Miracle-dz/UniFAR-FTUs huggingface dataset:
Induced Fit and Wit: Celebrating the Life of Daniel E. Koshland, Jr. (1920 ‐ 2007)

On a beautiful Sunday afternoon in September, scientists, friends, and family gathered in UC Berkeley’s newly-opened Stanley Hall to celebrate the life of Daniel E. Koshland, Jr., Professor of Biochemistry at UC Berkeley, former editor of Science, and human being extraordinaire. There were hugs, laughter, and reunions of friends who had not seen each other for decades. There was also sadness – for the loss of a friend and a giant. This seemingly disparate group of people had one common thread in the tapestry of their lives: they had all been touched by a visionary biochemist. An afternoon of science – a symposium called ‘Induced Fit: The Science and Wit of Daniel E. Koshland, Jr.’ – preceded a memorial. At the symposium, students whose careers had been launched by Koshland, colleagues who had been mentored and inspired by Koshland, and the two of his children who chose careers in science (Doug Koshland, Carnegie Institution and Gail Koshland, University of Arizona) presented research talks in which the enormous influence of Dan Koshland and his incomparable humor permeated the outstanding scientific presentations. Koshland received a BSc in Chemistry from UC Berkeley in 1941. In 1949, the same year his wife, Marian (Bunny) Koshland earned her PhD in Immunology, he was awarded a PhD in inorganic chemistry, working with Wendell Latimer, from the University of Chicago. He joined the Manhattan Project, working with Glenn Seaborg in Chicago, and could have earned his reputation as an inorganic chemist. Instead, with the type of bold action that he repeated numerous times throughout his scientific career, he immersed himself in biochemistry. After two years of postdoctoral work at Harvard working in Fritz Lipmann’s laboratory, he and his wife moved to Brookhaven, where they raised their five children. He was recruited back to UC Berkeley in 1958. As he liked to explain, he told Marian that if they moved to Berkeley he would be nice to her forever, but if they stayed in Brookhaven, she would need to be nice to him forever. They moved. In 1958, in a symposium on amino acid activation, Koshland proposed a revolutionary theory that he coined ‘induced fit’ (see ‘Application of a theory of enzyme specificity to protein synthesis’ (1)). The title of the paper revealed nothing about the theory or its importance. Koshland suggested that ‘the substrate may cause an appreciable change in the three-dimensional relationship of the amino acids at the The late Daniel E. Koshland, Jr. Dr. Koshland was a founding editor of IUBMB Life (The photograph was taken by permission from the University of California at Berkeley website: http://www.berkeley.edu/news/media/download/)
Results of re‐irradiation for cerebral metastases

After an initial course of radiation, 56 patients with cerebral metastases had their brain retreated at least once for recurrent neurologic symptoms. The most common primary was from either the lung or breast. The frequent symptoms were headache, weakness, seizures, visual problems, and/or mental changes. Forty‐two (75%) of these patients responded to the second course of treatment. The median duration of response was 10 weeks and median survival was 14 weeks.
Uma avaliação do perfil nutricional de adolescentescom síndrome de down para um eficienteaconselhamento dietético

O presente estudo teve como objetivo avaliar o perfil nutricional dos 18 adolescentes com sindrome de Down, residentes na Regiao Sul do Estado do Tocantins, com idade entre 10 e 19 anos. Para a concretizacao deste estudo foi utilizado o metodo de avaliacao de contexto que permite definir e descrever o meio ambiental concernente a um fenomeno. Na avaliacao antropometr ica utilizou- se a distribuicao de referencia recomendada pela Or ganizacao Mundial da Saude para adolescentes da populacao em geral, que indica o indice de massa corpor al associado a mensuracao das pr egas cutâneas tricipital e subescapular. Para a avaliacao da qualidade alimentar foi aplicado um Questionario de Frequencia Alimentar para Adolescentes e adaptado para o presente estudo, cujos dados foram comparados com a Pirâmide Alimentar Adaptada. Neste estudo, 61% dos individuos apresentaram excessiva massa cor poral. Destes, pelas medidas das dobras cutâneas, 63,6% tem gor dura acima do desejavel, com resultado confirmatorio de obesidade. Os habitos alimentares se mostraram inadequados, uma vez constatado consumo menor que o recomendado de hortalicas, frutas, leite e produtos lacteos, bem como o consumo exagerado de carnes, ovos, acucares, cereais, paes, tuberculos e raizes. Concluiu-se que os individuos com sindrome de Down apresentam tendencia a ter em peso excessivo e mesmo obesidade, problema que pode ser agravado pelos habitos alimentares inadequados detectados no estudo. Entendeu-se como necessar ia a reeducacao alimentar destes individuos, tendo, esta avaliacao de contexto contribuido para o planejamento de uma eficiente inter vencao nutricional para esse grupo populacional, podendo trazer beneficios para suas vidas
SIC/ALN PIEZOELECTRIC ENERGY HARVESTERS FOR PULSED PRESSURE SOURCES IN HARSH ENVIRONMENT APPLICATIONS

Piezoelectric micromachined circular diaphragm energy harvesters for pulsed pressure sources have been fabricated and characterized. These devices utilize silicon carbide (SiC) as the structural material and aluminum nitride (AlN) as the active piezoelectric element to enable operation within harsh environments. In particular, the SiC/AlN energy harvesting device yields an output power density of 20 μW/cm and rms voltage of 0.2 V under pressure pulses of 1.09 psi (rms) at 2 kHz. Fabricated SiC/AlN harvester has been characterized at elevated temperatures as high as 250°C. This work not only demonstrates the first harsh environment energy harvesters based on SiC and AlN for a pulsed pressure environment, but also addresses its potentials for integrating energy harvesting power source with SiC circuitry and enabling self-powered wireless sensors. This type of sensing system can be used for the real-time monitoring of harsh environment energy system such as automotive engines, gas turbines and geothermal wells.
Autocatalytic growth of biofunctionalized antibacterial silver nanoparticles

Development of eco‐friendly processes for nanosynthesis is gaining importance owing to the widespread application of nanoparticles (NPs). In the present study, we have explained the mechanism and kinetics of bioreduction in the biosynthesis of silver nanoparticles (AgNPs) using aqueous leaf extract of Rhizophora apiculata. Spectrophotometric methods were employed to quantify the bioactive molecules present before and after the reduction process. The results showed that the polyphenols were the main components responsible for the biosynthesis of AgNPs, which was further confirmed by Fourier transform infrared spectroscopy. The kinetics of formation of AgNPs were monitored by time‐resolved spectrophotometric and X‐ray diffraction studies, which revealed that the NP formation is an autocatalytic process with a rate constant of 1.9 × 10−2 Min−1. The NPs were characterized using spectroscopic and microscopic techniques like ultraviolet–visible absorption spectroscopy, dynamic light scattering, transmission electron microscopy, scanning electron microscopy–energy‐dispersive X‐ray spectroscopy, and X‐ray diffraction. The biogenic AgNPs showed substantial inhibitory activity to Proteus mirabilis, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus with minimum inhibitory concentration values of 2.5, 12.5, 2.5, and 31.25 μg/mL, respectively. The current research provides an insight into the mechanistic aspects of bioreduction and formation of AgNPs.
Anoxybacillusgeothermalis sp. nov., a facultatively anaerobic, endospore-forming bacterium isolated from mineral deposits in a geothermal station.

A novel endospore-forming bacterium designated strain GSsed3T was isolated from deposits clogging aboveground filters from the geothermal power platform of Groß Schönebeck in northern Germany. The novel isolate was Gram-staining-positive, facultatively anaerobic, catalase-positive and oxidase-positive. Optimum growth occurred at 60 °C, 0.5 % (w/v) NaCl and pH 7-8. Analysis of the 16S rRNA gene sequence similarity indicated that strain GSsed3T belonged to the genus Anoxybacillus, and showed 99.8 % sequence similarity to Anoxybacillus rupiensis R270T, 98.2 % similarity to Anoxybacillus tepidamans GS5-97T, 97.9 % similarity to Anoxybacillus voinovskiensis TH13T, 97.7 % similarity to Anoxybacillus caldiproteolyticus DSM 15730T and 97.6 % similarity to Anoxybacillus amylolyticus MR3CT. DNA-DNA hybridization (DDH) indicated only 16 % relatedness to Anoxybacillus rupiensis DSM 17127T. Furthermore, DDH estimation based on genomes analysis indicated only 19.9 % overall nucleotide similarity to Anoxybacillus amylolyticus DSM 15939T. The major respiratory menaquinone was MK-8. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unknown phosphoglycolipid and one unknown phospholipid. The predominant cellular fatty acids were iso-C15 : 0, iso-C17 : 0, C16 : 0, iso-C16 : 0 and anteiso-C17 : 0. The peptidoglycan type was A1γ meso-Dpm-direct. The genomic DNA G+C content of the strain was 46.9 mol%. The phenotypic, genotypic and chemotaxonomic characterization indicated that strain GSsed3T differs from related species of the genus. Therefore, strain GSsed3T is considered to be a representative of a novel species of the genus Anoxybacillus, for which the name Anoxybacillus geothermalis sp. nov. is proposed. The type strain of Anoxybacillus geothermalis is GSsed3T (=CCOS808T =ATCC BAA2555T).
A Missense Mutation in the Sodium Channel β2 Subunit Reveals SCN2B as a New Candidate Gene for Brugada Syndrome

Brugada Syndrome (BrS) is a familial disease associated with sudden cardiac death. A 20%–25% of BrS patients carry genetic defects that cause loss‐of‐function of the voltage‐gated cardiac sodium channel. Thus, 70%–75% of patients remain without a genetic diagnosis. In this work, we identified a novel missense mutation (p.Asp211Gly) in the sodium β2 subunit encoded by SCN2B, in a woman diagnosed with BrS. We studied the sodium current (INa) from cells coexpressing Nav1.5 and wild‐type (β2WT) or mutant (β2D211G) β2 subunits. Our electrophysiological analysis showed a 39.4% reduction in INa density when Nav1.5 was coexpressed with the β2D211G. Single channel analysis showed that the mutation did not affect the Nav1.5 unitary channel conductance. Instead, protein membrane detection experiments suggested that β2D211G decreases Nav1.5 cell surface expression. The effect of the mutant β2 subunit on the INa strongly suggests that SCN2B is a new candidate gene associated with BrS.
E-learning 2.0

When we think of learning content today, we probably think of a learning object [https://edtechbooks.org/-nLgm]. Originating in the world of computer-based delivery (CBT) systems, learning objects were depicted as being like lego blocks [https://edtechbooks.org/-gjo] or atoms [https://edtechbooks.org/-pPc], little bits of content that could be put together or organized. Standards bodies have refined the concept of learning objects into a rigorous form [http://ltsc.ieee. org/wg12] and have provided specifications on how to sequence and organize these bits of content into courses [https://edtechbooks.org/-CVBg] and package them for delivery [http://www.intrallect. com] as though they were books or training manuals.
Outbreak of Mupirocin-Resistant Staphylococci in a Hospital in Warsaw, Poland, Due to Plasmid Transmission and Clonal Spread of Several Strains

ABSTRACT An outbreak of mupirocin-resistant (MuR) staphylococci was investigated in two wards of a large hospital in Warsaw, Poland. Fifty-three MuR isolates of Staphylococcus aureus, S. epidermidis, S. haemolyticus, S. xylosus, and S. capitis were identified over a 17-month survey which was carried out after introduction of the drug for the treatment of skin infections. The isolates were collected from patients with infections, environmental samples, and carriers; they constituted 19.5% of all staphylococcal isolates identified in the two wards during that time. Almost all the MuR isolates were also resistant to methicillin (methicillin-resistant S. aureus and methicillin-resistant coagulase-negative staphylococci). Seven of the outbreak isolates expressed a low-level-resistance phenotype (MuL), whereas the remaining majority of isolates were found to be highly resistant to mupirocin (MuH). The mupA gene, responsible for the MuH phenotype, has been assigned to three different polymorphic loci among the strains in the collection analyzed. The predominant polymorph, polymorph I (characterized by a mupA-containingEcoRI DNA fragment of about 16 kb), was located on a specific plasmid which was widely distributed among the entire staphylococcal population. All MuR S. aureus isolates were found to represent a single epidemic strain, which was clonally disseminated in both wards. The S. epidermidis population was much more diverse; however, at least four clusters of closely related isolates were identified, which suggested that some strains of this species were also clonally spread in the hospital environment. Six isolates of S. epidermidis were demonstrated to express the MuL and MuH resistance mechanisms simultaneously, and this is the first identification of such dual MuR phenotype-bearing strains. The outbreak was attributed to a high level and inappropriate use of mupirocin, and as a result the dermatological formulation of the drug has been removed from the hospital formulary.
Acute Hypertension, but Not Thrombolysis, Increases the Incidence and Severity of Hemorrhagic Transformation Following Experimental Stroke in Rabbits

Hemorrhagic transformation (HT) is a poorly understood yet frequent complication of stroke. A transient increase in blood pressure (BP) occurs immediately after experimental embolization in rabbits and we evaluated the relationship between this acute hypertensive response and subsequent hemorrhagic transformation, as well as the attenuation of this hypertensive response with an anesthetic dose of halothane. We also examined embolism-induced HT during infusion of the thrombolytic agents tissue plasminogen activator and streptokinase. A blood clot embolus was injected into the internal carotid artery and flushed into the middle cerebral artery. In the first experiment, BP was monitored in anesthetized or unanesthetized rabbits for 20 min prior to and up to 1 h after embolization. In the second experiment, animals were embolized half-way through an infusion of tPA (3.0 mg/kg; 20% administered as an iv bolus, with the remainder infused over 30 min) or streptokinase (30,000 U/kg iv infused over 30 min). In unanesthetized animals, the HT score (number of brain sections displaying visible HT) was significantly correlated with the peak mean arterial pressure recorded at embolization (r = 0.60, n = 24, P < 0.01). No relationship was observed between BP and HT score in animals anesthetized with halothane. Although HT incidence and extent were significantly related to elevated BP in the unanesthetized animals, halothane administration actually increased HT incidence. Embolization during thrombolytic infusion did not increase the occurrence or severity of HT. These data suggest that acute hypertension, but not ongoing thrombolysis, is a significant risk factor for HT following cerebral embolization.
Apelin Enhances Cardiac Neovascularization After Myocardial Infarction by Recruiting Aplnr+ Circulating Cells

Rationale: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development. However, the role of apelin signaling in stem cell recruitment after ischemia is unknown. Objective: To investigate the role of apelin signaling in recruitment after ischemia. Methods and Results: Aplnr was specifically expressed in circulating cKit+/Flk1+ cells but not in circulating Sca1+/Flk1+ and Lin+ cells. cKit+/Flk1+/Aplnr+ cells increased significantly early after myocardial ischemia but not after hind limb ischemia, indicative of an important role for apelin/Aplnr in cell recruitment during the nascent biological repair response after myocardial damage. In line with this finding, apelin expression was upregulated in the infarcted myocardium. Injection of apelin into the ischemic myocardium resulted in accelerated and increased recruitment of cKit+/Flk1+/Aplnr+ cells to the heart. Recruited Aplnr+/cKit+/Flk1+ cells promoted neovascularization in the peri-infarct area by paracrine activity rather than active transdifferentiation, resulting into cardioprotection as indicated by diminished scar formation and improved residual cardiac function. Aplnr knockdown in the bone marrow resulted in aggravation of myocardial ischemia–associated damage, which could not be rescued by apelin. Conclusions: We conclude that apelin functions as a new and potent chemoattractant for circulating cKit+/Flk1+/Aplnr+ cells during early myocardial repair, providing myocardial protection against ischemic damage by improving neovascularization via paracine action.
Clinical needs assessment of middle and high school students following the 1995 Oklahoma City bombing.

OBJECTIVE This clinical assessment was designed to identify middle and high school students in need of formal evaluation for posttraumatic response symptoms following the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City. METHOD A clinical needs assessment instrument was developed and administered to grade 6 through 12 students 7 weeks after the bombing (N = 3,218). RESULTS More than 40% of the students reported knowing someone injured, and more than one-third reported knowing someone killed in the blast. Posttraumatic stress symptoms at 7 weeks significantly correlated with gender, exposure through knowing someone injured or killed, and bomb-related television viewing. CONCLUSIONS This study documents the intensity of community exposure to the bombing and the lingering symptoms of stress. The assessment was used in planning for clinical service delivery, training professional responders, and supporting funding requests.
Hepatitis C virus infection: the new global epidemic

Hepatitis C virus infects an estimated 170 million people worldwide. It is a major cause of liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. It is also a leading cause of liver transplant in the USA. The virus is primarily transmitted parenterally, but there is significant mother-to-child transmission. Partly due to the virus’s genetic diversity, it evades the host immune response and it has been difficult to identify candidate vaccines. However, significant advances have been made in the treatment of chronic hepatitis C virus infection. Currently, the combination of pegylated interferon-α and ribavirin is the standard treatment for chronic hepatitis C virus infection, and leads to long-term eradication of the virus in approximately 54% of people. Treatment response is dependent on the infecting genotype, with 76 to 80% of those with genotypes 2 and 3, but only approximately 40% with genotype 1 or 4 achieving a sustained virologic response. Since treatment is expensive and associated with significant adverse effects, more effective strategies for the prevention of transmission are needed, especially in resource-limited countries, where the burden of disease is the highest.
Determination of respiratory system mechanics during inspiration and expiration by FLow-controlled EXpiration (FLEX): a pilot study in anesthetized pigs.

BACKGROUND Differences between inspiratory and expiratory lung mechanics result in the hysteresis of the pressure volume-loop. While hysteresis area is a global parameter describing the difference between inspiration and expiration in mechanics under quasi-static conditions, a detailed analysis of this difference under the dynamic conditions of mechanical ventilation is feasible once inspiratory and expiratory compliance (Cin/Cex) are determined separately. This requires uncoupling of expiratory flow rate and volume (V). METHODS Five piglets were mechanically ventilated at positive end-expiratory pressure (PEEP) levels ranging from 0 to 15 cmH2O. Expiratory flow rate was linearized by a computer-controlled resistor (flow-controlled expiration). The volume-dependent Cin(V) and Cex(V) profiles were calculated from the tracheal pressure volume-loops. RESULTS The intratidal curve-progression of Cex(V) was altogether higher with a steeper slope compared to Cin(V). With increasing positive end-expiratory pressure (PEEP) dynamic hysteresis area decreased and Cex(V) tended to run more parallel to Cin(V). CONCLUSION The relation between inspiratory and expiratory compliance profiles is associated with the hysteresis area and behaves PEEP dependent. Analysing the Cin-Cex-relation might therefore potentially offer a new approach to titrate PEEP and tidal volume.
Investigating time patterns of variation in radiation cancer associations

Aims: In occupational settings, carcinogenic exposures are often repeated or protracted over time. The time pattern of exposure accrual may influence subsequent temporal patterns of cancer risk. The authors present several simple models that may be used to evaluate the influence of time since exposure or age at exposure on cancer incidence or mortality in an occupational cohort. Methods: A cohort of 40 415 nuclear industry workers was identified via the Canadian National Dose Registry. Vital status and cause of death were ascertained through 1994. Associations between ionising radiation and mortality due to lung cancer, leukaemia, and cancers other than lung and leukaemia were quantified using conditional logistic regression models with risk sets constructed by incidence density sampling. A step function, a bilinear function, and a sigmoid function were used to evaluate temporal variation in exposure effects. Results: Step and sigmoid functions were used to explore latency and morbidity periods. For analyses of lung cancer, leukaemia, and other cancers the best fitting models were obtained when exposure assignment was lagged by 13, 0, and 5 years, respectively. A bilinear function was used to evaluate whether exposure effects diminished with time since exposure. In analyses of lung cancer and leukaemia, there was evidence that radiation effects attenuated with protracted time since exposure. In analyses of age at exposure, there was evidence of variation in radiation mortality associations for analyses of lung cancer and leukaemia; discounting radiation doses accrued at younger ages (for example, 15–35 years) led to significant improvements in model fit. Conclusions: This paper illustrates empirical approaches to evaluating temporal variation in the effect of a protracted exposure on disease risk.
REDD1 is required for RAS-mediated transformation of human ovarian epithelial cells

REDD1 is a gene induced by hypoxia and stimuli from multiple DNA damage. Here we show that REDD1 expression was elevated in RAS-transformed ovarian epithelial cells lines and that this overexpression increased these cells’ growth rate and anchorage-independent growth on soft agar. Injection of immortalized ovarian epithelial cells overexpressing REDD1 into nude mice resulted in tumor growth that developed into papillary serous carcinoma in the peritoneal cavity. Knockdown of REDD1 expression blocked the RAS-mediated transformation of these cell lines. Apoptosis was markedly decreased by increased expression of Bcl-xL or Bcl-2 and decreased expression of FADD, caspase1, caspase8, caspase 9, caspase 10, BAX, Bad and Bcl-Xs, which confirmed by the tunnel assay. Our data demonstrated that REDD1 is a key mediator in RAS-mediated transformation through an effect on anti-apoptosis.