Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Basis for Substrate Fatty Acyl Chain Specificity

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a member of the family of acyl-CoA dehydrogenases (ACADs). Unlike the other ACADs, which are soluble homotetramers, VLCAD is a homodimer associated with the mitochondrial membrane. VLCAD also possesses an additional 180 residues in the C terminus that are not present in the other ACADs. We have determined the crystal structure of VLCAD complexed with myristoyl-CoA, obtained by co-crystallization, to 1.91-Å resolution. The overall fold of the N-terminal ∼400 residues of VLCAD is similar to that of the soluble ACADs including medium-chain acyl-CoA dehydrogenase (MCAD). The novel C-terminal domain forms an α-helical bundle that is positioned perpendicular to the two N-terminal helical domains. The fatty acyl moiety of the bound substrate/product is deeply imbedded inside the protein; however, the adenosine pyrophosphate portion of the C14-CoA ligand is disordered because of partial hydrolysis of the thioester bond and high mobility of the CoA moiety. The location of Glu-422 with respect to the C2-C3 of the bound ligand and FAD confirms Glu-422 to be the catalytic base. In MCAD, Gln-95 and Glu-99 form the base of the substrate binding cavity. In VLCAD, these residues are glycines (Gly-175 and Gly-178), allowing the binding channel to extend for an additional 12Å and permitting substrate acyl chain lengths as long as 24 carbons to bind. VLCAD deficiency is among the more common defects of mitochondrial β-oxidation and, if left undiagnosed, can be fatal. This structure allows us to gain insight into how a variant VLCAD genotype results in a clinical phenotype.
Measures of Maternal Stress and Mood in Relation to Preterm Birth

OBJECTIVE: To investigate the relationships between psychological and physiologic measures of stress, mood, and gestational age at delivery and preterm birth. METHODS: This prospective cohort study recruited healthy women in the early second trimester who were 18–45 years of age. Validated psychological measures of perceived stress, depressive symptoms, and anxiety were completed at 16, 22, 28, 34, and 40 weeks of gestation. Cortisol concentration was measured in maternal hair at 16, 28, and 40 weeks of gestation to approximate first-, second-, and third-trimester levels of physiologic stress. Statistical methods included: analyses of variance, t tests, &khgr;2, Pearson correlations, regression modeling, and mediation analysis as appropriate. Hair cortisol concentrations were natural log-transformed to normalize values. RESULTS: Eleven (12%) of the 90 included women had a spontaneous preterm birth or preterm premature rupture of membranes. Perceived stress at 16 weeks of gestation correlated with both second-trimester cortisol concentration (r=0.28, P=.007) and earlier gestational age at delivery (r=−0.30, P<.01). Gestational age at delivery was also negatively correlated with cortisol concentration in the second trimester (r=−0.25, P=.02) and second-trimester cortisol concentration was higher in preterm- (2.7±0.4 log-transformed pg/mg) compared with term- (2.0±0.7 log-transformed pg/mg, P<.001) delivered women. Using mediation statistics, the association between the psychological measure, the physiologic measure, and gestational age at delivery was mainly driven by increased physiologic stress (hair cortisol concentration) in the second trimester (difference in coefficients [standard error]=−0.05 [0.02]). CONCLUSION: Higher perceived stress in the second trimester is associated with both elevated second-trimester hair cortisol concentration and gestational age at delivery. Physiologic measure of stress in the second trimester appears most strongly associated with preterm birth. Identification and amelioration of early pregnancy stressors may attenuate physiologic stress and ultimately affect preterm birth.
Lagrangian Relaxation Based Inter-Layer Signal Via Assignment for 3-D ICs

Three-dimensional integrated circuits (3-D ICs), i.e., stacked dies, can alleviate the interconnect problem coming with the decreasing feature size and increasing integration density, and promise a solution to heterogenous integration. The vertical connection, which is generally implemented by the through-the-silicon via, is a key technology for 3-D ICs. In this paper, given 3-D circuit placement or floorplan results with white space reserved between blocks for inter-layer interconnections, we proposed methods for assigning inter-layer signal via locations. Introducing a grid structure on the chip, the inter-layer via assignment of two-layer chips can be optimally solved by a convex-cost max-flow formulation with signal via congestion optimized. As for 3-D ICs with three or more layers, the inter-layer signal via assignment is modeled as an integral min-cost multi-commodity flow problem, which is solved by a heuristic method based on the lagrangian relaxation. Relaxing the capacity constraints in the grids, we transfer the min-cost multi-commodity flow problem to a sequence of lagrangian sub-problems, which are solved by finding a sequence of shortest paths. The complexity of solving a lagrangian sub-problem is $O(n_{nt}n_g^2)$, where nnt is the number of nets and ng is the number of grids on one chip layer. The experimental results demonstrated the effectiveness of the method.
The use of the Karnofsky index in the assessment of clinical state in patients with chronic subdural hematoma: the first observation from Vojvodina.

AIM To evaluate clinical status of patients with chronic subdural hematoma (CSDH) on hospital admission and to predict their outcome after the neurosurgery treatment using Karnofsky index scale (KI). METHODS Clinical and surgery data of patients with CSDH were collected prospectively. Fifty 50 adults aged over 41 with CSDH diagnosed and hospitalized between November 2010 and April 2012 were investigated. In the analyzed sample there were more CSDHs in males than in females (1.5:1). The diagnosis of CSDH on hospital admission in patients was confirmed by non-contrast computed tomography (CT). Forty-three patients had undergone surgery with Burr-hole drainage and craniotomy, while seven patients were treated conservatively. The KI was used for evaluation of the patient's clinical state before neurosurgery treatment and the quality of survival in all patients, six months after hospital discharge. RESULTS A statistically significant difference was found between the KI values in patients with CSDHs on hospital admission and KI after the surgical treatment. Six months after, out of 43 patients who underwent surgery in 24 (55.8%) patients KI was between 80-100%, in nine (20.9%) patients KI was between 50-70% and in 10 (23.2%) patients KI was 0-40%. CONCLUSION Although the elderly with CSDHs are vulnerable because of their age, associated diseases and risk of recurrence of CSDH, their outcome assessed by KI after surgical treatment was good. The Glasgow Coma Scale (GCS) is used for rapid assessment of the state of consciousness in patients on admission and monitoring of the changes in their condition. KI scale could be used as a complementary assessment tool for the general condition of patients with chronic subdural hematoma. This study highlighted that the KI scale had a predictive value for patient's outcome with chronic subdural hematoma.
[Acquired regressive cutaneous non-Langerhans-cell histiocytosis in an infant].

INTRODUCTION Cutaneous histiocytosis of childhood often regresses spontaneously without treatment. In some cases however, it is difficult to differentiate aggressive forms and electron microscopy and immunohistochemistry can be a valuable help. We report a case of cutaneous histiocytosis in a child which illustrates the difficulties encountered in the classification of histiocytosis. CASE REPORT An 18-month old girl was brought to consultation with a cutaneous nodule which had developed at the age of 15 months on the labia majora. A second nodule on the chin had regressed spontaneously. Histology showed evidence of dermal histiocyte proliferation. Immunohistochemistry demonstrated is non Langerhans nature which was confirmed by electron microscopy. The clinical course was benign after surgical exeresis of the lesion on the labia majora. DISCUSSION Different forms of histiocytosis can be classed on the basis of 4 criteria: Langerhans origin or not, acquired or congenital forms, cutaneous or visceral involvement, benign or malignant course. Four diagnosis were possible in our case: histiocytosis X, self-healing congenital histiocytosis, benign cephalic histiocytosis, juvenile xanthogranuloma. We preferred to use the descriptive term of acquired regressive cutaneous non-X histiocytosis of childhood.
Predictive Value of Pelvic Incidence in Progression of Spondylolisthesis

Study Design. Retrospective analysis of pelvic incidence and other radiographic parameters as a predictor of progression of isthmic spondylolisthesis. Objectives. To evaluate the predictive value of various radiographic parameters, including pelvic incidence, in determining the risk for progression of lumbosacral isthmic spondylolisthesis. Summary of Background Data. Although pelvic incidence has recently been shown to be positively correlated to the severity of spondylolisthesis, it has not been confirmed as a predictor of spondylolisthetic progression. Materials and Methods. Thirty-six patients who have undergone primary posterior lumbosacral fusion for isthmic spondylolisthesis at our institution from 1977 to 2001 were retrospectively analyzed. There were 24 females and 12 males with a mean age of 21.3 ± 2.0 years (range, 12 to 53 y). Twenty-two patients had high-grade (Meyerding class III, IV, V) and 14 patients had low-grade (Meyerding class I, II) spondylolisthesis, respectively. Factors evaluated included age, gender, neurologic deficits, reason for surgery, and documented evidence of progression. Slip percentage, high-grade or low-grade slip, slip angle, sacral inclination, sacral rounding, trapezoidal L5 vertebra, and pelvic incidence were measured from immediate preoperative standing lateral radiographs. These factors were statistically analyzed for risk of progression. Continuous variables were analyzed using one-way analysis of variance. Nominal variables were analyzed using &khgr;2 test. Results. Pelvic incidence (P = 0.66) was not predictive of spondylolisthetic progression. Of the other radiographic measurements, slip percentage (P < 0.001), slip angle (P = 0.016), and high-grade spondylolisthesis (P < 0.0001) were highly predictive of progression. Interestingly, sacral inclination (P = 0.33) was not predictive of progression. Conclusions. Pelvic incidence cannot adequately predict the probability of spondylolisthetic progression. Analysis of the other clinical and radiographic parameters revealed that slip percentage and high-grade spondylolis thesis remain the most positive predictors of progression.
Import of proteins into yeast mitochondria: the nuclear MAS2 gene encodes a component of the processing protease that is homologous to the MAS1‐encoded subunit.

The mas2 mutant of Saccharomyces cerevisiae is temperature sensitive for import of proteins into mitochondria. To identify the lesion in this mutant, we have cloned and sequenced the wild‐type MAS2 gene and determined the intracellular location of its protein product. MAS2 encodes an essential 53‐kd protein that is located in the mitochondrial matrix and is homologous to the MAS1 protein, a previously identified subunit of the protease that cleaves presequences from mitochondrial precursor proteins. The activity of this enzyme is temperature sensitive in mas2 cells. Together with the results of the accompanying study these results show that MAS2 and MAS1 encode the two subunits of the processing protease.
Regulation of growth, protein synthesis, and maturation of fetal bovine epiphyseal chondrocytes grown in high‐density culture in the presence of ascorbic acid, retinoic acid, and dihydrocytochalasin B

Phenotypic expression of chondrocytes can be modulated in vitro by changing the culture technique and by agents such vitamins and growth factors. We studied the effects of ascorbic acid, retinoic acid (0.5 and 10 μM), and dihydrocytochalasin B (3, 10, 20 μM DHCB), separately or in combination (ascorbic acid + retinoic acid or ascorbic acid + DHCB), on the induction of maturation of fetal bovine epiphyseal chondrocytes grown for up to 4 weeks at high density in medium containing 10% fetal calf serum and the various agents. In the absence of any agent or with retinoic acid or DHCB alone, the metabolic activity of the cells remained very low after day 6, with no induction of type I or X collagen synthesis nor increase in alkaline phosphatase activity. Chondrocytes treated with fresh ascorbic acid showed active protein synthesis associated with expression of types I and X after 6 and 13 days, respectively. This maturation was not accompanied by obvious hypertrophy of the cells or high alkaline phosphatase activity. Addition of retinoic acid to the ascorbic acid‐treated cultures decreased the level of type II collagen synthesis and delayed the induction of types I and X collagen, which were present only after 30 days. A striking increase in alkaline phosphatase activity (15–20‐fold) was observed in the presence of both ascorbic acid and the highest dose of retinoic acid (10 μM). DHCB was also a potent inhibitor of the maturation induced by treatment with ascorbic acid, as the chondrocytes maintained their rounded shape and synthesized type II collagen without induction of type I or X collagen. The pattern of protein secretion was compared under all culture conditions by two‐dimensional gel electrophoresis. The different regulations of chondrocyte differentiation by ascorbic acid, retinoic acid, and DHCB were confirmed by the important qualitative and quantitative changes in the pattern of secreted proteins observed by two‐dimensional gel electrophoresis along the study. J. Cell. Biochem. 76:84–98, 1999. © 1999 Wiley‐Liss, Inc.
Maximal and submaximal aerobic tests for wheelchair-dependent persons with spinal cord injury: a systematic review to summarize and identify useful applications for clinical rehabilitation

Abstract Purpose: To summarize the available maximal and submaximal aerobic exercise tests for wheelchair-dependent persons with a spinal cord injury (SCI) and to identify useful applications for clinical rehabilitation. Method: The databases of PubMed, CINAHL®, EMBASE, and PsycINFO® were searched for English-language studies published prior to March 2015. Two independent raters identified and examined studies that reported on laboratory-based aerobic exercise tests in persons with an SCI, according to the PRISMA statement. Results: The test protocols of maximal (n = 105) and submaximal (n = 28) exercise tests, covered by 95 included studies, were assessed. A large variety in patient characteristics, test objectives, test protocols, exercise modes, and outcome parameters was reported. Few studies reported on adherence to recommendations, adverse events, and peak outcome validation. Conclusions: An incremental test protocol with small, individualized, increments per stage seems preferable for testing maximal aerobic capacity, but additional validation of the available test modes is required to draw conclusions. Submaximal testing is relevant for assessing the performance at daily life intensities and for estimating VO2peak. Consensus regarding reporting test procedures and outcomes needs to be achieved to enhance comparability of rehabilitation results. Implications for Rehabilitation Regularly testing the cardiovascular capacity during SCI rehabilitation will enable us to monitor the impact of rehabilitation interventions on an individual level. The incremental arm ergometry test with small increments per stage is most relevant for the assessment of the peak cardiovascular capacity. For the assessment of daily life functioning, the submaximal wheelchair ergometer test is preferable. Hand cycling is a promising exercise mode for both testing and training. Systematically reporting on test termination, criteria for attaining valid peak outcomes and adverse events is necessary to enhance comparability of results.
Examining the Effects of Anabolic–Androgenic Steroids on Repetitive Mild Traumatic Brain Injury (RmTBI) Outcomes in Adolescent Rats

Background: Repetitive mild traumatic brain injury (RmTBI) is increasingly common in adolescents. Anabolic–androgenic steroid (AAS) consumption among younger professional athletes is a significant risk factor for impaired neurodevelopment. Given the increased rates and overlapping symptomology of RmTBI and AAS use, we sought to investigate the behavioural and neuropathological outcomes associated with the AAS Metandienone (Met) and RmTBI on rats. Methods: Rats received either Met or placebo and were then administered RmTBIs or sham injuries, followed by a behavioural test battery. Post-mortem MRI was conducted to examine markers of brain integrity and qRT-PCR assessed mRNA expression of markers for neurodevelopment, neuroinflammation, stress responses, and repair processes. Results: Although AAS and RmTBI did not produce cumulative deficits, AAS use was associated with detrimental outcomes including changes to depression, aggression, and memory; prefrontal cortex (PFC) atrophy and amygdala (AMYG) enlargement; damaged white matter integrity in the corpus callosum; and altered mRNA expression in the PFC and AMYG. RmTBI affected general activity and contributed to PFC atrophy. Conclusions: Findings corroborate previous results indicating that RmTBI negatively impacts neurodevelopment but also demonstrates that AAS results in significant neuropathological insult to the developing brain.
Spore heat resistance and specific mineralization

Spores of Bacillus megaterium ATCC 19213, Bacillus subtilis niger and Bacillus stearothermophilus ATCC 7953 were converted to fully demineralized, but viable, H forms by controlled acid titration. H forms were more heat sensitive than were native forms, but z values were greater for killing of H spores than those for native spores. Therefore, the differences in heat sensitivity between native and H forms decreased with increasing killing temperature. The increase in heat sensitivity associated with demineralization did not appear to be due to damage to cortex lytic enzymes of the germination system because it could not be moderated by decoating heated H spores and plating them on medium with added lysozyme. H spores could be remineralized by means of back titration with appropriate base solutions. The remineralized spores, except for the Na form, were then more heat resistant than were H spores. Ca and Mn were more effective in restoring resistance than were Mg and K. Generally, the remineralized forms (except for the Na form) had z values greater than those of the native forms but still less than those of the H forms. At lower killing temperatures, the reinstatement of resistance could be related to the extent of remineralization. However, at higher killing temperatures, only a fraction of the mineral was effective in restoring resistance, and higher levels of remineralization did not result in greater resistance. Mineralization is clearly an important factor in spore heat resistance, but the relationship between resistance and mineralization is complex and dependent on killing temperature.
Prolonged but reversible neutrophil dysfunctions differentially sensitive to granulocyte colony‐stimulating factor in children with acute lymphoblastic leukaemia

Treatment of average‐risk acute lymphoblastic leukaemia (ALL) in children consists of 6 months of intensive chemotherapy followed by 18 months of maintenance therapy. Polymorphonuclear leucocyte (PMN) functions from children with ALL were studied in order to evaluate and compare the toxicity of the initial intensive treatment with the toxicity of the subsequent less intensive maintenance treatment. H2O2 and O−2 production, evaluated by chemiluminescence, were significantly decreased during the intensive period but returned to normal values when maintenance therapy began. In contrast, bactericidal activity against Gram‐positive and Gram‐negative micro‐organisms remained at low levels throughout the treatment but returned to normal values in patients off chemotherapy. PMN from patients on maintenance therapy exhibited an excess of morphological changes associated with apoptosis. This was confirmed by standard two‐colour flow cytometry which revealed an increase in the number of hypodiploid cells, and increased expression of membrane phosphatidylserine together with a drastic reduction in the expression of the Fcγ receptor IIIB (CD16). These defective PMN were differentially sensitive to the effects of granulocyte colony stimulating factor (G‐CSF): G‐CSF induced similar increase in chemiluminescence in control and patient PMN; GSF partially corrected the defective bactericidal activity; G‐CSF did not affect the accelerated PMN apoptosis. These observations indicate that ALL children undergoing chemotherapy present PMN defective functions which are partially sensitive or even resistant to G‐CSF.
Linear and Nonlinear Mixed‐Effects Models for Censored HIV Viral Loads Using Normal/Independent Distributions

Summary HIV RNA viral load measures are often subjected to some upper and lower detection limits depending on the quantification assays. Hence, the responses are either left or right censored. Linear (and nonlinear) mixed‐effects models (with modifications to accommodate censoring) are routinely used to analyze this type of data and are based on normality assumptions for the random terms. However, those analyses might not provide robust inference when the normality assumptions are questionable. In this article, we develop a Bayesian framework for censored linear (and nonlinear) models replacing the Gaussian assumptions for the random terms with normal/independent (NI) distributions. The NI is an attractive class of symmetric heavy‐tailed densities that includes the normal, Student's‐t, slash, and the contaminated normal distributions as special cases. The marginal likelihood is tractable (using approximations for nonlinear models) and can be used to develop Bayesian case‐deletion influence diagnostics based on the Kullback–Leibler divergence. The newly developed procedures are illustrated with two HIV AIDS studies on viral loads that were initially analyzed using normal (censored) mixed‐effects models, as well as simulations.
Quantitative magnetic resonance imaging of subcutaneous adipose tissue

Background/purpose: Quantitative transverse relaxation time (T2) magnetic resonance (MR) imaging has been used with the aim to characterize subcutaneous adipose tissue. Protons in adipose tissue have a fast exchange behavior giving bi‐component transverse relaxation processes with short and long relaxation time values depending on the tissue properties.