cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancement of DNA ligase I level by gemcitabine in human cancer cells

Purpose: DNA ligase I is an essential enzyme for completing DNA replication and DNA repair by ligating Okazaki fragments and by joining single-strand breaks formed either directly by DNA-damaging agents or indirectly by DNA repair enzymes, respectively. In this study, we examined whether the DNA ligase I level could be modulated in human tumor cell lines by treatment with gemcitabine (2′, 2′-difluoro-2′-deoxycytidine), which is a nucleoside analogue of cytidine with proven antitumor activity against a broad spectrum of human cancers in clinical studies. Experimental Design: To determine the effect of gemcitabine on DNA ligase I expression, Western blot analysis was used to measure the DNA ligase I levels in MiaPaCa, NGP, and SK-N-BE cells treated with different concentrations of gemcitabine and harvested at different time intervals. Cell cycle analysis was also performed to determine the underlying mechanism of DNA ligase I level enhancement in response to gemcitabine. In addition, other agents that share the same mechanism of action with gemcitabine were used to elucidate further details. Results: When different types of tumor cell lines, including MiaPaCa, NGP, and SK-N-BE, were treated with gemcitabine, the level of DNA ligase I increased severalfold despite significant cell growth inhibition. In contrast, other DNA ligases (III and IV) either remained unchanged or decreased with treatment. Cell cycle analysis showed that arrest in S-phase corresponded to an increase of DNA ligase I levels in gemcitabine treated cells. Other agents, such as 1-β-d-arabinofuranosylcytosine and hydroxyurea, which partly share mechanisms of action with gemcitabine by targeting DNA polymerases and ribonucleotide reductase, respectively, also caused an increase of DNA ligase I levels. However, 5-fluorouracil, which predominantly targets thymidylate synthase, did not cause an increase of DNA ligase I level. Conclusions: Our results suggest that an arrest of DNA replication caused by gemcitabine treatment through incorporation of gemcitabine triphosphate into replicating DNA and inhibition of ribonucleotide reductase would trigger an increase in DNA ligase I levels in cancer cells. The elevated presence of DNA ligase I in S-phase-arrested cells leads us to speculate that DNA ligase I might have an important role in repairing DNA damage caused by stalled replication forks.
Inferring the Number of Contributors to Mixed DNA Profiles

Forensic samples containing DNA from two or more individuals can be difficult to interpret. Even ascertaining the number of contributors to the sample can be challenging. These uncertainties can dramatically reduce the statistical weight attached to evidentiary samples. A probabilistic mixture algorithm that takes into account not just the number and magnitude of the alleles at a locus, but also their frequency of occurrence allows the determination of likelihood ratios of different hypotheses concerning the number of contributors to a specific mixture. This probabilistic mixture algorithm can compute the probability of the alleles in a sample being present in a 2-person mixture, 3-person mixture, etc. The ratio of any two of these probabilities then constitutes a likelihood ratio pertaining to the number of contributors to such a mixture.
Modeling and feedback control of nonholonomic mobile vehicles

A complete dynamic model of mobile vehicles moving on nonplanar surfaces under nonholonomic and dynamic constraints is presented. The kinematic control of such systems is examined, and the invariant manifold technique is introduced for steering a nonholonomic mobile vehicle to an invariant manifold which is relatively locally-locally controllable. A closed-loop control strategy based on the invariant manifold technique is formulated and applied to the control of nonholonomic vehicles. Tracking control of such vehicles is demonstrated with both holonomic and nonholonomic reference trajectories. >
Proof-Load Determination for Pressure Vessels Wound with Aramid Fiber

The paper presents a method of determining the proof pressure that can guarantee a design lifetime for Kevlar-49/epoxy pressure vessels. The method is based on the assumption that, when taken from the same population, a statically strong vessel is also strong in stress rupture. The lifetime data available at higher pressures are extrapolated to estimate the lifetime distributions at lower pressures. In so doing, we assume that the lifetime distribution is exponential and that the characteristic lifetime is related exponentially to the applied pressure divided by the average burst pressure. Two examples are given to illustrate the method.
Optimal timing of chemotherapy in androgen independent prostate cancer

Abstract Purpose To interpret available docetaxel clinical trial data in order to define optimal timing of the initiation of chemotherapy in androgen independent prostate cancer (AIPC). Materials and methods Published literature on the natural history of nonmetastatic AIPC was reviewed. Phase III clinical trials using docetaxel-based therapy were analyzed as well as their associated quality of life (QOL) findings. Trials using docetaxel in earlier stage of the disease, as well those using novel agents were examined. Results Based on one report, non-metastatic AIPC is relatively indolent, and there is currently no evidence that supports the use of chemotherapy in this disease subset. The results of TAX 327 and SWOG 9916 demonstrate that chemotherapy is indicated for metastatic AIPC. However, based on available data, more than one hormonal maneuver can be offered to patients before chemotherapy is initiated. Timing of docetaxel therapy can further be individualized based on risk, clinical status, and patients' values and preferences. Building on the success of docetaxel, several novel agents that target different pathways are being tested in combination with, or as an alternative to, docetaxel-based therapy in Phase III clinical trials. Conclusions Currently, docetaxel therapy should be reserved for patients with metastatic AIPC who have progressed despite one or more hormonal therapies. In most patients, more than one hormonal treatment can be offered before chemotherapy is initiated. Studies that test the efficacy of chemotherapy early in the natural history of prostate cancer are under way or are planned.
R-Card fence applications for indoor anechoic chamber

It is shown in this paper that properly designed R-Card fences can be installed in indoor measurement facility to reduce the multipath signals in the chamber. The design is especially more effective when the transmit antenna is closer to the absorber wall. The traditional foam absorber works well when the angle of incidence is less than 50 degrees if the thickness is about 2 wavelengths. The R-Card fences greatly improve the chamber performance when the angle of incidence is greater than 50 degrees. Furthermore, it may be possible to use smaller size of absorber (less than 2 wavelengths) with the R-Card fence when the overall chamber size is limited. It is then possible to measure larger size of AUT/UUT in an existing chamber as well as extend the frequency range of the chamber to the lower end.
Ring H/hydroxyl H scrambling before loss of water from salicylic acid molecular ions

Scrambling before formation of the [M — 18] ion from salicylic acid is considerably reduced in comparison with scrambling before formation of the [M — 17] ion from benzoic acid.
Estimated paediatric mortality associated with influenza virus infections, United States, 2003-2010.

Abstract Death certificate reports and laboratory-confirmed influenza deaths probably underestimate paediatric deaths attributable to influenza. Using US mortality data for persons aged <18 years who died during 28 September 2003 to 2 October 2010, we estimated influenza-attributable deaths using a generalized linear regression model based on seasonal covariates, influenza-certified deaths (deaths for which influenza was a reported cause of death), and occurrence during the 2009 pandemic period. Of 32 783 paediatric deaths in the death categories examined, 853 (3%) were influenza-certified. The estimated number of influenza-attributable deaths over the study period was 1·8 [95% confidence interval (CI) 1·3-2·8] times higher than the number of influenza-certified deaths. Influenza-attributable deaths were 2·1 (95% CI 1·5-3·4) times higher than influenza-certified deaths during the non-pandemic period and 1·1 (95% CI 1·0-1·8) times higher during the pandemic. Overall, US paediatric deaths attributable to influenza were almost twice the number reported by death certificate codes in the seasons prior to the 2009 pandemic.
Process centered displays and cognitive models for command applications

The purpose of this paper is to discuss the theoretical and operational considerations for knowledge representation using process-centered display concepts for modern military applications. The command and control environment of an Army maneuver brigade is described in enough detail to establish its inherent complexity. Theoretical models of human knowledge are contrasted to perceptual principles of display representation and the importance of process knowledge for command decision making is discussed. After defining the elements of a process-centered display environment, a general experimental framework is proposed to ensure the scientific validity as well as the operational usefulness of the display concepts being developed.
Space-charge transport limits of ion beams in periodic quadrupole focusing channels

It has been empirically observed in both experiments and particle-in-cell simulations that space-charge-dominated beams suffer strong growth in statistical phase-space area (degraded quality) and particle losses in alternating gradient quadrupole transport channels when the undepressed phase advance {sigma}{sub 0} increases beyond about 85{sup o} per lattice period. Although this criterion has been used extensively in practical designs of strong focusing intense beam transport lattices, the origin of the limit has not been understood.We propose a mechanism for the transport limit resulting from classes of halo particle resonances near the core of the beam that allow near-edge particles to rapidly increase in oscillation amplitude when the space-charge intensity and the utter of the matched beam envelope are both sufficiently large. When coupled with a diffuse beam edge and/or perturbations internal to the beam core that can drive particles outside the edge, this mechanism can result in large and rapid halo-driven increases in the statistical phase-space area of the beam, lost particles, and degraded transport. A core-particle model is applied to parametrically analyze his process. Extensive self-consistent particle in cell simulations are employed to better quantify space-charge limit and verify core-particle model predictions.
Active Contour Texture Segmentation in Modulus Wavelet Feature Spaces

In this paper we discuss a model that is able to segment textures using active contours. Our technique is based on active contour techniques using curve evolution. We build our model on properties of human vision, in that we segment the textures in a certain feature space. We will show the advantages of using modulus feature spaces. Wavelet coefficients are shown to exhibit local features both in space and frequency domains. We will implement our model in modulus wavelet subbands.
May I Interrupt? The effect of SPAM Probe Questions on Air Traffic Controller Performance☆

Abstract The use of probe questions for measuring situation awareness is often regarded as being intrusive on operator performance and workload (Pierce, 2012). Moreover, the probe questions themselves may change the operator's situation awareness. However, the intrusive effects of probe questions can be diminished through optimized presentation and collection of responses (Bacon & Strybel, 2013). The present study analyzed data from a large sample of 54 student controllers to determine whether an optimized presentation method for administering Situation Present Assessment Method (SPAM) probe questions negatively impacted the students’ workload or performance. Results were consistent with prior research (e.g., Bacon & Strybel, 2013) showing that probe questions were not intrusive and could be used as a method for measuring SA in experimental studies.
Determination of in Vivo Enzyme Occupancy Utilizing Inhibitor Dissociation Kinetics.

During drug discovery, assessment of in vivo target occupancy by therapeutic candidates is often required for predicting clinical efficacy. Current strategies for determining target occupancy include using radiolabeled or irreversible surrogates, which can be technically challenging, and the results are often not sufficiently quantitative. We developed a straightforward method by applying slow-dissociation kinetics to quantitatively determine enzyme occupancy without using specialized reagents. We applied this method to determine occupancy of Cathepsin K inhibitors in bone tissues harvested from rabbit femurs. Tissues from dosed animals were harvested, flash frozen, lysed, then analyzed by a jump-dilution assay with substrate. The rate of substrate turnover was monitored continuously until reaching steady state and progress curves were fit with the equation [product] = vst + ((vi – vs)/kobs)(1 – exp(−kobst)). The initial rate vi represents the residual activity of the enzyme before inhibitor dissociation;...
The preventive services use self-efficacy (PRESS) scale in older women: development and psychometric properties.

Preventive services offered to older Americans are currently under-utilized despite considerable evidence regarding their health and economic benefits. Individuals with low self-efficacy in accessing these services need to be identified and provided self-efficacy enhancing interventions. Scales measuring self-efficacy in the management of chronic diseases exist, but do not cover the broad spectrum of preventive services and behaviors that can improve the health of older adults, particularly older women who are vulnerable to poorer health and lesser utilization of preventive services. This study aimed to evaluate the psychometric properties of a new preventive services use self-efficacy scale, by measuring its internal consistency reliability, assessing internal construct validity by exploring factor structure, and examining differences in self-efficacy scores according to participant characteristics. The Preventive Services Use Self-Efficacy (PRESS) Scale was developed by an expert panel at the University of Pittsburgh Center for Aging and Population Health - Prevention Research Center. It was administered to 242 women participating in an ongoing trial and the data were analyzed to assess its psychometric properties. An exploratory factor analysis with a principal axis factoring approach and orthogonal varimax rotation was used to explore the underlying structure of the items in the scale. The internal consistency of the subscales was assessed using Cronbach’s alpha coefficient. The exploratory factor analysis defined five self-efficacy factors (self-efficacy for exercise, communication with physicians, self-management of chronic disease, obtaining screening tests, and getting vaccinations regularly) formed by 16 items from the scale. The internal consistency of the subscales ranged from .81 to .94. Participants who accessed a preventive service had higher self-efficacy scores in the corresponding sub-scale than those who did not. The 16-item PRESS scale demonstrates preliminary validity and reliability in measuring self-efficacy in the use of preventive services among older women. It can potentially be used to evaluate the impact of interventions designed to improve self-efficacy in the use of preventive services in community-dwelling older women.
Biofeedback therapy for defecatory dysfunction: "real life" experience.

Background:Biofeedback therapy (BF) is a well-established treatment modality for patients with dyssynergic defecation and fecal incontinence (FI). Randomized controlled trials from highly specialized tertiary care centers report response rates of 70% to 80% for dyssynergic defecation and 55% to 75%
An Experimental Study of the Rudimentary Landing Gear

Fluid dynamic and aeroacoustic wind tunnel experiments are performed on a rudimentary landing gear model. The primary objective of these tests is to provide a set of acoustic data for verification of computational fluid dynamic and aeroacoustic simulations. Data acquired include mean and fluctuating surface pressures and acoustic measurements obtained by a linear array of 10 free-field microphones. Two primary configurations are tested, the first with one side bounded by a large aluminum baffle plate on the wing side of the model and the second with the plate removed. Mean surface pressure and acoustic measurements are obtained at speeds from Mach 0.09 up to Mach 0.18 and fluctuating surface pressures are obtained up to Mach 0.12. Surface pressure measurements are compared to data acquired by the National Aerospace Laboratories in a closed-jet wind tunnel. Similar trends are obtained with noticeable differences occurring due to the differences between the openand closed-jet configurations. Analysis of the acoustic data show that the bounding plate acts as a significant reflection source. The far-field sound pressure levels for either case do not scale with Mach number to the 6 th power or Strouhal number alone, but do collapse well when both scaling parameters are applied together.
A Study of the Content of Professional Courses in Physical Education

(1939). A Study of the Content of Professional Courses in Physical Education. Research Quarterly. American Association for Health, Physical Education and Recreation: Vol. 10, No. 2, pp. 78-83.
The Impact of Media on Traditional Communities

This editorial provides a brief historical overview of research on the impact of media on traditional communities, and introduces the articles featured in this issue.
Helping them cope.

1. Self-help groups for individuals with sarcoidosis (a noncontagious multisystem disorder characterized by granulomas in many organs) are rare despite the physical and emotional problems associated with this disease. 2. The stimulus for the development of the group arose when staff in a pulmonary clinic identified that sarcoidosis patients were helping each other cope with problems and concerns related to their disease and feelings of isolation. 3. Nurses play a significant role in creating vehicles of help and service to facilitate and support patients experiencing fear and anxiety about their disease. Nurses must recognize the role self-help groups play in assisting individuals to maintain their quality of life as they adapt to the psychosocial, physiological, and medical aspects of their illness.
Co-Opting the Genetic Redundancy of the Pax Family to Treat PAX5 Mutated Pre-B ALL

Pre-B cell ALL is the most common pediatric malignancy. More than a third of cases acquire loss-of-function mutations of PAX5 , a regulatory transcription factor which is required for the differentiation of B lymphocytes. Additionally, germline loss of function PAX5 mutation is a cause of familial pre-B cell ALL. These observations indicate that loss of PAX5 activity drives leukemogenesis. We have seen that PAX5 re-expression in PAX5 -mutated pre-B cell ALL restores differentiation capacity and promotes apoptosis. However, because the gene is deleted or otherwise mutated it may not be possible to easily repair or restore PAX5 expression in leukemic cells. Nevertheless, PAX5 possesses two closely related paralogs, PAX2 and PAX8 , which are structurally and functionally similar to PAX5, yet are neither expressed in lymphocytes nor mutated in ALL. Toward the goal of exploiting PAX family genomic redundancy for therapeutic purposes, we have tested the ability of PAX2 and PAX8 to replace PAX5 in pre-B ALL cell lines. Preliminary results indicate that both PAX2 and PAX8 rescue B cell differentiation and function similarly to PAX5 in this context. These results include modulation of B cell developmental markers, CD10, CD19 and CD22, as well as induction of PAX5 target genes, CD79a and BACH2 . Cells also display a reduction in size which may be indicative of the large to small B cell transition and importantly show increased levels of cell death following PAX2 and PAX8 expression. We have further investigated the epigenetic status of PAX2 and PAX8 promoters in B cells and find that both loci are hypermethylated, suggesting that demethylation with agents such as methotrexate, may represent a therapeutic entry point for activating expression of PAX5 paralogs. Finally, based on observations that electrical polarization during early embryogenesis regulates developmental transcription factor expression, including for PAX genes, we have tested the ability of approved drugs targeting ion channels for their ability to induce PAX factor expression and thereby complement for loss of PAX5 in pre-B cell ALL. The anti-parasitic drug ivermectin, which activates chloride channels, is one of several compounds that appear promising in early studies. Disclosures No relevant conflicts of interest to declare.
Evidence for the Role of Biologically Active Exosomes in Acute Myeloid Leukemia Relapse

Abstract Introduction: Despite of the notable achievements of multi-modality treatments in patients with acute myeloid leukemia (AML), leukemic relapse remains a formidable clinical challenge. Studies in AML patients have shown that tumor-induced impairments of immune cells contribute to leukemia progression. One recently identified immunosuppressive mechanism operating in AML is the release by leukemia blasts of virus-size (30-100nm) membrane-bound vesicles called exosomes. We have reported that plasma of patients with newly-diagnosed AML prior to any therapy contains higher levels of exosomal proteins than that of normal donors. AML exosomes carry an immunosuppressive cargo, including membrane-associated TGF-β1, MICA/MICB and markers of myeloid blasts. We hypothesize that persistence of these exosomes may contribute to the high relapse rates seen in AML. Methods: Venous blood (20-50 mL) was obtained from patients newly diagnosed with AML prior to any treatment, from AML patients who achieved CR following initial therapy and from age-matched healthy volunteers (NC). Exosome fractions were isolated from plasma by using mini-size exclusion chromatography with Sepharose 2A. Exosome protein levels, numbers and size of exosomes (qNano) and their morphology by transmission electron microscopy were determined. Exosomes were characterized by western blots for expression of exosome markers, Tsg101 and CD81, and myeloid cell-surface markers associated with AML, interleukin-3 receptor alpha chain (CD123) and C-type lectin-like molecule-1 (CLL-1), CD44 and CD96. Isolated normal human NK cells were co-incubated with AML exosomes and multiparameter flow cytometry was used to monitor changes in expression levels (mean fluorescence intensity) of NKG2D on NK cells. Results: Exosome fractions isolated from AML patients' plasma at diagnosis (n=16) had higher mean protein content than fractions obtained from NC plasma (96 vs 37 µg protein/mL plasma, p=0.03). In exosome fractions isolated from plasma of AML patients in CR (n=13) protein levels remained elevated (mean value=120 µg protein/mL plasma) at the time when leukemic blasts were undetectable in the bone marrow by conventional hematopathological methods. AML exosomes in patients in CR carried blast markers, CD123, CLL-1, CD44, CD96 and were enriched in TGF-β1. Co-incubation of these exosomes with activated NK cells resulted in down-regulation of NKG2D expression with a concomitant reduction of NK-cell cytotoxicity. Ten/13 AML patients in CR whose plasma exosome levels remained elevated eventually relapsed. Conclusion: The persistently elevated levels of biologically-active TGF-β1+ exosomes carrying leukemia blast markers in plasma of AML patients in CR impair anti-leukemia immune responses and might contribute to leukemia relapse. Disclosures No relevant conflicts of interest to declare.
Parameter optimization for transitions between memory states in small arrays of Josephson junctions

Coupled arrays of Josephson junctions possess multiple stable zero voltage states. Such states can store information and consequently can be utilized for cryogenic memory applications. Basic memory operations can be implemented by sending a pulse to one of the junctions and studying transitions between the states. In order to be suitable for memory operations, such transitions between the states have to be fast and energy efficient. In this paper we employed simulated annealing, a stochastic optimization algorithm, to study parameter optimization of array parameters which minimizes times and energies of transitions between specifically chosen states that can be utilized for memory operations (Read, Write, and Reset). Simulation results show that such transitions occur with access times on the order of 10–100 ps and access energies on the order of 10−19–5×10−18 J. Numerical simulations are validated with approximate analytical results.
How to Develop Faculty Mentors

The absence of financial incentives is a major obstacle to developing faculty mentors. Structured approaches are needed to develop faculty mentors. Recruiting individuals with vested interests, providing protected time, and monetary and career incentives will help develop faculty mentors. Structured written evaluation and objective verbal feedback are mandatory for optimal development of faculty mentors. There are resolvable and irresolvable causes of faculty discontent. Current needs to develop faculty mentors provide opportunities for research.
Marriage Equality, Parentage (In)Equality

Recently, several quite distinguished commentators have asked how, if at all, the U.S. Supreme Court will speak, after its same sex marriage ruling in Obergefell v. Hodges, to interstate inequalities involving the federal constitutional rights of childcaring parents. Specifically, Professor Mayeri notes in the Yale Law Journal that today the “constitutional law of the family stands at a critical turning point,” leaving us to ponder whether the “advent of marriage equality,” which “disrupted conventional definitions of parenthood” by demoting “marriage and biology in favor or a more intent-based and functional criteria,” will heighten or diminish the federal “constitutional significance of marital status” in parentage matters. Professor NeJamie worries in the Harvard Law Review that Obergefell “may reduce incentives to achieve laws that recognize unmarried, nonbiological parents,” though there is the “potential” for it to “yield more robust recognition for some unmarried parents.” And Dean Murray, while recognizing this “potential,” worries in the California Law Review that Obergefell may not be read to “sanction and facilitate … methods of family formation … that credit nonmarriage.” Obergefell did not directly address any issues involving national parentage equality. It is not likely that the ruling will prompt the U.S. Supreme Court to address national parentage equality any time soon. The Court has historically deferred to state parentage laws while recognizing their significant interstate variations. While interstate parental childcare equality issues are important, they pale in significance to issues of intrastate equality for marital and biological parents, as well as for nonmarital, nonbiological, nonadoptive parents who care for children and who are often deemed de facto or presumed parents, which can include grandparents and/or stepparents. In the article I offer a few thoughts on intrastate parental childcare equality after explaining why interstate inequalities will likely remain unaddressed by the U.S. Supreme Court.
A methodology for hierarchical thermal simulation of ICs from gate-level to architecture design

Thermal simulations for semiconductor chip design at different levels are usually based on simplified models with severe assumptions due to intensive computational effort needed in numerical simulations. This work presents a unique methodology based on proper orthogonal decomposition, together with the concept of building block, that is able to substantially reduce the numerical degree of freedom in thermal simulation of semiconductor IC structure with different spatial resolutions. Such an approach could offer efficient multi-scale hierarchical thermal simulations for cost-effective thermal-aware design of semiconductor chips at different levels.
The Effect of Temperature on Moisture Transport in Concrete

Most concrete structures and buildings are under temperature and moisture variations simultaneously. Thus, the moisture transport in concrete is driven by the moisture gradient as well as the temperature gradient. This paper presents an experimental approach for determining the effect of different temperature gradients on moisture distribution profiles in concrete. The effect of elevated temperatures under isothermal conditions on the moisture transport was also evaluated, and found not to be significant. The non-isothermal tests show that the temperature gradient accelerates the moisture transport in concrete. The part of increased moisture transfer due to the temperature gradient can be quantified by a coupling parameter DHT, which can be determined by the present test data. The test results indicated that DHT is not a constant but increases linearly with the temperature variation. A material model was developed for DHT based on the experimental results obtained in this study.
“I Shut the Door”: Interactions, tensions, and negotiations from a location-based social app:

Location-based social apps leverage mobile phones to provide face-to-face (FtF) social opportunities for physically proximate individuals, such as finding nearby people to socialize, date, or hook ...
C-H Insertions by Iron Porphyrin Carbene: Basic Mechanism and Origin of Substrate Selectivity.

Recent experimental reports of heme carbene C-H insertions show promising results for sustainable chemistry due to good yield and selectivity, low cost of iron, and low/no toxicity of hemes. But mechanistic details are mostly unknown. Despite structural similarity and isoelectronic nature between heme carbene and the FeIV =O intermediate, our quantum chemical studies with detailed geometric and electronic information for the first time reveal an FeII -based, concerted, hydride-transfer mechanism, which is different from the FeIV -based stepwise hydrogen atom transfer mechanism for C-H functionalization by native heme enzymes. A trend of broad range experimental C-H insertion yields (0-88 %) of five different C-H bonds, including mostly non-functionalized moieties, was well reproduced. Results suggest that the substrate selectivity originates from the hydride formation capability. The predicted kinetic isotope effects were also in excellent agreement with experiment. Useful geometry, charge, and energy parameters well correlated with barriers were reported. These results provide the first theoretical evidence that carbene formation is the overall rate-limiting step, and suggest a key role of the formation of strong electrophilic heme carbene in developing heme-based C-H insertion catalysts and biocatalysts.
High Dietary Protein Intake and Protein-Related Acid Load on Bone Health

Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.
GW100: Comparison of Methods and Accuracy of Results Obtained with the WEST Code.

The reproducibility of calculations carried out within many-body perturbation theory at the G0W0 level is assessed for 100 closed shell molecules and compared to that of density functional theory. We consider vertical ionization potentials (VIP) and electron affinities (VEA) obtained with five different codes: BerkeleyGW, FHI-aims, TURBOMOLE, VASP, and WEST. We review the approximations and parameters that control the accuracy of G0W0 results in each code, and we discuss in detail the effect of extrapolation techniques for the parameters entering the WEST code. Differences between the VIP and VEA computed with the various codes are within ∼60 and ∼120 meV, respectively, which is up to four times larger than in the case of the best results obtained with DFT codes. Vertical ionization potentials are validated against experiment and CCSD(T) quantum chemistry results showing a mean absolute relative error of ∼4% for data obtained with WEST. Our analysis of the differences between localized orbitals and plane-...
The Highway Beautification Act: Towards improving efficiency of the Federal Outdoor Advertising Control Program

Abstract The Highway Beautification Act, signed in 1965, aims to establish an effective control of the outdoor advertising signs, devices, and displays that are located in a close proximity to the National Interstate System. The Act imposes requirements for specific types of advertising signs, including on-property signs, directional and official signs, and new signs in commercial and industrial areas. Over the years, many issues have been surrounding the Highway Beautification Act, such as attitude and relationship issues, organizational issues, and substantive issues. In order to address the aforementioned issues, this study performs a comprehensive survey among the State Departments of Transportation. Throughout the survey, the data are gathered using a detailed questionnaire, which captures the major aspects of the Federal Outdoor Advertising Control Program. All 50 States and District of Columbia participated in the study. Based on analysis of the collected data, the key regulatory difficulties and inconsistencies, associated with outdoor advertising signs, are determined. A set of baseline standards is proposed to assist the State and Federal agencies with resolving the identified regulatory difficulties and inconsistencies, including the following: lack of uniform requirements in terms of spacing, size, and lighting for advertising signs; clear definition of the areas for effective control; challenges related to the new technologies implementation for outdoor advertising; maintenance and continuation of nonconforming signs; vegetation control challenges; and others. Findings from the conducted survey and the proposed baseline standards are expected to improve effectiveness of the Federal Outdoor Advertising Control Program implementation across the nation.
Solving partial differential equations using ILLIAC IV

The solution of the Benard-Rayleigh convection problem using ILLIAC IV is reviewed and comments about solving partial differential equations using this computer are made. This includes a brief look at possible uses of parallelism in designing arithmetic logic units, at the Institute for Advanced Computations, at the ARPA communications network and at the ILLIAC IV. An explicit solution of the prognostic convection equations is considered and the use of iterative and direct methods for solving the Poisson streamfunction equation discussed. Storage considerations are emphasized. Closing remarks on algorithmic parallelism, others using ILLIAC and I-O and programming language considerations for ILLIAC are included.
Cerebral Atrophy and Leukoencephalopathy Following Cranial Irradiation

The delayed adverse neurologic sequelae of radiation therapy, including radiation leukoencephalopathy, hydrocephalus, and cerebral atrophy, represent an increasingly important problem as advances in cancer therapy lead to prolonged patient survival. A variety of pathophysiologic mechanisms for late radiation injury have been proposed, including neurovascular injury, impaired neurogenesis secondary to neural progenitor cell injury, and inflammatory changes. Patient age and comorbidities, as well as radiation dose schedule and the use of concurrent chemotherapy, all appear to be important determinants of long-term outcome. Leukoencephalopathy, or diffuse white matter injury, is associated with progressive and irreversible neurocognitive decline, as well as personality changes, neuropsychiatric abnormalities, Parkinsonism, tremor, and seizures. Hydrocephalus is a common sequela, leading to cognitive impairment, gait instability and urinary incontinence. Radiation therapy is also known to result in progressive brain volume loss, with particular vulnerability in regions associated with higher-order cognitive performance and endogenous neural repair mechanisms. Management strategies are supportive, including CSF diversion in cases of hydrocephalus and neurostimulants and acetylcholinesterase inhibitors in radiation-associated dementia. More work on strategies aimed at neuroprotection and brain repair is needed to serve this growing patient population.
Design Researchers Leading Interdisciplinary Teams

This special issue of Disena seeks to articulate and describe interdisciplinary examples of design-led research, posing questions such as: in what ways are such projects addressing matters of concern, what are the defining traits of such projects, and what has design brought that other disciplines could not? What legitimates the designer as a leader? What authority, expertise, or qualifications must a designer possess to lead? What is the tradeoff between a specific ability to form knowledge and an ability to assemble discrete pieces into a unified whole? What are the design methods or strategies used in research? And, are these methods succinctly defined at the commencing of a project or developed as the research unfolds?
Beta-blockers and physical frailty in patients with end-stage liver disease.

Author(s): Kuo, Selena Z; Lizaola, Blanca; Hayssen, Hilary; Lai, Jennifer C | Abstract: AimTo investigate beta-blocker (BB) use in patients with cirrhosis and determine their effects on physical frailty and overall survival.MethodsAdult outpatients with cirrhosis listed for liver transplantation underwent testing of physical frailty using the performance-based Liver Frailty Index, comprised of chair stands, grip strength, and balance testing, as well as self-reported assessments of exhaustion and physical activity. BB use was assessed from medical chart review. Univariable and multivariable logistic regression were performed to determine BB use and their association with measures of physical frailty. Competing risk analyses were performed to determine the effect of BB use on wait-list mortality, as defined by death or delisting for being too sick for transplant.ResultsOf 344 patients, 35% were female, median age was 60, median model for end stage liver disease was 15, and 53% were prescribed a BB. Compared to those not on BB, patients on BB were similar except for percentage female (25% vs 46%; P l 0.001) and BMI (29 vs 28; P = 0.008). With respect to tests of physical frailty, BB use was not associated with increased odds of frailty (by the Liver Frailty Index), exhaustion, or low physical activity. BB use was, however, significantly associated with a decreased adjusted risk of mortality (SHR 0.55; P = 0.005).ConclusionIn patients with cirrhosis awaiting liver transplantation, BB use is not associated with physical frailty. We confirmed the known survival benefits with BB use, and concerns about adverse effects should not deter their utilization when indicated.
HSPB5 engages multiple states of a destabilized client to enhance chaperone activity in a stress-dependent manner

Small heat shock proteins (sHSPs) delay protein aggregation in an ATP-independent manner by interacting with client proteins that are in states susceptible to aggregation, including destabilized states related to cellular stress. Up-regulation of sHSPs under stress conditions supports their critical role in cellular viability. Widespread distribution of sHSPs in most organisms implies conservation of function, but it remains unclear whether sHSPs implement common or distinct mechanisms to delay protein aggregation. Comparisons among various studies are confounded by the use of different model client proteins, different assays for both aggregation and sHSP/client interactions, and variable experimental conditions used to mimic cellular stress. To further define sHSP/client interactions and their relevance to sHSP chaperone function, we implemented multiple strategies to characterize sHSP interactions with α-lactalbumin, a model client whose aggregation pathway is well defined. We compared the chaperone activity of human αB-crystallin (HSPB5) with HSPB5 variants that mimic states that arise under conditions of cellular stress or disease. The results show that these closely related sHSPs vary not only in their activity under identical conditions but also in their interactions with clients. Importantly, under nonstress conditions, WT HSPB5 delays client aggregation solely through transient interactions early in the aggregation pathway, whereas HSPB5 mutants that mimic stress-activated conditions can also intervene at later stages of the aggregation pathway to further delay client protein aggregation.
An Analytical Bond Order Potential for Mg−H Systems

Magnesium-based materials provide some of the highest capacities for solid-state hydrogen storage. However, efforts to improve their performance rely on a comprehensive understanding of thermodynamic and kinetic limitations at various stages of (de)hydrogenation. Part of the complexity arises from the fact that unlike interstitial metal hydrides that retain the same crystal structures of the underlying metals, MgH2 and other magnesium-based hydrides typically undergo dehydrogenation reactions that are coupled to a structural phase transformation. As a first step towards enabling molecular dynamics studies of thermodynamics, kinetics, and (de)hydrogenation mechanisms of Mg-based solid-state hydrogen storage materials with changing crystal structures, we have developed an analytical bond order potential for Mg-H systems. We demonstrate that our potential accurately reproduces property trends of a variety of elemental and compound configurations with different coordinations, including small clusters and bulk lattices. More importantly, we show that our potential captures the relevant (de)hydrogenation chemical reactions 2H (gas)→H2 (gas) and 2H (gas)+Mg (hcp)→MgH2 (rutile) within molecular dynamics simulations. This verifies that our potential correctly prescribes the lowest Gibbs free energies to the equilibrium H2 and MgH2 phases as compared to other configurations. It also indicates that our molecular dynamics methods can directly reveal atomic processes of (de)hydrogenation of the Mg-H systems.
Students' Conceptions of and Feelings about Land Use: Building a Conceptual Framework for Teaching and Learning about Land Use.

AbstractThe purpose of this study was to investigate students’ conceptions of and feelings about land use. Specifically: (1) What are students’ conceptions of and feelings about land use? And (2) i...
Contrast between Vitamin-Responsive Inherited Metabolic Diseases and Vitamin Use in Schizophrenia

I am not a psychiatrist. I am an internist and a medical geneticist who has become interested in the question of the use of large doses of vitamins in the therapy of schizophrenia because of my involvement with a number of inherited metabolic diseases which I would like to tell you about briefly. In 1954, Hunt and his colleagues described two female siblings with neonatal convulsions whose seizure disorder was not controlled by the usually prescribed anticonvulsants or by physiologic doses of pyridoxine. When these girls were given 10 to 20 times the physiologic requirement, however, seizures stopped abruptly and recurred only after cessation of the pyridoxine supplements. This pattern of seizure control by large amounts of pyridoxine followed by exacerbation after vitamin withdrawal led Hunt to propose that these children were “dependent” on increased amounts of pyridoxine to prevent central nervous system hyperactivity. Thus, the concept of vitamin-dependent metabolic disorders was born. It is interesting, I think, to note that Hunt’s study was reported at about the same time that Dr. Osmond first suggested that nicotinic acid was beneficial in schizophrenia. Since these early observations, the two fields of “vitamin-responsive” or “vitamin-dependent” inborn metabolic disorders and so-called “megavitamin-responsive” schizophrenia have followed very divergent courses. I shall underscore this divergence by first summarizing the pattern of investigation followed in the vitamin-responsive inborn errors of metabolism.
Person-Environment Fit at Work: Relationships with Workplace Behaviours.

The fit between the values of an individual and the work environment (person–organisation fit) is related to organisational citizenship behaviours and counterproductive work behaviours. Research ha...
Forecasting Seasonal Vibrio parahaemolyticus Concentrations in New England Shellfish.

Seafood-borne Vibrio parahaemolyticus illness is a global public health issue facing resource managers and the seafood industry. The recent increase in shellfish-borne illnesses in the Northeast United States has resulted in the application of intensive management practices based on a limited understanding of when and where risks are present. We aim to determine the contribution of factors that affect V. parahaemolyticus concentrations in oysters (Crassostrea virginica) using ten years of surveillance data for environmental and climate conditions in the Great Bay Estuary of New Hampshire from 2007 to 2016. A time series analysis was applied to analyze V. parahaemolyticus concentrations and local environmental predictors and develop predictive models. Whereas many environmental variables correlated with V. parahaemolyticus concentrations, only a few retained significance in capturing trends, seasonality and data variability. The optimal predictive model contained water temperature and pH, photoperiod, and the calendar day of study. The model enabled relatively accurate seasonality-based prediction of V. parahaemolyticus concentrations for 2014–2016 based on the 2007–2013 dataset and captured the increasing trend in extreme values of V. parahaemolyticus concentrations. The developed method enables the informative tracking of V. parahaemolyticus concentrations in coastal ecosystems and presents a useful platform for developing area-specific risk forecasting models.