cssi/SciSciGPT-SciSciNet huggingface dataset:
A Variance-Stabilizing Transformation to Mitigate Biased Variogram Estimation in Heterogeneous Surfaces with Clustered Samples

Due to the inherent variance heterogeneity in clustered preferential sampling, the underlying variogram cannot be estimated directly. A variance-stabilizing declustering method is proposed here using a modified Box–Cox transformation. In contrast to the traditional Box–Cox transformation that aims at achieving normally distributed data, its modified version has the objective to match the variance in clustered sample observations to the variance of the remaining more dispersed background sample observations. The proposed approach leads to predictions with lower standard errors than alternative proposed methods.
FLLL32, a curcumin analog, ameliorates intestinal injury in necrotizing enterocolitis.

Background Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that primarily affects premature infants. It is characterized by inflammation and leukocyte infiltration that can progress to intestinal necrosis, perforation, systemic inflammatory response, and death. In this study, we examined the effect of FLLL32, a curcumin analog, on an NEC-like neonatal intestinal injury model. Methods NEC was induced in CD-1 mice pups using the Paneth cell ablation and Klebsiella infection model. Pups were divided into sham, NEC, and NEC + FLLL32 groups. At the end of the experiment, pups were euthanized; whole blood and small intestines were harvested. Intestinal inflammatory cytokine profile, in vivo intestinal permeability using serum fluorescein isothiocyanate-dextran, and histological injury scores were compared between the groups. Results and conclusion FLLL32-treated pups had lower intestinal injury, improved intestinal permeability, and lower proinflammatory cytokine profiles compared to those in untreated pups with NEC. These results suggest that FLLL32 plays a protective role in NEC.
A REVIEW OF FOOD SECURITY AND HUMAN NUTRITION ISSUES IN NEPAL

Nepal faces multiple development challenges, including chronic and widespread food insecurity and adult and child malnutrition. Due to population growth, agricultural stagnation and a range of institutional failures, the threat of a serious food crisis in Nepal is substantial. The recent scaling back of WFP assistance means that food security conditions in some parts of Nepal will undoubtedly worsen in the near future. This paper presents a brief review of topics and available evidence regarding food security, malnutrition and related subjects in Nepal. It is intended to document important source material and provide an overview of topics for non-specialists or those moving into new areas of concern.
Long range femtosecond atmospheric light bullet

Ultrafast femtosecond laser pulses are able to deliver extreme local fields on point targets, avoiding avalanche ionization and any significant collateral damage. In the context of long range atmospheric propagation of multi-TW femtosecond laser pulses, the Ti:Sapphire laser has been the standard workhorse and has promoted atmospheric studies ranging from femtosecond LIDAR [1], remote LIBS [2], white light generation [3], discharge triggering and guiding [4], lightning control [5]. However, high density accumulated plasmas tend to strongly defocus the wavepacket and abruptly terminate individual filaments preventing their sustained long-range propagation. Despite the remarkable swath of applications that have been enabled with this ultra-intense laser source [6], the ability to launch a super-intense intact electromagnetic pulse over long distances remains elusive. The reason for this has been understood for some time and is due to the tendency of a relatively wide 800nm multi-TW beam to break up into tens or hundreds of light filaments with typical waists on the order of 100µm, originally initiated via modulational instability.
The Determination of Posttranscriptional Modification in RNA

Significant progress has been made in recent years in recognition and understanding of the diversity of functional roles played by posttranscriptional modification in RNA (e.g., Bjork et al., 1987; Cunningham et al., 1990; Bjork et al., 1992). The functional aspects of modification have been most extensively studied in the case of tRNA (Bjork et al., 1987; Bjork et al., 1992) in which approximately 80 different posttranscriptionally modified nucleosides have been identified (Sprinzl et al., 1989; Edmonds et al., 1991). Although at an earlier time the structural characterization of modified nucleosides was usually undertaken in conjunction with their recognition during sequence determination (McCloskey and Nishimura, 1977), advances in structural methods based on mass spectrometry (McCloskey, 1991) have more recently resulted in the discovery of a number of new nucleosides in unfractionated tRNA, for which sequence locations are not yet known. We presently summarize recent progress in the development of three mass spectrometry-based methods, using instrumentation now commercially available, for the determination of posttranscriptional modification in RNA, with recent examples of their applications.
Genotyping-by-Sequencing

Genotyping-by-sequencing (GBS) refers to a suite of related methods that obtain genotype data from samples by using restriction enzyme digestion followed by high-throughput sequencing. GBS is a refinement of restriction site-associated DNA sequencing (RADseq) methods, with a goal of being able to perform library preparations quickly, cost-effectively, and in a high-throughput manner. This protocol contains the steps necessary to go from purified DNA to Illumina-ready libraries. It also covers the considerations that go into planning a GBS experiment. © 2017 by John Wiley & Sons, Inc.
CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma

Abstract Objectives In accordance with the Precision Medicine Initiative, new treatment strategies for head and neck squamous cell carcinoma (HNSCC) are needed to yield better therapeutic outcomes. The purpose of this study was to establish and validate chimeric antigen receptor (CAR)-T cells targets in HNSCC. Methods Putative CAR-T antigens were identified in The Cancer Genome Atlas database. To validate antigen suitability, quantitative RT-PCR, flow cytometry, and immunofluorescent staining were performed. A retroviral human CD70 CAR construct, using truncated CD27 conjugated with 4-1BB and CD3-zeta costimulatory molecules, was used to transduce activated human T cells to generate CD70 CAR-T cells. Cell-based cytotoxicity and cytokine ELISAs were used to measure efficacy of killing. Results Nine potential CAR-T targets (CD276, EGFR, MICA, MICB, MAGE-A4, FAP, EPCAM, CD70, B4GALNT1) were identified based on their high expression in tumors compared to flanking control tissues. CD70 was selected for further proof-of-principle analysis based on its differential expression in several tumor subtypes, and showed substantial heterogeneity in individual tumors analyzed. Cell surface CD70 protein and CD70 mRNA were detected from low to high levels in established HNSCC cancer cell lines. CD70 was highly expressed in 4 of 21 tumor biopsies (19%), and 3 of 4 specimens showed strong CD70 expression on the tumor cell surface. CD70-specific CAR-T cells were generated and further demonstrated to recognize and kill CD70-positive HNSCC cells efficiently, but not CD70-negative cancer cells. Conclusion CD70-specific CAR-T cells specifically recognized and efficiently eliminated CD70-positive HNSCC cells. This study provides the basis for further investigation into CD70 and other CAR-T targets.
MAIT cells and microbial immunity

Mucosal-associated invariant T (MAIT) cells, the most abundant T-cell subset in humans, are increasingly being recognized for their importance in microbial immunity. MAIT cells accumulate in almost every mucosal tissue examined, including the lung, liver and intestinal tract, where they can be activated through T-cell receptor (TCR) triggering as well as cytokine stimulation in response to a host of microbial products. In this review, we specifically discuss MAIT cell responses to bacterial and fungal infections, with a focus on responses that are both MR1-dependent and -independent, the evidence for diversity in MAIT TCR usage in response to discrete microbial products, protective immunity induced by MAIT cells, and MAIT cell antimicrobial functions in the context of these infections.
Tools for Successful Student–Teacher–Scientist Partnerships

Student–teacher–scientist partnership (STSP) programs are cooperative relationships in which students, with the support of their teachers, participate in and contribute to the research of scientists. This paper examines one of the world's largest STSPs—an international environmental science education program called GLOBE (Global Learning and Observations to Benefit the Environment)—and proposes recommendations to scientists about how they can get the most out of their research and teaching relationship with students and their teachers. GLOBE is an international K–12 STSP that engages students in Earth's Systems investigations. Extensive training is needed for students to collect and report accurate data to scientists, and special preparatory curricula are needed to make their partnership effective and motivating. Recognizing these issues, this research was conducted specifically to identify and recommend a set of training material design criteria for implementation of STSPs in the elementary and middle school levels. The conclusions—the result of background research, extensive interviews and consultation with teachers—provide guidance to GLOBE and other STSP programs to enhance the development of effective and engaging training materials.
Probability and Moment Approximations Using Limit Theorems

So far we have described the methods for determining the exact probability of events using probability mass functions (PMFs) for discrete random variables and probability density functions (PDFs) for continuous random variables. Also of importance were the methods to determine the moments of these random variables. The procedures employed were all based on knowledge of the PMF/PDF and the implementation of its summation/integration. In many practical situations the PMF/PDF may be unknown or the summation/integration may not be easily carried out. It would be of great utility, therefore, to be able to approximate the desired quantities using much simpler methods. For random variables that are the sum of a large number of independent and identically distributed random variables this can be done. In this chapter we focus our discussions on two very powerful theorems in probability–the law of large numbers and the central limit theorem. The first theorem asserts that the sample mean random variable, which is the average of lID random variables and which was introduced in Chapter 14, converges to the expected value, a number, of each random variable in the average. The law of large numbers is also known colloquially as the law of averages. Another reason for its importance is that it provides a justification for the relative frequency interpretation of probability. The second theorem asserts that a properly normalized sum of lID random variables converges to a Gaussian random variable.
Brittle Fracture: Micromechanics

Publisher Summary This chapter elaborates the formation of flaws. It describes the principal relationships between the flaw type and size and the ultimate failure stress. Fracture in brittle solids results from discrete flaws, activated by an applied or concentrated stress. Fracture in brittle solids can be considered to occur either by the direct activation of noninteracting pre-existent flaws or by flaw generation and coalescence processes. In the classes of brittle solids that fail by the extension of pre-existent flaws, three principal flaw categories can be distinguished: surface cracks, fabrication defects, and environmentally induced defects. The flaws that pre-exist in brittle solids can be characterized by a statistical distribution that encompasses both the flaw size and the volume sampled. The operational strengths of brittle materials usually scale with the fracture toughness, as reflected in relations between the fracture strength and the flaw dimensions. It is important to recognize the existence of multiple flaw populations as typical failure sources and to understand the failure process associated with each significant population that exists in a specific material.
ASIA, WEST | Palaeolithic Cultures

Prehistoric research in Western Asia began in the mid-nineteenth century by European scholars who were later joined by Americans and more recently by local archaeologists. The site of Dmanisi (Republic of Georgia), dated to 1.7 Ma, is where several skulls of Homo ergaster were found with stone artifacts and animal bones. ‘Ubeidiya, in the Jordan valley (Israel), dated to 1.4 Ma marks the earliest Acheulian in the region. The rest of the Lower Paleolithic sequence is mainly of Acheulian sites with rare exceptions of sites where flake and core assemblages are the dominant ones. In the later time prior to the appearance of the Middle Paleolithic Mousterian complex around 0.25 Ma, blade industries (Qesem cave), rich Acheulo-Yabrudian (with small bifaces and thick scrapers, sometimes with blades) are known from the Levant. The Mousterian complex demonstrate in the Levant a lower entity characterized by blades and points, a middle one rich in flakes (and burials of archaeic Modern humans) and the latter entity with plenty of Levallois points (with a few local Neanderthals skeletal remains). The Zagros and the Taurus are characterized by a rich scraper and retouched point Mousterian assemblages. The Upper Paleolithic (from 50/45 000 BP marks the advent of Modern humans from Africa is generally rich in blades, appearance of some body decorations and ephemeral bone tools. The sequence is punctuated by the arrival of the typical European Aurigancian around 34–29 000 BP both in the Levant and in the Zagros, but not in the Caucasus mountains. The latter part and the Epi-Paleolithic are characterized by blade and microlithic industries. The final phase in the Levant is known as the Natufian culture. While the entire sequence reflects the residues of hunting and gathering societies, within the changing environment, the Natufian (14 500–11 500 cal BP) indicates semi-sedentary groups, who domesticated the dogs and harvested efficiently the wild stands of cereals.
Molecular Cloning of Nitrogen Fixation Genes from Rhizobium Meliloti

Until recently, the focus of interest in our laboratory has been on cloning nif genes from the free-living nitrogen-fixing species Klebsiella pneumoniae (Cannon et al., 1977; Cannon et al., 1979; Riedel et al., 1979). K. pneumoniae was chosen for the first attempts to clone nif genes because its close resemblance to Escherichia coli allowed it to be directly studied by E. coli genetic techniques.
Human Flourishing in Cross Cultural Settings. Evidence From the United States, China, Sri Lanka, Cambodia, and Mexico.

This paper investigates human flourishing in five culturally distinct populations. Empirical differences in human flourishing were examined using the recently proposed Flourish Index (FI) and Secure Flourish Index (SFI). Five domains for human flourishing are proposed for FI: (D1) happiness and life satisfaction; (D2) physical and mental health; (D3) meaning and purpose; (D4) character and virtue; and (D5) close social relationships. Specification of SFI was augmented by an additional financial and material stability domain (D6). Psychometric properties of FI and SFI were examined with data from the Health and Well-Being Survey. Between June 2017 and March 2018, a total of 6,373 respondents participated in the study – in the US (4083 participants), Sri Lanka (1284 participants), Cambodia (587 participants), China (419 participants) and Mexico (2500 participants). Exploratory and confirmatory factor models were used to validate the proposed indices. An exploratory approach informed analysis for item groupings. Confirmatory factor models were used to investigate the hierarchical structure of the indices. Configural, metric and scalar measurement invariance were established, which not only supported the universal character of the indices but also validated use of indices in culturally distinct populations. Findings from our study enrich our knowledge about human flourishing, providing unique comparative results for five populations. With the exception of happiness and life satisfaction, respondents in the US, despite enjoying the highest financial and material stability, scored the lowest in all other domains of human flourishing. Respondents in China excelled in close social relationship and health domains. In addition to life satisfaction and happiness, character and virtue were blooming in Cambodia. Respondents in Mexico, despite having the lowest scores in financial and material stability, had the greatest meaning and purpose to their lives. Respondents in Sri Lanka were the least happy and satisfied with life.
A Comparison of Heat and Interchromosomal Effects on Recombination and Interference in DROSOPHILA MELANOGASTER.

Heat and interchromosomal effects on recombination have been compared for 23 regions comprising the predominantly euchromatic portions of the five arms of the Drosophila genome. Patterns of response are strikingly similar, with both modifiers causing proximal and distal increases and minimal effects in the middle of the arms. Changes in interference for the same regions in the presence of the two modifiers reveal little similarity, except for the X chromosome. The question of independent control of interference and recombination, as well as alternatives for their temporal sequence, is discussed. Recombination response to the two modifiers in the centric heterochromatin of chromosoaime 2 is markedly different from that found in euchromatin. The interchromosomal effect is absent here, whereas heat induces an increase roughly an order of magnitude greater than that found in euchromatin and totally unlike the lack of response in the proximal heterochromatin of the X chromosome. It is proposed that the sequestering of DNA satellite I (thermal dissociation 9–20° lower than that of the other major satellites) in the centromeric heterochromatin of chromosome 2 (but not in X or 3) may account for the increase.
The Evolving Role of Thiopurines in Inflammatory Bowel Disease

With the advent of biologic therapies for the treatment of inflammatory bowel disease, the roles of thiopurines have continued to evolve. This review will focus on recent advances in pharmacology and the safety and efficacy of thiopurines as maintenance therapies for steroid-induced remissions and post-surgical maintenance of remission and as combination therapies to reduce immunogenicities of biologic agents. Due to pharmacogenetics of thiopurine S-methyltransferase, thiopurine dosing is more effectively based on monitoring of thiopurine metabolites rather than weight-based dosing. Thiopurines continue to have a role as maintenance therapy after steroid-induced remissions and in combination with biologics to induce and maintain remission. Safety monitoring includes measurements of blood counts, liver chemistries, and dermatologic evaluations and protection from sun exposure. Thiopurines appear to be safe during pregnancies and while very uncommon, lymphomas (including hepatosplenic T cell lymphomas) remain a recognized risk, particularly in younger and older males.
CHAPTER VIII – FOOD

Publisher Summary This chapter discusses different commissions and their work toward food. Rome was the venue for two major meetings on issues related to food in 1976. The first was the United Nations Conference on the Establishment of an International Fund for Agricultural Development (IFAD). The second was the meeting of the World Food Council. The 1974 World Food Conference had pin-pointed a crucial element in economic development—the urgent need to increase the growth rate of food production in the developing world. The proposal to set up an International Fund for Agricultural Development was adopted by the World Food Conference in Rome in 1974. Three meetings of interested countries—in Geneva in May 1975, in Rome in October 1975 and in February 1976—worked out details of a draft agreement for the fund. It is conceived of as a development fund that will disburse grants and loans on highly concessional terms to increase food production in the developing world.
Research on Transformer State Evaluation Method Based on Fault Feature Extraction

In order to realize the dynamic evaluation of transformer status and gradually improve the level of equipment fault diagnosis, a transformer condition assessment method based on fault feature extraction was proposed in this paper. Based on the data of the key state quantity of dissolved gas in transformer oil, this method extracted the transformer fault characteristics through various mathematical methods such as hypothesis testing and logistic language regression, and selected new indexes that could better reflect the operating state of transformer, so as to judge the operating state of transformer. In this paper, a large number of indicators were screened, and the regression method was used to find the indicators to judge the fault, without other external conditions. The analysis results showed that the average prediction accuracy of the proposed method was more than 95% under multiple cross validation, which had high engineering application value.
Competing on AAG’s Career Ladder

This chapter illustrates the competitive nature of teaching at Eclipse and explores consequences for teachers’ everyday realities. Informal career tracks—promotion, plateau, turnover—emerged as a way to motivate some and drive out nonperformers. These tracks are communicated to teachers and their peers in formal and informal methods. Although some resist tracking, many become invested and actively police boundaries. These teachers’ relationships with one another eliminate their desire and ability to work together. While market-based reforms characterize declining collective bargaining as a “win” for student learning, my data suggest that competition and career tracking are just the opposite. Competing teachers resist collaboration, prioritizing short-term performance just to be promoted out of the classroom. Schools like Eclipse become a revolving door at the expense of collaboration and stability—known contributors to success (Kyriakides and Creemers 2008; Ronfeldt, Farmer, McQueen, and Grissom 2015).
Topiramate rectal suspensions in pediatric patients.

Abstract We report our experience with topiramate rectal suspensions in a single center case series of three patients
Integration time adjusted completeness

Future, large-scale, exoplanet direct-imaging missions will be capable of discovering and characterizing Earth-like exoplanets. These mission designs can be evaluated using completeness, the fraction of planets from some population that are detectable by a telescope at an arbitrary observation time. However, the original formulation of completeness uses instrument visibility limits and ignores additional integration time and planetary motion constraints. Some of the sampled planets used to calculate completeness may transit in and out of an instrument’s geometric and photometric visibility limits while they are being observed, thereby causing the integration time agnostic calculation to overestimate completeness. We present a method for calculating completeness that accounts for the fraction of planets that leave the visibility limits of the telescope during the integration time period. We define completeness using the aggregate fraction of an orbital period during which planets are detectable, calculated using the specific times that planets enter and leave an instrument’s visibility limits and the integration time. To perform this calculation, we derive analytical methods for finding the planet-star projected separation extrema, times past periastron that these extrema occur, and times past periastron that the planet-star projected separation intersects a specific separation circle. We also provide efficient numerical methods for calculating the planet-star difference in magnitude extrema and times past periastron corresponding to specific values Δmag. Our integration time adjusted completeness shows that, for a planned star observation at 25 pc with 1-day and 5-day integration times, integration time adjusted completeness of Earth-like planets is reduced by 1% and 5% from the integration time agnostic completeness, respectively. Integration time adjusted completeness calculated in this manner also provides a computationally inexpensive method for finding dynamic completeness—the completeness change on subsequent observations.
Implementation of a Socially Distanced In-Person Laboratory Experience across the Chemistry Curriculum during the COVID-19 Pandemic at a Small, Liberal Arts University

The COVID-19 pandemic resulted in the mass shutdown of universities across the United States in the spring of 2020. As the pandemic progressed, regional regulations resulted in a broad range of teaching modalities for the 2020-2021 academic year. While some regions remained tightly locked down (resulting in online-only instruction), others allowed limited or full campus operations within higher education. Located in Spokane, WA, Whitworth University is a small, liberal arts university which was allowed limited operations under a socially distanced model. While the pandemic resulted in some obvious campus changes (for example, masks were required on campus), more subtle changes were required at the curricular level. Adopting a flex model where students and faculty were allowed the option to participate online only while in-person classes were offered, Whitworth maintained in-person education through the 2020-2021 academic year. This FLEX model presented specific difficulties to laboratory courses due to social distancing restrictions. In this work, we describe five models developed in the Whitworth University Department of Chemistry toward teaching laboratories in a socially distanced manner with reduced room capacity. The primary modes of instruction were (1) a reduction of in-person laboratory time so that only half of the students were working in the laboratory at any given time, (2) an alternating weeks model where students came to the laboratory every other week and performed online laboratory experiences in the off weeks, (3) a split room model where one faculty member oversaw two laboratory spaces containing one-half of the normal number of students, (4) a higher number of smaller lab sections where social distancing could be maintained, and (5) a hybrid technique utilizing several of these concepts dependent upon the learning outcomes of the laboratory procedure each week. Benefits and challenges for each model are described by faculty herein. End-of-semester student course evaluation scores provide a comparison of student perceptions of learning outcomes and experiences in the laboratory in the various models. In addition, grade point averages were compared to prior years. Finally, departmental leadership provides insight on the administrative challenges of implementing these course models. Statistically, the models presented no significant change in student perceptions of learning or grade point averages for most courses regardless of the model when compared to prior offerings of these courses. Overall, the implementation of these protocols allowed students hands-on laboratory experiences with a minimal impact on the curriculum presented. ©
Effects of La-addition to the structure, hydrogen storage, and electrochemical properties of C14 metal hydride alloys

Abstract The structure of a series AB2 metal hydride alloys, in which La substitutes for Zr (Ti12Zr22.8−xV10Cr7.5Mn8.1Co7.0Ni32.2LaxAl0.4, x = 0 to 5), is studied and correlated to various hydrogen storage properties in both gaseous phase and electrochemical systems. La, instead of entering the main Laves phase, forms a LaNi secondary phase which has very limited solubility with other elements. This phase improves activation of both capacity and high-rate dischargeability through a dramatic increase in surface area due to pulverization. The presence of LaNi phase also improves the high-rate dischargeability, facilitating the bulk diffusion of protons through synergetic effects with the main Laves phase. La-content in the alloys also suppresses the TiNi secondary phase due to competition of Ni with the LaNi phase. The lattice constants and unit cell volume of the main C14 phase decreases as more Zr (relatively large) is substituted out, which leads to a less stable hydride with higher equilibrium plateau pressure, higher ΔH, and lower hydrogen storage capacity. With the addition of La in the alloy samples, C14 and LaNi phase abundances increase while C15 and TiNi phase abundances decrease. At −40 °C, the charge-transfer resistance of the La-containing alloys decreases as a result of increased catalytic ability in the main phase. The lowest overall charge-transfer resistance obtained from electrochemical impedance spectroscopy analysis measured at −40 °C is 11 Ω g.
A nonlinear system model of isometric force.

The analysis of isometric force may provide early detection of certain types of neuropathology such as Parkinson's disease. Our long term goal is to determine if there are detectable differences between model parameters of healthy and unhealthy individuals. In this study we used system identification techniques to estimate the parameters of dynamic system models of the isometric force exerted by the index finger and focused on a single category of subjects, healthy young adults. The experiments involved subjects exerting isometric force over a range from 5% to 95% of maximal voluntary contraction. The coefficients of the differential equation models depended on the target force level. This finding suggests that a nonlinear dynamic system model provides the best fit for isometric force experiments. I.
[6] Use of antisense RNA to block peptide-processing enzyme expression

Publisher Summary This chapter discusses the use of antisense RNA to block peptide- processing enzyme expression. The basic idea of the antisense method is to lower the rate of synthesis of one specific target protein and then to investigate the consequences for peptide processing in a neuroendocrine cell that is synthesizing biologically interesting peptides. The method may involve the introduction into cells of RNA complementary to the normal coding or sense strand of RNA. The RNA can be introduced into the cell directly or made by the cell that is expressing an appropriate DNA vector, and the antisense RNA will then pair with only the targeted endogenous mRNA. Alternatively, a synthetic oligonucleotide (DNA) is introduced into the cell and pairs with the endogenous sense RNA. The hope in either approach is that the antisense RNA or DNA will alter expression of only the targeted protein.
United Kingdom and United States Responses to the Regulatory Challenges of Modern Financial Markets

The modernization of world financial markets over the last 20 years has raised profound regulatory challenges. Our article considers whether the United States' Gramm-Leach-Bliley Act of 1999 (GLB) and the United Kingdom's Financial Services and Markets Act 2000 (FSMA) meet those challenges. We posit that the most compelling regulatory issue is not whether the financial industry should be allowed to consolidate. Rather, we believe that the organization and practices of the regulators, i.e., the question of which agencies regulate which firms and under what set of laws, should be the focal point. We call this an issue of regulatory modernization. We examine how regulatory modernization has been addressed under the GLB and the FSMA. We show how the United States and the United Kingdom have taken distinct approaches to the issue and highlight the weaknesses of each approach. We compare the approaches of the United States and United Kingdom to trends in other countries and offer predictions on the future of reform.
A model for random genetic damage directing selection of diploid or aneuploid tumours

Objectives: To test whether genetic instability may determine whether tumours become aneuploid or diploid. Materials and methods: We have identified genes needed for cell survival or replication by combining Affymetrix gene expression array data from 12 experimental cell lines with in silico GEO+GNF and expO databases. Specific loss of heterozygosis (LOHs), chromosomal abnormalities (called derivative chromosomes) and numbers of normal homologues were identified by SNP and SKY analyses. Random gene losses were calculated under the assumption that bi-allelic MMR gene inactivation causes a 20-fold increase in rate of gene loss. Results: There were ∼1.23 × 104 genes widely dispersed throughout the genome and possibly expressed by all cells for survival or proliferation, many of these genes performed housekeeping functions. Conservation of the genes may explain the complete haploid genomes found for 15 different cell types and derivative chromosomes selectively retained in aneuploid cancer cell lines after LOH formations, and normal homologue losses. Loss of cell survival/replication genes was calculated to be higher in colon stem cells of carriers of MMR gene mutations than carriers of APC gene mutations. Conclusion: Random loss of cell survival/replication genes was calculated to be low enough for colon stem cells with APC gene mutations to ‘select’ LOH and derivative chromosome combinations favouring tumour cell proliferation. However, cell survival/replication gene loss was calculated to be too high for colonic stem cells lacking MMR genes to survive chromosomal instability, explaining why MMR mutations only produce tumours with diploid chromosome cells.
Call-by-Value Combinatory Logic and the Lambda-Value Calculus

Since it is unsound to reason about call-by-value languages using call-by name equational theories, we present two by-value combinatory logics and translations from the λ-value (λv) calculus to the logics. The first by-value logic is constructed in a manner similar to the λv-calculus: it is based on the byname combinatory logic, but the combinators are strict. The translation is non-standard to account for the strictness of the input program. The second by-value logic introduces laziness to K terms so that the translation can preserve the structure of functions that do not use their argument. Both logics include constants and delta rules, and we prove their equivalence with the λv-calculus.
Analysis of vestibular schwannoma size: A literature review on consistency with measurement techniques

Abstract Introduction Vestibular schwannoma (VS) tumor size, a significant prognostic indicator, is closely analyzed in patients undergoing observation or treatment. It has historically been reported in terms of linear size; however, volumetric assessments can now be performed routinely. We examine the use of described measurement techniques in large published clinical series to assess their consistency. Methods Computerized searches of the MEDLINE database (Pubmed) from 1975 to August 2014 were conducted with the purpose of identifying large series describing the management of VSs. Articles that reported tumor size measurements were included if they described greater than 600 patients. Results 19 studies were found fitting the inclusion criteria, consisting of large retrospective studies with sample sizes ranging from 614 to 2991. A total of 17 studies reported linear measurements, while 2 studies reported volumetric assessments of tumor size. Significant variations were found regarding methods for linear measurement. Furthermore, several papers did not provide any details regarding the measurement technique. Inclusion of intracanalicular portions of the tumor was highly variable. Volume assessments were performed by segmented volume analysis. Conclusions Among the large published series on VSs, significant variation exists regarding the utilized measurement technique to assess size. Volumetric assessments have the greatest clinical utility, sensitivity and accuracy in measuring tumor size and growth. Standardization of volume assessments will provide the best method for producing consistent literature findings.
TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: PHYSIOLOGICAL REACTIVITY TO TRAUMA IMAGERY AS AN OBJECTIVE MEASURE OF TREATMENT RESPONSE.

Background Physiological reactivity to trauma-related cues is a primary symptom of PTSD and can be assessed objectively using script-driven imagery paradigms. However, subjective self-reported symptom measures are the most common outcome indices utilized in PTSD treatment trials and clinic settings. We examined physiological reactivity during a short trauma imagery task as an objective index of response to PTSD treatment, optimized for use in routine clinical care settings. Methods Participants were 35 male combat veterans receiving prolonged exposure (PE) therapy in a Veterans Affairs outpatient clinic. In addition to traditional subjective self-reported and clinician-rated symptom measures, patients also completed a script-driven imagery task in which heart rate (HR) and skin conductance (SC) were recorded at three assessment points across treatment. We examined changes in subjective symptom measures and objective trauma-specific physiological reactivity over the course of PE, and investigated the association between pretreatment physiological reactivity and treatment response. Results Patients who completed PE showed significantly diminished HR and SC reactivity to trauma imagery across therapy. Additionally, individuals showing greater trauma-specific HR reactivity at pretreatment showed greater reductions in subjectively reported PTSD symptoms after the first session of imaginal exposure, and at posttreatment. Conclusions Findings support the utility of physiological reactivity during trauma imagery as an objective outcome measure that has the potential to be incorporated into evidence-based PTSD treatment in routine clinical settings, or prospective studies related to the individualization of care at pretreatment.
Fully-Lagrangian and lattice-Boltzmann methods for solving systems of conservation equations

Abstract A class of "fully-Lagrangian" methods for solving systems of conservation equations is defined. The key step in formulating these methods is the definition of a new set of field variables for which Lagrangian discretization is trivial. Recently popular lattice-Boltzmann simulation schemes for solving such systems are shown to be a useful sub-class of these fully-Lagrangian methods in which (a) the conservation laws are satisfied at each grid point, (b) the Lagrangian variables are expanded perturbatively, and (c) discretization error is used to represent physics. Such schemes are typically derived using methods of kinetic theory. Our numerical analysis approach shows that the conventional physical derivation, while certainly valid and fruitful, is not essential, that it often confuses physics and numerics and that it can be unnecessarily constraining. For example, we show that lattice-Boltzmann-like methods can be non-perturbative and can be made higher-order, implicit and/or with non-uniform grids. Furthermore, our approach provides new perspective on the relationship between lattice-Boltzmann methods and finite-difference techniques. Among other things, we show that the lattice-Boltzmann schemes are only conditionally consistent and in some cases are identical to the well-known Dufort-Frankel method. Through this connection, the lattice-Boltzmann method provides a rational basis for understanding Dufort-Frankel and gives a pathway for its generalization. At the same time, that Dufort Frankel is no longer much used suggests that the lattice-Boltzmann approach might also share this fate.
The Flipped Classroom: Student-Driven Library Research Sessions for Nutrition Education

This article reports on the use of a flipped classroom technique to teach library research skills to upper-level undergraduate nutrition students. A public university Health Sciences librarian and two Nutrition faculty members collaborated to implement a flipped classroom model utilizing online videos and brief assignments packaged in a course-specific library guide for pre-class preparation. Implementation, materials examples, and an evaluation of the method are included. This method provided pre-class learning and increased in-class, hands-on practice in library research for students in an active learning environment. Students found and applied evidence from scientific research studies to course assignments.
Parameters of LRP5 from a structural and molecular perspective.

Abstract LRP5, along with LRP6 and their Drosophila homolog, Arrow, constitute a novel subclass of the LDL receptor superfamily. The arrangement of structural motifs in these receptors is different from the other members of the superfamily, and only recently have we begun to understand the functional importance of human LRP5 (and LRP6). Whole genome positional cloning studies have identified a number of mutations in LRP5 that underlie inherited human diseases/phenotypes, particularly those involving the skeleton and the eye. A number of studies have illustrated the importance of Lrp5/6/Arrow as a co-receptor with Frizzled for the Wnt proteins and their critical role in the regulation of the Wnt/beta-catenin signaling pathway. The cataloging of these human mutations, in combination with engineered mutations in mice and other studies involving gene/protein modifications, has led to a better understanding of the function of the various domains in LRP5/6. In this review, we discuss a number of studies that have revealed a wide variety of protein-protein interactions that occur with the various structural motifs in the Lrp5 protein. Ultimately, these interactions regulate the activity of the Wnt/beta-catenin signaling pathway and the role it plays in processes such as bone mass accrual and vision.
Oxidative stress is the new stress.

Emotional stress may increase anxiety, but in mice, a different kind of stress—oxidative stress—may also contribute to anxious behavior.
O-antigen structure in a virulent strain of Aeromonas hydrophila

Lipopolysaccharide (LPS) was isolated from a strain of Aeromonas hydrophila which had displayed serological, bacteriophage attachment and virulence properties similar to those found in strains of Aeromonas salmonicida. The structure of the O-antigen was determined and had many points of similarity with that previously elucidated for the O-antigen of A. salmonicida. Methylation analysis, chromium trioxide oxidation and 1H-n.m.r. were used to confirm that the repeating unit of the O-chain had the following structure:
Estimating soil temperatures and frost in the lake effect snowbelt region, Michigan, USA

Abstract A physically-based computer model is developed for estimating soil temperatures at 0.05, 0.1, 0.2, and 0.5 m in sandy, forested soils, using only daily precipitation and minimum and maximum air temperatures as input data. The algorithm is evaluated by comparing its output to 490 soil temperature observations for 1990–1993 at 10 sites in Michigan, USA. The mean bias of the errors of the soil temperature estimates ranges from +0.6° to– .6°C, depending upon depth and season, thus comparing favorably to models requiring more detailed input. The model is applied to 14 stations across lower Michigan, using 1951–1991 US National Weather Service data, in order to examine regional trends in soil temperature and freezing and to compare these trends to patterns of snow thickness and air temperature. Simulations reveal that soils seldom freeze within the deep lake-effect snow belt of southern Michigan and along the coast of Lake Michigan. Soil freezing is more common at non-snowbelt, interior locations. Based on simulation data, new “potential freeze day” indices are presented that correlate better with annual minimum soil temperatures and “number of days frozen” than do other, more commonly used indices of freezing not specifically formulated for soils.
Augmentation of some aspects of wound healing by a “Skin Respiratory Factor”

Skin Respiratory Factor (SRF), a water soluble extract of Brewer’s Yeast, Saccharomyces cerevisiae, was brought to the attention of our laboratory by the Review Panel on Over-The-Counter Hemorrhoidal Preparations, an advisory committee of the Food and Drug Administration. The Panel, which is assessing SRF as an ingredient in a proprietary hemorrhoidal product, Preparation H, requested us to evaluate SRF as a wound-healing agent. Since there was evidence from the manufacturer that SRF influences oxygen consumption by fibroblasts [2], and since some aspects of wound healing, including collagen formation, epithelization, and wound strength, can be influenced by agents altering oxygen consumption, this laboratory considered undertaking an evaluation of SRF to be a matter of scientific interest. Our evaluation of SRF utilized a number of established methods of studying wound healing, and the results were of sufficient interest to warrant publication. The commercial material is standardized as units with 1 unit (U) of SRF increasing the uptake of oxygen by minced rat abdominal skin (1 mg dry weight) by 1% in a I-hr measurement by Warburg manometry. Yeast extracts contained 8000-12,000 U/g, and the material supplied by the manufacturer for this study contained 8100 U/g.2
Cerebral Glucose and Energy Utilization during the Evolution of Hypoxic—Ischemic Brain Damage in the Immature Rat:

The cerebral metabolic rate for glucose (CMRg1) and cerebral energy utilization (CEU) were assessed in immature rats during recovery from cerebral hypoxia-ischemia. CMRg1 was determined using a modification of the Sokoloff technique with 2-deoxy-[14C]glucose (2-DG) as the radioactive tracer. CEU was determined using the Lowry decapitation technique. Seven-day postnatal rats underwent unilateral common carotid artery ligation, followed 4 h thereafter by exposure to 8% oxygen at 37 degrees C for 3 h. At 1, 4, or 24 h of recovery, the rat pups underwent those procedures necessary for the measurement of either CMRg1 or CEU. At 1 h of recovery, the CMRg1 of the cerebral hemisphere ipsilateral to the carotid artery occlusion was 97% of the control rate (8.7 mumol 100 g-1 min-1) but was only 48% of the control in the contralateral hemisphere. At 4 h of recovery, the CMRg1 was increased 49% above baseline in the ipsilateral hemisphere, decreasing thereafter to 84% of the control at 24 h. The CMRg1 of the contralateral hemisphere normalized by 4 h of recovery. An inverse correlation between endogenous concentrations of ATP or phosphocreatine and CMRg1 in the ipsilateral hemisphere was apparent at 4 h of recovery. CEU in the ipsilateral cerebral hemisphere was 64 and 46% of the control (3.47 mmol approximately P/kg/min) at 1 and 24 h, respectively (p < 0.05) and 77% of the control at 4 h of recovery. CEU in the contralateral hemisphere was unchanged from the control at all measured intervals. Correlation of the alterations in CMRg1 with those in CEU at the same intervals indicated that substrate supply exceeds energy utilization during early recovery from hypoxia-ischemia. The discrepancy combined with a persistent disruption of the cerebral energy state implies the existence of an uncoupling of mitochondrial oxidative phosphorylation as one mechanism for the occurrence of perinatal hypoxic-ischemic brain damage.
Development of a CCD-based optical fluorescence imaging system

An optical fluorescence imaging system was developed using a custom CCD camera. The system is designed and implemented to image an area of 20 mm by 20 mm with a spatial resolution of approximately 3.2 lp/mm. The temporal resolution is 490 frames per second. Comprehensive measurements were performed and the results have shown that the system is capable of providing high spatial resolution while maintaining good temporal resolutions and wide dynamic range. The system is a useful research tool in some biomedical experiments.