Miracle-dz/UniFAR-FTUs huggingface dataset:
The Extracytoplasmic Function-Type Sigma Factor SigM of Corynebacterium glutamicum ATCC 13032 Is Involved in Transcription of Disulfide Stress-Related Genes

ABSTRACT The gene for the extracytoplasmic function (ECF) sigma factor SigM was deleted from the chromosome of the gram-positive soil bacterium Corynebacterium glutamicum to elucidate the role of the SigM protein in the regulation of gene expression. Comparative DNA microarray hybridizations of the C. glutamicum wild type and sigM-deficient mutant C. glutamicum DN1 revealed 23 genes with enhanced expression in the sigM-proficient strain, encoding functions in the assembly of iron-sulfur clusters (suf operon), thioredoxin reductase (trxB), thioredoxins (trxC, trxB1), chaperones (groES, groEL, clpB), and proteins involved in the heat shock response (hspR, dnaJ, grpE). Deletion of the sigM gene rendered the C. glutamicum cells more sensitive to heat, cold, and the presence of the thiol oxidant diamide. Transcription of the sigM gene increased under different stress conditions, including heat shock, cold shock, and disulfide stress caused by diamide treatment, suggesting a regulatory role for SigM under thiol-oxidative stress conditions. Stress-responsive promoters were determined upstream of the suf operon and of the trxB, trxC, and trxB1 genes. The deduced SigM consensus promoter is characterized by the −35 hexamer gGGAAT and the −10 hexamer YGTTGR. Transcription of the sigM gene is apparently controlled by the ECF sigma factor SigH, since a sigH mutant was unable to enhance the expression of sigM and the SigM regulon under thiol-oxidative stress conditions. A typical SigH-responsive promoter was mapped upstream of the sigM gene. The ECF sigma factor SigM is apparently part of a regulatory cascade, and its transcription is controlled by SigH under conditions of thiol-oxidative stress.
Transmission through the Dorsal Spinocerebellar and Spinoreticular Tracts: Wakefulness versus Thiopental Anesthesia

Background Most of what is known regarding the actions of injectable barbiturate anesthetics on the activity of lumbar sensory neurons arises from experiments performed in acute animal preparations that are exposed to invasive surgery and neural depression caused by coadministered inhalational anesthetics. Other parameters such as cortical synchronization and motor ouflow are typically not monitored, and, therefore, anesthetic actions on multiple cellular systems have not been quantitatively compared. Methods The activities of antidromically identified dorsal spinocerebellar and spinoreticular tract neurons, neck motoneurons, and cortical neurons were monitored extracellularly before, during, and following recovery from the anesthetic state induced by thiopental in intact, chronically instrumented animal preparations. Results Intravenous administration of 15 mg/kg, but not 5 mg/kg, of thiopental to awake cats induced general anesthesia that was characterized by 5–10 min of cortical synchronization, reflected as large-amplitude slow-wave events and neck muscle atonia. However, even though the animal behaviorally began to reemerge from the anesthetic state after this 5–10-min period, neck muscle (neck motoneuron) activity recovered more slowly and remained significantly suppressed for up to 23 min after thiopental administration. The spontaneous activity of both dorsal spinocerebellar and spinoreticular tract neurons was maximally suppressed 5 min after administration but remained significantly attenuated for up to 17 min after injection. Peripheral nerve and glutamate-evoked responses of dorsal spinocerebellar and spinoreticular tract neurons were particularly sensitive to thiopental administration and remained suppressed for up to 20 min after injection. Conclusions These results demonstrate that thiopental administration is associated with a prolonged blockade of motoneuron output and sensory transmission through the dorsal spinocerebellar and spinoreticular tracts that exceeds the duration of general anesthesia. Further, the blockade of glutamate-evoked neuronal responses indicates that these effects are due, in part, to a local action of the drug in the spinal cord. The authors suggest that this combination of lumbar sensory and motoneuron inhibition underlies the prolonged impairment of reflex coordination observed when thiopental is used clinically.
The Grief Experienced by Spousal Caregivers of Dementia Patients: The Role of Place of Care of Patient and Gender of Caregiver

A comparison of the grief responses of spousal caregivers who cared for their demented partners at home with those who provided ongoing nursing home care, together with an examination of gender differences, is reported here. Four psychological states of grief were examined: anxiety, sadness, anger, and guilt. Sixty spousal caregivers participated in the study: thirty husbands and thirty wives, with equal numbers of home and nursing home caregivers. Content analysis scales were scored to assess the four psychological states. A self-rating, adjective mood scale was also used as a secondary measure of those states. A personal construct model of spousal caregivers' bereavement for their demented partners was developed and provided the two hypotheses about differences in grieving. As predicted, nursing home caregivers expressed significantly higher levels of sadness and guilt than home caregivers. Against prediction, home caregivers expressed significantly more anger than nursing home caregivers. Home caregiving wives were found to be the most angry cohort. Also, as predicted, caregiving wives expressed significantly higher levels of anxiety, sadness, and anger than caregiving husbands. The results of the content analysis scales were confirmed by the secondary measure, but the former measure proved more powerful for detecting statistically significant differences. The inclusion of severity of the patients' dementia, and the spiritually and age of the spousal caregivers as covariates in the statistical analyses showed place of care and gender of caregiver to remain the most powerful predictors of the four psychological states of grief.
Fatigue Behavior of RC Beams Strengthened with NSM CFRP Rods

This paper presents experimental results of reinforced concrete beams strengthened using near-surface mounted (NSM) carbon fiber-reinforced polymer (CFRP) reinforcement. A total of nine beam specimens were tested under fatigue loads. In addition, two specimens were tested for monotonic capacity. The beams were 3,500 mm long with a cross section of 254 mm deep by 152 mm wide. Different load ranges were considered in the fatigue tests to construct the fatigue life curves. The test results showed that under monotonic loading, the beam strengthened with NSM CFRP rod exhibited increases of 26 and 50% in the yield and ultimate load over the control beam, respectively. Under cyclic loading, the fatigue life for the strengthened beams was 24% higher than that of the control unstrengthened beams. An analytical model using sectional analysis and strain-life approach was developed to estimate the fatigue life of the specimens at various cyclic load ranges. A good agreement between the experimental results and analyt.
The relationship between eye movement and vision develops before birth

While the visuomotor system is known to develop rapidly after birth, studies have observed spontaneous activity in vertebrates in visually excitable cortical areas already before extrinsic stimuli are present. Resting state networks and fetal eye movements were observed independently in utero, but no functional brain activity coupled with visual stimuli could be detected using fetal fMRI. This study closes this gap and links in utero eye movement with corresponding functional networks. BOLD resting-state fMRI data were acquired from seven singleton fetuses between gestational weeks 30–36 with normal brain development. During the scan time, fetal eye movements were detected and tracked in the functional MRI data. We show that already in utero spontaneous fetal eye movements are linked to simultaneous networks in visual- and frontal cerebral areas. In our small but in terms of gestational age homogenous sample, evidence across the population suggests that the preparation of the human visuomotor system links visual and motor areas already prior to birth.
Gaussian upper bounds for the heat kernel on arbitrary manifolds

The history of the heat kernel Gaussian estimates started with the works of Nash [25] and Aronson [2] where the double-sided Gaussian estimates were obtained for the heat kernel of a uniformly parabolic equation in IR in a divergence form (see also [15] for improvement of the original Nash’s argument and [26] for a consistent account of the Aronson’s results and related topics). In particular, the Aronson’s upper bound for the case of time-independent coefficients which is of interest for us reads as follows:
Complex interactions between the sinoatrial node and atrium during reentrant arrhythmias in the canine heart.

BACKGROUND Numerous studies implicate the sinoatrial node (SAN) as a participant in atrial arrhythmias, including atrial flutter (AFL) and atrial fibrillation (AF). However, the direct role of the SAN has never been described. METHODS AND RESULTS The SAN was optically mapped in coronary perfused preparations from normal canine hearts (n=17). Optical action potentials were recorded during spontaneous rhythm, overdrive atrial pacing, and AF/AFL induced by acetylcholine (ACh; 0.3 to 3 micromol/L) and/or isoproterenol (Iso; 0.2 to 1 micromol/L). An optical action potential multiple component algorithm and dominant frequency analysis were used to reconstruct SAN activation and to identify specialized sinoatrial conduction pathways. Both ACh and Iso facilitated pacing-induced AF/AFL by shortening atrial repolarization. The entire SAN structure created a substrate for macroreentry with 9.6+/-1.7 Hz (69 episodes in all preparations). Atrial excitation waves could enter the SAN through the sinoatrial conduction pathways and overdrive suppress the node. The sinoatrial conduction pathways acted as a filter for atrial waves by slowing conduction and creating entrance block. ACh/Iso modulated filtering properties of the sinoatrial conduction pathways by increasing/decreasing the degree of the entrance block, respectively. Thus, the SAN could beat independently from AF/AFL reentrant activity during ACh (49+/-39%) and ACh/Iso (62+/-25%) (P=0.38). Without ACh, the AF/AFL waves captured the SAN and overdrive suppressed it. Spontaneous SAN activity could terminate or convert AFL to AF during cholinergic withdrawal. CONCLUSIONS The specialized structure of the SAN can be a substrate for AF/AFL. Cholinergic stimulation not only can slow sinus rhythm and facilitate AF/AFL but also protects the intrinsic SAN function from the fast AF/AFL rhythm.
Causality and audio-visual integration

Schutz and Lipscomb (2007) reported an audio-visual illusion in which the length of the gesture used to produce a sound alters the perception of the sound’s duration. This contradicts the widely accepted claim that the auditory system dominates in temporal tasks (such as estimating duration) because of the superior quality of its temporal information (the optimal integration hypothesis). In the first of four experiments we show that impact gestures influence the duration rating of percussive sounds but not of sustained ones. In the second experiment we show that the illusion is present even if the percussive sound occurs up to 700 ms after the visible impact, and that it disappears if the percussive sound precedes the visible impact. In the third experiment we show that only the motion after the visible impact influences the perceived tone duration. The fourth experiment — in which we replaced the video gestures with the text “Long” and “Short” — shows that the phenomenon is not due to response bias. We conclude that causality plays an important role in sensory integration.
Structural Connectivity Networks of Transgender People

Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.
Essential Role for Class II Phosphoinositide 3-kinase α-Isoform in Ca2+-Induced, Rho- and Rho Kinase-Dependent Regulation of Myosin Phosphatase and Contraction in Isolated Vascular Smooth Muscle Cells

The laser confocal fluorescent microscope-based observation of contractile responses in green fluorescent protein-expressing differentiated vascular smooth muscle cells, combined with the RNA interference-mediated gene-silencing technique, allowed us to determine the role of phosphoinositide 3-kinase (PI3K) class II α-isoform (PI3K-C2α) as a novel, Ca2+-dependent regulator of myosin light-chain phosphatase (MLCP) and contraction. The Ca2+-ionophore ionomycin induced a robust contractile response with an increase in the intracellular free Ca2+ concentration ([Ca2+]i). The PI3K-C2α-specific short interfering RNA (siRNA) induced a selective and marked reduction in PI3K-C2α protein expression. The siRNA-mediated knockdown of PI3K-C2α, but not class I PI3K p110α, suppressed ionomycin-induced contraction without altering Ca2+-mobilization. PI3K-C2α is uniquely less sensitive to the PI3K inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) than the other PI3K members, including p110α. Ionomycin-induced contraction was inhibited only by a relatively high concentration of LY294002. Consistent with our previous observations showing that ionomycin and membrane depolarization induced Rho activation in vascular smooth muscle tissues in a Ca2+-dependent manner, ionomycin-induced contraction was dependent on Rho and Rho-kinase. Ionomycin induced phosphorylation of the MLCP-regulatory subunit myosin targeting protein 1(MYPT1) at Thr850 and the 20-kDa myosin light chain (MLC) in a Rho kinase-dependent manner. Knockdown of PI3K-C2α suppressed phosphorylation of both MYPT1 and MLC. The receptor agonist noradrenaline, which induced a rapid increase in the [Ca2+]i and Ca2+-dependent contraction, stimulated phosphorylation of MYPT1 and MLC, which was also dependent on Ca2+, PI3K-C2α, and Rho-kinase. These observations indicate that PI3K-C2α is necessary for Ca2+-induced Rho- and Rho kinase-dependent negative regulation of MLCP and consequently MLC phosphorylation and contraction.
Event-triggered Control of Infinite-dimensional Systems

We consider the event-triggered control of continuous-time linear infinite-dimensional systems. We show that an event trigger that measures the difference of a control input leads to the positive minimum inter-event time if a feedback operator is compact. Moreover, under certain natural assumptions on the infinite-dimensional system, we show that there exists an event trigger such that the closed-loop system is exponentially stable.
Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG).

BACKGROUND Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNalpha-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. PATIENTS AND METHODS In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 mug peg-IFNalpha-2b s.c. per week and oral TMZ 200 mg/m(2) (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. RESULTS In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. CONCLUSIONS The efficacy of TMZ plus peg-IFNalpha-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNalpha-2b seems to be similar to non-peg-IFN when combined with TMZ.
Single PEM Fuel Cell Analysis for the Evaluation of Current Ripple Effects

In this paper, the results of an experimental analysis performed on a polymer electrolyte membrane fuel cell (FC) for the evaluation of the current ripple effects are reported. The polarization curve (PC) and the impedance spectrum measured for a single FC with a Nafion membrane are presented discussing some advantages and disadvantages of the two adopted techniques from the measurement point of view. The ohmic and activation resistance values provided by the PC are compared to the frequency limits of the equivalent resistance estimated by the spectroscopic analysis to evaluate the additional losses and the system efficiency reduction introduced by the current ripple. The presence of a voltage–current hysteretic behavior is discussed throughout the paper, and some comments on how such a relationship can impact on the identification of the indicated parameters are included.
Gastrointestinal hormones regulating appetite

The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood–brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain–gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance. The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain–gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity.
Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity

Significance Major histocompatibility complex (MHC) molecules play crucial roles in the immune response to pathogens and tumors by presenting protein fragments (peptides) to T lymphocytes. Recently, it has become clear that the breadth of peptide presentation by MHC class I molecules is inversely correlated with the level of cell surface expression, a relationship that is correlated with resistance to Marek’s disease in chickens and with progression to AIDS in humans. In this article, evidence is presented that class I molecules vary in a suite of correlated properties, including thermostability, that are influenced, at least in part, by the breadth of peptide translocation by the transporters for antigen presentation (TAPs) that pump peptides to be loaded. The chicken major histocompatibility complex (MHC) has strong genetic associations with resistance and susceptibility to certain infectious pathogens. The cell surface expression level of MHC class I molecules varies as much as 10-fold between chicken haplotypes and is inversely correlated with diversity of peptide repertoire and with resistance to Marek’s disease caused by an oncogenic herpesvirus. Here we show that the average thermostability of class I molecules isolated from cells also varies, being higher for high-expressing MHC haplotypes. However, we find roughly the same amount of class I protein synthesized by high- and low-expressing MHC haplotypes, with movement to the cell surface responsible for the difference in expression. Previous data show that chicken TAP genes have high allelic polymorphism, with peptide translocation specific for each MHC haplotype. Here we use assembly assays with peptide libraries to show that high-expressing B15 class I molecules can bind a much wider variety of peptides than are found on the cell surface, with the B15 TAPs restricting the peptides available. In contrast, the translocation specificity of TAPs from the low-expressing B21 haplotype is even more permissive than the promiscuous binding shown by the dominantly expressed class I molecule. B15/B21 heterozygote cells show much greater expression of B15 class I molecules than B15/B15 homozygote cells, presumably as a result of receiving additional peptides from the B21 TAPs. Thus, chicken MHC haplotypes vary in several correlated attributes, with the most obvious candidate linking all these properties being molecular interactions within the peptide-loading complex (PLC).