Miracle-dz/UniFAR-FTUs huggingface dataset:
Getting to the nucleus of mitochondrial disorders: identification of respiratory chain-enzyme genes causing Leigh syndrome.

In 1951, Denis Leigh first described a striking neuropathology that occured in a child who died of a neurodegenerative disease (Leigh 1951). The paper focused on the patient's distinct neuropathological abnormalities, which we now associate with Leigh disease, or Leigh syndrome (MIM 256000). Definite diagnosis of this neurodegenerative disorder still depends on the identification, either in postmortem samples or by use of neuroimaging techniques, of the characteristic neuropathology of focal, bilaterally symmetrical spongiform lesions, especially in the thalamus and brain stem regions.
Martian Thermospheric Response to an X8.2 Solar Flare on 10 September 2017 as Seen by MAVEN/IUVS

We report the response of the Martian upper atmosphere to a strong X‐class flare on 10 September 2017 as observed by the Imaging Ultraviolet Spectrograph (IUVS) instrument aboard the Mars Atmosphere Volatile EvolutioN (MAVEN) mission. The solar flare peaked at 16:24 hr UT, and IUVS dayglow observations were taken about an hour after the flare peak. Retrieved temperatures from IUVS dayglow observations show a significant increase during the flare orbit, with a mean value of ∼270 K and a maximum value of ∼310 K. The retrieved temperatures during the flare orbit also show a strong latitudinal gradient, indicating that the flare‐induced heating is limited between low and middle latitudes. During this event IUVS observed an ∼70% increase in the observed brightness of CO 2+ ultraviolet doublet and CO Cameron band emission at 90 km, where high‐energy photons (< 10 nm) deposit most of their energy.
Ataxia, peripheral neuropathy, and anti-gliadin antibody. Guilt by association?

Some authors contend that patients with idiopathic neurological disease who are also anti-gliadin antibody seropositive are gluten sensitive. However, anti-gliadin antibodies lack disease specificity being found in 10% of healthy blood donors. We report a study comparing anti-gliadin antibody with other food antibodies in patients with idiopathic ataxia (20), hereditary ataxias (seven), or idiopathic peripheral neuropathy (32). Patients were HLA typed. IgA anti-tissue transglutaminase antibodies (tTG) were measured. No case was positive for IgA anti-tTG making occult coeliac disease unlikely. HLA DQ2 and HLA DQ8 were found distributed equally across all patient groups and unrelated to gliadin antibody status. HLA DQ2 expressing, anti-gliadin antibody positive cases (so called “gluten ataxia”) were rare in our clinics (four cases in 2 years from a population of 2 million). We conclude that coeliac disease per se is not commonly associated with either idiopathic ataxia or idiopathic peripheral neuropathy. Our study also casts doubt on the nosological status of “gluten ataxia” as a discreet disease entity. All food antibodies tested, particularly IgG, were a common finding in both ataxia and peripheral neuropathy groups. No particular food antibody was associated with any patient group. Food antibodies were equally common in hereditary ataxias. We conclude they are a non-specific finding.
Pathogen-associated molecular pattern-triggered immunity and resistance to the root pathogen Phytophthora parasitica in Arabidopsis

The cellulose binding elicitor lectin (CBEL) of the genus Phytophthora induces necrosis and immune responses in several plant species, including Arabidopsis thaliana. However, the role of CBEL-induced responses in the outcome of the interaction is still unclear. This study shows that some of CBEL-induced defence responses, but not necrosis, required the receptor-like kinase BAK1, a general regulator of basal immunity in Arabidopsis, and the production of a reactive oxygen burst mediated by respiratory burst oxidases homologues (RBOH). Screening of a core collection of 48 Arabidopsis ecotypes using CBEL uncovered a large variability in CBEL-induced necrotic responses. Analysis of non-responsive CBEL lines Ws-4, Oy-0, and Bla-1 revealed that Ws-4 and Oy-0 were also impaired in the production of the oxidative burst and expression of defence genes, whereas Bla-1 was partially affected in these responses. Infection tests using two Phytophthora parasitica strains, Pp310 and Ppn0, virulent and avirulent, respectively, on the Col-0 line showed that BAK1 and RBOH mutants were susceptible to Ppn0, suggesting that some immune responses controlled by these genes, but not CBEL-induced cell death, are required for Phytophthora parasitica resistance. However, Ws-4, Oy-0, and Bla-1 lines were not affected in Ppn0 resistance, showing that natural variability in CBEL responsiveness is not correlated to Phytophthora susceptibility. Overall, the results uncover a BAK1- and RBOH-dependent CBEL-triggered immunity essential for Phytophthora resistance and suggest that natural quantitative variation of basal immunity triggered by conserved general elicitors such as CBEL does not correlate to Phytophthora susceptibility.
Nonlinear Codes: The Product Construction

The standard product construction is discussed with respect to nonlinear codes. Thus, so-called nonlinear product codes are obtained that are better than linear product codes of similar length and code rate, and at the same time, amenable for encoding/decoding. On the other hand, it is shown that certain notorious nonlinear codes have an augmented product construction, namely, they can be constructed by taking the union of a product code and certain of its cosets. The binary Hamming codes are shown to have similar construction. A simple two-stage decoder is proposed for nonlinear product (NLP) codes. The decoder is shown to be a bounded-distance (BD) information decoder that is the nonlinear equivalent of the BD decoder employed for linear codes. A list-based maximum-likelihood decoder is also discussed.
Diffusive Promotion by Velocity Gradient of Cytoplasmic Streaming (CPS) in Nitella Internodal Cells

Cytoplasmic streaming (CPS) is well known to assist the movement of nutrients, organelles and genetic material by transporting all of the cytoplasmic contents of a cell. CPS is generated by motility organelles that are driven by motor proteins near a membrane surface, where the CPS has been found to have a flat velocity profile in the flow field according to the sliding theory. There is a consistent mixing of contents inside the cell by CPS if the velocity gradient profile is flattened, which is not assisted by advection diffusion but is only supported by Brownian diffusion. Although the precise flow structure of the cytoplasm has an important role for cellular metabolism, the hydrodynamic mechanism of its convection has not been clarified. We conducted an experiment to visualise the flow of cytoplasm in Nitella cells by injecting tracer fluorescent nanoparticles and using a flow visualisation system in order to understand how the flow profile affects their metabolic system. We determined that the velocity field in the cytosol has an obvious velocity gradient, not a flattened gradient, which suggests that the gradient assists cytosolic mixing by Taylor–Aris dispersion more than by Brownian diffusion.
Dissecting gene expression at the blood-brain barrier

The availability of genome-wide expression data for the blood-brain barrier is an invaluable resource that has recently enabled the discovery of several genes and pathways involved in the development and maintenance of the blood-brain barrier, particularly in rodent models. The broad distribution of published data sets represents a viable starting point for the molecular dissection of the blood-brain barrier and will further direct the discovery of novel mechanisms of blood-brain barrier formation and function. Technical advances in purifying brain endothelial cells, the key cell that forms the critical barrier, have allowed for greater specificity in gene expression comparisons with other central nervous system cell types, and more systematic characterizations of the molecular composition of the blood-brain barrier. Nevertheless, our understanding of how the blood-brain barrier changes during aging and disease is underrepresented. Blood-brain barrier data sets from a wider range of experimental paradigms and species, including invertebrates and primates, would be invaluable for investigating the function and evolution of the blood-brain barrier. Newer technologies in gene expression profiling, such as RNA-sequencing, now allow for finer resolution of transcriptomic changes, including isoform specificity and RNA-editing. As our field continues to utilize more advanced expression profiling in its ongoing efforts to elucidate the blood-brain barrier, including in disease and drug delivery, we will continue to see rapid advances in our understanding of the molecular mediators of barrier biology. We predict that the recently published data sets, combined with forthcoming genomic and proteomic blood-brain barrier data sets, will continue to fuel the molecular genetic revolution of blood-brain barrier biology.
GLADE: a scalable framework for efficient analytics

In this paper we introduce GLADE, a scalable distributed framework for large scale data analytics. GLADE consists of a simple user-interface to define Generalized Linear Aggregates (GLA), the fundamental abstraction at the core of GLADE, and a distributed runtime environment that executes GLAs by using parallelism extensively. GLAs are derived from User-Defined Aggregates (UDA), a relational database extension that allows the user to add specialized aggregates to be executed inside the query processor. GLAs extend the UDA interface with methods to Serialize/Deserialize the state of the aggregate required for distributed computation. As a significant departure from UDAs which can be invoked only through SQL, GLAs give the user direct access to the state of the aggregate, thus allowing for the computation of significantly more complex aggregate functions. GLADE runtime is an execution engine optimized for the GLA computation. The runtime takes the user-defined GLA code, compiles it inside the engine, and executes it right near the data by taking advantage of parallelism both inside a single machine as well as across a cluster of computers. This results in maximum possible execution time performance (all our experimental tasks are I/O-bound) and linear scaleup.
Developing Hydro-Meteorological Thresholds for Shallow Landslide Initiation and Early Warning

Consistent relations between shallow landslide initiation and associated rainfall characteristics remain difficult to identify, due largely to the complex hydrological and geological processes causing slopes to be predisposed to failure and those processes that subsequently trigger failures. Considering the importance of hillslope hydrology for rainfall-induced landsliding, we develop and test a method for identifying hybrid hydro-meteorological thresholds to assess landslide initiation potential. We outline a series of steps for using a landslide inventory in combination with triggering rainfall and antecedent wetness to identify empirical thresholds that can inform landslide early warning systems. The method is semi-automated but remains flexible enough to allow threshold developers to consider data inputs and various performance metrics with different priorities for balancing failed versus false alarms. We demonstrate the utility of our approach for two monitoring sites near Seattle, Washington and in Portland, Oregon, USA, to develop daily bilinear thresholds within a two-dimensional parameter space, which rely on accurate 24 h forecasts, measured recent rainfall and in situ soil saturation. Although there were no prior landslide thresholds for Portland, our new hybrid threshold for the Seattle area outperforms established rainfall-only thresholds for the same region. Introducing subsurface hydrologic monitoring into landslide initiation thresholds has the potential to greatly improve early warning capabilities and help reduce losses.
VEGF, VEGFR‐1, and CTGF cell densities in tendon are increased with cyclical loading: An in vivo tendinopathy model

Tendon injuries can occur in athletes and workers whose tasks involve repetitive, high‐force hand activities, but the early pathophysiologic processes of tendinopathy are not well known. The purpose of this animal study was to evaluate the effects of cyclical tendon loading on the densities of cells producing growth factors such as vascular endothelial growth factor (VEGF), its receptor, vascular endothelial growth factor receptor 1 (VEGFR‐1), and connective tissue growth factor (CTGF) in the Flexor Digitorum Profundus (FDP) tendon at the epicondyle. The FDP muscles of nine New Zealand rabbits were electrically stimulated to contract repetitively for 80 h of cumulative loading over 14 weeks. The contralateral limbs served as controls. The tendons at the medial epicondyle insertion sites were harvested, and sections were immunostained with antibodies directed against VEGF, VEGFR‐1, or CTGF. Positive‐staining cells were counted in six regions of interest: three along the enthesis, and three corresponding regions 1500 microns distal to the enthesis. VEGF (p = 0.0001), VEGFR‐1 (p = 0.046), and CTGF (p = 0.0001) cell densities were increased in the tendon of the loaded limb compared to the nonloaded limb. In addition, regional differences in VEGF, VEGFR‐1, and CTGF cell densities were found. VEGF, VEGFR‐1, and CTGF are increased in tendon experiencing cyclical loading and may play a role in the early vascular changes in the progression to tendinosis. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:393–400, 2006
Ontogeny-related changes in proliferative potential of human hematopoietic cells

Blood cells originate from hematopoietic stem cells that are located at different sites during ontogeny. Production of human stem cells and their progeny in culture is expected to have important implications for experimental therapeutic strategies involving gene transfer and transplantation. Here we report striking differences between primitive hematopoietic cells purified from adult bone marrow, umbilical cord blood, and fetal liver in cytokine-supplemented, serum-free cultures. In such cultures both the fraction of responding cells and their ability to produce CD34+ progenitor cells decreased markedly with the age of the cell donor. These results document extensive, ontogeny- related functional differences between primitive hematopoietic cells.
Kinetic properties of the Na+/H+ antiport of heart mitochondria.

The fluorescence of 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) has been used to follow the Na+/H+ antiport activity of isolated heart mitochondria as a Na+-dependent extrusion of matrix H+. The antiport activity measured in this way shows a hyperbolic dependence on external Na+ or Li+ concentration when the external pH (pHo) is 7.2 or higher. The apparent Km for Na+ decreases with increasing pHo to a limit of 4.6 mM. The Ki for external H+ as a competitive inhibitor of Na+/H+ antiport averages 3.0 nM (pHo 8.6). The Vmax at 24 degrees C is 160 ng ion of H+ min-1 (mg of protein)-1 and does not vary with pHo. Li+ reacts with the antiporter with higher affinity, but much lower Vmax, and is a competitive inhibitor of Na+/H+ antiport. The rate of Na+/H+ antiport is optimal when the pHi is near 7.2. When pHo is maintained constant, Na+-dependent extrusion of matrix H+ shows a hyperbolic dependence on [H+]i with an apparent Km corresponding to a pHi of 6.8. The Na+/H+ antiport is inhibited by benzamil and by 5-N-substituted amiloride analogues with I50 values in the range from 50 to 100 microM. The pH profile for this inhibition seems consistent with the availability of a matrix binding site for the amiloride analogues. The mitochondrial Na+/H+ antiport resembles the antiport found in the plasma membrane of mammalian cells in that Na+, Li+, and external H+ appear to compete for a common external binding site and both exchanges are inhibited by amiloride analogues. (ABSTRACT TRUNCATED AT 250 WORDS)
Clinical prediction rules for failed nonoperative reduction of intussusception

Purpose The nonoperative reduction of intussusception in children can be performed safely if there are no contraindications. Many risk factors associated with failed reduction were defined. The aim of this study was to develop a scoring system for predicting the failure of nonoperative reduction using various determinants. Patients and methods The data were collected from Chiang Mai University Hospital and Siriraj Hospital from January 2006 to December 2012. Inclusion criteria consisted of patients with intussusception aged 0–15 years with no contraindications for nonoperative reduction. The clinical prediction rules were developed using significant risk factors from the multivariable analysis. Results A total of 170 patients with intussusception were included in the study. In the final analysis model, 154 patients were used for identifying the significant risk factors of failure of reduction. Ten factors clustering by the age of 3 years were identified and used for developing the clinical prediction rules, and the factors were as follows: body weight <12 kg (relative risk [RR] =1.48, P=0.004), duration of symptoms >48 hours (RR =1.26, P<0.001), vomiting (RR =1.63, P<0.001), rectal bleeding (RR =1.50, P<0.001), abdominal distension (RR =1.60, P=0.003), temperature >37.8°C (RR =1.51, P<0.001), palpable mass (RR =1.26, P<0.001), location of mass (left over right side RR =1.48, P<0.001), ultrasound showed poor prognostic signs (RR =1.35, P<0.001), and the method of reduction (hydrostatic over pneumatic, RR =1.34, P=0.023). Prediction scores ranged from 0 to 16. A high-risk group (scores 12–16) predicted a greater chance of reduction failure (likelihood ratio of positive [LR+] =18.22, P<0.001). A low-risk group (score 0–11) predicted a lower chance of reduction failure (LR+ =0.79, P<0.001). The performance of the scoring model was 80.68% (area under the receiver operating characteristic curve). Conclusion This scoring guideline was used to predict the results of nonoperative reduction and forecast the prognosis of the failed reduction. The usefulness of these prediction scores is for informing the parents before the reduction. This scoring system can be used as a guide to promote the possible referral of the cases to tertiary centers with facilities for nonoperative reduction if possible.
Allele-Specific Quantification of Structural Variations in Cancer Genomes

One of the hallmarks of cancer genome is aneuploidy, resulting in abnormal copy numbers of alleles. Structural variations (SVs) can further modify the aneuploid cancer genomes into a mixture of rearranged genomic segments with extensive range of somatic copy number alterations (CNAs). Indeed, aneuploid cancer genomes have significantly higher rate of CNAs and SVs. However, although methods have been developed to identify SVs and allele-specific copy number of genome (ASCNG) separately, no existing algorithm can simultaneously analyze SVs and ASCNG. Such integrated approach is particularly important to fully understand the complexity of cancer genomes. Here we introduce a new algorithm called Weaver to provide allele-specific quantification of SVs and CNAs in aneuploid cancer genomes. Weaver uses a probabilistic graphical model by utilizing cancer whole genome sequencing data to simultaneously estimate the digital copy number and inter-connectivity of SVs. Our simulation evaluation, comparison with single-molecule Optical Mapping analysis, and real data applications (including MCF-7, HeLa, and TCGA whole genome sequencing samples) demonstrated that Weaver is highly accurate and can greatly refine the analysis of complex cancer genome structure.
[Nonvascular phalangeal transfer from toes to hand in congenital aphalangia].

OBJECTIVES Free transfer of the toe phalanges to the hand without vascular anastomosis is a proposed option for reconstruction of congenital aphalangia. We evaluated the growth behavior of the phalanges in patients after transfer. METHODS Six patients with congenital aphalangia underwent 18 nonvascular phalangeal transfers from toes to the hand. The anomaly was bilateral in one patient. Except for one patient who was 11.5 years old, the mean age at the time of surgery was 27 months (range 14 to 48 months). The patients were followed-up for a mean of 2.5 years (range 2 to 4 years) with respect to functional results, yearly longitudinal growth, epiphysial closure, bone resorption or necrosis, digital tip necrosis, fracture, angulation, subluxation, infections, and donor site morbidity. RESULTS The mean yearly longitudinal growth rate of transferred phalanges was 2.4 mm. On final radiographic examinations, epiphysial closure was not completed in 14 phalanges (78%). Functional improvements included stabilization using the affected digit in three patients, and performing further movements in three patients. One patient underwent reoperation for postoperative subluxation. No fractures or angulation above 15 degrees were seen. Bone resorptions were partial in three patients (16%), and total in one patient (5%). Concerning soft tissue complications, digital tip necrosis developed in one patient (5%). No infections were encountered during the follow-up. All the patients exhibited minimal donor digit shortening. CONCLUSION Nonvascular phalangeal transfer is an alternative rehabilitation method by which use of prosthetics may be facilitated and functional capacity may be increased in congenital hand anomalies such as congenital aphalangia, in which vascular phalanx transfer is not suitable.
Evidence for Direct Activation of mTORC2 Kinase Activity by Phosphatidylinositol 3,4,5-Trisphosphate*

mTORC2 (mammalian target of rapamycin complex 2) plays important roles in signal transduction by regulating an array of downstream effectors, including protein kinase AKT. However, its regulation by upstream regulators remains poorly characterized. Although phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) is known to regulate the phosphorylation of AKT Ser473, the hydrophobic motif (HM) site, by mTORC2, it is not clear whether PtdIns(3,4,5)P3 can directly regulate mTORC2 kinase activity. Here, we used two membrane-docked AKT mutant proteins, one with and the other without the pleckstrin homology (PH) domain, as substrates for mTORC2 to dissect the roles of PtdIns(3,4,5)P3 in AKT HM phosphorylation in cultured cells and in vitro kinase assays. In HEK293T cells, insulin and constitutively active mutants of small GTPase H-Ras and PI3K could induce HM phosphorylation of both AKT mutants, which was blocked by the PI3K inhibitor LY294002. Importantly, PtdIns(3,4,5)P3 was able to stimulate the phosphorylation of both AKT mutants by immunoprecipitated mTOR2 complexes in an in vitro kinase assay. In both in vivo and in vitro assays, the AKT mutant containing the PH domain appeared to be a better substrate than the one without the PH domain. Therefore, these results suggest that PtdIns(3,4,5)P3 can regulate HM phosphorylation by mTORC2 via multiple mechanisms. One of the mechanisms is to directly stimulate the kinase activity of mTORC2.