cssi/SciSciGPT-SciSciNet huggingface dataset:
Autologous point-of-care cellular therapies variably induce equine mesenchymal stem cell migration, proliferation and cytokine expression.

Summary Reasons for performing study: Autologous cellular therapy products including adipose-derived stromal vascular fraction (SVF), bone marrow mononuclear cells (BMMNs), cord blood mononuclear cells (CBMNs) and platelet rich plasma are options for treatment of acute orthopaedic lesions while mesenchymal stem cells (MSCs) are culture expanded. These products may contribute to healing by secreting matrix proteins or growth factors, but they may also act on endogenous MSCs to facilitate healing. Objectives: To determine the effects of cell therapy products on MSCs function in vitro. The hypothesis was that cell therapy products promote MSCs functions including proliferation, migration and mediator release. Methods: Fat, bone marrow (BM), cord blood and platelets were obtained from 6 Quarter Horses. The BM-MSCs and their autologous cell therapy products were co-incubated in transwells. Mesenchymal stem cells proliferation, migration, gene expression and cytokine concentrations were determined. Results: All cell therapy products increased MSCs proliferation, but SVF induced significantly more proliferation than any other product. Also SVF elicited more MSCs chemotaxis and, along with BMMNs, significantly more MSCs chemoinvasion. Cord blood mononuclear cells stimulated MSCs to produce high concentrations of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and prostaglandin E2 (PGE2). Stromal vascular fraction and platelet lysate did not stimulate MSCs but SVF and platelet lysate themselves contained high concentrations of PGE2 and IL-6 (SVF) and TGF-β1 (platelet lysate). Conclusions: Autologous cell products variably stimulate MSCs functions with 2 primary patterns apparent. Products either contained preformed mediators that may have intrinsic healing function, or products stimulated MSCs to secrete mediators. Potential relevance: The specific clinical indications for these products may differ to include administration as a sole treatment modality prior to MSCs injection for intrinsic cell and cytokine activity (i.e. SVF) or administration concurrently with MSCs to activate MSCs for treatment of chronic lesions (i.e. CBMNs).
Molecular phylogenetics and biogeography of the Neotropical redstarts (Myioborus; Aves, Parulinae).

Abstract Montane areas in the Neotropics are characterized by high diversity and endemism of birds and other groups. The avian genus Myioborus (Parulinae) is a group of insectivorous warblers, characteristic of cloud forests, that represents one of the few Parulinae genera (New World warblers) that has radiated substantially in South America. The genus is distributed throughout most montane regions from the southwestern United States to northern Argentina. Here, I use mitochondrial sequences from the cytochrome b, ND2, and ND3 genes to present the first hypothesis of phylogenetic relationship among all Myioborus species level taxa. Phylogenetic reconstructions based on maximum parsimony, maximum likelihood, and Bayesian methods produced similar results and suggest a northern origin for the genus Myioborus with subsequent colonization of the Neotropical Montane Region. The lower-montane species, M. miniatus, is the sister taxon to a clade in which all taxa occupy upper-montane habitats. These “highland” taxa diverged early in the history of the genus and produced two well-defined monophyletic lineages, a Central-northern Andean clade formed by M. albifrons, M. ornatus, and M. melanocephalus, and a Pantepui (table-mountains of southern Venezuela, northern Brazil, and western Guyana) clade consisting of M. castaneocapillus, M. albifacies, and M. cardonai, and probably M. pariae. M. brunniceps, M. flavivertex, and M. torquatus were included in this upper-montane clade but without clear relationships to other taxa. Lack of resolution of nodes defining the upper-montane species clade is likely to result from a period of rapid diversification mediated by geological and climatic events during the Late Pliocene. These results suggest that an interplay of dispersal and vicariance has shaped the current biogeographic patterns of Myioborus.
Development of a high‐vacuum wear test apparatus mounted in a scanning electron microscope

The lubrication of sliding components in vacuum conditions offers unique challenges. High vacuum precludes the use of many conventional liquid lubricants because of vaporisation, while the lack of a naturally-occurring oxide film on metal surfaces may cause instant seizure following the failure of a lubricant. Solid lubricants, such as molybdenum disulphide and tungsten disulphide, are also used, but are less effective than more complex liquid lubrication mechanisms. New surface treatment processes, such as diamond-like carbon (DLC), are becoming available and may further reduce wear. The purpose of the present paper is to describe an apparatus that can evaluate solid lubricants under a wide range of contact conditions at vacua down to 3 × 10−7 Torr. The wear test stage is mounted in the chamber of a Scanning Electron Microscope (SEM), which allows real-time high magnification photography of the contact area. The complete stage may be moved in three planes to facilitate observation of the complete contact area. Realtime measurement of applied load and friction coefficient is also provided.
Commentary: studies on binge-like ethanol drinking may help to identify the neurobiological mechanisms underlying the transition to dependence.

Alcohol (ethanol) dependence and relapse in abstinent alcoholics are major health problems in the United States and neurochemical pathways that modulate these disorders are currently under investigation. However, heavy alcohol use and binge alcohol drinking patterns, which can emerge prior to the onset of dependence, have received far less attention. A ‘binge’ is defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as a pattern of drinking that produces blood ethanol concentrations (BECs) greater than 0.08% (80 mg/dl) (NIAAA, 2004). The pattern of alcohol drinking required to produce these BECs is about 5 and 4 drinks in 2-hours for the average adult male and female, respectively. Interestingly, while about 90% of the ethanol consumed by individuals under the age of 21 in the United States is in the form of binge drinking, 70% of binge drinking episodes in the US involve adults age 26 years and older (Naimi et al., 2003). Thus, binge drinking is not restricted to the young but is a risky behavior prevalent in adults. As with all abusive patterns of alcohol drinking, frequent binge drinking is associated with numerous negative short- and long-term consequences. Binge drinking increases the risk of mood disorders (Okoro et al., 2004), increases aggressive and violent behavior (Shepherd et al., 2006), and impairs decision making and judgment (Goudriaan et al., 2007). Furthermore, heavy binge drinking has been linked to long-term health consequences including heart disease, high blood pressure, and type 2 diabetes (Fan et al., 2008). Perhaps most alarming is the finding of increased risk for developing alcohol dependence in individuals that binge drink early in life (Hingson et al., 2005; Miller et al., 2007). Thus, it is of paramount importance to identify neurochemical pathways in the brain that modulate binge drinking as such knowledge may provide insight into novel pharmaceutical treatments that could protect against this dangerous behavior. The manuscript by Kaur and colleagues (Kaur et al., in press) in the current volume of Alcoholism: Clinical and Experimental Research is an exciting example of recent work aimed at identifying the neurobiology of binge alcohol drinking.
Feldspathization as a Result of Deformation

A model for metamorphic differentiation relying on the contrasting equilibria between the intergranular solution and both mineral recrystallization reactions and surface exchange reactions has been developed. Deformation at constant temperature and pressure will tend to increase the surface area of the minerals present, which in turn will increase the relative influence of surface reactions on the chemistry of the intergranular solution. In the examples described, cation exchange on muscovite surfaces shifts the alkali/H + activity ratio of the solution into a feldspar stability field. This results in the crystallization of feldspar.
Dynamic topography produced by lower crustal flow against rheological strength heterogeneities bordering the Tibetan Plateau

SUMMARY Dynamic stresses developed in the deep crust as a consequence of flow of weak lower crust may explain anomalously high topography and extensional structures localized along orogenic plateau margins. With lubrication equations commonly used to describe viscous flow in a thin-gap geometry, we model dynamic stresses associated with the obstruction of lower crustal channel flow due to rheological heterogeneity. Dynamic stresses depend on the mean velocity ( ¯ U ), viscosity (µ) and channel thickness (h), uniquely through the term µ ¯ U/h 2 . These stresses are then applied to the base of an elastic upper crust and the deflection of the elastic layer is computed to yield the predicted dynamic topography. We compare model calculations with observed topography of the eastern Tibetan Plateau margin where we interpret channel flow of the deep crust to be inhibited by the rigid Sichuan Basin. Model results suggest that as much 1500 m of dynamic topography across a region of several tens to a hundred kilometres wide may be produced for lower crustal material with a viscosity of 2 × 10 18 P asfl owing in a 15 km thick channel around a rigid cylindrical block at an average rate of 80 mm yr −1 .
Spatial and Temporal Features of the Growth of a Bacterial Species Colonizing the Zebrafish Gut

ABSTRACT The vertebrate intestine is home to microbial ecosystems that play key roles in host development and health. Little is known about the spatial and temporal dynamics of these microbial communities, limiting our understanding of fundamental properties, such as their mechanisms of growth, propagation, and persistence. To address this, we inoculated initially germ-free zebrafish larvae with fluorescently labeled strains of an Aeromonas species, representing an abundant genus in the zebrafish gut. Using light sheet fluorescence microscopy to obtain three-dimensional images spanning the gut, we quantified the entire bacterial load, as founding populations grew from tens to tens of thousands of cells over several hours. The data yield the first ever measurements of the growth kinetics of a microbial species inside a live vertebrate intestine and show dynamics that robustly fit a logistic growth model. Intriguingly, bacteria were nonuniformly distributed throughout the gut, and bacterial aggregates showed considerably higher growth rates than did discrete individuals. The form of aggregate growth indicates intrinsically higher division rates for clustered bacteria, rather than surface-mediated agglomeration onto clusters. Thus, the spatial organization of gut bacteria both relative to the host and to each other impacts overall growth kinetics, suggesting that spatial characterizations will be an important input to predictive models of host-associated microbial community assembly. IMPORTANCE Our intestines are home to vast numbers of microbes that influence many aspects of health and disease. Though we now know a great deal about the constituents of the gut microbiota, we understand very little about their spatial structure and temporal dynamics in humans or in any animal: how microbial populations establish themselves, grow, fluctuate, and persist. To address this, we made use of a model organism, the zebrafish, and a new optical imaging technique, light sheet fluorescence microscopy, to visualize for the first time the colonization of a live, vertebrate gut by specific bacteria with sufficient resolution to quantify the population over a range from a few individuals to tens of thousands of bacterial cells. Our results provide unprecedented measures of bacterial growth kinetics and also show the influence of spatial structure on bacterial populations, which can be revealed only by direct imaging.
NATIONAL SURVEY ON PROPHYLACTIC CRANIAL IRRADIATION: DIFFERENCES IN PRACTICE PATTERNS BETWEEN MEDICAL AND RADIATION ONCOLOGISTS

Purpose: Prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer (SCLC) patients remains controversial in the oncology community because of its potential for long-term toxicity and unproven survival benefit in randomized trials. A national survey of 9176 oncologists was conducted to characterize the use of PCI with regard to physician demographics, patient characteristics, and oncologists’ beliefs. Methods: Data was collected via a questionnaire letter survey. Biographical data, treatment patterns, and clinical impressions were analyzed by the generalized linear model and generalized estimating equations method. Results: There were 1231 responders overall (13.4% of those surveyed), including 628 (51%) radiation oncologists (RO), 587 (48%) medical oncologists (MO), 8 (0.6%) surgical oncologists, and 8 (0.6%) from other oncology subspecialties. Of respondents, 74% overall recommend PCI in limited-stage patients, including 65% of MO and 82% RO (p = 0.001). Of responders who recommend PCI in limited-stage patients, 67% do so only after complete response to initial therapy. Only 30% of respondents recommend PCI for extensive-stage SCLC patients (p = 0.001), and 94% of these recommend PCI only when those patients have a complete response after initial therapy. Interestingly, 38% of responding MO feel that PCI improves survival of limited-stage patients, but only 11% believe PCI improves quality of life. Of the RO, 48% believe PCI improves survival in limited-stage SCLC, and 36% feel PCI improves quality of life (p < 0.05 and p < 0.01, respectively). MO responders believe PCI causes late neurological sequelae more often than do RO responders (95% vs. 84%, p < 0.05), with impaired memory (37%), chronic fatigue (19%), and loss of motivation (13%) as most commonly seen side effects. Only 1.5% overall, however, routinely obtain neuropsychiatric testing in PCI patients, and 42% overall never obtain them. Conclusion: Results confirm that oncologic subspecialists have statistically significant differences in opinion regarding the use of PCI. However, these differences may not translate into large differences in clinical practice. Most oncologists continue to recommend PCI in limited-stage SCLC patients, despite many believing PCI may not provide a survival advantage nor improve quality of life.
FENZI: GPU-Enabled Molecular Dynamics Simulations of Large Membrane Regions Based on the CHARMM Force Field and PME

When studying membrane-bound protein receptors, it is necessary to move beyond the current state-of-the-art simulations that only consider small membrane patches and implicit solvent. Limits of traditional computer platforms negatively impact the model's level of realism and the computational scales achievable. On the other hand, multi-core platforms such as GPUs offer the possibility to span length scales in membrane simulations much larger and with higher resolutions than before. To this end, this paper presents the design and implementation of an advanced GPU algorithm for Molecular Dynamics (MD) simulations of large membrane regions in the NVT, NVE, and NPT ensembles using explicit solvent and Particle Mesh Ewald (PME) method for treating the conditionally-convergent electrostatic component of the classical force field. A key component of our algorithm is the redesign of the traditional PME method to better fit on the multithreading GPU architecture. This has been considered a fundamentally hard problem in the molecular dynamics community working on massively multithreaded architecture. Our algorithm is integrated in the code FENZI (textit{yun dong de FEN ZI} in Mandarin or textit{moving molecules} in English). The paper analyzes both the performance and accuracy of large-scale GPU-enabled simulations of membranes using FENZI, showing how our code can enable multi-nanosecond MD simulations per day, even when using PME.
Manganese-induced Trafficking and Turnover of the cis-Golgi Glycoprotein GPP130

Manganese is an essential element that is also neurotoxic at elevated exposure. However, mechanisms regulating Mn homeostasis in mammalian cells are largely unknown. Because increases in cytosolic Mn induce rapid changes in the localization of proteins involved in regulating intracellular Mn concentrations in yeast, we were intrigued to discover that low concentrations of extracellular Mn induced rapid redistribution of the mammalian cis-Golgi glycoprotein Golgi phosphoprotein of 130 kDa (GPP130) to multivesicular bodies. GPP130 was subsequently degraded in lysosomes. The Mn-induced trafficking of GPP130 occurred from the Golgi via a Rab-7–dependent pathway and did not require its transit through the plasma membrane or early endosomes. Although the cytoplasmic domain of GPP130 was dispensable for its ability to respond to Mn, its lumenal stem domain was required and it had to be targeted to the cis-Golgi for the Mn response to occur. Remarkably, the stem domain was sufficient to confer Mn sensitivity to another cis-Golgi protein. Our results identify the stem domain of GPP130 as a novel Mn sensor in the Golgi lumen of mammalian cells.
Laparoscopic fundoplication and gastrostomy.

Minimally invasive surgical approaches to various pediatric surgical disease processes are becoming the standard of care. Laparoscopic Nissen fundoplication is transitioning toward the preferred method for the surgical correction of gastroesophageal reflux (GER) disease in infants and children that do not respond to medical management or have complications from their GER. This approach offers a shorter hospitalization, reduced discomfort, and cosmetic advantages when compared with the open operation. This report discusses the pathophysiology of GER, its clinical manifestations, and the diagnostic evaluation for this disorder. Also, the laparoscopic Nissen fundoplication technique currently utilized at Children's Mercy Hospital is described.
Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation

Background. Obliterative bronchiolitis (OB) is the main chronic complication after heart-lung (HLTx) and lung transplantation (LTx), limiting the long-term success of both transplant procedures. Methods. Since 1981, 135 HLTxs and 61 isolated LTxs were performed in 184 patients at Stanford University. Results. The overall prevalence of OB in patients surviving longer than 3 months postoperatively was 64% after HLTx and 68% after LTx. The actuarial freedom from OB was 72%, 51%, 44%, and 29% at 1, 2, 3, and 5 years, respectively, after HLTx and LTx. An analysis of potential risk factors revealed that the frequency and severity of acute rejection episodes ( p p p Conclusions. Early diagnosis of OB using pulmonary function tests or transbronchial biopsy is possible and important, because immediate treatment initiation has led to acceptable survival rates, with nearly 50% of affected patients still alive 5 years after transplantation. Current experimental research on OB suggests that immune injury is the main pathogenetic event of airway obliteration in animal models; rapamycin and leflunomide are new immunosuppressive agents that may have the potential to prevent and treat airway obliteration.
Estrogen binding in the rat and human.

The interaction of estrogens with human target tissues has received scant attention as compared with other species. Early reports demonstrated that radioactive estradiol is concentrated by the human uterus in vivo (1), and is specifically bound in cytosol prepared from human endometrium (2,3,M. However, a specific cytoplasmic 8S estrogen receptor similar to that found in the rat and other species has been demonstrated in human tissues only recently by Siiteri et al. (5). The possible role of estrone in estrogen action is uncertain although several reports have shown its formation in human uterine tissue (6,7). Our interest in this problem arose from studies which demonstrated that the estrogen target organs of the human postmeno-pausal female are exposed principally to estrone rather than estradiol (8,9)• Together with similar observations made in a variety of clinical conditions which are associated with a high incidence of endometrial carcinoma, such as the polycystic ovarian syndrome, severe obesity, liver disease, and a variety of ovarian tumors, these findings indicate that exclusive production of estrone is a common endocrinologic feature of this form of neoplasia. The possibility of a causal role for estrone in the development of endometrial cancer must therefore be considered. For these reasons investigations of the interaction of the human uterine estrogen receptor system with both estradiol and estrone have been carried out.
Mindfulness Meditation to Promote Wellness and Manage Chronic Disease: A Systematic Review and Meta-Analysis of Mindfulness-Based Randomized Controlled Trials Relevant to Lifestyle Medicine

Lifestyle medicine is a patient-engaged field that has grown in tandem with our increasing knowledge of the importance of lifestyle factors and modifiable health behaviors for disease prevention, health promotion, and the management of chronic illness. Stress is at the epicenter of many negative behaviors that contribute to unhealthy lives, such as smoking, overeating, and unhealthy diets, and lack of activity. Mindfulness meditation is a stress reduction practice that teaches awareness, appreciation, and nonjudgmental acceptance of one’s present experience, thereby short-circuiting reactive, automatic stress reactions. Our systematic review and meta-analysis focuses on the application of randomized controlled mindfulness intervention studies across a broad range of populations and conditions that are relevant to lifestyle medicine. In addition to organizing and highlighting mindfulness research studies that are relevant to the field of lifestyle medicine, we also empirically examine the impact of study d...
Simultaneous target and multipath positioning with MIMO radar

This paper presents an approach for jointly estimating target locations and uncertain multipath propagation channel parameters with a multi-input multi-output (MIMO) radar system. The multipath channel is modelled with geometrical features such as flat planes and point reflectors, whose locations are uncertain. The practical issue of data association between radar returns and multipath modes in the presence of missed detections and false alarms is solved via a multihypothesis data association algorithm. Simulation results demonstrate enhanced target tracking performance in the presence of multipath even when the direct path is occasionally unobservable. (6 pages)
Step climbing cooperation primitives for legged robots with a reversible connection

Cooperation primitives for climbing steps were developed for a system of two 10 cm long VelociRoACH hexapedal legged robots with a removable connection. When performed sequentially, the set of primitives allow the team of two robots to climb a step on the order of their body length. These primitives use a tether between the robots actuated by a winch on one of the robots to form and release connections, run synchronously while connected, and provide a tether assist force while running. For a step with a coefficient of friction of 1 and a height of 6.5 cm, quasi-static analysis correctly predicts that the two connected robots can raise the front robot over the top of the step, while a single robot can only pitch upward against the step. The winch module designed to perform the cooperative climbing experiments meets the system goals of providing controllable forces greater than each robot's body weight while driving a removable connection between the robots. Experiments demonstrate that the robot system can perform each cooperation primitive individually with a reliability of at least 50% using simple strategies of maintaining a constant bounding frequency with the drive motors of each robot and a set tether tension with the winch.
Analysis of blood flow in the tympanic membrane: the use of intravital fluorescence microscopy.

The successful healing of the tympanic membrane (TM) following myringotomy or tympanoplasty is dependent upon the maintenance of the blood supply to the injured area of the TM. The blood supply of the TM is derived from the manubrial plexus and the peripheral plexus of vessels. This study concentrated on measuring blood flow derived from the manubrial vessels. The TM of the guinea pig was used as an in vivo model. Ten Outbred Hartley guinea pigs were anesthetized with Inactin 100 mg/kg, the common carotid artery cannulated, and FITC-dextran 150 injected intra-arterially. Blood pressures (mean 66.0 mmHg +/- 5.0 mmHg) and heart rates (330 bpm +/- 12.0 bpm) remained relatively constant throughout the experiment. Following injection of FITC-dextran 150, the TM was visualized under fluorescence microscopy and images recorded by video recorder; measurements of vessel diameter, blood velocity, and blood flow were made. Analysis of the in vivo studies revealed blood flow in the tympanic membrane to travel in two directions: down the manubrial artery towards the periphery and up the manubrial veins from vessels in the periphery. The manubrial artery divides and branches into a series of arcading vessels that extend towards the periphery of the TM. Manubrial artery diameter was measured (mean 0.0521 mm +/- 0.0004 mm) and blood flow calculated (mean 0.0439 mm3/min +/- 0.0007 mm3/min). Blood flow from the manubrial artery supplying the superior quadrants (0.18 mm3/min +/- 0.01) was statistically greater when compared to the blood flow in the inferior quadrants (0.08 mm3/min +/- 0.007) (p less than .001).
Pindar's Poetics of Immortality

Modern scholarship tends to focus on the social, political and economic information that can be gleaned from Pindar's treatment of the subject of his victory odes - the athlete who brings immortality to his family and polis. In this book, Asya C. Sigelman offers a new approach to the odes, exploring the fact that Pindar's language and imagery suggest that the athlete's victory is only a weaker version of the poet's immortalizing feat. Examining several central Pindaric images, Sigelman shows that they are fundamentally reflexive, structured as expressions of poetic creativity engaged in a perpetual synthesis of intra-poetic time - of the unity of the past, present and future of the world of Pindar's song. As the book's case studies of several of the odes demonstrate, this synthesis is key to Pindar's notion of immortalization and constitutes the central poetic subject of Pindar's song which underlies and informs its praise of the victorious athlete.
Beyond Redress: Japanese Americans' Unfinished Business

I am honored to be here at such a diverse gathering. This Day of Remembrance will likely mean many different things for different people. It will mean one thing for those who suffered the internment, struggled for redress and received an apology and reparations. It will mean something different for children and grandchildren of internees who have lived with the family tremors of the racial incarceration. And it will mean something else for Chinese, Korean, Filipino, Southeast and South Asians, and for Native Hawaiians, Latinos and African Americans as well as for those who are politically active in social justice movements. I hope to speak to all of you today, and especially to those drawn by the theme for today's commemoration: Remembrance Through Action. I will begin by weaving together three stories that illuminate the experiences we commemorate today.
The hidden risk: Incorporating inflammation and HIV serostatus into coronary artery disease screening

CAD is a well-established comorbidity associated with HIV infection. This association is in large part due to ongoing inflammation propagated by viremia and dysregulation of the immune system. Despite this knowledge, evidence to guide clinical management and screening for CAD among HIV-infected patients is lacking. The following editorial discusses recent evidence that HIV-infected patients with abnormal cardiovascular stress testing are more likely to undergo subsequent percutaneous coronary intervention. Importantly, the cardiovascular consequences of HIV infection and potential clinical implications are discussed.
Measuring Impairment with the Neuropsychological Impairment Scale

The Neuropsychological Impairment Scale (NIS; 2009) is a screening instrument designed to serve as an “early warning system” (Lezak, 1983, p. 135), which can be used to identify areas of neuropsychological weakness, focus treatment efforts, or to determine service efficiency. Many times, and for a variety of reasons, individuals do not report symptoms or medical histories that may be diagnostically relevant. Further, the routine clinical examination may overlook or fail to elicit pertinent information pertaining to neuropsychological impairment. The structured, efficiently administered NIS inventory addresses both global impairment and the following specific symptom areas: attention, memory, and linguistic functioning (Robins, 1980).
Radical Orthodoxy, Pentecostalism, and Embodiment in Exodus 20: Re-envisioning a Pentecostal Hermeneutic for a Formative Liturgy

Yoon Shin works to integrate a “holistic anthropological doxology” into a theology of Pentecostal worship that follows from a rejection of univocal theological language in favor of the analogical. He engages Exodus 20 and resources the Radical Orthodoxy theological sensibility in order to address liturgical existence for Pentecostal communities and the “formative power of existence as being-in-the-world.”
Human aminoacyl-tRNA synthetases in diseases of the nervous system

Aminoacyl-tRNA synthetases (AaRSs) are ubiquitously expressed enzymes that ensure accurate translation of the genetic information into functional proteins. These enzymes also execute a variety of non-canonical functions that are significant for regulation of diverse cellular processes and that reside outside the realm of protein synthesis. Associations between faults in AaRS-mediated processes and human diseases have been long recognized. Most recent research findings strongly argue that 10 cytosolic and 14 mitochondrial AaRSs are implicated in some form of pathology of the human nervous system. The advent of modern whole-exome sequencing makes it all but certain that similar associations between the remaining 15 ARS genes and neurologic illnesses will be defined in future. It is not surprising that an intense scientific debate about the role of translational machinery, in general, and AaRSs, in particular, in the development and maintenance of the healthy human neural cell types and the brain is sparked. Herein, we summarize the current knowledge about causative links between mutations in human AaRSs and diseases of the nervous system and briefly discuss future directions.
Ascorbate protects the diheme enzyme, MauG, against self-inflicted oxidative damage by an unusual antioxidant mechanism.

Ascorbate protects MauG from self-inactivation that occurs during the autoreduction of the reactive bis -Fe IV state of its diheme cofactor. The mechanism of protection does not involve direct reaction with reactive oxygen species in solution. Instead, it binds to MauG and mitigates oxidative damage that occurs via internal transfer of electrons from amino acid residues within the protein to the high-valent hemes. The presence of ascorbate does not inhibit the natural catalytic reaction of MauG, which catalyzes oxidative post-translational modifications of a substrate protein that binds to the surface of MauG and is oxidized by the high-valent hemes via long-range electron transfer. Ascorbate was also shown to prolong the activity of a P107V MauG variant that is more prone to inactivation. A previously unknown ascorbate peroxidase activity of MauG was characterized with a k cat of 0.24 s −1 and a K m of 2.2 µM for ascorbate. A putative binding site for ascorbate was inferred from inspection of the crystal structure of MauG and comparison with the structure of soybean ascorbate peroxidase with bound ascorbate. The ascorbate bound to MauG was shown to accelerate the rates of both electron transfers to the hemes and proton transfers to hemes which occur during the multistep autoreduction to the diferric state which is accompanied by oxidative damage. A structural basis for these effects is inferred from the putative ascorbate-binding site. This could be a previously unrecognized mechanism by which ascorbate mitigates oxidative damage to heme-dependent enzymes and redox proteins in nature.
Inferring long-distance dispersal modes in American amphitropically disjunct species through adaptive dispersal structures.

PREMISE OF THE STUDY A repeated pattern of American amphitropical disjunct species or sister species distributed on either side of the equator has long-fascinated botanists, but the modes of these disjunctions remain untested. We evaluated diaspore morphology to generate hypotheses on probable dispersal mechanisms. METHODS The sizes and structures of diaspores, habit, habitat, distribution, and dispersal units were collected for 108 species from literature searches and herbarium specimens. Variation was evaluated with summary statistics, χ2 tests with Monte Carlo simulations, ANOVAs, and the nonparametric Mann-Whitney test. KEY RESULTS Seeds were the dispersing diaspore in 38.0% of the species, 45.4 were dispersed as fruits, and the remaining were dispersed as infructescences or spores. Diaspores were epizoochorous (52.8%), anemochorous (20.4%), achorous (15.7%), endozoochorous (8.3%), and hydrochorous (2.8%). Epizoochory was significantly greater than expected. Zoochory occurred more frequently than expected when considering achorous diaspores as animal-dispersed. Most species were associated with wetland, woodland, and grassland habitats. An ANOVA revealed that diaspores associated with hydrochory were larger and anemochory was smaller; all other syndromes were not significantly different. CONCLUSIONS Botanists have long-held the assumption that bird migrations are responsible for amphitropical disjunctions. Our results support this hypothesis, with the majority of these events occurring by external attachment of small fruits. However, our results also indicate that anemochory might play a greater role in producing amphitropical distributions than previously thought and at a greater rate than endozoochory or hydrochory.
Evaluation of Selected Preemergence Herbicides in Field-Grown Landscape Crops in Kentucky

Abstract Research was conducted during 1990 and 1991 at the Horticultural Research Farm in Lexington, Kentucky, to evaluate the efficacy of herbicides available for use on woody landscape plants (s...
Conceptual framework for an automated battle planning system in combat simulations

Automated planning is a key to unlocking the next generation of human behavior modeling for military simulations. Automated planning is distinguished from other dynamic behavior by its ability to reason with predictions or assumptions about future outcomes, which has traditionally been left to the meticulous effort of human modelers. In this paper, we present a conceptual planning framework as an architectural roadmap for the development of this kind of capability in support of modeling and simulation. This paper also presents an initial implementation of the framework in a representative combat simulation for exploring potential future opportunities for community advancement of the planning techniques.
The Labour governments 1974–1979: social democracy abandoned?

The driving forces behind the decline of the social democratic postwar consensus in Great Britain is much debated. One prominent school of thought, particularly common in Marxist studies, focuses on the structural changes in the global economy that occurred in the 1970s, specifically the collapse of the Bretton Woods system of fixed exchange rates, the end of the long boom, and the emergence of a second age of globalization. Those following a structural approach have found support for their position in the claim that it was the 1974–1979 Labour governments rather than the more ideologically committed 1979–1997 Conservative governments that first responded to the changing global economy by abandoning the social democratic postwar consensus. In this article, I set out to challenge this approach by arguing that the Labour government did not fundamentally abandon the social democratic postwar consensus, and that such an abandonment was highly undesirable given the political make-up of the Labour Party and its reliance on trade union support.
Optimal Path and Illumination Design for Multiframe Motion Deblurring

We propose an extension of coded illumination design for motion deblurring to multiframe imaging, where a large field-of-view sample is recovered from many motion-blurred measurements captured while scanning the sample continuously under coded illumination.
Spine and Musculoskeletal Medicine

Neck pain is a very common complaint, affecting up to 70% of the population at some point in their lives. This makes neck pain the second most common presenting musculoskeletal complaint (second only to low back pain). Any structure that receives innervation can be a likely pain generator in the neck. Potential causes of mechanical neck pain include muscle spasm, strain, osteoarthritis (OA), discogenic, and zygapophysial (Z)-joint disease.
Clustering at the phase transition

Many problem ensembles exhibit a phase transition that is associated with a large peak in the average cost of solving the problem instances. However, this peak is not necessarily due to a lack of solutions: indeed the average number of solutions is typically exponentially large. Here, we study this situation within the context of the satisfiability transition in Random 3SAT. We find that a significant subclass of instances emerges as we cross the phase transition. These instances are characterized by having about 85-95% of their variables occurring in unary prime implicates (UPIs), with their remaining variables being subject to few constraints. In such instances the models are not randomly distributed but all lie in a cluster that is exponentially large, but still admits a simple description. Studying the effect of UPIs on the local search algorithm WSAT shows that these "single-cluster" instances are harder to solve, and we relate their appearance at the phase transition to the peak in search cost.
Validation of Predictive Dynamics Tasks

This chapter focuses on the description of procedure used to validate the predictive dynamics tasks. The validation approach, motion capture system, and methodology used to record the data are described. The marker placement protocol used to capture the motion is presented. Normalization of the captured data and the validation methodology are described. The concept of using determinants of the motion, for each task, is introduced and defined, and the validation methodology is demonstrated for the walking and the lifting tasks.
Regulation of osteoclast differentiation and skeletal maintenance by histone deacetylases

Bone is a dynamic tissue that must respond to developmental, repair, and remodeling cues in a rapid manner with changes in gene expression. Carefully-coordinated cycles of bone resorption and formation are essential for healthy skeletal growth and maintenance. Osteoclasts are large, multinucleated cells that are responsible for breaking down bone by secreting acids to dissolve the bone mineral and proteolytic enzymes that degrade the bone extracellular matrix. Increased osteoclast activity has a severe impact on skeletal health, and therefore, osteoclasts represent an important therapeutic target in skeletal diseases, such as osteoporosis. Progression from multipotent progenitors into specialized, terminally-differentiated cells involves carefully-regulated patterns of gene expression to control lineage specification and emergence of the cellular phenotype. This process requires coordinated action of transcription factors with co-activators and co-repressors to bring about proper activation and inhibition of gene expression. Histone deacetylases (HDACs) are an important group of transcriptional co-repressors best known for reducing gene expression via removal of acetyl modifications from histones at HDAC target genes. This review will cover the progress that has been made recently to understand the role of HDACs and their targets in regulating osteoclast differentiation and activity and, thus, serve as potential therapeutic target.
On the regulation of glutaminase in E. coli: Metabolite control

Abstract Escherichia coli has been shown to possess two glutaminases A and B, with pH optima at 5 and 7 respectively. Glutaminase B, the subject of this communication, is a cold labile enzyme which is subject to regulation by many metabolites. Preincubation of the enzyme at 4° C with di- and tri-carboxylic acids and cyclic 3′, 5′ AMP results in a marked activation of catalytic activity while preincubation with adenine nucleoside di- and tri-phosphates leads to inactivation. Metabolite regulation of glutaminase B prevents the operation, with glutamine synthetase, of a futile cycle in which the cellular energy stores might be consumed.
An Improved Procedure for the Conversion of 3,3-Disubstituted 1,4-Cyclohexadienes to 2,5-Cyclohexadien-1-ones.

The 1,4-cyclohexadienes (I) are converted into the cyclohexadienones (II) by oxidation with tert-butyl hydroperoxide and pyridinium dichromate.
Determining a Positive Causal Relationship of Immigration on Living Standards

This project investigates the complex relationship between American citizens and America’s forty million plus immigrants by analyzing changes in the living standards of native-born Americans versus the immigrant population size. We aggregate data collected from the American Community Survey’s Public Use Microdata Samples from 2010 to 2015 at the Public Use Microdata Area level. Using the method of instrumental variables, we assess if and how immigrants affect the living standards of native-born Americans. With the number of ports of entry per state as the instrument, we find preliminary evidence to suggest a positive causal, not just correlational, relationship between percent of immigrants in an area and the average living standard of the area’s native-born citizens. As data availability improves, our methodology will allow for a stronger case to support a causal relationship between immigration and American living standards. It has the potential to provide data-driven policy recommendations that improve the economic opportunities of native-born citizens while also supporting immigration.
Free Fibula Flap for Restoration of Spinal Stability after Oncologic Vertebrectomy Is Predictive of Bony Union.

BACKGROUND Nonvascular bone grafts larger than 4 cm have a 50 percent nonunion rate in spine surgery. Vascular bone flaps are one potential solution; however, their utility in spine surgery has not been fully elucidated. The authors hypothesized that the addition of a free fibula flap after oncologic vertebrectomy would safely potentiate bone union. METHODS The authors performed a retrospective analysis, including all patients who underwent oncologic vertebrectomy for a primary bone tumor at their institution from 2002 to 2017. Patients were divided into two groups: those who underwent spinal reconstruction with nonvascularized bone graft and an alloplastic cage (control) and those whose reconstruction was augmented with a free fibula flap. RESULTS Forty patients were included (free fibula flap, n = 16; control, n = 24). Adjuvant therapies and medical comorbidities were similar between the two groups. Chordoma was the most common abnormality in both groups. The median number of vertebrae resected in the free fibula flap group was two, compared to one in the cage group (p = 0.08). Despite the smaller mean resection size, there were significantly more nonunions (41.7 percent versus 6.3 percent; p = 0.02), instrumentation complications (33.3 percent versus 6.3 percent; p = 0.04), and neurologic complications (25 percent versus 0 percent; p = 0.03) in the control group. Multivariate logistic regression revealed a control reconstruction significantly predictive of nonunion (OR, 57.04; 95 percent CI, 1.17 to 2773; p = 0.04). Free fibula flap patients demonstrated evidence of bony union at a mean of 4.8 months versus 22.4 months in the control group (p < 0.001). CONCLUSIONS Free fibula flap surgery in spinal reconstruction after oncologic vertebrectomy is safe and effective. Free fibula flap surgery is independently protective against nonunion and is associated with more rapid union compared with the control. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.
Pediatric Sarcoma Patients with Worse Physical Function but Better Peer Relationships and Depressive Symptoms than U.S. Pediatric Population as Measured by PROMIS

Background Pediatric patients with sarcomas are at risk of poor quality of life outcomes. The National Institutes of Health (NIH)-funded Patient-reported Outcomes Measurement Information System (PROMIS®) improves our ability to capture patient-reported outcomes. Do physical function, social, and mental health PROMIS outcomes for pediatric patients with non-metastatic malignant sarcomas differ from the U.S. pediatric population? Methods Six pediatric PROMIS short forms were collected for patient visits to orthopedic oncology at a tertiary referral center from September 1, 2016, to March 31, 2017. Mean T-scores differed from the reference population by a one-sample t-test. Results Of the 30 eligible patients, five had soft-tissue sarcomas and 25 (83%) had bone sarcomas. The mean age of the cohort was 13 years (5-17). The study cohort had a mean physical function T-score of 39.8 (SD 9.8), which was worse than the reference population. In contrast, the mean peer relationship T-score of 54.3 (SD 8.8) and mean depression T-score of 42.0 (SD 9.1) were better than the reference population. Conclusions Pediatric patients with non-metastatic sarcomas had a worse physical function but a better peer relationship and depression scores than the U.S. PROMIS reference population. Ceiling and flooring effects were reported. The level of evidence was III.
ELP2IM: Efficient and Low Power Bitwise Operation Processing in DRAM

Recently proposed DRAM based memory-centric architectures have demonstrated their great potentials in addressing the memory wall challenge of modern computing systems. Such architectures exploit charge sharing of multiple rows to enable in-memory bitwise operations. However, existing designs rely heavily on reserved rows to implement computation, which introduces high data movement overhead, large operation latency, large energy consumption, and low operation reliability. In this paper, we propose ELP2IM, an efficient and low power processing in-memory architecture, to address the above issues. ELP2IM utilizes two stable states of sense amplifiers in DRAM subarrays so that it can effectively reduce the number of intra-subarray data movements as well as the number of concurrently opened DRAM rows, which exhibits great performance and energy consumption advantages over existing designs. Our experimental results show that the power efficiency of ELP2IM is more than 2X improvement over the state-of-the-art DRAM based memory-centric designs in real application.