Miracle-dz/UniFAR-FTUs huggingface dataset:
An Experimental Large Animal Model for the Assessment of Bioartificial Liver Support Systems in Fulminant Hepatic Failure

Background: Pre-clinical assessment of bioartificial liver support systems requires a highly reproducible large animal model. The main objective of the present study was to develop a valid large animal model for assessing novel bioartificial liver support systems in fulminant hepatic failure. Methods: A complete liver devascularization procedure was performed in 10 female pigs weighing 25-38 kg. Five matched pigs were sham-operated and served as controls. Results: Pigs with fulminant hepatic failure developed a hyperdynamic circulation, with increased cardiac index ( P GT < .0001), decreased systemic vascular resistance index ( P GT < .0001) and mean arterial pressure ( P GT = .001). Furthermore, intracranial hypertension developed ( P GT < .0001), with increased common carotid artery flow ( P GT < .0001) and decreased common carotid resistance ( P G = .003). Femoral artery flow increased ( P = .036), while hindleg resistance ( P < .001) and renal artery resistance decreased ( P = .019). Oxygen consumption ( P GT = .050) and oxygen extraction ratio ( P GT = .001) increased compared to controls. Arterial ammonia, venous aspartate aminotransferase and bilirubin levels increased ( P GT < .0001, respectively). Abnormal haemostasis developed with significant loss of platelets ( P GT = .010), decreasing fibrinogen levels ( P G = .001) and increasing international normalized ratio ( P GT = .012) and activated clotting time ( P GT < .001). Urine became hypo-osmotic ( P < .001, P G = .011), with decreased sodium levels ( P = .08) and increased potassium levels ( P G = .025). Conclusions: This study characterizes a reproducible large animal model for fulminant hepatic failure that seems suitable for the assessment of bioartificial liver support systems.
Functionality of Root-Associated Bacteria along a Salt Marsh Primary Succession

Plant-associated bacteria are known for their high functional trait diversity, from which many are likely to play a role in primary and secondary succession, facilitating plant establishment in suboptimal soils conditions. Here we used an undisturbed salt marsh chronosequence that represents over 100 years of soil development to assess how the functional traits of plant associated bacteria respond to soil type, plant species and plant compartment. We isolated and characterized 808 bacterial colonies from the rhizosphere soil and root endosphere of two salt marsh plants, Limonium vulgare and Artemisia maritima, along the chronosequence. From these, a set of 59 strains (with unique BOX-PCR patterns, 16S rRNA sequence and unique to one of the treatments) were further screened for their plant growth promoting traits (siderophore production, IAA production, exoprotease production and biofilm formation), traits associated with bacterial fitness (antibiotic and abiotic stress resistance – pH, osmotic and oxidative stress, and salinity) and metabolic potential. An overall view of functional diversity (multivariate analysis) indicated that the distributional pattern of bacterial functional traits was driven by soil type. Samples from the late succession (Stage 105 year) showed the most restricted distribution, harboring strains with relatively low functionalities, whereas the isolates from intermediate stage (35 year) showed a broad functional profiles. However, strains with high trait performance were largely from stage 65 year. Grouping the traits according to category revealed that the functionality of plant endophytes did not vary along the succession, thus being driven by plant rather than soil type. In opposition, the functionality of rhizosphere isolates responded strongly to variations in soil type as observed for antibiotic resistance (P = 0.014). Specifically, certain Pseudomonas sp. and Serratia sp. strains revealed high resistance against abiotic stress and antibiotics and produce more siderophores, confirming the high plant-growth promoting activity of these two genera. Overall, this study contributes to a better understanding of the functional diversity and adaptation of the microbiome at typical salt marsh plant species across soil types. Specifically, soil type was influential only in the rhizosphere but not on the endosphere, indicating a strong plant-driven effect on the functionality of endophytes.
A phylogenetic study of Drosophila splicing assembly chaperone RNP-4F associated U4-/U6-snRNA secondary structure

The rnp-4f gene in Drosophila melanogaster encodes nuclear protein RNP-4F. This encoded protein is represented by homologs in other eukaryotic species, where it has been shown to function as an intron splicing assembly factor. Here, RNP-4F is believed to initially bind to a recognition sequence on U6-snRNA, serving as a chaperone to facilitate its association with U4-snRNA by intermolecular hydrogen bonding. RNA conformations are a key factor in spliceosome function, so that elucidation of changing secondary structures for interacting snRNAs is a subject of considerable interest and importance. Among the five snRNAs which participate in removal of spliceosomal introns, there is a growing consensus that U6-snRNA is the most structurally dynamic and may constitute the catalytic core. Previous studies by others have generated potential secondary structures for free U4- and U6-snRNAs, including the Y-shaped U4-/U6-snRNA model. These models were based on study of RNAs from relatively few species, and the popular Y-shaped model remains to be systematically re-examined with reference to the many new sequences generated by recent genomic sequencing projects. We have utilized a comparative phylogenetic approach on 60 diverse eukaryotic species, which resulted in a revised and improved U4-/U6-snRNA secondary structure. This general model is supported by observation of abundant compensatory base mutations in every stem, and incorporates more of the nucleotides into base-paired associations than in previous models, thus being more energetically stable. We have extensively sampled the eukaryotic phylogenetic tree to its deepest roots, but did not find genes potentially encoding either U4- or U6-snRNA in the Giardia and Trichomonas data-bases. Our results support the hypothesis that nuclear introns in these most deeply rooted eukaryotes may represent evolutionary intermediates, sharing characteristics of both group II and spliceosomal introns. An unexpected result of this study was discovery of a potential competitive binding site for Drosophila splicing assembly factor RNP-4F to a 5’-UTR regulatory region within its own premRNA, which may play a role in negative feedback control.
Identification of Cleavage Sites Leading to the Shed Form of the Anti-Aging Protein Klotho

Membrane protein shedding is a critical step in many normal and pathological processes. The anti-aging protein klotho (KL), mainly expressed in kidney and brain, is secreted into the serum and CSF, respectively. KL is proteolytically released, or shed, from the cell surface by ADAM10 and ADAM17, which are the α-secretases that also cleave the amyloid precursor protein and other proteins. The transmembrane KL is a coreceptor with the FGF receptor for FGF23, whereas the shed form acts as a circulating hormone. However, the precise cleavage sites in KL are unknown. KL contains two major cleavage sites: one close to the juxtamembrane region and another between the KL1 and KL2 domains. We identified the cleavage site involved in KL release by mutating potential sheddase(s) recognition sequences and examining the production of the KL extracellular fragments in transfected COS-7 cells. Deletion of amino acids T958 and L959 results in a 50–60% reduction in KL shedding, and an additional P954E mutation results in further reduction of KL shedding by 70–80%. Deletion of amino acids 954–962 resulted in a 94% reduction in KL shedding. This mutant also had moderately decreased cell surface expression, yet had overall similar subcellular localization as that of WT KL, as demonstrated by immunofluorescence. Cleavage-resistant mutants could function as a FGFR coreceptor for FGF23, but they lost activity as a soluble form of KL in proliferation and transcriptional reporter assays. Cleavage between the KL1 and KL2 domains is dependent on juxtamembrane cleavage. Our results shed light onto mechanisms underlying KL release from the cell membrane and provide a target for potential pharmacologic interventions aimed at regulating KL secretion.
Systematic Aβ Analysis in Drosophila Reveals High Toxicity for the 1-42, 3-42 and 11-42 Peptides, and Emphasizes N- and C-Terminal Residues

Brain amyloid plaques are a hallmark of Alzheimer's disease (AD), and primarily consist of aggregated Aβ peptides. While Aβ 1-40 and Aβ 1-42 are the most abundant, a number of other Aβ peptides have also been identified. Studies have indicated differential toxicity for these various Aβ peptides, but in vivo toxicity has not been systematically tested. To address this issue, we generated improved transgenic Drosophila UAS strains expressing 11 pertinent Aβ peptides. UAS transgenic flies were generated by identical chromosomal insertion, hence removing any transgenic position effects, and crossed to a novel and robust Gal4 driver line. Using this improved Gal4/UAS set-up, survival and activity assays revealed that Aβ 1-42 severely shortens lifespan and reduces activity. N-terminal truncated peptides were quite toxic, with 3-42 similar to 1-42, while 11-42 showed a pronounced but less severe phenotype. N-terminal mutations in 3-42 (E3A) or 11-42 (E11A) resulted in reduced toxicity for 11-42, and reduced aggregation for both variants. Strikingly, C-terminal truncation of Aβ (1-41, -40, -39, -38, -37) were non-toxic. In contrast, C-terminal extension to 1-43 resulted in reduced lifespan and activity, but not to the same extent as 1-42. Mutating residue 42 in 1-42 (A42D, A42R and A42W) greatly reduced Aβ accumulation and toxicity. Histological and biochemical analysis revealed strong correlation between in vivo toxicity and brain Aβ aggregate load, as well as amount of insoluble Aβ. This systematic Drosophila in vivo and in vitro analysis reveals crucial N- and C-terminal specificity for Aβ neurotoxicity and aggregation, and underscores the importance of residues 1-10 and E11, as well as a pivotal role of A42.
Patterns of debris flow initiation and periglacial sediment sourcing in the Colorado Front Range

During an extreme storm in the Colorado Front Range in September 2013, 11 debris flows initiated at high elevations in Rocky Mountain National Park. We characterized these debris flows to determine controls on their initiation and found that eight of the 11 initiated in areas of convergent topography, and eight initiated at elevations > 2800 m. The high proportion of debris flows in areas of convergent topography emphasizes the importance of local topographic control on initiation. Debris flows at high elevations in the Front Range are atypical; this event broadens our understanding of debris flow regimes in the Front Range. Survey data (scarp dimensions, transport distance) suggest that transport is influenced by downslope processes rather than characteristics of the initiation site. At one site with evidence of multiple debris flows sourced from the same colluvial hollow, we obtained relative ages of debris flow deposits through geomorphic mapping and fan stratigraphy. We used radiocarbon and beryllium‐10 (10Be) analysis to age stratigraphic deposits and debris flow levees. Radiocarbon ages (n = 6) were highly variable and were interpreted to reflect secondary hillslope processes rather than debris flow ages. Large ranges in cosmogenic exposure age and anomalously old samples indicate that sampled boulders (n = 14) contained inherited 10Be concentrations. Beryllium‐10 concentrations were likely acquired as exposed bedrock surfaces or during intermediate storage in the colluvial hollow. We suggest that 10Be inheritance limits the utility of cosmogenic exposure dating of debris flows with short transport distances (10−1 to 101 km). Despite these limitations, we documented field evidence for four to seven debris flows in the last 75 ka, including two in the last 8 ka. Considered collectively, 10Be sample ages from all levees suggest that greatest sediment production occurred during Quaternary glacial stages due to periglacial processes. Subsequent evacuation of the colluvial hollow likely occurred during wetter periods of the mid‐Holocene. © 2018 John Wiley & Sons, Ltd.
High-resolution variability of the enrichment of fluorescence dissolved organic matter in the sea surface microlayer of an upwelling region

Enrichment of fluorescence dissolved organic matter (FDOM) in the sea surface microlayer (SML) provides insights into biogeochemical processes occurring at the sea surface, including cycling of organic matter, photochemistry, and air-sea gas exchange. We present data concerning the variability of FDOM enrichment in the SML during upwelling events in the Baltic Sea (Cruise M117). Our results show that FDOM is frequently enriched (75% of all samples) and that enrichment factors are significantly higher in SMLs located in regions with upwelling (pooled median = 1.4) compared to a non-upwelling region (median = 1.1). The enrichment factor of FDOM showed short time-scale variability, changing by 6% within ten-minute intervals. Larger variabilities (standard deviation up to ±0.14 μg L–1 compared to background of ±0.01 μg L–1) occurred when fronts were present and when the SML was mixed with underlying bulk water. Small-scale patchiness, indicated by changes in the variability of FDOM enrichment in SML, was a common feature of the sea surface. Wind speed played a potential role in controlling the enrichment of FDOM in the SML, but the effects of solar radiation on photochemical processes, mixing and upwelling of water masses, and biological processes as a source of FDOM also influence enrichment at this critical interface between ocean and atmosphere.
A Systematic Review of the Efficacy of Creative Arts Therapies in the Treatment of Adults With PTSD

Objective: There is a growing body of literature supporting the use of creative arts therapies; however, the efficacy of creative arts therapies in the treatment of posttraumatic stress disorder (PTSD) has not been systematically evaluated. The aim of this systematic review was to examine the efficacy of creative arts therapy including music therapy, art therapy, dance/movement therapy, and drama therapy, in the treatment of PTSD. Method: Ten databases were searched for peer-reviewed literature published from inception to December 2016. Studies were included in the review if they used a randomized controlled trial (RCT), a pseudo RCT, or a controlled study design; tested the efficacy of one of the creative arts therapies described above; and reported changes to PTSD diagnosis or symptomatology. Results: From an initial yield of 1,918 records, 1,653 records were screened on title and abstract and 125 were screened at full-text. Seven studies met the inclusion criteria for review, with four studies investigating art therapy, two studies investigating music therapy, and a final study investigating drama therapy. Individual studies were initially rated on a standardized quality and bias checklist, and then GRADE was used to rate the overall evidence for each intervention. The evidence for music therapy, art therapy, and drama therapy was ranked as low to very low, with no studies found for dance/movement therapy. Generally, the quality of the trials was very poor. Future directions for this field of research are to improve the scientific quality of the research trials in this area.
Genetic Epidemiology of Arterial Blood Pressure : A Review

Worldwide hypertension affects almost 20% of the adult population. The rates of hypertension have shown an increasing trend in recent times especially among the developed and developing countries. A comprehensive review of the literature on the genetics of blood pressure and hypertension encompassing the pre-molecular and molecular phase of the research is being presented. Many studies have used the familial nature, family history, twins and family based approaches to establish the genetic nature of BP and hypertension. Most studies have found that environmental variables also play an important role in BP regulation. Studies trying to establish the mode of inheritance (major/minor genes) of BP/hypertension, in the pre-molecular phase, have been either inconclusive or gave conflicting results. Molecular genetic approaches in the investigation of the genetic basis of BP and hypertension have largely relied on rare Mendelian forms of hypertension, candidate gene approaches, comparative mapping and genome wide screening in both animal and human models, using linkage and association studies. Genome wide scan studies have shown that all human chromosomes except 13 and 20 have shown regions of significant association with BP or hypertension. However, the lack of consistency in the nature of associations found is glaringly apparent which may be due to the complex nature of the BP/hypertension phenotype, probably determined by multi-factorial inheritance. Future studies on traditional and transitional homogenous populations with proper sampling of individuals hold the key to further resolving the problem of hypertension. Studies on Indian populations because of their endogamous nature might be fruitful in establishing the precise nature of association between BP and gene polymorphisms. 284 A. NIRMALA, P. CHENGAL REDDY, VIKAL TRIPATHY AND B. M. REDDY © Kamla-Raj Enterprises 2007 Anthropology Today: Trends, Scope and Applications Anthropologist Special Volume No. 3: 263-284 (2007) Veena Bhasin & M.K. Bhasin, Guest Editors Authors’ Addresses: A. Nirmala, Vikal Tripathy and B. M. Reddy, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, Andhra Pradesh, India P. Chengal Reddy, Department of Anthropology, Sri Venkateswara University, Tirupati, Andhra Pradesh,
Effect of tiotropium on lung function decline in early-stage of chronic obstructive pulmonary disease patients: propensity score-matched analysis of real-world data

Background Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1. However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients. The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%. Methods We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. The inclusion criteria were as follows: age ≥40 years, postbron-chodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year. Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist. The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug. Results Of the 587 patients enrolled in the study, 257 took tiotropium. Following propensity score matching, 404 patients were included in the analysis. The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively. Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13). Conclusion Therefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%.
Comparisons of GnRH antagonist versus GnRH agonist protocol in poor ovarian responders undergoing IVF.

BACKGROUND In view of the discrepancies about the GnRH antagonist (GnRH-ant) ovarian stimulation protocols having some potential advantages compared with the GnRH agonist (GnRH-a) protocols in poor ovarian responders IVF/ICSI, a meta-analysis of the published data was performed to compare the efficacy of GnRH-ant versus GnRH-a protocols for ovarian stimulation in IVF poor response patients. METHODS We searched for all published articles indexed in MEDLINE (1950-2010), EMBASE (1974-2010) and China National Knowledge Infrastructure (CNKI, 1994-2010). Any randomized controlled study that compared the GnRH-ant with GnRH-a in ovarian stimulation protocols for poor responders undergoing IVF/ICSI was included, and data were extracted independently by two reviewers. The searches yielded 64 articles, from which 14 studies met the inclusion criteria. We performed this meta-analysis involving 566 IVF patients in a GnRH-ant protocol group and 561 patients in a GnRH-a protocol group with Review Manager 4.2 software. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were used to evaluate dichotomous and continuous data, respectively. RESULTS Fourteen eligible studies were included in this meta-analysis. GnRH-ant protocols resulted in a statistically significantly lower duration of stimulation compared with GnRH-a protocols (P = 0.04; WMD: -1.88, 95% CI: -3.64, -0.12), but there was no significant difference in the number of oocytes retrieved (P = 0.51; WMD: -0.17, 95% CI -0.69, 0.34) or the number of mature oocytes retrieved (P = 0.99; WMD: -0.01, 95% CI: -1.14, 1.12). Moreover, no significant difference was found in the cycle cancellation rate (CCR, P = 0.67; OR: 1.01, 95% CI: 0.71-1.42) or clinical pregnancy rate (CPR, P = 0.16; OR: 1.23, 95% CI: 0.92, 1.66). CONCLUSIONS Clear advantage was gained in duration of stimulation with GnRH-ant in poor ovarian responders undergoing IVF, although there was no statistical difference in the number of oocytes retrieved, the number of mature oocytes retrieved, the CCR and CPR between GnRH-ant and GnRH-a protocols. These results may be helpful to our clinical practice. However, further controlled randomized prospective studies with larger sample sizes are needed.
Temporal pole and mesiotemporal epilepsy: introductory remarks.

It is now half a century since temporal lobe epilepsy was first identified and recognized as the most common type of refractory, focal epilepsy. The neuronal systems responsible for the seizures which characterize this form of epilepsy fail to respond to currently available anti-epileptic drugs in fully one third of cases although the exact reasons for this non-responsiveness are not yet understood. In contrast, the discharge responsible [. ]
A Level Algorithm for Preemptive Scheduling

Muntz and Coffman give a level algorithm that constructs optimal preemptive schedules on identical processors when the task system is a tree or when there are only two processors available. Their algorithm is adapted here to handle processors of different speeds. The new algorithm is optimal for independent tasks on any number of processors and for arbitrary task systems on two processors, but not on three or more processors, even for trees. By taking the algorithm as a heuristic on m processors and using the ratio of the lengths of the constructed and optimal schedules as a measure, an upper bound on its performance is derived in terms of the speeds of the processors. It is further shown that 1.23√m is an upper bound over all possible processor speeds and that the 1.23√m bound can be improved at most by a constant factor, by giving an example of a system for which the bound 0.35√m can be approached asymptotically.