cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of molecular pathologies sufficient to cause neuropathic excitability in primary somatosensory afferents using dynamical systems theory.

Pain caused by nerve injury (i.e. neuropathic pain) is associated with development of neuronal hyperexcitability at several points along the pain pathway. Within primary afferents, numerous injury-induced changes have been identified but it remains unclear which molecular changes are necessary and sufficient to explain cellular hyperexcitability. To investigate this, we built computational models that reproduce the switch from a normal spiking pattern characterized by a single spike at the onset of depolarization to a neuropathic one characterized by repetitive spiking throughout depolarization. Parameter changes that were sufficient to switch the spiking pattern also enabled membrane potential oscillations and bursting, suggesting that all three pathological changes are mechanistically linked. Dynamical analysis confirmed this prediction by showing that excitability changes co-develop when the nonlinear mechanism responsible for spike initiation switches from a quasi-separatrix-crossing to a subcritical Hopf bifurcation. This switch stems from biophysical changes that bias competition between oppositely directed fast- and slow-activating conductances operating at subthreshold potentials. Competition between activation and inactivation of a single conductance can be similarly biased with equivalent consequences for excitability. “Bias” can arise from a multitude of molecular changes occurring alone or in combination; in the latter case, changes can add or offset one another. Thus, our results identify pathological change in the nonlinear interaction between processes affecting spike initiation as the critical determinant of how simple injury-induced changes at the molecular level manifest complex excitability changes at the cellular level. We demonstrate that multiple distinct molecular changes are sufficient to produce neuropathic changes in excitability; however, given that nerve injury elicits numerous molecular changes that may be individually sufficient to alter spike initiation, our results argue that no single molecular change is necessary to produce neuropathic excitability. This deeper understanding of degenerate causal relationships has important implications for how we understand and treat neuropathic pain.
Absolute and convective instability of axisymmetric jets with external flow

The stability of an axisymmetric jet was examined in the presence of external co‐flow and counterflow. Spatio‐temporal theory was used to distinguish regions of absolute and convective instability in a parameter space including the velocity ratio, density ratio, Mach number, and the shear layer thickness. The absolute‐convective transition was identified for two distinct axisymmetric modes. One of these modes became absolutely unstable in the presence of ambient co‐flow while the other mode required external counterflow to admit an absolutely unstable solution. In general, the former mode was most unstable in low density jets, while the latter became more unstable as the jet density was increased relative to the surrounding fluid. In the range of parameters studied, both modes became increasingly unstable with decreasing jet density and for lower Mach numbers. The results of the spatiotemporal theory are also compared to globally unstable modes identified in laboratory jets.
A data fusion framework for real-time risk assessment on freeways

Abstract The increased deployment of non-intrusive detection systems such as Automatic Vehicle Identification (AVI) and Remote Traffic Microwave Sensors (RTMSs) provides access to real-time traffic data from multiple sources. The availability of such rich data enhances the reliability of travel time estimation and route guidance systems, however, utilization of these data is absent in the context of proactive safety management systems. This paper presents a framework for real-time risk assessment on a freeway in Colorado by fusing data from two different detection systems (AVI and RTMS), real-time weather and roadway geometry. Stochastic Gradient Boosting (SGB), a relatively recent and promising machine learning technique is used to calibrate the models. SGB’s key strengths lie in its capability to fit complex nonlinear relationships, handling different types of predictors (nominal and categorical) and accommodating missing values with no need for prior transformation of the predictor variables or elimination of outliers. Boosting multiple simple trees together overcomes the drawback of single tree models of poor prediction accuracy and provides fast and superior predictive performance. The proposed framework is considered a good alternative for real-time risk assessment on freeways because of its high estimation accuracy, robustness and reliability.
Session summaries and abstracts from the 11th Biennial Graylyn Conference on women’s cognitive health, 24–26 October 2007.

Keywords are included on the first page of each session summary. There are 7 session summaries.
Constructing and Deconstructing the Body Malleable through Mother–Daughter Interactions

This interpretive study explores how mothers and their adolescent daughters respond to and interact about the body malleable ideology, or cultural discourses that normalize thinness and promote the body as changeable. In-depth interviews were conducted with 20 mothers and their daughters. Grounded theory analysis revealed two responses to the body malleable ideology-the acceptance or rejection of the body as a malleable object. Participants expressed ambivalence about this ideology and related cultural discourses. Further, through their interactions, mothers and daughters both constructed and deconstructed the ideology of a malleable body. Three patterns of dyadic experience were identified: Pattern A, in which both the mother and daughter accepted the body malleable ideology, Pattern B, in which both the mother and daughter rejected the body malleable ideology, and Pattern C, in which the mother rejected and the daughter accepted the body malleable ideology. In taking an in-depth look at the cases of three dyads, we explore defining characteristics of these patterns. We also present a grounded theory model developed to illustrate relationships discovered in this study.
Discrete domain wall positioning due to pinning in current driven motion along nanowires.

Racetrack memory is a novel storage-class memory device in which a series of domain walls (DWs), representing zeros and ones, are shifted to and fro by current pulses along magnetic nanowires. Here we show, by precise measurements of the DW’s position using spin-valve nanowires, that these positions take up discrete values. This results from DW relaxation after the end of the current pulse into local energy minima, likely derived from imperfections in the nanowire.
Factors affecting the distribution of enamel hypoplasias within the human permanent dentition.

Frequencies and morphological and chronological distributions of enamel hypoplasias are presented by tooth type (permanent I1 to M2s), based on a sample of 30 prehistoric Amerindians with complete and unworn dentitions. There is nearly a tenfold variation in frequency of defects by tooth, ranging from 0.13 per mandibular second molar to 1.27 per maxillary central incisor. The six anterior teeth average between 0.70 and 1.27 defects/tooth, whereas the eight posterior teeth average between 0.43 and 0.13 defects/tooth. Earlier developing teeth, such as incisors, have earlier peak frequencies of defects (2.0–2.5 years), while later developing teeth, such as second molars, have subsequent peak frequencies (5.0–6.0 years). These variations are relevant when comparing hypoplasia data based on different teeth. Differences in hypoplasia frequencies among teeth are not solely due to variation in time of crown development, as is usually reported. Rather, there is evidence for biological gradients in susceptibility to ameloblastic disruption. Anterior teeth are more hypoplastic than posterior teeth. More developmentally stable “polar” teeth are more hypoplastic than surrounding teeth. Polar teeth may be more susceptible to hypoplasias because their developmental timing is less easily disrupted. In all teeth, hypoplasias are most common in the middle and cervical thirds. Crown development and morphological factors, such as enamel prism length anddirection, may influence the development and expression of enamel surface defects.
Counseling perimenopausal women

Provision of accurate and understandable information by health care providers is critical in order for perimenopausal women to make informed decisions about hormonal and nonprescription remedies. Influences on these decisions include both external information and internal individual factors. It is important to understand the individual's needs and priorities when providing counseling.
MC SCF molecular gradients and hessians: Computational aspects

Abstract Molecular gradients and hessians for multiconfigurational self-consistent-field wavefunctions are derived in terms of the generators of the unitary group using exponential unitary operators to describe the response of the energy to a geometrical deformation. Final expressions are cast in forms which contain reference only to the primitive non-orthogonal atomic basis set and to the final orthonormal molecular orbitals; all reference to intermediate orthogonalized orbitals is removed. All of the deformation-dependent terms in the working equations reside in the one- and two-electron integral derivatives involving the atomic basis orbitals. The deformation-independent terms, whose contributions can be partially summed, involve symmetrized density matrix elements which have the same eight-fold index permutational symmetry as te one- and two-electron integral derivatives they multiply. This separation of deformation-dependent and -independent factors allows for single-pass integral-derivative-driven implementation of the gradient and hessian expressions.
A Phase I and pharmacokinetic study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma

BACKGROUND The authors have previously demonstrated that tamoxifen (TAM) is synergistic with cisplatin (DDP) in patients with metastatic melanoma. In vitro studies have demonstrated that TAM/DDP synergy is dependent on a TAM effect that is currently under investigation. In an attempt to improve the complete response rate of this regimen, the authors initiated a Phase I trial to determine the maximum tolerated dose (MTD) of TAM that could be safely administered with weekly DDP. METHODS TAM was started on Day 1 at a dose of 80 mg/day and was increased by 40 mg to the MTD in groups of 3 patients. DDP (80 mg/m2) was begun on Day 2 and repeated weekly for a total of 3 weeks. During Week 4, the patients were not treated with DDP but instead evaluated for response. If disease stabilization or regression was documented, the patients received a second 3-week cycle of DDP and were then reevaluated for response. Patients with progressive disease were removed from the study. RESULTS In 25 consecutive patients, the overall response rate was 20%. No responses were observed in patients treated with TAM at a dose of <240 mg/day. Among 13 patients treated at or above this dose, there were 2 complete responses, 3 partial responses, 2 mixed responses, and 6 patients with progressive disease. The overall response rate for patients treated with 240 mg of TAM or higher was 38.5%. Dose-limiting toxicity, which occurred at a TAM dose of 280 mg/day, was primarily hematologic and gastrointestinal in nature. There was one toxic death (due to septic neutropenia) at this dose. There were no episodes of thrombosis. CONCLUSIONS A TAM dose of 240 mg/day is the recommended Phase II dose. Based on the 38.5% overall response rate at this dose, the authors have initiated a Phase II study. Cancer 1997; 79:1037-43. © 1997 American Cancer Society.
CB-64D and CB-184: ligands with high σ2 receptor affinity and subtype selectivity

Abstract Four members of a novel class of sigma (σ) ligands were investigated for σ subtype selectivity. (−)-1 S ,5 S - and (+)-1 R ,5 R -( E )-8-Benzylidene-5-(3-hydroxyphenyl)-2-methylmorphan-7-one (CB-64L and CB-64D, respectively) exhibited σ 1 K 1 = 10.5 nM and 3063 nM; σ 2 K i = 154 nM and 16.5 nM, respectively. The corresponding 3,4-dichloro derivatives, (−)-1 S ,5 S - and (+)-1 R ,5 R -( E )-8-(3,4-dichlorobenzylidene)-5-(3-hydroxyphenyl)-2-methylmorphan-7-one (CB-182 and CB-184, respectively) were also examined. CB-182 ((−)-isomer) showed σ 1 and σ 2 K i = 27.3 nM and 35.5 nM, respectively, whereas CB-184 ((+)-isomer) exhibited σ 1 and σ 2 K i = 7436 nM and 13.4 nM, respectively. Thus, the two σ subtypes showed opposite enantioselectivity for these compounds, with (−) > (+) at σ 1 and (+) > (−) at σ 2 . Importantly, CB-64D and CB-184 showed high σ 2 affinity and, respectively, 185-fold and 554-fold selectivity for σ 2 receptors over σ 1 . While high σ 2 selectivity relative to σ 1 was achieved with these compounds, they both exhibited high affinity at mu (μ) opioid receptors ( K i = 37.6 nM and 4.5 nM, respectively). Despite this, CB-64D and CB-184 will be useful tools for further characterization of σ 2 receptors.
Understanding EHDA and Protein Stability

Therapeutic proteins can be difficult to work with due to the fact that each protein has properties and functions that are unique. These exclusive properties are in part due to the proteins three-dimensional shape (secondary and tertiary structure). This shape is determined by bends in the amino acid sequence generated by electrostatic interactions, hydrogen bonds, and hydrophobic-hydrophilic interactions between neighboring amino acids. These bonding interactions are weak and can be severed by chemical or physical forces. Thus, therapeutic proteins can be denatured during manufacture and by methods used to deliver them to the body.Copyright © 2007 by ASME
Iris Image Quality Testing and Iris Verification

The purpose of this study was to investigate the iris image quality and iris verification of eyes in brown, hazel, green, and blue, respectively, and the iris image quality and iris verification under different conditions such as the changed stand-off distances, the motions of the head and eyes, with glasses, and without glasses. A comparative study of three eye colors in brown, hazel, and green was conducted using a non-parametric method based on the H test. The H test results show that there is no significant difference in the iris image quality of eyes in brown, hazel, or green when the level of significance is 0.05. DOI: http://dx.doi.org/10.11591/ijece.v3i4.2769
THE ROLE OF DIOLEOYL PHOSPHATIDYLETHANOLAMINE IN CATIONIC LIPOSOME MEDIATED GENE TRANSFER

In a reported gene assay, cationic liposomes containing the cationic lipid 3 beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-Chol) and a neural phospholipid dioleoylphosphatidylethanolamine (DOPE) showed high transfection activity. DNA/liposome complex which contained low amount of liposomes could bind to the cell surface but failed to transfect the cells. We have designed a two-step protocol to examine this phenomenon in more detail. A431 human cells were incubated on ice (pulse) with DNA complexed to a low level of cationic liposomes. The cells were washed and incubated at 37 degrees C (chase) with or without free cationic liposomes of various composition (helper liposomes). Only liposomes enriched with DOPE showed helper activity; liposomes containing dioleoylphosphatidylcholine (DOPC), a structural analog of DOPE, had no helper activity. The delivery was inhibited by the lysosomotropic agent chloroquine and was optimal if the helper liposome chase was initiated immediately after the pulse. An endocytosis model of DNA delivery by cationic liposomes is proposed in which the principal function of the chase liposomes is to destabilize the endosome membrane and allow the release of DNA into the cytosol. This model is consistent with the known activity of DOPE to assume non-bilayer structures, hence destabilizing the endosome membrane.
Gas Hydrate Surface Simulating Seismic Reflectors In the Prudhoe Bay-Kuparuk River Region of North Alaska

Access to approximately 200 km of multic h a n n e l s e i s m i c d a t a i n t h e P r u d h o e B a y Kuparuk River region, courtesy of the Exxon Company, p r o v i d e s n e w i n s i g h t i n t o t h e s t r u c t u r a l a n d s t r a t i g r a p h i c f r a m e w o r k o f t h i s a r e a . T h e s e a r e t h e f i r s t m o d e r n s e i s m i c d a t a a v a i l a b l e t o o u r s t u d y o f g a s hydra tes in the Sagavani rk tok Format ion , a project partly funded by the U.S. Department o f E n e r g y . P r e l i m i n a r y a n a l y s i s o f t h e seismic data confirms the northeast-trending regional dip and northward-expanding thickness o f the Sagavani rk tok Format ion . The clinoform style of progradation, well demons t r a t e d t o t h e w e s t i n t h e N a t i o n a l P e t r o leum Reserve in Alaska , con t inues th rough the Prudhow Bay-Kuparuk River reg ion ; the S a g a v a n i r k t o k r e p r e s e n t i n g t h e t o p s e t a n d the coeva l Canning Format ion represen t ing t h e f o r e s e t a n d b o t t o m s e t p a r t s o f t h e clinoform sequence.
Uncertainty in particle number modal analysis during transient operation of compressed natural gas, diesel, and trap-equipped diesel transit buses.

The relationships between transient vehicle operation and ultrafine particle emissions are not well-known, especially for low-emission alternative bus technologies such as compressed natural gas (CNG) and diesel buses equipped with particulate filters/traps (TRAP). In this study, real-time particle number concentrations measured on a nominal 5 s average basis using an electrical low pressure impactor (ELPI) for these two bus technologies are compared to that of a baseline catalyst-equipped diesel bus operated on ultralow sulfur fuel (BASE) using dynamometer testing. Particle emissions were consistently 2 orders of magnitude lower for the CNG and TRAP compared to BASE on all driving cycles. Time-resolved total particle numbers were examined in terms of sampling factors identified as affecting the ability of ELPI to quantify the particulate matter number emissions for low-emitting vehicles such as CNG and TRAP as a function of vehicle driving mode. Key factors were instrument sensitivity and dilution ratio,...
Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging.

Direct bone marrow chromosome studies were carried out on 165 males, 3 months to 94 years of age. Forty-one males were found to have 45,X cell lines in their bone marrow. The number of males exhibiting Y chromosome loss correlated with age, but the degree of Y chromosome loss did not correlate with age. The loss of Y chromosome appears to be a permanent event. The longest follow-up period in this study was 13 months. The incidence of 45,X cell lines in the bone marrow is much greater than that in peripheral blood leukocyte cultures. The presence of 45,X cell lines in the bone marrow or peripheral blood of aging males should be recognized as a common event, and the finding should not be considered evidence for the presence of a specific disease state.
THE EFFECTS OF EPIDERMAL GROWTH FACTOR (EGF) ON THE DEVELOPMENT OF EGF-RECEPTOR (EGF-R) BINDING IN FETAL RABBIT LUNG ORGAN CULTURE. ▴ 404

THE EFFECTS OF EPIDERMAL GROWTH FACTOR (EGF) ON THE DEVELOPMENT OF EGF-RECEPTOR (EGF-R) BINDING IN FETAL RABBIT LUNG ORGAN CULTURE. ▴ 404
High-resolution LCD-projection-based color head-up display

There are many technical approaches to replacement of the CRT image source for a Head-Up Display (HUD). LCD projectors promise to greatly lower the cost of the HUD because the cost of these displays continues to drop while the cost of CRTs remains stable. LCD projectors allow the realization of multi-colors in the HUD. Their high luminance provides bright raster images, where CRTs are limited by the constraints of the scanning electron beam. Finally, LCD projectors have a digital interface. There are none of the high voltage power supplies, A/D converters, and deflection amplifiers found in CRT drive systems, further improving cost and reliability. This paper describes the performance requirements and achieved performance of an LCD projection image source for use in a wide field of view head-up display (HUD) optical system.
Global variance reduction for Monte Carlo reactor physics calculations

Over the past few decades, hybrid Monte-Carlo-Deterministic (MC-DT) techniques have been mostly focusing on the development of techniques primarily with shielding applications in mind, i.e. problems featuring a limited number of responses. This paper focuses on the application of a new hybrid MC-DT technique: the SUBSPACE method, for reactor analysis calculation. The SUBSPACE method is designed to overcome the lack of efficiency that hampers the application of MC methods in routine analysis calculations on the assembly level where typically one needs to execute the flux solver in the order of 10{sup 3}-10{sup 5} times. It places high premium on attaining high computational efficiency for reactor analysis application by identifying and capitalizing on the existing correlations between responses of interest. This paper places particular emphasis on using the SUBSPACE method for preparing homogenized few-group cross section sets on the assembly level for subsequent use in full-core diffusion calculations. A BWR assembly model is employed to calculate homogenized few-group cross sections for different burn-up steps. It is found that using the SUBSPACE method significant speedup can be achieved over the state of the art FW-CADIS method. While the presented speed-up alone is not sufficient to render the MC method competitive with themore » DT method, we believe this work will become a major step on the way of leveraging the accuracy of MC calculations for assembly calculations. (authors)« less
An output-sensitive variant of the baby steps/giant steps determinant algorithm

In the first half of 2000, two new algorithms were discovered for the efficient computation of the determinant of a (dense) matrix with integer entries. Suppose that the dimension of the matrix is n x n and that the maximum bit length of all entries is b. The algorithm by [10] requires (n3.5b2.5)1+o(1) fixed precision, that is, bit operations. Here and in the following we use the exponent "+o(1)" to capture missing polylogarithmic factors O((log n)C1(log b)C2), where C1, C2 are constants ("soft-O"). As it has turned out an algorithm in [15], which in turn is based on one by [31] and which uses the baby steps/giant steps algorithm design technique, can be adapted to the dense integer matrix determinant problem and then has bit complexity (n3.5b)1+o(1) [20, Section 2]. Both algorithms use randomization and the algorithm in [10] is Monte Carlo--always fast and probably correct--and the one in [20] is Las Vegas--always correct and probably fast. Both algorithms can be speeded by asymptotically fast subcubic matrix multiplication algorithms a la Strassen [8, 7, 14]. By blocking [6, 16, 29, 30] the baby steps/giant steps algorithm can be further improved, which yields the currently fastest known algorithms [20, Section 3] of bit complexity (n3+1/3b)1+o(1), that without subcubic matrix multiplication and without the FFT-based polynomial "half" GCD procedures a la Knuth [23; 2, Chapter 8], and of bit complexity n2.698b1+o(1) with subcubic matrix multiplication and FFT-based polynomial GCD procedures.
Clinical, Histopathologic, and Biologic Features of Pleomorphic Lobular (Ductal-Lobular) Carcinoma In Situ of the Breast: A Report of 24 Cases

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.
High-contrast plasma-electrode Pockels cell

A plasma-electrode Pockels cell (PEPC) has been developed for use on the OMEGA extended performance (EP) laser system that can be used in a high-contrast optical switch, as required for isolation of the system from retroreflected pulses. Contrast ratios reliably exceeded 500:1 locally everywhere in the clear aperture. The key to achieving this improvement was the use of circular windows simply supported on compliant O rings, which is shown to produce very low stress-induced birefringence despite vacuum loading. Reliable operation was achieved operating at a relatively high operating pressure, low operating pressures being found to be strongly correlated to occurrences of local loss of plasma density.
Late-life anxiety disorders among Puerto Rican primary care patients: impact on well-being, functioning, and service utilization.

Abstract With the growing population of older Hispanic adults there is a need for additional research on the mental health care of this patient group. This study explored the impact of anxiety disorders on the health status of 291 older (≥50 years) Puerto Rican primary care patients ( n =65 with anxiety disorders, n =226 without anxiety disorders). All analyses controlled for potential confounding variables, including depression diagnosis and physical health burden. Logistic regression indicated that anxiety disorders were associated with higher psychological distress, suicidality, and emergency room service utilization, as well as lower instrumental functioning and perceived health quality. Analysis of covariance indicated that both anxiety disorder status and history of ataque de nervios were related to higher percentages of lifetime somatic symptoms. These data highlight the need for improved recognition and treatment of anxiety disorders in older Puerto Rican adults.
Assessment of mitral valve E point-septal separation as an index of left ventricular performance in patients with acute and previous myocardial infarction

Abstract A new echocardiographic index of left ventricular function, mitral valve E point-septal separation, was compared with the radionuclide ejection fraction determined using the first pass method in 60 patients (73 studies) with ischemic heart disease. Thirty-eight patients had acute myocardial infarction and 22 patients were studied an average of 24 months after acute infarction. In 30 normal subjects, E point-septal separation ranged from 0 to 5.4 mm (average 1.3 mm). In 57 studies (78 percent) E point-septal separation correctly identified patients with a normal or reduced ejection fraction (less than 0.52), but in 13 studies (18 percent) E point-septal separation was normal and ejection fraction depressed. In only three studies (4 percent) was there a normal ejection fraction and an abnormal E point-septal separation. Results did not differ between patients with acute infarction and those studied late after infarction. An E point-septal separation of more than 5.5 mm was highly specific (92 percent) for a reduced ejection fraction, but the sensitivity rate was only 65 percent. Abnormal wall motion as assessed with echocardiography or videotracking, or both, occurred equally among patients with normal and increased E point-septal separation, but this measure was less accurate in patients with more severe wall motion abnormalities. E point-septal separation was unrelated to heart rate; an abnormal value was equally distributed among patients with a normal and those with an enlarged left ventricular end-diastolic dimension on echocardiography. E point-septal separation was superior to other echocardiographic indexes of left ventricular function (percent of fractional shortening, mean rate of diameter shortening and ejection fraction). Thus, E point-septal separation is a simple noninvasive measure of left ventricular function. We conclude that an abnormal E point-septal separation is useful for identifying depressed left ventricular function in patients with acute myocardial infarction and chronic ischemic heart disease. However, 28 percent of our patients with a normal E point-septal separation had a depressed radionuclide ejection fraction. Therefore a normal value for E point-septal separation does not exclude the presence of abnormal left ventricular function in such patients.
Partial characterization of human leukemia U-937 cell sublines resistant to 9-nitrocamptothecin.

: Human leukemia U-937 cell sublines exhibiting various levels of resistance to 9-nitrocamptothecin (9NC) were developed after exposure to progressively increased 9NC concentrations. Increases in 9NC resistance of the cells were accompanied by decreases in proliferation rate; appearance of morphological and functional features that correlate with granulocytic maturation; decreased synthesis of topoisomerase I; increased synthesis of topoisomerase II; and inability or decreased ability to induce tumors when xenografted in nude mice. 9NC-resistant cells, transferred and propagated in 9NC-free media for 6 months, continue to exhibit resistance and other features similar to cells propagated in continual presence of 9NC. Finally, 9NC-resistant U-937 cells respond to physiological and non-physiological agents of cell differentiation, indicating that alternative treatments can be successfully used to inhibit growth of 9NC-resistant U-937 cells and tumors.
Involvement of tobacco in alcoholism and illicit drug use.

Summary Survey data from the United States indicate that tobacco use is associated with the initiation of use of other addicting substances, and that increasing levels of tobacco use are associated with increasing levels of use of other psychoactive substances. Furthermore, factors affecting initiation, abstinence, and relapse to the use of tobacco, alcohol, and opioids are similar in nature. In addition, there are similarities in the addictive processes underlying the use of these substances. Taken together, these data suggest that tobacco use is involved, possibly more than by simple association, in the use of other substances containing psychoactive chemicals. In the present paper we discuss the involvement of tobacco in the use of alcohol, opioids, cocaine, and other substances, as well as some of the implications of these observations for researchers and clinicians. One such implication is that it may be possible to use tobacco and nicotine as models for phenomena of interest to other substance use researchers. For example, drug abuse treatment and prevention strategies could be explored using tobacco use as a target behavior, and biological phenomena such as the development of tolerance and physical dependence may be more readily studied with nicotine than with many other drugs. Certain pharmacologic differences across substances are also discussed in tight of their implications for development of treatment and drug control policies.
Determination of GL(3) Cusp Forms by Central Values of GL(3) × GL(2) L-functions

Let f be a self-dual Hecke-Maass cusp form for GL(3). We show that f is uniquely determined by central values of GL(2) twists of its L-function. More precisely, if g is another self-dual GL(3) Hecke-Maass cusp form such that for all holomorphic Hecke eigenforms for all k ≡ 0 (mod 4), then f = g.
A High Resolution Detection System for Positron Tomography

The feasibility of using a hybrid detection system, consisting of multiple narrow bismuth germanate (BGO) crystals coupled to one photomultiplier for coincidence timing, and individual mercuric iodide (HgI2) photodetectors coupled to each BGO crystal to identify crystals of interaction, was investigated for application to positron tomography. The match between the emission spectrum of BGO and the photoresponse spectrum of HgI2 in combination with recently developed HgI2 x-ray detector and low noise preamplifier technology provided the appropriate high sensitivity, low noise environment required to detect the low levels of scintillation light produced in the absorption of 511 keV gamma-rays in BGO. Energy resoluton of 24% for 511 keV was obtained with the BGO-HgI2 detector, compared to 18% for BGO with a PMT. Coincidence resolving time for the HgI2-BGO detector was measured to be 105 nanoseconds. This performance of a non-optimized detector system is nominally adequate for appropriately designed tomographs.
Aflibercept (VEGF Trap) in Inoperable Stage III or Stage IV Melanoma of Cutaneous or Uveal Origin

Purpose: Aflibercept is a soluble decoy VEGF receptor and angiogenesis inhibitor with potent preclinical antitumor activity in melanoma. We conducted a multicenter phase II study in patients with inoperable stage III or IV melanoma and no prior chemotherapy. Experimental Design: A two-stage design was adopted to evaluate 4-month progression-free survival rate (PFSR) and response rate. Aflibercept was given at 4 mg/kg intravenously every 2 weeks. Response was assessed every 8 weeks. First-stage accrual of 21 patients was specified and with an adequate 4-month PFSR accrual continued to a total of 41. Results: Forty-one patients of ages 23 to 84 (median = 57) were enrolled. Thirty-nine had American Joint Committee on Cancer stage IV (5 M1a, 7 M1b, and 27 M1c) and 2 had inoperable stage IIIC (N3). Eastern Cooperative Oncology Group (ECOG) performance status was 0 (27 patients) or 1 (14 patients). Ten patients had primary uveal melanoma, 28 cutaneous, and 3 had unknown primaries. A median of 7 cycles were initiated (range: 1–56). Grade 3 and 4 toxicities included hypertension in 9 patients (22%) and proteinuria in 6 (15%). Among 40 patients evaluable for efficacy (those who initiated aflibercept), 3 (7.5%) had a confirmed partial response and 20 had progression-free survival of 4 months or above. The predicted 1-year survival rate derived from the Korn meta-analysis model is 36% ( N = 39), whereas we observed a corresponding 56.4% survival rate at 1 year (95% CI, 43–74, P Conclusions: Aflibercept showed promising activity in patients with metastatic melanoma of cutaneous or uveal origin. Further evaluation of aflibercept as a single agent and in combination is warranted. Clin Cancer Res; 17(20); 6574–81. ©2011 AACR .
Echocardiographic Evaluation of Pulmonary Hypertension

Echocardiographic studies of the pulmonary valve were obtained in 63 adults. Patients with normal pulmonary artery pressure (22 cases) showed an oblique position of the valve images in diastole, slow valve opening slopes (≤ 300 mm/sec), sizable (> 2 mm) posterior displacement of the cusp echoes with atrial systole (`a' dip), and a relatively short right ventricular pre-ejection period. In contrast, pulmonary valves in pulmonary hypertension (mean pressure > 20 mm Hg, 41 cases) appeared straight in diastole with rapid opening slopes (> 350 mm/sec) and prolonged pre-ejection periods (P 40 mm Hg) when uncomplicated by severe right heart failure. In the latter instance rapid valve opening slopes were associated with large `a' dips. Echocardiography appears to ...
Size matters: molecular weight affects the efficiency of poly(ethylenimine) as a gene delivery vehicle.

Poly(ethylenimine) (PEI) samples of various molecular weights and pHs were used to transfect endothelial cells to achieve levels of gene expression for comparison. PEIs with nominal molecular weights of 600, 1200, 1800, 10,000, and 70,000 Da were examined at pHs of 5. 0, 6.0, 7.0, and 8.0, and the results were recorded in terms of transfection efficiencies at 24, 48, 68, 92, and 120 h post-transfection. Trials were performed on the human endothelial cell-derived cell line EA.hy 926. We found that, for the polymers tested, transfection efficiency increased as the molecular weight of PEI increased. Representative values of PEIs at pH 6 and molecular weight 70,000 produced average transfection efficiencies of 25.6 +/- 7.9% (n = 8) at the greatest average expression levels, while PEI of molecular weight 10,000 yielded efficiencies of only 11.4 +/- 1.7% (n = 6). Transfection efficiencies for molecular weight 1,800 PEI were essentially zero, and PEIs of lower molecular weights produced no transfection at all. In contrast, the pH of the PEI solutions had no discernible effect on transfection. Optimal expression of the green fluorescent protein reporter occurred between 2 and 3 days post-transfection. The amount of reporter expression also was noted, as determined by the brightness of fluorescing cells under UV. The data obtained demonstrate that the molecular weight of the PEI carrier has an effect on transfection efficiency while the pH of the PEI solutions prior to DNA complexation has no such effect.
Reliability Growth Modeling for In-service Electronic Systems Considering Latent Failure Modes

A latent failure mode is a type of failure that may not occur until the system has operated in the field for a certain period of time. Predicting latent failures is often difficult, but it has a great importance for reliability management in terms of system maintenance and warranty services. This paper proposes a stochastic model to predict the reliability growth for field or in-service electronic systems considering latent failures. The proposed model can be applied to electronics industries where extended in-house reliability testing cannot be implemented due to the tight design schedule. Based on the new method, the product management can proactively implement corrective actions against key failure modes using relevant engineering resources. A discussion between the effectiveness of corrective actions and the associated cost is also provided. Finally, field failure data collected from a fleet of automatic test equipment are used to demonstrate the applicability and performance of the model.
Organization of the hamster paraventricular hypothalamic nucleus

The hamster periventricular hypothalamic area has been the focus of functional research concerning photoperiodic time measurement. These studies have relied upon the extensive analysis of rat paraventricular nucleus because there has been a general absence of anatomical description in the hamster. The present work sought to remedy this problem by investigating the structure of the hamster paraventricular nucleus with respect to the localization of cells immunoreactive to vasopressin, oxytocin, or corticotropin-releasing factor and of cells projecting to the spinal cord or to vascular sites outside the blood-brain barrier. The hamster paraventricular nucleus includes the medial, lateral, and posterior magnocellular divisions, the main parvicellular division, as well as the periventricular area and dorsal cap, which are also parvicellular. The magnocellular divisions are characterized by many large neurons immunoreactive to oxytocin and vasopressin, which are generally absent from the parvicellular divisions. In contrast, corticotrophin-releasing hormone-immunoreactive cells are plentiful in most of the parvicellular areas. Spinally projecting cells are found in two rostral areas, one dorsally and a second, more ventral area. More caudally, the two regions merge within the posterior magnocellular division. Cells of the ventral group are frequently immunoreactive for one of the three peptides. Cells identified by peripheral injection of retrograde label are found in the rostral magnocellular divisions but not in the caudal posterior magnocellular division. Areas in which these cells also contain peptide are also described. The features of the hamster paraventricular nucleus are compared to those in the rat and apparent species differences are discussed.
'Social Partnership' not for Export

Sweden was once held up as a model welfare state for Britain to emulate. But Swedes are having doubts. Lately Austria has been offered as a model for the achievement of low unemployment and little inflation through wage regulation by incomes policy. An Austrian and a British observer appraise the argument with differing degrees of scepticism.
An Incomplete-Data Quasi-likelihood Approach to Haplotype-Based Genetic Association Studies on Related Individuals.

We propose an incomplete-data, quasi-likelihood framework for estimation and score tests that accommodates both dependent and partially observed data. The motivation comes from genetic association studies, where we address the problems of estimating haplotype frequencies and testing association between a disease and haplotypes of multiple, tightly linked genetic markers, using case-control samples containing related individuals. We consider a more general setting in which the complete data are dependent with marginal distributions following a generalized linear model. We form a vector, Z, whose elements are conditional expectations of the elements of the complete-data vector, given selected functions of the incomplete data. Assuming that the covariance matrix of Z is available, we create an optimal linear estimating function based on Z, which we solve by an iterative method. This approach addresses key difficulties in haplotype frequency estimation and testing problems in related individuals: (a) dependen...
Adaptation of injected thermoplasticized gutta-percha in the absence of the dentinal smear layer

The adaptation of thermoplasticized, injected gutta-percha to prepared dentine devoid of smear layer was examined with SEM. Findings indicate a penetration of gutta-percha into the patient dentinal tubules with or without root canal sealer. The clinical implications of these findings are discussed.
Thermal and structural analysis of the TPX divertor

The high heat flux on the surfaces of the TPX divertor will require a design in which a carbon-carbon (C-C) tile material is brazed to water cooled copper tubes. Thermal and structural analyses were performed to assist in the design selection of a divertor tile concept and C-C material. The relevancy of finite element analysis (FEA) for evaluating tile design was examined by conducting a literature survey to compare FEA stress results to subsequent brazing and thermal test results. The thermal responses for five tile concepts and four C-C materials were analyzed for a steady-state heat flux of 7.5 MW/m/sup 2/. Elastic-plastic stress analyses were performed to calculate the residual stresses due to brazing C-C tiles to soft copper heat sinks for the various tile designs. Monoblock and archblock divertor tile concepts were analyzed for residual stresses in which elevated temperature creep effects were included with the elastic-plastic behavior of the copper heat sink for an assumed braze cooldown cycle. As a result of these 2D studies, the archblock concept with a 3D fine weave C-C was initially found to be a preferred design for the divertor. A 3D elastic-plastic analysis for brazing of the arch block tile was performed to investigate the singularity effects at the C-C to copper interface in the direction of the tube axis. This analysis showed that the large residual stresses at the tube and tile edge intersection would produce cracks in the C-C and possible delamination along the braze interface. These results, coupled with the difficulties experienced in brazing archblocks for the Tore Supra limiter, required that other tile designs be considered. Recent developments at Tore Supra and JET have shown that a robust divertor design can be achieved by a macroblock concept. This concept utilizes a large C-C plate in which multiple coolant tubes are brazed or cast by processes that greatly minimize defects at the C-C/copper interface. Thermal analysis results for a 2D C-C macroblock concept incorporating two coaxial counterflow coolant tubes are presented.
The Preferments and ‘Adiutores’ of Robert Grosseteste

In many fields of activity Robert Grosseteste was an important figure in thirteenth-century England. Bishop of Lincoln for nearly two decades (1235–1253), he pursued a vigorous policy as statesman and churchman. He was already a distinguished teacher and chancellor of the University of Oxford. His voluminous writings were more acceptable to his contemporaries than those of any other author. His scientific achievements were such that Professor Sarton has styled a volume of his monumental History of Science, From Robert Grosseteste to Roger Bacon . In death his memory was revered as that of a saint.
Small molecule screening in context: Lipid-catalyzed amyloid formation

Islet Amyloid Polypeptide (IAPP) is a 37-residue hormone cosecreted with insulin by the β-cells of the pancreas. Amyloid fiber aggregation of IAPP has been correlated with the dysfunction and death of these cells in type II diabetics. The likely mechanisms by which IAPP gains toxic function include energy independent cell membrane penetration and induction of membrane depolarization. These processes have been correlated with solution biophysical observations of lipid bilayer catalyzed acceleration of amyloid formation. Although the relationship between amyloid formation and toxicity is poorly understood, the fact that conditions promoting one also favor the other suggests related membrane active structural states. Here, a novel high throughput screening protocol is described that capitalizes on this correlation to identify compounds that target membrane active species. Applied to a small library of 960 known bioactive compounds, we are able to report identification of 37 compounds of which 36 were not previously reported as active toward IAPP fiber formation. Several compounds tested in secondary cell viability assays also demonstrate cytoprotective effects. It is a general observation that peptide induced toxicity in several amyloid diseases (such as Alzhiemer’s and Parkinson’s) involves a membrane bound, preamyloid oligomeric species. Our data here suggest that a screening protocol based on lipid-catalyzed assembly will find mechanistically informative small molecule hits in this subclass of amyloid diseases.