cssi/SciSciGPT-SciSciNet huggingface dataset:
Para-Aminobenzoic Acid (PABA) enhances responses to low and high dose rate radiotherapy (RT) in glioblastoma cell lines

586 Objective: Glioblastoma multiforme is the most common primary brain tumor in adults. Median survival is approximately one year with surgical resection and postoperative RT, and is improved by three months with the addition of the alkylating agent temozolomide (TMZ). Additional therapeutic developments are urgently needed to improve the dismal outcome of this disease. Recent studies show that radiation delivery with Tomotherapy, at dose rates 4-5 times higher compared to conventional techniques, enhance cell killing. In addition, we have shown that PABA enhances RT responses in various cancers both in-vitro and in-vivo. In this study, we investigate the impact of dose rate and PABA in three high-grade glioma cell lines as a function of their resistance to RT and alkylating damage. Materials and Methods: T98G (radiation/TMZ resistant), U118, and U87MG, were irradiated to give total doses of 6, 12 and 18 Gy via two dose rates; low dose rate (LDR) of 100 cGy/min and high dose rate (HDR) of 2200cGy/min. Cells were synchronized by serum starving prior to treatment. PABA (100 ug/mL) was added at 6 hrs prior and for 96 hrs after RT. TMZ exposure (100uM) was for 7 days. Modified MTT (performed 96 hours post RT) and clonogenic assays were performed. Results: When compared to LDR, HDR increased growth inhibition (GI) across all cell lines and dose groups. Specifically, in radioresistant T98G cells, HDR resulted in a 100% (6Gy), 54% (12 Gy) and 13% (18 Gy) increase in cell death compared to LDR. The addition of PABA to LDR augmented GI in all cell lines by 68-146% (6 Gy), 50-82% (12 Gy) and 7-37% (18 Gy). This GI was greater or equal to that observed with HDR alone. For the HDR group, the addition of PABA resulted in a more moderate increase in GI by 7-46% (6 Gy) and 10-36% (12 Gy). With TMZ alone and no RT, GI rates were 26% (T98G), 75% (U118) and 90% (U87MG). With PABA alone and no RT, GI rates were 57% (T98G), 55% (U118) and 73% (U87MG). The combination of PABA and TMZ with no RT increased GI to 52% only in the TMZ-resistant T98G cells. Conclusions: PABA enhances radiation responses both with LDR and HDR radiation. HDR radiation improves cell killing in all three cell lines. Without RT, PABA alone or in combination with TMZ doubles tumor GI in TMZ-resistant cells. This is the first in-vitro study to demonstrate modulation of radiation responses with LDR and HDR RT and show significant PABA modulation at LDR in glioblastoma cells. Currently, we are combining pre-treatment with PABA and TMZ followed by HDR and LDR RT in these and other glioblastoma cell lines. p21 and key signaling pathways are being examined by Western Blot, and apoptotic responses are being assessed. With the clinical availability of Tomotherapy, it becomes relevant to further study the mechanism of action of this combined therapy and assess the role of PABA as potential adjuvant to RT in malignant brain tumors. Supported in part by The Chemotherapy Foundation and Cancer Innovations, Inc.
Macrophage-Mediated Clofazimine Sequestration Is Accompanied by a Shift in Host Energy Metabolism.

Abstract Prolonged (8 weeks) oral administration of clofazimine results in a profound pharmacodynamic response—bioaccumulation in macrophages (including Kupffer cells) as intracellular crystal-like drug inclusions (CLDIs) with an associated increase in interleukin-1 receptor antagonist production. Notably, CLDI formation in Kupffer cells concomitantly occurs with the formation of macrophage-centric granulomas. Accordingly, we sought to understand the impact of these events on host metabolism using 1 H-nuclear magnetic resonance metabolomics. Mice received a clofazimine or vehicle-enriched (sham) diet for at least 8 weeks. At 2 weeks, the antimicrobial activity of clofazimine was evident by changes in urine metabolites. From 2 to 8 weeks, there was a striking change in metabolite levels indicative of a reorientation of host energy metabolism paralleling the onset of CLDI and granuloma formation. This was evidenced by a progressive reduction in urine levels of metabolites involved in one-carbon metabolism with corresponding increases in whole blood, and changes in metabolites associated with lipid, nucleotide and amino acid metabolism, and glycolysis. Although clofazimine-fed mice ate more, they gained less weight than control mice. Together, these results indicate that macrophage sequestration of clofazimine as CLDIs and granuloma formation is accompanied by a profound metabolic disruption in energy homeostasis and one-carbon metabolism.
The origins of developmental gene regulation

The leap from simple unicellularity to complex multicellularity remains one of life's major enigmas. The origins of metazoan developmental gene regulatory mechanisms are sought by analyzing gene regulation in extant eumetazoans, sponges, and unicellular organisms. The main hypothesis of this manuscript is that, developmental enhancers evolved from unicellular inducible promoters that diversified the expression of regulatory genes during metazoan evolution. Promoters and enhancers are functionally similar; both can regulate the transcription of distal promoters and both direct local transcription. Additionally, enhancers have experimentally characterized structural features that reveal their origin from inducible promoters. The distal co-operative regulation among promoters identified in unicellular opisthokonts possibly represents the precursor of distal regulation of promoters by enhancers. During metazoan evolution, constitutive-type promoters of regulatory genes would have acquired novel receptivity to distal regulatory inputs from promoters of inducible genes that eventually specialized as enhancers. The novel regulatory interactions would have caused constitutively expressed genes controlling differential gene expression in unicellular organisms to become themselves differentially expressed. The consequence of the novel regulatory interactions was that regulatory pathways of unicellular organisms became interlaced and ultimately evolved into the intricate developmental gene regulatory networks (GRNs) of extant metazoans.
A Rough Set Based Feature Selection Approach Using Random Feature Vectors

Feature selection is the process of selecting a subset of features that provides maximum of the information, present otherwise in entire dataset. The process is very helpful when input for different tasks including classification, clustering, rule extraction and many others, is large. Rough Set Theory, right from its emergence, has been widely used for feature selection due to its analysis friendly nature. Various approaches exist in literature for this purpose. However, majority of them are computationally too expensive and suffer a significant performance bottleneck. In this paper we have proposed a new feature selection approach based on rough set theory, using random feature vector generation method. The proposed approach is a two steps method. At first, it generates a random feature vector and verifies its suitability for being a potential candidate solution. If it fulfills the criteria, it is selected and optimized, otherwise a new subset is formed. The proposed approach was verified using five publicly available datasets. Results have shown that proposed approach is computationally more efficient and produces optimal results.
Motorcycle-Helmet Laws and Public Health.

Motorcyclists are much more likely to die or be injured in a crash than passenger-car occupants. Helmet use has been shown to reduce the severity of injuries from motorcycle crashes and increase the likelihood of survival, but most states don’t have laws requiring it.
Osteogenic Growth Factors and Cytokines and Their Role in Bone Repair

Ontogenetic development is initiated at the time of fertilization and terminates with the differentiation, growth, and maturation of specialized tissues and organs. These developmental processes are characterized by molecular specialization that accompanies cellular differentiation and tissue morphogenesis. Most developmental processes terminate after birth or when animals reach sexual maturity, but some morphogenetic processes are reinitiated in response to injury in specific tissues. One such regenerative process is the repair of skeletal fractures and bone tissue after surgery, a process that recapitulates specific aspects of the initial developmental processes in the course of healing [58, 209]. Several aspects of the postnatal tissue environment of fracture healing, however, are unique and differ from what occurs in embryological and postnatal development.
Distribution and variability of the dissolved inorganic carbon system in the Cariaco Basin, Venezuela

Abstract A study was conducted to characterize the variability of dissolved inorganic carbon concentration and speciation in surface waters (upper 100 m) of the southern Caribbean Sea in the Cariaco Basin, located off Venezuela. The spatial distribution of total CO 2 (TCO 2 ), partial pressure of CO 2 ( p CO 2 ), and the saturation state with respect to aragonite (Ω arg ) was evaluated by measuring pH and total alkalinity (TA) in transects across the Basin during upwelling (dry season in March 2004 and 2009) and during the rainy season (September 2006 and 2008). Alkalinity was more strongly related to salinity in the western half of the Cariaco Basin (R 2 = 0.87 and R 2 = 0.80 for September 2008 and March 2009, p 2 = 0.20, p > 0.01 for March 2004, and R 2 = 0.37 and R 2 = 0.31 for September 2008 and March 2009, p > 0.001). In the western sub-basin, high pH (> 8.1) and low p CO 2 ( p CO 2 was high (> 400 μatm) in surface waters during upwelling. The TA-salinity relationship followed a two end-member mixing model (upwelled waters and river input). p CO 2 in surface waters ranged from 366 to 525 μatm during upwelling (March), and 385 to 452 μatm during the rainy period (September). Waters were supersaturated with respect to aragonite saturation state throughout the Cariaco Basin. The Basin was typically over-saturated with CO 2 with respect to the atmosphere. Under-saturation was only observed near the coast, such as near the mouth of the Tuy River. The flux of CO 2 over most of the Cariaco Basin was generally from the ocean to the atmosphere in both seasons. Fluxes tend to remain between 0 and 10 mmol CO 2 m − 2 day − 1 , with average values for the whole basin of 11.39 ± 17.17 mmol CO 2 m − 2 day − 1 in March 2004, 7.19 ± 2.17 mmol CO 2 m − 2 day − 1 in September 2006, 6.32 ± 2.42 mmol CO 2 m − 2 day − 1 in September 2008 and 4.35 ± 3.97 mmol CO 2 m − 2 day − 1 in March 2009.
Finding the Signal of Dynamic Capabilities: A Bayesian Analysis of Performance Variations

Do dynamic capabilities play a significant role in firms' value appropriation patterns over time? So far it has been challenging to find the signal of dynamic capabilities in large-N empirical stud...
Economic Impact of Combinatorial Materials Science on Industry and Society [1]

Research and development (R&D) funding within the chemical process industry averages 3.5% of sales, or about $12–14 billion annually in the United States, and is focused mostly on process development and support of downstream activities. This R&D supports annual sales of chemicals of over $400 billion that in turn feed into critical US industries and account for over $1.2 trillion in product sales and service in downstream value.
Multilayered Cellulosic Material as a Leather Alternative in the Footwear Industry

The purpose of this study was to develop a biodegradable material that could be used as a leather alternative material for the footwear industry, leading to reduce the negative environmental impact...
Rescue of CFTR NBD2 mutants N1303K and S1235R is influenced by the functioning of the autophagosome.

The missing phenylalanine at position 508, located in nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane regulator (CFTR), is the most common cystic fibrosis mutation. Severe disease-causing mutations also occur in NBD2. To provide information on potential therapeutic strategies for mutations in NBD2, we used a combination of biochemical, cell biological and electrophysiological approaches and newly created cell lines to study two disease-causing NBD2 mutants, N1303K and S1235R. We observed that neither was sensitive to E64, a cysteine protease inhibitor. However, further investigation showed that when treated with a combination of correctors, C4 + C18, both mutants also responded to E64. Further exploration to assess aggresome throughput using the autophagy regulator LC3 as a marker showed that, in the absence of correctors, N1303K showed a stalled throughput of LC3-II to the aggresome. The throughput became active again after treatment with the corrector combination C4 + C18. Confocal microscopic studies showed that the N1303K and S1235R mutant proteins both co-localized with LC3, but this co-localization was abolished by the corrector combination and, to a lesser extent, by VX-809. Both the corrector combination and VX-809 increased the CFTR chloride channel function of both mutants. We conclude that correctors have a dual effect, particularly on N1303K: they improve trafficking and function at the plasma membrane and reduce the association with autophagosomes. After treatment with correctors persistent degradation by the autophagosome may limit restoration of function. Thus, mutations in NBD2 of CFTR, in contrast to ΔF508-CFTR, may require additional personalized strategies to rescue them.
Relating Technology, Education Reform and Economic Development

This article examines research on the relationships among information and communications technology (ICT), education, and economic development. Drawing on economic theory, it proposes a conceptual framework to posit causal connections between the use of technology and economic development in the context of other corollary changes that may be needed in education if the use of technology is to contribute to economic improvement. Case studies of the recent economic development in Singapore and Finland and their corresponding ICT and educational policies are used to explore the implications of this framework.
Replication of poliovirus in Xenopus oocytes requires two human factors.

Abstract We described a novel system to study poliovirus replication in Xenopus oocytes. Poliovirus RNA microinjected into Xenopus oocyte initiates a complete cycle of viral replication, yielding a high level of infectious viruses. Two distinct HeLa cell activities are required, one involved in initiation of translation and the other in RNA synthesis. The translation factor is a large cytoplasmic protein or complex, which is specifically used for initiation of poliovirus translation. The replication factor is required at early stages of RNA synthesis. Formation of infectious poliovirus is highly temperature dependent. At temperatures below 27 degrees C, capsid assembly appears to be impaired. The oocyte system described here could be useful in identifying and characterizing viral and cellular factors involved in virus replication.
Accelerating Venture Milestone Achievement: Examining the Impact of Resource Acquisition Timing

This study examines how resource acquisition timing affects a venture's ability to accelerate milestone achievement. We examine acquisition timing decisions for three types of resources: material resources, facilities and equipment resources, and human resources. Two venture milestones are examined: accomplishment of the first sale and achievement of positive cash flows. We theorize that resource acquisition timing can impact the degree of resource availability delays and the rate of resource-driven cash outflows/inflows, which, in turn, determine the time to first sale and the time to positive cash flows, respectively. Our results demonstrate that decisions concerning resource acquisition timing could have contradictory effects vis-a-vis shortening the time to first sale versus shortening the time to positive cash flows. These findings highlight the difficult tradeoffs that ventures have to navigate when making resource acquisition decisions, which have implications for multiple milestones across a venture's lifecycle. Finally, the paper demonstrates how technological novelty moderates, and, in fact, radically alters, the relationship between the timing of resource acquisitions and the time to venture milestone achievement.
Gravesia serratifolia (Melastomataceae: Sonerileae), a new species from Marojejy National Park, Madagascar

Gravesia serratifolia , a new species from upper elevations of Marojejy National Park in northeastern Madagascar, is herein described, illustrated, mapped, and compared with similar species. It is readily characterized by its sparingly branched habit, leaf blades coarsely serrate with a moderate to sparse lepidote indumentum on both surfaces, inflorescence of few-flowered dichasia, calyx obsolete or evident as depressed truncate undulations with prominent calyx teeth that are laterally compressed when fresh, filaments with rusty-brown glandlike indumentum, and dorso-basal staminal appendages linear-oblong and widely spreading to coiled. A conservation assessment of Vulnerable is recommended for this species based on IUCN Red List Categories and Criteria.
Wavelet Compression Performance of MMS/FPI Plasma Count Data with Plasma Environment

The Fast Plasma Investigation onboard the Magnetospheric Multiscale mission uses a discrete wavelet transform and bit plane encoder for data compression. This is the first plasma spectrometer suite to use this method of compression and thus serves as a benchmark for future plasma spectrometers. Flight data from MMS confirm viability of this compression algorithm in large areas of the magnetosphere. Because much of the FPI data were compressed losslessly on orbit, this flight data can be used as seed data to investigate performance of the DWT/BPE‐based compression at increased rates of compression. In this study, data from several representative regions of the magnetosphere have been compressed to increasingly small sizes and the resulting error was analyzed. Wavelet‐based compression is shown to be effective in all regions of the magnetosphere and solar wind for plasma count data, with performance varying with local environment. Specifically, plasma distributions that are characterized by low temperature and/or low density are compressed better leading to excellent performance in plasma regions such as solar wind and the magnetosheath. In general, ion data are compressed better than electron data, primarily due to a higher drift velocity of ions relative to their thermal speed and lower count rates. DWT/BPE compression can therefore be recommended for future instruments measuring count data in Earth's magnetosphere and in solar wind.
Trajectory optimization for car races using genetic algorithms

In this paper, we present an application of genetic algorithms to a problem of optimizing a car trajectory in a closed loop car race setting. The goal is to minimize the amount of turning that the car needs to do such that it can drive faster, or the total distance that it needs to travel to finish the race. We compare the results with a procedurally computed trajectory and with an optimized version of it using smoothing methods.1
Microvascular free tissue transfer and cochlear implants: A case series and literature review.

Objective The use of microvascular free tissue transfer (MVFTT) for defects of the scalp and lateral temporal bone in patients with cochlear implants (CI) is uncommon. Herein, we report our experience with the utility, indications, and outcomes for MVFTT in patients with cochlear implants. Methods A retrospective review of patients at our institution from September 2016 to December 2017 identified subjects with coexistent cochlear implant and ipsilateral MVFTT of the lateral temporal bone or scalp. Information including demographics, indication for MVFTT, timing of CI and MVFTT, donor site, and previous radiation to the head and neck was collected. To assess the current literature on MVFTT in CI patients, a MEDLINE search was performed using key search terms. Results Two patients with cochlear implants and MVFTT of the ipsilateral temporal bone or scalp were identified. One patient underwent MVFTT for advanced device extrusion with stable audiometric parameters rather than locoregional reconstruction or device explantation. The second patient had primary cochlear implantation at oncologic lateral temporal bone resection (LTBR) and MVFTT for locally advanced squamous cell carcinoma and concurrent profound sensorineural hearing loss (SNHL). A literature review identifies MVFTT as an option for advanced device extrusion, treatment of osteoradionecrosis, and reconstruction after primary oncologic surgery. Conclusion MVFTT is an important reconstructive tool for patients with functional, exposed cochlear implants. Cochlear implantation for severe to profound SNHL should be considered at the time of primary oncologic surgery and MVFTT of the lateral temporal bone or scalp. Level of evidence IV Laryngoscope, 130:1552-1557, 2020.
Virtual Reality-Based Executive Function Rehabilitation System for Children With Traumatic Brain Injury: Design and Usability Study.

Background: Traumatic brain injury (TBI) poses a significant threat to children’s health. Cognitive rehabilitation for pediatric TBI has the potential to improve the quality of life following the injury. Virtual reality (VR) can provide enriched cognitive training in a life-like but safe environment. However, existing VR applications for pediatric TBIs have primarily focused on physical rehabilitation. Objective: This study aims to design and develop an integrative hardware and software VR system to provide rehabilitation of executive functions (EF) for children with TBI, particularly in 3 core EF: inhibitory control, working memory, and cognitive flexibility. Methods: The VR training system was developed by an interdisciplinary team with expertise in best practices of VR design, developmental psychology, and pediatric TBI rehabilitation. Pilot usability testing of this novel system was conducted among 10 healthy children and 4 children with TBIs. Results: Our VR-based interactive cognitive training system was developed to provide assistive training on core EF following pediatric TBI. Pilot usability testing showed adequate user satisfaction ratings for both the hardware and software components of the VR system. Conclusions: This project designed and tested a novel VR-based system for executive function rehabilitation that is specifically adapted to children following TBI.
Examining associations between racism, internalized shame, and self-esteem among African Americans

Shame, originating from social threats to social bonds, self-esteem and/or social status, has been associated with poor mental and physical outcomes. Despite theoretical assumptions indicating sham...
Modeling Heterogeneity of the Level-1 Error Covariance Matrix in Multilevel Models for Single-Case Data

Previous research applying multilevel models to single-case data has made a critical assumption that the level-1 error covariance matrix is constant across all participants. However, the level-1 error covariance matrix may differ across participants and ignoring these differences can have an impact on estimation and inferences. Despite the importance of this issue, the effects of modeling between-case variation in the level-1 error structure had not yet been systematically studied. The purpose of this simulation study was to identify the consequences of modeling and not modeling between-case variation in the level-1 error covariance matrices in single-case studies, using Bayesian estimation. The results of this study found that variance estimation was more sensitive to the method used to model the level-1 error structure than fixed effect estimation, with fixed effects only being impacted in the most extreme heterogeneity conditions. Implications for applied single-case researchers and methodologists are discussed.
Plasma and water fluoride levels and hyperuricemia among adolescents: A cross-sectional study of a nationally representative sample of the United States for 2013–2016

Abstract Exposure to excessive fluoride has been associated with a number of adverse health outcomes; however, there is a lack of evidence on the relation between fluoride exposure and serum uric acid levels, especially in human populations. The present study examined a potential relationship between fluoride exposure, measured as both plasma and water fluoride concentrations, and uric acid levels in an adolescent population. A nationally representative subsample of 1933 adolescents, aged 12–19 years, in the 2013–2016 National Health and Nutrition Examination Survey was analyzed for the association of fluoride concentrations with serum uric acid levels using multivariate general linear and logistic regression models, adjusting for potential confounders. Since uric acid levels change during development, hyperuricemia was defined in this study as over the mean plus one standard deviation for each sex and age group of adolescents. Of the study participants, 276 adolescents (weighted prevalence, 16.56%) had hyperuricemia. A significant and dose-dependent increase in prevalence of hyperuricemia was seen among the participants cross increasing quartiles of plasma fluoride (p-trend = 0.0017). After adjusting for potential confounders, we found that adolescents in the higher quartiles of plasma fluoride (≥0.32 µmol/L) and in the highest quartile of water fluoride (≥0.73 mg/L) had significantly increased odds of hyperuricemia compared with those in the lowest quartile. A 1.95-fold increased odds (95% CI: 1.37, 2.77) of hyperuricemia was also observed when analyzing plasma fluoride concentrations as continuous variable. A general linear model revealed that a 1 µmol/L increase in ln-plasma fluoride was associated with a 0.212 mg/dL (p
Introducing the Journal of Chemical Education's Special Issue on Chemical Safety Education: Methods, Culture, and Green Chemistry

The Journal of Chemical Education’s Special Issue on Chemical Safety Education: Methods, Culture, and Green Chemistry is a collection of 38 peer-reviewed papers on the topic of chemical safety educ...
Associations between mental health shortage areas and county-level suicide rates among adults aged 25 and older in the USA, 2010 to 2018.

Abstract Objective Suicide is a serious public health concern, but little is known about the relationship between access to mental health care and suicide deaths, and whether suicide rates differ by mental health provider Health Professional Shortage Areas (HPSAs). This study investigated the associations between mental health HPSAs and suicide rates. Method We used generalized linear mixed models to test the associations between HPSAs and suicide rates from 2010 to 2018. For each county during a 3-year period, the total number of suicides was obtained from Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (WONDER). Results Mental health HPSAs had higher suicide rates (adjusted incidence rate ratio (IRR), 1.06 [95% CI, 1.03–1.09]). The interaction terms of mental health HPSAs and time (adjusted IRR, 1.01 [95% CI, 1.00–1.01]) showed that the association between mental health shortage areas and suicide rates has increased over time. Conclusions Suicide rates are more common in mental health provider shortage areas, and this association has been growing over time. The study's findings suggest that many communities in the US are likely facing simultaneous challenges of limited access to mental health care, social and economic disadvantage, and high burden of suicide.
Using Dictyostelium to Develop Therapeutics for Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) involves damage to lungs causing an influx of neutrophils from the blood into the lung airspaces, and the neutrophils causing further damage, which attracts more neutrophils in a vicious cycle. There are ~190,000 cases of ARDS per year in the US, and because of the lack of therapeutics, the mortality rate is ~40%. Repelling neutrophils out of the lung airspaces, or simply preventing neutrophil entry, is a potential therapeutic. In this minireview, we discuss how our lab noticed that a protein called AprA secreted by growing Dictyostelium cells functions as a repellent for Dictyostelium cells, causing cells to move away from a source of AprA. We then found that AprA has structural similarity to a human secreted protein called dipeptidyl peptidase IV (DPPIV), and that DPPIV is a repellent for human neutrophils. In animal models of ARDS, inhalation of DPPIV or DPPIV mimetics blocks neutrophil influx into the lungs. To move DPPIV or DPPIV mimetics into the clinic, we need to know how this repulsion works to understand possible drug interactions and side effects. Combining biochemistry and genetics in Dictyostelium to elucidate the AprA signal transduction pathway, followed by drug studies in human neutrophils to determine similarities and differences between neutrophil and Dictyostelium chemorepulsion, will hopefully lead to the safe use of DPPIV or DPPIV mimetics in the clinic.
Yap/Taz-Activated Expansion of Tert-Expressing Acinar Cells Are Required for Pancreatic Regeneration

The expression of TERT (telomerase reverse transcriptase) has been implicated in stem and progenitor cells, which are essential for tissue homeostasis and regeneration. However, the roles of TERT-expressing cells in the pancreas remain elusive. Employing genetically engineered Tert knock-in mouse model, herein, we located a rare population of Tert+ acinar cells. While Tert+ cells are quiescent in normal conditions, acinar cell injury leads to mitotic activation of Tert+ cells and subsequent generation of new acinar cells. Moreover, the genetic ablation of Tert+ cells impairs pancreatic regeneration. We further found that Yap/Taz activation is required for the expansion of Tert+ acinar cells. Our results identified Tert+ acinar cells as a distinct subset of acinar cells, which contributes to pancreatic regeneration via Yap/Taz activation.
DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons.

Lithium has been a drug for bipolar disorders (BD) for over 70 years; however, its usage has been limited by its narrow therapeutic window (between 0.6 and 1.2 mM). Understanding the cellular distr...
Mitochondrial DNA Copy Number in Peripheral Blood and Melanoma Risk

Mitochondrial DNA (mtDNA) copy number in peripheral blood has been suggested as risk modifier in various types of cancer. However, its influence on melanoma risk is unclear. We evaluated the association between mtDNA copy number in peripheral blood and melanoma risk in 500 melanoma cases and 500 healthy controls from an ongoing melanoma study. The mtDNA copy number was measured using real-time polymerase chain reaction. Overall, mean mtDNA copy number was significantly higher in cases than in controls (1.15 vs 0.99, P<0.001). Increased mtDNA copy number was associated with a 1.45-fold increased risk of melanoma (95% confidence interval: 1.12-1.97). Significant joint effects between mtDNA copy number and variables related to pigmentation and history of sunlight exposure were observed. This study supports an association between increased mtDNA copy number and melanoma risk that is independent on the known melanoma risk factors (pigmentation and history of sunlight exposure).
Effect of Plane of Nutrition on Mammary Gland Development in Prepubertal Goats

A high plane of nutrition fed prior to puberty has been shown to negatively affect mammary gland development in heifers by decreasing secretory tissue and increasing adipose tissue (Sejrsen et al.,1982; Stelwagen and Grieve, 1990). Heifers reared on a high plane of nutrition have been shown to have depressed milk yields throughout their productive lives (Peri et al., 1992). Presently, it is not known why a high plane of nutrition inhibits mammary parenchymal development. Hormones and local growth factors play an important role in mammary gland development (Plaut, 1993). It is possible that a high plane of nutrition alters levels of hormones or growth factors that are needed for parenchymal development. Because heifers take up to 10 months to reach puberty, research in this area has been limited. Goats reach puberty 3–5 months sooner than heifers, therefore a similar study of caprine mammary development could be carried out in almost half the time. This study was conducted to test the usefulness of goats for such studies, and to test if a high plane of nutrition affects prepubertal mammary development.
Molar Growth Yields as Evidence for Oxidative Phosphorylation in Streptococcus faecalis Strain 10C1

During the aerobic growth of Streptococcus faecalis strain 10C1, with limiting levels of glucose as the substrate, a molar growth yield (Y) of 58.2 g (dry weight) per mole of glucose was obtained. Under these conditions of growth, glucose was dissimilated primarily to acetate and CO2. The incorporation of 14C-glucose into cell material was no greater under aerobic conditions than during anaerobic growth. Assuming an adenosine triphosphate coefficient of 10.5, the aerobic Y cannot be explained solely on the basis of substrate phosphorylation and would appear to substantiate previous enzymatic evidence for oxidative phosphorylation in this cytochromeless species. With mannitol as the substrate, an aerobic Y of 64.6 was obtained. Extracts of mannitol-grown cells contained a nicotinamide adenine dinucleotide (NAD)-linked mannitol-1-phosphate (M-1-P) dehydrogenase. The difference in aerobic Y values with mannitol and glucose as substrates would indicate that the in vivo P/O ratio from the oxidation of reduced NAD generated by the oxidation of M-1-P approximates 0.6. The Y values with pyruvate and glycerol as substrates under aerobic conditions were 15.5 and 24.7, respectively.
Immune-complex disease in guinea pig lungs: I. Elicitation by aerosol challenge, suppression with cobra venom factor, and passive transfer with serum

Abstract Immune-complex disease was elicited in the lungs of ovalbumin-sensitized guinea pigs following an aerosol challenge with specific antigen. An acute inflammatory reaction, characterized by peribronchial polymorphonuclear leukocyte infiltration, edema, and hemorrhage, was observed 2 hr following aerosol challenge. This focal reaction developed into a diffuse reaction within 6 to 12 hr postchallenge. By 24 hr postchallenge, the acute inflammatory process had begun to resolve. The active disease was suppressed with cobra venom factor and was transferred to normal guinea pigs with immune serum.
Transamidating enzymes. I. Rapid chromatographic assays.

Abstract Quantitative chromatographic methods were developed for measuring the activities of transamidases that catalyze exchange reactions on γ-carbonyl groups of glutamine residues. Radioactive histamine, putrescine, and the fluorescent monodansylcadaverine were used as amine donors. Glutamine-containing acceptor substrates varied from the small peptide benzyloxycarbonylglutaminylglycine to α-casein and β-lactoglobulin. The transamidases studied were obtained from liver (guinea pig liver transglutaminase), muscle (lobster muscle transpeptidase or tissue coagulin), and blood plasma (fibrinoligase or thrombin-activated fibrinstabilizing factor). Advantages of the chromatographic methods over all other currently available transamidase assays, both for the standardization of these enzymes and for measuring their activities in cells and tissues, are being emphasized.
Diverse functions and dynamic expression of neuronal sodium channels.

Nearly a dozen genes encode different Na channels, sharing a common overall motif but with subtly different amino acid sequences. Physiological signatures have now been established for some Na+ channels and it is clear that, from a functional point of view, Na+ channels are not all the same: different channels can have different physiological characteristics, and they can play different roles in the physiology of excitable cells. Moreover, the expression of Na+ channels within neurons is not a static process. Plasticity of Na+ channel gene expression occurs in the normal nervous system, where it accompanies transitions between different physiological states (e.g. low-frequency versus high-frequency firing states) in some types of neurons. Maladaptive changes in Na+ channel gene expression also occur in some pathological neurons. For example, transection of the peripheral axons of spinal sensory neurons triggers downregulation of some Na+ channel genes and up-regulation of others, resulting in changes in Na+ current expression that produce hyperexcitability, thereby contributing to chronic pain. There is also recent evidence for the expression of normally silent Na+ channel genes in Purkinje cells in experimental models of demyelinating diseases and in a human disease, multiple sclerosis; this dysregulation of Na+ channel expression may interfere with neuronal function in these disorders. The diversity and dynamic nature of Na+ channel expression introduce a high degree of complexity into the nervous system and present challenges for neuroscientists. In addition, they may present therapeutic opportunities as selective modulators for various Na+ channel subtypes become available.
Differential characteristics of salicylic acid-mediated signaling in potato

Potato (Solanum tuberosum) has key differences in salicylic acid (SA) metabolism and signaling from tobacco and Arabidopsis such as high basal salicylic acid concentrations in all tissues examined, including roots and tubers. Potato has high levels of basal PR-1 expression and this appears to be a consequence of the high SA levels, because the expression is reduced in nahG plants. Despite the high basal SA levels, potato was nevertheless responsive to exogenous SA and as little as 250 mM SA-induced PR-1 when sprayed on plants. However, plants grown in field conditions appeared less responsive to BTH at certain times. In spite of the high total SA concentrations, some potato varieties are able to maintain free SA levels as low as 0.5% of the total SA. Potato is also unusual in that PR-1 is strongly induced in leaf discs in the absence of any additional treatment. Furthermore, potato leaf discs are hypersensitive to BTH, with concentrations as low as 1 mM causing extensive cell death, whereas concentrations as high as 500 mM had no such effect on tobacco. Published by Elsevier Ltd.
Communication Sensei's Storytelling: Projecting Identity into Critical Pedagogy:

Identity politics in culturally diverse U.S.-American higher education is so complex that it is difficult to completely account for all of its elements. As a communication sensei, I enter this arena taking an approach informed by critical pedagogy and employing performative and/or autoethnographic writing as a mode of critical interrogation. Via storytelling, I investigate my becoming and the role of a critical pedagogue as a sociotemporal actor in today's culturally diverse U.S.-American education. Critical pedagogues should enter education as an intersubjective identity project where educational participants' stories meet, and their “hoped-for future” emerges from their storytelling.
Analyzing Arthropods for the Presence of Bacteria

Bacteria within arthropods can be identified using culture-independent methods. This unit describes protocols for surface sterilization of arthropods, DNA extraction of whole bodies and tissues, touchdown PCR amplification using 16S rDNA general bacteria primers and profiling the bacterial community using denaturing gradient gel electrophoresis.
Genetic engineering of glycinebetaine production toward enhancing stress tolerance in plants: metabolic limitations.

Glycinebetaine (betaine) affords osmoprotection in bacteria, plants and animals, and protects cell components against harsh conditions in vitro. This and a compelling body of other evidence have encouraged the engineering of betaine production in plants lacking it. We have installed the metabolic step for oxidation of choline, a ubiquitous substance, to betaine in three diverse species, Arabidopsis, Brassica napus, and tobacco (Nicotiana tabacum), by constitutive expression of a bacterial choline oxidase gene. The highest levels of betaine in independent transgenics were 18.6, 12.8, and 13 μmol g−1 dry weight, respectively, values 10- to 20-fold lower than the levels found in natural betaine producers. However, choline-fed transgenic plants synthesized substantially more betaine. Increasing the choline supplementation further enhanced betaine synthesis, up to 613 μmol g−1 dry weight in Arabidopsis, 250 μmol g−1 dry weight in B. napus, and 80 μmol g−1 dry weight in tobacco. These studies demonstrate the need to enhance the endogenous choline supply to support accumulation of physiologically relevant amounts of betaine. A moderate stress tolerance was noted in some but not all betaine-producing transgenic lines based on relative shoot growth. Furthermore, the responses to stresses such as salinity, drought, and freezing were variable among the three species.
CYTOSKELETAL ASSOCIATION IS IMPORTANT FOR DIFFERENTIAL TARGETING OF GLUCOSE TRANSPORTER ISOFORMS IN LEISHMANIA

The major glucose transporter of the parasitic protozoan Leishmania enriettii exists in two isoforms, one of which (iso-1) localizes to the flagellar membrane, while the other (iso-2) localizes to the plasma membrane of the cell body, the pellicular membrane. These two isoforms differ only in their cytosolic NH2-terminal domains. Using immunoblots and immunofluorescence microscopy of detergent-extracted cytoskeletons, we have demonstrated that iso-2 associates with the microtubular cytoskeleton that underlies the cell body membrane, whereas the flagellar membrane isoform iso-1 does not associate with the cytoskeleton. Deletion mutants that remove the first 25 or more amino acids from iso-1 are retargeted from the flagellum to the pellicular membrane, suggesting that these deletions remove a signal required for flagellar targeting. Unlike the full-length iso-1 protein, these deletion mutants associate with the cytoskeleton. Our results suggest that cytoskeletal binding serves as an anchor to localize the iso-2 transporter within the pellicular membrane, and that the flagellar targeting signal of iso-1 diverts this transporter into the flagellar membrane and away from the pellicular microtubules.
Physician Management of Patients With Heart Failure and Normal Versus Decreased Left Ventricular Systolic Function

A questionnaire was administered to a random sample of family practitioners, internists, cardiologists, and geriatricians to examine the current management of heart failure patients with preserved versus reduced left ventricular systolic function. In patients with preserved systolic function, electrocardiogram at rest, chest x-ray, echocardiography, digitalis, angiotensin-converting enzyme inhibitors, and restriction of dietary sodium and physical activity are used less often, whereas calcium channel blockers and beta blockers are given more often than to patients with reduced systolic function.
What is Genetic Discrimination and When and How Can it Be Prevented

The public policy debate concerning the desirability and scope of legislation prohibiting discrimination has become increasingly volatile. Last year, a provocative opinion piece urging citizens to "gather courage to discriminate genetically" was widely syndicated. Another commentator suggested that genetic discrimination is "both rational and inevitable." On the other hand some prominent genetic scientists and legislators as well as disease support groups, continue to make passage of laws with strong protections for affected individuals one of their top priorities. Genetic researchers and clinicians need to recognize the unarticulated assumptions about discrimination that shape the debate and understand the underlying tensions between differing accounts of justice and fairness. In this article, we explore some of the nuances of the term discrimination and some of the sources of disagreement, before asking when and how genetic discrimination can be prevented.
Development of an ELISA for the N‐dealkylated s‐triazines: Application to environmental and biological samples

A sensitive and rugged ELISA for the detection of the N‐dealkylated metabolites of atrazine and simazine was developed and applied to environmental and biological samples. The limits of detection were approximately 10 ng ml‐1 for water samples, 40 ng ml‐1 for human urine when analyzed without any sample preparation and approximately 45 ng g‐1for solvent‐extracted soil. This assay was tolerant to changes in pH, salt and solvent effects. Comparison of the results from this ELISA with nominal values for a series of tap water samples spiked in a blind fashion resulted in a good correlation coefficient between the values found and those spiked. However, the ELISA systematically underestimated concentrations. Examination of the source of this error revealed that the dealkylated triazine concentrations of the samples declined with time. The assay was used to monitor the presence and loss of dealkylated triazines in a variety of samples. These data indicated that caution must be used in the analysis and interpret...
From social butterfly to modern‐day Medea: Elizabeth Broderick's portrayal in the press

This essay examines the press’ portrayal of Elizabeth Broderick and her trial for the November 5, 1989, murder of her ex‐husband and his wife. The central contention of this essay is that the press’ construction of Elizabeth Broderick's image can best be understood as a cautionary tale directed at men and women who might deviate from normative heterosexual gender roles. Specifically, it is suggested here that the press demonized her as a unique individual rather than casting her as acting in response to institutionalized patterns of power manifested in a hostile social environment. Additionally, by suggesting that she endangered her children, she was cast as committing a fundamental transgression against her gender, and hence of gender itself, thereby entering the domain of the inhuman. Going beyond the question of her guilt, I would content that the press de‐personalized Broderick. In this context, the analysis generates questions about the counter‐hegemonic narratives about justice as well as the comple...
Effects of the surface Miller index on the resonant neutralization of hydrogen anions near Ag surfaces

We compare the resonant neutralization dynamics of hydrogen anions in front of plane Ag surfaces of symmetries (100) and (111) using a Crank--Nicholson wave-packet propagation method. For the $\text{Ag}(100)$ surface, the surface state, degenerate with the valence band, rapidly decays while being populated by the ion. For $\text{Ag}(111)$, in contrast, the population of a quasi-local Shockley surface state inside the projected $L$-band gap impedes the electron decay into the bulk along the direction normal to the surface. This difference in the decay pattern strongly affects the survival of $1\phantom{\rule{0.3em}{0ex}}\text{keV}$ ions scattered from these surfaces. Scattering off the $\text{Ag}(111)$ surface results in about an order of magnitude higher ion-survival as a function of the exit angle with respect to the surface plane compared to that off $\text{Ag}(100)$. Results for $\text{Ag}(111)$ show good agreement with measurements [Guillemot and Esaulov, Phys. Rev. Lett. 82, 4552 (1999)].