cssi/SciSciGPT-SciSciNet huggingface dataset:
WSTF does it all: a multifunctional protein in transcription, repair, and replication

Williams syndrome transcription factor (WSTF) has emerged as an incredibly versatile nuclear protein. WSTF and the ATP-dependent chromatin remodeling complexes in which it exists, WINAC, WICH, and B-WICH, have been studied in a variety of organisms. This research has revealed roles for WSTF in a number of diverse molecular events. WSTF function includes chromatin assembly, RNA polymerase I and III gene regulation, vitamin D metabolism, and DNA repair. In addition to functioning as a subunit of several ATP-dependent chromatin remodeling complexes, WSTF binds specifically to acetylated histones and is itself a histone kinase as well as a target of phosphorylation. This review will describe the three known WSTF-containing complexes and discuss their various roles as well as mechanisms of regulating WSTF activity.
Matrix metalloproteinase induction in fibrosis and fibrotic nodule formation due to silica inhalation

Matrix metalloproteinases (MMPs) are the principle enzymes that initiate degradation of collagen. We examined the role of MMPs during alveolar wall fibrosis and fibrotic nodule formation from silic...
Eliminating SQL Injection Attacks - A Transparent Defense Mechanism

The widespread adoption of web services as an instant means of information dissemination and various other transactions, has essentially made them a key component of today?s Internet infrastructure. Web-based systems comprise both of infrastructure components and of applicationspecific code. Various organizations have started extensively deploying Intrusion Detection/Prevention Systems and Firewalls as a means of securing their vital installations. However, very little emphasis is laid on securing the applications that run on these systems, apart from frequent updates and patching. SQL-Injection Attacks are a class of attacks that many of these systems are highly vulnerable to, and there is no known fool-proof defense against such attacks. In this paper, we propose a technique, which combines static application code analysis with runtime validation to detect the occurrence of such attacks. The deployment of this technique eliminates the need to modify source code of application scripts, additionally allowing seamless integration with currently-deployed systems. We provide various optimizations improving overall efficiency, and also preliminary evaluation of prototype developed.
The Myb domain of the largest subunit of SNAPc adopts different architectural configurations on U1 and U6 snRNA gene promoter sequences

The small nuclear RNA (snRNA) activating protein complex (SNAPc) is essential for transcription of genes that encode the snRNAs. Drosophila melanogaster SNAPc (DmSNAPc) consists of three subunits (DmSNAP190, DmSNAP50 and DmSNAP43) that form a stable complex that recognizes an snRNA gene promoter element called the PSEA. Although all three subunits are required for sequence-specific DNA binding activity, only DmSNAP190 possesses a canonical DNA binding domain consisting of 4.5 tandem Myb repeats homologous to the Myb repeats in the DNA binding domain of the Myb oncoprotein. In this study, we use site-specific protein–DNA photo-cross-linking technology followed by site-specific protein cleavage to map domains of DmSNAP190 that interact with specific phosphate positions in the U6 PSEA. The results indicate that at least two DmSNAP190 Myb repeats contact the DNA in a significantly different manner when DmSNAPc binds to a U6 PSEA versus a U1 PSEA, even though the two PSEA sequences differ at only 5 of 21 nucleotide positions. The results are consistent with a model in which the specific DNA sequences of the U1 and U6 PSEAs differentially alter the conformation of DmSNAPc, leading to the subsequent recruitment of different RNA polymerases to the U1 and U6 gene promoters.
Creating Capacity Through Health Education: What We Know and What We Don't:

Researchers in health education have rarely convened to outline research priorities in the field. This article discusses the results of a meeting to develop a research agenda aimed at creating capacity to promote and maintain health. Salient research findings related to individual and community health are summarized and priority issues for future research are presented.
Roles of the Regulatory Proteins FlhF and FlhG in the Vibrio cholerae Flagellar Transcription Hierarchy

Vibrio cholerae , the causative agent of the human diarrheal disease cholera, is a motile bacterium with a single polar flagellum, and motility has been inferred to be an important aspect of virulence. The V. cholerae flagellar hierarchy is organized into four classes of genes. The expression of each class of genes within a flagellar hierarchy is generally tightly regulated in other bacteria by both positive and negative regulatory elements. To further elucidate flagellar biogenesis in V. cholerae , we characterized the roles of the three putative regulatory genes, flhF , flhG , and VC2061. V. cholerae flhF and flhG mutants appeared nonmotile in a soft agar assay. Electron microscopy revealed that the flhF mutant lacked a polar flagellum, while interestingly, the flhG mutant possessed multiple (8 to 10) polar flagella per cell. The transcriptional activity of class III and class IV gene promoters in the flhF mutant was decreased, suggesting that FlhF acts as a positive regulator of class III gene transcription. The transcription of all four classes of flagellar promoters was increased in the flhG mutant, suggesting that FlhG acts as a negative regulator of class I gene transcription. Additionally, the ability to colonize the infant mouse intestine was reduced for the flhG mutant (∼10-fold), indicating that the negative regulation of class I flagellar genes enhances virulence. The V. cholerae VC2061 mutant was motile and produced a polar flagellum indistinguishable from that of the wild type, and the transcriptional activities of the four classes of flagellar promoters were similar to that of the wild type. Our results indicate that FlhG and FlhF regulate class I and class III flagellar transcription, respectively, while VC2061 plays no detectable role in V. cholerae flagellar biogenesis.
Effects of Extracellular pH on the Metabolic Pathways in Sulfur-Deprived, H2-Producing Chlamydomonas reinhardtii Cultures

Sustained photoproduction of H(2) by the green alga, Chlamydomonas reinhardtii, can be obtained by incubating cells in sulfur-deprived medium [Ghirardi et al. (2000b) Trends Biotechnol. 18: 506; Melis et al. (2000) Plant Physiol. 122: 127]. The current work focuses on (a) the effects of different initial extracellular pHs on the inactivation of photosystem II (PSII) and O(2)-sensitive H(2)-production activity in sulfur-deprived algal cells and (b) the relationships among H(2)-production, photosynthetic, aerobic and anaerobic metabolisms under different pH regimens. The maximum rate and yield of H(2) production occur when the pH at the start of the sulfur deprivation period is 7.7 and decrease when the initial pH is lowered to 6.5 or increased to 8.2. The pH profile of hydrogen photoproduction correlates with that of the residual PSII activity (optimum pH 7.3-7.9), but not with the pH profiles of photosynthetic electron transport through photosystem I or of starch and protein degradation. In vitro hydrogenase activity over this pH range is much higher than the actual in situ rates of H(2) production, indicating that hydrogenase activity per se is not limiting. Starch and protein catabolisms generate formate, acetate and ethanol; contribute some reductant for H(2) photoproduction, as indicated by 3-(3,4-dichlorophenyl)-1,1-dimethylurea and 2,5-dibromo-6-isopropyl-3-methyl-1,4-benzoquinone inhibition results; and are the primary sources of reductant for respiratory processes that remove photosynthetically generated O(2). Carbon balances demonstrate that alternative metabolic pathways predominate at different pHs, and these depend on whether residual photosynthetic activity is present or not.
Contribution to stator flux orientation vector control of an induction machine

The paper presents a control strategy for induction motor supplied by voltage inverter. The induction machine with control strategy should provide, at the constraining requests, response with high performances in electromagnetic torque and speed. Using the Matlab/Simulink software, we test Indirect and direct field oriented control (IFOC, and DFOC). Both of them achieve the goals for dynamic of torque and stator flux, but are both depending on the unpredictable machine parameters variation.
BNIP3 mediates cell death by different pathways following localization to endoplasmic reticulum and mitochondrion

BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) is a BH3-only proapoptotic member of the Bcl-2 family. Because the interaction of Bcl-2 proteins with intracellular Ca2+ stores has been linked to apoptosis, the role of Ca2+ transfer between endoplasmic reticulum (ER) and mitochondria in BNIP3-mediated cell death was determined in a rat dopaminergic neuronal cell line, Mes 23.5. BNIP3 mutants were constructed to target either ER or mitochondria. Localization of BNIP3 to the ER membrane facilitated release of Ca2+ and subsequently increased uptake of Ca2+ into mitochondria. Excessive accumulation of mitochondrial Ca2+ decreased mitochondrial membrane potential (ΔΨm), resulting in execution of a caspase-independent cell death. Reduction of ER Ca2+ induced by ER-targeted BNIP3 and the subsequent cell death was blocked by the antiapoptotic protein, Bcl-2. On the other hand, mitochondria-targeted BNIP3 initiated apoptosis by a Ca2+-independent mechanism by inducing mitochondrial pore transition and dis...
ECONOMIC AND ENVIRONMENTAL CONCERNS AND LOCAL DEVELOPMENT POLICY Tourism From the Perspective of the "Host Population"

Local government development policy and associated public works investments can have important long-term implications for quality of life. Therefore, citizen val- ues and priorities should be used to guide policy decisions. The infusion of citizen values into development policy is particularly important because of the tension be- tween economic and environmental concerns. This research articulates this tension by classifying citizens based on their combined economic and environmental val- ues using a survey of more than 700 residents of Daytona Beach, Florida. The economy-environment classification system provides a framework for understand- ing community support for selected local-development strategies. This classifica- tion system allows us to look through the eyes of citizens based on their combined economic and environmental orientation to better understand the values of the host community. This research demonstrates the importance of infusing development policy with citizen values and proposes a strategy to promote economic- environmental and citizen-professional value convergence by engaging citizens in decision-making processes.
Revisiting the omitted variables argument: Substantive vs. statistical adequacy

The problem of omitted variables is commonly viewed as a statistical misspecification issue which renders the inference concerning the influence of X t on yt unreliable, due to the exclusion of certain relevant factors W t . That is, omitting certain potentially important factors W t may confound the influence of X t on yt . The textbook omitted variables argument attempts to assess the seriousness of this unreliability using the sensitivity of the estimator to the inclusion/exclusion of W t , by tracing that effect to the potential bias/inconsistency of . It is argued that the confounding problem is one of substantive inadequacy in so far as the potential error concerns subject‐matter, not statistical, information. Moreover, the textbook argument in terms of the sensitivity of point estimates provides a poor basis for addressing the confounding problem. The paper reframes the omitted variables question into a hypothesis testing problem, supplemented with a post‐data evaluation of inference based on sever...
Continuous sliding mode control of a TV transmission tower under stochastic wind

An active mass damper has been designed to be installed on the upper observation deck of the 310 m Nanjing TV transmission tower in China in order to reduce the acceleration response under strong wind gusts. In this paper, we present a continuous sliding mode control (CSMC) strategy using dynamic output feedback for application to the active mass damper system based on acceleration feedbacks. Emphasis is placed on the performance and practical application of active controllers, such as actuator limitations and noise pollution. A systematic modulation of the control effort for the CSMC controller is proposed by introducing a prefilter to the control force. The wind loads acting on the tower are defined by a cross-power spectral density matrix. The spatial correlation of wind loads is accounted for in the design of the observer for the CSMC controller. The power spectral densities and rms of acceleration responses of the tower equipped with an active mass damper have been computed. Simulation results demonstrate that the CSMC strategy is suitable for full-scale implementations of the active mass damper and its control performance is quite remarkable.
The Quantum and Classical Capacitance Limits of InSb and InAs Nanowire FETs

A comparison of nanowire FETs (NWFETs) of identical geometries but operating in two different regimes, namely, the quantum capacitance (QC) and classical capacitance (CC) regimes, is presented. n-type InSb and InAs NWFETs up to ~50 nm in diameter operate in the QC limit (QCL), and the corresponding p-type NWFETs operate in the CC limit. Drive currents at a fixed gate overdrive for the n- and p-type devices are found to be well matched. Nevertheless, the p-type devices have twice the delay times, half the intrinsic cutoff frequencies, twice the power-delay products, and four to five times the energy-delay products of the n-type devices, assuming transport is ballistic. Analytical expressions are derived for the QC, the current, the charge, the power-delay product, the energy-delay product, the gate delay time, and the cutoff frequency for a single-moded device operating in the QCL. The expressions for the power-delay product, energy-delay product, and the cutoff frequency are fundamental limits for such devices.
Bidirectional triode P-N-P-N switches

The theory of operation, construction, and electrical characteristics of a new family of silicon thyristors for use as bidirectional (ac) switches are discussed. With these p-n-p-n devices, load current flow in either direction can be controlled by the application of a low voltage, low current pulse between a gate trigger terminal and one of the load current terminals. Blocking current and voltage characteristics are similar to those of a silicon-controlled rectifier (SCR); but unlike SCR's they can switch load current of either polarity. Devices have been made which, in the blocking state, will support several hundred volts with very little current flow; yet, when in the conducting state, will carry many amperes with a voltage drop of approximately a volt. Static power switching with these devices in such applications as lamp dimming, temperature controls, small motor speed controls, etc., appears to be particularly important. For triggering, these new devices depend on the manipulation of lateral current paths. The potential differences created by the flow of current in these paths determine, in turn, the lateral distribution of injected charge carriers within the device during the triggering interval. This paper presents an analysis of lateral biasing effects and the parameters which control them.
Identification of an Allosteric Binding Site for Zn2+on the β2 Adrenergic Receptor *

The activity of G protein-coupled receptors (GPCRs) can be modulated by a diverse spectrum of drugs ranging from full agonists to partial agonists, antagonists, and inverse agonists. The vast majority of these ligands compete with native ligands for binding to orthosteric binding sites. Allosteric ligands have also been described for a number of GPCRs. However, little is known about the mechanism by which these ligands modulate the affinity of receptors for orthosteric ligands. We have previously reported that Zn(II) acts as a positive allosteric modulator of the β2-adrenergic receptor (β2AR). To identify the Zn2+ binding site responsible for the enhancement of agonist affinity in the β2AR, we mutated histidines located in hydrophilic sequences bridging the seven transmembrane domains. Mutation of His-269 abolished the effect of Zn2+ on agonist affinity. Mutations of other histidines had no effect on agonist affinity. Further mutagenesis of residues adjacent to His-269 demonstrated that Cys-265 and Glu-225 are also required to achieve the full allosteric effect of Zn2+ on agonist binding. Our results suggest that bridging of the cytoplasmic extensions of TM5 and TM6 by Zn2+ facilitates agonist binding. These results are in agreement with recent biophysical studies demonstrating that agonist binding leads to movement of TM6 relative to TM5.
Genotype-Specific Recurrence Risks as Indicators of the Genetic Architecture of Complex Diseases

A statistic is introduced that relates discoveries made in genome-wide association (GWA) studies to patterns of disease risks among relatives. The genotype-specific recurrence risk (GSR) is the genotype-specific risk to relatives of known relationship to affected probands. The GSRs can be used for three purposes. (1) They can provide an independent test of whether an allele identified in a GWA study is associated with the disease. (2) They can provide a test of whether interactions among loci affecting the disease are multiplicative. (3) They can be used by genetic counselors to incorporate information from GWA studies for predicting the risk to relatives of known genotype. Under a multiplicative model of disease causation, the GSRs for a locus are the genotypic risks in probands for that locus multiplied by λR/λjR, where λR is Risch's recurrence risk ratio and λjR is the contribution to λR from the locus of interest. If there is saturation of risk with increasing numbers of causative alleles, then observed GSRs for individuals with high-risk genotypes will be lower than predicted by the multiplicative model.
Uniform Crime Reports as Organizational Outcomes: Three Time Series Experiments

John Kitsuse and Aaron Cicourel have suggested that official crime rates are a function of the organizational structures of police departments. In three "natural experiments," we examine this hypothesis with time series analyses of Uniform Crime Reports. Our findings suggest that official crime rates are a function of organizational structures related to (1) formal complaint investigation; (2) hierarchial control of crime processing; and (3) dispatching routines. We propose a minimal theory of official crime rates as organizational outcomes. The oldest, most comprehensive source of crime statistics in the United States is the Uniform Crime Reports (UCRs), published annually by the Federal Bureau of Investigation. UCRs are not the only source of crime statistics, nor are they more valid or reliable than alternative statistics. The shortcomings of UCRs as measures of "real" crime have been widely noted. UCRs ignore crimes which do not fit neatly into established "index" categories, for example, as well as crimes which are not reported to local police agencies (Hindelang, 1976; Skogan, 1974, 1976). Federal, state, and local governments nevertheless rely heavily on UCRs to monitor crime control programs; when politicians complain that crime rates are up or brag that crime rates are down, they invariably mean that UCR crime rates are up or down. UCRs in this most important sense represent the status quo: they provide the official crime statistics for most U.S. cities and states. This paper examines organizational structures which threaten the validity of UCRs, a problem which has been referred to as the "production of crime rates" (Black, 1970; Maxfield et al., 1980). Kitsuse and Cicourel provide the best general statement of this problem:
The Effects of Digital Noise Reduction on the Acceptance of Background Noise

Modern hearing aids commonly employ digital noise reduction (DNR) algorithms. The potential benefit of these algorithms is to provide improved speech understanding in noise or, at the least, to provide relaxed listening or increased ease of listening. In this study, 22 adults were fitted with 16-channel wide-dynamic-range compression hearing aids containing DNR processing. The DNR includes both modulation-based and Wiener-filter-type algorithms working simultaneously. Both speech intelligibility and acceptable noise level (ANL) were assessed using the Hearing in Noise Test (HINT) with DNR on and DNR off. The ANL was also assessed without hearing aids. The results showed a significant mean improvement for the ANL (4.2 dB) for the DNR-on condition when compared to DNR-off condition. Moreover, there was a significant correlation between the magnitude of ANL improvement (relative to DNR on) and the DNR-off ANL. There was no significant mean improvement for the HINT for the DNRon condition, and on an individual basis, the HINT score did not significantly correlate with either aided ANL (DNR on or DNR off). These findings suggest that at least within the constraints of the DNR algorithms and test conditions employed in this study, DNR can significantly improve the clinically measured ANL, which may result in improved ease of listening for speech-in-noise situations.
Self-assessment of second language ability: the role of response effects

The role of response effects (tendencies to respond to factors other than item content) in the self-assessment of second language ability was investigated through a split-ballot procedure using positively- and negatively-worded ques tions and graded (i.e. level-specific questions). Results indicate that both an acquiescence effect (a tendency to respond positively regardless of item con tent) and overestimation were present. Although both effects were present at all levels of subjects, they were most evident for less experienced learners. Discussion focuses on explanation of these effects and implications for both test construction and pedagogy.
Simulations of the Interannual Variability of Stratospheric Water Vapor

Abstract Observations and model results indicate that the quasi-biennial oscillation (QBO) modulation of stratospheric water vapor results from two causes. Dynamical redistribution of water vapor from the QBO-induced mean meridional circulation dominates the observed variability in the middle and upper stratosphere. In the lower stratosphere, the QBO water vapor variability is dominated by a “tape recorder” that results from the dehydration signal accompanying the QBO variation of the tropical cold point tropopause. It is suggested that another low frequency tape recorder exists due to ENSO modulations of the tropical tropopause, but insufficiently long observations of stratospheric water vapor exist to identify this in the observations.
miRNA–target chimeras reveal miRNA 3′-end pairing as a major determinant of Argonaute target specificity

microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins, which mediate posttranscriptional silencing of target messenger RNAs. Despite their importance in many biological processes, rules governing AGO-miRNA targeting are only partially understood. Here we report a modified AGO HITS-CLIP strategy termed CLEAR (covalent ligation of endogenous Argonaute-bound RNAs)-CLIP, which enriches miRNAs ligated to their endogenous mRNA targets. CLEAR-CLIP mapped ∼130,000 endogenous miRNA-target interactions in mouse brain and ∼40,000 in human hepatoma cells. Motif and structural analysis define expanded pairing rules for over 200 mammalian miRNAs. Most interactions combine seed-based pairing with distinct, miRNA-specific patterns of auxiliary pairing. At some regulatory sites, this specificity confers distinct silencing functions to miRNA family members with shared seed sequences but divergent 3'-ends. This work provides a means for explicit biochemical identification of miRNA sites in vivo, leading to the discovery that miRNA 3'-end pairing is a general determinant of AGO binding specificity.
Participation, process and policy: the informational value of politicised judicial review

We develop a model of “notice and comment” rulemaking, focussing on strategic issues facing agencies and interest groups in light of judicial review in this process. Specifically, we analyse the incentives for agencies and groups to produce and reveal information during rulemaking. We show that judicial review can produce informed policymaking, but that participatory rulemaking can bias agency policymaking in favour of groups with access to the rule-making process. In addition, the model allows an analysis of doctrines of judicial review of agency policymaking. The model reveals that “politicised” judicial review can be beneficial because of its effects on agency incentives for information acquisition in policymaking. Accordingly, socially optimal judicial review may be “legally irrational” and, contrary to standard doctrines of judicial review in the United States, judicial deference to rules with thin records can be optimal.
Myocardial infarction in a young man receiving chemotherapy for acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is characterized by rapid proliferation of immature lymphocytes in the bone marrow, blood, and other organs.1 An estimated 5330 new cases of ALL were diagnosed in 2010 in the United States.2,3 In adults, ALL has a 5-year overall survival rate of only 30% to 40%.4,5 Patients with ALL can be risk stratified based on adverse prognostic features, which include age, leukocyte count, immunophenotype, genotype, and early treatment response.6 Analyses of multiple pediatric and adult study group trials show complete induction remission rates of approximately 98% in children and 85% in adults following multidrug induction chemotherapy.6 Combination chemotherapy is the primary treatment for patients with newly diagnosed ALL, and induction remission treatment for this condition commonly includes the administration of vincristine and a glucocorticoid, usually with the addition of L-asparaginase, an anthracycline, or both.6,7 The overall risk of symptomatic thrombosis in children with ALL is estimated to be 5.2%. Approximately half of these thromboses occur in the central nervous system; the remaining ones comprise deep vein thrombosis, pulmonary embolism, right atrial thrombosis, and superficial thrombosis.8 The thrombotic risk may be up to 8-fold higher in ALL patients with a genetic hypercoagulable defect.8 Agents used in induction therapy for ALL also have been associated with thrombotic complications.8-15 We present a case of sequential myocardial infarctions (MIs) in a young man without significant cardiovascular risk factors while receiving induction remission chemotherapy for newly diagnosed B-cell ALL, and review the literature on this topic. Case Presentation
Modern Pollen—Vegetation Relationships

The establishment of the field of Quaternary paleoecology is commonly considered to be Lennart von Post’s presentation before the 16th Convention of Scandinavian Naturalists held in Oslo, Norway, in 1916. In his lecture entitled “Forest tree pollen in south Swedish peat.bog deposits”, von Post described his pioneering efforts to examine fossil-pollen assemblages preserved within late-Quaternary peat deposits of Scandinavian bogs. By counting a number of grains of different pollen types at each of many levels within the peat deposits, von Post noted the succession of changing pollen assemblages that he interpreted in terms of the postglacial development of plant communities. He identified the replacement of mixed oak forest by beech—spruce forest and interpreted this change in terms of changing climate, immigrations of tree species, and competition at both the species and community level. Von Post was the first to recognize the need for documentation of modern pollen—vegetation relationships as a prerequisite for interpreting changes in forest communities through time. According to von Post (1916, translated by Davis and Faegri 1967), “As long as we have no indices to express the relative pollen productivity of the various trees, nor to express the different degrees to which their pollen is dispersed, we have no right to seek in the [pollen] percentage figures an adequate expression of the composition of the [past] forest communities” (p. 390, words in brackets added for clarification).
Zwitterionic Antifouling Coatings for the Purification of High-Salinity Shale Gas Produced Water.

Fouling refers to the undesirable attachment of organic molecules and microorganisms to submerged surfaces. It is an obstacle to the purification of shale gas produced water and is currently without an effective solution due to the highly contaminated nature of produced water. Here, we demonstrate the direct vapor application of a robust zwitterionic coating to a variety of substrates. The coating remains unprecedentedly hydrophilic, smooth, and effectively antifouling in extremely high salinity solutions (with salt concentration of 200 000 ppm). The fouling resistance is assessed rapidly and quantitatively with a molecular force spectroscopy-based method and corroborated using quartz crystal microbalance system with dissipation monitoring. Grazing angle attenuated total reflectance Fourier transform infrared is used in combination with X-ray photoelectron spectroscopy, atomic force microscope, and in situ spectroscopic ellipsometry to lend insight into the underlying mechanism for the exceptional stabili...
Vitamin D: Role in Pathogenesis of Multiple Sclerosis

Abstract Background: Epidemiological data support a potential relationship between vitamin D deficiency and an increased risk of developing multiple sclerosis (MS). In vitro studies have expanded the potential role of vitamin D and its receptor beyond calcium modulation, regulation, and maintenance of bone mineralization to include immune modulation. Review Summary: Whether vitamin D’s immunomodulatory effects can be translated into clinical benefits in MS patients is still a matter of debate. A review of biochemistry of vitamin D and its synthesized derivatives is discussed in the context of treating vitamin D deficiency. Animal studies, which have led to some human studies, are also discussed. Future studies are pending and will likely yield conclusive results as to the benefit and possible synergistic effects of vitamin D with other disease-modifying therapies of MS. Conclusion: Further prospective studies are needed to identify vitamin D levels during the various phases of MS, including relapses, remissions, and progression, and to determine whether correcting vitamin D during any or all of these phases may affect the incidence or even the course of the disease.
Electronic Structure and Magnetic Properties of Y2Ti(μ-X)2TiY2 (X, YH, F, Cl, Br) Isomers

The electronic structure and magnetic properties of homodinuclear titanium(III) molecules with halide and hydride ligands have been studied using single- and multireference methods. Natural orbital occupation numbers suggest that the singlet states are essentially diradical in character. Dynamic electron correlation is required for calculating quantitatively accurate energy gaps between the singlet and triplet states. Isotropic interaction parameters are calculated, and three of the compounds studied are predicted to be ferromagnetic at the MRMP2/ TZV(p) level of theory. Zero-field splitting parameters are determined using CASSCF and MCQDPT spinorbit coupling with three different electron operator methods. Timings for these methods are compared. Calculated dimerization energies suggest that all dimers studied are lower in energy than the corresponding monomers. Monomer structures and vibrational frequencies are reported.
MODEL PREDICTIONS OF NONBREAKING SHOALING WAVES

The predictions of linear and nonlinear (Boussinesq) shoaling wave models for nonbreaking unidirectional surface gravity waves are compared to field observations, with particular emphasis on quantities that may be important for cross-shore sediment transport. The extensive data sets were obtained on two natural beaches, span water depths between 1-10 m, and include incident wave power spectra with narrow, broad, and bimodal shapes. Significant wave heights varied between approximately 30 and 100 cm and peak periods between approximately 8 and 18 seconds. Only the nonlinear theory predicts the increasingly asymmetric sea-surface elevations and horizontal velocities (pitched-forward wave shape) and the weaker variation of skewness (difference between crest and trough profiles) which are observed to occur during shoaling. The nonlinear theory also models qualitatively well the large skewed accelerations which occur during the passage of asymmetric waves.
Upper Ordovician tempestites from Swatara Gap, Pennsylvania; depositional processes affecting the sediments and paleoecology of the fossil faunas

The Upper Ordovician, Reedsville Formation at Swatara Gap, Lebanon County, Pennsylvania contains two benthic fossil faunas. The stratigraphically lowest strata of the Swatara Gap exposures (interbedded siltstones and shales) contain a shallow subtidal fossil fauna which includes diverse brachiopods, trilobites, mollusks, echinoderms, and a eurypterid. Although diverse, the fauna is dominated by organisms well suited to live on and in a muddy substrate, such as small sowerbyellids (Sowerbyella and Thaerodonta), flat strophomenids (Rafinesquina), and the trilobite Cryptolithus. The stratigraphically highest strata, which contain shales and lack siltstones, include the burrowing, inarticulate brachiopod Pseudolingula, infaunal pelecypods, and the trilobite Cryptolithus. Other fossils from the stratigraphically lower Swatara Gap rocks are noticeably absent from these upper shales. Both the silty and the muddy substrate faunas were preserved by storm sedimentation. The silt-rich rocks record distal storm processes-but not as distal as the siltpoor rocks (mud tempestites). Although the result of distal storm processes, these mud tempestites indicate high sedimentation rates, and the fossil fauna buried by the mud tempestites includes organisms well adapted to living in, or escaping from, thick muddy deposits. The benthic fossils found in the silty and muddy Reedsville rocks do not readily fit published paleobathymetric models. This is probably because factors other than absolute depth-such as substrate and sedimentation ratewere primary controls on organisms' occurrences.
Simple Partitions of Space

Consider an arrangement of n planes in general position in Euclidean 3-space, where by "general position" we mean that at most three of the planes pass through each point, no more than two of the planes pass through each line, there are no parallel planes, and no lines of intersection are parallel to planes of the arrangement. Into how many cells is space divided? This problem is studied from the heuristic point of view by G. P6lya in [4] and again in his film, "Let Us Teach Guessing." The solution,
Alkenes as Alkyne Equivalents in Radical Cascades Terminated by Fragmentations: Overcoming Stereoelectronic Restrictions on Ring Expansions for the Preparation of Expanded Polyaromatics

Chemoselective interaction of aromatic enynes with Bu3Sn radicals can be harnessed for selective cascade transformations, yielding either Sn-substituted naphthalenes or Sn-indenes. Depending on the substitution at the alkene terminus, the initial regioselective 5-exo-trig cyclizations can be intercepted at the 5-exo stage via either hydrogen atom abstraction or C–S bond scission or allowed to proceed further to the formal 6-endo products via homoallylic ring expansion. Aromatization of the latter occurs via β-C–C bond scission, which is facilitated by 2c,3e through-bond interactions, a new stereoelectronic effect in radical chemistry. The combination of formal 6-endo-trig cyclization with stereoelectronically optimized fragmentation allows the use of alkenes as synthetic equivalents of alkynes and opens a convenient route to α-Sn-substituted naphthalenes, a unique launching platform for the preparation of extended polyaromatics.
Improved needle visualization with electronic beam steering: proof of concept.

Purpose The objective of this study was to evaluate electronic beam steering to improve needle visualization. Methods Various needles ranging from 27 to 12 gauge were evaluated with a modified CX50 (Philips Ultrasound, Bothell, Wash) using a 12-MHz linear probe. For proof of concept, the needles were placed in a pork roast at various random angles. The ultrasound beam was electronically steered at angles from 0 to 50 degrees. Images were obtained at the various angles and compared. Two patients undergoing a thyroid biopsy, one patient undergoing biopsy of the supraclavicular node, and one undergoing a breast biopsy were evaluated using electronic beam steering at various angles. The images were stored and subjectively compared. Results All needles were better visualized when the ultrasound beam was steered as close to perpendicular to the needle as possible. Significant improvements in needle including tip visualization by subjective visual inspection were found by applying the appropriate beam angle. Conclusions Electronic beam steering has the potential to significantly improve needle visualization.
The Importance of Worsening Heart Failure in Ambulatory Patients: Definition, Characteristics, and Effects of Amino-Terminal Pro-B-Type Natriuretic Peptide Guided Therapy

Abstract Objectives The goal of this study was to define and assess the significance of worsening heart failure (WHF) in patients with chronic ambulatory heart failure with reduced ejection fraction (HFrEF). Background WHF has been identified as a potentially relevant clinical event in patients with acute heart failure (HF) and is increasingly used as an endpoint in clinical trials. No standardized definition of WHF exists. It remains uncertain how WHF relates to risk for other HF events or how treatment may affect WHF. Methods A total of 151 symptomatic patients with chronic HFrEF were randomized to standard of care HF management or a goal to lower N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentrations ≤1,000 pg/ml in addition to standard of care. WHF was prospectively defined as: 1) new or progressive symptoms and/or signs of decompensated HF; and 2) unplanned intensification of diuretic therapy. Results Over a mean follow-up of 10 months, 45 subjects developed WHF. At baseline, patients developing incident WHF had higher ejection fraction (31% vs. 25%; p = 0.03), were more likely to have jugular venous distension and edema (p Conclusions In chronic HFrEF, WHF was associated with substantial risk for morbidity and mortality. NT-proBNP–guided care reduced risk for WHF.
SU-F-T-400: Clinical Comparison of An IMRT Plan Computed with Four Algorithms

Purpose: This work demonstrates clinical differences in a prostate IMRT plan DVH depending on which of four common algorithms is used for computation. Previous comparisons were often based on simple static or re-optimized IMRT plans which may not be clearly indicative of the clinical end result due solely to the computation algorithm. Methods: A step and shoot prostate multiple field IMRT plan was created in Pinnacle with a Collapsed Cone Convolution Superposition (CCCS) algorithm. The computed patient plan with corresponding dose and the control points without dose were both independently exported to Eclipse. Using the same patient image and structure data sets the control points were recomputed with the Anisotropic Analytical Algorithm (AAA) and Acuros XB for dose-to-water in medium (AXBwater) and dose-to-medium in medium (AXBmedium). All DVH values were measured in Eclipse to eliminated known differences between various DVH systems. A 0.3cm3 volume was created at the isocenter for point dose (PD) comparison. Results: The prostate target Acuros dose-to-medium in medium is clearly different than the others with a mean value of 101.7 cGy versus 103.8, 103.5 and 103.1 cGy for AAA, CCCS and AXBwater respectively. The difference in other clinical parameters such as volume at 105% dose (V105) is also unexpectedly different with values of 1.6, 23.9, 16.0 and 11.6 % respectively. The mean value in a small volume around the isocenter was 99.6, 102.4, 102.2 and 101.5 respectively which though not a great difference could affect the plan normalization and add to other effects in all regions of interest. The V102 is 25% larger for AAA compared to AXBwater. The variation in V50 for the bladder and rectum was approximately 5%. Conclusion: This work demonstrates how an individual plan can be recomputed and compared directly between various algorithms and that clinical parameters can indeed vary according to which algorithm is used for computation.
Framing the Discussion: Elections as Components of Larger Political and Cultural Geographies

It is important to remember that elections are but one piece—albeit an important one—of much larger processes of politics and governance. Moreover, in the United States they are increasingly implic...
Where’s the loo? An analysis of the spatial distribution of private latrines in Pompeii

The location of sanitation facilities has important social and cultural implications concerning waste management. The aims of this paper are to (1) examine the city-wide distribution of downpipes and latrines to determine if the distribution reflects a pattern in urban development; (2) evaluate the hypothesis that almost every house in Pompeii had a latrine; and (3) evaluate the hypothesis that most latrines were found in kitchens. Several seasons of field work have led to a precise understanding of private latrines and downpipes in Pompeii. The spatial distribution of downpipes and latrines across Pompeii indicates a relationship between properties and sanitation features. The location of Roman latrines, historically, has been attributed to residential kitchens, but new data indicate that latrines are also commonly found near entrances to residences in dedicated small rooms. Business sanitation facilities are closely associated with downpipes from upper stories. The patterns are statistically tested. Chi-square results indicate that while there is a significant association between residential latrines and kitchens, there is no association between kitchen latrines and any size class of houses. For residential latrines, there is a correlation between small houses and front entrances, and between medium-sized houses and rear entrances. For businesses, there is a significant association between downpipes and the front room of workshops. Studying downpipes in conjunction with latrines provides the opportunity to increase our knowledge of Roman sanitation.
Simple thermal evaluation of building envelopes containing phase change materials using a modified admittance method

Abstract This paper extends the admittance method to predict the diurnal energy flux reduction Er associated with adding microencapsulated phase change materials (PCMs) to single and multilayer building envelopes. The effects of phase change on the thermal load through composite building walls were accounted for by modifying the decrement factor fAM and time lag ϕAM. The procedure was demonstrated for single and multilayer PCM-composite walls subjected to a constant indoor temperature and to (i) a sinusoidal sol-air outdoor temperature, (ii) a non-sinusoidal idealized sol-air temperature, or (iii) a sol-air temperature based on weather data for three different days in California climate zone 9 (Los Angeles, CA). In all cases, the analytical results for the daily thermal load passing through PCM-composite walls agreed very well with those predicted using detailed finite element simulations. The computational speed and simplicity of this procedure can enable straightforward evaluation of the energy benefits of PCM-composite walls via user-friendly design tools and platforms.
MutSα's Multi-Domain Allosteric Response to Three DNA Damage Types Revealed by Machine Learning

MutSalpha is a key component in the mismatch repair (MMR) pathway. This protein is responsible for initiating the signaling pathways for DNA repair or cell death. Herein we investigate this heterodimer’s post-recognition, post-binding response to three types of DNA damage involving cytotoxic, anti-cancer agents – carboplatin, cisplatin, and FdU. Through a combination of supervised and unsupervised machine learning techniques along with more traditional structural and kinetic analysis applied to all-atom molecular dynamics (MD) calculations, we predict that MutSalpha has a distinct response to each of the three damage types. Via a binary classification tree (a supervised machine learning technique), we identify key hydrogen bond motifs unique to each type of damage and suggest residues for experimental mutation studies. Through a combination of a recently developed clustering (unsupervised learning) algorithm, RMSF calculations, PCA, and correlated motions we predict that each type of damage causes MutS↵to explore a specific region of conformation space. Detailed analysis suggests a short range effect for carboplatin – primarily altering the structures and kinetics of residues within 10 angstroms of the damaged DNA – and distinct longer-range effects for cisplatin and FdU. In our simulations, we also observe that a key phenylalanine residue – known to stack with a mismatched or unmatched bases in MMR – stacks with the base complementary to the damaged base in 88.61% of MD frames containing carboplatinated DNA. Similarly, this Phe71 stacks with the base complementary to damage in 91.73% of frames with cisplatinated DNA. This residue, however, stacks with the damaged base itself in 62.18% of trajectory frames with FdU-substituted DNA and has no stacking interaction at all in 30.72% of these frames. Each drug investigated here induces a unique perturbation in the MutS↵complex, indicating the possibility of a distinct signaling event and specific repair or death pathway (or set of pathways) for a given type of damage.
A VARIATIONAL APPROACH TO SOLVING SEMILINEAR EQUATIONS AT RESONANCE

Publisher Summary This chapter discusses a variational approach to solving semilinear equations at resonance. Equations at resonance have received considerable attention since the pioneering work of Landesman and Lazer. The idea of splitting an equation at resonance into two coupled equations in complementary subspaces has been used extensively since Cesari combined the techniques of functional analysis with the Lyapunov–Schmidt method. The chapter presents the abstract results obtained and discusses their application to semilinear ordinary and partial differential equations. To demonstrate the way in which the given theorem may be applied to show existence, multiplicity, or nonexistence of solutions to some nonlinear differential equations, simple examples are presented in the chapter.