cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5796: Modulation of transcription factor landscape through BET family protein inhibition is dependent on specific driver mutations in pancreatic cancer

Targeting of bromodomain and extra-terminal domain (BET) family protein activity has the potential to reduce proliferation in many cancers. However, changes in transcription factor (TF) landscape can be influenced by different mutational profiles of specific cancers. Within this mutational background, BET proteins can target these TFs and create an oncogenic phenotype. To exploit these altered TF readouts, we tested the hypothesis that inhibition of BET activity in different genetic mutations of pancreatic cancer will lead to antiproliferative effects. Towards this, we treated pancreatic cancer cell lines that had mutations in KRAS, CDKN1A, SMAD4 and TP53 with a bromodomain inhibitor. We showed that cell lines with CDKN1A deletion and wild-type SMAD4 were highly resistant to BET inhibition and had a high nanomolar IC50 concentration. Through targeted transcription factor gene expression profiling of over 400 TFs, we discovered that LMO2, GTF2B, ID1, and CREB1 were upregulated, while SALL4, TCF4, and TP63 were downregulated in these cell lines. This suggests that these TFs may be partly responsible for resistance to BET inhibition. Furthermore, we showed dramatic changes in TF landscapes in pancreatic cancer cells sensitive to BET treatment compared to the resistant cells. This indicates that for antiproliferative effects in pancreatic cancer cells, modulating BET activity may be necessary to switch on or off specific TFs. Together, these results suggest that BET inhibitors may be useful in pancreatic cancer treatment and that mutation-specific differences in TF targets of BETs may dictate the progression of pancreatic cancer. Citation Format: Mikele G. Weldon, Albert R. Wang, Hope A. Beyer, Shannon G. Stiles, Gopal Iyer. Modulation of transcription factor landscape through BET family protein inhibition is dependent on specific driver mutations in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5796.
Diet and colon: what matters?

Purpose of review Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer-related deaths worldwide. Diet has a significant impact on the risk of developing CRC, but though processed meat is a known positive contributor, the effects of other dietary components are largely mixed. This review focuses on dietary patterns to describe the complexity of dietary diversity and overall food consumption and to examine the relationship between dietary patterns and risk of CRC. Recent findings After searching human studies published in 2017-2018, we selected and evaluated 30 articles, including meta-analyses, cohort studies, and prospective studies. These studies suggest that the prudent or Mediterranean dietary pattern significantly decreases the risk of CRC compared to the Western dietary pattern; a lower dietary inflammatory index or a higher dietary quality index associates with a lower risk of CRC; closely following all aspects of the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines and recommendations correlates with a reduced risk of CRC. Summary The risk of developing CRC can be reduced by adopting a healthier lifestyle. More studies of the impact of diet on clinical outcomes of CRC are needed.
Hispanic Dementia Family Caregiver's Knowledge, Experience, and Awareness of Self-Management: Foundations for Health Information Technology Interventions.

Purpose:As a first step toward developing a web-based Family-Health Information Management System intervention, we explored Hispanic dementia family caregiver’s knowledge, use, and awareness of sel...
Military cultural competence in the context of cognitive behavioural therapy

Current work in multicultural competency has emphasized factors such as race and ethnicity, age, disability status, socioeconomic status, sexual orientation and gender. For those clinicians who work with military and veteran populations, grounding in military cultural competence is also critical as a prerequisite for providing quality care. We believe that engaging these populations from a specifically cognitive behavioural orientation allows bridging of cultural gaps and that there is a natural alignment between cognitive behavioural therapy (CBT) and many aspects of warrior culture. This paper outlines several factors related to the values of military culture and strategies of the CBT therapist to better understand and use these values effectively in clinical practice, including lessons learned from an intensive outpatient program providing speciality care to veterans and military service members.
Native oxidation resistance of Al20Nb30Ta10Ti30Zr10 refractory complex concentrated alloy (RCCA)

Abstract The native oxidation resistance of an Al20Nb30Ta10Ti30Zr10 (at.%) refractory complex concentrated alloy (RCCA) was evaluated at 1000 °C in air. Oxidation tests revealed that the alloy exhibits linear oxidation kinetics out to 4 h of oxidation, with an adherence to parabolic, diffusion-controlled oxidation from 4 to 100 h. This transition was ultimately attributed to the formation of an outer oxide consisting primarily of TiO2 and Ti7Al2O15 layers. The 100 h oxide product contained multiple internal layers, but the overall oxidation kinetics was proposed to be controlled by the outer composite oxide layer. While this layer was morphologically continuous, it consisted of a non-continuous mixture of NbAlO4, ZrO2, Ti7Al2O15, and Ta2Nb4O15. The observed oxide scales are discussed relative to the oxidation behaviors of less-complex alloys.
Inverse design of radiative thermal meta-sources via discrete dipole approximation model

The radiation from conventional thermal infrared sources is incoherent and unpolarized. It has been recently shown that patterning plasmonic materials into metasurfaces can enhance the coherence of thermal radiation through thermal excitation of localized resonant modes in meta-atoms, enabling realization of thermal emitting metasurfaces—metasources—with high directivity and spectral selectivity. Toward achieving flexible modulation of radiative heat using metasurfaces and realization of complex functionalities, the design rules and modeling tools should be modified to take into account the incoherent nature of thermal radiation. In this paper, we utilize a robust formulation based on discrete dipole approximation within the framework of fluctuation dissipation theorem, which can efficiently characterize the thermal emission from large-area finite thermal metasources consisting of nanostructured materials. We employ an evolutionary lattice approach for the inverse design of radiative thermal metasources through topology optimization without relying on the phase analysis based on the assumption of coherency. To this end, the interaction matrix of dipolar equations is initialized for a lattice of subwavelength blocks and the arrangement of the blocks is subsequently optimized via a genetic algorithm toward achieving a certain spatial emission pattern with minimal computational cost. This approach enables fast and efficient design of large-scale thermal metasources with arbitrary functionalities. In particular, we investigate steering, focusing, and arbitrary shaping of partially coherent thermal radiation via finite silicon carbide gratings supporting surface phonon polaritons. Moreover, we demonstrate that the use of electro-optical materials such as graphene enables active tuning of thermal emission and realization of geometrically fixed multifunctional thermal metasources.
Post-project evaluation of Tule Ponds in Fremont, California : Integration of stormwater treatment and wetland restoration

Stormwater can contaminate water supplies and cause biological impacts to streams, estuaries, and coastal zones due to excess sediment, nutrients, pesticides, or heavy metals. Best management practices (BMPs) for stormwater control are implemented with greater frequency now that municipalities are required to have a National Pollutant Discharge Elimination System (NPDES) permit according to Clean Water Act revisions. After BMP construction, however, engineers and hydrologists rarely conduct follow-up assessments or evaluations. For this project, we evaluated the effectiveness of the Tule Ponds in Fremont, a constructed permanent wetland designed to simultaneously treat urban runoff and provide wildlife habitat. Using survey measurements of the pond dimensions and elevations, wildlife observations, and conversations with the site manager, we analyzed the success of the original wetland design. While our findings indicate the ponds did not function exactly as intended, they still succeeded in reaching overall intended objectives. The ponds catch, retain, and treat stormwater; however, the banks were unstable and have eroded, and the system dries out almost every summer due to infiltration into the ground. Based on current BMP guidelines, the ponds are too deep in winter, their banks are too steep, and emergent vegetation is insufficient. These factors may limit the ability of the wetland to support aquatic wildlife, and may limit contaminant removal. In addition, excess pond depth and algal growth result in low oxygen levels. Still, the site is populated with common birds (Canada geese, mallards and egrets), amphibians (bullfrogs and Pacific treefrogs), and insects (dragonflies and damselflies). We examine trade-offs between multiple use aims of this wetland system. In addition, because the site is only accessible through scheduled classroom field trips and is not generally open to the public, Tule Ponds may represent a missed opportunity for broader public education about urban ecology and stormwater management.
Women and Men Were Proportionally Represented Among Speakers at Major National Neurology Conferences in 2017

Abstract Objective To determine whether speaking roles at five major neurology conferences in 2017 show disproportionate representation by men. Methods This study consisted of two cross-sectional analyses. In the first part, we compared speaker characteristics across meetings and by gender using descriptive statistics. In the second part, we linked presenters to the American Medical Association (AMA) Masterfile. For the primary analysis in the second part using linked AMA speaker data, we built models to estimate the influence of gender on speaker roles. Results 1493 speakers were identified and included in our cross-sectional analysis. Women made up 28% of presenters from the US and 18% of presenters from other countries. After adjusting for years from medical school graduation and subspecialty, no effect of gender on speaker activity was observed (odds ratio [OR] for women 0.91; 95% confidence interval [CI], 0.77-1.07). Conclusions Factors aside from national conference speaking activity should be investigated to better understand sex differences in rank at top-ranked academic neurology programs.
Forced Relocation: Catalyst for Indigenous Resistance on Nicaragua’s Atlantic Coast, 1980–1990

Over the course of this paper, the author carefully illustrates how Sandinista programs of cultural assistance and social reconstruction that were intended to benefit the peoples of Nicaragua’s Atlantic Coast actually served to alienate large segments of the indigenous population. Likewise, he shows how the apparent ignorance of the Frente Sandinista Liberacion Nacional (FSLN) in regard to their understanding of indigenous social and political formations produced high levels of indifference among the Coast communities toward the revolutionary process. As a result, he demonstrates how increasingly repressive responses on the part of the Sandinista government toward popular dissension helped to transform the fundamental character of the indigenous opposition from one of political apathy to that of armed resistance. However, to reach such valid conclusions, the author first retraces the origins and evolution of the Miskito, Sumu, Rama, and Creole peoples within the context of their continuing struggle against the Nicaraguan state to maintain their own separate cultural and ethnic identities. In addition, he discusses the arrival of the Sandinistas on the Atlantic Coast and how their social and political interaction with the Costenos precipitated hostilities. Finally, the author examines the Sandinista decision to forcibly relocate large numbers of Miskito civilians and how it related to subsequent indigenous emigration and the emergence of an armed conflict.
Building a virtual community to support and celebrate the success of Latinx scientists

In February 2019, we co-founded LatinXinBME to build a diverse and welcoming virtual community of Latinx researchers in biomedical engineering (BME). We leverage digital tools and community mentoring approaches to support our members and to build safe spaces in academia, with the aim to diversify the academic workforce in STEM.
Stress-responses to ostracism: Examining cortisol and affective reactivity to in-person and online exclusion:

Ostracism is associated with poor outcomes, but it is unclear if online versus in-person ostracism elicits divergent psychological and physiological responses. Participants (N = 54) were randomly a...
Examining adolescents' opioid knowledge and likelihood to Utilize an educational game to promote medication safety.

Abstract Background Adolescents' knowledge on opioids is seldom studied, despite the fact young people are one of the groups most affected by the opioid crisis within the United States. There is a need to understand adolescents’ perceptions about opioid misuse and safety to create the necessary tools to educate adolescents on safe opioid use. Objective This study sought to understand adolescents’ knowledge and perceptions of opioid use and safety as well as their receptiveness to using an educational game for improving medication safety knowledge. Methods A 67-item survey was developed to assess adolescents' opioid perceptions, knowledge, and the likelihood of an educational game to enhance their opioid medication safety. A nationally representative sample of US adolescents aged 12 to 18 were recruited via a Qualtrics participant panel to complete the online survey from October through November 2020. Survey questions were grouped into 10 categories to represent key concepts and summarized into concept scores. Concepts were described through means, median, and range as well as percent correct for individual questions. Differences between groups were assessed using Kruskal-Wallis tests. Concept scores and their relation to the participant's age were described by the Pearson's correlation coefficient and the linear model coefficient. Results A total of 592 responses were analyzed. Male and older participants reported greater perceived opioid knowledge than females. White participants reported higher rates of perceived opioid knowledge, behavioral intent, and knowledge of safe medication disposal than any other racial group. About 80% of participants were receptive to the use of an educational game to increase their opioid safety knowledge. Conclusions There are discrepancies in adolescents' knowledge on opioid safety and harm amongst genders, race, and age. Study findings support the use of an educational game to increase adolescents’ opioid knowledge. Future studies should design an educational game intended for a diverse audience.
Detection of tip-vortex signatures behind a 2.5 MW wind turbine

abstract The near-ﬁeld signature of the vortical structures shed from the blade tips behind a 2.5 MW horizontalaxis wind turbine in a stably-strati ﬁed atmospheric boundary layer (ABL) was quanti ed for the rsttime. This study utilizes wind velocity measurements from sonic anemometers installed on a meteor-ological tower, which offers continuous characterization of wind conditions in the ﬁeld, at elevationscoinciding with the bottom, hub and top tip heights of the turbine. Using the stringent criteria on windspeed, direction and steadiness, we are able to subsample the dataset in which the sonic anemometersare positioned near the edge of the turbine wake. The spectral analysis of this dataset shows a distinctpeak at the turbine rotational frequency (f T ) for hub and top tip height measurements. Based on recentliterature, we infer that this peak is the signature of tip-vortices, and the shift of this signature fromblade-passing frequency (3f T )tof is likely to be caused by vortex grouping phenomena. Slight changes ofmeanwind direction in other data samples result in the absence of the spectral peak, suggesting the verylocal extent of tip vortices.& 2015 Elsevier Ltd. All rights reserved.
CHAPTER 12 – BIOSYNTHETIC PRODUCTS FOR ANTICANCER DRUG DESIGN AND TREATMENT: THE BRYOSTATINS

The chapter focuses on the use of bryostatins for anticancer drug design and treatment. The field of anticancer drug discovery based on natural products is vast and covers many areas, including isolation, chemical identification, and synthesis, preclinical evaluation, both in vitro and in vivo, and clinical trials. The U.S. National Cancer Institute (NCI) research programs directed at discovery of new and clinically useful animal, plant, and microorganism anticancer constituents were implemented in September 1957, and quickly demonstrated that 2–4% of plant specimens produce a great variety of anticancer agents. Because of this vitally important NCI endeavor, new antineoplastic and/or cytotoxic biosynthetic products are now being discovered worldwide at an increasing rate, and the potential for discovery of new animal, plant, and microorganism biosynthetic products for treatment of human cancer is truly extraordinary, and offers great promise of many curative approaches to the cancer problem. The experiments conducted by Dr. Blumberg in the NCI showed that the potent anticancer activity of bryostatin and bryostatins was primarily based on modulation of protein kinase C (PKC). Compared to various PKC interactive substances, bryostatin has proved to be a very potent antitumor-promoting agent, and a very promising anticancer drug. Bryostatin was also found to be an immune stimulant. Bryostatin was also found to stimulate the normal production of interleukin-2 (IL-2) and interferon, and it has provided curative levels of activity against a variety of murine experimental cancer systems.
Univalent Cations as Allosteric Activators of Muscle Adenosine 5'-Phosphate Deaminase

Abstract The allosteric properties of crystalline adenosine 5'-phosphate deaminase prepared from rabbit muscle were investigated. The enzyme was demonstrated to have homotropic effects with its substrate, AMP. The apparent Km is 0.9 mm and the Hill slope (n) is 2.2. In the presence of potassium, linear Michaelis-Menten kinetics was obtained, giving a Km for AMP of 0.4 mm and a Hill slope of 1.1. The Vmax is the same in the presence or absence of KCl. In the absence of KCl, the enzyme is also activated by ADP and ATP. These results show that a univalent cation can act as an allosteric activator of muscle AMP deaminase and that K+ is not required for the catalysis.
Summation and Conclusions

“First study the science. Then practice the art which is born of that science.” These words of Leonardo da Vinci have served as the guiding spirit of this volume. Perhaps more than any other pathological process, stress arousal represents the epitome of mind/body interaction. I have suggested earlier in this volume that proper clinical understanding and treatment of such conditions that so intimately intertwine psychology and physiology demand that the clinician’s attention be directed toward the “science” of physiology (and pathophysiology) as well as the art/science of behavior change. Thus, to be consistent with this stated bias, this volume has first introduced the reader to a rather detailed exploration of the physiological nature and foundations of the human stress response. This, as a preface to the subsequent chapters that directly addressed the treatment of excessive stress arousal and its pathological consequences.
Development of HepG2-derived cells expressing cytochrome P450s for assessing metabolism-associated drug-induced liver toxicity.

The generation of reactive metabolites from therapeutic agents is one of the major mechanisms of drug-induced liver injury (DILI). In order to evaluate metabolism-related toxicity and improve drug efficacy and safety, we generated a battery of HepG2-derived cell lines that express 14 cytochrome P450s (CYPs) (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5 and 3A7) individually using a lentiviral expression system. The expression/production of a specific CYP in each cell line was confirmed by an increased abundance of the CYP at both mRNA and protein levels. Moreover, the enzymatic activities of representative CYPs in the corresponding cell lines were also measured. Using our CYP-expressed HepG2 cells, the toxicity of three drugs that could induce DILI (amiodarone, chlorpromazine and primaquine) was assessed, and all of them showed altered (increased or decreased) toxicity compared to the toxicity in drug-treated wild-type HepG2 cells. CYP-mediated drug toxicity examined in our cell system is consistent with previous reports, demonstrating the potential of these cells for assessing metabolism-related drug toxicity. This cell system provides a practical in vitro approach for drug metabolism screening and for early detection of drug toxicity. It is also a surrogate enzyme source for the enzymatic characterization of a particular CYP that contributes to drug-induced liver toxicity.
Alzheimers disease: review of emerging treatment role for intravenous immunoglobulins.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Currently available therapies are symptomatic but do not alter underlying disease progression. Immunotherapeutic approaches such as anti As peptide active vaccination trials have had limited success to date. Intravenous immunoblobulin (IVIg) is widely used in immune-mediated neurological disorders such myasthenia gravis and Guillain-Barre syndrome. These preparations have been obtained from the pooled plasma of healthy human donors and contain natural anti-amyloid antibodies and are well tolerated. A small pilot study of passive immunotherapy using IVIg has suggested cognitive improvement. A multicenter phase III trial is ongoing and will determine whether or not this treatment can ameliorate cognitive deficits in mild-to-moderate AD. Here, we briefly review the pathogenic role of amyloid and tau in AD, as well as immunotherapeutic efforts to date. We also summarize what is known about naturally occurring anti-As and tau antibodies in IVIg with a view toward explaining potential mechanisms underlying their therapeutic effects.
Facile Detection of Protein−Protein Interactions by One-Dimensional NMR Spectroscopy†

Two methods for detecting protein−protein interactions in solution using one-dimensional (1D) NMR spectroscopy are described. Both methods rely on measurement of the intensity of the strongest methyl resonance (SMR), which for most proteins is observed at 0.8−0.9 ppm. The severe resonance overlap in this region facilitates detection of the SMR at low micromolar and even sub-micromolar protein concentrations. A decreased SMR intensity in the 1H NMR spectrum of a protein mixture compared to the added SMR intensities of the isolated proteins reports that the proteins interact (SMR method). Decreased SMR intensities in 1D 13C-edited 1H NMR spectra of 13C-labeled proteins upon addition of unlabeled proteins or macromolecules also demonstrate binding (SMRC method). Analysis of the interaction between XIAP and Smac, two proteins involved in apoptosis, illustrates both methods. A study showing that phospholipids compete with the neuronal core complex for Ca2+-dependent binding to the presynaptic Ca2+-sensor synap...
Connecting to Our Community: Extending Librarians' Roles Through Collaboration

In order to reach out to diverse segments of the Himmelfarb Health Sciences Library's patron base, librarians developed new initiatives and roles to expand their scope of responsibilities. New outreach initiatives included a film series with panel discussions, an instructional technology series by faculty for faculty, two exhibits, an annual art show, and a faculty authors reception. Each initiative broadened the skills of the participating librarians, extended the presence of the library into the community, and brought individuals from different corners of the institution together at the various events.
Enhancement of natural convection heat transfer from an array of discrete heat sources

Abstract Single-phase, natural convection heat transfer data have been obtained for an array of highly-finned, discrete heat sources mounted to one wall of a cavity filled with a dielectric liquid (FC-77). Dense, parallel plate fin arrays were considered for both vertical and horizontal cavity orientations, and the finned surfaces were found to enhance heat transfer by as much as a factor of 24. Thermal resistances approaching 2 cm 2 °C W −1 were realized, while maintaining the temperature difference between the fin base and an opposing cold plate below 70°C. In a parallel numerical study, flow and heat transfer conditions were calculated by treating the fin array as a porous medium characterized by the Brinkman-Forchheimerextended Darcy model. The model provided a reasonable approximation which captured the experimental trends and predicted the data to within 30%.
Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid signalling cross-talk

A fundamental goal in cancer biology is to identify the cells and signalling pathways that are keys to induce tumour regression. Here we use a spontaneously self-regressing tumour, cutaneous keratoacanthoma (KAs), to identify physiological mechanisms that drive tumour regression. By using a mouse model system that recapitulates the behaviour of human KAs, we show that self-regressing tumours shift their balance to a differentiation programme during regression. Furthermore, we demonstrate that developmental programs utilized for skin hair follicle regeneration, such as Wnt, are hijacked to sustain tumour growth and that the retinoic acid (RA) signalling pathway promotes tumour regression by inhibiting Wnt signalling. Finally, we find that RA signalling can induce regression of malignant tumours that do not normally spontaneously regress, such as squamous cell carcinomas. These findings provide new insights into the physiological mechanisms of tumour regression and suggest therapeutic strategies to induce tumour regression.
THE GROWTH WITHOUT GROWTH HORMONE SYNDROME

Abstract The phenomenon of growth without GH has been recognized for over a quarter of a century in various physiologic or near-physiologic situations, including the fetal state and obesity, and in various obviously pathologic states, including postsurgical resection of suprasellar/hypothalamic tumors, most notably craniopharyngiomas, and in acromegaloidism. The mechanism or mechanisms responsible for this fascinating clinical syndrome are unknown. The available data implicate, at least in some of these subjects, a role for hypothalamic injury leading to obesity and insulin resistance which, in turn, leads to elevated circulating concentrations of insulin to which the body retains mitogenic sensitivity. Alternatively, in other subjects with this syndrome, evidence exists to support the presence of a circulating as yet incompletely characterized potent growth-promoting factor which appears in the serum. Further studies of this syndrome should help to enhance our knowledge of the mechanisms governing both normal and abnormal human growth.
Response to Influence of stochastics on quantitative PCR in the detection of minimal residual disease by Rawer et al

Response to Influence of stochastics on quantitative PCR in the detection of minimal residual disease by Rawer et al
Synthesis and Photopolymerization of 1-Propenyl Ether Functional Siloxanes

A variety of mono-, di-, and multifunctional 1-propenyl ether functional siloxanes were readily prepared in high yields by the transition-metal-catalyzed condensation of α-(1-propenyl) ω-vinyl ethers with various linear and cyclic hydrogen functional siloxanes. Under these conditions, hydrosilation takes place regioselectively at the vinyl ether site of the α-(1-propenyl) ω-vinyl ether. Using onium salt photoinitiators, these new monomers and oligomers undergo rapid polymerization under the influence of UV light. To study these very fast photopolymerizations, extensive use of Fourier transform real-time infrared spectroscopy was made. Employing this technique, the effects of monomer and photoinitiator structure on the rates of polymerization were studied.
Rigid, Sterically Diverse N-Heterocyclic Carbene-Pyridine Chelates: Synthesis, Mild Palladation, and Palladium-Catalyzed Allylic Substitution

A series of four 1-(pyridin-2-yl)benzimidazolium salts was synthesized as precursors to rigid, bidentate N-heterocyclic carbene-pyridine ligands. With the goal of exploring the interplay between steric and electronic asymmetry in catalysis, the ligands are constructed with very small (H, Me) or very bulky (2,6-diisopropylphenyl, 2,4,6-triisopropylphenyl) groups adjacent to the nitrogen and carbon donor atoms. Cationic palladium-allyl complexes were synthesized under mild conditions, using triethylamine as base and potassium or silver hexafluorophosphate as counterion source. The structures of three complexes were verified using X-ray crystallography. All four palladium complexes were active catalysts for the allylic substitution reaction between allylic carbonates and either sodium diethyl-2-methylmalonate or N-methylbenzylamine, although significant ligand-controlled effects on regioselectivity were not observed under the conditions studied.
Peroxynitrite formation and apoptosis in transgenic sickle cell mouse kidneys

Peroxynitrite formation and apoptosis in transgenic sickle cell mouse kidneys. Background In a previous study, nitric oxide synthases (NOS) were found to be strongly expressed in the tubular epithelium of kidneys of a transgenic mouse model of sickle cell disease (α H β S [β MDD ]). Because NOS activity is often associated with peroxynitrite formation when superoxide radical ( • O − 2 ) is present in abundance, we examined the kidneys of sickle cell mice for nitrotyrosine, considered to be a footprint of ONOO - . Methods Western blot and immunohistochemistry for nitrotyrosine was carried out. Since peroxynitrite and other reactive oxygen radicals are capable of causing apoptosis, we also performed agarose gel electrophoresis of kidney DNA and TUNEL staining of nuclei, indicators of apoptosis. Results Nitration of tyrosine residues of three proteins (kD 66, 57 and 22) was found on Western blot of kidney protein extracts of the sickle cell mice. The degree of tyrosine nitration of the 66 kD protein was not significantly different in the control versus transgenic mice, whereas tyrosine nitration of the 57 and 22 kD proteins was clearly increased in transgenic mice. Strong immunostaining for nitrotyrosine was seen in tubular epithelial cells of the sickle cell mice, in close proximity to positive immunostaining of iNOS. Neither iNOS nor nitrotyrosine was expressed in the control mice. DNA "laddering" was found localized to the same zones of the kidney as nitrotyrosine and iNOS immunostaining. TUNEL assay on mouse kidney tissue sections showed minimal tubular cell apoptosis in normal mouse with hypoxia, mild tubular cell apoptosis in sickle cell mouse in room air, and moderate tubular cell apoptosis in sickle cell mouse with hypoxia. Conclusions The observations suggest that ONOO - and perhaps other reactive oxygen species are being produced in the sickle cell kidney. The mechanism may be ischemia/reperfusion due to intermittent vascular occlusion by sickle cells. The resulting hypoxia could result in iNOS activation, superoxide radical and peroxynitrite formation. Two consequences of these reactions appear to be nitration of tyrosine residues of some renal proteins and enhanced apoptosis.
Sarcoidosis: clinical manifestations, epidemiology, therapy, and pathophysiology.

Sarcoidosis is an idiopathic granulomatous disease involving one or more multiple organ systems, characterized by the histologic finding of noncaseating epithelioid cell granulomas. The disease has a predilection for intrathoracic structures; the musculoskeletal system is less frequently involved. Most osseous lesions in sarcoidosis are visible in the small joints of the hands and feet. Articular disease may present as an acute or chronic polyarthritis. Muscle involvement in sarcoidosis is generally asymptomatic. Neurologic findings of the central and peripheral nervous systems may occur in sarcoidosis. Subcutaneous nodules are of diagnostic value. Sarcoid vasculitis may involve small and large blood vessels. Sarcoidosis of the exocrine glands may mimic Sjogren's syndrome. Spontaneous remission of disease often occurs. Treatment with nonsteroidal anti-inflammatory agents, corticosteroids, antimalarials, radiation therapy, and immune-modulating drugs may be beneficial in the treatment of sarcoidosis.
Comments on “The Generalized Wiener Process for Colored Noise”

Galleani and Cohen (see ibid., vol.13, no.10, p.608-11, Oct. 2006) have developed a new approach to the study of random differential equations. Recently, they applied their method to the interesting case that they called the generalized Wiener process. We show that while the phase space equation they derived is correct, their solution to the equation is not the full solution but holds only under certain conditions. We obtain the general solution and discuss under what circumstances their solution is exact, and under what circumstances their solution is a good approximation to the exact solution. In addition, we pinpoint where in their method of solution they neglected a term, and give the correction. In many cases, their approach may be accurate enough, and hence preferable, as it is a simpler calculation than the exact solution. However, for processes with long correlation times (i.e., autocorrelation functions that do not decay rapidly to zero), the complete method of solution presented here may be required.
Exploring the Opportunities and Challenges with Exercise Technologies for People who are Blind or Low-Vision

People who are blind or low-vision may have a harder time participating in exercise due to inaccessibility or lack of experience. We employed Value Sensitive Design (VSD) to explore the potential of technology to enhance exercise for people who are blind or low-vision. We conducted 20 semi-structured interviews about exercise and technology with 10 people who are blind or low-vision and 10 people who facilitate fitness for people who are blind or low-vision. We also conducted a survey with 76 people to learn about outsider perceptions of hypothetical exercise with people who are blind or low-vision. Based on our interviews and survey, we found opportunities for technology development in four areas: 1) mainstream exercise classes, 2) exercise with sighted guides, 3) rigorous outdoors activity, and 4) navigation of exercise spaces. Design considerations should include when and how to deliver auditory or haptic information based on exercise and context, and whether it is acceptable to develop less mainstream technologies if they enhance mainstream exercise. The findings of this work seek to inform the design of accessible exercise technologies.
Antireflection Coatings for Astronomical Silicon Imagers

We have developed a process for broadband antireflection coating of fully fabricated silicon imagers. We discuss modeling, deposition, and optical testing. Results show that many detector goals can be met with a silicon nitride/oxide structure.
Non-destructive current-ramp dielectric breakdown (IRDB) for fast BEOL reliability monitoring

A fast current-ramp dielectric breakdown (IRDB) method is developed for critical dielectric reliability assessment. Unlike the conventional voltage-ramp method, the nondestructive nature of IRDB still allows wafers to be shipped for revenue after reliability monitoring. This is an important criterion for reduced-cost, high-volume manufacturing.
Identification of Two Transmembrane Regions and a Cytosolic Domain of Rat Mitochondrial Glycerophosphate Acyltransferase

Abstract The topography of rat glycerophosphate acyltransferase (GAT) in the transverse plane of the mitochondrial outer membrane (MOM) was investigated. Computer analysis of the amino acid (aa) sequence derived from rat mitochondrial GAT cDNA (GenBank™ accession nos. U36771 and AF021348) predicts the presence of two possible transmembrane domains (aa 473–493 and 574–594) separated by an 80-aa stretch (aa 494–573). To determine the actual orientation of the native protein, we prepared anti-peptide antibodies to three regions: one in between (aa 543–559) and the other two (aa 420–435 and 726–740) flanking the two putative transmembrane regions. Both immunoreaction and immunoprecipitation experiments employing intact and solubilized mitochondria indicate that regions on the N- and C-terminal sides of the transmembrane regions are sequestered on the inner surface of the MOM, while the region between the transmembrane domains is present on the cytosolic face of the MOM. Additionally, two green fluorescent protein (GFP) fusion proteins consisting of full-length GAT fused to GFP at either the C terminus or inserted 115 amino acids from the N terminus were also constructed to determine the orientation of the N and C termini. COS-1 cells expressing these fusion proteins were fractionated to obtain mitochondria. Protease digestion of intact and solubilized COS-1 cell mitochondria revealed that the GFP domains of these fusion proteins are sequestered on the inner side of the MOM. The present findings indicate that GAT is a dual-spanning, transmembrane protein adopting an inverted “U” conformation in the transverse plane of the MOM, where the N and C termini are sequestered on the inner surface of the MOM, while aa 494–573 are exposed on the cytosolic surface of the MOM.
Change in velocity of high frequency transverse sound at the superconducting transition temperature

Abstract The change in velocity of transverse sound at the transition temperature consists of two parts (1) a static part (usually estimated to be 1–10 ppm arising from the difference in the elastic constants between the superconducting and normal states, and (2) a purely dynamical effect due to Meissner Screening of the transverse electromagnetic fields at the transition temperature. It is shown that under suitable conditions, as first suggested by Ozaki and Mikoshiba, the second mechanism can give rise to much larger changes in the velocity of high frequency sound. In fact for Al at a sound wave frequency of 106 c s and ql = 10 (here q is the wave number of the sound wave and l is the electron mean free path) the relative change in velocity can be as much as 1 part per thousand. The results of a detailed microscopic calculation of the relative change in velocity (v s −v n ) v n are presented for weak coupling type I superconductors.
A molecular dissection of the carboxyterminal tails of the major neurofilament subunits NF-M and NF-H

We have initiated a multidisciplinary project that aims to dissect and ultimately define the functions of the long and unusual C-terminal "tail" sequences of the two high molecular weight neurofilament subunits, NF-M and NF-H. A series of recombinant fusion proteins containing selected NF-M and NF-H tail sequences were constructed using appropriate cDNAs. These fusion proteins were used to further define the epitopes for a variety of widely used neurofilament antibodies, including NN18 and N52, which are now available commercially from several companies. We also measured the SDS-PAGE mobility of the fusion proteins and found that, like the native neurofilament tails, the fusion proteins ran considerably slower than predicted from their molecular weight. Since all fusion proteins produced so far exhibit this characteristic we conclude that all segments of the NF-M and NF-H tail share this unusual property. Finally we were able to produce novel and potentially useful polyclonal and monoclonal antibodies to selected segments of NF-M and NF-H sequence. These antibody studies showed that the extreme C-termini of NF-M and NF-H are immunologically absolutely distinct from one another and also indicate that the extreme C-terminus of NF-M is immunologically much more conserved than the analogous region of NF-H. These findings are in complete agreement with our conclusions derived from amino acid sequence analysis, and further underline the possible functional importance of the extreme C-terminus of NF-M. We also show that the unusual immunological properties of the bovine NF-M tail we have previously observed do not extend to the extreme C-terminal region, which appears immunologically no different from the analogous region of other NF-M molecules. The peculiarities of bovine NF-M could be explained by the presence of a KSP motif that resembles the NF-H KSP prototype.
Modeling recystallization kinetics in a deformed iron single crystal

The kinetics of recrystallization of a (111) {\(\left[ {\bar 1\bar 12} \right]\)} single crystal of pure iron deformed 70 pct by rolling were characterized experimentally at temperatures between 450°C and 600°C, using quantitative metallography. The method of Laplace transforms was applied to the overall recrystallization kinetic behavior to separate nucleation from interface migration kinematics. A comprehensive nucleation and growth model was developed to explain all observations quantitatively. the model consisted of the following important features: (a) nucleation sites were distributed randomly; (b) nucleation was site-saturated and occurred with no practical incubation time at all annealing temperatures; (c) recrystallized grains grew three-dimensionally and were spheroidally shaped; (d) all recrystallized grains grew at approximatelly the same rate within experimental error; and (e) interface migration rates were not constant but decreased with time according to at−0.38 law at all temperatures. The time dependency of the interface migration rate was rationalized in terms of deformation-induced, nonuniform distribution of stored energy, Recovery processes competing with recrystallization were evident at long annealing times at the two lowest annealing temperatures.
Emerging challenges and potential futures for thermally enhanced oil recovery

Abstract Thermal recovery, and specifically steam injection, is arguably the most successful technique for enhancing oil recovery implemented to date. Heat thins heavy oils reducing viscosity, improving producibility substantially, and shifts rock wettability to conditions more favorable for oil recovery. While thermal recovery is typically applied to heavy and viscous oils in sand matrices, thermal techniques are also applicable to lighter oils and to more heterogeneous formations. Because most thermal oil production is achieved today using steam generated on the surface by burning natural gas, thermal recovery has an environmental footprint that is larger when compared to conventional oil production. The relatively large surface footprint, water demand, and carbon dioxide emissions from steam generation have all emerged as challenges for thermally enhanced oil production. This article outlines the current technical, economic, and environmental issues associated with thermal oil recovery. It also presents potential solutions and mitigation measures. Techniques such as solar heat to displace fossil fuels for steam generation, in-situ combustion, and downhole heat generation have great potential as next-generation thermal recovery methods.
Revitalizing Higher Education in Bangladesh: Insights from Alumni and Policy Prescriptions

Higher education in Bangladesh must become more responsive to the needs of a major constituency: its students. How this might be accomplished is examined in this study using a nine-factor model to explain the satisfaction of alumni with their education. These factors include teacher quality, method and content, peer quality, facilities and resources, the effectiveness of the administration, campus politics, gender, and year of graduation. A probability sample was selected using a combination of cluster and systematic sampling. Multiple regression was used to test the hypotheses. The results indicated that five of the nine variables were significant in the model and explained 47% of the variation in the dependent variable. Policy implications of the model are discussed.
Evolution of activity signatures during the main sequence phase

Abstract We review recent work on the decay of magnetic activity signatures, such as chromospheric/transition region/coronal emission as well as mean flare emission, with age for solar and later type stars. Both implicit and explicit evolutionary representations are discussed. In terms of magnetic flux, as measured by excess chromospheric CaII luminosity, we show that a simple dynamo-rotation relation that incorporates both a saturated state with its characteristic critical rotation (or scale factor) as well as an asymptotic linear power law, i.e. a scale free relation, fits the extant data that includes the dMe stars. Introducing the saturated dynamo state, as exemplified by the dMe stars, into activity power-power diagrams, allows us to not only specify the saturated state, but to define evolutionary tracks that represent the decay from the saturated state. Using the quiescent coronal X-ray power (luminosity) as a basic measure of magnetic activity, we find simple monomial relations for both the saturated state (linear) and for the evolutionary tracks governing both quiescent activity and mean flare activity. In particular, the coronal power loss is found to vary quadratically with the chromospheric power loss, hence with magnetic flux.
College students and quick-service restaurants: how students perceive restaurant food and services.

The current generation of college students has grown up with many quick-service restaurants. In the United States, the top three quick-service restaurants are McDonald's, Burger King, and Wendy's. A survey of 499 college students was conducted regarding their satisfaction levels with quick-service restaurant foods and services. The results indicated that if the quick-service restaurant wants to attract college students, they must concentrate on providing outstanding “quality value” and “practical value.” Wendy's received the highest satisfaction scores over McDonald's and Burger King. The results from this study can assist executives and managers in developing strategic plans appropriate for the college student market.
The Genain Quadruplets

The Genain quadruplets are a unique set of monozygous women who are concordant for schizophrenia but discordant for the severity of their disorder. They were studied by David Rosenthal and colleagues at the National Institute of Mental Health in the late 1950's when they were in their twenties and again in 1981 when they were 51. They are faring about as well now as they ever have in their adult lives. The results of psychological tests, some of which were repeated more than 20 years apart, are discussed, as are the effects of medication on attention and memory. The differential response of the Genains to neuroleptic drugs, as well as certain other findings in the 1981 study, leads to a different conclusion about the discordant severity of their disorder from that reached in 1963 by Rosenthal and Quinn. These observations emphasize the value of long-term followup studies in genetically related individuals, with repeated assessments of the same functions.