cssi/SciSciGPT-SciSciNet huggingface dataset:
Challenges in executing large parameter sweep studies across widely distributed computing environments

Large parameter sweep studies are common in a broad range of scientific disciplines. However, many challenges exist in supporting this type of computation in a widely distributed computing environment. These challenges exist because contributing sites in a federated distributed computing environment usually expose only a very narrow resource-sharing interface. This paper looks at the challenges encountered by parameter sweep studies using two concrete application examples. The paper also shows how a system for building personal clusters on demand has been developed to solve many of these problems.
Protein Kinase D Links Gq-coupled Receptors to cAMP Response Element-binding Protein (CREB)-Ser133 Phosphorylation in the Heart

Many growth regulatory stimuli promote cAMP response element-binding protein (CREB) Ser133 phosphorylation, but the physiologically relevant CREB-Ser133 kinase(s) in the heart remains uncertain. This study identifies a novel role for protein kinase D (PKD) as an in vivo cardiac CREB-Ser133 kinase. We show that thrombin activates a PKCδ-PKD pathway leading to CREB-Ser133 phosphorylation in cardiomyocytes and cardiac fibroblasts. α1-Adrenergic receptors also activate a PKCδ-PKD-CREB-Ser133 phosphorylation pathway in cardiomyocytes. Of note, while the epidermal growth factor (EGF) promotes CREB-Ser133 phosphorylation via an ERK-RSK pathway in cardiac fibroblasts, the thrombin-dependent EGFR transactivation pathway leading to ERK-RSK activation does not lead to CREB-Ser133 phosphorylation in this cell type. Adenoviral-mediated overexpression of PKCδ (but not PKCϵ or PKCα) activates PKD; PKCδ and PKD1-S744E/S748E overexpression both promote CREB-Ser133 phosphorylation. Pasteuralla multocida toxin (PMT), a direct Gαq agonist that induces robust cardiomyocyte hypertrophy, also activates the PKD-CREB-Ser133 phosphorylation pathway, leading to the accumulation of active PKD and Ser133-phosphorylated CREB in the nucleus, activation of a CRE-responsive promoter, and increased Bcl-2 (CREB target gene) expression in cardiomyocyte cultures. Cardiac-specific Gαq overexpression also leads to an increase in PKD-Ser744/Ser748 and CREB-Ser133 phosphorylation as well as increased Bcl-2 protein expression in the hearts of transgenic mice. Collectively, these studies identify a novel Gαq-PKCδ-PKD-CREB-Ser133 phosphorylation pathway that is predicted to contribute to cardiac remodeling and could be targeted for therapeutic advantage in the setting of heart failure phenotypes.
Stigmatic Attitudes of Arabs and Arab Americans toward Schizophrenia

The authors of this article tested the hypothesis that individuals in a collectivistic culture will be more likely than those in an individualistic culture to attribute schizophrenia to external factors. Comparing Arabs from the United Arab Emirates to Arabs from the United States, results confirmed this hypothesis. The authors also tested the hypothesis that a woman with schizophrenia will be viewed less negatively than a man with schizophrenia, due to schizophrenia being seen as gender-atypical for women. Findings showed partial support for this hypothesis, but also demonstrated that culture and participant gender played a role in these results.
Maintenance of Gastrointestinal Function After Bowel Surgery and Immediate Enteral Full Nutrition. II. Clinical Experience, with Objective Demonstration of Intestinal Absorption and Motility

Eighteen patients undergoing colorectal excision had gastrointestinal function preserved. Paralytic ileus was avoided by efficient exclusion of swallowed air by aspiration of the esophagus. Full strength elemental diet was delivered into the duodenum immediately postoperatively at 100-150 ml/ hour. Virtually stoichiometric digestion, absorption, and utilization of dietary protein was demonstrated in six patients, for whom 125I-albumin was added to the initial feedings. The 24-hour urine contained 94 ± 4% of the activity. The same group of patients had hourly determinations of nitrogen balance. Each had achieved positive protein balance by 5 ± 3 hours postoperatively.The morning following surgery (17-24 hours postoperatively) the special nasogastric device was removed and intravenous feedings were discontinued, with transition to per os intake of elemental diet. Twelve patients had oral barium motility studies initiated at this time, with continued oral intake of elemental diet. On serial x-rays, each show...
Combinatorial chemistry methods for coating development: VI. Correlation of high throughput screening methods with conventional measurement techniques

Abstract Combinatorial chemistry has proven to be a valuable tool for the development of new compounds. In the pharmaceutical industry, where combinatorial chemistry began, the approach has been instrumental in the high-speed development of new drugs. Due to the overwhelming success of the combinatorial methodology in the pharmaceutical industry, it has been recently applied to materials development. We have recently developed a combinatorial factory capable of preparing and evaluating on the order of 100 organic clear coatings in a day. One of the most challenging aspects of the creation of the combinatorial factory was the development of the high throughput screening (HTS) methods for the primary coating properties of interest such as optical clarity, abrasion resistance, adhesion, and weatherability. For each property, an entirely new method was developed that allowed for rapid measurement of these properties on very small samples. This paper describes various aspects of the development of these novel measurement systems including the correlation of the HTS methods with conventional, industry standard measurement methods.
AIDS in India: When Denial Kills

India is facing a rise in the number of people living with HIV/AIDS. The majorities of new cases of HIV/AIDS victims are women having sex with one partner or husband. In many of these situations, their partners and/or husbands are having sex with prostitutes infected with the AIDS virus. The most vulnerable population of women is those who have minimal education living in poverty. Frequently these women have not heard of HIV, and if they are aware of this virus they lack the knowledge about the route of transmission. The purpose of this article is to review the HIV/AIDS epidemic among people living in poverty in India and to discuss strategies of how to deal with this growing epidemic.
Back from the edge of existence: A critical anthropology of trauma

How do local responses to trauma articulate with understandings of subjectivity, personhood, and meaning making? What therapeutic mechanisms seem to be at play? And how can the analytic lenses of anthropology help us understand—and maybe even facilitate—processes of recovery? In engaging these questions, the papers in this Special Issue lay the groundwork for what we might call a critical anthropology of trauma that bridges the divide between micro-level and macrolevel analyses of radical ruptures from the everyday. As several of the authors note, what we now call trauma is hardly a new topic for anthropologists, who have long paid special attention to events that push people to the very edges of their own existence, as well as the various ways they find their way back, often radically transformed (e.g., Crapanzano, 1985; LeviStrauss, 1963; Obeyesekere, 1984; Rosaldo, 1989; Spiro, 1987; Turner 1967). Such edge-of-existence experiences hinge on what Scarry (1985) calls the unmaking and remaking of worlds. Pushed to the very precipice of physical and/or psychological annihilation, the bonds that tether a person to the everyday world become stretched, distorted, and even torn; sometimes irreparably so. Such a state of ontological alienation is profoundly distressing. To regain their footing, people often turn to culturally available practices, symbols, and structures to help reorient them to the world. Anthropologists have used exegeses of such processes as the foundation for theories of the work of culture (Obeyesekere, 1990). By the mid-1990s, anthropological engagements with such edge-of-existence experiences had turned away from questions of psychological process and towards an examination of the social life of the category of such experiences; “trauma” as a cultural construct becamemarked as a distinct object of study (Young, 1995).Works in this vein are less concerned with underlying psychological mechanisms of trauma as with the social and cultural processes through which some experiences are recognized as “traumatic” and others are not, what this reveals about local understandings of moral responsibility, and the pathways by which recovery is imagined.
Least-Squares Finite Element Methods and Algebraic Multigrid Solvers for Linear Hyperbolic PDEs

Least-squares finite element methods (LSFEMs) for scalar linear partial differential equations (PDEs) of hyperbolic type are studied. The space of admissible boundary data is identified precisely, and a trace theorem and a Poincare inequality are formulated. The PDE is restated as the minimization of a least-squares functional, and the well-posedness of the associated weak formulation is proved. Finite element convergence is proved for conforming and nonconforming (discontinuous) LSFEMs that are similar to previously proposed methods but for which no rigorous convergence proofs have been given in the literature. Convergence properties and solution quality for discontinuous solutions are investigated in detail for finite elements of increasing polynomial degree on triangular and quadrilateral meshes and for the general case that the discontinuity is not aligned with the computational mesh. Our numerical studies found that higher-order elements yield slightly better convergence properties when measured in terms of the number of degrees of freedom. Standard algebraic multigrid methods that are known to be optimal for large classes of elliptic PDEs are applied without modifications to the linear systems that result from the hyperbolic LSFEM formulations. They are found to yield complexity that grows only slowly relative to the size of the linear systems.
Enhancement of an efficient liveness-enforcing supervisor for flexible manufacture systems

This paper presents an enhanced efficient control method to obtain a maximally permissive deadlock prevention policy for flexible manufacturing systems (FMSs) based on Petri nets and the theory of regions. It is well known that the marking/transition-separation instances (MTSIs) method with the theory of regions has been extensively studied as one of optimal policies (i.e., maximally permissive) in FMS deadlock problems. However, all MTSIs are required to identify for controlling the deadlock problems. Therefore, this paper proposes novel crucial MTSIs (CMTSIs) to alleviate the computation cost due to the involvement of few MTSIs. This article elucidates CMTSI is the foundation of MTSI. Moreover, a maximally permissive liveness-enforcing supervisor with efficient computation can be implemented based on the experimental results, demonstrating that the proposed control policy is the most efficient algorithm among the closely related approaches.
Ferromagnetic coupling to muscle receptors as a basis for geomagnetic field sensitivity in animals

Over the past decade several investigators have provided convincing evidence that the orientation of pigeons and other birds during homing and migrational activities is significantly affected by Earth-strength (less than or equal to 0.5 G) magnetic fields. The presumed mediator of such effects would be a highly sensitive magnetoreceptor which the birds would normally use to extract navigational information from the geomagnetic field. The recently reported measurement of magnet remanence in honeybees and in homing pigeons has stimulated interest in the possibility that the magnetically sensitive structure may be constructed from permanently magnetic material. Here we report the detection of permanently magnetic material in the neck musculature of pigeons (Columba livia) and migratory white-crowned sparrows (Zonotrichia leucophrys). We propose that a magnetic field detector might involve the coupling of magnetic particles to a sensitive muscle receptor such as a spindle. A detection mechanism of this kind could account for the difficulties encountered in conditioning immobile homing pigeons to magnetic field changes and for the puzzling requirement of movement in other behavioural experiments involving pigeons and magnetic fields.
Role of IL-1 in poststroke depressive-like behavior in mice.

Background Poststroke depression (PSD) leads to impaired functional recovery and increased mortality, yet physiological mechanisms are unknown. The present study investigates the roles of glucocorticoids and interleukin-1 (IL-1) in poststroke anhedonia. Methods Adult male mice underwent middle cerebral artery occlusion (MCAO), and were recovered 7 days. Mice were treated with metyrapone (100 mg/kg intraperitoneally), mifepristone (50 mg/kg subcutaneously), or vehicle injections on reperfusion days 4–7. A separate cohort of mice was implanted with cannulae and was administered IL-1 receptor antagonist (IL-1ra) or vehicle (6 μg intracerebroventricularly) on reperfusion days 6 and 7. After the final injection or infusion, sucrose consumption was recorded for 6 hours. Results Mice in the sham-treated group consumed significantly more sucrose solution than water, whereas MCAO-treated mice consumed similar amounts of each, suggesting anhedonia among MCAO-treated mice. A separate experiment assessed whether stroke-induced increases in corticosteroids or IL-1 contribute to anhedonia. Only IL-1ra restored sucrose consumption in MCAO-treated mice. Vehicle-MCAO–treated mice drank significantly less sucrose solution than did both IL-1ra and vehicle-sham treatment groups, whereas IL-1ra–MCAO-treated mice drank similar amounts to both sham-treated groups. Conclusions Poststroke anhedonia, a symptom of depression in human beings, can be reproduced in a mouse model of stroke and appears to involve altered IL-1 transmission in the brain.
Sensitivity Analysis of Data Set Sizes for Highway Safety Manual Calibration Factors

The Highway Safety Manual (HSM), Part C, presents crash prediction models for three types of facilities. Each of these models was developed with data from a few states. As noted in the HSM, "The general level of crash frequencies may vary substantially from one jurisdiction to another for a variety of reasons. … Therefore, for the Part C predictive models to provide results that are meaningful and accurate for each jurisdiction, it is important that they be calibrated for application in each jurisdiction." However, states may find the data requirements for calibration to be challenging. The HSM offers general recommendations for the size of the calibration data sets, but not much research is available to provide guidance to the states on how the quality of the calibration factor relates to the size of the calibration data set. This research uses data from Washington State for rural two-lane, rural multilane, and urban or suburban arterial highway segments and evaluates the quality of the calibration facto...
Coalition strategies and the BJP's expansion, 1989–2004

This paper analyses the expansion of the Bharatiya Janata Party (BJP) across India's states from 1989 to 2004 through its strategy of coalition-building. The paper shows that the BJP leveraged its perceived pivotality as a third party in several states to form state-level electoral coalitions on progressively better terms with state-level first or second parties, so to be able to expand across states, exploiting the incentives facing parties at the state level in India's electoral system.
Characteristics of the turnover of uncoupling protein 3 by the ubiquitin proteasome system in isolated mitochondria

Uncoupling protein 3 (UCP3) is implicated in mild uncoupling and the regulation of mitochondrial ROS production. We previously showed that UCP3 turns over rapidly in C2C12 myoblasts, with a half-life of 0.5-4h, and that turnover can be reconstituted in vitro. We show here that rapid degradation of UCP3 in vitro in isolated brown adipose tissue mitochondria required the 26S proteasome, ubiquitin, ATP, succinate to generate a high membrane potential, and a pH of 7.4 or less. Ubiquitin containing lysine-48 was both necessary and sufficient to support UCP3 degradation, implying a requirement for polyubiquitylation at this residue. The 20S proteasome did not support degradation. UCP3 degradation was prevented by simultaneously blocking matrix ATP generation and import, showing that ATP in the mitochondrial matrix was required. Degradation did not appear to require a transmembrane pH gradient, but was very sensitive to membrane potential: degradation was halved when membrane potential decreased 10-20mV from its resting value, and was not significant below about 120mV. We propose that matrix ATP and a high membrane potential are needed for UCP3 to be polyubiquitylated through lysine-48 of ubiquitin and exported to the cytosolic 26S proteasome, where it is de-ubiquitylated and degraded.
Two new alkaloids in cacti.

The plant Thelocactus aacromeris (Engelm.) L. Benson, Coryphantha. macromeris (Engelm.) Lem., Britton and Rose, has been found to contain three alkaloids by gas chromatography. The alkaloids were extracted on a large sc8le from the plant by standard methods.a The principal alkaloid was separated from the minor constituents by chromatography on alumina, The main alkaloid, "macramerine", gave mol. wt. 240 2 25 GLCS, (213 vapor pressure lowering), m.p. 66-67.5" and rotation of ( [o]Es 147.01, c = 0.0390 g/ml, CHCl,; PIBS 42.61, c 0.0200 g/ml, absolute ethanol). The structure, according to spectral data discussed below, is (I):
Holistic Conservation and Cultural Triage: American Indian Perspectives on Cultural Resources

The National Environmental Policy Act and other laws require American Indian cultural resource studies as part of the environmental impact assessment of development projects. Indian people make two general types of responses: holistic conservation ("this land is mine, go away") and cultural triage ("if you go ahead with the project then these are the cultural resources that require most protection"). The analysis is based on 11 cultural resource projects. The major findings are that (1) more policy impacts can be achieved by having both types of responses, (2) the research methods can influence whether or not both types of responses will be provided by Indian people, and (3) Indian people experience emotional and social risks when they engage in cultural triage.
Heteropolypeptides on Titan

Since hydrogen cyanide is a component of Titan's hazy atmosphere, HCN polymers might also be present by way of a low energy pathway leading initially to the synthesis of polyaminomalonitrile. Subsequent reactions of HCN with the activated nitrile groups of this HCN homopolymer would then yield heteropolyamidines, readily converted to heteropolypeptides following contact with frozen water on the surface of Titan. Similar HCN polymers in the reducing atmospheres of Jupiter and Saturn could be major contributors to the yellow-brown-orange appearance of these giant planets. Any detection of such HCN chemistry by the Voyager missions or the pending Galileo probe would constitute evidence for the hypothesis that heteropolypeptides on the primitive Earth were synthesized directly from hydrogen cyanide and water without the intervening formation of α-amino acids.
Classification of a Novel Surface Phase Transition: The Knight‐Move Phase

The knight move or (square root(5) x square root(5)) R27 degree phase occurs on some surfaces relevant for growth of high-T(c) superconducting films and other technologically significant surfaces. The nature of the disordering transition of this phase has not been determined. We demonstrate via simulation that this disordering transition is first-order (discontinuous), a result with important implications for preparation of the surfaces in question.
Phagocytic capabilities of the pigment epithelium.

Abstract The ability of the pigment epithelium (PE) to phagocytize polystyrene spheres, native Sarcina subflava and a mixture of these two particles was studied at short time intervals following injection into the subretinal space in Rana pipiens tadpoles. Polystyrene spheres were interiorized as quickly as 30 min following injection and by 3 hr polystyrene spheres were found throughout the cytoplasm of the PE cells. Sarcina subflava when presented alone were not phagocytized at any interval studied up to 24 hr post injection. Following presentation of the mixed suspension of bacteria and polystyrene spheres large numbers of bead profiles were present within the PE cells indicating that the PE is active phagocytically in the presence of the micrococcus. Occasionally mixed phagosomes containing polystyrene spheres and Sarcina subflava were observed, though the overwhelming majority of the experimental phagosomes contained only polystyrene spheres. These results indicate that the nature of the material presented to the PE can determine whether or not that material will be phagocytized.
Determination of denominator functions for a NSFD scheme for the Fisher PDE with linear advection

We examine and discuss the general problem of how ''denominator functions'' are to be calculated when using nonstandard finite difference (NSFD) methods for constructing discrete models of differential equations. Using the example of the Fisher PDE with linear advection, we show that the denominator functions follow from a simple algorithm. An important class of equations for which this method can be applied are those evolution PDE's describing nonlinear wave phenomena.
Ozone increases amino- and carboxy-terminal atrial natriuretic factor prohormone peptides in lung, heart, and circulation

Ozone can cause pulmonary edema and simultaneously decrease blood pressure. Atrial natriuretic peptides may mediate both of these effects in that they increase pulmonary capillary permeability resulting in edema formation and are potent vasodilating peptides. To examine this possibility, the lungs of Fischer 344 rats were exposed to ozone (0.5 ppm) for 8 hours which resulted in a three- to fourfold increase in atrial natriuretic peptides. Ozone also increased atrial natriuretic peptides in the heart two- to fivefold from 266 +/- 25, 226 +/- 22, and 288 +/- 40 ng/g (room air) to 716 +/- 26, 471 +/- 14, and 1473 +/- 235 ng/g recognized by the proANFs 1-30 and 31-67 and atrial natriuretic factor radioimmunoassays, respectively. Ozone also doubled the concentrations of pro-ANFs 1-30, 31-67, and 1-98 and ANF in the circulation. This study demonstrates that ozone increases atrial natriuretic peptides within the heart, lung, and circulation, suggesting that atrial natriuretic peptides may mediate the decreased blood pressure and pulmonary edema observed with ozone exposure. Since the proANF 31-67 radioimmunoassay exclusively recognizes the ANF prohormone within the heart, this study further indicates that ozone can increase the synthesis of the ANF prohormone.
What the Woodpecker Saw

Threading his personal story through a history of the notion of Arcadia in 19th-century United States, Sachs reflects on our tendency to deny both death and environmental limits.
The Use of Triptans for Pediatric Migraines

Migraine headaches frequently occur in the pediatric population, with a prevalence of 3% in children 2–7 years of age, 4–11% in children 7–11 years of age, and 8–23% in children 11 years of age and older. Migraine without aura is more than twice as common as migraine with aura in children. Headaches are the third leading cause of emergency room referrals and rank in the top five health problems of children. The 2004 American Academy of Neurology’s treatment parameter for migraine in children and adolescents recommended that nasal sumatriptan be considered for acute treatment; however, data were lacking to make a decision regarding the available oral triptans at that time. The more recently released European guidelines discuss three different triptans for use in children but no specific triptan was recommended. Currently, six of the seven available triptans have been studied for efficacy and safety in the pediatric population; however, only a few well controlled clinical studies have been conducted. Sumatriptan has the most available data on outcomes in general, with nasal sumatriptan showing the most positive results. Nasal sumatriptan is approved in children older than 12 years of age in Europe. Oral sumatriptan does not show any clinical benefit versus placebo in children. Rizatriptan and zolmitriptan have conflicting efficacy and safety data, with most studies favoring the use of oral rizatriptan and nasal zolmitriptan. Almotriptan is the first triptan to obtain a US FDA indication in adolescents with migraines lasting 4 or more hours. This approval was based upon two studies, one large clinical trial and one very small, open-label, pilot study. At this time, there are insufficient data to recommend naratriptan and eletriptan for first- or second-line use in pediatric patients with migraines. There are currently no efficacy data for frovatriptan in pediatric patients, which limits its use in this population. Adverse effects of triptans and pharmacokinetic data in children and adolescents are similar to those in adults. The triptan class should be considered as an acute treatment option for children and adolescents with migraines, although their use is mostly ‘off-label’. Of the available triptans, there are more positive efficacy data for sumatriptan and zolmitriptan nasal sprays, and rizatriptan and almotriptan tablets than for the other triptans.
The effects of calcium at the crayfish neuromuscular junction

Abstract 1. 1. Calcium is required for the glutamate depolarization of crayfish muscle. 2. 2. Replacing calcium with other polyvalent cations does not restore the response. 3. 3. Synaptic currents produced by bath application of 0.2 mM glutamate were measured under voltage clamp. 4. 4. The dependence of response amplitude upon the calcium concentration suggests that two calcium ions must bind to the glutamate receptor for the receptor to function. 5. 5. Potentiation of the glutamate current by the addition of 0.1 mM kainic acid does not alter the dependence on calcium concentration.
Numerical recognition of unconstrained handwriting

This paper investigates the collaboration of three numeral recognition techniques that will detect unconstrained handwritten numerals. Our research focuses on a feature-based approach, a method using eigenimages, and a structural analysis approach using wavelet transforms. These approaches will generate an estimate for the input numeral and a corresponding confidence value that in combination, yield a final decision. This paper shows that each individual method performs with a detection rate of better than 80%, and by combining the detection strategies, detection rates up to 94% are observed.
Hepatic chromium content in diabetic subjects

It has previously been suggested that chronic chromium deficiency could be partly responsible for the glucose intolerance seen in older subjects and that chromium supplementation might have a beneficial effect. To evaluate such a possibility further, hepatic chromium content has been determined in postmortem tissue from diabetic and control subjects. A total of 92 persons were examined, 31 of whom were diabetic. Independent variables of ischemic heart disease and hypertensive cardiovascular disease were evaluated because of their frequency in diabetic subjects. The mean hepatic chromium was 12.7 μg/g of ash for the control group, 10.2 for the hypertensive group, 9.96 for the arteriosclerotic group, and 8.59 for diabetic subjects. Only the last group was significantly decreased in regard to the control population with p=0.05. This study suggests that further consideration of chromium deficiency as a cause of diabetes in elderly subjects might be worthwhile.
Remembering information related to one's self ☆

Abstract How does memory for an incident vary depending on whether, and how, the person relates the information to himself? Trait adjectives are better remembered if they were judged in reference to oneself rather than judged for meaning or sound. Our first experiment found a similar mnemonic advantage of referring a described episode or object to some event from one's life. Pleasant events were remembered better than unpleasant ones. A second experiment found incidental memory for trait adjectives was equally enhanced by judging each directly in reference to one's self-concept or indirectly by retrieving an episode either from one's life or from one's mother's life. Contrariwise, memory was poorer when traits were judged in reference to a less familiar person. Thus, good memory depends on relating the inputs to a well-differentiated memory structure.
Palladium Mediated Formation of Δ1- and Δ2-Carbapenems by Cyclofunctionalization of 4-Allenylazetidinones and 4-(2-Propynyl)azetidinones.

Abstract A palladium catalyzed cyclofunctionalization of a 4-allenylazetidinone to Δ1-carbapenems and of 4-(2-propynyl)-azetidinones to Δ2-carbapenems is described. A palladium(+2) catalyst induces nucleophilic closure of the azetidinone nitrogen on a pendant allene or alkyne, and the resulting vinyl palladium intermediate reacts in a subsequent step with allyl halides or activated alkenes (CH2CHE, E = COOEt, COMe, CHO, CN) to provide 2-functionalized carbapenems. The allylation is catalytic in palladium, while the reaction with CH2CHE, as currently performed, is stoichimetric in palladium.
A new theory of amoeboid locomotion.

Abstract Amoeboid locomotion is analysed upon the basis of the theory that intracellular movements result from the impelling of cytoplasmic matrix by longitudinally-propagated pulsatory pumping actions of the membranous elements of the endoplasmic reticulum. Pumping of matrix by the unfixed tubular and vesicular elements is believed to lead to their progression by jet propulsion. In this view, the mass streaming of the endoplasm (plasmasol) of amoebae is a counter-current process in which these unfixed elements (and inclusions enmeshed between them) move in one direction, while the matrix is ejected in the opposite direction. On the other hand, pumping of matrix by fixed double-membrane lamellae in the ectoplasm (plasmagel) is believed to result in the displacement of the matrix alone. It is proposed that as a result of these actions the matrix circulates from hyaline caps backward through the streaming endoplasm to the tail piece and thence back through the ectoplasm to the hyaline caps of advancing regions. The impelling of matrix through the ectoplasm of the attached animal is postulated to be the basic process bringing about transfer of cell mass into new regions. Locomotion is viewed essentially as a process of “ramrod” extension of hyaline caps by matrix pumped underneath the plasmalemma from the ectoplasm, and the subsequent consolidation of these caps. Consolidation appears to occur both by the entrance into the caps of jet-propelled unfixed elements of the endoplasmic reticulum (and accompanying inclusions), and by bulk displacement of cap fluid by endoplasm squeezed in under hydrostatic pressure. Each cycle of extension and consolidation of a hyaline cap appears to be the result of several concatenated, partly independent actions-variations in the individual rates and effectiveness of which can lead to extensive differences in overall pattern. It is proposed that control of site, time and direction of streaming are related to alterations of matrix composition brought about by: (a) selective filtration on being taken into the lumina of pumping elements; (b) metabolic processes accompanying pumping; and (c) being expressed under and coming in contact with the plasmalemma. Sol-gel transformations of the cytoplasm of amoebae, and probably of cytoplasm in general, may depend in large part upon alterations of the degree to which the interstitial and luminal matrix of different regions has been evacuated (or augmented) by the bunching together (or dilation and separation) of their membranous elements. The rapid transitions occurring between endoplasm and ectoplasm, particularly hyaline ectoplasm, suggest a lability and ready interconversion of components of the endoplasmic reticulum between double-membrane lamellae and tubular (and vesicular) structures.
Molecular predictors of cognitive involvement in female carriers of fragile X syndrome.

Objective. —Fragile X syndrome is caused by a mutation involving expansion of a CGG trinucleotide repeat segment in the fragile X mental retardation—1 ( FMR1 ) gene on the long arm of the X chromosome. This study was undertaken to determine the relative impact of three molecular characteristics of the FMR1 mutation— number of CGG repeats, methylation status, and X inactivation ratio—on the cognitive involvement of female carriers of fragile X syndrome. Design. —Retrospective study with new DNA analysis of known female carriers of fragile X syndrome. Setting. —Molecular studies were conducted in a university-based DNA diagnostic laboratory. Patients were originally ascertained through a regional fragile X clinic in a university-affiliated pediatric hospital. Patients. —Forty-eight female carriers of fragile X syndrome were studied, including 22 with a premutation (a small expansion to approximately 50 to 200 CGG repeats), 23 with a full mutation (a full expansion to >200 CGG repeats), and three with both types of mutations (mosaics). Results. —Median IQ score was significantly lower for females with a full mutation than for females with a premutation. No significant relationship was found between IQ score and number of CGG repeats or percentage methylation of the mutant allele within each mutation category. In addition, no significant relationship was found between IQ score and the proportion of normal FMR1 alleles on the active X chromosome in the carrier female group as a whole or in either mutation subgroup. Comparisons of leukocytes and saliva-borne epithelial cells in certain full-mutation carriers revealed striking differences in FMR1 mutation sizes. Conclusions. —Mutation category remains the most important predictor of affectedness in female carriers of fragile X syndrome. Our data do not support use of the proportion of normal FMR1 alleles on the active X chromosome as a predictor of cognitive involvement in female carriers with full mutations. Individual tissue-specific differences exist in the heterogeneous sizes of full mutations and in the presence of premutation/full-mutation mosaicism. ( JAMA . 1994;271:507-514)
2D line and polygon clipping based on space subdivision

This paper introduces a new approach to 2D line and polygon clipping against a rectangular clipping region, using space subdivision into cells, with the clipping region as the central cell. The line segment path is traced through the cells, and entries into and out of the cell corresponding to the clipping region enable computation of the intersection of the line segment with crossed cell edges. Tracing the line segment path is computationally very simple, leading to an algorithm that only computes intersections that the are part of the clipped line segment. The new algorithm is compared to other standard line clipping algorithms with simulations and operation counts.
Drosophila melanogaster Germ‐line Transformation

The ability to genetically transform and modify Drosophila melanogaster was originally made possible through the use of transposable elements (TEs). These proved to be efficient mutagens leading to the generation of many libraries containing TE-tagged genes and enhancers throughout much of the genome. TEs were also efficient at introducing genes into this insect. A limitation of this technology was the inability to direct where transposons insert in the genome. However, recent advances made with the development of targeting systems based on protein-based and RNA-based guidance of endonucleases to specific target sites have provided a solution to this problem. As a consequence, the genetic toolbox of Drosophila geneticists have considerably expanded and will have a dramatic impact on our ability to understand genetic pathways in this insect. Key Concepts: Class II transposable elements form the basis of versatile genetic technology. Homologous recombination technologies have been problematic but progress has been made. Site-specific recombinases add an additional dimension to the genetic toolbox. Homologous recombination technologies have been problematic but progress has been made. Zinc finger nucleases provide an alternate approach to site-specificity. TALENs facilitate another approach to directed integration into the genome. CRISPRs will lead to a new generation of approaches to site-specific medication in Drosophila. Keywords: transposable element; homologous recombination; zinc finger nucleases; TALENs; CRISPR/Cas9
The effect of hyperbaric oxygen on memory

The effect of oxygen at high pressure (OHP) on memory was investigated. Multiple exposures to OHP after training in a Lashley III maze produced significant retention deficits, confirming a previous study. However, exposures to OHP failed to produce retention deficits of a T-maze position habit. The results suggest that the Lashley III maze deficit was produced by alterations in activation and not by a memory deficiency.
Enhanced coupling of subterahertz radiation with semiconductor periodic slot arrays.

In this work, a theoretical study of the coupling of TM polarized subterahertz (THz) radiation with periodic semiconductor rectangular slot arrays was conducted, using InSb as an example. Simulation results showed that the structure with $4--12\text{ }\ensuremath{\mu}\mathrm{m}$ thickness provides over a 20--30-fold increase in the electric field at slot edges in a nanosize region ($\ensuremath{\sim}500\text{ }\text{ }\mathrm{nm}$). The enhancement of the THz electromagnetic field extends across the slots and reaches peak values at the edges due to discontinuity effects. Because of the strong local electromagnetic field enhancement, the structure can potentially be used for the development of novel biophotonic sensors, leading to improved detection sensitivity.
Identifying points of conflict

Philanthropic leadership is being challenged to lead change and elevate the status and value of health care philanthropy.
Diagnosis and management of stage I/II melanoma.

Objectives To describe the clinical features and histologic subtypes of cutaneous melanoma; to review the diagnosis, clinical, and pathologic staging of melanoma and the associated prognostic factors; and to review the treatment and management of AJCC stage I and II melanoma. Data Sources Scientific and review articles, textbooks, and clinical practice. Conclusions Management of melanoma depends on accurate diagnosis, staging, and interpretation of prognostic factors. The treatment of choice for stage I and II melanoma is surgery, ranging from simple excision to lymph node dissection. Implications for Nursing Practice Familiarity with the clinical features of melanoma assists nurses in the screening and early detection of melanoma. Knowledge of AJCC staging guides education regarding treatment and lifelong surveillance.
Beyond LDL-cholesterol reduction: the way ahead in managing dyslipidaemia

Observational cohort studies and analysis of the populations of intervention trials at baseline reveal a strong inverse association between circulating levels of high-density lipoprotein (HDL)-cholesterol at baseline and the risk of a fatal or non-fatal cardiovascular event. Intervention with a statin is as effective, in absolute terms, in reducing the risk of coronary events in patients across a wide range of dyslipidaemic phenotypes, including those with low HDL-cholesterol. However, statins exert little effect on the levels of HDL-cholesterol, and treatment with a statin does not eliminate the excess risk associated with low HDL-cholesterol. Additional therapy is clearly required to address this residual risk. The success of clinical evaluations of agents that increase HDL-cholesterol, such as nicotinic acid or fibrate drugs, in reducing the incidence of cardiovascular events points to a way forward. Evidence from outcome studies already points to superior cardiovascular risk reductions in patients receiving a statin plus nicotinic acid, and intensive multi-drug regimens based on such combinations probably represent the way to achieve cardiovascular risk reductions greater than those possible with a statin alone. Accurate and well-validated assays for measuring HDL-cholesterol and more precise definition of optimal levels of HDL-cholesterol in patients with different levels of cardiovascular risk are required. These advances will facilitate the future drafting of guidelines that include correction of low HDL-cholesterol alongside reduction of low-density lipoprotein cholesterol within clinical algorithms for reducing cardiovascular risk.
Neuroendocrine Protein 7B2 Can Be Inactivated by Phosphorylation within the Secretory Pathway

Abstract The prohormone convertases play important roles in the maturation of neuropeptides and peptide hormone precursors. Prohormone convertase-2 (PC2) is the only convertase that requires the expression of another neuroendocrine protein, 7B2, for expression of enzyme activity. In this study, we determined that 7B2 can be phosphorylated in Rin cells (a rat insulinoma cell line) and cultured chromaffin cells, but not in AtT-20 cells (derived from mouse anterior pituitary). Phosphoamino acid analysis of Rin cell 7B2 indicated the presence of phosphorylated serine and threonine. Phosphorylation of Ser115 (located within the minimally active 36-residue peptide) was confirmed by mutagenesis, although Ser115 did not represent the sole residue phosphorylated. Two independent assays were used to investigate the effect of phosphorylated 7B2 on PC2 activation: the ability of 7B2 to bind to pro-PC2 was assessed by co-immunoprecipitation, and activation of pro-PC2 was assessed in a cell-free assay. Phosphorylated 7B2 was unable to bind pro-PC2, and the phosphorylated 7B2 peptide (residues 86–121, known to be the minimally active peptide for pro-PC2 activation) was impaired in its ability to facilitate the generation of PC2 activity in membrane fractions containing pro-PC2. In vitro phosphorylation experiments using Golgi membrane fractions showed that 7B2 could be phosphorylated by endogenous Golgi kinases. Golgi kinase activity was strongly inhibited by the broad-range kinase inhibitor staurosporine and partially inhibited by the protein kinase C inhibitor bisindolylmaleimide I, but not by the other protein kinase A, Ca2+/calmodulin-dependent kinase II, myosin light chain kinase, and protein kinase G inhibitors tested. We conclude that phosphorylation of 7B2 functionally inactivates this protein and suggest that this may be analogous to the phosphorylating inactivation of BiP, which impairs its ability to bind substrate.
Silicone implant replacement arthroplasty of the trapezium

Abstract Modifications in surgical technique over the past three decades have made silicone trapezium replacementarthroplasty more predictable and reproducible. Pain relief is routinely achieved while range of motion and strength are preserved. Attention to detail is essential to prevent complications
Spectroscopic Applications of External Cavity Quantum Cascade Laser with Fast Tuning

Littrow-based folded external cavity QCL capable of tuning up to 7cm-1 at kHz rates is presented. Laser capabilities in pulsed and cw modes are demonstrated by performing absorption spectroscopy of ammonia and ethylene at ~10?m.
BCL::EM-Fit: rigid body fitting of atomic structures into density maps using geometric hashing and real space refinement.

Cryo-electron microscopy (cryoEM) can visualize large macromolecular assemblies at resolutions often below 10 A and recently as good as 3.8-4.5 A. These density maps provide important insights into the biological functioning of molecular machineries such as viruses or the ribosome, in particular if atomic-resolution crystal structures or models of individual components of the assembly can be placed into the density map. The present work introduces a novel algorithm termed BCL::EM-Fit that accurately fits atomic-detail structural models into medium resolution density maps. In an initial step, a ''geometric hashing'' algorithm provides a short list of likely placements. In a follow up Monte Carlo/Metropolis refinement step, the initial placements are optimized by their cross correlation coefficient. The resolution of density maps for a reliable fit was determined to be 10 A or better using tests with simulated density maps. The algorithm was applied to fitting of capsid proteins into an experimental cryoEM density map of human adenovirus at a resolution of 6.8 and 9.0 A, and fitting of the GroEL protein at 5.4 A. In the process,
Quantum chemical characterization of the structures, thermochemical properties, and doublet-quartet splittings of tridehydropyridinium cations.

Structural and energetic properties are predicted for the six tridehydropyridinium cation isomers in their lowestenergy doublet and quartet states by using density functional, multireference second-order perturbation, and coupled-cluster theories. Doublet-quartet splittings and triradical stabilization energies are examined to gain insight into the degree of interaction between the three radical centers, with comparison being made to analogous tridehydrobenzenes.
Design for variability in DSM technologies [deep submicron technologies]

Process-induced parameter variations cause performance fluctuations and are an important consideration in the design of high performance digital ICs. Until recently, it was sufficient to model die-to-die shifts in device (active) and wire (passive) parameters, leading to a natural worst-case design methodology. In the deep-submicron era, however, within-die variations in these same device and wire parameters become just as important. In fact, current integrated circuits are large enough that variations within the die are as large as variations from die-to-die. Furthermore, while die-to-die shifts are substantially independent of the design, within-die variations are profoundly influenced by the detailed physical implementation of the IC. This changes the fundamental view of process variability from something that is imposed on the design by the fabrication process to something that is co-generated between the design and the process. This paper starts by examining the sources and historical trends in device and wire variability, distinguishing between inter-die and intra-die variations, and proposes techniques for design for variability (DOV) in the presence of both types of variations.