cssi/SciSciGPT-SciSciNet huggingface dataset:
Telomerase expression on aortic wall endothelial cells is attenuated in abdominal aortic aneurysms compared to healthy nonaneurysmal aortas.

Objective Linear chromosomes carry specific DNA structures at their ends called telomeres. The latter shorten with each successive cell division making their length a marker of cell age. Telomerase prevents such telomere attrition by adding back telomeric repeats at the telomere ends, thus playing an important role in cell aging. On the other hand, an abdominal aortic aneurysm (AAA) represents an age-related degenerative disorder. The aim of the present study was to investigate a potential correlation of telomerase expression with AAA formation. Methods Aortic wall tissue samples were collected from 49 patients (mean age, 63.8 ± 4.4 years) with AAAs during open elective repair and from 24 deceased organ donors as controls (mean age, 60.5 ± 3.9 years). Telomerase expression on endothelial cells was detected by immunohistochemistry. Associations of telomerase positivity with AAAs and epidemiologic and clinical variables were investigated. Results Telomerase expression was significantly decreased in patients with AAAs (11 of 49; 22.4%) compared to controls (19 of 24; 79.2%; P Conclusion Patients with AAAs have attenuated telomerase endothelial expression compared to controls, implying a protective role of telomerase against AAA formation. Further investigation of pathways involved in vascular aging may contribute to elucidation of AAA pathogenetic mechanisms.
CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity

The ability to precisely modify endogenous genes can significantly facilitate biological studies and disease treatment, and the clustered regularly interspaced short palindromic repeats (CRISPR) systems have the potential to be powerful tools for genome engineering. However, the target specificity of CRISPR systems is largely unknown. Here we demonstrate that CRISPR/Cas9 systems targeting the human hemoglobin β and C-C chemokine receptor type 5 genes have substantial off-target cleavage, especially within the hemoglobin δ and C-C chemokine receptor type 2 genes, respectively, causing gross chromosomal deletions. The guide strands of the CRISPR/Cas9 systems were designed to have a range of mismatches with the sequences of potential off-target sites. Off-target analysis was performed using the T7 endonuclease I mutation detection assay and Sanger sequencing. We found that the repair of the on-and off-target cleavage resulted in a wide variety of insertions, deletions and point mutations. Therefore, CRISPR/Cas9 systems need to be carefully designed to avoid potential off-target cleavage sites, including those with mismatches to the 12-bases proximal to the guide strand protospacer-adjacent motif.
Lower Left Thalamic Myo-Inositol Levels Associated with Greater Cognitive Impulsivity in Marijuana-Dependent Young Men: Preliminary Spectroscopic Evidence at 4T

The effects of chronic marijuana (MRJ) use on neurochemistry are not well characterized. Previously, altered global myo-Inositol (mI) concentrations and distribution in white matter were associated with impulsivity and mood symptoms in young MRJ-dependent men. The objective of this study was to retrospectively examine previously collected data, to investigate the potential regional specificity of metabolite levels in brain regions densely packed with cannabinoid receptors. Spectra were acquired at 4.0 Tesla using 2D J-resolved proton magnetic resonance spectroscopic imaging (MRSI) to quantify the entire J-coupled spectral surface of metabolites from voxels in regions of interest. For the current regional spectral analyses, a 2D-JMRSI grid was positioned over the central axial slice and shifted in the x and y dimensions to optimally position voxels over regions containing thalamus, temporal lobe, and parieto-occipital cortex. MRJ users exhibited significantly reduced mI levels in the left thalamus (lThal), relative to non-using participants, which were associated with elevated cognitive impulsivity. Other regional analyses did not reveal any significant group differences. The current findings indicate that reduced mI levels are regionally specific to the lThal in MRJ users. Furthermore, findings suggest that mI and the lThal uniquely contribute to elevated impulsivity.
Abstract 677: Inhibition of Receptor-interacting Protein Kinase 1 With Necrostatin-1 and -1s Ameliorates Aneurysm Progression in the Elastase-induced Mouse Model of Abdominal Aortic Aneurysms (AAAs)

Objective: Abdominal aortic aneurysm (AAA) is a common vascular disease with a progressive nature. Currently, no pharmacological treatment is approved to effectively slow aneurysm growth or prevent rupture. We have recently demonstrated that receptor interacting protein kinase 3 (RIP3), a critical mediator of necroptosis, contributes to smooth muscle depletion and vascular inflammation associated with AAA. In this study, we tested the hypothesis that inhibition of necroptosis may mitigate aneurysm progression using Necrostatin-1 (Nec-1) or an optimized form of Nec-1 called Nec-1s (7-Cl-O-Nec-1), known inhibitors of another necroptosis mediator RIP1. Approach and Results: Using elastase perfusion model, we first demonstrated that Nec-1 attenuated aneurysm formation when administered daily by intraperitoneal (IP) injection started 30 min before aneurysm induction. Nec-1 also profoundly reduced elastin fragmentation, macrophage infiltration and SMC necrosis after elastase perfusion. To test whether RIP1 inhibitors can inhibit AAA progression, we randomly divided mice to four groups 7 days after elastase perfusion when aortic dilatation is small but significant. Group 1 was sacrificed to obtain a baseline aortic dilatation, while Group 2, 3, and 4 received daily IP injections of DMSO, Nec-1 (3.2 mg/kg/day) or Nec-1s (1.6mg/kg/day), respectively. 14 days after perfusion, mice in Group 2 displayed larger aneurysmal expansion as compared to Group 1 ( P 0.05), indicating insignificant aneurysmal growth. Furthermore, real-time PCR and histological analyses demonstrated that RIP1 inhibition significantly reduced aortic accumulation of proinflammatory cytokines and inflammatory cell infiltration. Conclusions: Taken together, our study suggests that necroptosis may serve as a therapeutic target for AAAs. Pharmacological inhibition of RIP1 kinase activity prevented aneurysm formation and stabilized pre-existing aneurysms in mice.
The feasibility of general task systems with precedence constraints on multiprocessor platforms

Feasibility analysis determines (prior to system execution-time) whether a specified collection of hard-real-time jobs executed on a processing platform can meet all deadlines. In this paper, we derive near-optimal sufficient tests for determining whether a given collection of jobs can feasibly meet all deadlines upon a specified multiprocessor platform assuming job migration is permitted. The collection of jobs may contain precedence constraints upon the order of execution of these jobs. The derived tests are general enough to be applied even when the collection of jobs is incompletely specified. We discuss the applicability of these tests to the scheduling of collections of jobs that are generated by systems of recurrent real-time tasks. We also show that our feasibility conditions may be used to obtain global-EDF schedulability conditions.
Shift of the flux-pinning force curve in Nb/sub 3/Sn thin films with very fine grain size

Nb/sub 3/Sn thin films were made by sputter deposition of Nb onto bronze substrates at various temperatures. Deposition at 660/spl deg/C produced a Nb/sub 3/Sn reaction immediately, which resulted in films with 20-50 nm grains. The peak of F/sub p/(H) for one of these films was at 0.35 to 0.38 H*, higher than the field where the standard flux-shear curve peaks, 0.2 H*. Deposition at 400/spl deg/C produced Nb films that were later reacted to form Nb/sub 3/Sn films with 50-250 nm grains. These films also exhibited F/sub p/(H) curves with peaks higher than 0.2 H*, but the shift was not as pronounced as for the rapidly formed films. The shift of the pinning force curve to higher fields is discussed in terms of the grain size difference and a recent flux-pinning model. All of the films exhibited an expanded Nb/sub 3/Sn lattice parameter and degraded superconducting properties, due to disorder and interstitial impurities.
Metabotropic Glutamate Receptor 1-Induced Upregulation of NMDA Receptor Current: Mediation through the Pyk2/Src-Family Kinase Pathway in Cortical Neurons

The mechanism underlying the upregulation of NMDA receptor function by group I metabotropic glutamate receptors (mGluRs), including mGluR1 and 5, is not known. Here we show that in cortical neurons, brief selective activation of group I mGluRs with (S)-3,5-dihydroxy-phenylglycine (DHPG) induced a Ca(2+)-calmodulin-dependent activation of Pyk2/CAKbeta and the Src-family kinases Src and Fyn that was independent of protein kinase C (PKC). Activation of Pyk2 and Src/Fyn kinases led to increased tyrosine phosphorylation of NMDA receptor subunits 2A and B (NR2A/B) and was blocked by a selective mGluR1 antagonist, 7-(hydroxyamino)cyclopropa[b]chromen-1a-carboxylate ethyl ester, but not an mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine. Functional linkage between mGluR1 activation and NR2A tyrosine phosphorylation through Pyk2 and Src was also demonstrated after expression of these elements in human embryonic kidney 293 cells. Supporting functional consequences, selective activation of mGluR1 by DHPG induced a potentiation of NMDA receptor-mediated currents that was blocked by inhibiting mGluR1 or Src-family kinases. Furthermore, antagonizing calmodulin or mGluR1, but not PKC, reduced the basal tyrosine phosphorylation levels of Pyk2 and Src, suggesting that mGluR1 may control the basal activity of these kinases and thus the tyrosine phosphorylation levels of NMDA receptors.
How are select chronic pancreatitis patients selected for total pancreatectomy with islet autotransplantation? Are there psychometric predictors?

Background Selected patients with chronic pancreatitis can benefit from total pancreatectomy with islet autotransplantation. Patient selection is challenging and outcomes assessment is essential. Study Design A prospective database of total pancreatectomy with islet autotransplantation patients was reviewed. Attention was given to psychometric assessments, including Short Form-12 Quality of Life Survey (SF-12), Center for Epidemiologic Studies 10-Item Depression scale, and Current Opioid Misuse Measure in the preoperative period, and SF-12 in the postoperative period. Results One hundred and twenty-seven patients (76% women, mean age 40.5 years) underwent total pancreatectomy with islet autotransplantation. Preoperatively, the mean SF-12 physical quality of life score (physQOL) was 27.24 (SD 9.9) and the mean psychological QOL score (psychQOL) was 38.5 (SD 12.8), with a score of 50 representing the mean of a healthy population. Mean improvements in physQOL relative to baseline at 1 year, 2 years, and 3 years post surgery were 7.1, 5.8, and 7.8, respectively, which represented significant change (all p r [54] = 0.33, p = 0.02). Conclusions Total pancreatectomy with islet autotransplantation improves QOL for selected patients with chronic pancreatitis. The physQOL improves quickly after surgery, and psychQOL improvements are more gradual. Opioid misuse can predict physQOL improvement.
INFLUENCE OF LOGGING, FIRE, AND FOREST TYPE ON BIODIVERSITY AND PRODUCTIVITY IN SOUTHERN BOREAL FORESTS

The effects of logging on ecosystem sustainability are controversial. Sur- prisingly, existing data are inadequate to allow a comprehensive evaluation of logging effects on biodiversity, composition, and productivity since appropriate comparisons of stands of similar ages and differing disturbance histories are rare. We addressed this issue using a study of 2000 plots in 80 southern boreal forest stands in northern Minnesota, USA, wherein we contrasted naturally regenerated aspen (Populus tremuloides), jack pine (Pinus banksiana), and black spruce (Picea mariana) stands established following logging or the dominant natural disturbance, wildfire, for stands of two age classes (25-40 and 70-100 yr old). For young stands, those established postlogging had higher vascular plant diversity than those postwildfire. Otherwise, we found no evidence of differing species diversity (including canopy tree, shrub, herbaceous, and bryophyte species), composition, produc- tivity, or nitrogen cycling, in forest stands of comparable age and forest type that originated after logging compared to after wildfire. These variables, however, differed significantly among forest types, with aboveground net primary productivity and plant species diversity generally higher in aspen than jack pine stands, even when growing on comparable soils, and lowest in black spruce. Although there is evidence that logging has increased the proportional landscape dominance by aspen, a forest type with higher diversity, nutrient cycling, and productivity than other types, our evidence refutes the idea that disturbance by logging has diminished stand-scale productivity or plant diversity in comparison to the common natural disturbance, wildfire.
Make a sound garden grow: Exploring the new media potential of social soundscaping

The Walkman and iPod have often been viewed as individualizing technologies. People use these forms of mobile media to impart a sound track of their own choosing over their experience of physical space. However, newer mobile projects have examined the links that tie mobile media and sound to experiences of movement. These projects focus on the collaborative construction of shared soundscapes through mobile media, in a sense responding to the individualizing tendencies of dominant auditory mobile media. This article draws from literature in sound studies, media studies, and locative media art to examine these relatively new forms of what we call social soundscaping. Through our analysis, we show the potential for new mobile sound practices that allow for the more participatory production of public soundscapes.
The Shiva Target Alignment And Viewing Instrument

To view and align Shiva laser targets, two new telemicroscopic instruments integral with TV camera and HeNe laser illuminator have been designed. The common requirement of both instruments is the capability of imaging two objects of different sizes on a TV screen: the large surrogate target (5 mm diameter) and the laser fusion target (0.250 mm diameter) with the same resolution (better than 7 μm). Both instruments have an optical relay which images the targets on a fixed reference reticle; the object is to center each target on the reticle. One of the instruments reimages the reticle plane onto the TV detector using a zoom arrangement. This instrument translates the TV,camera-zoom assembly in three axes and is thereby capable of exploring an object-space volume of 1 cm3. In the other instrument, the reticle plane is reimaged by a zoom lens and this enlarged image is relayed to the TV detector by a cluster of five lenses. Four lateral lenses image the periphery of the surrogate target and the reticle for coincidence. The central objective images the center of the reticle and the fusion target when it is centered.© (1978) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Microfracture and The Compressive Failure of Polycrystalline Ice

This paper discusses strain rate and grain size effects on the process of microcrack nucleation in freshwater polycrystalline ice. It also examines crack nucleation mechanisms that are likely to operate under conditions of practical concern. Special attention is paid to the ductile-to-brittle transition and the role of grain size in the transition region.
An Implementation and Process Evaluation of the Louisiana 22nd Judicial District’s Behavioral Health Court

The national offender reentry movement, Second Chance Act, and the widespread transfer of offender programming to community corrections have coalesced to substantially increase treatment for mental health and substance disorders within the criminal justice system. Intervention commonly entails program evaluation for accountability and empirical evidence by which to specify what works. Though mixed methods evaluation is preferable to a singular qualitative or quantitative approach, process steps are commonly overlooked. This paper relates an implementation and process design and evaluation midpoint findings for the Louisiana 22nd Judicial District’s Behavioral Health Court program, a post-conviction treatment initiative for mental health offenders. Interview guides and a fidelity instrument facilitated site visit data collection. Findings inform program implementation intensity, performance, improvement opportunities, and related fidelity research.
'Teaching Videos' in Mediation Training: Why Use Them, and How to Do It Well

Teaching videos are commonly used in mediation and ADR classes in law schools as a supplementary teaching method to live role play simulations. In contrast, teaching videos are not typically employed in community mediation trainings, which rely on live demonstrations and role plays. The author advocates for increased use of teaching videos in community mediation training, explores the advantages and disadvantages of video compared to live role plays, and presents effective teaching techniques for using videos.
Keep the Checking in Hockey

(2000). Keep the Checking in Hockey. The Physician and Sportsmedicine: Vol. 28, No. 2, pp. 16-127.
A Quick SEED Tutorial

A number of different government‐funded seismic data centers offer free open‐access data (e.g., U.S. Geological Survey, National Earthquake Information Center, the Incorporated Research Institutions for Seismology (IRIS), and Data Management System), which can be freely downloaded and shared among different members of the community (Lay, 2009). To efficiently share data, it is important that different data providers follow a common format. The Standard for the Exchange of Earthquake Data (SEED) provides one such format for storing seismic and other geophysical data. The SEED format is widely used in earthquake seismology; however, SEED and its structure can be difficult for many first‐time users (ourselves included). Below is a quick tutorial that outlines the basic structure of SEED format. This write‐up is in no way intended to replace the comprehensive SEED manual (Ahern et al. , 2009), and instead of going into the details of any specific part of the SEED format we refer the reader to the manual for additional details. The goal of this write‐up is to succinctly explain the basic structure of SEED format as well as the associated jargon, as most commonly used now, in a colloquial way so that novice users of SEED can become more familiar with the format and its application quickly. Our goal is to give the reader the necessary background so that when problems or questions about SEED format arise they will have some understanding of where they should look for more details or from where the problem might be stemming. As a secondary goal, we hope to help the reader become familiar with the SEED manual (Ahern et al. , 2009), which contains detailed information about all aspects of the SEED format. SEED format logically breaks down into the part containing time‐series data, called miniSEED, and the other stuff, which is called dataless SEED …
Impact of ASTM Standard E722 update on radiation damage metrics

The impact of recent changes to the ASTM Standard E722 is investigated. The methodological changes in the production of the displacement kerma factors for silicon has significant impact for some energy regions of the 1-MeV(Si) equivalent fluence response function. When evaluating the integral over all neutrons energies in various spectra important to the SNL electronics testing community, the change in the response results in an increase in the total 1-MeV(Si) equivalent fluence of 2 7%. Response functions have been produced and are available for users of both the NuGET and MCNP codes.
Representation of Women in Postsecondary Computing: Disciplinary, Institutional, and Individual Characteristics

An in-depth study of two decades of data from the IPEDS database examines trends in the participation of women in postsecondary academic computing programs at the bachelor's, master's, and doctoral levels. Emphasis is placed on determining differences among the various disciplines within the computing field and differences based on institutional and citizenship/ethnicity characteristics.
Serotonin Antagonism in the Treatment of Systemic Hypertension: The Role of Ketanserin

Serotonin has various hemodynamic effects, and may play a role in systemic hypertension. Ketanserin is a specific S2 serotonergic receptor blocker with possible adrenergic blocking activities that has clinical utility in the treatment of hypertension. The drug may have particular advantages for various patient populations.
The use of intraoperative PTH-measurement in the prediction of post-operative hypocalcemia for thyroid surgery: a meta-analysis

INTRODUCTION: Hypocalcemia is a common occurrence in the early postoperative period following thyroid surgery. The intraoperative parathyroid hormone (IOPTH) assay has been proposed by many groups as a tool for early risk assessment, though a definitive evaluation of its’ predictive value for post thyroidectomy hypocalcemia has not been made. We investigate the prognostic value of IOPTH assay for post thyroid surgery hypocalcemia via meta-analysis of current literature.
CENTRAL INDICES OF AORTIC STIFFNESS PREDICT SEVERITY AND BURDEN OF CORONARY ARTERY DISEASE BEYOND TRADITIONAL RISK MODELS

Atherosclerotic cardiovascular disease (ASCVD) risk prediction model includes risk factors such as age, sex, race, cholesterol, and systolic blood pressure (BP). However, routinely used peripheral BP differs from central (ascending aorta) BP with age. Hence traditional models may not accurately
Premeditation and Sensation Seeking Moderate the Reasoned Action and Social Reaction Pathways in the Prototype/Willingness Model of Alcohol Use

ABSTRACTBackground: Drinking can occur because of expectations to drink (reasoned pathway) or because of willingness to drink under certain circumstances (reactive pathway). These pathways are thought to be influenced by different cognitions such as alcohol-related attitudes, norms, or drinking prototypes (Gerrard et al., 2008). Impulsive traits reflect individual differences in the influence of reasoned or reactive factors, however little research has investigated whether impulsivity moderates the effects of cognitive factors predicting alcohol use. Objectives: We tested whether differences in three impulsivity traits (premeditation, sensation seeking and negative urgency) moderated associations of reasoned (risk/disapproval attitudes and social norms) and reactive (prototype) pathway variables on expectation/willingness to drink and recent alcohol use. Methods: We collected data from n = 409 college students; the sample was 67% female, 43% Asian American, with Mdnage = 19. Hypotheses were tested using m...
Felt Surface, Visible Image: Lorna Simpson's Photography and the Embodiment of Appearance

AbstractIn 1994, Lorna Simpson began serigraphing photographic images onto felt. Simpson is known for overtly engaging issues of race and gender in her work, often juxtaposing images of black female bodies with provocative text. Her felt photographs, however, remove the figure and explore the atmospheric, sculptural, and narrative qualities available in its absence. Many critics viewed this as a shift from political content to formal experimentation. This article will argue, however, that the temporal and tactile dimensions of Simpson's felt pieces relate her early and recent photography, developing conceptual and formal concerns that her work consistently engages. It focuses on the role of hair in Simpson's images, from early depictions of the back of African American women's heads, to images of braids and wigs, to photographs printed on matted hair. Recalling historical and theoretical connections between hair and photography, it explores how Simpson's engagement of race and gender is structured by a br...
The correlation study between adenoid hypertrophy and chronic rhinosinusitis in pre-school children

Objective: To evaluate the correlation between adenoid hypertrophy and chronic rhinosinusitis in pre-school children.Methods: 60 cases of pre-school children with adenoid hypertrophy and chronic rhinosinusitis underwent CT consecutively.Grade of rhinosinusitis and A/N ration of adenoid were measured,furthermore the correlation analysis between them was performed.Results: There were 18 cases with grade 1 adenoid hypertrophy,whose mean CT score was(6.3±2.5),while 23 cases with grade 2 and(11.4±3.1) scores,19 cases with grade 3 and(13.8±4.3) scores.There was a significant difference in CT score and A/N ration between different grades(r=0.435,P0.05).Conclusion: The correlation between adenoid hypertrophy and chronic rhino sinusitis does exist,we should be aware of that while diagnosis and treat either of the two diseases.
SIMULATIONS OF THE CHEMISTRY IN THE SMALL MAGELLANIC CLOUD

The Large (LMC) and Small (SMC) Magellanic Clouds are irregular satellite galaxies of the Milky Way. Both are metal- and dust-poor, although the SMC is significantly poorer in both. We have recently simulated the chemistry in cold dense regions of the LMC and found that a rich chemistry exists in the gas-phase. In this paper, we report a companion study of the chemistry of dense regions of the SMC, confining our attention to cold regions of dense clouds with a variety of densities, visual extinctions, and grain temperatures, and a fixed gas-phase temperature. With a gas-to-dust ratio and elemental abundances based on observations and scaling, we found that for molecules like CO and N2, which are predominantly formed in the gas phase, their abundances are consistent with the reduced elemental abundances of their constituent elements above 25 K; however, for species that are produced fully (e.g., CH3OH) or partially on the grain surface (e.g., H2CO, NH3), the dependence on metallicity can be complex. Most of the major gas-phase species observed in our Galaxy are produced in the SMC although in lower quantities. With our simulations, we are able to explain observed gas-phase abundances reasonably well in the dense sources N27 and LIRS 36. We have also compared our calculated abundances of selected ices with limited observations in dense regions in front of young stellar objects.
Herpesvirus Type 2: Study of Semen in Male Subjects with Recurrent Infections

Abstract Semen from 30 healthy male subjects with recurrent infections with herpesvirus type 2 was obtained when subjects were free of lesions and surveyed by tissue culture for an infectious virus in an attempt to elucidate the transmission of this disease. Inclusion bodies compatible with herpesvirus were found in tissue cultures of semen from 2 participants but an infectious virus could not be cultured directly from any sample. The data suggest that herpevirus type 2 is not ubiquitous in semen of male subjects with recurrent genital infections. The possible role of seminal inhibitors and a defective virus in causing the observed results is discussed, as are the current theories of herpes virus type 2 transmission.
Temperature-induced decay of persistent currents in a superfluid ultracold gas

We study how temperature affects the lifetime of a quantized, persistent current state in a toroidal Bose-Einstein condensate. When the temperature is increased, we find a decrease in the persistent current lifetime. Comparing our measured decay rates to simple models of thermal activation and quantum tunneling, we do not find agreement. We also measured the size of the hysteresis loops in our superfluid ring as a function of temperature, enabling us to extract the critical velocity. The measured critical velocity is found to depend strongly on temperature, approaching the zero-temperature mean-field solution as the temperature is decreased. This indicates that an appropriate definition of critical velocity must incorporate the role of thermal fluctuations, something not explicitly contained in traditional theories.
An Anticipative Adaptive Array for Frequency-Hopping Communications

Adaptive antenna array processing and wideband frequency hopping are two of the most powerful methods for providing interference rejection in military communication systems. However, for the full exploitation of the theoretical processing gain achievable when these two methods are combined, frequency compensation is required. This paper examines an anticipative adaptive filter that adapts the complex weights at each antenna element to the appropriate values for a carrier frequency before that frequency is transmitted. The underlying adaptive alogrithm is the Maximin algorithm which has major advantages compared with other algorithms. Computer simulation results are used to compare different versions of anticipative processing. These results show that an appropriate version can ensure the rapid convergence of weights to values that provide wideband nulling of the interference and noise.
Switching Death Pathways in AML; Induction of Necrosis by Arsenic, Ascorbic Acid and Antabuse (AAA).

Abstract Virtually all chemotherapy drugs induce apoptosis. Cancer cells have multiple mechanisms of resistance to this form of cell death. Necrosis may have fewer mechanisms of resistance, providing a rationale to discover ways to switch cell death pathways from apoptosis to necrosis. Arsenic trioxide (ATO) is clinically effective against acute promyelocytic leukemia and studies have suggested efficacy in treating other malignancies, including other leukemias. ATO increases the intracellular concentration of reactive oxygen species and inhibits glutathione (GSH) reduction resulting in redox changes which activate caspases and induce apoptosis. Ascorbic acid (AA) and other agents which reduce glutathione concentrations and increase hydrogen peroxide concentrations have been shown to enhance the antitumor activity of ATO in vitro. This combination of agents is currently in clinical trials. In previous experiments using pancreatic cancer cell lines, disulfiram (DSF), in clinical use as an inhibitor of aldehyde dehydrogenasel, was added to the ATO/AA combination. Synergistic induction of cell death occurred. We sought to test this combination in myeloid cell lines. We tested the ATO/AA/DSF (AAA) combination ([ATO], 1uM; [AA], 100uM; [DSF], 0.125 uM) on two myeloid leukemia cell lines, KG1 and K562. After treatment for 48 hours in AAA, annexin and propidium iodide staining revealed an increase in annexin(+) PI(+) cells (necrosis) in the KG1 cell line that was similar to the effect in pancreatic cancer cells. Nearly five fold more KG1 cells underwent necrosis after exposure to AAA than with arsenic alone. Arsenic combined with ascorbic acid or disulfiram yielded an approximately two fold increase in necrosis. We propose that the mechanism of action of disulfiram is through quenching peroxide (H2O2) radicals generated by ATO and AA. The reducion of DSF leads to oxidation of GSH and NADH which decrease [ATP]i, shifting the cells from apoptosis to necrosis. K562 cells were largely resistant to the triple combination, remaining in a state of cytostasis after exposure to AAA. BCR-ABL positive cell lines, such as K562, have a relative increase in intracellular ROS. The lack of necrosis in K562 was surprising, and suggests that the activated BCR-ABL kinase may override this proposed mechanism. Imatinib has been shown to induce necrosis, and combinations including imatinib will be tested in BCR-ABL positive cell lines. To study the potential safety of this combination for human trials, AAA was tested on peripheral blood stem cells from normal donors (obtained after informed consent) and did not appear to have synergistic effects on colony formation as compared to the drugs applied individually. These results suggest a new mechanism of cell death, switching from apoptosis to necrosis, that can be targeted to treat leukemias and other malignancies. More studies to confirm the mechanism of this cell death are underway.
Key Points from the Updated Guidelines on Exercise and Diabetes

No doubt remains that the adoption and maintenance of physical activity is important for overall health and blood glucose management in individuals with diabetes and prediabetes. Recently, the American Diabetes Association (ADA) published updated recommendations and precautions about physical activity and exercise in people with type 1 diabetes, type 2 diabetes, and gestational diabetes (1). Given the importance of these topics, it is worth discussing the key changes and updates included in this ADA position statement (PS). Pre-Exercise Health Screening and Evaluation This PS reiterates that “pre-exercise medical clearance is not necessary for asymptomatic, sedentary individuals who wish to begin low- or moderate-intensity physical activity not exceeding the demands of brisk walking or everyday living” (1). This stance directly opposes a recent recommendation from the American College of Sports Medicine (ACSM) (2) that requires anyone with a metabolic disease (in this case, diabetes) who desires to begin exercising at any level—even doing light activities—to obtain medical clearance from a health-care provider first. The authors of the ADA PS did not agree with this restriction and took the same stance as the prior ADA PS on type 2 diabetes and exercise (3), which I believe is a much better recommendation. Making adults obtain any type of medical clearance prior to starting walking, for example, is an unnecessary barrier that will not necessarily make exercising any safer for them. However, ADA agrees with ACSM that adults with diabetes who plan to exercise at higher intensities than currently undertaken or who would be considered at high risk for cardiovascular disease (e.g., have elevated blood cholesterol, smoke, have a strong family history, etc.) or other health complications from doing such activities are recommended to obtain a pre-training examination from a health-care provider who may or may not recommend exercise stress testing (3).
GUI Robots: Using Off-the-Shelf Robots as Tangible Input and Output Devices for Unmodified GUI Applications

Traditional GUI applications provide limited support for tangible interaction, as most applications are not programmed to support tangible input, and most input devices do not provide haptic feedback. To address this limitation, we introduce GUI Robots, a software framework that enables developers to repurpose off-the-shelf robots as tangible input and haptic output devices, and to connect them to unmodified desktop applications. We introduce the GUI Robots framework and present several proof-of-concept applications, including a haptic scroll wheel, force feedback game controllers, a 3D mouse, and a self-driving notification robot. To evaluate whether GUI Robots can be used to prototype tangible interfaces for existing applications, we conducted a user study in which developers created customized tangible interfaces for two applications. Study participants were able to create tangible user interfaces for these applications in less than an hour. GUI Robots allows developers to easily extend applications with tangible input and haptic output.
Concluding Remarks and Some Future Research

The normal and Student’s distributions are two of the most important distributions in statistics. This book has reviewed the normal and Student’s distributions, and their applications.
Iodinated contrast agents in neuroradiology

Iodinated contrast materials, which are commonly used in neuroradiological applications, are an unusual and somewhat enigmatic class of drugs. We frequently give intravascular injections of these agents in large volumes, yet they have no therapeutic value. Their value lies instead in their ability to attenuate X-rays, a property imparted to them only by the constituent iodine atoms that make up a small fraction of their molecules. The ideal model contrast medium would yield superb radiographic contrast, would be thoroughly soluble and have low viscosity, would be rapidly excreted from the body, and would have no toxic side effects. Although currently available iodinated contrast agents approach these ideals, some limitations persist.
Acute Decompensated Heart Failure: Systolic and Diastolic

Heart failure is a chronic disease characterized in part by intermittent exacerbations of worsening symptoms that increase in frequency with disease progression. Despite a trend towards reduced heart failure hospitalization over the last decade, heart failure remains the most common cause of hospitalization in the Medicare population. Hospitalization for worsening symptoms is a sentinel event that identifies heart failure patients at high risk for subsequent morbidity and mortality. Initial assessment should include confirmation of the diagnosis (recognizing that patient may present with atypical signs and symptoms), measurement of left ventricular function with appropriate imaging procedures, identification of precipitating factors, clinical assessment of the hemodynamic status based on physical findings of congestion and tissue perfusion, and formulation of an individualized treatment plan. Decongestion therapy with intravenous loop diuretics is the most common therapeutic intervention with similar treatment approaches in patients with preserved or reduced ejection fraction. The cardiology consultant should also assess prognosis based on clinical findings and biomarkers and make recommendations for palliative care options in patients with poor prognosis who are not eligible for advanced therapies such as left ventricular assist device or cardiac transplantation. The cardiology consultant should also arrange appropriate transition of care at discharge with plans for post-discharge optimization of medical and device therapy and for high-risk patients, referral to a heart failure disease management program.
Comprehension of Nonroutine Transactions During Audit Planning: Evidence from Free Recalls and Inferences

This study examines the effect of experience on both the quality (importance) and quantity of recalls made and inferences drawn in evaluating the effects of nonroutine transactions in the auditor's planning process. Consistent with expectations drawn from previous research, our results indicate that experienced subjects recalled a greater proportion of critical idea units and drew a larger proportion of critical inferences than inexperienced subjects. Ancillary analysis suggests that transaction-specific experience results in a further improvement in the ability to recall critical idea units beyond general accounting/auditing experience; no such improvement was noted for the ability to draw critical inferences. The results did not support the contention that experienced subjects' performance would not be affected by the complexity of the environment (amount of information provided). The ability of experienced auditors to discriminate between more- and less-important information has important implications on their ability to conduct more efficient and effective audit examinations.
Louisiana Prenuptial Agreements: Issues for Contemporary Spouses

Prenuptial agreements can benefit nearly all couples. The stereotypical second-marriage couple and the couple with a large wealth disparity remain candidates for prenuptial agreements. But, the market is much larger than that. All couples, particularly those in Louisiana, can benefit from a prenuptial agreement. The default legal regime of community property presents a number of likely unintended and unexpected consequences for many spouses. Moreover, modern spouses likely have different concerns than the stereotypical prenuptial agreement candidates. This paper examines important demographic changes among married couples and attempts to identify some possible concerns and scenarios raided by these changes that could be addressed in a prenuptial agreement.
The Use of Lignosulfonates as Water Reducing Agents in the Manufacture of Gypsum Wallboard

The chemical treatment of woody materials to produce fibers (pulps) also produces a nearly equal amount of soluble chemicals consisting mainly of modified lignin and carbohydrate degradation products. In most chemical pulp mills, this material is burned to create energy for the recycling of pulping chemicals. A small number of pulp mills, mostly acid sulfite mills, purify the lignin streams and market this material commercially. In 1998, close to one million tons of lignosulfonates were used worldwide in a variety of industrial applications.1 The largest use of this material is as a dispersant of particle slurries such as concrete, clays, gypsum, and dyes.2 In these applications, lignosulfonates must compete with synthetic dispersants such as condensation polymers of formaldehyde with sulfonated naphthalene. Much effort, therefore, has been directed towards increasing the dispersing ability of lignosulfonates in these systems through chemical modifications and physical separations. These processes, however, can also affect other properties of the particle slurries such as setting time, air entrainment, and color. It is very important, therefore, to look at the entire system when considering a lignin modification. In this chapter, the effect that lignosulfonate components and chemical modification reactions have on the function of lignosulfonate dispersants in the manufacture of gypsum wallboard will be discussed.
History of childhood emotional abuse predicts lower resting-state high-frequency heart rate variability in depressed women

Abstract Childhood emotional abuse impairs emotion regulation and increases risk for major depressive disorder in adulthood. Mounting evidence suggests that decreased resting-state high-frequency heart rate variability, an index of parasympathetic function, represents a transdiagnostic biomarker of emotion dysregulation. We propose that adults with histories of major depressive disorder and childhood emotional abuse represent a subpopulation at particularly high risk to exhibit deficits in parasympathetic control. The current report compared resting-state high-frequency heart rate variability across three groups: (1) depressed women who endorsed childhood emotional abuse (N = 11); (2) depressed women without childhood emotional abuse (N = 19), and (3) never-depressed women without childhood emotional abuse (N = 22). Participants completed childhood trauma self-reports and assessment of resting-state high-frequency heart rate variability. ANCOVAs comparing the three groups after controlling for health-related, psychiatric, and respiratory factors were significant. Depressed women with childhood emotional abuse exhibited lower high-frequency heart rate variability than both groups without childhood emotional abuse (d’s ranging from 0.81—0.92). Surprisingly, psychiatric factors were non-significant predictors, indicating that childhood emotional abuse may have a unique impact on autonomic functioning. Future research on larger samples is needed to disentangle the relative and synergistic burdens of depression and childhood trauma on physiologic indicators of emotion dysregulation.
Seismic risk and house prices: Evidence from earthquake fault zoning

Abstract In 1972, the Alquist-Priolo Zoning Act provided for the publication of earthquake fault maps in California. I exploit revisions in these official maps over time to estimate the rate of capitalization of seismic risk into property values using a difference-in-differences framework. Using geographically consistent data from 1970 to 2010 at the census tract level, I find that on average property values decline by 6.6 percent after the delineation of the fault zone, while rents decline by around 3.3 percent. I also examine the risk gradient and heterogeneity in willingness to pay using individual sales transactions, assessors' records, and publicly available mortgage data for the City of Los Angeles. The analysis of micro transactions data from 1997 to 2016 reveals that, on average, house prices increase by 1.8 percent for a one-mile increase in distance from the fault zone. The evidence also indicates that holding income and gender constant, Blacks and Hispanics are less willing than Whites to trade other forms of consumption to avoid earthquake risk.
Diagnostic Yield and Accuracy of Bedside Echocardiography in the Emergency Department in Hemodynamically Stable Patients.

Objectives The goal of this study was to determine the diagnostic yield of focused cardiac ultrasound (FOCUS) in hemodynamically stable patients in the emergency department and secondarily to confirm the accuracy of these studies when compared to formal echocardiography. Methods All hemodynamically stable adult patients who had an emergency physician-performed FOCUS examination completed over a 1-year period were identified using our electronic ultrasound database. Hemodynamic stability was defined as presenting systolic blood pressure higher than 90 mm Hg and not requiring any form of positive pressure ventilation. Results There were 1198 FOCUS examinations performed: 976 in hemodynamically stable patients who were included in our analysis. Twenty-seven percent of patients had new findings, including 154 (16%) new diagnoses of reduced left ventricular function, 105 (11%) new pericardial effusions, and 44 (5%) new diagnoses of RV dilatation. Dyspnea as an indication for the FOCUS examination was the strongest predictor of a positive study. Of patients included, 28% underwent formal echocardiography within 2 days and were analyzed for concordance with regard to left ventricular function and the presence of pericardial effusion. Of 270 studies, 208 were accurate, and 62 were inaccurate, for raw agreement of 77% (κ = 0.53). When stratified by sonographer experience, there was no impact on accuracy. Conclusions Focused cardiac ultrasound in the emergency department for hemodynamically stable patients revealed new findings in 27% of studies, with a modest correlation with formal echocardiography. In stable patients, FOCUS has the potential for rapid diagnosis of cardiac disease, particularly in patients with dyspnea.
Analgesia, Opioids, and Other Drug Use During Pregnancy and Neonatal Abstinence Syndrome

When opioid misuse rises in the United States, pregnant women and their neonates are affected. This article summarizes the use of Food and Drug Administration-approved products, including methadone, buprenorphine, and the combination formulation of buprenorphine and naloxone to treat adult opioid use disorder during the perinatal period. All labels include pregnancy, neonatal, and lactation information and note the accepted use of these medications during the perinatal period if the benefits outweigh the risks. A summary of the neonatal abstinence syndrome definition, its assessment tools, treatment approaches, and future genetic directions are provided.
Postimperial Indifference, Fragmentation, and Nostalgia in Costumbrismo.

This article analyzes costumbrismo as the first literary genre to develop the notion of postimperial nostalgia in nineteenth-century Spain. The article argues that a postimperialist analysis of this literature can shed light on the rather, idiosyncratic history of nineteenth-century Spanish literature (literature of manners and historical novel > almost no realism > naturalism). It also establishes the bases for a more cultural and political understanding of nostalgia and modernity in Spain and the Hispanic Atlantic as well as the (postmodern) Global North, so that Spanish nationalism is redefined as an (in-different) postimperial discourse about colonial loss. More theoretically, the article aims at redefining nineteenth-century Spanish history in Lacanian terms by arguing that Spain as a nation is simply an imaginary formation of a symbolic order that is ultimately Atlantic and post/imperial, wherein the colonial loss points to the traumatic irruption of the Real.