cssi/SciSciGPT-SciSciNet huggingface dataset:
Prenatal stress suppresses hunger-induced rat-pup killing in Long-Evans rats

During each of the last 5 days of pregnancy, Long-Evans and Wister rats received 45 min of whole-body restraint and intense illumination. When they were 87 days old, they were placed on complete food deprivation until Day 90. At this time, all animals were tested with 1-day-old rat pups and adult mice (Mus musculus). The stress procedure suppressed the level of rat-pup killing induced by the food deprivation in the Long-Evans rats. The 3 days of food deprivation did not induce rat-pup killing in the other groups or mouse killing in any of the groups.
Mandated Preparation Program Redesign: Kentucky Case

This case study presents a chronicle of events spanning a decade in Kentucky that led to state policy changes for principal preparation and details the response to those mandated changes by profess...
Enhanced lipolysis from broiler adipocytes pretreated with pancreatic polypeptide.

Broiler adipocytes in culture were used to determine whether prolonged preincubation with an antilipolytic hormone, pancreatic polypeptide, enhances lipolysis by inducing desensitization of lipolysis inhibition. Preincubation of broiler adipocytes with pancreatic polypeptide resulted in a dose-response and time-dependent enhancement (P < .05) of basal and glucagon-stimulated lipolysis. Lipolysis was enhanced at 4 and 24 h but not at .5 h of pretreatment. Acute inhibition of basal lipolysis was unaffected by long-term (24 h) exposure of adipocytes to a maximally effective dose (12 nM) of pancreatic polypeptide. Thus, desensitization of lipolysis inhibition cannot explain the enhanced lipolysis from pancreatic polypeptide-treated adipocytes. However, preincubation with 12 nM pancreatic polypeptide for 24 h reduced (P < .05) pancreatic polypeptide and somatostatin inhibition of lipolysis stimulated by glucagon. Moreover, basal lipolysis and submaximal lipolysis were enhanced to a similar extent (27 vs 29 nmol/h) but to a greater (P < .05) extent (27 vs 13 nmol/h) than maximal lipolysis when adipocytes were exposed to 12 nM pancreatic polypeptide for 24 h. These results suggest that the enhanced lipolysis induced by prolonged exposure of adipocytes to pancreatic polypeptide resulted from increased activity of hormone-sensitive lipase and activators of this enzyme and not from attenuation of lipolysis inhibition.
Disappearance of cytogenetic abnormalities and clinical remission during therapy with 13-cis-retinoic acid in a patient with myelodysplastic syndrome: inhibition of growth of the patient's malignant monocytoid clone

Median survival is as little as 6 months for patients with refractory anemia with excess blasts who demonstrate an abnormal karyotype in the majority of marrow cells. We treated a patient who presented with 29% marrow blasts and 90% abnormal metaphases with 13-cis-retinoic acid. He achieved a complete clinical and cytogenetic remission during therapy. To determine the mechanism of the response, serial studies were done of the effects of 13-cis-retinoic acid and dexamethasone on in vitro growth of his marrow cells. During clinical remission, when the drug was not administered, marrow growth remained significantly depressed. During relapse, the remission growth pattern was replaced by overgrowth of the karyotypically abnormal monocytoid clone. Clonal growth occurred in cultures containing colony-stimulating activity or dexamethasone but was absent in cultures containing concentrations of 13-cis-retinoic acid achieved in vivo. After the drug was reinstituted, a second clinical stabilization developed. Since 13-cis-retinoic acid inhibits normal monocyte colony growth, we postulate that the patient's unusual clinical responses to the drug were due to in vivo growth inhibition of the malignant monocytoid clone.
HER3 Targeting Sensitizes HNSCC to Cetuximab by Reducing HER3 Activity and HER2/HER3 Dimerization: Evidence from Cell Line and Patient-Derived Xenograft Models.

Purpose: Our previous work suggested that HER3 inhibition sensitizes head and neck squamous cell carcinoma (HNSCC) to EGFR inhibition with cetuximab. This study aimed to define the role of HER3 in cetuximab resistance and the antitumor mechanisms of EGFR/HER3 dual targeting in HNSCC. Experimental Design: We treated cetuximab-resistant HNSCC UMSCC1-C and parental UMSCC1-P cell lines with anti-EGFR antibody cetuximab, anti-HER3 antibody MM-121, and their combination. We assessed activities of HER2, HER3, and downstream signaling pathways by Western blotting and cell growth by sulforhodamine B (SRB) and colony formation assays. HER3-specific shRNA was used to confirm the role of HER3 in cetuximab response. The combined efficacy and alterations in biomarkers were evaluated in UMSCC1-C xenograft and patient-derived xenograft (PDX) models. Results: Cetuximab treatment induced HER3 activation and HER2/HER3 dimerization in HNSCC cell lines. Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited the PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone. HER3 knockdown reduced HER2 activation and resensitized cells to cetuximab. Cetuximab-resistant xenografts and PDX models revealed greater efficacy of dual EGFR and HER3 inhibition compared with single antibodies. In PDX tissue samples, cetuximab induced HER3 expression and MM-121 reduced AKT activity. Conclusions: Clinically relevant PDX models demonstrate that dual targeting of EGFR and HER3 is superior to EGFR targeting alone in HNSCC. Our study illustrates the upregulation of HER3 by cetuximab as one mechanism underlying resistance to EGFR inhibition in HNSCC, supporting further clinical investigations using multiple targeting strategies in patients who have failed cetuximab-based therapy. Clin Cancer Res; 23(3); 677–86. ©2016 AACR .
Conservation presence, not socioeconomics, leads to differences in pastoralist perceived threats to argali

Abstract Community-based conservation approaches that keep people on landscapes increasingly complement preservationist models of reserves without people. Evaluations of community conservation have shown that economic incentives and socioeconomics primarily drive people’s attitudes and perceptions. Work at Mongolia’s Ikh Nart Nature Reserve demonstrates how to achieve successful conservation by integrating local people into the overall program. Using a short questionnaire, we interviewed pastoralist families across two soums (similar to a U.S. county) in Ikh Nart. We examined (1) pastoralists’ perceived threats to argali sheep (Ovis ammon), (2) socioeconomic differences among pastoralists, and (3) differences between pastoralists from different soums. We found that 15 years of conservation activities—education, research, and modest ecotourism—that occurred in the northern soum led to influences on people’s perceptions toward argali conservation. Compared with pastoralists from southern Ikh Nart, pastoralists from the northern part of the reserve more likely knew that argali are protected and understood primary threats to the species. Socioeconomic factors, such as age, sex, and wealth, did not significantly influence responses. The negligible economic incentives in Ikh Nart did not lead to response differences. Our results demonstrate that conservation can influence people across socioeconomic classes without providing large economic incentives.
Endemic, Rare, and Endangered Soils

Hole (1974) was a forerunner in recognizing the need to protect the “wild” soils surrounding our wild rivers. He identified “wild” soils as those which still function as integral parts of native ecosystems. He used the Pine-Popple Rivers basin in Florence County as an example of an area with wild soils. These soils were considered to be “wild” because of their importance in protecting riparian resources. Drohan and Farnham (2006) proposed that rare and threatened soils be recognized in the USA.
Pharmacological Ascorbate in Combination with Standard-Of-Care Radio-Chemotherapy Enhances Tumor Response in an Orthotopic Sarcoma Model

Soft tissue sarcomas represent a rare group of cancers (> 150 histological subtypes) that represent Supported by The Carver Research Program of Excellence in Redox Biology, T32 CA078586, P30 CA086862, T32GM007337, UIHC Department of Radiation Oncology, and the Holden Comprehensive Cancer Center.
Cross-cultural work and family research: A review of the literature

Abstract Research aimed at understanding the intersection of employees' work and family lives has blossomed over the past few years, and, in more recent times, has begun to have an increasingly global focus. Conducting research in diverse cultural settings is important given that work and family dynamics are entrenched in larger societal contexts, such as gender role norms, national policies, and cultural values. However, the literature has not developed in a programmatic way, making it difficult to build upon the current knowledge base. The goal of this study is to review extant cross-cultural work and family published research in an effort to synthesize and assess the current state of the literature, with a focus on theoretical logic and methodology. We do this by reporting descriptive statistics regarding which global regions have received the most attention, the way culture is considered analytically and theoretically, and information about measurement. Through this review we aim to provide scholars with a more complete understanding of the state of cross-cultural work-family knowledge and offer recommendations for future research that will facilitate theoretical advancement.
Amino acids disorders

Disorders of amino acid metabolism are a major source of diseases of inborn errors of metabolism (IEM). This class of disorders is usually hallmarked by derangement in the normal concentrations of amino acids in body fluids. Amino acids can be measured in plasma, urine, cerebrospinal fluid, and dried blood spots, and the profile of results may be interpreted to aid in or make a diagnosis of various IEM. Amino acids are also measured to follow-up treatment. This chapter reviews aminoacidopathies and their diagnosis based on amino acid profiles.
Data-driven prediction of adverse drug reactions induced by drug-drug interactions.

The expanded use of multiple drugs has increased the occurrence of adverse drug reactions (ADRs) induced by drug-drug interactions (DDIs). However, such reactions are typically not observed in clinical drug-development studies because most of them focus on single-drug therapies. ADR reporting systems collect information on adverse health effects caused by both single drugs and DDIs. A major challenge is to unambiguously identify the effects caused by DDIs and to attribute them to specific drug interactions. A computational method that provides prospective predictions of potential DDI-induced ADRs will help to identify and mitigate these adverse health effects. We hypothesize that drug-protein interactions can be used as independent variables in predicting ADRs. We constructed drug pair-protein interaction profiles for ~800 drugs using drug-protein interaction information in the public domain. We then constructed statistical models to score drug pairs for their potential to induce ADRs based on drug pair-protein interaction profiles. We used extensive clinical database information to construct categorical prediction models for drug pairs that are likely to induce ADRs via synergistic DDIs and showed that model performance deteriorated only slightly, with a moderate amount of false positives and false negatives in the training samples, as evaluated by our cross-validation analysis. The cross validation calculations showed an average prediction accuracy of 89% across 1,096 ADR models that captured the deleterious effects of synergistic DDIs. Because the models rely on drug-protein interactions, we made predictions for pairwise combinations of 764 drugs that are currently on the market and for which drug-protein interaction information is available. These predictions are publicly accessible at http://avoid-db.bhsai.org . We used the predictive models to analyze broader aspects of DDI-induced ADRs, showing that ~10% of all combinations have the potential to induce ADRs via DDIs. This allowed us to identify potential DDI-induced ADRs not yet clinically reported. The ability of the models to quantify adverse effects between drug classes also suggests that we may be able to select drug combinations that minimize the risk of ADRs. Almost all information on DDI-induced ADRs is generated after drug approval. This situation poses significant health risks for vulnerable patient populations with comorbidities. To help mitigate the risks, we developed a robust probabilistic approach to prospectively predict DDI-induced ADRs. Based on this approach, we developed prediction models for 1,096 ADRs and used them to predict the propensity of all pairwise combinations of nearly 800 drugs to be associated with these ADRs via DDIs. We made the predictions publicly available via internet access.
Pore characteristics regulate priming and fate of carbon from plant residue

Abstract Decomposition of the plant residue added to soil affects fate of native soil organic matter (SOM) via magnitude and direction of priming effect (PE). Soil pore characteristics, namely, pore size distribution (PSD), regulate air and liquid fluxes, as well as transport of solubilized decomposing residue to microorganisms. The goal of this study was to assess the effect of PSD on plant residue decomposition and PE as modulated by i) residue quality, ii) soil moisture status, and iii) long-term management history. We combined labeling and imaging approaches to visualize loss of decomposing residue and link it to PE in soils with two contrasting PSDs, dominated by small (5–10 μm) pores and by a combination of very small ( 30 μm) pores, respectively. The microcosms were incubated with 13 C-labeled corn and soybean leaves, in soils from long-term conventional and biologically based managements. X-ray computed micro-tomography scanning was utilized to visualize loss of intact leaves at early stages (7, 14, 24 d) of decomposition. We found that PSD of soil adjacent to the decomposing plant residue played a major role in the fate of the residue and of its decomposition products. In microcosms with prevalence of small (5–10 μm) pores decomposition of corn leaves was slower, movement of decomposition products into the adjacent soil was greater, and proportion of CO 2 that originated from the residue was lower than in the microcosms with prevalence of large pores. Greater positive PE took place in microcosms with small than with large pores. While these tendencies were observed in all studied soil moisture levels, management practices, and plant residue substrates, they were most pronounced in microcosms with more labile residue (soybean) in the soil from long-term biologically based management. Across treatments, the intensity of PE was greater for soils under conventional than biologically-based management. The findings emphasize importance of accounting for soil PSD when assessing processes of soil C accrual and priming.
The Visible Infrared Imaging Radiometer Suite

The Visible Infrared Imaging Radiometer Suite (VIIRS) is used to obtain measurements of the Earth’s oceans, land surface and atmosphere to make a wide range of Environmental Data Records (EDR’s). These standard products, which have been defined in the Integrated Operational Requirements Document (IORD) (JARG, 2005), are listed in Table 11.1. VIIRS is designed to provide global coverage at least once per day, with moderate (better than 1 km) spatial resolution. This combination of spatial and temporal scales has been chosen to provide needed input to operational weather and environmental models while sampling the natural variability of biological processes on the land surface and in the oceans. It has very high radiometric and geometric fidelity, enabling its use in the acquisition of long-term data records suitable for the study of climate and climate change as well as being a powerful tool for studies designed to increase our understanding of specific geophysical processes such as the interaction of the biological and physical mechanisms in ocean plankton blooms.
Cervical Cancer Risk Factors among Female High School Students in Baguio city

Objective: To determine and correlate the prevalence of cervical cancer risk factor exposures such as smoking, sexual activity, use of condoms, contraceptives pills, and history of STIs according to age and high school year level in Baguio city high-school students, Philippines. Background: Cervical cancer is the second cause of cancer deaths among women in the Philippines and the second most frequent cancer in women ages 15-44 [1]. Methods: The risk stratification level of cervical cancer development was determined using a questionnaire adapted from Siteman Cancer Center and Barnes- Jewish Hospital and Washington University School of Medicine. A coding manual was created for each of the risk factors and the level stratification of the risk factors. The study size was computed with the use of Open Epi, Version 2, open source calculator—SSPropo, an internet based epidemiologic calculator. Results: 98.3% of the study group was classified to have much below average risk of developing cervical cancer. 1.2% of the study group was of below average risk and 0.5% of the study group was with above average risk of cervical cancer with significant relationship to age of first sexual contact and number of sexual partners. Conclusion: An increased risk of cervical cancer among these students were associated with early onset of sexual activity, increasing number of sexual partners and early parity.
Modeling Maher's Attribution Theory of Delusions as a Cusp Catastrophe

Maher's (1974, 1988) attribution theory of delusions was reformulated as a cusp catastrophe model and tested using 193 percipients' paranormal beliefs, paranormal experiences, and fear of the paranormal as measured by Kumar et al.'s (1994) Anomalous Experiences Inventory, and their tolerance of ambiguity as measured by McDonald's (1970) AT-20. The magnitude of the difference between percipients' fear and belief was used as the dependent variables, whereas experience and tolerance of ambiguity were used as asymmetry and bifurcation variables, respectively. Using the GEMCAT II software it was shown that this cusp provided a superior fit to the data than competing linear, fold, and cusp models. Consistent with Maher's formulation, two basic states were found to exist: one in which fear dominates belief, and a second in which belief dominates fear. Further, fear of the paranormal increased with greater intolerance of ambiguity while belief decreased with increasing tolerance. The model explains why paranormal beliefs are resistant to change in the face of counterargument or contradictory evidence.
Deoxycytidine pathway in separated normal and leukemic leukocytes with effects of cell culture.

Enzymes of dC metabolism were studied in glass-column-separated normal and leukemic cells. Supernatants of sonicated cells were incubated with dC-3H or dCMP-3H and the end products separated with paper chromatography. Greatest recovery of dCTP, dUMP, and TTP occurred with myeloblasts and monoblasts. Mature granulocytes, and normal and leukemic lymphocytes gave the greatest breakdown to uracil. Myelocytes and lymphoblasts gave intermediate results. Leukemic lymphocytes from different patients varied greatly in their end products, but most did show evidence of TMP synthetase activity contrary to previous reports. Recovery of products of TMP synthetase and, to a lesser extent, dCMP deaminase and dC kinase activities was greatest in cells having or developing a potential for mitosis. CLL-L whose extracts showed appreciable production of dCTP, dUMP, and TdR compounds, however, did not regularly produce blast cells in response to PHA in culture. Cellular extracts of N-L, or CLL-L from cases which responded to PHA did show, on the other hand, a considerable increase in accumulation of these compounds from initial low values during culture.
Propagation of a nonlinear wave packet driven in a relaxed magnetohydrodynamic plasma

We report the observation of a nonlinear wave packet propagating through a relaxed Taylor state in the Swarthmore Spheromak eXperiment (SSX) device. The wave packet is launched by a fast, pulsed, high current ( ) single-turn theta-pinch coil mounted outside the plasma vessel. The theta-pinch coil is energized by discharging a 40 kV, 2 kJ capacitor circuit. The wave packet velocity is super-thermal and super-Alfvenic; its group velocity is more consistent with a whistler pulse than other characteristic velocities. We also observe a fast density pulse which indicates that it is not Alfvenic in nature.
Drop-Off Detection in the Touch Technique:

Using a theoretical model of walking with the cane, drop-off detection in the touch technique was analyzed. Sufficient cane length for detecting curb drop-offs was found to be measurable and a char...
Cost-effectiveness of Short-Course Radiation Therapy vs Long-Course Chemoradiation for Locally Advanced Rectal Cancer.

Importance Although both short-course radiotherapy and long-course chemoradiotherapy have been practiced in parallel for more than 15 years, no cost-effectiveness analysis comparing these 2 approaches in patients with locally advanced rectal cancer has been published. Objective To analyze the cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy for the treatment of patients with locally advanced rectal cancer. Design, Setting, and Participants This economic evaluation used a cost-effectiveness model simulating 10-year outcomes for 1 million hypothetical patients aged 65 years with locally advanced rectal cancer treated with either short-course radiotherapy or long-course chemoradiotherapy, followed by surgery and chemotherapy. Utilities and probabilities from the literature and costs from the Healthcare Bluebook and Medicare fee schedules were used to determine incremental cost-effectiveness ratios. It was assumed that long-course chemoradiotherapy would result in higher rates of low anterior resection (LAR). To model preference-sensitive care, a 2-way sensitivity analysis was conducted in which the utilities of the no-evidence-of-disease (NED) states with LAR and abdominoperineal resection (APR) were simultaneously varied. The analysis was repeated for patients with distal rectal tumors. Analysis was conducted from January to October 2018. Exposures Short-course radiotherapy and long-course chemoradiotherapy. Main Outcomes and Measures Incremental cost-effectiveness ratios. Results Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy (incremental cost-effectiveness ratio, $133 495 per quality-adjusted life-year). Two-way sensitivity analysis revealed that the cost-effective approach for a given patient depended on the utilities for the NED-LAR and NED-APR states. Assuming that a greater proportion of patients with locally advanced distal tumors undergoing long-course chemoradiotherapy (39%) would proceed to LAR compared with those treated with short-course radiotherapy (19%), long-course chemoradiotherapy was the cost-effective approach (incremental cost-effectiveness ratio, $61 123 per quality-adjusted life-year). Conclusions and Relevance Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy for patients with locally advanced rectal cancer. The cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy was sensitive to the utilities of the NED-LAR and NED-APR health states, highlighting the importance of care that is sensitive to patient preference. Long-course chemoradiotherapy was the cost-effective approach for patients with distal tumors.
Equilibrium Stability in 1-Dimensional Systems

In this chapter, a global analysis of equilibrium stability in 1-dimensional nonlinear dynamical systems is presented. The classification of dynamical systems is given first, and infinite-equilibrium systems are defined. The 1-dimensional dynamical systems with single equilibrium are discussed first. The 1-dimensional dynamical systems with two and three equilibriums are discussed. Simple equilibriums and higher order equilibriums in 1-dimensional dynamical systems are analyzed, and herein a higher order equilibrium is an equilibrium with higher order singularity. The separatrix flow of equilibriums in 1-dimensional systems in phase space is illustrated for a better understanding of the global stability of equilibriums in 1-dimensional dynamical systems.
Verrucous Keratoses Associated with Checkpoint Inhibitor Immunotherapy

Introduction:Checkpoint inhibitor immunotherapy is associated with numerous adverse events, including eruptive keratoacanthomas and squamous cell carcinomas. However, no cases of immunotherapy-associated verrucous keratoses (VKs) have been reported. VKs are proliferative lesions generally considered benign, although they have been suggested to represent premalignant lesions.Cases:We present the first case series of three patients with immunotherapy-associated VKs. The patients were receiving nivolumab for renal cell carcinoma, combination ipilimumab/nivolumab for non-small cell lung carcinoma, and pembrolizumab for malignant melanoma. The VKs appeared 3-7 months after initiation of immunotherapy. Lesions were treated with shave removal or cryosurgery without recurrence. This report adds to the spectrum of cutaneous squamoproliferative lesions induced by checkpoint inhibitor immunotherapy.
Demonstration of a self-healing all-polymer distributed Bragg reflector laser

Self-healing of an all-polymer distributed Bragg reflector laser is demonstrated. The lasing medium is a glycol-modified poly(ethylene terephthalate) co-polymer doped with rhodamine 6G. After the light output is reduced to 1/3 of its pristine value through photodegradation due to the pump, the laser is placed in the dark to allow it to heal. The laser fully recovered to its pre-damaged output power. A similar laser made with the rhodamine B chromophore is observed to only partially recover after photodegradation.
Prospective interactive influence of financial strain and emotional nonacceptance on problematic alcohol use during the COVID-19 pandemic.

Background: Researchers have highlighted the risk for alcohol use problems in the context of COVID-19, although the factors associated with this risk remain unclear. Objectives: This study examined...
The 'Legal' Marijuana Industry's Challenge for Business Entity Law

In recent years many states have legalized the use and sale of marijuana for medical or even recreational purposes. This has led to the booming growth of a “legal” marijuana industry. Businesses openly growing and selling marijuana products to the consuming public are faced with some unusual legal hurdles. Significantly, although the sale of marijuana may be legal at the state level, it is still illegal under federal law. This article explores the conflict between state and federal marijuana laws from a business entity law perspective. For example, managers owe a fiduciary duty of good faith to their businesses and equity holders. One of the ways in which managers can violate this duty is by causing their business to intentionally violate the law. This is a problem for the marijuana industry because its managers constantly and intentionally violate federal law and therefore violate their fiduciary duties by growing and selling marijuana. This article concludes that the industry’s ability to attract professional stakeholders is harmed by marijuana business stakeholders’ inability to take advantage of key business law protections, such as limited liability. This article proposes a state law exception that allows for marijuana businesses to operate normally under state business entity law, with normal business entity law protections, despite their continuing violation of federal law.
Deuterium Oxide (D2O) Induces Early Stress Response Gene Expression and Impairs Growth and Metastasis of Experimental Malignant Melanoma

There are two stable isotopes of hydrogen, protium (1H) and deuterium (2H; D). Cellular stress response dysregulation in cancer represents both a major pathological driving force and a promising therapeutic target, but the molecular consequences and potential therapeutic impact of deuterium (2H)-stress on cancer cells remain largely unexplored. We have examined the anti-proliferative and apoptogenic effects of deuterium oxide (D2O; 'heavy water') together with stress response gene expression profiling in panels of malignant melanoma (A375V600E, A375NRAS, G361, LOX-IMVI), and pancreatic ductal adenocarcinoma (PANC-1, Capan-2, or MIA PaCa-2) cells with inclusion of human diploid Hs27 skin fibroblasts. Moreover, we have examined the efficacy of D2O-based pharmacological intervention in murine models of human melanoma tumor growth and metastasis. D2O-induction of apoptosis was substantiated by AV-PI flow cytometry, immunodetection of PARP-1, and pro-caspase 3 cleavage, and rescue by pan-caspase inhibition. Differential array analysis revealed early modulation of stress response gene expression in both A375 melanoma and PANC-1 adenocarcinoma cells elicited by D2O (90%; ≤6 h) (upregulated: CDKN1A, DDIT3, EGR1, GADD45A, HMOX1, NFKBIA, or SOD2 (up to 9-fold; p < 0.01)) confirmed by independent RT-qPCR analysis. Immunoblot analysis revealed rapid onset of D2O-induced stress response phospho-protein activation (p-ERK, p-JNK, p-eIF2α, or p-H2AX) or attenuation (p-AKT). Feasibility of D2O-based chemotherapeutic intervention (drinking water (30% w/w)) was demonstrated in a severe combined immunodeficiency (SCID) mouse melanoma metastasis model using luciferase-expressing A375-Luc2 cells. Lung tumor burden (visualized by bioluminescence imaging) was attenuated by D2O, and inhibition of invasiveness was also confirmed in an in vitro Matrigel transwell invasion assay. D2O supplementation also suppressed tumor growth in a murine xenograft model of human melanoma, and median survival was significantly increased without causing adverse effects. These data demonstrate for the first time that systemic D2O administration impairs growth and metastasis of malignant melanoma through the pharmacological induction of deuterium (2H)-stress.
Lives Saved from Age-Prioritised COVID-19 Vaccination

Abstract BACKGROUND The criteria used to allocate scarce COVID-19 vaccines are hotly contested. While some are pushing just to get vaccines into arms as quickly as possible, others advocate prioritization in terms of risk. OBJECTIVE Our aim is to use demographic models to show the enormous potential of vaccine risk-prioritization in saving lives. METHODS We develop a simple mathematical model that accounts for the age distribution of the population and of COVID-19 mortality. This model considers only the direct live-savings for those who receive the vaccine, and does not account for possible indirect effects of vaccination. We apply this model to the United States, Japan, and Bangladesh. RESULTS In the United States, we find age-prioritization would reduce deaths during a vaccine campaign by about 93 percent relative to no vaccine and 85 percent relative to age-neutral vaccine distribution. In countries with younger age structures, such as Bangladesh, the benefits of age-prioritization are even greater. CONTRIBUTION For policy makers, our findings give additional support to risk-prioritized allocation of COVID-19 vaccines. For demographers, our results show how the age-structures of the population and of disease mortality combine into an expression of risk concentration that shows the benefits of prioritized allocation. This measure can also be used to study the effects of prioritizing other dimensions of risk such as underlying health conditions.
Minimal brain adaptation for representational prioritization in non-native parsing: Evidence from a time-frequency analysis of recursion in Wh-dependencies in French

Abstract We report on a time-frequency analysis of electroencephalographic activity as native speakers (NSs) and non-native speakers (NNSs) resolve anaphoric reference at the recursive edge of embedded clauses in multi-clausal filler-gap dependencies. The fillers in these wh-dependencies involve lexically selected noun complements (Comp): quelle decision a propos de lui/a son sujet ‘which decision about him’ or unselected NP-modifiers (Mod): quelle decision le concernant ‘which decision regarding him’; they also involve the lexical encoding of antecedent gender (lui/elle ‘3p.sing.masc/fem’) or not (son ‘3p.sing.gen’) in a pronoun. We propose that NNSs adapt to processing a non-native language by directing more resources toward computing lexically encoded properties than toward inferences that go beyond lexical information. At the recursive clause edge, a population-wide asymmetry between conditions arose at 15–16Hz in induced power: Lexical selection and gender specification led to diminished power for Comp son vs. Mod le/la and for specified lui/elle vs. unspecified son in Comps. This was also found at 17–22Hz in induced power in NSs whereas asymmetries were reversed in NNSs, with computations of lexically encoded properties demanding greater power. At 41–44Hz in induced power, group differences emerged: More power was directed at gender-specified le/la and lui/elle in NNSs, but at unspecified son in NSs. These asymmetries suggest that non-native processing seems characterized by resources directed toward lexically encoded properties in computations.
The National Interscholastic Cycling Association Mountain Biking Injury Surveillance System: 40,000 Student-Athlete-Years of Data.

ABSTRACT A web-based injury surveillance system was implemented through a collaboration between University of Utah researchers and the National Interscholastic Cycling Association (NICA) to better understand injury characteristics in mountain biking. Data were collected from NICA leagues during the 2018 and 2019 seasons. Injuries were tracked in 41,327 student-athlete-years, identifying 1750 unique injuries during 1155 injury events. Rider-dependent and rider-independent variables were analyzed. The most commonly reported injuries were concussion (23.6%), injuries to the wrist/hand (22.3%), and shoulder (15.6%). Half of all injury events occurred on downhills. Men and women reported similar yet significantly different injury rates (2.69% and 3.21%, respectively; P = 0.009). Women sustained more lower-limb injuries (37.8% vs 28.3%; P = 0.003). Nearly 50% of crashes resulted in an emergency room visit. Youth mountain bike racing is a rapidly growing sport. Acute traumatic injuries are common. Injury surveillance system data are now being used to inform injury prevention strategies and direct future research.
Developing an Evidence-Based Clinical Decision-Support System to Enhance Prosthetic Prescription:

With the rapid increase in the global amputee population, there is a clear need to assist amputee care providers with their decision-making during the prosthetic prescription process. To achieve th...
Optimizing Part Placement for Improving Accuracy of Robot-Based Additive Manufacturing

Robotic manipulators are increasingly being used to perform additive manufacturing. The accuracy of a built part is dependent on the trajectory execution error of the manipulator. For articulated manipulators, the trajectory execution error and achievable build accuracy vary considerably over the workspace. Therefore, the build accuracy depends on where the part is placed in the manipulator workspace. If the part is small compared to the manipulator workspace, its placement can be optimized to improve the accuracy. This paper provides experimental evidence that the placement of the parts changes its build accuracy. We model the trajectory execution error of the manipulator for additive manufacturing. We validate these errors by comparing the predicted errors with the experimental errors. Finally, we present an algorithm to optimize the part placement for improving built part accuracy during robot-based additive manufacturing.
Reproducible Histopathologic Features in Cases of Basal Cell Carcinoma With Neuroendocrine Expression: A Clinicopathologic Study of 24 Cases With a Potential Diagnostic Pitfall.

ABSTRACT Basal cell carcinomas (BCCs) are common malignancies that usually show clear histomorphologic features, but in certain instances, it can display different patterns of differentiation leading to potential diagnostic confusion. BCCs with neuroendocrine differentiation/expression have been mentioned only briefly in the literature. In this study, we present cases of BCCs with neuroendocrine differentiation/expression that demonstrate reproducible histopathological features. Twenty-four cases were included in the study. All tumors showed conventional histopathologic features that are seen in BCCs, but in addition, all the tumors showed large, hyperchromatic, pleomorphic, mononuclear, and multinucleate cells with intracytoplasmic inclusions and intranuclear cytoplasmic invaginations, with rare cases showing stippled nuclei (salt-and-pepper appearance). These histologic features were somewhat concerning for a neuroendocrine carcinoma; thus, immunohistochemistry studies were performed in all cases at the time of diagnosis. By immunohistochemistry, all tumors showed expression of neuroendocrine markers. CD56 was expressed in all cases 24/24, chromogranin was positive in 17/24 cases, and synaptophysin 8/24 was positive in cases. This study confirms a subset of histopathologic features that are present in cases of BCC that are associated with neuroendocrine expression that can potentially be interpreted differently and can create a diagnostic pitfall. Neuroendocrine expression in BCCs is yet uncertain, and further studies are required to fully understand this phenomenon. To avoid diagnostic pitfalls, dermatopathologists must be aware of these unusual histopathologic features and aberrant immunostaining in such tumors; hence, it is advised to perform a thorough histologic inspection.
Geopolymer pervious concrete modified with granulated blast furnace slag: Microscale characterization and mechanical strength

Geopolymer is green cementitious material that can be produced from industry waste or abundant earth materials through alkali-activated reaction. This study aims to conduct microscale characterization of geopolymer paste and mechanical properties of pervious concrete. Metakaolin (MK) and fly ash (FA) were used to synthesize geopolymer with granulated blast furnace slag (GBFS) as admixture. The experimental results showed that the room temperature curing was sufficient for strength formation of MK based geopolymer paste as compared to high temperature. The microscale characterization indicated that GBFS had introduced new crystal phases and better surface integrity was realized with the optimum content of GBFS. The GBFS had prominent effect on mechanical strength enhancement, and the optimum content was 10% and 30% for MK and FA based geopolymer paste and pervious concrete, respectively. In addition, mechanical strength of geopolymer pervious concrete was inversely proportional to the porosity caused by different aggregate gradations. However, when the porosity was similar, the smaller aggregate size induced the higher compressive but the lower splitting tensile strength.
A fracture mechanics based parametric study with dimensional variables of the Cu-Cu direct thermo-Compression bonded interface using FEA

Through-silicon via (TSV) technology with micro joint has been highlighted to overcome the limitations of I/O density and system performance enhancement of the conventional flip chip packages. However, the conventional joining methods, represented by the solder joint, cause many reliability problems, such as: intermetallic compound (IMC), thermal expansion coefficient (CTE) mismatch, creep and thermal fatigue problems. As an alternative, copper-to-copper direct bonding (CuDB) has been considered, especially located between a chip and an interposer as a substitute for the micro bump. CuDB enables reduction in fabrication process steps, and obtaining higher interconnect density and enhanced thermal conductivity. However, the CuDB interface has potential reliability risk since the bonding is typically performed at high temperature with a constant downward force in an inert atmosphere. Several papers have reported small voids between the interfaces that can lead crack propagation and delamination. The defect can result in fracture failure of an entire package during its fabrications and operation. This work is a quantitative parametric study about crack propagation at the CuDB interface using finite element methods (FEM). A pre-crack is assigned at the interface of the CuDB to reflect a small void which can be formed during the thermal compressive bonding process. Initial crack length and location, Cu bump diameter and pitch, and TSV diameter and pitch are varied to determine their impact on the crack propagation of the CuDB. As a computational domain, a unit cell including the outermost C4 solder ball, which is under the maximum warpage, is chosen. The unit cell consists of an intermediate layer, two silicon tiers, and a Cu microbump connected to a TSV with total 20 um width and 108 um height. The strain energy release rate (ERR) around the crack tip is calculated for a quantitative assessment. The results are verified with the J-integral method. As results, this study provides design recommendations that can minimize interfacial failure of the CuDB and modeling method, which can be used for efficient prediction of its failure possibility.
Abstract ES1-2: Reconstruction for the high risk patient: challenges of chemotherapy, radiation therapy and patient selection

Breast surgical oncology and breast reconstruction are intimately integrated into the multi-disciplinary management of women with breast carcinoma. The primary goal of care for the breast surgical oncologist and reconstruction surgeon remains the optimal treatment of the breast cancer, while the reconstruction surgeon strives to achieve a soft, symmetric, sensate and scar free breast mound. Factors that must be accounted for include the unpredictable nature of radiated structures and the inability to reliably determine the need for radiation. Next the timing or sequencing of chemotherapy and targeted therapy must be adequately addressed in relation to healing before or after surgery. Patient factors such as age, body habitus, donor site availability and institutional expertise are integral in the decision making process. Finally, the patient9s lifestyle and preferences must be counterbalanced with co-morbidities, donor site availability and limitations in implant size and shape. Citation Format: Mehra Golshan. Reconstruction for the high risk patient: challenges of chemotherapy, radiation therapy and patient selection [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES1-2.
Evidence that the asparagine 322 mutant of the lactose permease transports protons and lactose with a normal stoichiometry and accumulates lactose against a concentration gradient.

The single asparagine 322 mutant of the lactose permease was made by constructing a hybrid plasmid which contained the amino-terminal coding sequence from the wild-type permease gene and the carboxyl-terminal coding sequence from a previously characterized double mutant permease which contained an asparagine residue at position 322. Since histidine at position 322 has been postulated to be critically involved with H+ transport and the active accumulation of sugars, the ability of the Asn-322 mutant to couple H+ and sugar transport was carefully examined. Measurements of proton/lactose stoichiometries gave very similar values for the wild-type (0.78) and the Asn-322 strain (0.82). Moreover, the Asn-322 mutant was able to effectively accumulate lactose against a concentration gradient although the levels of accumulation in the Asn-322 mutant (approximately 5-7-fold) were significantly less than that of the wild-type strain (approximately 30-40-fold). Overall, these results are inconsistent with the notion that an ionizable histidine residue at position 322 is obligatorily required for H+ transport or the active accumulation of galactosides against a concentration gradient. The ability of the Asn-322 mutant to recognize a variety of sugars was compared with wild-type, Val-177, and Val-177/Asn-322 strains. The Asn-322 mutant exhibited an ability to recognize and transport maltose (an alpha-glucoside) which was significantly better than the wild-type strain but not as good as either the single Val-177 mutant or the double Val-177/Asn-322 mutant. Both the Asn-322 and the Val-177/Asn-322 strain showed a relatively poor recognition for alpha-galactosides (i.e. melibiose), beta-galactosides (lactose and thiodigalactoside), and beta-glucosides (cellobiose). In contrast, the single Val-177 strain exhibited a normal recognition for these sugars.
A chemical procedure for determination of the C14-distribution in labelled D-fructose and other ketoses.

A procedure is described for determining the activity of the individual carbon atoms in D-fructose labelled with C14, which is suitable for as little as 1 millimole of the sugar. The D-fructose is degraded by lead tetraacetate oxidation and the product is hydrolyzed to glycolic acid, formic acid, and D-glyceraldehyde. Glycolic acid is oxidized to formaldehyde (carbon-1) and carbon dioxide (carbon-2), and formic acid to carbon dioxide (carbon-3). D-Glyceraldehyde is degraded to carbon dioxide (carbons-4 and -5, combined) and formaldehyde (carbon-6); after reduction of a second portion of the D-glyceraldehyde to glycerol, the degradation products obtained are carbon dioxide (carbon-5) and formaldehyde (carbons-4 and -6, combined). The activity of carbon-1, -2, -3, -5, or -6 is thus determined directly, and of carbon-4 by difference in two ways. The procedure should also be applicable to C14-labelled L-sorbose. Lead tetraacetate oxidation of sedoheptulose followed by hydrolysis yields glycolic acid, formic a...
Who enrolls in prevention trials? Discordance in perception of risk by professionals and participants.

Experiences in our own Preventive intervention Research Center underscore that the way in which the program is presented may seriously influence which population subgroups are enrolled. Successful recruitment and retention often depend on whether there is congruence between the subjects' perceived needs and the stated agenda of the recruitment effort. Where there is discordance between the professionals' basis for concern and the client's agenda, there is potential for losing key segments of the target population. Solutions include recasting the intervention to maximize its relationship to the potential participants' perceived needs or integrating it into standard services. Research design should include collecting data from those who chose not to participate in the intervention or who drop out. Finally, it should be emphasized that many preventive interventions do not focus on risk status but use techniques intended to strengthen competence and skills and increase resiliency, and are directed at captive audiences or large scale populations (Roberts & Peterson, 1984). Such preventive interventions may be accepted on their intrinsic appeal or perceived merit, although they must avoid negative consequences and must not be viewed as too burdensome or they will discourage client participation. Regardless of the strategy selected, the only way to know the generalizability of the program is to collect data that provide an accurate description and documentation of how the sample and the intended target population differ.
A Consultation Model to Support Integrated Educational Services for Students with Severe Disabilities and Challenging Behaviors

Students with severe disabilities who also exhibit serious behavior problems are a significant challenge to the provision of integrated educational services in neighborhood public schools. This rep...