cssi/SciSciGPT-SciSciNet huggingface dataset:
Differential Increase in Taurine Levels by Low‐Dose Ethanol in the Dorsal and Ventral Striatum Revealed by Microdialysis With On‐Line Capillary Electrophoresis

Ethanol increases taurine efflux in the nucleus accumbens or ventral striatum (VS), a dopaminergic terminal region involved in positive reinforcement. However, this has been found only at ethanol doses above 1 g/kg intraperitoneally, which is higher than what most rats will self-administer. We used a sensitive on-line assay of microdialysate content to test whether lower doses of ethanol selectively increase taurine efflux in VS as opposed to other dopaminergic regions not involved in reinforcement (e.g., dorsal striatum; DS). Adult male rats with microdialysis probes in VS or DS were injected with ethanol (0, 0.5, 1, and 2 g/kg intraperitoneally), and the amino acid content of the dialysate was measured every 11 sec using capillary electrophoresis and laser-induced fluorescence detection. In VS, 0.5 g/kg ethanol significantly increased taurine levels by 20% for 10 min. A similar increase was seen after 1 g/kg ethanol, which lasted for about 20 min after injection. A two-phased taurine efflux was observed with the 2.0 g/kg dose, where taurine was increased by 2-fold after 5 min but it remained elevated by 30% for at least 60 min. In contrast, DS exhibited much smaller dose-related increases in taurine. Glycine, glutamate, serine, and -aminobutyric acid were not systematically affected by lower doses of ethanol; however, 2 g/kg slowly decreased these amino acids in both brain regions during the hour after injection. These data implicate a possible role of taurine in the mechanism of action of ethanol in the VS. The high sensitivity and time resolution afforded by capillary electrophoresis and laser-induced fluorescence detection will be useful for detecting subtle changes of
p-Type Electrical Transport of Chemically Doped Epitaxial Graphene Nanoribbons

We present the first demonstration of p-type electrical transport in chemically doped epitaxial graphene (EG) nanoribbons produced on silicon carbide (SiC). The thermal annealing of cross-linked thin films of hydrogen silsesquioxane (HSQ) is found to be capable of overcoming intrinsic n-type doping from the SiC substrate, resulting in p-type functionality. A smooth transition from n- to p-type carriers, spanning a Fermi shift of 0.45 eV, is observed by controlling the density and chemical composition of HSQ. This technique provides a route for complementary transistor and interconnect fabrication, as well as facilitating chemically doped p-n junctions in EG.
Multiscale Diversity in the Marshes of the Georgia Coastal Ecosystems LTER

Factors that maintain genetic and species diversity may act in concert in natural ecosystems. Here, we investigate correlations between genetic diversity (in eight salt marsh species) and community species diversity. A significant positive correlation existed between genetic diversity and species richness, although the relationship was not significant for any species individually. Nonetheless, four of the eight comparisons showed strong positive relationships between genetic and species diversity. Additionally, several abiotic variables were used in a model selection procedure to determine what site-level characteristics might drive differences in genetic diversity in this system. The rate of larval influx, as measured by barnacle abundance on Spartina alterniflora, was the strongest predictor of site-level genetic diversity in our samples. Our results suggest that estuarine management efforts should consider recruitment rates when selecting areas for protection.
Brownian Models of Queueing Networks with Heterogeneous Customer Populations

Consider an open queueing network with I single-server stations and K customer classes. Each customer class requires service at a specified station, and customers change class after service in a Markovian fashion. (With K allowed to be arbitrary, this routing structure is almost perfectly general.) There is a renewal input process and general service time distribution for each class. The correspondence between customer classes and service stations is in general many to one, and the service discipline (or scheduling protocol) at each station is left as a matter for dynamic decision making.
Biases in young children's communication about spatial relations: containment versus proximity.

Four experiments examined 3- and 4-year-olds' ability to communicate about containment and proximity relations. One hundred twenty-eight children either described where a miniature mouse was hiding in a dollhouse or they searched for the mouse after the experimenter described where it was hiding. The mouse was always hidden with a small landmark that was either in or next to a large landmark. When describing where the mouse was hiding, children were more likely to successfully disambiguate the small landmark when it was in the large landmark (e.g., under the plant in the dresser) than when it was next to the large landmark (e.g., under the plant next to the dresser). When searching for the mouse, 3-year-olds were faster to initiate their searches when the small landmark was in the large landmark than when it was next to the large landmark. Together, these results suggest that there are informational biases in young children's spatial communication.
Recommending just enough memory for analytics

MapReduce was designed by Google for large-scale data analysis on slow but cheap disk-based storage. Nevertheless, memory has declined in price to where cost-effective machines offer ever larger memory capacity. Furthermore, a more diverse data analyst community, with smaller datasets, has emerged. These trends motivate new parallel processing frameworks, like Spark [2], with better support for in-memory data analysis.
An information-theoretic framework for optimal location tracking in multisystem 4G wireless networks

An information-theoretic framework is developed for optimal location management in multisystem, fourth generation (4G) wireless networks. The framework envisions that each individual subsystem operates fairly independently, and does not require public knowledge of individual subnetwork topologies. To capture the variation in paging and location update costs in this heterogeneous environment, the location management problem is formulated in terms of a new concept of weighted entropy. The update process is based on the Lempel-Ziv compression algorithms, which are applied to a vector-valued sequence consisting of both the mobile's movement pattern and its session activity state. Three different tracking strategies which differ in their degrees of centralized control and provide trade off between the location update and paging costs, are proposed and evaluated. While both the proposed centralized and distributed location management strategies are endowed with optimal update capability, the proposed selective location management heuristic also offers a practical trade off between update and paging costs. Simulation experiments demonstrate that our proposed schemes can result in more than 50% savings in both update and paging costs, in comparison with the basic movement-based, multisystem location management strategy. These update strategies can be realized with only modest amounts of memory (12-15 Kbytes) on the mobile.
PFP: a computational framework for phylogenetic footprinting in prokaryotic genomes

Phylogenetic footprinting is a widely used approach for theprediction of transcription factor binding sites (TFBSs) through identificationof conserved motifs in the upstream sequences of orthologousgenes in eukaryotic genomes. However, this popular strategy may notbe directly applicable to prokaryotic genomes, where typically abouthalf of the genes in a genome form multiple-gene transcription unitsor operons. The promoter sequences for these operons are located in theinter-operonic rather than inter-genic regions, which require prediction ofTFBSs at the transcriptional unit instead of individual gene level. Wehave formulated as a bipartite graph matching problem the identificationof conserved operons (including both single-gene and multi-gene operons)whose individual gene members are orthologous between two genomesand present a graph-theoretic solution. By applying this method to Escherichiacoli K12 and 11 of its phylogeneticly neighboring species, wehave predicted 2, 478 sets of conserved operons, and discovered potentialbinding motifs for each of these operons. By comparing the predictionresults of our approach and other prediction approaches, we concludethat it is advantageous to use our approach for prediction of cis regulatorybinding sites in prokaryotes. The prediction software package PFPis available at http://csbl.bmb.uga.edu/~dongsheng/PFP.
A Mitogen-Activated Protein Kinase That Senses Nitrogen Regulates Conidial Germination and Growth in Aspergillus fumigatus

We show that the mitogen-activated protein (MAP) kinase pathway that responds to osmotic stress in Aspergillus fumigatus is also involved in nutritional sensing. This MAP kinase regulates conidial germination in response to the nitrogen source and is activated upon starvation for either carbon or nitrogen during vegetative growth.
Educational intervention: a tool for decreasing medication errors.

To the Editor: Adverse drug events are the most common cause of injury in hospitalized patients. A Computerized Physician Order Entry system (CPOE) has shown to be effective in decreasing the incidence of medical errors in hospitalized patients [1]. Factors associated with medication errors include the health care providers’ knowledge and the application of knowledge regarding drug therapy and its use regarding patient factors that affect drug therapy [2]. We present a systems-based method for decreasing medical errors in an in-patient setting that lacks CPOE. Methods Metformin therapy requires careful monitoring in certain situations and is inappropriately prescribed in 25–30% of inpatients [3]. We used a pre-post-test study design to assess the level of awareness among providers about contraindications and special precautions (renal insufficiency, heart failure, metabolic acidosis, intravenous contrast use) of metformin use in hospitalized patients and to identify the effectiveness of provider education in improving the awareness and decrease in inappropriate prescriptions. Thirty-three prescribers including internal medicine residents and physician assistants in a community hospital responded to a pre-test survey that was followed by an educational session about metformin therapy. A post-test survey was conducted 2 months later using the same questionnaire. Inappropriate metformin prescription rates were calculated using the same variables from pharmacy records for 3 months before and after the teaching session. Results A significant increase (P < 0.05) in the level of awareness was observed for all the study variables after the educational intervention: renal insufficiency (88 to 100%), congestive heart failure (24 to 55%), and contraindication during contrast use (21 to 42%). Furthermore, the increase in prescriber awareness translated into a 54% decrease in risk ratio (95% CI 28.8–73.8%) in inappropriate metformin prescription rates in the post-teaching session, thereby decreasing medication errors.
Chemical modification of the interfacial frictional properties of vanadium carbide through ethanol adsorption

Abstract The frictional properties of the (1 0 0) face of vanadium carbide have been measured with atomic force microscopy (AFM) as a function of ethanol exposure under ultrahigh vacuum conditions. Although exhibiting a small sticking coefficient, ethanol reacts upon adsorption at room temperature producing a thin chemisorbed layer. This reaction has been characterized through high resolution electron energy loss spectroscopy and temperature programmed desorption. These studies demonstrate the formation of a partially dehydrated species involving bonds to the surface through both oxygen and carbon atoms. The growth of this reaction layer film has been followed with X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and scanning tunneling microscopy. The results of these surface analytical measurements have been correlated with the frictional and adhesion properties measured with AFM. An approximate 40% reduction in frictional forces is observed upon the formation of a complete monolayer of a hydrocarbon reaction layer. Little change in the interfacial friction was detected at higher or lower exposures of ethanol. The origin of the friction reduction, which cannot be directly related to changes in interfacial adhesion, is assigned to a change in interfacial shear strength as a result of the growth of the ethanol decomposition species.
Proportion of Breast Cancer Cases in the United States Explained by Well-Established Risk Factors

Background : Few estimates of the fraction of cases of breast cancer attributable to recognized risk factors have been published. All estimates are based on selected groups, making their generalizability to the U.S. population uncertain. Purpose : Our goal was to estimate the fraction of breast cancer cases in the United States attributable to well-established risk factors (i.e., later age at first birth, nulliparity, higher family income, and first-degree family history of breast cancer), using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (NHEFS), the survey and follow-up of a probability sample of the U.S. population. Methods : From a cohort of 7508 female participants surveyed in the early 1970s, and followed up between 1982 and 1984 and again in 1987, 193 breast cancer cases were accrued for study. We calculated incidence rates, relative risks (RRs), and population attributable risks (PARs) for breast cancer risk factors and extended our results to the U.S. female population by using sample weights from the NHANES I survey. Results : Our PAR estimates suggest that later age at first birth and nulliparity accounted for a large fraction of U.S. breast cancer cases, 29.5% (95% confidence interval [CI] = 5.6%-53.3%); higher income contributed 18.9% (95% CI = -4.3% to 42.1%), and family history of breast cancer accounted for 9.1% (95% CI = 3.0%-15.2%). Taken together, these well-established risk factors accounted for approximately 47% (95% CI = 17%-77%) of breast cancer cases in the NHEFS cohort and about 41% (95% CI = 2%-80%) in the U.S. population. Conclusions : The RRs for most of these risk factors were modest, but their prevalence as a group was high, leading to estimates that suggest that a substantial proportion of breast cancer cases in the United States are explained by well-established risk factors. Implications : Elucidation of the determinants underlying recognized factors and study of other factors that may confer risk or protection are needed in efforts to advance understanding of breast cancer etiology and to aid in devising strategies for prevention.
Medical students' experience with musculoskeletal diagnoses in a family medicine clerkship

Many US medical schools require a family medicine clerkship, yet little is known about the quantity and diversity of the diagnoses the students experience. This study examines patients encountered with musculoskeletal diagnoses using quantitative data collected by family practice clerkship students. Over a two-year period, 445 students completed 7202 patient encounter forms for patients with a musculoskeletal diagnosis, noting their confidence level and responsibilities. Of the 78 854 diagnoses presented, 7850 were for musculoskeletal conditions. Students reported a lower level of confidence in diagnosing and treating musculoskeletal patients when compared with their confidence level in dealing with non-musculoskeletal patients. They are generally more actively involved with musculoskeletal patients by observing, seeing the patient before the preceptor, taking a history, suggesting treatment and discussing the case with the preceptor. At the study school, this fact may reflect that formal curricular teach...
The lithosphere-asthenosphere boundary and cratonic lithospheric layering beneath Australia from Sp wave imaging

Sp and Ps scattered wave receiver functions were calculated for nineteen stations across Australia and the island of Tasmania in order to image the lithosphere–asthenosphere boundary and layering within the lithosphere. Within Phanerozoic eastern Australia and the eastern margin of the South Australia Craton, prominent Sp phases from a negative velocity contrast were found at depths of 61 ± 11 km to 131 ± 9 km, consistent with the lithosphere–asthenosphere boundary depth range from surface wave tomography. These phases imply significant velocity drops over depth ranges of 30–40 km or less, and thus cannot be explained by a lithosphere–asthenosphere boundary that is controlled by temperature alone. Rather, they imply that the asthenosphere is hydrated with respect to a drier, depleted lithosphere or contains a small amount of partial melt. The shallowest Sp phases have the largest amplitudes and occur in regions with the most recent, voluminous volcanism, strengthening the link to partial melt at the base of the lithosphere. In contrast, no significant negative Sp phases were found at the base of the thick cratonic lithosphere at the stations in central and western Australia, implying that the cratonic lithosphere–asthenosphere velocity gradient is distributed over more than 50–70 km in depth. This gradient may be purely thermal in origin, although gradational changes in composition or melt content cannot be ruled out. A negative Sp phase was observed at depths of 69 ± 8 km to 85 ± 14 km at stations in central and western Australia, indicating the presence of a drop in velocity internal to the lithosphere. This interface within the lithosphere may be a relic of cratonic mantle formation, or the result of alteration by melt and metasomatism.
Estimated intensities and probable tectonic sources of historic (pre-1898) Honduran earthquakes

abstract A descriptive earthquake catalog of Honduras for the period prior to instrumental data has been compiled from numerous sources. Believed to be the most complete to date, it is the culmination of a detailed review of the literature for earthquakes between the years of 1539 and 1897 A.D. For each catalog entry magnitude ranges and tectonic source provinces were estimated. Available records were not sufficiently detailed to permit the assignment of epicentral locations. Based on estimates of an earthquake9s maximum Modified Mercalli intensity, Richter magnitudes for all earthquakes probably ranged from 3 to 8+. The major earthquakes of this period did not originate within Honduras, but in neighboring tectonic provinces. The most destructive of these was the earthquake of 4 August 1856, estimated to have had a magnitude of 7 to 8+, which caused widespread damage along the Caribbean coast. Earthquakes within the country were probably associated with Honduran Depression faults. The largest reported event occurred on 14 November 1851 and had an estimated magnitude of 6 to 6 1 2 .
Nixon on Conscious and Non-conscious Experience

To my mind (pace Heidegger) the enormous focus on consciousness and experience in contemporary philosophy is a continuation of metaphysical mistakes made by the Socratic philosophers and carried forward to this day, requiring “deconstruction” (in its technical postmodern sense). My view is that Existenz is “between-two,” between two quantum thermofield theoretical modes in the ground (vacuum) state of quantum brain dynamics. In the belonging-together (matching) of dual thermofield modes, Existenz is unfolded as explicate world-thrownness. Discussion of conscious and non-conscious experience, even at Nixon’s perspicuous level, are unfortunately off the mark.
MULTILEVEL RANDOM EFFECTS ANALYSIS OF MODAL USE CONSTRAINTS AND PERCEPTIONS ON PUBLIC TRANSPORTATION USING DATA FROM GERMANY

Multilevel random coefficient regression models account for hierarchical levels in survey data, control for the effects of explanatory variables, and provide estimates of the random variation contributed by each level. The nonlinear regression models in this paper use data from a series of interviews in Germany to analyze true and perceived constraints and dislikes of travelers. The presence or absence, for each trip, of these constraints and dispositions are explained using social and economic characteristics of the trip maker, place of residence, household resources, trip characteristics, and random effects at the trip, person, household and city of residence levels.
The "Publicness Puzzle" in Organization Theory: A Test of Alternative Explanations of Differences between Public and Private Organizations*

"Publicness" is defined as a characteristic of an organization which reflects the extent the organization is influenced by political authority. The concept, operationalized as a series of interval measures, is placed in direct competition with the traditional core definition of publicness as ownership (i. e., formal legal status). Using a sample of research and development laboratories, the two approaches are compared in terms of their ability to explain organizational outputs and process in the context of an explanatory model. The results suggest that both approaches tap unique characteristics of publicness and contribute to a more complete understanding of the role of publicness in the study of organizations.
The Handmaid's Tale of Fertility Tourism: Passports and Third Parties in the Religious Regulation of Assisted Conception

Infertility is a devastating global malady triggering worldwide demand for a vast array of reproduction assisting technologies. Infertility is particularly devastating those "pronatalist" societies marked by high rates of infertility and large disparities in access to medical services. Poverty in particular impedes large segments of the population in pronatalist Third World countries from gaining access even to very basic techniques of infertility treatment and consigns them to ineffective traditional remedies. In this Article drawing on both ethnographic work on infertility in the Third World and on Margaret Atwood's The Handmaid's Tale, Professor Storrow examines two starkly class-stratified societies where reproduction is regulated by means of rigid adherence to religious doctrine. He notes in particular that in such societies the participation of third-party gamete donors and surrogates in the reproductive process seems to depend upon whether the society in question is devoted to a program of repopulation. Where it is, Storrow finds a potent metaphor in fertility tourism where infertile couples of means treat third parties from disenfranchised groups as "passports" to reproduction. Storrow concludes that in resource-poor, pronatalist societies, programs of repopulation are a tipping point beyond which exploitation of third parties in infertility treatment is actively pursued and expediently justified.
Analysis on Riemannian co-compact covers

This is a survey on analysis on non-compact co-compact Riemannian covers and how it relates to random walks on finitely generated groups. The focus is on the long time behavior of the heat kernel and related topics such as Liouville theorems, scale invariant Harnack inequalities and isoperimetric profiles.
Pressure assessment of superior semicircular canal dehiscence repair techniques--a temporal bone study.

OBJECTIVE To develop a cadaveric temporal bone preparation to compare the strength of superior semicircular canal dehiscence (SCD) repair techniques. BACKGROUND Superior semicircular canal dehiscence syndrome is a clinical condition with a variety of auditory and vestibular symptoms resulting from a mobile third window into the inner ear. Patients with incapacitating symptoms often undergo surgical repair. There have been no previous studies to directly assess the strength of techniques used for repair of SCD. METHODS The ability of repair techniques to withstand prolonged pressure application was measured in prepared temporal bones (n = 5). Pressure changes were compared with the superior semicircular canal intact and with the dehiscence repaired via three repair techniques (resurfacing, plugging, and combined plugging and resurfacing). RESULTS Each of the three repair techniques resisted loss of applied pressure as well as the closed system before creation of the dehiscence at pressures comparable to high-normal intracranial pressure (23-25 cm H2O). At supra-physiologic pressure levels (45-55 cm H2O), the combined plugging and resurfacing technique showed consistent resistance to loss of pressure as compared to instances of failure with either of the single repair approaches. CONCLUSION Findings from the cadaveric temporal bone preparations revealed that even immediately after repair, each of the three main techniques are equally resistant to the application of high-normal intracranial pressure levels. However, with consistent resistance to loss of pressure across all trials, the combined plugging and resurfacing technique may offer improved resistance in instances where supra-physiologic pressures are encountered.
Benign mesenchymoma of the round ligament. A report of two cases with immunohistochemistry.

Benign mesenchymomas are tumors composed of an admixture of two or more mature mesenchymal tissue types. Clinically and histologically they are benign lesions. However, they are seldom encapsulated and therefore may recur locally if incompletely excised. The authors report on two benign mesenchymomas composed of mature fat, thin-walled small and medium size vessels, and spindle cells demonstrated to be smooth muscle by immunohistochemical studies. They were diagnosed in women in their SOs. Both were located in the round ligament of the uterus. One was discovered incidentally during hysterectomy, and the other was unusually large, being diagnosed preoperatively as a retroperitoneal liposarcoma. Most round ligament tumors are leiomyomas or fibromas. To the authors' knowledge, this is the first report of benign mesenchymomas occurring in this location.
Therapeutic Advances in Systemic Lupus Erythematosus

Objective: To review the progress in the treatment of systemic lupus erythematosus(SLE),in order to guide clinical practice.Methods: To summarize the therapies of systemic lupus erythematosus in recent years.Results: There was much progress of SLE,s treatment in recent years,and new therapies were clinically applied,especially in the application of new immunosuppressant.Conclusion: The early correct diagnosis and treatment were the keys to the successful treatment of SLE.The prognosis of patients would be improved when the new immunsupressant was used.
Pesticides, Selected Elements, and Other Chemicals in Adult Total Diet Samples, October 1978-September 1979

The U.S. Food and Drug Administration (FDA) conducts Total Diet Studies to determine the dietary intake of selected pesticides, industrial chemicals, and elements (including radionuclides). These studies involve the retail purchase and analysis of foods representative of the diets of infants, toddlers, and adults. The individual food items are separated into a number of food groups, each of which is analyzed as a composite. This report summarizes the results for adult Total Diet samples collected in 20 cities between October 1978 and September 1979. The average concentration, range of concentrations, and calculated average daily intake of each chemical found are presented by food group. The average daily intakes of the chemicals are similar to those found in the several preceding years and are within acceptable limits. The results for samples collected during the same period that represent the diets of infants and toddlers are reported separately.
Infrared Emission for Detection and Identification of Pesticides

The detection and identification of pesticides in our environment is a problem of increasing public interest. This paper describes the use of infrared emission from heated thin films of various samples to provide information essentially equivalent to that available from infrared absorbance spectroscopy.
An evanescent-mode tunable dual-band filter with independently-controlled center frequencies

This paper presents the design of a tunable dual-band bandpass filter based on evanescent-mode cavity resonators with two capacitive loadings which result in two independently tunable resonant frequencies. Small filter size is achieved since the two modes share the same physical volume of a single cavity. In addition, the internal and external couplings of the filter can be controlled independently at the two passbands to create flexible frequency responses. An example of the proposed filter design is prototyped in a substrate-integrated fashion having two tunable passbands, a lower tuning band of 1.156–1.741 GHz with 3-dB bandwidth of 76–156MHz and insertion loss of 3.137–1.109 dB, and an upper tuning band of 2.242–3.648 GHz with 3-dB bandwidth of 125–553MHz and insertion loss of 7.551–1.299 dB.
For better or for worse: reassessing the impact of tax and expenditure limitations on state expenditure

This study examines the fiscal impact of tax and expenditure limitations (TELs) on state spending by expanding the popular, narrow view of examining TELs and taking into account the scope, purpose, and restrictiveness of individual state TELs. Using an efficient estimator, called fixed effect vector decomposition I employ a set of panel data from all fifty states for the period 1997 - 2006. While a number of studies have been inconclusive about the impact of state TELs on spending, this study finds that having a TEL is not what matters. Rather, the impact of TELs depends on the actual features of the individual TEL. Further, TELs impact different categories of spending in different ways and, under the right conditions, TELs can have the desired impact and effectively reduce state spending.
Integration of a driving simulator and a traffic simulator case study: exploring drivers' behavior in response to variable message signs

Abstract For the first time, a driving simulator has been integrated with a traffic simulator at the network level to allow subjects to drive in a fairly realistic environment with a realistic traffic flow and density. A 10 mi2 (25 km2) network was developed in a driving simulator and then exported to a traffic simulator. About 30 subjects drove the simulator under different traffic and driving conditions and variable message sign (VMS) information, both with and without integration. Route guidance was available for the subjects. The challenges of the integration process are explained and its advantages investigated. The study concluded that traffic density, VMS reliability and compliance behavior are higher when driving and traffic simulators are integrated. To find factors affecting route diversion, researchers applied a binary logistic regression model. The results indicated that the original chosen route, displayed VMS information, subjects' attitude toward VMS information helpfulness, and their level of exposure to VMS affect route diversion. In addition, a multinomial logistic regression model was employed to investigate important factors in route choice. The results revealed that there is a significant correlation with driver route choice behavior and their actual travel time, the need for GPS, VMS exposure and also the designed scenarios. It should be noted that the paper was peer-reviewed by TRB and presented at the TRB Annual Meeting, Washington, D.C., January 2016.
The Relationship of Race, Oncotype DX, and Ki67 in a Population Highly Screened For Breast Cancer.

Oncotype DX recurrence score (ODX) can predict risk of invasive breast cancer recurrence and benefit of chemotherapy. Literature is limited on the relationship of ODX and race in women with hormone receptor positive and node negative/positive disease. Our study examines the relationship between race and clinical characteristics within a population of highly screened women with newly diagnosed breast cancer. The institutional Breast Cancer Database was queried for patients with newly diagnosed breast cancer between January2010 and March2015. We analyzed clinical and tumor characteristics including ODX. Statistical analyses included Pearson's Chi-Square and Fisher's Exact Tests. There were 2,092 women in our study cohort. The majority had college-level education (84%), regular screening (78%), and clinical breast exams (88%). The majority had invasive ductal carcinoma (IDC) (62%), early stage (0, I, II) tumors (93%), ER+ (84%), PR+ (71%), Her2 negative (86%), and node negative disease (83%). There was a significantly higher proportion of later stage disease among African-Americans (p = 0.001) and Asians (p = 0.006) and more triple negative breast cancers among African-Americans (p < 0.0001). A majority of patients had a low ODX (56%). While ODX was not different among the race categories (p = 0.97), there were significant racial differences in Ki-67 (p < 0.0001). In a population of highly screened women, differences were found between races regarding tumor histology. No statistical difference between race and ODX was noted, but there were racial differences in Ki67. Therefore we recommend that further research be focused on refining management algorithms by ethnicity.
Hunger and Satiety Gauge Reward Sensitivity.

Many of the neurocircuits and hormones known to underlie the sensations of hunger and satiety also substantially alter the activity of the dopaminergic reward system. Much interest lies in the ways that hunger, satiety, and reward tie together, as the epidemic of obesity seems tied to the recent development and mass availability of highly palatable foods. In this review, we will first discuss the basic neurocircuitry of the midbrain and basal forebrain reward system. We will elaborate how several important mediators of hunger – the agouti-related protein neurons of the arcuate nucleus, the lateral hypothalamic nucleus, and ghrelin – enhance the sensitivity of the dopaminergic reward system. Then, we will elaborate how mediators of satiety – the nucleus tractus solitaries, pro-opiomelanocortin neurons of the arcuate nucleus, and its peripheral hormonal influences such as leptin – reduce the reward system sensitivity. We hope to provide a template by which future research may identify the ways in which highly rewarding foods bypass this balanced system to produce excessive food consumption.
Joint Effects of Peer Presence and Fatigue on Risk and Reward Processing in Late Adolescence

Peers are thought to increase adolescents’ risk-taking behavior, at least in part, by heightening their sensitivity to rewards. In this study, we investigate whether the effect of peers on late adolescent males is exacerbated when youth are cognitively fatigued, a state characterized by weakened cognitive control and heightened orientation toward rewards, and well established as a factor that compromises decision making. We hypothesized that fatigued adolescents’ top-down regulation of reward-related impulses may be compromised, thereby potentially amplifying the effect of peers on reward- and risk-seeking behavior. Late adolescent males between 18 and 22 years old (mean age = 19.64, SD = 1.22; 61% Caucasian) completed a decision-making battery either alone or in the presence of 3 same-sex peers, and were either cognitively fatigued or non-fatigued. We compared behavior between four experimental groups—fatigued adolescents in a peer group, non-fatigued adolescents in a peer group, fatigued adolescents by themselves, and non-fatigued adolescents by themselves. The findings showed that cognitive fatigue and peer presence evinced independent effects on risk taking and sensitivity to rewards, but that these factors do not influence adolescent decision-making in an additive or synergistic fashion. To our surprise, being fatigued reduces (but does not eliminate) the effect of peers of risk taking. Moreover, the impact of peers on adolescent males’ ability to learn from negative consequences is not compromised when adolescents are in a state of mental fatigue. Our results suggest that mental fatigue increases late adolescent males’ reward sensitivity to the same extent as peer presence, but does not amplify the peer effect on risk-taking behavior. In this regard, grouping adolescents when they are fatigued may be less dangerous than when they are rested. Similarly, the added presence of peers does not further exacerbate the effect of fatigue on adolescent’s reward- and risk-seeking inclinations. In fact, given peers’ unique effect on adolescents’ ability to learn from costly decisions, our findings suggest that seeking the presence of peers—which is often a rewarding experience in and of itself—may be an adaptive response to mitigate the impact of fatigue on decision making.
Configurational Preference of the Glutamate Receptor Ligand Binding Domain Dimers

Ionotropic glutamate receptors are a family of tetrameric ion channels with functional states consisting of nonconducting, conducting, and desensitized states that are starting to become well characterized by electrophysiological and biophysical studies. However, the structure and relative energetics of these states beyond the general structure of the receptor are still not well understood. It is known that the interface between monomeric subunits of the tetramer plays a major role in distinguishing these functional states. We have used umbrella sampling and multimicrosecond molecular dynamics simulations of the GluA2 AMPA subtype glutamate receptor ligand-binding domain (LBD) dimers to characterize a natural propensity of the LBD dimers for various configurational states. Our results show a proposed desensitized conformation of the LBD dimer is a highly preferable conformation of the LBD dimer without the influence of other receptor domains or crystallographic conditions. This has been demonstrated by both free protein simulations of 5 μs duration, as well as by computed free energy difference between the active and desensitized states. At the same time, the simulations performed using the same protocols revealed that for the LBD mutant L483Y, known to lack desensitization, the postulated active state of the LBD dimer is indeed the preferred configurational state, which remained stable in the simulations. Our findings pave the path for developing more detailed hypotheses of the full receptor activation mechanism. Combined with the energetics of glutamate binding to the LBD and the energy required to open the transmembrane pore helices, our results strongly support a hypothesis that the low absolute free-energy state is the desensitized state of the intact AMPA receptor.
Physics of frequency modulated comb generation in semiconductor diode lasers

We investigate the nonlinear gain responsible for the generation of frequency modulated combs in semiconductor diode lasers, distilling the essential physics necessary for comb generation in quantum well, quantum dot, and quantum cascade systems.
Impact of Patient Age on Clinical Features, Serologic Test Reactivity and Long-Term Outcome of Culture-Confirmed Early Lyme Disease

Whether age at time of diagnosis impacts the clinical presentation or long-term outcome of early Lyme disease is unknown. Subjects enrolled in this study had culture-confirmed early Lyme disease and were followed up annually in a long-term prospective study. Subjects ≤50years of age were compared with those who were ≥51years of age at time of study entry. Of the 283 enrolled subjects, the ≥51year old age group was significantly more likely to be female (P=0.0095) and to be compliant with long-term follow-up of at least 11years duration (P=0.0119). There were no significant differences between the two age groups with regard to any of the other variables assessed at presentation. For the 128 subjects who were followed up for 11-20years, there was no significant difference between the two age groups in the frequency, number or type of residual symptoms. The older age group at study entry, however, was significantly more likely to develop an intercurrent comorbidity (P=0.0017), and there was a trend toward a greater likelihood of having an intercurrent hospitalization (P=0.0311). Among the 128 subjects followed up for 11-20years, the older age group at study entry returned for a significantly greater number of follow-up visits (P=0.0129). In conclusion, older age at the time of diagnosis of early Lyme disease did not impact the initial clinical features or long-term outcome of this infection. Not unexpectedly, older patients had more comorbidities during long-term follow-up.
Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology

Enzyme assays of skin fibroblasts from five children with familial hyperlysinemia from unrelated families are added to the previous report of three children from two unrelated families. In all instances there was a deficiency in lysine-ketoglutarate reductase, saccharopine dehydrogenase, and saccharopine oxidoreductase activities. To complete the studies on the enzymes associated with familial hyperlysinemia, saccharopine oxidoreductase was partially purified from human liver and characterized. The activity did not separate from that of lysine-ketoglutarate reductase or saccharopine dehydrogenase. A simple screening test for familial hyperlysinemia is described based on the evolution of 14CO2 from lysine-14C by skin fibroblasts. The test differentiated, without overlap, seven patients with familial hyperlysinemia from control subjects. The relation of the two genetic entities involving lysine degradation, familial hyperlysinemia and saccharopinuria, is discussed. It is suggested that familial hyperlysinemia, type I, be applied to patients with major defects in lysine-ketoglutarate reductase and saccharopine dehydrogenase, and that familial hyperlysinemia, type II, to be used to designate patients in whom significant amounts of lysine-ketoglutarate reductase are retained. The nomenclature would be consistent with that of an analogous disease, orotic aciduria.
Synthesis of aluminum oxide nanoparticles by laser ablation in liquids

Spherical aluminum oxide (γ-phase) nanoparticles with sizes below 30 nm were synthesized by pulsed laser ablation in liquids. The wavelength and energy fluence of the nanosecond laser were set at 1064 nm and ∼1x103 J/cm2, respectively. The optimal repetition rate to maximize the production of those nanoparticles was determined to be at 2,129±64 Hz. Therefore, the lifetime of the cavitation bubble was estimated to be around 0.47±0.01 ms.
Vision-Based Detection of Simultaneous Kicking for Identifying Movement Characteristics of Infants At-Risk for Neuro-Disorders

Neuro disorders such as Cerebral Palsy (CP) and Infantile Spasms (IS) in infants can cause a wide range of developmental coordination disorders (DCD). Simultaneous, non-complex, kicking patterns that persist in infants of 4-7 months of age is highly suggestive of a neuro-disorder. Early establishment of risk levels for infants at risk for neuro-disorders is beneficial for early intervention. To provide a method to track early infant kicking movements for determining risk-level, an automated method is established to track and classify periods of simultaneous (SM), non-simultaneous movements (NSM) and no movement (NM) during infant kicking actions. In this paper, a computer vision algorithm uses KAZE points to track infant kicking and collect kinematic data. Each movement type is classified by computing unique feature criterion and using a support vector machine (SVM) for learning a movement model. We discuss the significance of the classifier as well as analyze the percentage break down of movement types for typical infants and infants with IS.
Polymeric Micellar Delivery of Novel Microtubule Destabilizer and Hedgehog Signaling Inhibitor for Treating Chemoresistant Prostate Cancer

Castration-resistant prostate cancer that has become resistant to docetaxel (DTX) represents one of the greatest clinical challenges in the management of this malignancy. There is an urgent need to develop novel therapeutic agents to overcome chemoresistance and improve the overall survival of patients. We have designed a novel microtubule destabilizer (2-(4-hydroxy-1H-indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone (QW-296) and combined it with a newly synthesized hedgehog (Hh) signaling pathway inhibitor 2-chloro-N1-[4-chloro-3-(2-pyridinyl)phenyl]-N4,N4- bis(2-pyridinylmethyl)-1,4-benzenedicarboxamide (MDB5) to treat taxane-resistant (TXR) prostate cancer. The combination of QW-296 and MDB5 exhibited stronger anticancer activity toward DU145-TXR and PC3-TXR cells and suppressed tumor colony formation when compared with single-drug treatment. Because these drugs are hydrophobic, we synthesized the mPEG-p(TMC-MBC) [methoxy-poly(ethylene glycol)-block-poly(trimethylene carbonate-co-2-methyl-2-benzoxycarbonyl-propylene carbonate)] copolymer, which could self-assemble into micelles with loading capacities of 8.13% ± 0.75% and 9.12% ± 0.69% for QW-296 and MDB5, respectively. Further, these micelles provided controlled the respective drug release of 58% and 42% release of QW-296 and MDB5 within 24 hours when dialyzed against PBS (pH 7.4). We established an orthotopic prostate tumor in nude mice using stably luciferase expressing PC3-TXR cells. There was maximum tumor growth inhibition in the group treated with the combination therapy of QW-296 and MDB5 in micelles compared with their monotherapies or combination therapy formulated in cosolvent. The overall findings suggest that combination therapy with QW-296 and MDB5 has great clinical potential to treat TXR prostate cancer, and copolymer mPEG-p(TMC-MBC) could serve as an effective delivery vehicle to boost therapeutic efficacy in vivo.
Intrinsic Brain Network Biomarkers of Antidepressant Response: a Review

Poor treatment response is a hallmark of major depressive disorder. To tackle this problem, recent neuroimaging studies have sought to characterize antidepressant response in terms of pretreatment differences in intrinsic functional brain networks. Our aim is to review recent studies that predict antidepressant response using intrinsic network connectivity. We discuss current methodological limitations and directions for future antidepressant biomarker studies. Functional connectivity stemming from the subgenual and rostral anterior cingulate has shown particular consistency in predicting antidepressant response. Differences in this connectivity may prove fruitful in differentiating treatment responders to many antidepressant interventions. Future biomarker studies should integrate biological MDD subtypes to address the disorder’s inherent clinical heterogeneity. These clinical and scientific advancements have the potential to address this population marked by limited treatment response. Methodological considerations, including patient selection, response criteria, and model overfitting, will require future investigation to ensure that biomarkers generalize for prospective prediction of treatment response.
In older adults with acute ischemic stroke, the Clinical Frailty Scale predicted mortality at 28 days

Source Citation Evans NR, Wall J, To B, et al. Clinical frailty independently predicts early mortality after ischaemic stroke. Age Ageing. 2020. [Epub ahead of print]. 31951248
Project facilitate: A review of the FDA oncology center of excellence expanded access pilot program.

7023Background: Expanded Access (EA), also known as “compassionate use,” is a regulatory pathway in which a patient with an immediate life-threatening condition or disease can gain access to an inv...