IMPORTANCE: Hypoxic-ischemic encephalopathy (HIE) occurs in 1 to 8 per 1000 live births in developed countries. Historically, the clinician has had little to offer neonates with HIE other than ...systemic supportive care. Recently, the neuroprotective therapy of hypothermia has emerged as the standard of care, and other complementary therapies are rapidly transitioning from the basic science to clinical care. OBJECTIVE: To examine the pathophysiology of HIE and the state of the art for the clinical care of neonates with HIE. EVIDENCE REVIEW: We performed a literature review using the PubMed database. Results focused on reviews and articles published from January 1, 2004, through December 31, 2014. Articles published earlier than 2004 were included when appropriate for historical perspective. Our review emphasized evidence-based management practices for the clinician. FINDINGS: A total of 102 articles for critical review were selected based on their relevance to the incidence of HIE, pathophysiology, neuroimaging, placental pathology, biomarkers, current systemic supportive care, hypothermia, and emerging therapies for HIE and were reviewed by both of us. Seventy-five publications were selected for inclusion in this article based on their relevance to these topics. The publications highlight the emergence of serum-based biomarkers, placental pathology, and magnetic resonance imaging as useful tools to predict long-term outcomes. Hypothermia and systemic supportive care form the cornerstone of therapy for HIE. CONCLUSIONS AND RELEVANCE: The pathophysiology of HIE is now better understood, and treatment with hypothermia has become the foundation of therapy. Several neuroprotective agents offer promise when combined with hypothermia and are entering clinical trials.
Root endophytism and mycorrhizal associations are complex derived traits in fungi that shape plant physiology. Sebacinales (Agaricomycetes, Basidiomycota) display highly diverse interactions with ...plants. Although early-diverging Sebacinales lineages are root endophytes and/or have saprotrophic abilities, several more derived clades harbour obligate biotrophs forming mycorrhizal associations. Sebacinales thus display transitions from saprotrophy to endophytism and to mycorrhizal nutrition within one fungal order. This review discusses the genomic traits possibly associated with these transitions. We also show how molecular ecology revealed the hyperdiversity of Sebacinales and their evolutionary diversification into two sister families: Sebacinaceae encompasses mainly ectomycorrhizal and early-diverging saprotrophic species; the second family includes endophytes and lineages that repeatedly evolved ericoid, orchid and ectomycorrhizal abilities.Wepropose the name Serendipitaceae for this family and, within it, we transfer to the genus Serendipita the endophytic cultivable species Piriformospora indica and P. williamsii. Such cultivable Serendipitaceae species provide excellent models for root endophytism, especially because of available genomes, genetic tractability, and broad host plant range including important crop plants and the model plant Arabidopsis thaliana. We review insights gained with endophytic Serendipitaceae species into the molecular mechanisms of endophytism and of beneficial effects on host plants, including enhanced resistance to abiotic and pathogen stress.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
3.
Global Homophobia Weiss, Meredith L; Bosia, Michael J; Blasius, Mark ...
08/2013
eBook
While homophobia is commonly characterized as individual and personal prejudice, this collection of essays instead explores homophobia as a transnational political phenomenon. Contributors theorize ...homophobia as a distinct configuration of repressive state-sponsored policies and practices with their own causes, explanations, and effects on how sexualities are understood and experienced in a range of national contexts. The essays include a broad range of geographic cases, including Cameroon, Ecuador, Iran, Lebanon, Poland, Singapore, and the United States.
Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ...ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.
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•The structure of the insulin receptor ectodomain is improved to 3.3 Å resolution•The structure reveals new features within the receptor insert domain•The structure corrects errors in the first and third fibronectin type III domains•A new low-resolution crystallographic model-building strategy, iMDFF, is presented
Croll et al. describe a revised structure of the human insulin receptor ectodomain using diffraction data to 3.3 Å resolution. The revised structure allows improved resolution of the insert domain, an element critical to ligand binding and signal transduction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Spinal muscular atrophy (SMA) is a group of neurodegenerative disorders resulting from the loss of spinal motor neurons. 95% of patients share a pathogenic mechanism of loss of survival motor neuron ...(SMN) 1 protein expression due to homozygous deletions or other mutations of the SMN1 gene, with the different phenotypes influenced by variable copy numbers of the SMN2 gene. Advances in supportive care, disease modifying treatment and novel gene therapies have led to an increase in the prevalence of SMA, with a third of SMA patients now represented by adults. Despite the growing number of adult patients, consensus on the management of SMA has focused primarily on the pediatric population. As the disease burden is vastly different in adult SMA, an approach to treatment must be tailored to their unique needs. This review will focus on the management of the adult SMA patient as they age and will discuss proper transition of care from a pediatric to adult center, including the need for continued monitoring for osteoporosis, scoliosis, malnutrition, and declining mobility and functioning. As in the pediatric population, multidisciplinary care remains the best approach to the management of adult SMA. Novel and emerging therapies such as nusinersen and risdiplam provide hope for these patients, though these medications are of uncertain efficacy in this population and require additional study.
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This paper presents a novel lithium-ion cell model, which simulates the current voltage characteristic as a function of state of charge (0%–100%) and temperature (0–30 °C). It predicts the cell ...voltage at each operating point by calculating the total overvoltage from the individual contributions of (i) the ohmic loss η0, (ii) the charge transfer loss of the cathode ηCT,C, (iii) the charge transfer loss and the solid electrolyte interface loss of the anode ηSEI/CT,A, and (iv) the solid state and electrolyte diffusion loss ηDiff,A/C/E. This approach is based on a physically meaningful equivalent circuit model, which is parametrized by electrochemical impedance spectroscopy and time domain measurements, covering a wide frequency range from MHz to μHz. The model is exemplarily parametrized to a commercial, high-power 350 mAh graphite/LiNiCoAlO2-LiCoO2 pouch cell and validated by continuous discharge and charge curves at varying temperature. For the first time, the physical background of the model allows the operator to draw conclusions about the performance-limiting factor at various operating conditions. Not only can the model help to choose application-optimized cell characteristics, but it can also support the battery management system when taking corrective actions during operation.
•Impedance based battery model for the simulation of current voltage characteristics.•DRT analysis for the derivation of a physically meaningful equivalent circuit model.•Identification and quantification of all loss contributions in a lithium-ion cell.•Analysis of model parameter dependency on state of charge, temperature and current.•Practical relevance of the model for cell design and battery management systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Dominant mutations in the human insulin gene can lead to pancreatic β-cell dysfunction and diabetes mellitus due to toxic folding of a mutant proinsulin. Analogous to a classical mouse model (the ...Akita mouse), this monogenic syndrome highlights the susceptibility of human β-cells to endoreticular stress due to protein misfolding and aberrant aggregation. The clinical mutations directly or indirectly perturb native disulfide pairing. Whereas the majority of mutations introduce or remove a cysteine (leading in either case to an unpaired residue), non-cysteine-related mutations identify key determinants of folding efficiency. Studies of such mutations suggest that the evolution of insulin has been constrained not only by its structure and function, but also by the susceptibility of its single-chain precursor to impaired foldability.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Humans spontaneously invent songs from an early age. Here, we exploit this natural inclination to probe implicit musical knowledge in 33 untrained and poor singers (amusia). Each sang 28 ...long improvisations as a response to a verbal prompt or a continuation of a melodic stem. To assess the extent to which each improvisation reflects tonality, which has been proposed to be a core organizational principle of musicality and which is present within most music traditions, we developed a new algorithm that compares a sung excerpt to a probability density function representing the tonal hierarchy of Western music. The results show signatures of tonality in both nonmusicians and individuals with congenital amusia, who have notorious difficulty performing musical tasks that require explicit responses and memory. The findings are a proof of concept that improvisation can serve as a novel, even enjoyable method for systematically measuring hidden aspects of musicality across the spectrum of musical ability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Various methods exist for statistical inference about a prevalence that consider misclassifications due to an imperfect diagnostic test. However, traditional methods are known to ...suffer from truncation of the prevalence estimate and the confidence intervals constructed around the point estimate, as well as from under-performance of the confidence intervals’ coverage.
Methods
In this study, we used simulated data sets to validate a Bayesian prevalence estimation method and compare its performance to frequentist methods, i.e. the Rogan-Gladen estimate for prevalence,
RGE
, in combination with several methods of confidence interval construction. Our performance measures are (i) error distribution of the point estimate against the simulated true prevalence and (ii) coverage and length of the confidence interval, or credible interval in the case of the Bayesian method.
Results
Across all data sets, the Bayesian point estimate and the
RGE
produced similar error distributions with slight advantages of the former over the latter. In addition, the Bayesian estimate did not suffer from the
RGE
’s truncation problem at zero or unity. With respect to coverage performance of the confidence and credible intervals, all of the traditional frequentist methods exhibited strong under-coverage, whereas the Bayesian credible interval as well as a newly developed frequentist method by Lang and Reiczigel performed as desired, with the Bayesian method having a very slight advantage in terms of interval length.
Conclusion
The Bayesian prevalence estimation method should be prefered over traditional frequentist methods. An acceptable alternative is to combine the Rogan-Gladen point estimate with the Lang-Reiczigel confidence interval.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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