Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Course and Changes in High-Resolution Computed Tomography Findings in Patients with Idiopathic Pulmonary Fibrosis without Honeycombing

Some patients with idiopathic pulmonary fibrosis (IPF) do not have honeycombing on high-resolution computed tomography (HRCT) at their initial evaluation. The clinical course and sequential changes in HRCT findings in these patients are not fully understood. We reviewed the cases of 43 patients with IPF without honeycombing on initial HRCT from institutions throughout Japan. All patients were diagnosed with IPF based on a surgical lung biopsy. Multidisciplinary discussions were held five times between 2011 and 2014, to exclude alternative etiologies. We evaluated the sequential changes in HRCT findings in 30 patients with IPF. We classified these 30 patients into three groups based on their HRCT patterns and clarified the clinical characteristics and prognosis among the groups. The patterns of all 30 patients on initial HRCT corresponded to a possible usual interstitial pneumonia (UIP) pattern which was described in the 2011 International Statement. On long-term follow-up (71.0±38.7 standard deviation [SD] months), honeycombing was seen in 16 patients (53%, the HoneyCo group); traction bronchiectasis or cysts without honeycombing was observed in 12 patients (40%, the NoHoneyCo group), and two patients showed no interval change (7%, the NoChange group) on HRCT. The mean survival periods of the HoneyCo and NoHoneyCo groups were 67.1 and 61.2 months, respectively (p = 0.76). There are some patients with IPF whose conditions chronically progress without honeycombing on HRCT. The appearance of honeycombing on HRCT during the follow-up might not be related to prognosis.
Climate change: effects on culicoides--transmitted viruses and implications for the UK.

Changes in the distribution and abundance of insects are likely to be amongst the most important and immediate effects of climate change. We review here the risk that climate change poses to the UK's livestock industry via effects on Culicoides biting midges, the vectors of several arboviruses, including those that cause bluetongue (BT) and African horse sickness (AHS). The major old-world vector of BT and AHS viruses, C. imicola, occurs in southern Europe and will spread further north as global temperatures increase. It is unlikely, however, that in the foreseeable future it will reach and become established in the UK. As the distribution of C. imicola moves north, however, it may bring BT and AHS viruses into the range of other Culicoides species that are known to be competent vectors and which occur much further north. Once infected via this 'baton effect', these species may be able to spread the viruses over much of Europe, including the UK. Climate change may increase their vector competence further and will also increase the likelihood of viruses surviving from one year to the next. An additional risk is that the predicted increase in the frequency of short periods of hot temperatures may lead to the creation of novel vector species, by removing the barriers that in colder conditions make them refractory to viral infection.
The role of O2 supply in muscle fatigue.

It is well established that altering O2 delivery to contracting skeletal muscle affects human performance. In this respect, a reduced O2 supply (e.g., hypoxia) increases the rate of muscle fatigue, whereas increasing O2 supply (e.g., hyperoxia) reduces the rate of fatigue. Interestingly, the faster onset of fatigue in moderate hypoxia does not appear to be a consequence of mitochondrial O2 limitation because these effects occur at submaximal rates of O2 consumption for these conditions and at O2 tensions well above that which impairs mitochondrial O2 uptake in vitro. Alterations in O2 supply modulate the regulation of cellular respiration and may affect the onset of impaired Ca2+ handling with fatigue. Specifically, changes in O2 supply alter the coupling between phosphocreatine hydrolysis and O2 uptake in contracting muscles, which by determining the rate of inorganic phosphate (Pi) accumulation may affect Ca2+ release. Partial ischemia differs somewhat in that the reduction in force could be due to reduced O2 supply and/or impaired removal of metabolic by-products secondary to insufficient blood flow. Nonetheless, recent evidence shows a parallel decline and restoration of force with alterations in O2 supply but not blood flow alone during submaximal contractions. Furthermore, the causes of fatigue are similar when O2 is plentiful and when it is reduced.
Comparison of outcomes of kidney transplantation from donation after brain death, donation after circulatory death, and donation after brain death followed by circulatory death donors

There are three categories of deceased donors of kidney transplantation in China, donation after brain death (DBD), donation after circulatory death (DCD), and donation after brain death followed by circulatory death (DBCD) donors. The aim of this study was to compare the outcomes of kidney transplantation from these three categories of deceased donors.
Alkylamides from Echinacea Are a New Class of Cannabinomimetics

Alkylamides (alkamides) from Echinacea modulate tumor necrosis factor α mRNA expression in human monocytes/macrophages via the cannabinoid type 2 (CB2) receptor (Gertsch, J., Schoop, R., Kuenzle, U., and Suter, A. (2004) FEBS Lett. 577, 563–569). Here we show that the alkylamides dodeca-2E,4E,8Z,10Z-tetraenoic acid isobutylamide (A1) and dodeca-2E,4E-dienoic acid isobutylamide (A2) bind to the CB2 receptor more strongly than the endogenous cannabinoids. The Ki values of A1 and A2 (CB2 ∼60 nm;CB1 >1500 nm) were determined by displacement of the synthetic high affinity cannabinoid ligand [3H]CP-55,940. Molecular modeling suggests that alkylamides bind in the solvent-accessible cavity in CB2, directed by H-bonding and π -π interactions. In a screen with 49 other pharmacologically relevant receptors, it could be shown that A1 and A2 specifically bind to CB2 and CB1. A1 and A2 elevated total intracellular Ca2+ in CB2-positive but not in CB2-negative promyelocytic HL60 cells, an effect that was inhibited by the CB2 antagonist SR144528. At 50 nm, A1, A2, and the endogenous cannabinoid anandamide (CB2 Ki >200 nm) up-regulated constitutive interleukin (IL)-6 expression in human whole blood in a seemingly CB2-dependent manner. A1, A2, anandamide, the CB2 antagonist SR144528 (Ki <10 nm), and also the non-CB2-binding alkylamide undeca-2E-ene,8,10-diynoic acid isobutylamide all significantly inhibited lipopolysaccharide-induced tumor necrosis factor α, IL-1β, and IL-12p70 expression (5–500 nm) in a CB2-independent manner. Alkylamides and anandamide also showed weak differential effects on anti-CD3-versus anti-CD28-stimulated cytokine expression in human whole blood. Overall, alkylamides, anandamide, and SR144528 potently inhibited lipopolysaccharide-induced inflammation in human whole blood and exerted modulatory effects on cytokine expression, but these effects are not exclusively related to CB2 binding.
On the Origin of the Non-brittle Rachis Trait of Domesticated Einkorn Wheat

Einkorn and emmer wheat together with barley were among the first cereals domesticated by humans more than 10,000 years ago, long before durum or bread wheat originated. Domesticated einkorn wheat differs from its wild progenitor in basic morphological characters such as the grain dispersal system. This study identified the Non-brittle rachis 1 (btr1) and Non-brittle rachis 2 (btr2) in einkorn as homologous to barley. Re-sequencing of the Btr1 and Btr2 in a collection of 53 lines showed that a single non-synonymous amino acid substitution (alanine to threonine) at position 119 at btr1, is responsible for the non-brittle rachis trait in domesticated einkorn. Tracing this haplotype variation back to wild einkorn samples provides further evidence that the einkorn progenitor came from the Northern Levant. We show that the geographical origin of domesticated haplotype coincides with the non-brittle domesticated barley haplotypes, which suggest the non-brittle rachis phenotypes of einkorn and barley were fixed in same geographic area in today’s South-east Turkey.
Study of a high gain radial line slot antenna in Ka-band for space uses

A slot array design for a very high gain of more than 44dBi RLSA was reported in this paper. A conventional slot array design procedure based on the Method of Moments (MoM) was still applied, but needed to modify in order to adapt with a very large number of radiating elements and a complex, multilayer structure of the substrate. A fast analysis method based on a simplified but reliable equivalent model of the multilayer waveguide was established to estimate the antenna performance. Finally, several RLSAs having φ = 900mm diameter were fabricated and characterized by the near field measurement. In the optimum case, a directivity of 48.3dBi correspond to 73% aperture efficiency was obtained at 31.9GHz, at which the measured gain was 44.6dBi.
Temperature measurements of polymer melts in the heating barrel during injection molding. Part 2: Three‐dimensional temperature distribution in the reservoir

A new method has been developed to measure the three-dimensional temperature distribution of polymer melts in the reservoir of the heating barrel in the dynamic state. The procedure involves the use of a small-sheathed thermocouple in the nozzle of the machine. The tip of the thermocouple can be varied in depth from the surface to the center of the nozzle. The polymer melt of a shot is found to have a three-dimensional temperature distribution dependent on the geometry of the screw and the order of shot. These results reflect clearly the thermal histories of the polymer melt in the channel of the screw during plastication and conveyance, and indicate part of the dynamics of injection molding. Further, these measurements contribute to optimization of the design for the screw and the process conditions.
Trauma center angiography use in high-grade blunt splenic injuries: Timing is everything

BACKGROUND The use of angiography (ANGIO) in the management of high-grade (Abbreviated Injury Scale [AIS] score > 2) blunt splenic injury (BSI) remains controversial. We aimed to compare patient characteristics of those treated at high and low ANGIO centers, to compare the characteristics of the patients undergoing ANGIO at high and low ANGIO centers, and to determine the relationship among hospital ANGIO use, the timing of angiography, and splenectomy after angiography. METHODS The National Trauma Data Bank was used to identify patients 18 years and older with BSI (AIS score > 2) treated at Level I or II trauma centers that admitted at least 10 patients with high-grade BSI from 2007 to 2010. Timing of ANGIO and splenectomy was determined. Hospitals were stratified based on ANGIO use rates into three groups: 0% (no ANGIO); 1% to 19.9% (low ANGIO); and more than 20% (high ANGIO). Hierarchical logistic regression was used to control for patient clustering at the hospital level and to determine factors associated with splenectomy. Cox regression with ANGIO as a time-varying covariate was also used. RESULTS A total of 10,405 met inclusion criteria. After adjusting for hospital case mix, low ANGIO (odds ratio, 1.02; 95% confidence interval [CI], 0.70–1.48) and no ANGIO (odds ratio, 0.88; 95% CI, 0.59–1.31) centers showed no difference with regard to splenectomy compared with high ANGIO centers. ANGIO (Hazard Ratio = 0.52; 95% CI, 0.41–0.65) was protective of splenectomy on Cox regression analysis, taking into account ANGIO timing relative to splenectomy. CONCLUSION There were no differences in splenectomy rates after adjusting for case mix at high and low ANGIO centers. Early ANGIO, irrespective of hospital ANGIO use, is associated with splenic salvage. LEVEL OF EVIDENCE Therapeutic study, level III.
Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method.

A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow. A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracer binding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors. The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derived striatal extracellular dopamine levels with in vivo microdialysis and striatal binding levels with the dopamine D2/D3 positron-emission tomography radioligand [11C]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia. In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [11C]raclopride specific binding reductions. In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow. In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greater amphetamine-related reductions in [11C]raclopride specific binding (mean +/- SEM): -22.3% (+/-2.7) vs. -15.5% (+/-1.8),P = 0.04, respectively. Inferences from the preclinical study suggest that the patients' elevation in synaptic dopamine concentrations was substantially greater than controls. These data provide direct evidence for the hypothesis of elevated amphetamine-induced synaptic dopamine concentrations in schizophrenia.
Functional interaction of Parkinson's disease-associated LRRK2 with members of the dynamin GTPase superfamily

Mutations in LRRK2 cause autosomal dominant Parkinson's disease (PD). LRRK2 encodes a multi-domain protein containing GTPase and kinase domains, and putative protein–protein interaction domains. Familial PD mutations alter the GTPase and kinase activity of LRRK2 in vitro. LRRK2 is suggested to regulate a number of cellular pathways although the underlying mechanisms are poorly understood. To explore such mechanisms, it has proved informative to identify LRRK2-interacting proteins, some of which serve as LRRK2 kinase substrates. Here, we identify common interactions of LRRK2 with members of the dynamin GTPase superfamily. LRRK2 interacts with dynamin 1–3 that mediate membrane scission in clathrin-mediated endocytosis and with dynamin-related proteins that mediate mitochondrial fission (Drp1) and fusion (mitofusins and OPA1). LRRK2 partially co-localizes with endosomal dynamin-1 or with mitofusins and OPA1 at mitochondrial membranes. The subcellular distribution and oligomeric complexes of dynamin GTPases are not altered by modulating LRRK2 in mouse brain, whereas mature OPA1 levels are reduced in G2019S PD brains. LRRK2 enhances mitofusin-1 GTP binding, whereas dynamin-1 and OPA1 serve as modest substrates of LRRK2-mediated phosphorylation in vitro. While dynamin GTPase orthologs are not required for LRRK2-induced toxicity in yeast, LRRK2 functionally interacts with dynamin-1 and mitofusin-1 in cultured neurons. LRRK2 attenuates neurite shortening induced by dynamin-1 by reducing its levels, whereas LRRK2 rescues impaired neurite outgrowth induced by mitofusin-1 potentially by reversing excessive mitochondrial fusion. Our study elucidates novel functional interactions of LRRK2 with dynamin-superfamily GTPases that implicate LRRK2 in the regulation of membrane dynamics important for endocytosis and mitochondrial morphology.
Identification of Sumoylated Proteins by Systematic Immunoprecipitation of the Budding Yeast Proteome*

The identification of post-translational modifications to proteins is critical for understanding many important aspects of biology. Utilizing a collection of epitope-tagged yeast strains, we developed a novel approach to determine which proteins are modified by the small ubiquitin-related modifier (SUMO). We crossed traits useful for the detection of SUMO conjugation into 4246 tandem affinity purification-tagged strains and successfully immunoprecipitated and screened 2893 of these proteins for association with SUMO (∼70% of the expressed proteome detectable by immunoblot analysis). We found 82 proteins associated with SUMO, including many of low abundance. Because our screen was performed under non-denaturing conditions, we were able to identify multiple members of four complexes that were associated with SUMO: the RSC chromatin remodeling complex, the mediator complex, the TFIID complex, and the septin complex. In addition, we describe five new direct conjugates of SUMO, and we mutated SUMO conjugation sites in four proteins. This is the first attempt to immunoprecipitate a large fraction of the proteome of a eukaryote, and it demonstrates the utility of this method to identify post-translational modifications in the yeast proteome.
Validation of Visual Estimation of Portion Size Consumed as a Method for Estimating Food Intake by Young Indian Children

In this observational study, estimation of food intake was evaluated using recording of portion size consumed, instead of post-weighing, as a method. In total, 930 feeding episodes were observed among 128 children aged 12–24 months in which actual intake was available by pre- and post-weighing. For each offering and feeding episode, portion size consumed was recorded by an independent nutritionist—as none, less than half, half or more, and all. Using the pre-weighed offering, available intake was estimated by multiplying portion sizes by the estimated weight. The estimated mean intake was 510.4 kilojoules compared to actual intake of 510.7 kilojoules by weighing. Similar results were found with nestum (52.0 vs 56.2 g), bread (3.8 vs 3.7 g), puffed rice (1.7 vs 1.9 g), banana (31.3 vs 24.4 g), and milk (41.6 vs 44.2 mL). Recording portion size consumed and estimating food intake from that provides a good alternative to the time-consuming and often culturally-unacceptable method of post-weighing food each time after a feeding episode.
Phase-dependent modulation as a novel approach for therapeutic brain stimulation

Closed-loop paradigms provide us with the opportunity to optimize stimulation protocols for perturbation of pathological oscillatory activity in brain-related disorders. In this vein, spiking activity of motor cortex neurons and beta activity of local field potentials in the subthalamic nucleus have both been used independently of each other as neuronal signals to trigger deep brain stimulation for alleviating Parkinsonism. These approaches were superior to the standard continuous high-frequency stimulation protocols used in daily practice. However, they achieved their effects by bursts of stimulation that were applied at high-frequency as well, i.e., independent of the phase information in the stimulated region. In this context, we propose that, by timing stimulation pulses relative to the ongoing oscillation, an alternative approach, namely the targeted perturbation of pathological rhythms, could be obtained. In this modeling study, we first captured the underlying dynamics of neuronal oscillations in the human subthalamic nucleus by phased coupled neuronal oscillators. We then quantified the nature of the interaction between these coupled oscillators by obtaining a physiologically informed phase response curve from local field potentials. Reconstruction of the phase response curve predicted the sensitivity of the phase oscillator to external stimuli, revealing phase intervals that optimally maximized the degree of perturbation. We conclude that our specifically timed intervention based on the coupled oscillator concept will enable us to identify personalized ways of delivering stimulation pulses in closed-loop paradigms triggered by the phase of pathological oscillations. This will pave the way for novel physiological insights and substantial clinical benefits. In addition, this precisely phased modulation may be capable of modifying the effective interactions between oscillators in an entirely new manner.
INCREASING THE FLEXURAL CAPACITY OF TYPICAL REINFORCED CONCRETE BRIDGES IN TEXAS USING CARBON FIBER REINFORCED POLYMERS

A large portion of the off-system bridges and some on-system bridges in Texas were constructed in the 1950s using vehicle loads that are less than the current design standards. As a result, the legal load that is permitted to cross these bridges is often limited and many are scheduled for replacement. The use of carbon fiber reinforced polymer (CFRP) composites to increase the flexural capacity of reinforced concrete bridges was investigated in this research project. The overall goal was to develop design procedures for strengthening existing bridges using CFRP to avoid replacement of bridges that have been functioning satisfactorily for many years. The third phase of the research project is described in this report. Four full-scale specimens representative of bridge construction during the 1950s in Texas were constructed, strengthened, and tested in the laboratory to assess the effectiveness of the CFRP composites for increasing the flexural capacity. Results from the laboratory tests indicate that the composite materials may be used successfully to strengthen existing bridges. The strength of all specimens was controlled by debonding of the CFRP composites from the surface of the concrete. An analytical model was verified using the measured response of the laboratory specimens. The model was able to reproduce the overall response of the specimens, but did not reproduce the local modes of failure. Therefore, the model may be used to design strengthening systems for reinforced concrete bridges, but the maximum strain in the CFRP composites must be limited to reflect the observed modes of failure. Design guidelines for CFRP systems are presented.
Recombinant interleukin-1 beta activates the hypothalamic-pituitary-interrenal axis in rainbow trout, Oncorhynchus mykiss.

The present study provides the first direct evidence that implicates fish cytokines as the effector molecules by which the immune system signals the neuroendocrine system and activates the hypothalamic-pituitary-interrenal stress axis. I.p. injections of trout recombinant interleukin-1 beta (rIL-1 beta) or E. coli lipopolysaccharide (LPS), at concentrations known to induce immune/inflammatory responses in vivo (0.1-0.6 nmol/kg and 1.3 mg/kg respectively), significantly elevated plasma cortisol levels in a dose- and/or time-dependent manner. However, in contrast to general stress responses in fish, under the conditions employed in this study, no specific treatment effects on plasma glucose levels could be demonstrated. The trout IL-1 beta peptides (P1 and P3), which are homologous to receptor-binding sequences of human IL-1 beta, failed to influence the prevailing cortisol concentration even though an equivalent dose has been found to have immunostimulatory properties in vivo. Blockade of endogenous ACTH release by administration of the synthetic glucocorticoid dexamethasone prevented the rIL-1 beta/LPS-mediated elevation of plasma cortisol, suggesting that IL-1 beta and LPS modulate cortisol secretion via effects at the level of the hypothalamic-pituitary axis. These data indicate that, with respect to IL-1 beta, cytokine signalling between the immune and neuroendocrine systems in mammals appears to be conserved in lower vertebrates.