cssi/SciSciGPT-SciSciNet huggingface dataset:
PtCl2-Mediated Cyclopropane Opening: A Mechanistic Study

The platinum-mediated cyclopropane opening of [4 + 2 + 2] homo Diels–Alder cycloadducts has been probed through deuterium-labeling studies. The location of the deuterium in the olefinic products strongly supports an α-elimination mechanism that proceeds through a platinum carbene intermediate. Kinetic isotopic effects provide additional insights into the reaction mechanism, lending support to the platinum carbene formation as the rate-determining step.
Referred for management of mastocytosis

CASE REPORT A 19-year-old woman in otherwise excellent health was referred for management of mastocytosis. The onset of symptoms was 8 months earlier. At that time she developed red-brown macular lesions on her skin that periodically became inflamed. Accompanying these eruptions were episodes of acute illness including abdominal pain, diarrhea, flushing, headache, and lightheadedness. She presented to an emergency department on four occasions over the next two months. On one occasion she received diphenhydramine, on another cyproheptadine and rantidine, and on yet another epinephrine, methylprednisolone, and hydroxyzine. A skin biopsy was reported to show some mast cells. The patient was prescribed a long-acting aspirin preparation (1600 mg bid) for presumed mastocytosis but continued to have milder episodes, approximately once or twice a month. The episodes tended to occur with menses. Cromolyn sodium, 100 mg po qid, hydroxyzine, 25 mg qid, and cimetidine, 300 mg tid were added to the patient’s regimen without change in the clinical course. The patient was a student. No family members had similar rashes or illnesses. Physical examination performed when the patient was asymptomatic revealed 0.5 to 2.0 cm brown to slightly purplish macules, two on the face, two to three on each extremity, and several on the trunk. They were considered to elevate slightly when stroked. The rest of the examination was benign.
Leber hereditary optic neuropathy associated with use of ephedra alkaloids

Abstract Purpose We report a case of Leber hereditary optic neuropathy in a patient who was using ephedra alkaloids at the time of onset of his optic neuropathy. Design Observational case report. Methods Bilateral, painless, progressive loss of vision developed in a 30-year-old man. He reported a one pack-per day, 10-year history of tobacco use and drinking 18 to 24 cans of beer per day as well as the use of a dietary supplement containing ephedra and caffeine before the onset of vision loss. Results We report the bilateral, progressive, painless loss of vision in a patient with bilateral cecocentral scotomas and optic nerve pallor. Mitochondrial DNA testing confirmed a Leber hereditary optic neuropathy mutation site at loci 11778. Conclusions We propose that our patient’s use of a dietary supplement containing ephedra alkaloids played an additive role to his tobacco and alcohol use in causing stress to the already abnormal mitochondrial function, and thereby contributed to the onset of his optic neuropathy. We recommend that patients and families with known Leber hereditary optic neuropathy should be asked about the use of over-the-counter drugs or supplements, and it may be prudent to advise patients against using such dietary supplements.
Fear and Loathing in Late Modernity Reflections on the Cultural Sources of Mass Imprisonment in the United States

Mass imprisonment is based in some way on the intense fear of crime in the United States but how should we think about this fear? Douglas and Wildavsky (1982) provided a productive framework for examining the relationship between social organization and risk selection in their path-breaking study of environmentalism. Douglas and Wildavsky argued that the contemporary obsession with pollution risk indicated a drift in society toward sectarian forms of social organization with weak incentives and internal social controls. This article applies the Douglas and Wildavsky framework to the fear of crime in the United States since 1980 and concludes that crime has replaced pollution as the preferred risk for America's increasingly sectarian social order.
Noise probes of underlying static correlation lengths in the superconducting peak effect

The sensitivity of low-frequency noise to ac magnetic-field perturbations is explored in the plastic flow regime near the {open_quotes}peak effect{close_quotes} in the clean type-II superconductor NbSe{sub 2}. Very small ac magnetic fields (on the order of 1 Oe in a dc field of about 20000 Oe) substantially reduce the low-frequency spectral density by inducing rapid switching among metastable configurations present in the pinned state. This sensitivity to ac fields shrinks rapidly as H increases in the peak-effect regime, indicating reduced static correlation lengths as the peak is approached. {copyright} {ital 1998} {ital The American Physical Society}
Darwin's Methodological Evolution

A necessary condition for having a revolution named after you is that you are an innovator in your field. I argue that if Charles Darwin meets this condition, it is as a philosopher and methodologist. In 1991, I made the case for Darwin’s innovative use of “thought experiment” in the Origin. Here I place this innovative practice in the context of Darwin’s methodological commitments, trace its origins back into Darwin’s notebooks, and pursue Darwin’s suggestion that it owes its inspiration to Charles Lyell.
On the mechanism of phosphono- or phosphorofluoridate hydrolysis catalyzed by transition metal ions

Abstract Transition metal ions, such as manganese(II) or copper(II), catalyze the hydrolysis of O -isopropyl methylphosphonofluoridate (sarin) or O , O' -diisopropyl phosphorofluoridate (DFP). The rate law for the catalyzed path is first order in ester, metal(II) and hydroxide. Thus, the catalytic species could be the hydroxometal complex, or the catalysis could consist of a complex formed between the metal ion and phosphorus substrate which is subsequently attacked by hydroxide. Recently, we measured the solvolysis of sarin in an ethanol-water solution. By means of 31 P nuclear magnetic resonance (NMR), two products were seen to form from parallel attack on sarin by hydroxide and ethoxide. In the presence of zinc(II) chloride, it was shown that both reaction rates were significantly increased. If the increase in reactivity were attributed to a zinc hydroxide complex, then no change would be expected in the rate of attack by ethoxide ion. We further suggest the monitoring of relative rates of reaction in mixed solvents as a way to distinguish whether a metal ion catalyst acts as a Lewis acid or simply supplies a larger concentration of nucleophilic hydroxide ion.
Mechanisms of air‐sea CO2 flux variability in the equatorial Pacific and the North Atlantic

related to the El Nino/Southern Oscillation (ENSO) cycle in the equatorial Pacific. In contrast the air-sea O2 flux is controlled by two regions: the equatorial Pacific and North Atlantic. The model captures much of the interannual variability of the CO2 flux observed at Bermuda, with some correlation with the North Atlantic Oscillation (NAO) index. However, basin-scale air-sea CO2 flux anomalies are not correlated with the NAO due to a rapid neutralization of entrained DIC anomalies by biological uptake and export production in the subpolar gyre. CO2 flux variability estimates from our ocean model and the mean atmospheric inversion results of Bousquet et al. (2000) are in broad agreement in the equatorial Pacific, but not in the North Atlantic. This model suggests that the projection of air-sea flux anomalies onto the large-scale, mean air-sea flux pattern in atmospheric inversions may lead to an overestimate of the flux variability in the extra- tropics where the patterns of variability do not correspond to those of the mean flux. INDEX TERMS: 4215 Oceanography: General: Climate and interannual variability (3309); 4255 Oceanography: General: Numerical modeling; 4805 Oceanography: Biological and Chemical: Biogeochemical cycles (1615); 4806 Oceanography: Biological and Chemical: Carbon cycling; KEYWORDS: air-sea exchange, carbon flux, ocean modeling
Patterns of Life History and Habitat Use of an Important Recreational Fishery Species, Spotfin Croaker, and Their Potential Fishery Implications

Abstract Spotfin croakers Roncador stearnsii, a prized recreational catch, were collected throughout the Southern California Bight, primarily as bycatch from a long-term, scientific gill-net collection effort. The maximum otolith-based age in the present study was 24 years—14 years greater than in a previous scale-based aging study. Multiple models were used to estimate mean length at age, including models that utilize larvae as well as juveniles and adults, and the model selection results suggest sexual dimorphism in growth patterns. The juvenile and adult catch per unit effort reflected a clear pattern of habitat selectivity, with fish strongly preferring soft-bottom habitats. Catches in rocky-reef areas were limited but tended to increase with water temperature. The data also suggest that spotfin croakers segregate themselves sexually during the spawning season, when recreational fishing from jetties will target males and fish caught in bays and estuaries are more likely to be spawning females. These r...
The Nucleotide-Replacement Spectrum Under Somatic Hypermutation Exhibits Microsequence Dependence That Is Strand-Symmetric and Distinct from That Under Germline Mutation

Somatic mutation is a fundamental component of acquired immunity. Although its molecular basis remains undetermined, the sequence specificity with which mutations are introduced has provided clues to the mechanism. We have analyzed data representing over 1700 unselected mutations in V gene introns and nonproductively rearranged V genes to identify the sequence specificity of the mutation spectrum—the distribution of resultant nucleotides. In other words, we sought to determine what effects the neighboring bases have on what a given base mutates “to.” We find that both neighboring bases have a significant effect on the mutation spectrum. Their influences are complicated, but much of the effect can be characterized as enhancing homogeneity of the mutated DNA sequence. In contrast to what has been reported for the sequence specificity of the “targeting” mechanism, that of the spectrum is notably symmetric under complementation, indicating little if any strand bias. We compared the spectrum to that found previously for germline mutations as revealed by analyzing pseudogene sequences. We find that the influences of nearest neighbors are quite different in the two datasets. Altogether, our findings suggest that the mechanism of somatic hypermutation is complex, involving two or more stages: introduction of mis-pairs and their subsequent resolution, each with distinct sequence specificity and strand bias.
Multiple-access channels with memory with and without frame synchronism

The capacity region of frame-synchronous and frame-asynchronous, discrete, two-user multiple-access channels with finite memory is obtained. Frame synchronism refers to the ability of the transmitters to send their code words in unison. The absence of frame synchronism in memoryless multiple-access channels is known to result in the removal of the convex hull operation from the expression of the capacity region. It is shown that when the channel has memory, frame asynchronism rules out nonstationary inputs to achieve any point in the capacity region, thereby allowing only coding strategies that involve cooperation in the frequency domain but not in the time domain. This restriction drastically reduces the capacity region of some multiple-access channels with memory, and in particular the total capacity of the channel, which is invariant to frame asynchronism for memoryless channels. >
POSTER: PnP: improving web browsing performance over tor using web resource prefetch-and-push

Tor is a widely used network for anonymous communication. Its users frequently experience large communication delays, due to the high user-to-relay ratio, the bandwidth-intensive BitTorrent transfers of a small fraction of the user base, and the inherent latencies from routing traffic through multiple relay hops scattered around the world. These delays significantly degrade the user experience of web browsing, a dominant use of Tor.Improving web browsing performance of Tor has been a subject of much research. Targeting the network and transport layers, prior work includes proposals to throttle bandwidth-intensive connections or to prioritize interactive traffic such as web browsing. We attack the problem at the application layer, noting that a typical web page consists of multiple resources, each of which requires a one-round-trip HTTP request-response cycle to load in the browser. Thus, for a page with many resources, these round trips are a major contributor to the page load time. We investigate PnP (for Prefetch-and-Push), where the Tor exit prefetches resources of the web page a client is visiting and pushes them to the client. Our experiments show a significant reduction in page load times as well as higher client's privacy from web page fingerprinting by a local attacker.
Pediatric validity assessment.

Background Youth have been assumed historically to be less capable of deception than adults, even though acts of deception in childhood are not uncommon. Relatively little attention has focused on how frequently they feign or exaggerate during healthcare evaluations. Purpose The current article reviews the literature relevant to using validity tests in children and adolescents, as well as provides a case example of a young adolescent providing noncredible effort and exaggerated symptomatology during neuropsychological evaluation after a mild traumatic brain injury. Conclusion Numerous case reports and case series have documented clearly that medical and neuropsychological noncredible presentations occur in children, likely more often than many practitioners believe. Thus far, research has found that the base rates of pediatric noncredible presentations are highest in children seen frequently by rehabilitation providers (i.e., children with persistent problems after mild traumatic brain injury and children from families seeking disability benefits on their behalf). Subjective clinical judgment is apt to be ineffective in consistently detecting noncredible presentations. Fortunately, recent research supports the use of several stand-alone validity tests in identifying noncredible pediatric data including the Test of Memory Malingering, Word Memory Test, and Medical Symptom Validity Test. If feigning and exaggeration are not considered in work-ups by rehabilitation practitioners, mismanagement and iatrogenic harm to the child can result.
Repeated voltage biasing improves unit recordings by reducing resistive tissue impedances

Reactive tissue encapsulation of chronically implanted microelectrode probes can preclude long-term recording of extracellular action potentials. We investigated an intervention strategy for functionally encapsulated microelectrode sites. This method, known as "rejuvenation," involved applying a +1.5 V dc bias to an iridium site for 4 s. Previous studies have demonstrated that rejuvenation resulted in higher signal-to-noise ratios (SNRs) by decreasing noise levels, and reduced 1-kHz site impedances by decreasing the tissue interface resistances. In this study, we have investigated: 1) the duration of a single-voltage bias session and 2) the efficacy of multiple sessions. These questions were addressed through electrophysiological recordings, cyclic voltammetry, and modeling the electrode-tissue interface via an equivalent circuit model fit to impedance spectroscopy data. In the six implants studied, we found SNRs improved for 1-7 days with a peak typically occurring within 24 h of the voltage bias. Root-mean square (RMS) noise of the extracellular recordings decreased for 1-2 days, which paralleled a similar decrease in the adsorbed tissue resistance (R/sub en/) from the model. Implants whose SNR effects lasted more than a day showed stabilized reductions in the extracellular tissue resistance (R/sub ex/) and cellular membrane area (A/sub m/). Subsequent stimulus sessions were found to drop neural tissue parameters consistently to levels observed immediately after surgery. In most cases, these changes did parallel an improvement in SNR. These findings suggest that rejuvenation may be a useful intervention strategy to prolong the lifetime of chronically implanted microelectrodes.
Maximization of long-term productivity in a rat colony.

Maximization of intensive breeding in the animal colony can be approached using a simple mathematical treatment of the production-time curve. It has been found that in a colony of specified-pathogen-free albino rats whose breeding dams were averaging litters of 11 at 6-week intervals, the stock should be entirely replaced at intervals of 27-28 weeks to maximize the output of weanlings. Some data on litter size and sex ratio are also presented.
Housing: Commodity versus Right

The study of housing has a long history in sociology, but since the 1960s, it has been relatively hidden in a number of sociological subfields and scattered across a range of disciplines. The financial crisis of 2008 elevated housing issues to the level of national and international debate and protest, and it offers a framework for organizing the scholarship on housing into that which studies housing as a commodity, on one hand, and as a right, on the other. In the former category, I review the literature on mortgage financing; property values and wealth; and affordable rental housing, foreclosures, and evictions. In the latter category, I discuss the theoretical arguments for a right to housing and review the research on activist demands for that right. The tension between these two aspects of housing is discussed throughout. I conclude by proposing the actual home or apartment as a productive area for new sociological analysis.
BIOGEOGRAPHY AND COMMUNITY STRUCTURE OF NORTH AMERICAN SEED-HARVESTER ANTS

▪ Abstract Seed-harvester ants are a dominant and conspicuous insect group throughout arid portions of the southwestern United States and northern Mexico, and they include ∼75 species. Intense study in the late 1970s and early 1980s led to the paradigm that interspecific competition for limited seed resources is the primary factor that structures seed-harvester ant communities. This review attempts to adjust this paradigm, suggesting that interspecific competition for food is probably less important than previously thought, whereas intraspecific competition is common and strong. Abiotic-habitat factors also have important effects on local species composition and attributes. This review also emphasizes several aspects of seed-harvester ants that have been poorly studied, including historical factors, adaptive radiation, and biogeography, to provide a more detailed evolutionary background for understanding existing species assemblages.
In search of representativeness: evolving the environmental data quality model.

Environmental regulatory policy states a goal of "sound science." The practice of good science is founded on the systematic identification and management of uncertainties; i.e., knowledge gaps that compromise our ability to make accurate predictions. Predicting the consequences of decisions about risk and risk reduction at contaminated sites requires an accurate model of the nature and extent of site contamination, which in turn requires measuring contaminant concentrations in complex environmental matrices. Perfecting analytical tests to perform those measurements has consumed tremendous regulatory attention for the past 20-30 years. Yet, despite great improvements in environmental analytical capability, complaints about inadequate data quality still abound. This paper argues that the first generation data quality model that equated environmental data quality with analytical quality was a useful starting point, but it is insufficient because it is blind to the repercussions of multifaceted issues collectively termed "representativeness." To achieve policy goals of "sound science" in environmental restoration projects, the environmental data quality model must be updated to recognize and manage the uncertainties involved in generating representative data from heterogeneous environmental matrices.
Networks Matter at the Top: An Empirical Analysis of French Boardrooms

People commonly think that CEOs get appointed not only because of their talent or ability but also because of their social connections. In this paper, I use a unique database FIBEN, built at the Banque de France, of over 12000 firms and alumni directories for the three most prestigious Grandes Ecoles in France (HEC, Polytechnique and ENA) to explore this intuition. Results show that indeed, alumni tend to favor their peers in the voting process but also that there is rivalry between the three Ecoles. This last finding is original and supports the idea of a network effect. Indeed, if only the ability of alumni explained their success in elections to become CEOs, we would not observe rivalry.
Mass-spectrometric characterization of phospholipids and their hydroperoxide derivatives in vivo: effects of total body irradiation.

Abstract Combination of electrospray ionization mass spectrometry (ESI-MS), fluorescence high-performance liquid chromatography (HPLC), and 2D-high-performance thin-layer chromatography (2D-HPTLC) is a powerful approach to identify and quantitatively analyze oxidized phospholipids in vivo. We describe application of this methodology in assessments of phospholipid hydroperoxides using as an example their characterization and quantitative determinations in different tissues of mice exposed to total body irradiation (TBI, 10 and 15 Gy). Using ESI-MS, we identified individual molecular species - with particular emphasis on polyunsaturated molecules as preferred peroxidation substrates - in major classes of phospholipids: cardiolipin (CL), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) isolated from mouse brain, lung, muscles, small intestine, and bone marrow. We show that the pattern of phospholipid oxidation 24 h after TBI is nonrandom and does not follow the phospholipid abundance in tissues. The anionic phospholipids - CL, PS, and PI - are the preferred peroxidation substrates. We identified and structurally characterized individual hydroperoxides in these three classes of phospholipids. The protocols described may be utilized in studies of signaling functions of oxidized phospholipids in cell physiology and pathology.
Terminal differentiation and apoptosis in experimental lung metastases of human osteogenic sarcoma cells by wild type p53

Human SAOS-2 osteogenic sarcoma cells are not metastatic in nude mice and do not express p53. We have selected a variant line (SAOS-LM2) that is tumorigenic and metastatic in nude mice. These cells were transfected with the p53 wild-type (p53wt) or mutated (p53mut 143A) gene, whose expression was verified by reverse transcriptase PCR, cDNA sequencing, and protein immunoprecipitation. Cells were injected i.v. into nude mice, and 4 months later, the mice were necropsied. All cell lines produced a similar number of visible lung metastases, albeit of different sizes. Microscopic examination revealed that most lung metastases in mice injected with p53wt cells (but not p53mut 143A or control cells) consisted of osteoid matrix and apoptotic cells. Expression of either p53wt or p53mut 143A verified the origin of the metastases. These data suggest that transfection of SAOS-LM2 cells with p53wt is associated with in vivo induction of terminal differentiation and apoptosis that inhibit progressive growth of metastases.
12.9 A flying-domain DC-DC converter powering a Cortex-M0 processor with 90.8% efficiency

Modern SoC designs employed in battery-life-constrained mobile applications feature multiple power domains to dynamically scale power-performance trade-offs in response to application demands. Since each power domain requires a DC-DC converter, and since low-power mobile applications are also typically area-constrained, the employed DC-DC voltage regulators must: 1) be fully integrated, 2) support high efficiency across large dynamic current ranges spanning high-power active modes to low-power sleep modes where the overhead of complex control or multi-phasing is not feasible [1], and 3) support high power density to occupy minimal area overhead. Unfortunately, achieving both high efficiency and power density is difficult: integrated magnetic converters have limited efficiency and do not leverage CMOS scaling, while switched-capacitor (SC) converters suffer from fundamental power density-efficiency trade-offs due to ½C(ΔV)2f-based slow-switching-limit (SSL) losses. While recent work has employed high-density capacitors using ferroelectric or deep-trench technologies to achieve both high efficiency and high power density [2,3], such capacitor technologies are not available in all processes, and SSL losses still restrict the power density-efficiency trade-off, even with further scaling. Stacked-domain (SD) converters attempt to address this trade-off by achieving DC-DC conversion via stacked loads [4]; however, efficiency and density of SD converters approach the performance of the underlying charge-balance DC-DC converter required under load mismatch conditions, limiting the benefits of the SD approach for practical loads.
Characterizing Transcription and Splicing Kinetics by 3D Orbital Tracking

We describe our recent application of two photon laser scanning microscopy to characterize transcription and splicing rates in living cells with sub-diffraction limited spatial resolution and second to hour long temporal resolution by the application of 3D orbital tracking[1] and two color in vivo RNA labelling[2]. We find that measurements agree with previous studies utilizing widefield volumetric imaging but increase the temporal resolution 100 fold and the duration of each experiment by 10 fold characterizing protein-RNA binding, RNA synthesis and splicing and long timescale transcriptional bursting in a single measurement. This technique may have future applications for the study of both natural and synthetic gene regulation in eukaryotes.1. Levi V, Ruan Q, Gratton E. 3-D particle tracking in a two-photon microscope: application to the study of molecular dynamics in cells. Biophys J. 2005;88: 2919-2928. http://dx.doi.org/10.1529/biophysj.104.0442302. Coulon A, Ferguson ML, de Turris V, Palangat M, Chow CC, Larson DR. Kinetic competition during the transcription cycle results in stochastic RNA processing. Elife. 2014;3. http://dx.doi.org/10.7554/eLife.03939.
Skin Resistance as a Physiological Indicator for Quadriplegics with Spinal Cord Injuries During Activities of Daily Living

Approximately 30---50i¾?% of all persons with a spinal cord injury SCI are rehospitalized every year due to secondary health complications. One of the more common post-SCI health conditions is Autonomic Dysreflexia AD. Key physiological indicators in the detection of AD are paroxysmal increase of blood pressure and sweating above the spinal cord injury level. In this paper we developed a system to measure galvanic skin resistance and use it to study the changes in skin perspiration and pulse in nine individuals with cervical SCIs while they were performing activities of daily living ADL. A significantly lower skin resistance was detected above the injury site compared to areas below the injury site. As the subjects performed activities of different exertion levels, there was a significant decrease in the skin resistance above the injury site. Additionally, as anxiety levels increased during activities, skin resistance decreased. The application of skin resistance sensors has been shown to be a reliable detection method of naturally-occurring anomalous variations in the skin resistance among quadriplegics due to SCI in order to identify the onset of AD during typical ADL. A possible implication of this study is to provide long-term physiological monitoring of quadriplegics to alert them and their caregivers of the occurrence of AD.
Cross-VM Cache Attacks on AES

Cache based attacks can overcome software-level isolation techniques to recover cryptographic keys across VM-boundaries. Therefore, cache attacks are believed to pose a serious threat to public clouds. In this work, we investigate the effectiveness of cache attacks in such scenarios. Specifically, we apply the Flush+Reload and Prime+Probe methods to mount cache side-channel attacks on a popular OpenSSL implementation of AES. The attacks work across cores in the cross-VM setting and succeeds to recover the full encryption keys in a short time—suggesting a practical threat to real-life systems. Our results show that there is strong information leakage through cache in virtualized systems and the software implementations of AES must be approached with caution. Indeed, for the first time, we demonstrate the effectiveness of the attack across co-located instances on the Amazon EC2 cloud. We argue that for secure usage of world's most commonly used block cipher such as AES, one should rely on secure, constant-time hardware implementations offered by CPU vendors.
Deliberative Democracy and Party System

Deliberative democracy is a new theory of democracy that appeared in western countries in late 20th century.Though not practiced abundantly,it has aroused the concern of scholars at home and abroad.The core of deliberative democracy lies with the form of agreement in legislature and decision-making while party,an important basis for modern democratic politics,is the important participator in the completion of legislature and decision-making.Deliberative democracy will inevitably be connected with party and party politics.Present party system,competitive or non-competitive,will certainly be benefited from the idea of deliberative democracy though it may not necessarily follow its practices.
Targeting Sphingosine Kinase Induces Apoptosis and Regression Of Virus-Associated Lymphoma In Vivo

Background and Specific Aim Sphingosine kinase (SphK) is overexpressed by a variety of cancers, and its phosphorylation of sphingosine results in accumulation of sphingosine-1-phosphate (S1P) and activation of anti-apoptotic signal transduction. Existing data indicate a role for S1P in viral pathogenesis, but roles for SphK and S1P in virus-associated cancer progression have not been defined. The Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL)—a rapidly progressive tumor arising in body cavities which incurs a median survival time of around 6 months with standard therapeutic approaches. ABC294640 is an orally bioavailable small molecule inhibitor of SphK under evaluation in early-phase clinical trials, although no pre-clinical or clinical data are available for this agent for hematologic or virus-associated malignancies. Therefore, we sought to determine whether ABC294640 displays inhibitory effects for HIV/KSHV+ patient-derived PEL cells in vitro and in vivo , as well as potential mechanisms through which SphK regulates KSHV pathogenesis. Methodology Complementary in vitro assays were undertaken using RNAi and ABC294640 for targeting SphK1 and SphK2 in HIV/KSHV+ patient-derived PEL cell lines (uninfected B cell tumor lines were used as controls). qRT-PCR and immunoblots were used to quantify KSHV gene expression and signal transduction, respectively; MTT assays and flow cytometry were used to assess metabolic activity and apoptosis; and mass spectrometry was used to quantify different bioactive sphingolipid intermediates associated with SphK activity. ABC294640 was used in a murine PEL xenograft model to assess the effects of SphK inhibition on KSHV+ lymphoma progression in vivo . Results and Conclusions We find that targeting SphK induces caspase cleavage and apoptosis for KSHV+ patient-derived PEL cells in the presence or absence of co-infection with the Epstein-Barr virus (EBV), whereas uninfected B cell tumor lines are less readily affected. Validating these results, we find that systemic administration of ABC294640 induces tumor regression in the PEL xenograft model. Complimentary ex vivo and in vitro analyses revealed that ABC294640 suppresses constitutive signal transduction associated with proliferation and survival of PEL cells, and increases intracellular accumulation of pro-apoptotic sphingolipid intermediates as well as KSHV lytic genes previously associated with cancer cell death. These results justify additional studies to identify mechanisms for SphK and S1P regulation of virus-associated PEL pathogenesis. Importantly, they also justify evaluation of ABC294640 in clinical trials as a single agent, or in combination with existing approaches, for the treatment of PEL and possibly other malignancies associated with oncogenic viruses. Disclosures: No relevant conflicts of interest to declare.
DETERMINATION OF TWO COMPONENTS IN COMPOUND MINOXIDIL LINIMENT BY UV SPECTROPHOTOMETRY

A UV spectrophotometry has been developed for the simultaneous quantitation of minoxidil and tretinoin in compound minoxidil liniment.The method is based on measuring the first derivative signals(D)of minoxidil at 278.5 nm and the zero derivative signals(A) of tretinoin at 337 nm respectively.Without any interference from each other,or any other coexisting materials.The average recoveries of minoxidil and tretinoin were 101.2% and 98.4%. RSD was 0.78% and 0.82%.The results illustrate that the method is simple,rapid,accurate and sensitive.
A review of research on direct-care staff data collection regarding the severity and function of challenging behavior in individuals with intellectual and developmental disabilities

In working with individuals with intellectual and developmental disabilities (IDDs), it is direct care staff who are often required to collect data on individuals' behavior which is used as the basis for implementation of empirically based approaches for intervention and treatment. Due to limited resources, indirect and descriptive measures of challenging behaviors are employed to analyze the function of individuals' behaviors in place of the preferred method of multimodal assessment, which includes experimental functional analysis. To ensure the most effective services and support to individuals with IDDs, accurate and consistent data collection is critical. In this article, we highlight the importance of accurate data collection practices, conduct a comparison of data collection methods, and discuss limitations .… and barriers for staff. The article concludes with recommendations for best practices and future research.
What Difference Do Dividends Make

We evaluate the investment benefits of dividend-paying stocks and identify three major findings. First, high-dividend payers have the least risk yet return over 1.5% more per year than do nondividend payers. Second, the benefit of targeting dividend payers is conditional on investment style. Surprisingly, the benefit is largest for growth and small-cap stocks, the stocks of companies usually thought to benefit the most from reinvesting their cash flows. Third, long–short managers exploiting the value premium should focus on non-dividend-paying stocks as non-dividend-paying small-cap value stocks return 1% more per month than do non-dividend-paying small-cap growth stocks.
Influence of Calcium and Phosphorus on the Absorption of Manganese as Determined by Plasma Uptake Tests

An antagonistic interaction between calcium(Ca),phosphorus(P),and manganese(Mn) has been suggested in some1–3,but not a112–4,animal and human studies.The purpose of this study was to determine the effect that Ca and P have on the absorption of Mn in humans.
Journeys as Shared Human Experiences

Nie and colleagues' (2016) thoughtful and persuasive argument for altering war metaphors or emphasizing the alternative “journey” metaphor is especially useful because gradual shifts are more succe...
Scheduling non-uniform parallel loops on MIMD computers

Parallel loops are one of the main sources of parallelism in scientific applications, and many parallel loops do not have a uniform iteration execution time. To achieve good performance for such applications on a parallel computer, iterations of a parallel loop have to be assigned to processors in such a way that each processor has roughly the same amount of work in terms of execution time. A parallel computer with a large number of processors tends to have distributed-memory. To run a parallel loop on a distributed-memory machine, data distribution also needs to be considered. This research investigates the scheduling of non-uniform parallel loops on both shared-memory and distributed-memory parallel computers. We present Safe Self-Scheduling (SSS), a new scheduling scheme that combines the advantages of both static and dynamic scheduling schemes. SSS has two phases: a static scheduling phase and a dynamic self-scheduling phase that together reduce the scheduling overhead while achieving a well balanced workload. The techniques introduced in SSS can be used by other self-scheduling schemes. The static scheduling phase further improves the performance by maintaining a high cache hit ratio resulting from increased affinity of iterations to processors. SSS is also very well suited for distributed-memory machines. We introduce methods to duplicate data on a number of processors. The methods eliminate data movement during computation and increase the scalability of problem size. We discuss a systematic approach to implement a given self-scheduling scheme on a distributed-memory. We also show a multilevel scheduling scheme to self-schedule parallel loops on a distributed-memory machine with a large number of processors to eliminate the bottleneck resulting from a central scheduler. We proposed a method using abstractions to automate both self-scheduling methods and data distribution methods in parallel programming environments. The abstractions are tested using CHARM, a real parallel programming environment. Methods are also developed to tolerate processor faults caused by both physical failure and reassignment of processors by the operating system during the execution of a parallel loop. We tested the techniques discussed using simulations and real applications. Good results have been obtained on both shared-memory and distributed-memory parallel computers.
Why is There a Delay in the Increased Oxygen Consumption during the Rest-Work Transition in Skeletal Muscle?

During the rest-work transition in skeletal muscle it has long been known that the increase in oxidative supply of ATP lags the increase in consumption of ATP. The balance is supplied by muscle stores of phosphocreatine (PCr) and glycolysis leading to accumulation of lactate in the muscle. Several hypotheses have been advanced to account for the lag in increase of \(\dot{V}{{O}_{2}}\). These have focused on limits to the delivery of substrates to the mitochondrion: 1) limiting oxygen supply 2) limiting supply of reducing equivalents 3) limiting ADP and/or phosphate (Pi)
microRNA from brush biopsy to characterize oral squamous cell carcinoma epithelium

Few cancers are diagnosed based on RNA expression signatures. Oral squamous cell carcinoma (OSCC) is no exception; it is currently diagnosed by scalpel biopsy followed by histopathology. This study sought to identify oral tumor epithelial microRNA (miRNA) expression changes to determine if these changes could be used to diagnose the disease noninvasively. Analysis of miRNA profiles from surgically obtained OSCC tissue, collected under highly standardized conditions for The Cancer Genome Atlas, was done to determine the potential accuracy in differentiating tumor from normal mucosal tissue. Even when using small 20 subject datasets, classification based on miRNA was 90 to 100% accurate. To develop a noninvasive classifier for OSSC, analysis of brush biopsy miRNA was done and showed 87% accuracy in differentiating tumor from normal epithelium when using RT-qPCR or miRNAseq to measure miRNAs. An extensive overlap was seen in differentially expressed miRNAs in oral squamous cell carcinoma epithelium obtained using brush biopsy and those reported in saliva and serum of oral squamous cell carcinoma patients in several studies. This suggested that nonselective release of these miRNAs into body fluids from tumor epithelium was largely responsible for the changes in levels in these fluids seen with this disease. Using a variation in mirRPath we identified the KEGG pathway of neurotrophin signaling as a target of these miRNAs disregulated in tumor epithelium. This highlights the utility of brush biopsy of oral mucosa to allow simple acquisition of cancer relevant miRNA information from tumor epithelium.
Can Debt Crises Be Prevented

The financial crisis in Mexico in late 1994 and early 1995 came as a surprise to most observers, not so much because there was a major devaluation of the peso, but because the aftermath of this devaluation left the Mexican financial system and economy in a crisis from which it only in 1996, more than a year later, started to recover. The conventional wisdom, as presented by, for example, Dornbusch and Werner (1994), was that a devaluation was exactly what Mexico needed to spur exports and growth. Instead, the devaluation occurred more or less simultaneously with (and perhaps touched off) a debt crisis in which the Mexican government found itself unable to roll over its debt. Fears of a default of one sort or another totally paralyzed the economy in late December 1994 and January 1995. An explanation of the Mexican crisis that focuses on Mexico’s government debt has a puzzling aspect, however: in 1994 Mexico had a very low ratio of government debt to national product by international standards (see Table 1).
Muon beam ring cooler simulations using COSY INFINITY

In this paper we present simulations using COSY INFINITY to study the behavior of muon beams in a ring cooler designed by V. Balbekov[1]. Because of the substantial transversal emittance, the nonlinearities play a very important limiting role that must be understood and controlled well, which leads to the requirement of high order computation. We describe the system, the approaches for the simulations of the large aperture solenoids and magnetic sectors, and we show the nonlinear transfer maps as well as tracking simulations for different field models, and compare with other methods based on various approximations.
Physical Characteristics of Respiratory Gases and Media

This chapter contains many numerical values that should not be committed to memory. To write this section, I looked up all the numbers. The values are important and should be referred to when making calculations. It is more important to the understanding of gas exchange to keep in mind the relative magnitudes and their consequences. Everyone should be able to make rough estimates from memory. No one should rely on memory for important calculations. If you need the actual values, look them up, too. Otherwise, do not waste your brain storing facts; other media already do that so much better.
Social Norms, Law, and Disability

Doctors and advocates have recently argued that parents are increasingly willing to bring a pregnancy to term after a positive test for Down syndrome. They explain this change, in part, as the result of the landmark Americans with Disabilities Act (ADA), which Congress enacted to fight employment discrimination and enhance access to public accommodations. What they fail to appreciate is that these legal protections have not always brought with them the anticipated acceptance of having a child with disabilities. Yet our analysis of birth data reveals a staggering 25 percent decline in Down syndrome birthrates nationwide after the first President Bush signed the ADA into law. Controlling for medical, demographic, and technological variables from maternal age and marital status to abortion access and prenatal care, we found that about 15 fewer children per 100,000 were born with Down syndrome in the years after the law was passed, even as prenatal testing rates remained constant. It is true that newer methods like the “quad screen” are less intrusive than amniocentesis and more accurate than chorionic villa sampling in identifying fetal abnormalities. Yet our analysis shows the absence of any clear correlation between the quality or availability of prenatal screening and the incidence of Down syndrome births. The question remains: Why would fewer children be brought into the world just as they are being afforded greater opportunities in life? Part of the explanation lies in the unexpected messages that civil rights legislation can convey — through salient media and popular culture — to people vaguely familiar with the law or unaware it even exists. These “expressive externalities” arise from public reaction to the unforeseen costs of implementing laws like the ADA. Negative newspaper and television reports seeking to justify new disability protections, or bemoaning the cost of their implementation, can reinforce the anxiety that parents describe as they await genetic test results during pregnancy. They read over breakfast the recent report of local efforts to bar a boy with Down syndrome from playing on a high school basketball team. Or they watch on the evening news this story about another teen with Down syndrome who was kicked off a plane. Accounts like these underscore the power of expressive externalities to shore up ascriptions of blame for having a child with known disabilities.
A comparison of potency of and intracellular signaling events provoked by, small molecule and protein-based mpl agonists

e14624 Background: Thrombopoietin (TPO) interacts with its receptor (mpl) to initiate signal transduction and increase platelet production. Other mpl agonists have been developed for clinical use: ...
Regional Analgesia Techniques for Adult Patients Undergoing Solid Organ Transplantation

Organ transplantations often include major incisions that can be associated with significant postoperative pain. While these patients may theoretically benefit from regional anesthesia, many practitioners have avoided such techniques due to considerations, such as a low perceived benefit if the patient stays intubated postoperatively and concerns about the coagulation status in patients with end-stage liver/kidney disease and perioperative use of anticoagulation. With refinements in both surgical (laparoscopic and robot-assisted procedures) and regional anesthesia techniques (ultrasound guidance), new interest in nerve blocks for organ transplantation has emerged and flourished. While neuraxial anesthesia continues to be used, albeit less frequently for solid organ transplantation, peripheral nerve blocks and paravertebral blocks, in contrast, have increasingly been employed and studied. Specifically, transversus abdominis plane blocks and related fascial plane block techniques are safe to perform and easy to learn. Continuous peripheral nerve blocks are starting to rival the versatility and the widespread use of epidural analgesia with comparable results and lower risk, but validation in various settings is still needed.
A Model for Predicting the Occurrence of Regular Rings in AX2 Tetrahedral Glasses

Recent vibrational studies suggest that vitreous SiOz2 contains a modest concentration (∼2 percent) of small highly regular rings of bonds. This evidence is reviewed, and a simple model is developed that successfully predicts the existence of such rings. The model is then used to estimate the probability of occurrence of similar regular rings in several other AX2 tetrahedral glasses, including BeF2, GeO2, GeS2, GeSe2, SiS2, SiSe2 and ZnCI2. These predictions are supported by the appearance of anomalous sharp lines in the Raman spectra of the glasses, and some of these Raman spectra are presented in the paper. Most interesting is the prediction that v-GeO2 contains a large concentration of nearly planar 3-rings, an element of intermediate range order not seen in the crystalline forms of GeO2 and not included in earlier structural models for the glass.