Miracle-dz/UniFAR-FTUs huggingface dataset:
Implications of Magma Transfer Between Multiple Reservoirs on Eruption Cycling

Volcanic eruptions are episodic despite being supplied by melt at a nearly constant rate. We used histories of magma efflux and surface deformation to geodetically image magma transfer within the deep crustal plumbing of the Soufrière Hills volcano on Montserrat, West Indies. For three cycles of effusion followed by discrete pauses, supply of the system from the deep crust and mantle was continuous. During periods of reinitiated high surface efflux, magma rose quickly and synchronously from a deflating mid-crustal reservoir (at about 12 kilometers) augmented from depth. During repose, the lower reservoir refilled from the deep supply, with only minor discharge transiting the upper chamber to surface. These observations are consistent with a model involving the continuous supply of magma from the deep crust and mantle into a voluminous and compliant mid-crustal reservoir, episodically valved below a shallow reservoir (at about 6 kilometers).
Sex Differences in Dyslexia

Handbooks, annual reviews and journals devoted to schizophrenia are a longestablished feature of the psychiatric library and only recently have the affective disorders challenged this pre-eminence. The massive increase in research literature and other territorial gains made by the affective illnesses make a handbook devoted to them timely. Forty-six authors contribute thirty-three chapters covering the nosology, psychopathology, aetiology and management of manic-depressive disease, the neurotic depressions and anxiety states. The coverage is exhaustive with little unnecessary overlap between essays, and, in general, these are well-written, enjoyable and well-referenced. The American contributions suffer a little from the usual heavy circumlocutions but the authors or Editor have, on this occasion, exercised some restraint. Inevitably, perhaps, there is some unevenness in approach. Some contributions, such as the chapter on lithium are surprisingly brief whilst others, for example the chapter on personality and affective disorder, pursue the fine detail of their assignment. Some topics (drug treatment, amine hypothesis) have received extensive and repeated review in recent years and will be very familiar to many readers. Others (group psychotherapy for depression, depression in childhood, animal models) figure less frequently in the diet of general psychiatrists and physicians and will therefore be of more interest. In general, the literature is surveyed fairly but there are some surprising omissions: for example, the chapter on suicide does not refer to Stengel. The book is attractively produced and has a clear system of headings and a good subject index, essential in a handbook. However, the printed text is eccentrically placed on the page giving wide central and
Brain Vascular Pericytes Following Ischemia Have Multipotential Stem Cell Activity to Differentiate Into Neural and Vascular Lineage Cells

Brain vascular pericytes (PCs) are a key component of the blood‐brain barrier (BBB)/neurovascular unit, along with neural and endothelial cells. Besides their crucial role in maintaining the BBB, increasing evidence shows that PCs have multipotential stem cell activity. However, their multipotency has not been considered in the pathological brain, such as after an ischemic stroke. Here, we examined whether brain vascular PCs following ischemia (iPCs) have multipotential stem cell activity and differentiate into neural and vascular lineage cells to reconstruct the BBB/neurovascular unit. Using PCs extracted from ischemic regions (iPCs) from mouse brains and human brain PCs cultured under oxygen/glucose deprivation, we show that PCs developed stemness presumably through reprogramming. The iPCs revealed a complex phenotype of angioblasts, in addition to their original mesenchymal properties, and multidifferentiated into cells from both a neural and vascular lineage. These data indicate that under ischemic/hypoxic conditions, PCs can acquire multipotential stem cell activity and can differentiate into major components of the BBB/neurovascular unit. Thus, these findings support the novel concept that iPCs can contribute to both neurogenesis and vasculogenesis at the site of brain injuries. Stem Cells 2015;33:1962–1974
Diversity and Complexity in DNA Recognition by Transcription Factors

Transcriptional Regulation Gets More Complicated Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. A central goal in genome biology is to identify regulatory sequences in the genome; however, few proteins' DNA binding specificities have been characterized comprehensively. Badis et al. (p. 1720, published online 14 May) studied 104 known and predicted transcription factors (TFs), spanning 22 structural classes, in the mouse genome. While traditional models of TF binding sites are based on a single collection of highly similar DNA sequences, binding profiles were represented better by multiple motifs. Roughly half of the TFs recognized distinct primary and secondary motifs that are different from each other. At least some of these interaction modes appeared to be attributable to biophysically distinct protein conformations, adding to the complexity of transcriptional regulation. A broad survey of transcription factors reveals that related proteins can have multiple and differing DNA binding specificities. Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10–base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.
Wolbachia and Virus Protection in Insects

Wolbachia pipientis bacteria are common endosymbionts of insects that are best known for their ability to increase their prevalence in populations by manipulating host reproductive systems. However, there are examples of Wolbachia that exist in nature that seem to induce no reproductive parasitism trait and yet are able to invade populations. We demonstrate a fitness benefit for Wolbachia-infected insects that may explain this paradox. Drosophila melanogaster flies infected with Wolbachia are less susceptible to mortality induced by a range of RNA viruses. The antiviral protection associated with Wolbachia infection might be exploited in future strategies to reduce transmission of pathogens by insects.
An ultra-low-cost ESD-protected 0.65dB NF +10dBm OP1dB GNSS LNA in 0.18-μm SOI CMOS

An ESD-protected GNSS LNA, implemented in 0. 18μm SOI CMOS process, uses only one external series inductor as input matching. The input common-source transistor is biased in weak inversion region and operates at Class-AB mode, which greatly improves linearity and saves quiescent current. A bond wire to ground is adopted as source-degeneration and to realize input matching. Design trade-offs among NF, stability and ESD protection are analyzed. The LNA achieves an ultra-low NF of 0.65dB, a power gain of 19.2dB, an output P1dB of +10dBm, while consuming 5.9mA from 2.8V supply. The LNA is housed in a 6-pin LGA package with a die area (including pads) of 0.28mm2. It passes 2.5KV HBM, 200V MM and 250V CDM ESD tests.
Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells

Genetic cardiac diseases are major causes of morbidity and mortality. Although animal models have been created to provide some useful insights into the pathogenesis of genetic cardiac diseases, the significant species differences and the lack of genetic information for complex genetic diseases markedly attenuate the application values of such data. Generation of induced pluripotent stem cells (iPSCs) from patient‐specific specimens and subsequent derivation of cardiomyocytes offer novel avenues to study the mechanisms underlying cardiac diseases, to identify new causative genes, and to provide insights into the disease aetiology. In recent years, the list of human iPSC‐based models for genetic cardiac diseases has been expanding rapidly, although there are still remaining concerns on the level of functionality of iPSC‐derived cardiomyocytes and their ability to be used for modeling complex cardiac diseases in adults. This review focuses on the development of cardiomyocyte induction from pluripotent stem cells, the recent progress in heart disease modeling using iPSC‐derived cardiomyocytes, and the challenges associated with understanding complex genetic diseases. To address these issues, we examine the similarity between iPSC‐derived cardiomyocytes and their ex vivo counterparts and how this relates to the method used to differentiate the pluripotent stem cells into a cardiomyocyte phenotype. We progress to examine categories of congenital cardiac abnormalities that are suitable for iPSC‐based disease modeling. Stem Cells 2015;33:2643—2651
Barriers for Deriving Transgene‐Free Pig iPS Cells with Episomal Vectors

To date no authentic embryonic stem cell (ESC) line or germline‐competent‐induced pluripotent stem cell (iPSC) line has been established for large animals. Despite this fact, there is an impression in the field that large animal ESCs or iPSCs are as good as mouse counterparts. Clarification of this issue is important for a healthy advancement of the stem cell field. Elucidation of the causes of this failure in obtaining high quality iPSCs/ESCs may offer essential clues for eventual establishment of authentic ESCs for large animals including humans. To this end, we first generated porcine iPSCs using nonintegrating replicating episomal plasmids. Although these porcine iPSCs met most pluripotency criteria, they could neither generate cloned piglets through nuclear transfer, nor contribute to later stage chimeras through morula injections or aggregations. We found that the reprogramming genes in iPSCs could not be removed even under negative selection, indicating they are required to maintain self‐renewal. The persistent expression of these genes in porcine iPSCs in turn caused differentiation defects in vivo. Therefore, incomplete reprogramming manifested by a reliance on sustained expression of exogenous‐reprogramming factors appears to be the main reason for the inability of porcine iPSCs to form iPSC‐derived piglets. Stem Cells 2015;33:3228–3238
The Extent of Non–Born-Oppenheimer Coupling in the Reaction of Cl(2P) with para-H2

Elementary triatomic reactions offer a compelling test of our understanding of the extent of electron-nuclear coupling in chemical reactions, which is neglected in the widely applied Born-Oppenheimer (BO) approximation. The BO approximation predicts that in reactions between chlorine (Cl) atoms and molecular hydrogen, the excited spin-orbit state (Cl*) should not participate to a notable extent. We report molecular beam experiments, based on hydrogen-atom Rydberg tagging detection, that reveal only a minor role of Cl*. These results are in excellent agreement with fully quantum-reactive scattering calculations based on two sets of ab initio potential energy surfaces. This study resolves a previous disagreement between theory and experiment and confirms our ability to simulate accurately chemical reactions on multiple potential energy surfaces.
Male contraception

This editorial focuses on male contraception and explains the current status after a multi-center contraceptive efficacy clinical trial in China that tested injectable testosterone undecanoate (TU) in 1045 healthy Chinese men over a 30 month period. It discusses how TU was terminated due to side effects that outweighed potential benefits and touches on other major developments in the field of male contraception that lie outside of the hormonal-based approach.
Noncytotoxic Lytic Granule–Mediated CD8+ T Cell Inhibition of HSV-1 Reactivation from Neuronal Latency

Reactivation of herpes simplex virus type 1 (HSV-1) from neuronal latency is a common and potentially devastating cause of disease worldwide. CD8+ T cells can completely inhibit HSV reactivation in mice, with interferon-γ affording a portion of this protection. We found that CD8+ T cell lytic granules are also required for the maintenance of neuronal latency both in vivo and in ex vivo ganglia cultures and that their directed release to the junction with neurons in latently infected ganglia did not induce neuronal apoptosis. Here, we describe a nonlethal mechanism of viral inactivation in which the lytic granule component, granzyme B, degrades the HSV-1 immediate early protein, ICP4, which is essential for further viral gene expression.
An Asynchronous Divider Implementation

We present an asynchronous implementation of a novel division algorithm previously patented. Our implementation exploits the average-case behavior of the algorithm and uses the versatility of GasP circuits to implement the data-dependent latencies in the algorithm. On average, the delay per quotient bit for our implementation is 6.3 FO4 gate delays compared to 9.5 FO4 gate delays for a similar SRT divider implementation.
Competence in on-call physiotherapy part one: designing a framework

The Association of Physiotherapists in Respiratory Care identified concerns among its members regarding perceived variability of practice in the delivery of on-call physiotherapy. They responded by developing a national set of guidelines on competence and its assessment in cardiorespiratory physiotherapy. This is the first of a series of two articles concerning this project. Competency models are discussed and a proposal for adding specific competencies within a generic framework is outlined, which will form the basis for the project. The second article will discuss the project itself and issues around the development of the guidelines.
The Treatment Perspectives of Mentally Ill Offenders in Medium- and High-Secure Forensic Settings in Flanders

There is an increasing interest in mentally ill offenders’ (MIOs) treatment experiences in forensic settings. This study focuses on the treatment perspectives of MIOs in treatment as well as in prison settings in Flanders. Seventeen MIOs were interviewed about the treatment they received. Data were analyzed using thematic analysis to derive key themes while acknowledging the individuality of the participants’ experiences. Treatment perspectives of MIOs in both settings revolved around similar themes, including “good” staff and privacy. However, their views differed on two themes: MIOs in treatment settings reported on feelings of lacking control and experiencing too much pressure, whereas MIOs in prison settings reported the opposite. The positive experiences in prison settings may complicate the transition from prison to a forensic treatment setting. The study further underscores the major challenge to create more opportunities for MIOs to meet their needs of self-determination in secure forensic treatment settings.
Declining Coral Calcification on the Great Barrier Reef

Reef-building corals are under increasing physiological stress from a changing climate and ocean absorption of increasing atmospheric carbon dioxide. We investigated 328 colonies of massive Porites corals from 69 reefs of the Great Barrier Reef (GBR) in Australia. Their skeletal records show that throughout the GBR, calcification has declined by 14.2% since 1990, predominantly because extension (linear growth) has declined by 13.3%. The data suggest that such a severe and sudden decline in calcification is unprecedented in at least the past 400 years. Calcification increases linearly with increasing large-scale sea surface temperature but responds nonlinearly to annual temperature anomalies. The causes of the decline remain unknown; however, this study suggests that increasing temperature stress and a declining saturation state of seawater aragonite may be diminishing the ability of GBR corals to deposit calcium carbonate.
A Role for the ESCRT System in Cell Division in Archaea

Archaea are prokaryotic organisms that lack endomembrane structures. However, a number of hyperthermophilic members of the Kingdom Crenarchaea, including members of the Sulfolobus genus, encode homologs of the eukaryotic endosomal sorting system components Vps4 and ESCRT-III (endosomal sorting complex required for transport–III). We found that Sulfolobus ESCRT-III and Vps4 homologs underwent regulation of their expression during the cell cycle. The proteins interacted and we established the structural basis of this interaction. Furthermore, these proteins specifically localized to the mid-cell during cell division. Overexpression of a catalytically inactive mutant Vps4 in Sulfolobus resulted in the accumulation of enlarged cells, indicative of failed cell division. Thus, the archaeal ESCRT system plays a key role in cell division.
Pittsburgh compound B as a marker of cognitive decline

PET enables in vivo investigation of cerebral blood flow and metabolism, the function of various neurotransmitter systems and protein aggregations, notably β-amyloid deposits. These studies can be used to aid in the early detection, differential diagnosis and follow-up of dementia disorders. More recently, PET has been used in developing treatments and monitoring treatment response. [11C]6-OH-BTA-1 (11C Pittsburg compound B [PIB]) is a well characterized and widely used PET tracer for detecting β-amyloid accumulation in vivo. [11C]PIB PET shows a widespread increase in cortical uptake in patients with Alzheimer’s disease. In mild cognitive impairment, increased [11C]PIB uptake is seen in a considerable proportion of patients, and predicts conversion to AD during follow-up. In addition, many healthy elderly individuals may show elevated [11C]PIB uptake, which has been associated, although not consistently, with performance in global measures of cognition and episodic memory function in Alzheimer’s disease.
Concise Review: Lessons from Naïve Human Pluripotent Cells

The naïve state of pluripotency is actively being explored by a number of labs. There is some controversy in the field as to the true identity of naïve human pluripotent cells as they are not exact mirrors of the mouse. The various reports published, although in basic agreement, present discrepancies in the characterization of the various lines, which likely reflect the etiology of these lines. The primary lesson learned from these contributions is that a human naïve state reflecting the preimplantation human is likely to exist. The essential factors that will universally maintain the naïve state in human cells in vitro are not yet fully understood. These first need to be identified in order to describe the definitive characteristics of this state. Comparisons of naïve and primed human pluripotent cells have also highlighted consistencies between states and broadened our understanding of embryonic metabolism, epigenetic change required for development, embryonic DNA repair strategies and embryonic expression dynamics. Stem Cells 2017;35:35–41
Effects of Genetic Perturbation on Seasonal Life History Plasticity

Like many species, the model plant Arabidopsis thaliana exhibits multiple different life histories in natural environments. We grew mutants impaired in different signaling pathways in field experiments across the species' native European range in order to dissect the mechanisms underlying this variation. Unexpectedly, mutational loss at loci implicated in the cold requirement for flowering had little effect on life history except in late-summer cohorts. A genetically informed photothermal model of progression toward flowering explained most of the observed variation and predicted an abrupt transition from autumn flowering to spring flowering in late-summer germinants. Environmental signals control the timing of this transition, creating a critical window of acute sensitivity to genetic and climatic change that may be common for seasonally regulated life history traits.
Prostate cancer managed with active surveillance: role of anatomic MR imaging and MR spectroscopic imaging

urothelial carcinoma. There are a variety of reasons for false-negative diagnoses of ureteral and bladder cancer during MDCTurography. Early-enhanced thin-section MDCT of a full bladder with urine can decrease the number of false negatives bladder studies. This “bladder -wall phase “, obtained 60 seconds after contrast injection has superior accuracy for detection of small lesions in comparison with the excretory phase alone (bladder fully distended by opacified urine), as used by the authors. However small flat tumors that do not appear as filling defects and carcinoma in situ tumors, are almost impossible to be detected by MDCT-urography. For this reason, although not a perfect test, cystocopy remains the reference standard procedure in the investigation of hematuria.
A Competitive Inhibitor Traps LeuT in an Open-to-Out Conformation

Secondary transporters are workhorses of cellular membranes, catalyzing the movement of small molecules and ions across the bilayer and coupling substrate passage to ion gradients. However, the conformational changes that accompany substrate transport, the mechanism by which a substrate moves through the transporter, and principles of competitive inhibition remain unclear. We used crystallographic and functional studies on the leucine transporter (LeuT), a model for neurotransmitter sodium symporters, to show that various amino acid substrates induce the same occluded conformational state and that a competitive inhibitor, tryptophan (Trp), traps LeuT in an open-to-out conformation. In the Trp complex, the extracellular gate residues arginine 30 and aspartic acid 404 define a second weak binding site for substrates or inhibitors as they permeate from the extracellular solution to the primary substrate site, which demonstrates how residues that participate in gating also mediate permeation.