cssi/SciSciGPT-SciSciNet huggingface dataset:
Application of the method of moments to acoustic scattering from fluid-filled bodies of arbitrary shape

The method proposed in this paper provides a computational technique for solving acoustic scattering problems associated with arbitrarily shaped two- or three-dimensional fluid-filled bodies. In particular, using free-space Green's functions along with the associated boundary conditions on the surface of the body, a pair of coupled integral equations are derived. The equations are then solved by approximating scatterer geometry by either linear segments or triangular patches, for the two- or three-dimensional cases, respectively, and employing the method of moments. The method presented in this work is simple, efficient and applicable to truly arbitrary geometries. Numerical results are presented for certain canonical shapes and compared with other available data.
Derogation, Exclusion, and Unfair Treatment of Persons with Social Flaws Controllability of Stigma and the Attribution of Prejudice

The effect of controllability of stigma on the attribution of prejudice was investigated in a series of five experiments. In prior prejudice attribution research, the stigma that made the victim subject to discrimination was a characteristic beyond the individual's control, such as age or race. In the present research, controllability of the stigma was systematically varied. Subjects read scenarios in which persons with flaws of speech or appearance were subject to discriminatory behaviors of derogation, exclusion, or unfair treatment. The flaws were either within or beyond the control of the individual possessing them. More prejudice was attributed to those who behaved in a discriminatory way toward persons whose flaws were beyond their control. The theoretical explanation offered for the outcome is that discrimination can be thought of as form of harmdoing, and prejudice attribution as a form of blame attribution.
Nonlinear effects of salt concentrations on evaporation from porous media

[1] Evaporation from porous media saturated with salt solution is influenced by the interactions among the transport properties of porous media, thermodynamics of the evaporating solution and environmental conditions. To study the effects of salt concentrations on the evaporation dynamics, we conducted a series of evaporation experiments under constant atmospheric conditions using columns packed with sand particles saturated with various NaCl solutions differing in concentrations. Results show that the evaporation rate decreases as NaCl concentration increases only up to a certain level. When exceeding this level, any further increase of NaCl concentration results in higher evaporation rates which is described theoretically using the thermodynamics of the solution. Results also reveal a nonlinear relation between NaCl concentrations and onset of efflorescence which is described by the numerical solution of the classical convection-diffusion equation. Moreover, we found a strong correlation between the growth dynamics of precipitated salt at the surface and the evaporation rate such that the maximum rate of surface coverage by salt coincide with the end of stage-1 evaporation. This potentially offers a new method to nondestructively study the evaporation process from saline porous media.
Low copy number vectors for expression of fused genes to β-galactosidase in Escherichia coli

A series of six expression vectors, pXM184 Lac.A, B, C, pXM184Z.A, B, C, based on the low copy plasmid pACYC184 that allow for expression of proteins fused to β-galactosidase in Escherichia coli is described. A level of 50 000 units of β-galactosidase is routinely observed and is easily identifiable on protein gels. This paper also reports the tight regulation of expression of the Trc promoter in these vectors using the LacIq repressor.
Adventitious contamination of intravenous admixtures during sterility testing.

The extent to which contamination of intravenous fluids measured by inhospital sterility-testing may be due to adventitious contamination (i.e., contamination introduced during the sterility-testing procedure) was studied. All one-liter admixtures prepared during a three-day period in a busy centralized i.v. admixture service were studied. Samples of i.v. admixtures were cultured before and after administration by direct ioculation or by culturing the membrane through which the admixture was filtered. Samples of similarly cultured large-volume parenterals served as controls. Contamination rates for control and admixture samples were not significantly different (p = 0.23). Of 10 control and test (admixture) solutions showing contamination before administration, only one test solution again showed contamination after administration but this was with a different microbe. The results suggest that adventitious contamination during sampling/culturing procedures is a component of, and possibly a dominant factor in, the contamination rates detected by inhospital sterility tests. Combined with infection surveillance, sterility tests may be of value when infections are possibly related to admixture contamination.
Class E zero-voltage-switching rectifier with a series capacitor

A circuit of a class E rectifier with a series capacitor is derived from a class E amplifier, using the symmetry between a DC-to-AC inverter and a rectifier. The principle of the circuit's operation is described and verified experimentally. Since the rectifier diode turns on and off at zero voltage, the switching losses are considerably reduced. In addition, the rectifier diode turns off at zero current, reducing the effect of the reverse-recovery time. The rectifier can be used in high-frequency high-efficiency resonant DC/DC power converters. >
Surface vegetation patterning controls carbon accumulation in peatlands

[1] Localized ecohydrological feedbacks have been proposed as important internal drivers of patterns and processes in terrestrial ecosystems. However, there is a significant gap between the prominence of theoretical models and the paucity of observations describing linkages between ecosystem structure and functioning. Here we report empirical evidence for strong interactions between surface vegetation patterning and long-term carbon sequestration rates in four peat bogs in Patagonia on the basis of high-resolution stratigraphic analyses. Peatland development across the study region was characterized by repeated switches between wet- and dry-adapted plant communities, depicting changes between hollows (wet assemblages) and lawns (dry assemblages) that could represent past surface patterning. We found a site-specific relationship between the frequency of the wet-to-dry cycles and carbon accumulation rates that followed a power function, with rapid vegetation shifts causing high peat accumulation rates. Our results show strong evidence for internal regulation of vegetation dynamics and peatland growth, implying that understanding peatland processes is a prerequisite for peat-based paleoclimate reconstructions.
Geographic clustering of underage drinking and the influence of community characteristics

The aim of this paper was to examine the extent to which underage drinking clusters geographically in a sample of communities, and to investigate the manner in which community-level contexts are related to this process. We used data from a randomized community trial of underage drinking to provide the first quantitative estimates of the magnitude of the geographic clustering of underage drinking based upon pairwise odds ratios (PWORs). The Enforcing Underage Drinking Laws Randomized Community Trial provided data from repeated cross-sectional samples of youth aged 14–20 from 68 communities surveyed in 2004, 2006, and 2007 (n = 18,730). Past 30-day drinking, binge drinking, getting drunk, experiencing non-violent consequences as a result of drinking and making a purchase attempt all significantly clustered within-communities with PWORs ranging from 1.05 to 1.21. After adjustment for individual-level characteristics, results remained relatively unchanged. However, there was evidence that the magnitude of the clustering varied as a function of neighborhood disadvantage, neighborhood disorder, and family structure. Clustering of drunkenness and experiencing non-violent consequences as a result of drinking was greatest in the least economically disadvantaged and least disordered communities with the greatest percentage of married-couple families. The clustering of making a purchase attempt, however, was greatest in more disordered communities, specifically the largest communities with the highest degree of residential mobility and housing density. These findings that clustering of underage drinking behaviors varies by community context has the potential for identifying the types of communities to target for underage drinking behavior-specific preventive interventions. © 2009 Elsevier Ireland Ltd. All rights reserved.
Unmasking and provoking severe disease activity in a patient with NMO spectrum disorder

Neuromyelitis optica (NMO) is often not considered in patients with brain lesions in the absence of longitudinally extensive spinal cord lesions. When first-line therapies for multiple sclerosis (MS) fail, treatment is often escalated to natalizumab. We present a case of fulminant NMO spectrum disorder (NMOSD) relapse shortly after initiation of natalizumab in a patient previously suspected of having MS. This patient's course was complicated because disease activity continued even after transitioning to rituximab and having undetectable B cells.
A rapidly filled capillary mount for both dry powder and polycrystalline slurry samples

A method of rapid capillary sample loading of either dry powder or polycrystalline slurry has been developed. By embedding a Millipore filter in a Kapton capillary tube, one can then draw either loose dry powder or polycrystalline slurry into the tube and pack the solid against the filter, creating a dense column of powder suitable for a Debye–Scherrer powder diffraction experiment.
Long‐term hemodynamic and metabolic effects of trimazosin in essential hypertension

The long-term effects of trimazosin (TMZ) were studied in 26 male patients with mild essential hypertension. After a 2 wk single-blind placebo (P) period, 13 patients were randomly selected to receive TMZ and 13 P; they were followed for an additional 8 wk. TMZ was given in incremental doses of 25 to 50. 100 to 200, and finally 300 mg three times a day. The patients were seen at the clinic every 2 wk and their arterial pressures (AP) and heart rates (HRs) were measured in the supine (5 min) and upright (2 min) position. Blood chemistries, blood count, plasma volume (PV), plasma renin activity (PRA), plasma aldosterone (PA), and cardiac output (CO) were determined by ultrasound at the end of P and TMZ periods. TMZ decreased the AP and total peripheral resistance (TPR) at the higher dosages, but had no effect on PV, PRA, PA, CO, HR, or blood chemistry determinations. No effects were observed on any of the above parameters after P. We conclude that (1) TMZ is an effective and safe antihypertensive, (2) it lowers AP through reduction of TPR, and (3) its effect is dose related. Clinical Pharmacology and Therapeutics (1981) 30, 600–604; doi:10.1038/clpt.1981.210
Fast amplitude and phase characterization of optical frequency combs propagating over 50 km of optical fiber using dual quadrature spectral interferometry

We demonstrate fast retrieval(≪1.5µs) of amplitude and phase of optical frequency combs propagating over long lengths of optical fiber(>50km) and of user defined pulse shapes representing higher order propagation effects using dual quadrature spectral Interferometry.
Changes in the Geographic Patterns of Heart Disease Mortality in the United States: 1973 to 2010.

Background—Although many studies have documented the dramatic declines in heart disease mortality in the United States at the national level, little attention has been given to the temporal changes...
Academic Preparation for the Engineering Geologist

The engineering geologist is a geologist that acts as an interpreter—relating geologic processes to engineering products. The geologist must therefore be technologically bilingual. Academic training of engineering geologists must first be founded on a solid knowledge of geology with additional knowledge in engineering. A program that dilutes the geologic training in order to add engineering violates the definition of an engineering geologist. Almost any university could respond to a student9s interest in engineering geology by opening the academic communication lines between geology and engineering. Critical professional skills such as written and oral communications, problem identification, and thinking under pressure can easily be incorporated into geology courses.
Pulmonary vascular heterogeneity: microvascular vs. arterial generation of angiopoietin-2 (IRC5P.633)

Endothelial cell (EC) growth factors, Angiopoietin (Ang)-1 and Ang-2, are important mediators of EC function. Bound to a shared receptor, Tie2, expressed on ECs, they have opposing effects on EC activation. Ang-1/Tie2 promotes a quiescent while Ang-2/Tie2 promotes an activated phenotype and increased vascular permeability. Ang-2, stored preformed in EC Weibel Palade bodies (WPbs), is rapidly released from activated ECs. We have reported increased Ang-2 in the blood of trauma patients with ARDS, representing a potential therapeutic target. To assess lung EC activation and release of Ang-2, we used human pulmonary arterial ECs (hPAECs) and microvascular ECs (hPMECs) grown on electric cell-substrate impedance sensing arrays. These arrays measure changes in EC monolayer integrity in response to inflammatory stimulus. We show that, in response to TNF-a stimulation, hPMECs exhibited increased loss of barrier function compared to hPAECs. Also, Ang-2 in culture supernatant increased in both hPAECs and hPMECs compared to untreated controls. While ECs in larger vessels (arteries), contain WPbs, they are not observed in microvascular ECs (<10um diam). To further investigate, we inhibited WPb vesicle exocytosis. Our findings show that inhibition of WPb release decreased Ang-2 in supernatant from hPAECs, but not significantly from hPMECs, suggesting that the microvascular is a region with distinct responses potentially associated with their location and anatomic structure.
System support for resilience in large-scale parallel systems: from checkpointing to mapreduce

High-Performance Computing (HPC) has passed the Petascale mark and is moving forward to Exascale. As the system ensemble size continues to grow, the occurrence of failures is the norm rather than the exception during the execution of parallel applications. Resilience is widely recognized as one of the key obstacles towards Exascale computing. Checkpointing is currently the de-facto fault tolerant mechanism for parallel applications. However, parallel checkpointing at scale usually generates bursts of concurrent I/O requests, imposes considerable overhead to I/O subsystems, and limits the scalability of parallel applications. Despite the doubt in the feasibility of checkpointing continues to increase, there is still no promising alternative on the horizon yet to replace checkpointing. MapReduce is a new programming model for massive data processing. It has demonstrated a compelling potential in reshaping the landscape of HPC from various perspectives. The resilience of MapReduce applications and its potential in benefiting HPC fault tolerance are active research topics that require extensive investigation. This thesis work targets at building a systematic framework to support resilience in large-scale parallel systems. We address the identified checkpointing performance issue through a three-fold approach: reduce the I/O overhead, exploit storage alternatives, and determine the optimistic checkpointing frequency. This three-fold approach is achieved with three different mechanisms, namely system coordination and scheduling, the utilization of MapReduce framework, and stochastic modeling. To deal with the increasing concerns about MapReduce resilience, we also strive to improve the reliability of MapReduce applications, and investigate the tradeoffs in the programming model selection (e.g., MPI vs. MapReduce) from the perspective of resilience. This thesis provides a thorough study and a practical solution for solving the outstanding resilience problem of large-scale MPI-based HPC applications and beyond. It makes a noticeable contribution to the state-of-the-art and opens a new research direction for many to follow.
Carbon: The Soul of Future Nanoelectronics

Quantum transport in carbon allotropes emerging from graphene/graphite nanolayers is described. Nonequilibrium Arora’s distribution function (NEADF) includes the energy gained/lost in a mean free path (mfp) in the presence of an electric field. It is shown to organize the randomness in equilibrium to streamlined motion in extreme nonequilibrium leading to saturation of drift velocity and the current. A simple tanh form is obtained that is strictly valid for nondegenerate statistics, but is extended to degenerate statistics by defining a degeneracy temperature. Ballistic transport where device length is smaller than the scattering-limited mfp is shown to degrade the mobility. Resistance quantum is obtained in 1D configuration that is generalized to give contact resistance and channel resistance. Magnetotransport in graphene is discussed to demonstrate the utilization of magnetic field in characterization and performance evaluation.
Relationships among temperament, acute and chronic cortisol and testosterone concentrations, and breeding soundness during performance testing of Angus bulls.

Abstract The aim of this study was to examine relationships among temperament, endocrinology, and reproductive parameters of bulls enrolled in an 84-day performance test. Angus bulls (n = 60) were housed in six pens grouped by age and weight. Pen scores (PS; 1 = docile to 5 = very aggressive) were assigned on Days −1, 27, 55, and 83 of the performance test. On the following day, blood and hair samples were collected, and body weight (BW) and exit velocity (EV) were recorded. Bulls were split into two categories based on; Day −1 PS (PScalm = PS 1 or 2; PSexcitable = PS 3 or 4) and Day 0 EV (EVcalm = slowest 20 bulls; EVexcitable = fastest 20 bulls). Cortisol and testosterone concentrations in serum and hair did not differ (P > 0.10) between PS or EV temperament categories. Sampling day differences (P 0.10) over the sampling days. Serum testosterone concentration increased (P
Prevalence of cancer screening: A comprehensive study on cancer screening behavior and barriers in Asian Americans

A104 Objective : The purpose of this study was to determine Asian American subgroup differences in screening rates between Chinese, Koreans, Vietnamese and Cambodians for routine physical exams, breast cancer, cervical cancer, colorectal cancer, prostate cancer, and liver cancer (Hepatitis B) by surveying Asian Americans in community based organizations and to include Asian Americans in the study who may speak little or no English, often not included in national surveys. Methods : The overall sample consisted of 2,011 participants and included Chinese, 45.9% (n = 925), Korean, 19.1% (n = 384), Vietnamese, 18.1% (n = 362), and Cambodian, 16.9% (n=340). Adult Asian Americans 18 years of age or older were eligible to participate in the study. First, the relationship between each demographic and acculturation factor and ethnicity group was examined with chi square analysis. Additionally, the percentages across the four ethnicities were reviewed to identify group differences. Second, the relationship between each cancer screening variable and ethnicity group was examined with chi square analysis. The prevalence of cancer screening associated with each ethnicity was examined in order to identify high-risk ethnicities. For each chi square test, significance was set at p Results : The screening rates for never screened were high for all Asian groups and cancer screenings and there were racial/ethnic subgroup differences in rates. Cambodian mammogram never screening rate was 78.5%, more than double that of any other ethnic group, and Chinese the lowest proportion 20.1%. Cambodians had the lowest rate (11.4%) of compliance among those who reported being screened within 12 months. For PAP screening, 75.6% of Cambodians and 28.0% of Chinese reported never screened. For Hepatitis B screening, the overall never screening rate cross the four ethnicities was 71.4%; 89.3% for Cambodian, 79.7% for Vietnamese, 67.8% for Korean, and 62.1% for Chinese, respectively. Never screening for prostate cancer screening included Cambodian men (97.0%), Vietnamese (88.0%), Koreans (78.9%), and Chinese (56.7%). Never screening for Colorectal included Cambodians (94.9%) and Chinese (65.3%). Koreans had the highest never screened proportion (34.7%) of routine health check out of the four ethnicities. Conclusions : To meet cancer screening guidelines, differences between Asian American subgroups should be considered to enhance screening rates.
Postpartum Hemorrhage in a Conflict Setting

Mapendo is a 24-year-old woman who has just given birth to her fifth child after a 3-day labor. It is the middle of the night and although quite dark, the birth attendant can tell there has been too much bleeding.
Shall we play again? The effects of repetitive gameplay and self-efficacy on behavioural intentions to take earthquake precautions

ABSTRACTPlaying serious games may allow individuals to acquire essential disaster preparedness knowledge and skills. Playing such games repeatedly could generate self-efficacy, and consequently lead to behavioural intentions to take precautions. This study examines the effects of repetitive-play of an earthquake preparedness game on behavioural intentions, and the role of self-efficacy in mediating these positive outcomes. An experimental study was conducted, where repetitive-play was manipulated in a laboratory setting. An online self-administered survey was used to measure self-efficacy and behavioural intentions. Results showed that those in the repetitive-play condition had significant intentions to take precautions compared only to those in the no-play condition. The gradual increase in intentions from no-play to single-play to repetitive-play was not significant. Earthquake preparedness self-efficacy mediated the relationship between repetitive-play and behavioural intentions. Results of this study ...
Multiple Group Confirmatory Factor Analysis of the DASS-21 Depression and Anxiety Scales: How Do They Perform in a Cancer Sample?

The DASS-21 is a public domain instrument that is commonly used to evaluate depression and anxiety in psychiatric and community populations; however, the factor structure of the measure has not pre...
Field Evaluation and Cost Effectiveness of Crack Sealing in Flexible and Composite Pavements

One of the most common methods used to treat longitudinal and transverse cracks is crack sealing (CS), which is categorized as a preventive maintenance method. Field performance and cost-effectiven...
Serine catabolism is essential to maintain mitochondrial respiration in mammalian cells

Breakdown of serine by the enzyme serine hydroxymethyltransferase (SHMT) produces glycine and one-carbon (1C) units. These serine catabolites provide important metabolic intermediates for the synthesis of nucleotides, as well as methyl groups for biosynthetic and regulatory methylation reactions. Recently, it has been shown that serine catabolism is required for efficient cellular respiration. Using CRISPR-Cas9 gene editing, we demonstrate that the mitochondrial SHMT enzyme, SHMT2, is essential to maintain cellular respiration, the main process through which mammalian cells acquire energy. We show that SHMT2 is required for the assembly of Complex I of the respiratory chain. Furthermore, supplementation of formate, a bona fide 1C donor, restores Complex I assembly in the absence of SHMT2. Thus, provision of 1C units by mitochondrial serine catabolism is critical for cellular respiration, at least in part by influencing the assembly of the respiratory apparatus.
The relationships between compensatory stepping thresholds and measures of gait, standing postural control, strength, and balance confidence in older women.

Abstract Background Compensatory stepping thresholds evaluate the response to postural disturbances. Although such fall-recovery measures are a promising indicator of fall risk, the relationships between stepping thresholds and other measures used to predict falls are not well established. Research Question We sought to quantify the relationships between stepping thresholds and other measurements used to assess fall risk in older women, a population at high risk for falls and related injuries, including fractures. Methods We studied 112 ambulatory, community-dwelling women, age 65 years or older. Using a treadmill to deliver standing postural disturbances, we determined anterior and posterior single-stepping and multiple-stepping thresholds. These thresholds represented the magnitude of the disturbance that elicited one step or more than one step, respectively. We also assessed balance confidence, functional reach, unipedal stance time, isometric strength, obstacle crossing, postural sway, and gait kinematics. Outcomes were normalized to body size. Results After accounting for age, stepping thresholds were, at most, moderately correlated (Pearson partial correlation coefficients r = 0.20 to 0.40 and r = -0.21 to -0.31) to several assessments of gait, postural control, and strength. Approximately 24–52% of the variance in stepping thresholds was explained by a combination of age and other fall risk assessments, which frequently consisted of balance confidence, unipedal stance time, obstacle crossing, the Romberg ratio of postural sway, and/or strength. Significance Our results suggest that anteroposterior fall-recovery ability, as assessed by stepping thresholds, can only be partially inferred from age and a combination of assessments of sway, strength, unipedal tasks, and balance confidence. Compensatory stepping thresholds may provide information on stability maintenance unique from other assessments of fall risk. Further investigation would be necessary to determine whether stepping thresholds are better predictors of falls in older women.
Batons and ballots: The effectiveness of state violence in fighting against Catalan separatism

What are the consequences of police brutality in fighting against the Catalan secessionist movement? While Spanish authorities resorted to violence with the hope that forceful action would deter fu...
A Branched DNA Assay for Detecting TMPRSS2-ERG Fusions

The editorial comments provide an important counterbalance to our report of a new method for detecting TMPRSS2-ERG gene rearrangement in prostate cancer. This gene rearrangement juxtaposes a prostate-specific promoter (TMPRSS2) with a transcription factor that is not normally expressed in the prostate (ERG) and leads to expression of high levels of ERG by prostate cells that normally would not express ERG. The ERG transcription factor, in turn, can lead to expression of a host of other genes that are not expressed in normal prostate epithelium. Preliminary studies that discovered and validated this mutation suggested that it is present in over half of prostate cancers, making it one of the most common chromosomal aberrations in solid human tumors, suggesting the rearrangement may be a major breakthrough in prostate cancer biology. (1) However, the exact prevalence of such gene rearrangement remains unknown, in part due to technical limitations of the two currently available methods for detecting the rearrangement, that are based on RT-PCR and FISH. RT-PCR of human prostate tissue is problematic because RT-PCR is especially sensitive to interference from artifacts related to RNA degradation, and human prostate tissue has very high rates of RNAse activity and consequent RNA degradation. FISH evaluates the rearrangement at the level of DNA instead of RNA, but is laborious, technically challenging, and is limited in its ability to detect the myriad of possible chromosomal deletion or translocation events that could result in juxtaposition of TMPRSS2 and ERG. New methods with lower inter-assays variability than the known problems of quantitative RT-PCR and FISH are needed to help characterize the prevalence of TMPRSS2-ERG gene fusions and facilitate evaluating the clinical consequences of such gene fusion, which is not yet known. The branched DNA assay described in our report provides an alternative to RT-PCR or FISH for detecting TMPRSS2-ERG fusion. Branched DNA assays have inter-assay consistency that compares favorably to that of RT-PCR, and unlike FISH such assays are quantitative. A gold-standard assay that can detect TMPRSS2-ERG fusion in every case where such fusion is present has not yet been established. In this setting, a new assay that can detect fusions not detected by FISH and RT-PCR has the potential to be a useful tool for studies to characterize the true prevalence of TMPRSS2-ERG fusion in prostate cancer and facilitate determining the clinical consequence of this intriguing genetic rearrangement.
Isolation and Analysis of Chinese Hamster Cells Carrying Forward and Reverse Mutations in the Hypoxanthine-Guanine Phosphoribosyltransferase Locus

In studies of somatic cell genetics, mutagenesis, cell fusion, etc., the locus for hypoxanthine-guanine phosphoribosyltransferase (HGPRT) has received considerable attention (see Caskey and Kruh for a review1). The product of this gene in various mammalian systems is a protein of about 25,000 molecular weight which associates into oligomers that catalyze the formation of IMP or GMP from 5-phosphoribosyl pyrophosphate (PP-Ribose-P) plus hypoxanthine or guanine. A number of purine analogs such as 8-azaguanine and 6-thioguanine also serve as substrates for the enzyme and are converted to toxic nucleotides which kill normal cells and enable the isolation of HGPRT-deficient clones of cultured cells(2). Although the enzyme is normally not required for cell growth, agents such as aminopterin can be used to block de_ novo synthesis of purine nucleotides thus making cellular multiplication dependent on the presence of hypoxanthine and HGPRT activity and providing a reverse selective system for the locus(3). The realization that HGPRT-deficiency is the biochemical defect in human patients with the X-linked Lesch-Nyhan Syndrome(4) localized the locus for the enzyme to the X chromosome and focused additional attention on the gene and its product.
Balancing RAF, MEK, and EGFR Inhibitor Doses to Achieve Clinical Responses and Modulate Toxicity in BRAF V600E Colorectal Cancer

Recent years have seen dramatic clinical advances in targeting the ERK pathway with the FDA approval of several selective inhibitors of RAF and MEK1–5. Clinical trials of these agents indicate that near complete inhibition of pathway signaling is necessary to effectively inhibit tumor growth6. Targeted approaches have been most successful in BRAF V600E tumors because of the relatively wide therapeutic index of RAF inhibitors (vemurafenib and dabrafenib), which inhibit signaling in cells with BRAF V600 mutants but cause “paradoxical activation” of ERK signaling in normal cells that are wild-type for RAF kinases. In contrast, MEK inhibitors (trametinib and cobimetinib) suppress ERK signaling in all cells, and their clinical activity has been limited by a narrow therapeutic index. Combining these agents – with RAF and MEK inhibitors for BRAF V600E melanoma or lung cancer and with RAF, MEK, and EGFR inhibitors for BRAF V600E colorectal cancer – to profoundly inhibit ERK signaling has led to improved antitumor activity7. Combination therapy has also been shown to offset the toxicities caused by RAF inhibitors, such as the development of keratoacanthomas and squamous cell carcinoma, resulting from paradoxical ERK activation with these agents. The role of RAF inhibitors to offset MEK inhibitor toxicity and the need for dose intensity to modulate opposing toxicities is less clear. Recent observations in clinical trials have suggested that RAF inhibitors offset dermatologic toxicity from MEK or EGFR inhibitors. In the phase III trial of trametinib in melanoma, grade 3 or 4 acneiform dermatitis occurred in 8% of trametinib-treated patients, whereas in the phase III trial of the combination of dabrafenib and trametinib, no patient had grade 3 or 4 acneiform dermatitis8,9. Combinations of RAF and EGFR inhibitors have also had a lower incidence of acneiform rash than seen with EGFR inhibitors alone7,10,11. This is also likely due to the opposite effects of RAF and EGFR inhibitors on MEK activation in normal cells. However, the doses of RAF inhibitors needed for these clinically opposing effects and how these doses compare to clinically efficacious doses have not been studied. We now report the course of a patient with BRAF V600E CRC treated with dabrafenib, trametinib, and panitumumab in a phase II clinical trial, and within this patient characterize the effect on toxicities of different dose levels of these agents. Further, we find that, within the clinical dose range, there is a RAF inhibitor dose that is an inflection point for the toxicity and efficacy of this regimen.
Routine Versus Selective Adrenal Vein Sampling for Primary Aldosteronism

Primary aldosteronism (PA) represents a spectrum of conditions characterized by autonomous adrenal aldosterone secretion, and hypertension. Adrenalectomy is associated with excellent outcomes in patients with unilateral autonomous primary aldosteronism, whereas bilateral adrenal aldosteronism does not respond to unilateral adrenalectomy and such patients are better managed using medical therapy. Given the importance of lateralization on therapeutic decision-making and outcomes, the accuracy of lateralization tests is crucial.
Alginate/chitosan microparticles for gastric passage and intestinal release of therapeutic protein nanoparticles

Enzymes with intracellular activity have significant potential to treat diseases. Protein nanoparticles (NPs) considerably enhance intracellular delivery of enzymes. We have previously shown that a Salmonella effector enzyme, AvrA, delivered by NPs is capable of modulating inflammatory signals in a murine dextran sulfate sodium (DSS) colitis model. The NPs were instilled intrarectally, limiting delivery to the distal colon. Localized intestinal delivery of protein therapeutics via the oral route is a highly attractive alternative approach. However, the harsh conditions in the gastrointestinal tract can severely reduce protein function. The approach described here is to deliver therapeutic protein NPs encapsulated within gastro-protective microparticles (MPs) made from alginate and chitosan that subsequently release NPs in the small intestine and colon. A flow focusing microfluidic device was used to form alginate droplets encapsulating protein NPs. Droplets were then simultaneously crosslinked with calcium and coated with chitosan. Protein NPs encapsulated within crosslinked alginate/chitosan MPs were protected and retained their activity after incubation in simulated gastric fluid (SGF). Subsequent incubation in simulated intestinal fluid (SIF) induced release of bioactive protein NPs. Oral administration of AvrA NPs encapsulated in alginate/chitosan MPs delivered protein to intestinal epithelia and reduced clinical and histological scores of inflammation in a murine DSS-induced colitis model. Altogether, NPs in alginate/chitosan MPs are a potential oral delivery vehicle for protein therapeutics.
Antimicrobial blue light for decontamination of platelets during storage.

Platelet (PLT) storage is currently limited to 5 days in clinics in the United States, in part, due to an increasing risk for microbial contamination over time. In light of well-documented antimicrobial activity of blue light (405-470 nm), we investigated potentials to decontaminate microbes during PLT storage by antimicrobial blue light (aBL). We found that PLTs produced no detectable levels of porphyrins or their derivatives, the chromophores that specifically absorb blue light, in marked contrast to microbes that generated porphyrins abundantly. The difference formed a basis with which aBL selectively inactivated contaminated microbes prior to and during the storage, without incurring any harm to PLTs. In accordance with this, when contamination with representative microbes was simulated in PLT concentrates supplemented with 65% of PLT additive solution in a standard storage bag, all "contaminated" microbes tested were completely inactivated after exposure of the bag to 405 nm aBL at 75 J/cm2 only once. While killing microbes efficiently, this dose of aBL irradiation exerted no adverse effects on the viability, activation or aggregation of PLTs ex vivo and could be used repeatedly during PLT storage. PLT survival in vivo was also unaltered by aBL irradiation after infusion of aBL-irradiated mouse PLTs into mice. The study provides proof-of-concept evidence for a potential of aBL to decontaminate PLTs during storage.
THE INFLUENCE OF SOCIAL ISOLATION AND NEIGHBORHOOD DANGER ON OLDER ADULTS’ FUNCTIONAL STATUS

This is a pre-copyedited, author-produced version of an article accepted for publication in Innovation in Aging following peer review. The version of record Engel, I. J., & Baker, T. A. (2019). THE INFLUENCE OF SOCIAL ISOLATION AND NEIGHBORHOOD DANGER ON OLDER ADULTS’ FUNCTIONAL STATUS. Innovation in Aging, 3(Suppl 1), S529–S530. https://doi.org/10.1093/geroni/igz038.1947 is available online at: https://doi.org/10.1093/geroni/igz038.1947 This work is licensed under a Creative Commons Attribution 4.0 International License.
Efficient 1-Hour Technetium-99 m Pyrophosphate Imaging Protocol for the Diagnosis of Transthyretin Cardiac Amyloidosis

Background: Technetium-99 m pyrophosphate protocols for transthyretin cardiac amyloidosis diagnosis have variably used 1- and 3-hour imaging time points. We investigated whether imaging at 1 hour w...
CO2 Concentration in Chlamydomonas reinhardtii: Effect of the Pyrenoid Starch Sheath.

In the photosynthetic Calvin-Benson cycle, the enzyme Rubisco fixes CO2 into organic compounds. A major limitation of Rubisco is that oxygen can compete with CO2 for the active site of the enzyme, resulting in the wasteful process of photorespiration ([Bauwe et al., 2010][1]). Photosynthetic
Development or Disease: Caspases Balance Growth and Immunity in C. elegans.

Caspase proteases execute apoptosis but also function in development. In this issue of Developmental Cell, Weaver et al. report that C. elegans CED-3 caspase promotes animal growth through PMK-1/p38 kinase cleavage, and at the expense of pathogen and stress immunity, revealing an unexpected homeostatic relationship between development and disease.
Assessing the efficacy of autogenous vaccines in bovine diseases

Vaccination is an important tool for preventing disease. In human medicine and veterinary health, the eradication of smallpox and rinderpest are stellar examples of how effective vaccinations can be. Other outstanding examples include vaccines against measles, mumps, and rubella in humans. In animal health, most vaccines are marketed broadly for use on multiple animals and farms. However, autogenous vaccines, which are intended for use on a single farm, are also common in livestock health worldwide. For this presentation, I discuss concepts related to assessing the efficacy of vaccines and provide a summary of the publicly available evidence from the scientific literature regarding the efficacy of autogenous vaccines.
A Bayesian Network Approach to Evaluate Shipboard Launch and Recovery Performance in Early-Stage Ship Design

Vessel performance in shipboard launch and recovery operations is a critical element of its overall mission effectiveness. Both commercial and military vessels are required to launch and recover a variety of manned and unmanned platforms including submersibles, small boats, aircraft, and amphibious vehicles. A fundamental attribute of these launch and recovery operations is their dependence on a number of probabilistic factors such as environmental conditions and design factors associated with the vessel and the platforms. To facilitate effective launch and recovery operations, ship designers require a design method that takes into account these probabilistic factors to gain a better understanding the implications of launch and recovery on a variety of early stage design decisions. Recent advancements in design tools and methodologies have pushed critical decisions earlier in the design process which necessitates evaluating mission critical systems sooner as well.
Public Charge Rule and Its Impact on Child Health: A Call to Action.

* Abbreviation: CHIP — : Children’s Health Insurance Program Major policy changes have gone into effect that impact the health of some of the most vulnerable children in our nation, those of low-income immigrant families. This policy, better known as the public charge rule, is part of a compendium of highly controversial and litigated health-related federal immigration policies enacted by the Administration on the basis of financial criteria.1 The public charge rule has been traditionally used to determine ineligibility for immigration or residency status on the basis of health, education, and financial factors under the Immigration Act of 1882 and Immigration and Nationality Act of 1996. Recent changes reflect a redefinition and expansion of the term “public charge” for those applying for permanent residency.1 Under this new rule, US residency applicants who use any number of public benefits, including Medicaid, government housing, and the Supplemental Nutrition Assistance Program, are now also deemed a public charge, meaning that they are likely to become dependent on the government for subsistence.1 This label, along with other factors, can be used negatively in determinations for permanent residency applications. By tying the use of vital public health programs to immigration and residency status, the Administration is forcing a choice between seeking critical services or securing status in the United Status. Current antiimmigrant sentiment, rhetoric, and policy changes, such as the public charge rule, have resulted in a culture of fear, misinformation, distrust, and isolation, all of which have health implications for these … Address correspondence to Nina Patel, MS, College of Health Solutions, Arizona State University, 411 N Central Ave, Phoenix, AZ 85004. E-mail: ninapatel107{at}gmail.com
Ring-Closing Olefin Metathesis Catalyzed by Well-Defined Vanadium Alkylidene Complexes

Vanadium-based catalysts have shown activity and selectivity in ring-opening metathesis polymerization of strained cyclic olefins comparable to those of Ru, Mo, and W catalysts. However, the application of V alkylidenes in routine organic synthesis is limited. Here, we present the first example of ring-closing olefin metathesis catalyzed by well-defined V chloride alkylidene phosphine complexes. The developed catalysts exhibit tolerance to various functional groups, such as an ether, an ester, a tertiary amide, a tertiary amine, and a sulfonamide. The size and electron-donating properties of the imido group and the phosphine play a crucial role in the stability of active intermediates. Reactions with ethylene and olefins suggest that both 𝛽-hydride elimination of the metallacyclobutene and bimolecular decomposition are responsible for catalyst degradation.
The Disproportionate Impact Theory of Racial Discrimination

What is the relevance of the phenomenon of disproportionate racial impact to the constitutional right to the equal protection of the laws? Under the constitutional right to equal protection, properly understood, government may not disadvantage any human being based either on the view that she is morally inferior or on a sensibility to that effect—a sensibility such as (what Paul Brest termed) “racially selective sympathy and indifference,” namely, “the unconscious failure to extend to a [racial] minority the same recognition of humanity, and hence the same sympathy and care, given as a matter of course to one’s own group.” As Robin Kar and John Lindo have explained: “Many people who treat each other differently . . . exhibit unconscious patterns of attention, inference and concern, which make it easier for them to identify the interests of their in-group while overlooking those of out-groups. This explains why democratic processes cannot be relied upon to guarantee the equal treatment of persons under the law.” Robin Bradley Kar and John Lindo, “Race and the Law in the Genomic Age: A Problem for Equal Treatment under the Law,” in Roger Brownsword, Eloise Scotford, and Karen Yeung, eds., The Oxford Handbook of Law, Regulation and Technology 874 (2017), available at: https://ssrn.com/abstract=2629819. Kar and Lindo rightly conclude that the Supreme Court should “revise its interpretation of the Equal Protection Clause [so as to allow] for broader and more vigorous constitutional protection against disparate impact caused by either intentional discrimination or psychological processes that regularly function to cause disparate treatment.” See also Osagie K. Obasogie, “The Supreme Court Is Afraid of Racial Justice,” New York Times, June 7, 2016. I defended the same position at length—and in the course of doing so critiqued the U.S. Supreme Court’s then-recent decision in Washington v. Davis (1976)—in this article: “The Disproportionate Impact Theory of Racial Discrimination”. The relevance of the phenomenon of disproportionate racial impact remains an important and contested issue in equal protection theory, and my analysis and arguments in the article available here are no less sound today than they were in 1977, when the article was first published.
Assessment of coastal ecosystem services and its condition for policy management plan in East Nusa Tenggara, Indonesia

Abstract As a developing and archipelago country, Indonesia is expected to assess its coastal ecosystem services to unleash Indonesia’s coastal potential and to drive Indonesia’s economic development. With this line of reasoning, it is indeed to apply the concept of Ecosystem Services (ES) and its condition to measure how much natural potential we have in coastal ecosystems. However, there has been no comprehensive framework on how ES and its condition are holistically conducted. For that purpose, we pioneered integrated research to assess the spatial distribution of the ES (coastal protection and recreation) across districts of East Nusa Tenggara province and its condition toward habitat by applying integrated InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) models. InVEST model would acknowledge the potential ES that is available in the coastal ecosystem and its condition. Additionally, we also suggest the form of coastal management policy in East Nusa Tenggara that needs to be applied based on the available ES data. Our result indicated that West Manggarai and Southwest Sumba have the highest and lowest ES for coastal protection and tourism services. The HRA models showed that the condition of the coastal ecosystem in West Manggarai is at moderate risk; however, most of the seagrass is at high risk. The results suggested that conservation areas in West Manggarai intensified the existing ES provided there, whereas it also brings pressures to habitat conditions. Therefore, there is indeed to achieve an ideal coastal management practice in East Nusa Tenggara. It is also needed to consider ecological, social and economic aspects and involve all government levels to establish synergistic and inclusive policies. Simultaneously, it is also notable in paying attention to each area’s carrying capacity that can affect ecological functions.