Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing the fractions of tautomeric forms of the imidazole ring of histidine in proteins as a function of pH

A method is proposed to determine the fraction of the tautomeric forms of the imidazole ring of histidine in proteins as a function of pH, provided that the observed and chemical shifts and the protein structure, or the fraction of H+ form, are known. This method is based on the use of quantum chemical methods to compute the 13C NMR shieldings of all the imidazole ring carbons (13Cγ, , and ) for each of the two tautomers, Nδ1-H and Nϵ2-H, and the protonated form, H+, of histidine. This methodology enabled us (i) to determine the fraction of all the tautomeric forms of histidine for eight proteins for which the and chemical shifts had been determined in solution in the pH range of 3.2 to 7.5 and (ii) to estimate the fraction of tautomeric forms of eight histidine-containing dipeptide crystals for which the chemical shifts had been determined by solid-state 13C NMR. Our results for proteins indicate that the protonated form is the most populated one, whereas the distribution of the tautomeric forms for the imidazole ring varies significantly among different histidines in the same protein, reflecting the importance of the environment of the histidines in determining the tautomeric forms. In addition, for ∼70% of the neutral histidine-containing dipeptides, the method leads to fairly good agreement between the calculated and the experimental tautomeric form. Coexistence of different tautomeric forms in the same crystal structure may explain the remaining 30% of disagreement.
P2 Receptor Excitation of Rodent Hypoglossal Motoneuron ActivityIn Vitro and In Vivo: A Molecular Physiological Analysis

The role of P2 receptors in controlling hypoglossal motoneuron (XII MN) output was examined (1) electrophysiologically, via application of ATP to the hypoglossal nucleus of rhythmically active mouse medullary slices and anesthetized adult rats; (2) immunohistochemically, using an antiserum against the P2X2 receptor subunit; and (3) using PCR to identify expression of P2X2 receptor subunits in micropunches of tissue taken from the XII motor nucleus. Application of ATP to the hypoglossal nucleus of mouse medullary slices and anesthetized rats produced a suramin-sensitive excitation of hypoglossal nerve activity. Additional in vitro effects included potentiation of inspiratory hypoglossal nerve output via a suramin- and pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS)-sensitive mechanism, XII MN depolarization via activation of a suramin-sensitive inward current, decreased neuronal input resistance, and a slow-onset theophylline-sensitive reduction of inspiratory output likely resulting from hydrolysis of extracellular ATP to adenosine and activation of P1 receptors. Immunohistochemically, P2X2 receptors were detected in inspiratory XII MNs that were labeled with Lucifer yellow. These data, combined with identification of mRNA for three P2X2 receptor subunit isoforms within the hypoglossal nucleus (two of which have not been localized previously in brain) and the previous demonstration that P2X receptors are ubiquitously expressed in cranial and spinal motoneuron pools, support not only a role of P2 receptors in modulating inspiratory hypoglossal activity but a general role of P2 receptors in modulating motor outflow from the CNS.
Bidding marginal utility in simultaneous auctions

One of the key challenges autonomous bidding agents face is to determine how to bid on complementary and substitutable goods—i.e., goods with combinato-rial valuations—in simultaneous, or parallel, auctions (SAs). Complementary goods are goods with super-additive valuations: Sub-stitutable goods are goods with subadditive valuations: The simple bidding strategy "for each good x in auction x, bid its (independent) valuation" is inapplicable in this framework. Rather than attempt to reason about the independent valuations of goods, bidding agents that operate in this setting can reason about marginal valuations, or the valuation of a good x relative to a set of goods A r. If an agent holds the goods in A r , it can ask questions such as: "what is the marginal benefit of buying x? " or, "what is the marginal cost of selling xT To do so, the agent must reason about the set of goods or relative to the set X—the valuations of which arc well-defined. In reasoning about sets of goods bidding agents may pose and solve questions such as the following [Green-wald and Boyan, 2001]: 1. "Given only the set of goods I already hold, what is the maximum valuation I can attain, by arranging my individual goods into sets of goods? " 2. "Given the set of goods I already hold, and given market prices and supply, on what set of additional goods should I place bids so as to maximize my utility: i.e., valuation less purchase costs? " 3. "Given the set of goods I already hold, and given market prices, supply, and demand, on what set of goods should I place bids or asks so as to maximize my utility: i.e., valuation plus proceeds less costs? " The third, and most general, of these problems, which we call completion, provides a foundation for bidding strategies in simultaneous single-and double-sided auctions. The second problem, which we term acquisition, provides a foundation for bidding strategies in single-sided auctions. The first problem, allocation, is a special case of the others in which all goods cost either 0 or oo, and all goods are worth either 0 or These so-called bid determination problems are formally defined in [Greenwald and Boyan, 2001], where it is argued that completion can be reduced to acquisition. 1 Bidding Principles This paper advocates the following bidding principle for agents participating in simultaneous auctions for complementary and substitutable goods: "coherent" marginal utility bidding: i.e., bidding marginal utilities …
Cerebellar volume as imaging outcome in progressive multiple sclerosis

Background and purpose To assess whether cerebellar volumes changes could represent a sensitive outcome measure in primary-progressive MS. Material and methods Changes in cerebellar volumes over one-year follow-up, estimated in 26 primary-progressive MS patients and 20 controls with Freesurfer longitudinal pipeline, were assessed using Wilcoxon test and tested for their correlation with disability worsening by a logistic regression. Clinical worsening was defined as EDSS score increase or change of >20% for 25-foot walk test or 9-hole peg test scores at follow-up. Sample sizes for given treatment effects and power were calculated. The findings were validated in an independent cohort of 20 primary-progressive MS patients. Results Significant changes were detected in brain T1 lesion volume (p<0.01), cerebellar T2 and T1 lesion volume (p<0.01 and p<0.05), cerebellar volume, cerebellar cortex volume, and cerebellar WM volume (p<0.001). Only cerebellar volume and cerebellar cortex volume percentage change were significantly reduced in clinically progressed patients when compared to patients who did not progress (p<0.01; respectively AUC of 0.91 and 0.96). Cerebellar volume percentage changes were consistent in the exploration and validation cohorts (cerebellar volume -1.90±1.11% vs -1.47±2.30%; cerebellar cortex volume -1.68±1.41% vs -1.56±2.23%). Based on our results the numbers of patients required to detect a 30% effect are 81 per arm for cerebellar volume and 162 per arm for cerebellar cortex volume (90% power, type 1 error alpha = 0.05). Conclusions Our results suggest a role for cerebellar cortex volume and cerebellar volume as potential short-term imaging metrics to monitor treatment effect in primary-progressive MS clinical trials.
Cholesterol metabolism in the brain and dementia

Introduction: Cholesterol metabolism in the brain is implicated in the development of Alzheimer's disease (AD). Understanding the relationship between markers of brain cholesterol metabolism and the structural changes occurring in the aging brain has particular public health relevance to the treatment and prevention of AD. Methods: This dissertation consists of a systematic review of the literature and two papers of original research. Our systematic review: critically evaluates the literature regarding brain cholesterol metabolism and AD, identifies gaps in our current understanding, and proposes directions for future research. The two papers of original research were designed to address these gaps in knowledge. We examined the relationship between plasma oxysterol metabolites and cerebrovascular disease, amyloid deposition in the brain, and incident cognitive impairment using two longitudinal cohorts of older adults with extensive characterization of cognition and brain structure. Quantitative marker of brain structure were prior to clinical disease using magnetic resonance imaging (MRI) and positron emission tomography (PET). Results: Our review found inconsistent associations between brain-derived plasma oxysterols and AD. Epidemiological design issues and methodological limitations may explain these conflicting results; these include: residual confounding, lack of temporal of associations, and inconsistent direction of associations resulting from stage of the disease at which oxysterols were measured. A major methodological limitation is the scarcity of objective measures to quantify underlying structural changes occurring the brain. Our original research examined the longitudinal association between oxysterols, cognition and brain imaging markers in non-demented older adults. We found higher levels of brain-derived oxysterols were associated with MRI markers of cerebrovascular disease and a greater risk of cognitive impairment over 8 years of follow-up. Furthermore, we found that lipid-lowering drugs modify the association between plasma oxysterols levels and amyloid deposition in the brain, visualized using PET. Conclusions: There are important relationships between brain degeneration, cholesterol metabolism and dementia that need to be better understood. Brain-derived metabolites of cholesterol appear to be elevated in the early stages of disease prior to the onset of cognitive impairment. Brain-derived plasma oxysterols may be an important marker of underlying cerebrovascular disease preceding cognitive impairment and risk for developing cognitive impairment.
Mechanical, In Vitro Corrosion Resistance and Biological Compatibility of Cast and Annealed Ti25Nb10Zr Alloy

Compared to other alloys, Ti6Al4V is the most used in medicine. In recent years, concerns regarding the toxicity of Al and V elements found in the composition of Ti6Al4V have drawn the attention of the scientific community, due to the release of Al or V ions after long term exposure to human body fluids which can lead to a negative response of the human host. Based on this, the aim of the paper was to manufacture a Ti25Nb10Zr alloy consisting of biocompatible elements which can replace Ti6Al4V usage in medical applications. In order to prove that this alloy possessed improved properties, the mechanical, wear and corrosion resistance, wettability, and cell viability were performed in comparison with those of the Ti6Al4V alloy. The corrosion behavior of this new alloy in simulated body fluid (SBF) and Hank solutions is superior to that of Ti6Al4V. The cast Ti25Nb10Zr alloy has a good tribological performance in SBF, while annealed Ti25Nb10Zr alloy is better in Hank solution. Cell viability and proliferation assay after five days indicated that Ti25Nb10Zr presented a good viability and proliferation with values of approximately 7% and 10% higher, respectively, than the ones registered for pure Ti. When compared with Ti6Al4V, the obtained results for Ti25Nb10Zr indicated smaller values with 20% in the case of both tests. Overall, it can be concluded that cell proliferation and viability tests indicated that the biocompatibility of the Ti25Nb10Zr alloy is as good as pure Ti and Ti6Al4V alloy.
Gain-scheduled wheel slip reset control in automotive brake systems

Wheel slip control bases its effectiveness on operating in the maximum adherence zone, guaranteeing the correct handling of the vehicle in any moment. The use of brake-by-wire systems and electromechanical actuators makes possible to control each wheel slip independently, improving, as a result, the accuracy and performance of braking systems. In this paper, a new controller, based on reset control, is proposed to enhance the overall effectiveness of the braking maneuver. This improvement proceed from the reduction of the braking distance as well as a betterment of the outputs of the system such as the transient time and the overshooting. The robustness of the system to changes in the friction conditions is also improved by reset control. The design of the controller has been done based on the quarter car model considering only the longitudinal dynamics. The Pacejka model has been used to model the road-tire interaction.
Can fisheries-induced evolution shift reference points for fisheries management?

Biological reference points are important tools for fisheries management. Reference points are not static, but may change when a population's environment or the population itself changes. Fisheries-induced evolution is one mechanism that can alter population characteristics, leading to "shifting" reference points by modifying the underlying biological processes or by changing the perception of a fishery system. The former causes changes in "true" reference points, whereas the latter is caused by changes in the yardsticks used to quantify a system's status. Unaccounted shifts of either kind imply that reference points gradually lose their intended meaning. This can lead to increased precaution, which is safe, but potentially costly. Shifts can also occur in more perilous directions, such that actual risks are greater than anticipated. Our qualitative analysis suggests that all commonly used reference points are susceptible to shifting through fisheries-induced evolution, including the limit and "precautionary" reference points for spawning-stock biomass, B_lim and B_pa, and the target reference point for fishing mortality, F_0. 1. Our findings call for increased awareness of fisheries-induced changes and highlight the value of always basing reference points on adequately updated information, to capture all changes in the biological processes that drive fish population dynamics.
Fault Detection and Isolation of Actuator Faults in Spacecraft Formation Flight

This paper investigates the development of fault detection and isolation (FDI) filters for spacecraft formation flight. A MIMO architecture for formation flying control is considered. By utilizing a geometric FDI methodology, a local/decentralized detection filter is developed for detecting faults in other spacecraft by determining the required unobservability subspace of the local system. In the case when such an unobservability subspace does not exist, the required communication links between the spacecraft are specified. Simulation results presented demonstrate the effectiveness of our proposed methodology for FDI of formation flying systems
Changes in structural and metabolic muscle characteristics following exercise-based interventions in patients with COPD: a systematic review

ABSTRACT Patients with COPD suffer from lower-limb muscle dysfunction characterized by lower muscle oxidative capacity and muscle mass. Exercise-based training is expected to attenuate lower-limb intramuscular characteristics, but a detailed systematic approach to review the available evidence has not been performed yet. PUBMED and PEDro databases were searched. Twenty-five studies that implemented an exercise-based training program (aerobic and/or resistance training, high intensity interval training, electrical or magnetic stimulation) and reported muscle biopsy data of patients with COPD were critically appraised. The coverage of results includes changes in muscle structure, muscle protein turnover regulation, mitochondrial enzyme activity, oxidative and nitrosative stress, and inflammation after exercise-based training interventions. Study design and training modalities varied among studies, which partly explains the observed heterogeneous response in muscle characteristics. Gaps in the current knowledge are identified and recommendations for future research are made to enhance our knowledge on exercise training effects in patients with COPD.
Repetition Priming Across the Adult Lifespan—The Long and Short of It

ABSTRACT Previous reports suggest that repetition priming (i.e., enhanced processing of a stimulus after experience with that stimulus) is long lasting and impervious to the effects of age, in contrast to the pattern found with explicit memory. However, the nature of repetition priming in aged individuals remains unclear, as conflicting findings have also been reported. We used a longitudinal design to examine how repetition priming is affected by multiple stimulus repetitions (three presentations) and different delay intervals (no delay, 1 day, 1 week, and 1 month) in young adults, as well as in two groups of aging adults (young-elderly and old-elderly). Our findings extend previous reports that priming is long lasting, even when 1 month intervenes between the initial experience with an item and the subsequent priming test of that item (Cave, 1997), and is relatively impervious to the effects of age (Mitchell, et al., 1990). In addition, a more detailed characterization of priming and the effects of aging was revealed. Although priming is long lasting, remaining significant even at the month delay for all groups, it did decline over time and the rate of that decline differed with age. Both young-elderly and old-elderly groups showed a marked drop-off at 1 day, whereas young adults did not show a decline until 1 week. All groups benefited from multiple repetitions; however, this benefit disappeared at the month delay (in contrast to recognition memory, where the benefit remained significant). These findings support the assertion that repetition priming and explicit memory reflect the operation of distinct systems, and that these systems may undergo different rates of change in aging.
The Efficacy of Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 Probiotic Treatment in Infants with Rotavirus Infection

A total of 57 infants hospitalized with rotavirus disease were included in this study. The children were randomly divided into the study’s two treatment groups: three days of the oral administration of (i) a probiotics formula containing both Bifidobacterium longum BORI and Lactobacillus acidophilus AD031 (N = 28); or (ii) a placebo (probiotic-free skim milk, N = 29) and the standard therapy for diarrhea. There were no differences in age, sex, or blood characteristics between the two groups. When the 57 cases completed the protocol, the duration of the patients’ diarrhea was significantly shorter in the probiotics group (4.38 ± 1.29, N = 28) than the placebo group (5.61 ± 1.23, N = 29), with a p-value of 0.001. Symptoms such as duration of fever (p = 0.119), frequency of diarrhea (p = 0.119), and frequency of vomiting (p = 0.331) tended to be ameliorated by the probiotic treatment; however, differences were not statistically significant between the two groups. There were no serious, adverse events and no differences in the frequency of adverse events in both groups.
Nontuberculous Mycobacterial Infection of the Central Nervous System in Patients With AIDS

Infections due to nontuberculous mycobacteria (NTM) are especially common in patients with AIDS. Meningitis due to NTM, however, is rare. A search for CSF cultures positive for NTM over the past 11 years at our hospital yielded 16 cases. Of these, 15 were caused by Mycobacterium avium-intracellulare (MAI), and one was caused by M fortuitum. All patients with MAI infection had widespread dissemination and at least one risk factor for AIDS. Clinical features included weight loss, altered mentation, and seizures. Analysis of cerebrospinal fluid revealed a mildly elevated leukocyte count with lymphocyte predominance and normal protein and glucose values. All direct smears were negative for acid-fast bacilli. In-hospital mortality was 67%. The patient with infection due to M fortuitum had a preexisting diagnosis of AIDS and had a right upper lobe pneumonia and headaches. Cranial CT showed an enlarged infundibulum of the pituitary gland. Results of CSF analysis were essentially normal, and direct smears were negative. He left the hospital against medical advice. Our study indicates that the finding of MAI in the CSF in patients with AIDS is associated with an in-house mortality of 67% indicating a very poor prognosis.
A Folding Pathway Model of Mini-Protein BBA5

We present the folding pathway model of mini-protein BBA5, a bundle of secondary structures, α-helix and β-hairpin, by using action-derived molecular dynamics (ADMD) simulations. From ten independent ADMD simulations, we extracted common features of the folding pathway of BBA5, from which we found that the early stage chain compaction was followed by the formation of C-terminal α-helix. The N-terminal β-hairpin was observed to form only after α-helix was stabilized. This result is in good agreement with the experimental observation that BBA5 mutants were moderately cooperative folders, and their C-terminal helical fragments were of higher secondary structure propensity while the N-terminal hairpin fragments were of a random coil spectrum. We found that the most flexible part of BBA5 is the N-terminal four residues. Although both are made of the identical ββα motif, the secondary structure formation sequence of BBA5 is found to be different from that of FSD-1. Finally, a description of the folding pathway in terms of principal component analysis is presented to characterize the folding dynamics in reduced dimensions. With only three principal components, we were able to describe 83.4% of the pathway.
Antiretroviral drugs for preventing mother-to-child transmission of HIV in sub-Saharan Africa: balancing efficacy and infant toxicity

Objective: Antiretroviral drugs can prevent mother-to-child transmission of HIV infection, but in-utero antiretroviral exposure may be associated with neurologic symptoms due to mitochondrial toxicity. We sought to identify the currently recommended regimen to prevent mother-to-child transmission that optimally balances risks of pediatric HIV infection and neurologic mitochondrial toxicity. Design: Published MTCT and mitochondrial toxicity data were used in a decision analytic model of MTCT among women in sub-Saharan Africa. Methods: We investigated the HIV and mitochondrial toxicity risks associated with no antiretroviral prophylaxis and five recommended regimens ranging from single-dose nevirapine to three-drug antiretroviral therapy (ART). Sensitivity analyses varied all parameters, including infant feeding strategy and the disability of mitochondrial toxicity relative to HIV. Results: Provision of no antiretroviral drugs is the least effective and least toxic strategy, with 18-month HIV risk of 30.4% and mitochondrial toxicity risk of 0.2% (breastfed infants). With increasing drug number and duration, HIV risk decreases markedly (to 4.9% with three-drug ART), but mitochondrial toxicity risk also increases (to 2.2%, also with three-drug ART). Despite increased toxicity, three-drug ART minimizes total adverse pediatric outcomes (HIV plus mitochondrial toxicity), unless the highest published risks are true for both HIV and mitochondrial toxicity, or the disability from mitochondrial toxicity exceeds 6.4 times that of HIV infection. Conclusion: The risk of pediatric mitochondrial toxicity from effective regimens to prevent mother-to-child transmission is at least an order of magnitude lower than the risk of HIV infection associated with less-effective regimens. Concern regarding mitochondrial toxicity should not currently limit the use of three-drug ART to prevent mother-to-child transmission where it is available.