation and acceleromyography. Duration of action of succinylcholine was defined as the time to 90% recovery of first twitch in train-of-four (T1 90%), BChE activity was determined, and the presence of BCHE K and A (atypical) variants were determined using DNA analysis. RESULTS:The wild-type BCHE was present in 38 patients, and 21 were heterozygous for the K-variant. Mean (SD) T1 90% in patients heterozygous for the K-variant, 11.6 (3.5) minutes, was longer than in patients with the wild-type genotype, 9.5 (2.7) minutes (P = 0.023), with a mean (95% confidence interval) difference of 2.1 (0.3–4.0) minutes. Patients heterozygous for the K-variant had a BChE activity of 5978 U/L compared with 7703 U/L in the wild-type group (P = 0.0045). CONCLUSION:We conclude that the mean duration of action of succinylcholine is prolonged for the patient heterozygous for the K-variant allele by at most 4 minutes relative to the wild-type, but this difference is small relative to the wide variability and overlap in recovery times among all patients.
Insulin Resistance and Incident Heart Failure

harmacy Practice Division isconsin; yCardiovascula sachusetts; zDepartment , Chapel Hill, North C n University Feinberg t of Epidemiology and th Research, Johns Hopkins Department of Medicin , North Carolina; and t , Houston, Texas. The orted by National He 201100005C, HHSN268 08C, HHSN268201100 and HHSN26820110001 ips relevant to the conten pt received July 12, 201 y 25, 2013. his study was designed to assess the relationship between insulin resistance and incident heart failure (HF) in a community-based cohort.
Substrate Specificity of the Nonribosomal Peptide Synthetase PvdD from Pseudomonas aeruginosa

ABSTRACT Pseudomonas aeruginosa PAO1 secretes a siderophore, pyoverdinePAO, which contains a short peptide attached to a dihydroxyquinoline moiety. Synthesis of this peptide is thought to be catalyzed by nonribosomal peptide synthetases, one of which is encoded by the pvdD gene. The first module of pvdD was overexpressed in Escherichia coli, and the protein product was purified. l-Threonine, one of the amino acid residues in pyoverdinePAO, was an effective substrate for the recombinant protein in ATP-PPi exchange assays, showing that PvdD has peptide synthetase activity. Other amino acids, including d-threonine, l-serine, and l-allo-threonine, were not effective substrates, indicating that PvdD has a high degree of substrate specificity. A three-dimensional modeling approach enabled us to identify amino acids that are likely to be critical in determining the substrate specificity of PvdD and to explore the likely basis of the high substrate selectivity. The approach described here may be useful for analysis of other peptide synthetases.
Recombinant Activated Factor VII Is Reabsorbed in Renal Proximal Tubules and Is a Ligand to Megalin and Cubilin

Background/Aims: Recombinant activated factor VIIa (rFVIIa) is used for treatment of haemophilia patients with inhibitors. Tissue distribution studies in rats have shown that injected 125I-rFVIIa accumulates in organs such as the liver and the kidneys. In this study, we explored which mechanism could be involved in renal clearance of rFVIIa. Methods: Immunohistochemistry was used for examination of the renal distribution in detail after injection of rFVIIa to mice and rats. Surface plasmon resonance evaluated specific binding of rFVIIa to megalin and cubilin. The biological function of megalin and cubilin in rFVIIa endocytosis was explored in opossum kidney (OK) cells. Results: Staining of rFVIIa was observed only in endosomes and lysosomes within proximal convoluted tubules from renal cortex of mice and rats. Specific binding of rFVIIa to megalin and cubilin was in the presence of receptor-associated protein (RAP) obliterated and reduced by approximately 50%, respectively. Immunofluorescence microscopy and a quantitative cellular endocytosis showed uptake in OK cells of either rFVIIa or 125I-rFVIIa, and this uptake was significantly decreased in the presence of RAP. Conclusion: We suggest that the renal cortex plays a significant role in clearance of injected rFVIIa and that endocytosis and degradation of rFVIIa in proximal tubule cells is mediated via binding to megalin and cubilin.
Oxygen diffusion distance and development of necrosis in multicell spheroids.

The multicell spheroid in vitro tumor model was used to study the effects of diffusion limitations of metabolites on the development of necrosis in a tumor-like environment. Chinese hamster V79-171b cells were grown in suspension as multicellular spheroids in different oxygen or glucose concentrations to diameters where they developed central necrosis surrounded by an outer rim of viable cells. The range of oxygen concentrations used in the gas phase was 1 to 20.3%, in equilibrium with complete nutrient medium. For each oxygen concentration the thickness of the rim of viable cells was determined from measurements of histological sections. The square of the thickness of the viable rims of spheroids grown at different oxygen concentrations between 5 and 20.3% increased linearly with the theoretically derived oxygen diffusion distance, showing that the oxygen diffusion distance is a main factor controlling, either directly or indirectly, the development of necrosis in this concentration range. The data were interpreted as meaning spheroids grown at more than 5% O/sub 2/ contain a very small proportion of cells which were severely hypoxic or anoxic. The viable rim thickness was relatively less affected during growth at less than 5% oxygen, implying that an unknown mechanism controls the formationmore » of necrosis when the oxygen diffusion distance is less than approximately 80 . mu.m. Although alterations in the glucose concentration had some effect on viable rim thickness at these low oxygen concentrations, the effect was much less than expected if glucose alone were responsible for controlling viability in this outer region. « less
Soft tissue calcification in chronic dialysis patients.

Autopsy protocols and microscopic slides of 56 dialyzed and 18 nondialyzed chronically uremic patients were reviewed to assess the presence, extent, and severity of extraosseous soft tissue calcification. Calcification was identified in 79% of the dialysis patients and 44% of the nondialysis patients (P iss less than .025). Soft tissue calcification most frequently involved the heart, lungs, stomach, and kidneys. Lesions were severe in 36% of the dialysis patients and, when strategically located within the myocardium, were life-threatening. The deaths of 6 dialysis patients were attributed to severe calcification of the cardiac conduction system and/or myocardium. The presence and severity of soft tissue calcification was not related to duration of dialysis, patients' age, degree of parathyroid gland hyperplasia, radiographic evidence of soft tissue calcification, serum calcium and phosphate levels, Ca X P products, or type or severity of metabolic bone disease.
The History of Tipping - from Sixteenth-Century England to United States in the 1910s

Tipping is a multi-billion-dollar phenomenon that challenges the traditional assumption of selfish economic agents who have no feelings and do not care about social norms. This article reviews the early history of tipping and offers an economic analysis of different aspects of tipping. Using the historical evidence, it then addresses two major questions about tipping: why do people tip? And does tipping improve service quality? The reasons for tipping changed over the years, but conforming to social norms and avoiding embarrassment were generally the main reasons. Tipping seems to improve service quality; the extent of the improvement varies across occupations.
Adenosine-catecholamine Interaction in the Renal Vascular Response 1

Summary Renal vasoconstriction induced by intra-arterial administration of 1 μg of norepinephrine or renal nerve stimulation was enhanced during adenosine infusion in concentrations from approximately 2.5 × 10-9 to 10-7 g/ml while the vasoconstrictor response to adenosine itself was inhibited. Enhancement of the vasoconstrictor response to norepinephrine and inhibition of that to adenosine were dependent on the infusion rate of adenosine. After interruption of adenosine infusion, the initial responses to norepinephrine and adenosine recovered promptly. Thus it appears that adenosine modulates the adrenergic effect in the renal circulation.
Soft-x-ray magnetic circular dichroism at the L2,3 edges of nickel.

Le rapport d'intensite du dichroisme circulaire magnetique entre les limites L 2 et L 3 differe nettement de celui predit pour un simple modele decomposition/echange de la bande de valence. Tentative d'interpretation de structures fines imperceptibles dans les spectres d'absorption
Predictors of Long-Term Benzodiazepine Abstinence in Participants of a Randomized Controlled Benzodiazepine Withdrawal Program

Objective: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. Method: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in general practice. Results: Of 180 patients, we completed follow-up for 170 (94%). Of these, 50 (29%) achieved long-term success, defined as no use of benzodiazepines during follow-up. Independent predictors of success were as follows: offering a taper-off program with group therapy (hazard ratio [HR] 2.4; 95% confidence interval [CI], 1.5 to 3.9) or without group therapy (HR 2.9; 95%CI, 1.8 to 4.8); a lower daily benzodiazepine dosage at the start of tapering off (HR 1.5; 95%CI, 1.2 to 1.9); a substantial dosage reduction by patients themselves just before the start of tapering off (HR 2.1; 95%CI, 1.4 to 3.3); less severe benzodiazepine dependence, as measured by the Benzodiazepine Dependence Self-Report Questionnaire Lack of Compliance subscale (HR 2.4; 95%CI, 1.1 to 5.2); and no use of alcohol (HR 1.7; 95%CI, 1.2 to 2.5). Patients who used over 10 mg of diazepam equivalent, who had a score of 3 or more on the Lack of Compliance subscale, or who drank more than 2 units of alcohol daily failed to achieve long-term abstinence. Conclusions: Benzodiazepine dependence severity affects long-term taper outcome independent of treatment modality, benzodiazepine dosage, psychopathology, and personality characteristics. An identifiable subgroup needs referral to specialized care.
MiR-9a-5p regulates proliferation and migration of hepatic stellate cells under pressure through inhibition of Sirt1.

AIM To reveal the functions of microRNAs (miRNAs) with respect to hepatic stellate cells (HSCs) in response to portal hypertension. METHODS Primary rat HSCs were exposed to static water pressure (10 mmHg, 1 h) and the pressure-induced miRNA expression profile was detected by next-generation sequencing. Quantitative real-time polymerase chain reaction was used to verify the expression of miRNAs. A potential target of MiR-9a-5p was measured by a luciferase reporter assay and Western blot. CCK-8 assay and Transwell assay were used to detect the proliferation and migration of HSCs under pressure. RESULTS According to the profile, the expression of miR-9a-5p was further confirmed to be significantly increased after pressure overload in HSCs (3.70 ± 0.61 vs 0.97 ± 0.15, P = 0.0226), which resulted in the proliferation, migration and activation of HSCs. In vivo, the up-regulation of miR-9a-5p (2.09 ± 0.91 vs 4.27 ± 1.74, P = 0.0025) and the down-regulation of Sirt1 (2.41 ± 0.51 vs 1.13 ± 0.11, P = 0.0006) were observed in rat fibrotic liver with portal hypertension. Sirt1 was a potential target gene of miR-9a-5p. Through restoring the expression of Sirt1 in miR-9a-5p transfected HSCs on pressure overload, we found that overexpression of Sirt1 could partially abrogate the miR-9a-5p mediated suppression of the proliferation, migration and activation of HSCs. CONCLUSION Our results suggest that during liver fibrosis, portal hypertension may induce the proliferation, migration and activation of HSCs through the up-regulation of miR-9a-5p, which targets Sirt1.
Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and Hairless Mice

Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin‐6, and MMP‐1 were significantly suppressed, and type I procollagen expression was stimulated in UVB‐irradiated and GA‐treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP‐1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor‐β1. Our data indicate that GA is a potential candidate for the prevention of UVB‐induced premature skin aging. Copyright © 2014 John Wiley & Sons, Ltd.
Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.
Comparison of levels of chloroplast DNA diversity of two Shorea species with contrasting geographical distribution

1 Department of Agrotechnology, Faculty of Agriculture and Animal Science, State Islamic University of Sultan Syarif Kasim, Panam, Pekanbaru 28293, Riau, Indonesia 2 Alumni of Department of Silviculture, Faculty of Forestry, Bogor Agricultural University, Kampus IPB Darmaga, Bogor 1668, Indonesia 3 Department of Silviculture, Faculty of Forestry, Bogor Agricultural University, Kampus IPB Darmaga, Bogor 1668, Indonesia 4 Directorate General of Mineral, Coal and Geothermal, Ministry of Energy and Mineral Resources, Jakarta, 12870 Indonesia
38-43 GHz quadrature VCO on 90 nm VLSI CMOS with feedback frequency tuning

A 40 GHz voltage controlled oscillator with quadrature phase outputs is presented in this paper. Feedback is applied for frequency tuning. Thus, no varactors are required. The fully integrated circuit is fabricated in 90 nm VLSI SOI CMOS technology. A large tuning range of 5 GHz, an output power per channel of -4.7 to -7.4 dBm and a phase noise of -80 to -87 dBc/Hz at 3 MHz offset were measured.
A Polynomial Algorithm for the 2-Path Problem for Semicomplete Digraphs

This paper presents polynomially bounded algorithms for finding a cycle through any two prescribed arcs in a semicomplete digraph and for finding a cycle through any two prescribed vertices in a complete k-partite oriented graph. It is also shown that the problem of finding a maximum transitive subtournament of a tournament and the problem of finding a cycle through a prescribed arc set in a tournament are both NP-complete.