Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients

Utilizing Combined Methodologies to Define the Role of Plasma Membrane Delivery During Axon Branching and Neuronal Morphogenesis

During neural development, growing axons extend to multiple synaptic partners by elaborating axonal branches. Axon branching is promoted by extracellular guidance cues like netrin-1 and results in dramatic increases to the surface area of the axonal plasma membrane. Netrin-1-dependent axon branching likely involves temporal and spatial control of plasma membrane expansion, the components of which are supplied through exocytic vesicle fusion. These fusion events are preceded by formation of SNARE complexes, comprising a v-SNARE, such as VAMP2 (vesicle-associated membrane protein 2), and plasma membrane t-SNAREs, syntaxin-1 and SNAP25 (synaptosomal-associated protein 25). Detailed herein is a multi-pronged approach used to examine the role of SNARE mediated exocytosis in axon branching. The strength of the combined approach is data acquisition at a range of spatial and temporal resolutions, spanning from the dynamics of single vesicle fusion events in individual neurons to SNARE complex formation and axon branching in populations of cultured neurons. This protocol takes advantage of established biochemical approaches to assay levels of endogenous SNARE complexes and Total Internal Reflection Fluorescence (TIRF) microscopy of cortical neurons expressing VAMP2 tagged with a pH-sensitive GFP (VAMP2-pHlourin) to identify netrin-1 dependent changes in exocytic activity in individual neurons. To elucidate the timing of netrin-1-dependent branching, time-lapse differential interference contrast (DIC) microscopy of single neurons over the order of hours is utilized. Fixed cell immunofluorescence paired with botulinum neurotoxins that cleave SNARE machinery and block exocytosis demonstrates that netrin-1 dependent axon branching requires SNARE-mediated exocytic activity

Polynomial-Time Pseudodeterministic Construction of Primes

A randomized algorithm for a search problem is *pseudodeterministic* if it produces a fixed canonical solution to the search problem with high probability. In their seminal work on the topic, Gat and Goldwasser posed as their main open problem whether prime numbers can be pseudodeterministically constructed in polynomial time. We provide a positive solution to this question in the infinitely-often regime. In more detail, we give an *unconditional* polynomial-time randomized algorithm $B$ such that, for infinitely many values of $n$, $B(1^n)$ outputs a canonical $n$-bit prime $p_n$ with high probability. More generally, we prove that for every dense property $Q$ of strings that can be decided in polynomial time, there is an infinitely-often pseudodeterministic polynomial-time construction of strings satisfying $Q$. This improves upon a subexponential-time construction of Oliveira and Santhanam. Our construction uses several new ideas, including a novel bootstrapping technique for pseudodeterministic constructions, and a quantitative optimization of the uniform hardness-randomness framework of Chen and Tell, using a variant of the Shaltiel--Umans generator

Efficient safe learning for controller tuning with experimental validation

Optimization-based controller tuning is challenging because it requires formulating optimization problems explicitly as functions of controller parameters. Safe learning algorithms overcome the challenge by creating surrogate models from measured data. To ensure safety, such data-driven algorithms often rely on exhaustive grid search, which is computationally inefficient. In this paper, we propose a novel approach to safe learning by formulating a series of optimization problems instead of a grid search. We also develop a method for initializing the optimization problems to guarantee feasibility while using numerical solvers. The performance of the new method is first validated in a simulated precision motion system, demonstrating improved computational efficiency, and illustrating the role of exploiting numerical solvers to reach the desired precision. Experimental validation on an industrial-grade precision motion system confirms that the proposed algorithm achieves 30% better tracking at sub-micrometer precision as a state-of-the-art safe learning algorithm, improves the default auto-tuning solution, and reduces the computational cost seven times compared to learning algorithms based on exhaustive search

Achieving ultra-high strength and ductility in Mg–9Al–1Zn–0.5Mn alloy via selective laser melting

Fabrication of the Mg–9Al–1Zn–0.5Mn alloy with excellent mechanical performance using selective laser melting (SLM) technology is quite difficult owing to the poor weldability and low boiling point. To address these challenges and seek the optimal processing parameters, response surface methodology was systematically utilized to determine the appropriate SLM parameter combinations. Mg–9Al–1Zn–0.5Mn sample with high relative density (99.5 ​± ​0.28%) and favorable mechanical properties (microhardness ​= ​95.6 ​± ​5.28 HV0.1, UTS ​= ​370.2 ​MPa, and At ​= ​10.4%) was achieved using optimized SLM parameters (P ​= ​120 ​W, v ​= ​500 ​mm/s, and h ​= ​45 ​μm). Sample ​is dominated by a random texture and microstructure is primarily constituted by quantities of fine equiaxed grains (α-Mg phase), a small amount of β-Al12Mg17 structures (4.96 ​vol%, including spherical: [21¯1¯0]α// [111]β and long lath-like: [21¯1¯0]α// [11¯5]β or [1¯011]α// [32¯1¯]β), and some short rod-shaped Al8Mn5 nanoparticles. Benefiting from grain boundary strengthening, solid solution strengthening, and precipitation hardening of various nanoparticles (β-Al12Mg17 and Al8Mn5), high-performance Mg–9Al–1Zn–0.5Mn alloy biomedical implants can be fabricated. Precipitation hardening dominates the strengthening mechanism of the SLM Mg–9Al–1Zn–0.5Mn alloy.</p

Genetic diversity and population structure of Corollospora maritima sensu lato: new insights from population genetics

The study of genetic variation in fungi has been poor since the development of the theoretical underpinnings of population genetics, specifically in marine taxa. Corollospora maritima sensu lato is an abundant cosmopolitan marine fungus, playing a crucial ecological role in the intertidal environment. We evaluated the extent and distribution of the genetic diversity in the nuclear ribosomal internal transcribed spacer region of 110 isolates of this ascomycete from 19 locations in the Gulf of Mexico, Caribbean Sea and Pacific Ocean. The diversity estimates demonstrated that C. maritima sensu lato possesses a high genetic diversity compared to other cosmopolitan fungi, with the highest levels of variability in the Caribbean Sea. Globally, we registered 28 haplotypes, out of which 11were specific to the Caribbean Sea, implying these populations are genetically unique. We detected populations inhabiting human-impacted sites with null genetic variation. As long-term exposure to contaminants has been proven to decrease genetic diversity, a conservation genetics approach to assess this matter is urgent. Our results revealed the occurrence of five genetic lineages with distinctive environmental preferences and an overlapping geographical distribution, agreeing with previous studies reporting physiological races within this species

Childhood Physical Neglect Is Associated With Exaggerated Systemic and Intracellular Inflammatory Responses to Repeated Psychosocial Stress in Adulthood

Experiences of child maltreatment are associated with a host of adverse mental and physical health outcomes in adulthood. Altered reactivity to psychosocial stress exposure may partially explain known associations between early experiences of maltreatment and later life health. The present study focuses on examining whether experiences of child maltreatment are associated with physiological reactions to initial and repeated psychosocial stress in adulthood. To this end, 44 healthy adults (52% male, aged 18–65) completed the Childhood Trauma Questionnaire to provide information about exposure to child maltreatment and completed the Trier Social Stress Test (TSST) on 2 consecutive days. Peripheral blood was collected prior to as well as 30 and 120 min following the TSST on each day. Plasma Interleukin-6 (IL-6) and gene expression of IL-6, IL-1β, nuclear factor-kB (NF-kB), and inhibitor of kB (IkB) were measured from each blood sample. Total CTQ scores were unrelated to plasma IL-6 and gene expression (ps > .10) but a history of childhood physical neglect was associated with increased interleukin-1β (β =.35; p =.02; R2 =.19) and nuclear factor-kB (β =.30; p =.046; R2 =.13) expression following initial stress. Following repeated exposure to the TSST, childhood physical neglect was associated with increased plasma IL-6 reactivity (β =.34; p =.02; R2 =.16) and increased expression of nuclear factor-kB (β =.31; p =.04; R2 =.08). Finally, childhood physical neglect was associated with decreased habituation following repeated exposure to the TSST. Other CTQ subscales were not related to plasma IL-6 and gene expression when considered individually. Results from this study are suggestive of a unique effect of childhood physical neglect on the physiological stress response following initial and repeated exposure to a common psychosocial stressor. This provides important directions for future research because the effect of childhood physical neglect on long-term neglect are not well understood and in need of further investigation

Miocene Volcaniclastic Sequence Within the Xiyu Formation from Source to Sink: Implications for Drainage Development and Tectonic Evolution in Eastern Pamir, NW Tibetan Plateau

©2018. American Geophysical Union. All Rights Reserved. The formation of the Pamir salient and the Tashkorgan-Yarkand River is highly debated with the ages ranging from pre-Cenozoic to late Miocene. One approach to resolve these issues is to draw support from the sedimentary record in the surrounding basins. A volcaniclastic sequence, which divides into Lower and Upper Members, was identified in the southwestern Tarim Basin. The Lower Member was transported by dilute streamflows, which likely flowed during or soon after eruptions, while the Upper Member was formed by a syneruptive volcanic debris flow. Chronological, petrologic, and geochemical data consistently indicate that the sequence was derived from the Central Pamir at ~11 Ma. The ~11 Ma emplacement of the volcaniclastic sequence provides unique constraints for the evolution of the Tashkorgan-Yarkand River and the Pamir salient. Provenance data indicate a multistage evolutionary history of the Tashkorgan-Yarkand River. The paleo-Tashkorgan River was initially formed in the piedmont of the Pamir marginal range before ~15 Ma. This river cut back into the Tashkorgan region at ~15 Ma, after which it has eroded the Central Pamir by ~11 Ma. The N-S trending upper reaches of the Tashkorgan River and the Yarkand River were established after ~11 Ma. The emplacement of the volcanic debris flow, together with regional deformation evidence, indicates limited strike-slip motion between Pamir and the Tarim at least since ~11 Ma, which refutes hundreds of kilometers offset between the Pamir and the Tarim after this time and supports an earlier indention of the Pamir salient

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae