Miracle-dz/UniFAR-FTUs huggingface dataset:
The regulation of carbohydrate and fat metabolism during and after exercise.

The rate of carbohydrate utilization during prolonged, strenuous exercise is closely geared to the energy needs of the working muscles. In contrast, fat utilization during exercise is not tightly regulated, as there are no mechanisms for closely matching availability and metabolism of fatty acids to the rate of energy expenditure. As a result, the rate of fat oxidation during exercise is determined by the availability of fatty acids and the rate of carbohydrate utilization. Blood glucose and muscle glycogen are essential for prolonged strenuous exercise, and exhaustion can result either from development of hypoglycemia or depletion of muscle glycogen. Both absolute and relative (i.e. % of maximal O2 uptake) exercise intensities play important roles in the regulation of substrate metabolism. The absolute work rate determines the total quantity of fuel required, while relative exercise intensity plays a major role in determining the proportions of carbohydrate and fat oxidized by the working muscles. As relative exercise intensity is increased, there is a decrease in the proportion of the energy requirement derived from fat oxidation and an increase in that provided by carbohydrate oxidation. During moderately strenuous exercise of an intensity that can be maintained for 90 minutes or longer ( approximately 55-75% of VO2max), there is a progressive decline in the proportion of energy derived from muscle glycogen and a progressive increase in plasma fatty acid oxidation. The adaptations induced by endurance exercise training result in a marked sparing of carbohydrate during exercise, with an increased proportion of the energy being provided by fat oxidation. The mechanisms by which training decreases utilization of blood glucose are not well understood. However, the slower rate of glycogenolysis can be explained on the basis of lower concentrations of inorganic phosphate (Pi) in trained, as compared to untrained, muscles during exercise of the same intensity. The lower Pi level is a consequence of the increase in muscle mitochondria induced by endurance exercise training. A large increase in muscle glycogen concentration, far above the level found in the well-fed sedentary state, occurs in response to carbohydrate feeding following glycogen depleting exercise. It was recently found that this muscle "glycogen supercompensation" is markedly enhanced by endurance exercise training that induces an increase in the GLUT4 isoform of the glucose transporter in skeletal muscle.
Theranostic Nanoparticles

Theranostic nanoparticles hold the potential to revolutionize disease management. Over the last decade, there has been growing interest in the engineering of various kinds of theranostic nanoparticles for simultaneous cancer imaging and therapy in small animals. Efficient targeting of theranostic nanoparticles to the tumor site is critical for both diagnosis and therapy. However, difficulties still exist in the engineering of biocompatible theranostic nanoparticles with highly specific in vivo tumor-targeting capabilities. Here, we discuss the current and prospective status of theranostic nanoparticles that actively target tumors, as well as the challenges that still exist.
Skin toxicity and cosmesis after hypofractionated whole breast irradiation for early breast cancer.

OBJECTIVE To assess and compare the impact on skin reactions and cosmesis between hypofractionated whole breast and conventional irradiation for early breast cancer. MATERIAL AND METHOD Seventy-three patients with operable breast cancer (pT1-3pN0-1M0) who underwent breast-conserving surgery were assigned for irradiation to either conventional arm (50 Gy in 25 fractions) with a sequential electron boost of 15-16 Gy over five weeks or hypofractionated arm (43.2 Gy in 16 fractions) with a concomitant electron boost of 0.6 Gy over three weeks. RESULTS At 3-week follow-up, skin toxicities in the hypofractionated arm were significantly worse than that seen in the conventional arm, while at 6-week follow-up, the percentages of skin toxicities in the conventional arm were higher After a median follow-up of six months, there was no significant difference in skin toxicities between the two treatment groups. In addition, there were no significant differences in the mean scores of cosmetic outcome for patients between two regimens. CONCLUSION This hypofractionated radiotherapy regimen of 43.2 Gy in 16 fractions with a concomitant electron boost showed good results in terms of normal tissue effects and cosmesis. A long-term follow-up is needed to confirm these favorable results.
Brain systems for baroreflex suppression during stress in humans

The arterial baroreflex is a key mechanism for the homeostatic control of blood pressure (BP). In animals and humans, psychological stressors suppress the capacity of the arterial baroreflex to control short‐term fluctuations in BP, reflected by reduced baroreflex sensitivity (BRS). While animal studies have characterized the brain systems that link stressor processing to BRS suppression, comparable human studies are lacking. Here, we measured beat‐to‐beat BP and heart rate (HR) in 97 adults who performed a multisource interference task that evoked changes in spontaneous BRS, which were quantified by a validated sequence method. The same 97 participants also performed the task during functional magnetic resonance imaging (fMRI) of brain activity. Across participants, task performance (i) increased BP and HR and (ii) reduced BRS. Analyses of fMRI data further demonstrated that a greater task‐evoked reduction in BRS covaried with greater activity in brain systems important for central autonomic and cardiovascular control, particularly the cingulate cortex, insula, amygdala, and midbrain periaqueductal gray (PAG). Moreover, task performance increased the functional connectivity of a discrete area of the anterior insula with both the cingulate cortex and amygdala. In parallel, this same insula area showed increased task‐evoked functional connectivity with midbrain PAG and pons. These novel findings provide human evidence for the brain systems presumptively involved in suppressing baroreflex functionality, with relevance for understanding the neurobiological mechanisms of stressor‐related cardiovascular reactivity and associated risk for essential hypertension and atherosclerotic heart disease. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Positive selection optimizes the number and function of MHCII-restricted CD4+ T cell clones in the naive polyclonal repertoire

T cell receptors (TCRs) on T lymphocytes in an individual bind foreign peptides bound to major histocompatibility complex (MHC) molecules expressed in that individual (designated MHCA). Results from radiation bone marrow chimeras and TCR transgenic mice indicate that this complex form of antigen recognition is the result of positive selection of clones with low affinity for self peptide:MHCA complexes during development. Here we used a sensitive peptide:MHC tetramer enrichment method to quantify the role of positive selection in the generation of the preimmune polyclonal T cell repertoire in normal individuals. We made the surprising observation that mouse and human naive T cells capable of binding to foreign peptide:MHCA were present at the same frequency in hosts that expressed MHCA or a different MHC isoform (MHCB). However, most of the clones in MHCB hosts also recognized self peptide:MHCA complexes. When these “alloreactive” T cells were removed from the MHCB repertoire via negative selection in an MHCA host, the number of foreign peptide:MHCA-binding T cells was reduced to one fifth and many of the remaining cells did not respond to the peptide. Therefore, although positive selection on MHCA was not required to produce foreign peptide:MHCA-binding clones, it had a large effect on selecting responsive clones.
Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients.

BACKGROUND Delivery of antibiotics to the lower respiratory tract could potentially achieve antimicrobial bronchial drug concentrations without toxicity. AIM To assess bronchial and serum concentrations of imipenem or tobramycin obtained by nebulization or instillation in critically ill mechanically ventilated patients. METHODS Prospective randomized open trial. Eighteen patients ventilated for more than 48 h were included. Two doses of imipenem/cilastatin (1000/500 mg) separated by 8 h, or two doses of tobramycin 200 mg separated by 12 h were randomly nebulized or instilled into the tracheal tube. Five bronchoaspirates (two bronchoscopic, three blind) and five blood samples were collected on a timed schedule after the second dose. Respiratory and serum samples were analysed by HPLC, and a subset of blood samples was also evaluated by enzyme-immunoassay. RESULTS When instilled, imipenem/cilastatin obtained higher concentrations in respiratory secretions than when nebulized (P=0.022, 1 h after the last dose; P=0.029, 2 h after the last dose). Tobramycin showed equally high concentrations when nebulized or instilled. Instillation of tobramycin may result in significant accumulation in patients with renal failure. CONCLUSIONS High bronchial concentrations of imipenem could only be achieved by instillation, whereas tobramycin seems suitable for both modes of administration. Instillation of these antibiotics is a safe procedure that achieves high drug concentrations in respiratory secretions.
YMR313c/TGL3 Encodes a Novel Triacylglycerol Lipase Located in Lipid Particles of Saccharomyces cerevisiae*

Previous work from our laboratory (Athenstaedt, K., Zweytick, D., Jandrositz, A., Kohlwein, S. D., and Daum, G. (1999) J. Bacteriol. 181, 6441–6448) showed that the gene product of YMR313c (named Tgl3p) is a component of yeast lipid particles, and deletion of this gene led to an increase in the cellular level of triacylglycerols (TAG). These observations suggested that TGL3 may encode a TAG lipase of Saccharomyces cerevisiae. Here we demonstrate by cell fractionation and by microscopic inspection of a strain bearing a Tgl3p-GFP hybrid that this polypeptide is highly enriched in the lipid particle fraction but virtually absent from other organelles. The entire TAG lipase activity of lipid particles is attributed to Tgl3p, because the activity in this organelle is completely absent in a Δtgl3 deletion mutant, whereas it is significantly enhanced in a strain overexpressing Tgl3p. A His6-tagged Tgl3p hybrid purified close to homogeneity from a yeast strain overexpressing this fusion protein exhibited high TAG lipase activity. Most importantly, experiments in vivo using the fatty acid synthesis inhibitor cerulenin demonstrated that deletion of TGL3 resulted in a decreased mobilization of TAG from lipid particles. The amino acid sequence deduced from the open reading frame YMR313c contains the consensus sequence motif GXSXG typical for lipolytic enzymes. Otherwise, Tgl3p has no significant sequence homology to other lipases identified so far. In summary, our data identified Tgl3p as a novel yeast TAG lipase at the molecular level and by function in vivo and in vitro.
Experimental analysis of system performance in an EDFA with pump driven in PWM mode

This paper presents the analysis of the system performance of an EDFA (Erbium Doped Fiber Amplifier) with pump laser operating in a PWM (Pulse Width Modulation) mode, when compared to the typical linear operation mode (Continuous Wave — CW). Besides the fact that PWM driving mode significantly reduces the heat dissipation in the driver devices [1], it also avoids the use of big heat sinks and reduces the area occupied by the electronic circuit. We verified that it increases both the operation range and the efficiency of the laser in the low pump power region. To validate the EDFA performance in PWM mode, penalty parameters (such as bit error rates), gain control and transient suppression were analyzed in an experimental setup and compared to results obtained in CW mode. Measurements showed that the performance is not compromised when the PWM technique is implemented, suggesting that it can be used to reduce the high power consumption of the equipment.
Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal–subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD.
Tissue–Specific Insulin Signaling, Metabolic Syndrome, and Cardiovascular Disease

Impaired insulin signaling is central to development of the metabolic syndrome and can promote cardiovascular disease indirectly through development of abnormal glucose and lipid metabolism, hypertension, and a proinflammatory state. However, insulin’s action directly on vascular endothelium, atherosclerotic plaque macrophages, and in the heart, kidney, and retina has now been described, and impaired insulin signaling in these locations can alter progression of cardiovascular disease in the metabolic syndrome and affect development of microvascular complications of diabetes mellitus. Recent advances in our understanding of the complex pathophysiology of insulin’s effects on vascular tissues offer new opportunities for preventing these cardiovascular disorders.
N- and C-terminal Domains Direct Cell Type-specific Sorting of Chromogranin A to Secretory Granules*

Chromogranins are a family of regulated secretory proteins that are stored in secretory granules in endocrine and neuroendocrine cells and released in response to extracellular stimulation (regulated secretion). A conserved N-terminal disulfide bond is necessary for sorting of chromogranins in neuroendocrine PC12 cells. Surprisingly, this disulfide bond is not necessary for sorting of chromogranins in endocrine GH4C1 cells. To investigate the sorting mechanism in GH4C1 cells, we made several mutant forms removing highly conserved N- and C-terminal regions of bovine chromogranin A. Removing the conserved N-terminal disulfide bond and the conserved C-terminal dimerization and tetramerization domain did not affect the sorting of chromogranin A to the regulated secretory pathway. In contrast, removing the C-terminal 90 amino acids of chromogranin A caused rerouting to the constitutive secretory pathway and impaired aggregation properties as compared with wild-type chromogranin A. Since this mutant was sorted to the regulated secretory pathway in PC12 cells, these results demonstrate that chromogranins contain independent N- and C-terminal sorting domains that function in a cell type-specific manner. Moreover, this is the first evidence that low pH/calcium-induced aggregation is necessary for sorting of a chromogranin to the regulated secretory pathway of endocrine cells.
An Empirical Comparison Of Feature Selection Methods In Problem Transformation Multi-label Classification

Multi-label classification (MLC) is a supervised learning problem in which a particular example can be associated with a set of labels instead of a single one as in traditional classification. Many real-world applications, such as Web page classification or resource tagging on the Social Web, are challenging for existing MLC algorithms, because the label space grows exponentially as instance space increases. Under the problem transformation approach, the most common alternative for MLC, multi-label problems are transformed into several single label problems, whose outputs are then aggregated into a prediction to the whole classification problem. Feature selection techniques become crucial in large-scale MLC problems to help reducing dimensionality. However, the impact of feature selection in multi-label setting has not been as extensively studied as in the case of single-label data. In this paper, we present an empirical evaluation of feature selection techniques in the context of the three main problem transformation MLC methods: Binary Relevance, Pair-wise and Label power-set. Experimentation was performed across a number of benchmark datasets for multi-label classification exhibiting varied characteristics, which allows observing the behavior of techniques and assessing their impact according to multiple metrics.
Temporal and spatial characteristics of post-silent period electromyographic bursting in low back muscles: comparison between persons with and without low back pain

ABSTRACT Purpose/aim: Recently, a novel measure of cortical disinhibition was identified using transcranial magnetic stimulation (TMS). This measure, described as post-silent period electromyographic (EMG) bursting, may inform on the corticomotor control of movement in health and disease; however, it has not been investigated for muscles outside the hand or in musculoskeletal conditions. Thus, the aim of this study was to investigate the temporal and spatial characteristics of “EMG bursting” in individuals with and without low back pain (LBP). Materials and Methods: TMS was used to map the motor cortical representation of paraspinal muscles in 11 individuals with LBP and 11 pain-free controls. The latency, duration and magnitude of bursting, number of active burst sites, map volume and coordinates of the burst “hotspot” were compared between the groups. Results: In pain-free controls, the latency, duration and magnitude of bursts were similar to the hand; however, bursts occurred earlier and were of smaller magnitude in LBP. Bursting was widespread throughout the cortical representation in both groups; however, there was a trend towards smaller mean EMG burst and map volume in LBP. Conclusions: We confirm the presence of EMG bursting in back muscles and provide a description of the spatial profile of this mechanism. Our observations in LBP suggest that cortical disinhibition may be altered in this condition.
Introduction of a disulfide bond leads to stabilization and crystallization of a ricin immunogen

RTA1‐33/44‐198 is a catalytically inactive, single‐domain derivative of the ricin toxin A‐chain (RTA) engineered to serve as a stable protein scaffold for presentation of native immunogenic epitopes (Olson et al., Protein Eng Des Sel 2004;17:391–397). To improve the stability and solubility of RTA1‐33/44‐198 further, we have undertaken the design challenge of introducing a disulfide (SS) bond. Nine pairs of residues were selected for placement of the SS‐bond based on molecular dynamics simulation studies of the modeled single‐domain chain. Disulfide formation at either of two positions (R48C/T77C or V49C/E99C) involving a specific surface loop (44–55) increased the protein melting temperature by ∼5°C compared with RTA1‐33/44‐198 and by ∼13°C compared with RTA. Prolonged stability studies of the R48C/T77C variant (>60 days at 37°C, pH 7.4) confirmed a >40% reduction in self‐aggregation compared with RTA1‐33/44‐198 lacking the SS‐bond. The R48C/T77C variant retained affinity for anti‐RTA antibodies capable of neutralizing ricin toxin, including a monoclonal that recognizes a human B‐cell epitope. Introduction of either R48C/T77C or V49C/E99C promoted crystallization of RTA1‐33/44‐198, and the X‐ray structures of the variants were solved to 2. 3Å or 2.1 Å resolution, respectively. The structures confirm formation of an intramolecular SS‐bond, and reveal a single‐domain fold that is significantly reduced in volume compared with RTA. Loop 44 to 55 is partly disordered as predicted by simulations, and is positioned to form self‐self interactions between symmetry‐related molecules. We discuss the importance of RTA loop 34 to 55 as a nucleus for unfolding and aggregation, and draw conclusions for ongoing structure‐based minimalist design of RTA‐based immunogens. Proteins 2011. Published 2010 Wiley‐Liss, Inc.
The Complex Pattern of Cytokines in Sepsis Association Between Prostaglandins, Cachectin, and Interleukins

Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis. Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p ≤ 0.05) of plasma TNF until 10 hours, steadily increasing (p ≤ 0.05) IL-1 plasma levels, and enhanced (p ≤ 0.05) IL-6 plasma levels at all time points compared to the sham group. Prostaglandin E2 plasma levels were elevated (p ≤ 0.05) at 5 hours (153 ± 29 pg/mL; control: 47 ±11 pg/mL) and 10 hours (96 ± 16 pg/mL; control: 21 ± 5 pg/ mL). Prostaglandin E2 production by splenic macrophages (sMø) from septic animals was increased (p ≤ 0.05) at 5 hours (9.1 ±2.2 ng/mL) and 10 hours (5.6 ±1.5 ng/mL) compared to controls (3.3 ± 0.3. ng/mL at 5 hours; 1.3 ± 1.3 ng/mL at 10 hours). Incubation of sMø from septic animals with ibuprofen enhanced (p ≤ 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p ≤ 0.05). These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis.