cssi/SciSciGPT-SciSciNet huggingface dataset:
The development of ultrashort acting neuromuscular relaxant tropane derivatives

There is a need for neuromuscular relaxant (NMR) agents that are of the "nondepolarizing type" and produce rapidly developing and short-lasting skeletal muscle relaxation in anesthesiology. Many efforts have been directed to produce such agents. Our research focused on the design, synthesis, and evaluation of numerous "bisquaternary" derivatives of the cyclic aminoalkanes: tropane and granatane. Through systematic "steric structure-activity relationship" studies, we arrived at some new bisquaternary tropine and granatanol diesters, which in laboratory studies appeared to be the fastest and shortest acting NMRs recognized so far. Their ultrashort duration action-mechanism was, however, linked to the formation of nephrotoxic metabolites, precluding further development. Even so, we believe that the scientific information gained from more than a thousand such agents, will be useful toward developing the "ideal," ultrashort-acting NMR that could be clinically successful without the use of "reversing" agents, at least until "new biotechnology" may solve all problematic aspects of "transient" muscle relaxation.
Heat Distribution and Heating Efficiency in Selected Pans on Conventional and Glass/Ceramic Surfaced Electric Range Units

Heat distribution and heating efficiency were investigated on conventional and glass/cerami c surfaced electric ranges with saucepans of selected materials and bottom con formations. Loads were fat-f lour, water, and vegetable oil. Heating rate and efficiency but not patterns of heat distribution were better on the conventional electric range than on either of the two glass/ceramic cooking tops. A flat-bottomed pan with high thermal con ductivity performed best on all ranges.
Automatic term list generation for entity tagging

Motivation: Many entity taggers and information extraction systems make use of lists of terms of entities such as people, places, genes or chemicals. These lists have traditionally been constructed manually. We show that distributional clustering methods which group words based on the contexts that they appear in, including neighboring words and syntactic relations extracted using a shallow parser, can be used to aid in the construction of term lists. Results: Experiments on learning lists of terms and using them as part of a gene tagger on a corpus of abstracts from the scientific literature show that our automatically generated term lists significantly boost the precision of a state-of-the-art CRF-based gene tagger to a degree that is competitive with using hand curated lists and boosts recall to a degree that surpasses that of the hand-curated lists. Our results also show that these distributional clustering methods do not generate lists as helpful as those generated by supervised techniques, but that they can be used to complement supervised techniques so as to obtain better performance. Availability: The code used in this paper is available from http://www.cis.upenn.edu/datamining/software_dist/autoterm/ Contact: tsandler@seas.upenn.edu
Dynamic neural network control of nonlinear-time varying systems: stability analysis, optimal network structure, and on-line adaptation

In this paper, dynamic neural network control (DNNC) is presented as a control strategy which uses a neural network to model the process and then applies the mathematical inversion of the process model to design the controller. DNNC falls into the large class of model predictive controllers, many of which are now widely used in industry. The objectives of this paper are: to study the stability properties of DNNC; and to study the on-line adaptation properties of DNNC. In this study four basic assumptions are made. The process is modeled with continuous time functions. If the process is nonstationary, it is also necessary to assure that changes will be continuous and smooth over small intervals of time, i.e. that process parameters change in a continuous manner. The time between model adaptation is small relative to time scale of parameter changes. Process parameters will not change at once, but only a small subset of them.
A topological and temporal correlator network for spatiotemporal pattern learning, recognition, and recall

In this paper, we describe the design of an artificial neural network for spatiotemporal pattern recognition and recall. This network has a five-layered architecture and operates in two modes: pattern learning and recognition mode, and pattern recall mode. In pattern learning and recognition mode, the network extracts a set of topologically and temporally correlated features from each spatiotemporal input pattern based on a variation of Kohonen's self-organizing maps. These features are then used to classify the input into categories based on the fuzzy ART network. In the pattern recall mode, the network can reconstruct any of the learned categories when the appropriate category node is excited or probed. The network performance was evaluated via computer simulations of time-varying, two-dimensional and three-dimensional data. The results show that the network is capable of both recognition and recall of spatiotemporal data in an online and self-organized fashion. The network can also classify repeated events in the spatiotemporal input and is robust to noise in the input such as distortions in the spatial and temporal content.
Design of High-Speed Metal-Semiconductor-Metal Photodetectors by Finger Sizing Optimization

Finger sizing of interdigitated Schottky-barrier Metal-Semiconductor-Metal Photodetectors (MSM-PD) is discussed in this paper. We observe that the MSM-PD geometry with fast response speed can be determined by solving a special form of optimization problem, called reversed posynomial programs, which can be globally solved by, e.g., branch-and-bound methods. Our method, therefore, yields completely automated nger sizing of MSM-PD, directly from specifications.
The Central Variable Strategy of Str+ve

Str∔ve is an upgraded version of our 1980 general inequality theorem prover [6] that contains a restrictive implementation of the transitivity property of inequality and the interpolation property of dense fields. Its underlying system is complete for first order logic. In this paper, we formally present and discuss some of its features. Included is the central variable strategy (not part of the 1980 prover) which gives Str∔ve a “large step” capacity.
Insulin-like growth factors (IGFs) as autocrine/paracrine regulators of granulosa cell differentiation and growth: studies with a neutralizing monoclonal antibody to IGF-I.

Evidence that granulosa cells secrete and respond to insulin-like growth factors (IGFs) suggests, but does not prove, the importance of IGFs as intraovarian regulators. To further assess the role of these peptides in ovarian function, a neutralizing monoclonal antibody to IGF-I was employed to block the actions of IGFs in porcine follicular fluid and in granulosa cell-conditioned medium. In one series of experiments, granulosa cells from immature porcine follicles were cultured in medium containing porcine follicular fluid that had been charcoal-treated to remove steroids. As noted before, fluid from large follicles (LFF) stimulated progesterone production in a dose-dependent manner. The stimultuory effect of LFF (30% v/v) could be inhibited by greater than 50% by the anti -IGF monoclonal antibody. This inhibitory action was specific for the an:i-IGF antibody and could be overcome by the addition of excess exogenous IGFs. In another series of experiments, granulosa cells were made dependent on endogenously produced IGFs by culturing them in a serum-free medium without exogenous growth factors. The effects of follicle-stimulating hormone (FSH), estradiol (E2), growth hormone (GH), and combinations thereof on progesterone production were inhibited by approximately 50% by the anti-IGF antibody. The effects of IGFs on indices of cell growth (judged by the criterion of being inhibited by the anti-IGF antibody) were less dramatic. A modest 18% increase in cell number was observed with FSH and E2 treatment in serum-free medium; this effect was virtually abolished by the antibody. In contrast, cell numbers in cultures with LFF were reduced by only 11% by the antibody, and the stimulatory effect of follicular fluid on 3H-:hymidine incorporation was reduced by only 16%. These results suggest that the stimulatory effects of follicular fluid, FSH, estradiol, and GH on progesterone production are mediated at least in part by IGFs. In general, ovarian IGFs appear to be more important to granulosa cell cytodifferentiation than to cell replication. These studies provide the most direct evidence available supporting the concept of IGFs as auwcrine/paracrine regulators in the ovary.
The queueing equivalence to a manufacturing system with failures

The authors consider optimal production rate control in a failure prone manufacturing system. It is well known that the hedging point policy is the optimum controller for such a system. They show that under the hedging point policy the system can be treated as an M/M/1 queue. Therefore, existing results in queuing theory can be readily applied to obtaining the steady-state probability density function of the production surplus, based on which the optimal hedging point policy can be computed. To a large extent, the approach is based on sample path analysis. It not only provides an alternative way to solve the problem but also reveals some interesting insights. >
Emotional trait and memory associates of sleep timing and quality

Poor ability to remember the extinction of conditioned fear, elevated trait anxiety, and delayed or disrupted nocturnal sleep are reported in anxiety disorders. The current study examines the interrelationship of these factors in healthy young-adult males. Skin-conductance response was conditioned to two differently colored lamps. One color but not the other was then extinguished. After varying delays, both colors were presented to determine extinction recall and generalization. Questionnaires measured sleep quality, morningness-eveningness, neuroticism and trait anxiety. A subset produced a mean 7.0 nights of actigraphy and sleep diaries. Median split of mean sleep midpoint defined early- and late-"sleep timers". Extinction was more rapidly learned in the morning than evening only in early timers who also better generalized extinction recall. Extinction recall was greater with higher sleep efficiency. Sleep efficiency and morningness were negatively associated with neuroticism and anxiety. However, neuroticism and anxiety did not predict extinction learning, recall or generalization. Therefore, neuroticism/anxiety and deficient fear extinction, although both associated with poor quality and late timing of sleep, are not directly associated with each other. Elevated trait anxiety, in addition to predisposing directly to anxiety disorders, may thus also indirectly promote such disorders by impairing sleep and, consequently, extinction memory.
DYNORA: a real-time planning algorithm to meet response-time constraints in dynamic environments

Most real-time planning algorithms address either the issue of response-time constraints or the issue of dynamic environments. A new real-time planning algorithm, DYNORA, is proposed to address both of these issues simultaneously. DYNORA is structured as a sequence of partial planning and execution cycles to avoid obsolescence of planning solutions at the time of execution. DYNORA uses a stopping criterion to balance planning cost and execution cost to achieve near optimal response times. DYNORA was used for the routing problem to optimize total cost. It shows better average-case time complexity than traditional real-time algorithms. >
Distribution of Tetracycline in Red Blood Cells

The distribution of tetracycline into human red blood cells was studied in vitro at 37°. The drug was taken up rapidly by the cells, and its distribution equilibrium was reached after ~10 min of incubation. The steady-state distribution ratio of the drug between the red cells and extracellular fluid of 0.9% NaCl solution was 2.84, while the distribution ratio between the cells and the plasma solution was 0.9. The reduced cellular uptake in plasma was due to binding of the drug to plasma components. Calcium ions in plasma appeared to reduce tetracycline uptake by the red cells. The red cell distribution of tetracycline in dogs was in close agreement with the in vitro data using the washed human red cells. A dog suffering from severe hypoalbuminemia showed greater uptake of the drug by the erythrocytes, while a normal healthy dog exhibited the red cell-plasma distribution ratio of 0.98. The release rate of tetracycline from the preloaded cells into normal saline solution indicated that the release was directly proportional to the cellular concentration of the drug; the first-order release rate was ~1.38 hr−1.
Gene environment interplay: nonhuman primate models in the study of resilience and vulnerability.

Identifying how individual differences in risk for disease emerge is a major target for biomedical research. In many cases, however, the most lightly traversed avenues of this type of basic and clinical research are those that begin with a focus on early development. It appears likely that early influences may be pivotal in lifetime risk of disease and other adverse outcomes. Nonetheless, understanding the constellation of interacting biological, experiential, social factors that influence this risk has proved a relatively elusive target. Better specification of routes of interplay between these factors, as well as definitions of the mechanisms by which they affect change, are essential goals for numerous research areas. Furthermore, progress towards these goals is unlikely without meaningful integration of diverse disciplines, among them biology and developmental science. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 50: 48–59, 2008.
Integrative Theories of QOL

In this chapter, I will review several theories whose purpose is to integrate and unify ideas in QOL research. These include livability theory, capability theory, stocks and flows, the joyless economy, quality of the person + environment, homeostasis, QOL = happiness + life satisfaction + absence of ill-being, the bidirectional spillover model, dynamic well-being, ontological well-being and the 3P model, and the psychology of quality of life.
Sieve: cryptographically enforced access control for user data in untrusted clouds

Modern web services rob users of low-level control over cloud storage--a user's single logical data set is scattered across multiple storage silos whose access controls are set by web services, not users. The consequence is that users lack the ultimate authority to determine how their data is shared with other web services. In this paper, we introduce Sieve, a new platform which selectively (and securely) exposes user data to web services. Sieve has a user-centric storage model: each user uploads encrypted data to a single cloud store, and by default, only the user knows the decryption keys. Given this storage model, Sieve defines an infrastructure to support rich, legacy web applications. Using attribute-based encryption, Sieve allows users to define intuitively understandable access policies that are cryptographically enforceable. Using key homomorphism, Sieve can reencrypt user data on storage providers in situ, revoking decryption keys from web services without revealing new keys to the storage provider. Using secret sharing and two-factor authentication, Sieve protects cryptographic secrets against the loss of user devices like smartphones and laptops. The result is that users can enjoy rich, legacy web applications, while benefiting from cryptographically strong controls over which data a web service can access.
Hydroxyalkoxy radicals: importance of intramolecular hydrogen bonding on chain branching reactions in the combustion and atmospheric decomposition of hydrocarbons.

During both the atmospheric oxidation and combustion of volatile organic compounds, sequential addition of oxygen can lead to compounds that contain multiple hydrogen-bonding sites. The presence of two or more of these sites on a hydrocarbon introduces the possibility of intramolecular H-bonding, which can have a stabilizing effect on the reactants, products, and transition states of subsequent reactions. The present work compares the absolute energies of two sets of conformations, those that contain intramolecular H-bonds and those that lack intramolecular H-bonds, for each reactant, product, and transition state species in the 1,2 through 1,7 H-migrations and Cα–Cβ, Cα–H, and Cα–OH-bond scission reactions in the n-hydroxyeth-1-oxy through n-hydroxyhex-1-oxy radicals, for n ranging from 1 to 6. The difference in energy between the two conformations represents the balance between the stabilizing effects of H-bonds and the steric cost of bringing the two H-bonding sites together. The effect of intramolecul...
Optical Properties Of Tantalum Oxide Films Deposited On BK7 Substrates By Excimer Laser Ablation

Thin amorphous films of tantalum oxide were grown on borosilicate crown glass substrates by KrF excimer pulsed laser ablation of a Ta2O5 target, in an oxygen environment. The deposition was performed at a temperature of 250 or 400 °C, while the oxygen pressure was set in the range 5 to 30 mTorr. The optical properties of the tantalum oxide coatings, as evaluated by reflectance/transmittance spectrophotometry, were found to be dependent on the oxygen gas pressure. At a pressure of 5 mTorr, absorbing films were obtained, with extinction coefficients above 10-2 (at λ=633 nm), along with an optical energy band-gap as low as 0.7 eV. At a pressure of 10 mTorr and above, the coatings had refractive indices up to 2.25 (at λ=633 nm), extinction coefficients below 10-4 (for λ>390 nm), and an optical energy band-gap in the range 3.9 to 4.0 eV.
Creatinine clearance predictions in acutely ill patients

In acutely ill patients, predicted creatinine clearance (Clcr) values [obtained using the Siersbaek-Nielsen nomogram (SNN) and ideal body weight (IBW)] were compared with actual Clcr based on measured urine creatinine concentrations. Timed urine collections were obtained from 118 patients (423 collections from 68 men, 400 collections from 50 women) before, during, and after aminoglycoside therapy. Patients were in intensive care units for management of acute exacerbations of sepsis, pneumonia, or abscess; most had other complicating conditions and were chronically ill. Urine was collected for 8 to 24 hours (70% for 24 hours) from Foley-catheterized patients. Patients were divided into low (less than 15 mg/kg/day), normal (15-25 mg/kg/day), and elevated (greater than 25 mg/kg/day) urinary creatinine excretion groups. Actual body weight (ABW) was used in some patient subgroups to explore differences between using IBW and ABW. SNN most accurately predicted Clcr in the 20% of the urine collections characterized by normal urinary creatinine excretion (Ucr). Most study patients excreted significantly less creatinine than the age-matched population tested in developing the SNN. In acutely ill patients with low Ucr, SNN overpredicted Clcr by 10-20 ml/min. SNN also overpredicted Clcr values in obese patients, but use of IBW rather than ABW improved the correlation between measured and predicted values in this subgroup. The SNN nomogram is applicable to critically ill patients if adjustments are made in predicted values. The characteristics of patients with low Ucr and the mechanism responsible for the decreased Ucr deserve further study.
FANUC Corporation: Reassessing the Firm's Governance and Financial Policies

In February 2015, Daniel Loeb (an American activist investor at Third Point LLC) announced his firm had acquired a large position in FANUC, a leading producer of industrial robots and software for machine tools. Loeb was demanding that the Japanese firm change its financial and governance policies (e.g., distribute more cash, improve shareholder relations, and fix its “illogical” capital structure). FANUC’s CEO, Yoshiharu Inaba, and his board must decide if and how to respond. One the one hand, the firm had been very successful having built leading market shares in each of its core divisions. On the other hand, the Japanese government was also calling for financial and governance reform as part of the prime minister’s recently-announced economic growth strategy known as “Abenomics”. Although Inaba and his team had previously considered many of the proposed changes, the question was whether it was now time to actually make some of the changes.This case has four pedagogical objectives. First, it provides an introduction to Japanese corporate governance and a way to compare and contrast Japanese vs. US-based governance policies. As capital markets integrate and foreign ownership increases, differences in culture and governance can come into conflict. Second, it illustrates the rise of activist investors in a cross-border situation. Loeb is interested in FANUC specifically given its potential for improved profitability as well as Japan more generally given the country’s new economic growth strategy known as “Abenomics”. The policy includes three components (known as “arrows”): fiscal stimulus, expansionary monetary policy, and regulatory and governance reforms. The opportunity to analyze a firm operating under and possibly responding to the government’s new macroeconomic policies is the third objective. And finally, as part of the government’s reform policies, it created a new stock index (the JPX-Nikkei 400 Index) designed to recognize high-performing firms with good governance policies. This index excluded many leading firms such as Amada, Mazda, Olympus, Panasonic, and TEPCO — all members of the Nikkei 225 Index. Bloomberg, in fact, referred to the new index as the “shame index”. Students can debate to what extent governments should be involved with setting and driving corporate governance policies and how successful it is likely to be.In addition to the English version, a Japanese version of this case is available from Harvard Business Publishing Company. A spreadsheet supplement with case exhibits in electronic format (Excel workbook) is also available from HBP.
14C-isomazole disposition in man after oral administration.

A 50-mg dose containing 50 µCi 14C-isomazole was administered orally to five healthy male volunteers. Blood, plasma, urine, feces, and saliva were collected and measured for total 14C; in addition, all collections except feces were measured for parent drug (ISO) and three metabolites: hydroxyisomazole (OHISO) and sulfone (SULF) and hydroxysulfone (OHSULF) analogues. Urine and fecal recoveries accounted for 97.0% of the drug administered, with 62.6% excreted in urine and 32.4% in feces. Only 47% of the drug recovered in urine could be identified, with ISO the largest constituent. Total plasma 14C peaked at 1.5 hr, indicating rapid absorption, and produced a mean half-life of 3.7 hr. This was similar to the total 14C half-life found in blood (3.1 hr) but longer than in red blood cells (1.8 hr) or saliva (1.4 hr), suggesting that different ISO-related compounds contributed to the results found in each fluid or tissue. An unidentified metabolite(s) composed a large portion of circulating plasma 14C and produced the longer half-life encountered in plasma. ISO exhibited a short half-life (1.35 hr), a high oral clearance (ClS/F; 24.2 ml/min/kg), and some extravascular distribution (Vβ; 3.07 L/kg). Total 14C in red blood cells and saliva related very well to plasma ISO disposition, suggesting preferential distribution of parent drug across cellular membranes. The estimated RBC:plasma ISO ratio (1.79) confirmed this hypothesis. Saliva may be used as a noninvasive means to monitor ISO disposition.
ANALYSIS OF SUMMERTIME CLOUD WATER MEASUREMENTS MADE IN A SOUTHERN APPALACHIAN SPRUCE FOREST

This paper presents an analysis of cloud water measurements made during the summers of 1986 and 1987 at Whitetop Mountain, Virginia (36.639° N, 81.605° W). Analysis of cloud water chemistry, cloud type, and air mass origin are made for each cloud event occurring during one 3 to 4 week measurement ‘intensive’ per year. Regional source/receptor relationships are also investigated. Cloud water concentrations of major ions (i.e., H+, SO4 2−, NO3 −, and NH4 +) are consistently higher during orographically formed ‘cap’ cloud events. Differences in cloud liquid water content between cap and frontal cloud events explains most, but not all, of the cloud water ion concentration differences. The remaining difference can be explained by greater rainfall associated with frontal cloud events. Most of the cloud water sulfate measured at Whitetop Mountain is apparently due to nucleation of aerosol sulfate within cloud droplets and not to local in-cloud aqueous phase SO, oxidation. No strong source/ receptor relationships were evident from this analysis. Most 72 hr air trajectories arriving at Whitetop Mountain during the cloud events described in this paper originated in the southeastern United States. Few came from the Ohio River Valley or the northeastern United States.
Role of fine needle aspiration cytology and endoscopic biopsy in the preoperative assessment of pancreatic and peripancreatic malignancies

Sixty-seven of 207 patients with pancreatic and peripancreatic malignancies underwent preoperative fine needle aspiration cytology (FNA), and 24 patients underwent intraluminal endoscopic biopsies. All patients had confirmation of the diagnosis of malignancy either at operation, autopsy, or by clinical follow-up. FNA of liver metastases was positive for malignancy in 12 of 12 patients. FNA of the pancreas was performed on 44 patients with pancreatic adenocarcinoma and 11 patients with other pancreatic or peripancreatic malignancies. The diagnosis of cancer was established by FNA in 32 of 44 (72.4%) patients with pancreatic adenocarcinoma and 1 of 11 patients (9.1%) with other pancreatic or peripancreatic malignancies. In the patients with pancreatic adenocarcinoma, 17 of 18 patients (94.4%) who had no operative intervention, 12 of 18 (66.7%) patients who had palliative bypass procedures, and 3 of 8 (37.5%) patients resected had positive FNA. Eighteen of 24 patients (75%) who underwent intraluminal endoscopic biopsies, and 11 of 15 (73.3%) with ampullary carcinoma were positive. We believe that FNA is of limited value in the diagnosis of small resectable tumors of the pancreas as it identified cancer in only 3 of 8 patients in whom it was employed. False negative FNA may delay the diagnosis and treatment of pancreatic malignancies. Patients in whom there is a high index of suspicion of pancreatic or peripancreatic malignancy based on clinical presentation, CT scan, or ERCP assessment do not require preoperative, histologic proof of malignancy prior to pancreaticoduodenectomy. Patients deemed to be unresectable or candidates for bypass on the basis of the size of the tumors or suspected liver metastases should be considered for FNA cytology, which is mainly successful under these circumstances.
PdAu Alloy Nanoparticle Catalysts: Effective Candidates for Nitrite Reduction in Water

Well-defined palladium–gold nanoparticles (PdAuNPs) with randomly alloyed structures and broadly tunable compositions were studied in catalytic nitrite (NO2–) reduction. The catalysts were synthesized using a microwave-assisted polyol coreduction method. PdxAu100–xNPs with systematically varied compositions (x = 18–83) were supported on amorphous silica (SiO2) and studied as model catalysts for aqueous NO2– reduction in a batch reactor, using H2 as the electron donor. The reactions followed pseudo-first-order kinetics for ≥80% NO2– conversion. The PdxAu100–xNP-SiO2 catalysts showed a volcano-like correlation between NO2– reduction activity and x; the highest activity was observed for Pd53Au47, with an associated first-order rate constant of 5.12 L min–1 gmetal–1. Alloy NPs with greater proportions of Au were found to reduce the loss in catalytic activity due to sulfide fouling. Density functional theory calculations indicate that this is because Au weakens sulfur binding at PdAuNP surfaces due to atomic e...
Trace metal sediment loading in the Mill Creek: A spatial and temporal analysis of vehicular pollutants in suburban waterways

Vehicular wash-off introduces toxic heavy metals into riverine environments, but the delivery patterns of such contaminants are normally difficult to observe. This study examines the spatial and temporal heterogeneity in metal loading of riverbed sediments at two river fords in the Mill Creek Watershed located in suburban Philadelphia, Pennsylvania. Riverbed sediment samples were collected over the course of the 2015 driving season (April to December) upstream and downstream of the two fords, which greatly differ in traffic density, and analyzed for their trace metal concentrations (As, Cd, Cu, Ni, Pb, Zn) and percent particulate organic carbon (%POC). Overall, metal concentrations were in the upper range of literature values for road-derived sediments. Comparing the sites, the more heavily trafficked ford had significantly higher concentrations, confirming the role of traffic density on metal accumulation. Highly enriched concentrations of Cu and Zn coupled with diagnostic metal:Cu ratios points to the strong influence of brake lining dust. While an increase in metal concentration was observed over the driving season, the highly variable spatial and temporal signal suggests other factors such as local geomorphological and hydrological conditions also play a role in metal accumulation and dispersal. Metal concentrations in excess of levels known to impact aquatic ecosystems, coupled with strong correlations between metal concentrations and the %POC content of the sediments, suggest vehicular-derived metals may play a role in the historically observed decrease in macroinvertebrate diversity in the watershed. These findings add to a growing body of literature highlighting the potential for vehicular and road-sourced metals to persist and potentially impact riverine environments.
FALL INJURIES IN OLDER MEN AND WOMEN: NOVEL ASSESSMENTS AND PREDICTORS.

AbstractFalls are associated with reduced physical function in older adults. However few large epidemiologic cohort studies have characterized fall injuries that were self-treated or all injuries treated in outpatient and inpatient settings. The Study of Osteoporotic Fractures in Men (MrOS) is an ongoing cohort of ambulatory men (N=5,994; 10% minorities; 2000–02 enrollment) aged ≥65 years at 6 U.S. sites. The Study of Women’s Health Across the Nation (SWAN; N=3,302; 53% minority; 1996 enrollment) is an ongoing multi-racial/ethnic cohort of women from 7 U.S. sites followed through menopausal transition for 20 years and now in early old age. The Health, Aging and Body Composition (Health ABC) Study enrolled well-functioning, ambulatory Medicare beneficiaries, aged 70–79 years (N=3,075; 52% women, 42% black) at 2 U.S. sites in 1997–98. Each study collected self-reported falls and fall injuries, including non-fracture and fracture injuries. Additionally Health ABC linked Medicare Fee-For-Service claims from denominator, inpatient, outpatient, physician/supplier, and carrier files to treated fall injuries and fractures over 8 years. Perceived fatigue levels will be associated with fall risk in MrOS men (Welburn). Sensory peripheral nerve impairments will be described as fall and fall injury risk factors in SWAN women (Ylitalo). Quadriceps strength will be related to incident fall injuries in Health ABC (Winger). Medicare payments will be compared pre- vs. post-injury for non-fracture and fracture fall injuries in Health ABC (Strotmeyer). The Discussant (Buchner) will focus on the importance of all fall injuries, including self- or outpatient-treated, as these may be early signs of late life decline.
A phase II trial of temsirolimus plus low-dose weekly carboplatin and paclitaxel for recurrent/metastatic HNSCC.

6019^ Background: The PI3K/mTOR pathway is commonly altered in HNSCC, but single agent activity of mTOR inhibitors is modest. Following up on encouraging results of a phase I study of temsirolimus ...
Prediction of Psychiatric Symptoms from Case History Information

A sample of 196 psychiatric case histories, taken from 11 categories, was analyzed in terms of a theoretical model for reducing case history information to defined constructs. A preliminary χ2 analysis isolated 25 case history predictor variables of greatest use in predicting 18 symptom groups. Discriminant functions were computed for each symptom separately which proved to be about 70% successful in predicting symptoms in the experimental group of 147 cases and the validation group of 49 cases. In general, the symptom range predicted by the model is verified. With the use of high speed computer programs, it seems feasible for the personnel of psychiatric institutions to standardize their own discriminant functions in line with their particular modes of interacting with patients.
The role of short-term memory impairment in nonword repetition, real word repetition, and nonword decoding: A case study

In a companion study, adults with dyslexia and adults with a probable history of childhood apraxia of speech showed evidence of difficulty with processing sequential information during nonword repetition, multisyllabic real word repetition and nonword decoding. Results suggested that some errors arose in visual encoding during nonword reading, all levels of processing but especially short-term memory storage/retrieval during nonword repetition, and motor planning and programming during complex real word repetition. To further investigate the role of short-term memory, a participant with short-term memory impairment (MI) was recruited. MI was confirmed with poor performance during a sentence repetition and three nonword repetition tasks, all of which have a high short-term memory load, whereas typical performance was observed during tests of reading, spelling, and static verbal knowledge, all with low short-term memory loads. Experimental results show error-free performance during multisyllabic real word repetition but high counts of sequence errors, especially migrations and assimilations, during nonword repetition, supporting short-term memory as a locus of sequential processing deficit during nonword repetition. Results are also consistent with the hypothesis that during complex real word repetition, short-term memory is bypassed as the word is recognized and retrieved from long-term memory prior to producing the word.
Intestinal, but not hepatic, ChREBP is required for fructose tolerance

Increased sugar consumption is a risk factor for the metabolic syndrome including obesity, hypertriglyceridemia, insulin resistance, diabetes, and nonalcoholic fatty liver disease (NAFLD). Carbohydrate responsive element-binding protein (ChREBP) is a transcription factor that responds to sugar consumption to regulate adaptive metabolic programs. Hepatic ChREBP is particularly responsive to fructose and global ChREBP-KO mice are intolerant to diets containing fructose. It has recently been suggested that ChREBP protects the liver from hepatotoxicity following high-fructose diets (HFrDs). We directly tested this hypothesis using tissue-specific ChREBP deletion. HFrD increased adiposity and impaired glucose homeostasis in control mice, responses that were prevented in liver-specific ChREBP-KO (LiChKO) mice. Moreover, LiChKO mice tolerated chronic HFrD without marked weight loss or hepatotoxicity. In contrast, intestine-specific ChREBP-KO (IChKO) mice rapidly lost weight after transition to HFrD, and this was associated with dilation of the small intestine and cecum, suggestive of malabsorption. These findings were associated with downregulation of the intestinal fructose transporter, Slc2a5, which is essential for fructose tolerance. Altogether, these results establish an essential role for intestinal, but not hepatic, ChREBP in fructose tolerance.
Association between the North Carolina Medical Board opioid guideline update and opioid prescriptions in Medicare Part D beneficiaries.

Objective: To examine if North Carolina (NC) opioid prescribing guidelines were associated with changes in opioid prescribing. Method: Retrospective secondary analysis of the Medicare Provider Utilization and Payment Data: Part D Prescriber datasets from 2013 to 2015. Participants: Providers who prescribed at least one opioid from 2013 to 2015 and paid by Medicare Part D. Main outcome measure: Per-prescriber Medicare-population adjusted number of analgesic opioid claims and per-prescriber average day supply. Generalized estimating equations (GEE) were used to analyze the data. Results: There were significantly higher per-prescriber Medicare adjusted opioid claims in 2014 compared to 2015 (p < 0.001) but no difference between 2013 and 2015 (p = 0.584). GEE results also indicated that there was a significant increase in 2015 in per-prescriber average day supply, compared to 2013 and 2014 (both p < 0.0001). Conclusions: State opioid prescribing guidelines published in mid-2014 may have slowed the escalation of numbers of opioid prescriptions in NC. Future research should examine whether the guidelines were associated with changes in morphine equivalent dosing in NC during the same timeframe.
Influence of Composted Wastewater Sludge (CWS) on Lead and Copper Uptake by Radish (Raphanus sativus L.)

AbstractThe potential risk of increased metal concentrations through the application of composted wastewater sludge (CWS) is of concern. In particular, the high affinity of composted wastewater sludge for metals such as Pb, may influence the extent of metal uptake by plants. In this study, a sequential extraction protocol was employed to determine the fractionation and bioavailability of Pb, Cu, Cr, Cd, Zn, Ni, and Fe in CWS. To evaluate the influence of CWS on metal uptake, a fast growing plant Raphanus sativus L. (cultivated radish), was grown in CWS amended with perlite at four different compositions (0, 25, 50, 75, 100% w/w) treated with Pb and Cu. Plants were harvested after 3 weeks and analyzed for Pb and Cu concentrations. The extent of metal uptake, and intercompetitions between Cu and Pb upon application, at pH 7.3 and 5.8 was also assessed. Best growth was apparent at 25% to 50% (w/w) CWS composition, while an increase in the pH lowered Pb and Cu concentrations in plant tissues. Higher metal con...
The Utility of the U.S. Department of Commerce to Small Businesses: An Empirical Study

This study empirically tried to determine whether small to medium-sized exporters and non-exporters in West Virginia were (a) familiar with the export-related services offered by the U.S. Department of Commerce, (b) whether they had used any of these services before, and (c) whether they were satisfied with the services they had used. The findings of the survey are reported in this paper.
The role of sensory innervation in cornea-lens regeneration.

BACKGROUND Numerous sensory nerves in the cornea contribute to normal tissue homeostasis. Interestingly, cells within the basal corneal epithelium can regenerate new lenses in the frog, Xenopus. In this study, we investigated whether cornea sensory nerves or their neuropeptides are important for supporting cornea-lens regeneration. RESULTS Attempts to sever the trigeminal nerve trunk, which provides sensory nerve branches to the cornea, did not inhibit lens regeneration. However, using this approach we found that it was not possible to completely disrupt sensory innervation, as these nerves are able to quickly regenerate back to the cornea. On the other hand, attenuation of neuropeptide levels with capsaicin was found to significantly inhibit lens regeneration, as visualized by a reduction of Substance P. These treatments also led to a reduction of cornea sensory innervation. Interestingly, inhibition of the Substance P-preferred receptor NK-1 with Spantide II did not affect lens-regeneration rates. CONCLUSIONS This study provides evidence that cornea nerves support cornea-lens regeneration, which could occur through the release of various neurotrophic factors. Substance P, however, does not appear to be the critical component of this signaling pathway. Further studies are needed to investigate what role other known neurotrophic factors may play in this process.
An Energy-Efficient Classifier via Boosted Spin Channel Networks

With diminishing energy and delay benefits via CMOS scaling, there is much interest in exploring the use of alternative state variables such as electronic spin. Multiple research efforts are underway exploring both Boolean and non-Boolean design space using spin devices in order to make their energy and delay benefits competitive to CMOS. In this paper, we propose spin channel networks (SCNs) — spin-based circuits that exploit exponential decay of spin current to efficiently realize multi-bit dot product computation. We show that proposed SCNs can be employed with adaptive boosting (AdaBoost) learning algorithm to efficiently realize a binary classifier for breast cancer detection. The proposed SCN implementation achieves 112× and 14× lower energy per decision compared to the conventional all spin logic (ASL) and 20nm CMOS designs, respectively, for identical decision throughput.
S-Nitrosylation: An Emerging Paradigm of Redox Signaling

Nitric oxide (NO) is a highly reactive molecule, generated through metabolism of L-arginine by NO synthase (NOS). Abnormal NO levels in mammalian cells are associated with multiple human diseases, including cancer. Recent studies have uncovered that the NO signaling is compartmentalized, owing to the localization of NOS and the nature of biochemical reactions of NO, including S-nitrosylation. S-nitrosylation is a selective covalent post-translational modification adding a nitrosyl group to the reactive thiol group of a cysteine to form S-nitrosothiol (SNO), which is a key mechanism in transferring NO-mediated signals. While S-nitrosylation occurs only at select cysteine thiols, such a spatial constraint is partially resolved by transnitrosylation, where the nitrosyl moiety is transferred between two interacting proteins to successively transfer the NO signal to a distant location. As NOS is present in various subcellular locales, a stress could trigger concerted S-nitrosylation and transnitrosylation of a large number of proteins involved in divergent signaling cascades. S-nitrosylation is an emerging paradigm of redox signaling by which cells confer protection against oxidative stress.
Technical Perspective: How Do Humans and Data Systems Establish a Common Query Language?

We all structure information in our brains: without structure, we would not be able to deal with the huge quantities of highly heterogenous information we process. However, each of us structures this information slightly differently, often leading to misunderstandings or requiring additional rounds of dialog to clarify. Database schema are also designed by humans. The structure imposed on the information by the schema reflects the human designers' perspective on the world, even if mediated through formal design techniques or computer software. Therefore, the structured data querying task can be viewed as having a schema mapping problem at its core: mapping between the "schema" the human has in her brain and the schema used to organize the database.
Nonlocal Subsystem Density Functional Theory

By invoking a divide-and-conquer strategy, subsystem DFT dramatically reduces the computational cost of large-scale, ab initio electronic structure simulations of molecules and materials. The centr...
Facile Accelerated Specific Therapeutic (FAST) Platform to Counter Multidrug-Resistant Bacteria

ABSTRACT Multidrug-resistant (MDR) bacteria pose a grave concern to global health. This problem is further aggravated by a lack of new and effective antibiotics and countermeasure platforms that can sustain the creation of novel antimicrobials in the wake of new outbreaks or evolution of resistance to antibiotics. To address this, we have developed a Facile Accelerated Specific Therapeutic (FAST) platform that can develop effective therapies against MDR bacteria within a week. Our FAST platform combines four essential modules- design, build, test, and delivery-of drug development cycle. The design module comprises a bioinformatics toolbox that predicts sequence-specific peptide nucleic acids (PNAs) that target non-traditional pathways and genes of bacteria in minutes. The build module constitutes in-situ synthesis and validation of selected PNAs in less than four days and efficacy testing within a day. As a proof of concept, these PNAs were tested against MDR clinical isolates. Here we tested Enterobacteriaceae including carbapenem-resistant Escherichia coli, extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae, New Delhi Metallo-beta-lactamase-1 carrying Klebsiella pneumoniae and MDR Salmonella enterica. PNAs showed significant growth inhibition for 82% of treatments, with nearly 18% of the treatments leading to more than 97% decrease. Further, these PNAs are capable of potentiating antibiotic activity in the clinical isolates despite presence of cognate resistance genes. Finally, FAST offers a novel delivery approach to overcome limited transport of PNAs into mammalian cells to clear intracellular infections. This method relies on repurposing the bacterial Type III secretion system in conjunction with a kill switch that is effective at eliminating 99.6% of an intracellular Salmonella infection in human epithelial cells. Our findings demonstrate the potential of the FAST platform in treating MDR bacteria in a rapid and effective manner.