Miracle-dz/UniFAR-FTUs huggingface dataset:
The subunit structure of rabbit-skeletal-muscle phosphorylase kinase, and the molecular basis of its activation reactions.

Phosphorylase kinase was isolated from rabbit skeletal muscle in a state approaching homogeneity as judged by the criteria of ultracentrifugal analysis, ion-exchange chromatography, and antigen-antibody precipitation in agar. The purified enzyme showed four protein-staining components upon acrylamide gel electrophoresis in the presence of sodium dodecylsulphate, termed α, α′, β and γ. A variety of precautions designed to eliminate the possible action of proteases and ensure complete reduction and denaturation of the protein had no influence on the gel pattern. The molecular weights of the four components determined by gel electrophoresis, and supported by sedimentation equilibrium in the presence of 6 M guanidinium chloride, following partial separation of the chains by gel filtration on Sephadex G-200 in the presence of sodium dodecylsulphate, were:–α= 145000, α′= 140000, β= 128000 and γ= 45000. The α' component was present only in trace amounts and the evidence suggests it may be derived from the α component. The three subunits α, β, and γ, were found to exist in equimolar quantities by densitometric analysis of acrylamide gels, by gel filtration on Sephadex G-200 in the presence of sodium dodecylsulphate, and by carboxymethylation with iodo[14C]acetate, suggesting a minimal binding molecular weight, αβγ, of 318000. The molecular weight of the native enzyme was determined as 1.28 × 106, demonstrating that phosphorylase kinase is composed of 4.0 αβγ units. Activation of the enzyme by incubation with adenosine-3′:5′-phosphate-dependent protein kinase, adenosine 3′:5′-phosphate and Mg-ATP, was accompanied by the phosphorylation of one site on the β subunit, although a second site on the α subunit was phosphorylated at a slower rate. Activation of the enzyme by proteolysis resulted from a limited cleavage of the α subunit. The products of proteolytic attack suggest that the α and β subunits may be structurally related. The γ subunit was not phosphorylated, was resistant to proteolysis and distinct from the (α+β) subunits in its amino acid composition. The possible functions of the chains, and the implications of the activation reactions to the nervous and hormonal control of glycogenolysis in vivo are discussed.
Comparison of a primal and a dual decomposition for distributed MPC in smart districts

This paper deals with energy management in smart districts using distributed model predictive control (DMPC). We investigate two decomposition methods, primal and dual decomposition, for problems where a shared resource has to be distributed optimally amongst sub systems. The objective is to compare these two decomposition methods with a focus on how well they are suited in the context of smart district energy management. In primal decomposition a coordinator layer is directly affecting resource limits to the sub problems whereas in dual decomposition virtual prices are used to stimulate the sub areas to change their resource consumption behavior in a desired way. Both methods are demonstrated to be able to converge to the globally optimal energy distribution in simulations, provided that the limit on the shared resource is chosen in a reasonable range. This result is particularly interesting regarding the fact that in the dual decomposition case, the number of degrees of freedom of the coordinator problem is only a fraction of the number of degrees of freedom in primal decomposition.
Analytical HFET <formula formulatype="inline"><tex>$I$</tex></formula>– <formula formulatype="inline"><tex>$V$</tex></formula> Model in Presence of Current Collapse

A compact analytical model of short-channel AlGaN/GaN HEMTs in the presence of a current collapse is presented. The model is based on an experimentally established trapping mechanism at the gate edges and relies on significant differences between the characteristic carrier capture-escape times and typical RF signal periods. For the first time, we implement the theory describing electric field distributions in the HEMT gate-to-drain spacing region, with and without trapped charge distributions. By consequently accounting for velocity saturation effects in gated and trapped regions of the device, the presented model shows good agreement with the experimental data. The model uses a minimal number of fitting parameters, most of which are physical parameters describing velocity-field dependence of the carriers.
Atividade física habitual e densidade mineral óssea em homens adultos e idosos

Objetivo: Verificar a correlacao entre a atividade fisica habitual (AFH) ao longo da vida e a densidade mineral ossea (DMO) em homens adultos e idosos. Metodos: Analisa 326 homens com idade igual ou superior a 50 anos, voluntarios, residentes no municipio de Sao Paulo. Os dados de DMO foram coletados atraves de densitometria ossea das regioes de corpo total, do colo do femur, do triângulo de ward, do trocanter e da coluna lombar (L2-L4) e expressos em gramas por centimetro ao quadrado (gr/cm2). Os dados de AFH foram coletados atraves de questionarios com questoes referentes a pratica de exercicios fisicos juntamente com atividades fisicas, nos periodos de 10 a 20 anos de idade, de 21 a 30 anos de idade, de 31 a 50 anos de idade e dos ultimos 12 meses e atividades de locomocao dos ultimos 12 meses. A relacao entre as variaveis foi analisada atraves do coeficiente de correlacao de Spearman e de regressao linear multipla ajustada por idade e indice de massa corporal (IMC). Resultados: Existe uma diminuicao progressiva da pratica de exercicios fisicos/atividades fisicas da adolescencia para as fases adulta e idosa. Os exercicios fisicos de lazer foram correlacionados significativamente na analise univariada nos periodos com a DMO. As atividades fisicas de locomocao foram correlacionadas significativamente. As atividades fisicas ocupacionais foram correlacionadas significativamente na analise univariada dos ultimos 12 meses com a DMO do colo do femur e do triângulo de ward. Na analise multivariada, as variaveis independentes que melhor explicaram a variacao da DMO em todos os locais analisados foram os exercicios fisicos de lazer praticados no periodo de 10 a 20 anos e as atividades fisicas de locomocao dos ultimos 12 meses, alem das atividades fisicas ocupacionais dos ultimos 12 meses para o colo do femur. Conclusao: Evidencia que a atividade fisica habitual, principalmente os exercicios fisicos de lazer praticados na adolescencia e as atividades fisicas de locomocao do cotidiano podem contribuir para aumento e preservacao da densidade mineral ossea e prevencao da osteoporose em homens adultos e idosos brasileiros
RESOLVING ETHICAL DILEMMAS IN PRIVATE FAMILY PRACTICE IN SINGAPORE

A family physician in private practice in Singapore faces many situations where ethical dilemmas have to be made during the consultation. From an ongoing discussion of a group of 5 doctors on-line, these situations have been broadly classified into four: conflict due to administrative imperatives and the doctor’s professionalism; conflict of patient’s choices and best practice; and conflicts between the patient’s wishes and the doctor’s professionalism. In resolving these dilemmas, it is most important to always put the patient as the central focus. The choice of action could be defended from a set of four ethical solutions: the theory of decided path; the preferred path; the lesser of two evils; or slippery slope. It is proposed that a two tier framework formed by firstly, identifying the ethical dilemma and secondly, finding the choice of action can aid the busy family physician in private practice to arrive at a decision more quickly and soundly when faced with an ethical dilemma. This framework can also be used to collect data to form a pool of unique experiences pertaining to family practice in Singapore. Such a framework of classifying ethical dilemmas will allow, over time, ethical discussions to be better guided. In addition, the archived ethical dilemmas and experiences can form a rich resource for reference that could be retrieved efficiently.
A Response to Cosco, Blossom, and Brayne

We would like to thank the Journal of Applied Gerontology for the opportunity and space to respond to the interesting points raised by Cosco, Blossom, and Brayne in response to our article “Aging Populations’ Everyday Life Perspectives on Healthy Aging: New Insights for Policy and Strategies at the Local Level. ” This article reports on a study that investigated how aging individuals experience healthy aging in their locality to strengthen interventions on healthy aging. One of the main conclusions of this study was that there is a mismatch between the way older individuals perceive healthy aging and the way healthy aging interventions are designed. Older people perceive health within the context of everyday life whereas health professionals address health themes as isolated topics (Naaldenberg, Vaandrager Koelen, & Leeuwis, 2011). The commentary by Cosco et al. raises important issues with regard to the ambiguity and lack of consensus in the labeling of positive states of aging and, consequently, the impeded ability to compare cross-study results. First, we would like to offer our views on the ambiguity of definitions of healthy aging. Cosco et al. correctly state that the ease of labeling the presence of disease stands in stark contrast with the ambiguity in labeling positive states of aging. This very issue can also be found in the definition of health in general. In 1948, the WHO defined health as a state of complete physical, mental, and social well-being, more than the absence of disease alone (WHO,
Terrain parameter estimation and traversability assessment for mobile robots

The estimation of terrain characteristics is an important missions of Martian exploration rovers. Since only limited resources and human supervision are available, efficient and autonomous method of estimation are required. In this thesis, an on-line estimation method of two important terrain parameters, cohesion and internal friction angle, is developed. The method uses onboard rover sensors and is computationally efficient. Terrain parameter estimation is of scientific interest, and can also be useful in predicting rover mobility on rough-terrain. A method to estimate traversability of a rover on deformable terrain using on-board sensors is presented. Simulation and experimental results show that the proposed methods can accurately and efficiently estimate traversability of deformable terrain. Thesis Supervisor: Steven Dubowsky Title: Professor of Mechanical Engineering
Localization and mobility of coenzyme Q in lipid bilayers and membranes

We have studied the mobility of coenzyme Q (CoQ) in lipid bilayers and mitochondrial membranes in relation to the control of electron transfer activities. A molecular dynamics computer simulation in the vacuum yielded a folded structure for CoQ10, with a length of only 21 Å. Using this information we were able to calculate diffusion coefficients in the range of 10−6 cm2/s in good agreement with those found experimentally by fluorescence quenching of pyrene derivatives. To investigate if CoQ diffusion may represent the rate‐limiting step of electron transfer, we reconstituted complexes I and III and assayed the resulting NADH‐cytochrome c reductase activity in presence of different CoQ10 levels and at different distances between complexes; the experimental turnovers were higher than the collision frequencies calculated using diffusion coefficients of 10−9 cm2/s but compatible with values found by us by fluorescence quenching. Since the experimental turnovers are independent of the distance between complexes, we conclude that CoQ diffusion is not rate‐limiting for electron transfer.
Mitochondrial Glycerol-3-Phosphate Acyltransferase-Deficient Mice Have Reduced Weight and Liver Triacylglycerol Content and Altered Glycerolipid Fatty Acid Composition

ABSTRACT Microsomal and mitochondrial isoforms of glycerol-3-phosphate acyltransferase (GPAT; E.C. 2.3.1.15) catalyze the committed step in glycerolipid synthesis. The mitochondrial isoform, mtGPAT, was believed to control the positioning of saturated fatty acids at the sn-1 position of phospholipids, and nutritional, hormonal, and overexpression studies suggested that mtGPAT activity is important for the synthesis of triacylglycerol. To determine whether these purported functions were true, we constructed mice deficient in mtGPAT. mtGPAT−/− mice weighed less than controls and had reduced gonadal fat pad weights and lower hepatic triacylglycerol content, plasma triacylglycerol, and very low density lipoprotein triacylglycerol secretion. As predicted, in mtGPAT−/− liver, the palmitate content was lower in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. Positional analysis revealed that mtGPAT−/− liver phosphatidylethanolamine and phosphatidylcholine had about 21% less palmitate in the sn-1 position and 36 and 40%, respectively, more arachidonate in the sn-2 position. These data confirm the important role of mtGPAT in the synthesis of triacylglycerol, in the fatty acid content of triacylglycerol and cholesterol esters, and in the positioning of specific fatty acids, particularly palmitate and arachidonate, in phospholipids. The increase in arachidonate may be functionally significant in terms of eicosanoid production.
An algorithm for fast direct calculation of quantized LSP parameters

Line Spectrum Pairs (LSP) are commonly used in speech coding for spectral quantization. Usually, the LSPs are first calculated, and then quantized. When scalar quantization is used, computational saving can be achieved by direct calculation of the quantized LSPs, searching zero-crossings on the grid formed by the values of the quantization tables (quantized-domain search). In a previous publication we have shown that by combining Kabal’s LSP calculation method with a quantized-domain search on a 34-bit quantization table, the number of polynomial evaluations is reduced from 150 to 71. In this paper we consider the use of a binary-tree quantizeddomain search to further decrease the complexity. It is explained why this type of search cannot be combined with Kabal’s method, and it is shown that Saoudi's LSP calculation method can be easily combined with a binary-tree quantized-domain search, obtaining a fast algorithm for direct quantized LSP calculation. The proposed algorithm reduces computational complexity and improves quantization performance.
Myelosuppressive Therapies Significantly Increase Pro‐Inflammatory Cytokines and Directly Cause Bone Loss

Skeletal‐related events resulting from accelerated bone loss are common complications in patients treated for a range of cancers. However, the mechanisms and rate of bone loss after myelosuppression are unclear. We, therefore, investigated this in mice and humans. We treated mice with different myelosuppressive therapies (chemotherapy or irradiation with or without transplantation) and studied their effects on bone structure. Myelosuppression of mice rapidly caused an increase in bone resorption that was not matched by bone formation. The resultant significant and persistent bone loss early after therapy was associated with increased inflammatory cytokines, in particular, monocyte chemoattractant protein 1 (MCP1). Therapy‐induced bone loss was prevented with a single dose of the bisphosphonate zoledronic acid (ZA), administered before myelosuppression. Importantly, ZA treatment of mice did not impair hematopoiesis, including hematopoietic stem cell function. Furthermore, examination of serum from patients before and after autologous or allogeneic stem cell transplantion (SCT) revealed altered levels of bone turnover markers and elevated inflammatory cytokines. MCP1 levels in serum obtained between days 7 and 14 post‐SCT positively correlated with bone loss observed at 100 days after allogeneic SCT. Similar to that observed in our studies in mice, the bone loss was long term, persisting at 12 months post‐SCT. Furthermore, patients who received chemotherapy less than 100 days before SCT had significantly more bone loss at the hip. In these patients, serum levels of MCP1, but not routine biomarkers of bone turnover, including C‐terminal cross‐linking telopeptide of type‐1 collagen (β‐CTx), positively correlated with their bone loss. Hence, myelosuppressive therapies increase inflammation and directly contribute to bone loss. Administration of an osteoclast inhibitor before the initiation of cancer therapy is likely to have the best outcome in preventing bone loss in patients with cancer. © 2014 American Society for Bone and Mineral Research.
Serotonergic transmission at Merkel discs: modulation by exogenously applied chemical messengers and involvement of Ih currents

The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ‐afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ‐afferent endings. In this study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers. We found that SA1 responses were potentiated by serotonin at low concentration (10 μM) but almost completely occluded by serotonin at high concentration (2 mM). In contrast, SA1 responses were not significantly affected by ATP and its metabolically stable analog α,β‐methylene‐ATP, glutamate, γ‐aminobutyric acid (GABA), and histamine. SA1 responses were also not affected by antagonists for P2X receptors, ionotropic glutamate receptors, and ionotropic GABA and glycine receptors. Whole‐cell patch‐clamp recordings reconfirm the presence of both ionotropic and metabotropic 5‐HT receptors on afferent neurons and their terminals innervating whisker hair follicles. All whisker afferent neurons expressed hyperpolarization‐activated inward currents (Ih), which are potentiated by serotonin through the activation of metabotropic 5‐HT receptors. Taken together, the findings substantiate the serotonergic mechanism of tactile transmission at Merkel discs and identify the involvement of Ih currents in postsynaptic excitatory actions of serotonin. In addition, the findings do not favor any significant involvement of ATP, glutamate, histamine, GABA, or glycine in tactile transmission at the Merkel discs of whisker hair follicles.
Aggregators' Optimal Bidding Strategy in Sequential Day-Ahead and Intraday Electricity Spot Markets

This paper proposes a probabilistic optimization method that produces optimal bidding curves to be submitted by an aggregator to the day-ahead electricity market and the intraday market, considering the flexible demand of his customers (based in time dependent resources such as batteries and shiftable demand) and taking into account the possible imbalance costs as well as the uncertainty of forecasts (market prices, demand, and renewable energy sources (RES) generation). The optimization strategy aims to minimize the total cost of the traded energy over a whole day, taking into account the intertemporal constraints. The proposed formulation leads to the solution of different linear optimization problems, following the natural temporal sequence of electricity spot markets. Intertemporal constraints regarding time dependent resources are fulfilled through a scheduling process performed after the day-ahead market clearing. Each of the different problems is of moderate dimension and requires short computation times. The benefits of the proposed strategy are assessed comparing the payments done by an aggregator over a sample period of one year following different deterministic and probabilistic strategies. Results show that probabilistic strategy reports better benefits for aggregators participating in power markets.
Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses

Influenza remains a serious public health threat throughout the world. Vaccines and antivirals are available that can provide protection from infection. However, new viral strains emerge continuously because of the plasticity of the influenza genome, which necessitates annual reformulation of vaccine antigens, and resistance to antivirals can appear rapidly and become entrenched in circulating virus populations. In addition, the spread of new pandemic strains is difficult to contain because of the time required to engineer and manufacture effective vaccines. Monoclonal antibodies that target highly conserved viral epitopes might offer an alternative protection paradigm. Herein we describe the isolation of a panel of monoclonal antibodies derived from the IgG+ memory B cells of healthy, human subjects that recognize a previously unknown conformational epitope within the ectodomain of the influenza matrix 2 protein, M2e. This antibody binding region is highly conserved in influenza A viruses, being present in nearly all strains detected to date, including highly pathogenic viruses that infect primarily birds and swine, and the current 2009 swine-origin H1N1 pandemic strain (S-OIV). Furthermore, these human anti-M2e monoclonal antibodies protect mice from lethal challenges with either H5N1 or H1N1 influenza viruses. These results suggest that viral M2e can elicit broadly cross-reactive and protective antibodies in humans. Accordingly, recombinant forms of these human antibodies may provide useful therapeutic agents to protect against infection from a broad spectrum of influenza A strains.
Selective treatment of multiple sclerosis.

Natalizumab, a recombinant monoclonal antibody against α4 integrins, is the first selective immunomodulating drug for the treatment of multiple sclerosis and, by several criteria, is an advance over current therapies. The antibody was developed to block the adhesion of activated T cells to endothelial cells and thereby reduce the inflammatory feature of the multiple sclerosis plaque. Parenthetically, this advance attests to the value of translational research in a disease for which there is only partial knowledge of the mechanism. Natalizumab has also evinced interest for the treatment of Crohn's disease and rheumatoid arthritis but with less certain results in .