cssi/SciSciGPT-SciSciNet huggingface dataset:
GPU-accelerated analysis and visualization of large structures solved by molecular dynamics flexible fitting

Hybrid structure fitting methods combine data from cryo-electron microscopy and X-ray crystallography with molecular dynamics simulations for the determination of all-atom structures of large biomolecular complexes. Evaluating the quality-of-fit obtained from hybrid fitting is computationally demanding, particularly in the context of a multiplicity of structural conformations that must be evaluated. Existing tools for quality-of-fit analysis and visualization have previously targeted small structures and are too slow to be used interactively for large biomolecular complexes of particular interest today such as viruses or for long molecular dynamics trajectories as they arise in protein folding. We present new data-parallel and GPU-accelerated algorithms for rapid interactive computation of quality-of-fit metrics linking all-atom structures and molecular dynamics trajectories to experimentally-determined density maps obtained from cryo-electron microscopy or X-ray crystallography. We evaluate the performance and accuracy of the new quality-of-fit analysis algorithms vis-a-vis existing tools, examine algorithm performance on GPU-accelerated desktop workstations and supercomputers, and describe new visualization techniques for results of hybrid structure fitting methods.
Using modeling to inform patient-centered care choices at the end of life

Aim: Advance directives are often under-informed due to a lack of diseasespecific prognostic information. Without well-informed advance directives patients may receive default care that is incongruent with their preferences. We aimed to further inform advance care planning in patients with severe chronic obstructive pulmonary disease by estimating outcomes with alternative advance directives. Methods: We designed a Markov microsimulation model estimating outcomes for patients choosing between the Full Code advance directive (permitting invasive mechanical ventilation), and the Do Not Intubate directive (only permitting noninvasive ventilation). Results: Our model estimates Full Code patients have marginally increased one-year survival after admission for severe respiratory failure, but are more likely to be residing in a nursing home and have frequent rehospitalizations for respiratory failure. Conclusion: Patients with severe chronic obstructive pulmonary disease may consider these potential tradeoffs between survival, rehospitalizations and institutionalization when making informed advance care plans and end-of-life decisions. We highlight outcomes research needs for variables most influential to the model’s outcomes, including the risk of complications of invasive mechanical ventilation and failing noninvasive mechanical ventilation.
Parsing and Translation of (Attributed) Expansive Graph Languages for Scene Analysis

In this paper, we suggest a class of (attributed) expansive graph grammars which generate languages contained in a graph family ?. It turns out that by means of node renumbering using a very effi-cient algorithm, any graph in ? can be converted into a standard form, which enables the use of related string representation for that graph to facilitate the syntax analysis. As a consequence, the syntax analysis of (attributed) expansive graph language is very efficient and almost like the parsing of tree languages. Furthermore, a syntax-directed transla-tion can be established for mapping one (attributed) expansive graph language to another. Finally, since many relational graphs for scene analysis can be considered as belonging to these graph languages, the proposed graph grammar model appears to be quite attractive from the application point of view.
Epinephrine delivery during neonatal resuscitation : Comparison of direct endotracheal tube vs catheter inserted into endotracheal tube administration

OBJECTIVES: The optimal method for epinephrine administration during neonatal resuscitation is not known. We hypothesized that epinephrine will be delivered more efficiently when administered via a feeding catheter inserted into the endotracheal tube (C-ETT) vs when administered directly into the ETT (D-ETT). Our objectives were to (1) compare the delivery of epinephrine to the distal end of the ETT when administered via D-ETT vs C-ETT; (2) measure the retention of epinephrine within the ETT vs the feeding catheter used for the drug delivery; and (3) compare the delivery of the drug with and without an air flush after administration via C-ETT. METHODS: All experiments were performed in vitro, simulating epinephrine administration during neonatal resuscitation, according to the standard guidelines. Radiolabeled epinephrine, diluted to 1 μCi/ml, was used and experiments were repeated at least 4 times. Epinephrine administration via D-ETT was followed by one manual breath via a self-inflating bag attached to the ETT. Epinephrine delivery via C-ETT was followed by 1 ml saline flush, and in some experiments, this was also followed by a 1 cm3 air flush. Epinephrine delivery and retention were assessed by measuring the radioactive content of the effluent fluid and that of the ETT or of the feeding catheter used for drug delivery. RESULTS: Significantly higher dosage of the drug was delivered when administered via D-ETT vs C-ETT, if air flush following C-ETT method was not used. However, with an air flush following the saline flush after the drug instillation, there was no difference in the amount of epinephrine delivered between the two methods. Retention in the ETT wall or the catheter was <7.5% of the administered dose with either method. CONCLUSIONS: Without an air flush following C-ETT method of epinephrine delivery, higher dosage of the drug is delivered via D-ETT vs C-ETT method. An air flush following the saline flush during C-ETT method improves drug delivery. Given that the C-ETT method is more cumbersome and time consuming, and does not improve drug delivery, D-ETT administration should be the method of choice for epinephrine delivery during neonatal resuscitation.
Ethnic dimensions in contemporary Latvian politics: Focusing forces for change

(1992). Ethnic dimensions in contemporary Latvian politics: Focusing forces for change. Soviet Studies: Vol. 44, No. 4, pp. 609-639.
Primary idiopathic hypothalamic hypothyroidism. Report of four cases.

Abstract One man and three women with hypothalamic hypothyroidism are described; they had isolated thyrotropin-releasing hormone deficiency, otherwise normal pituitary function, and no identifiable central nervous system anatomic abnormality. Serum thyrotropin levels were low and thyrotropic response to thyrotropin-releasing hormone was uniformly present, consistent with a hypothalamic cause of hypothyroidism. In two patients, hypothyroidism was transient and spontaneously resolved; in one of them, it was recurrent. Because hypothalamic hypothyroidism is miled and potentially reversible, it is suggested that such patients have follow-up evaluation before therapy is initiated in order to avoid unnecessary treatment.
Monocyte-plasmablast crosstalk during dengue.

Dengue virus infection induces a dramatic expansion of B cell plasmablasts. In this issue, Kwissa et al. (2014) begin with transcriptomic analysis and then integrate studies in human clinical samples, nonhuman primates, and coculture of primary human cells to identify a role for CD14+CD16+ monocytes in generating plasmablast responses during dengue virus infection.
Prostaglandin E2 and its antagonists: effects on autonomic transmission in the isolated sino-atrial node.

Abstract Prostaglandin E2 (PGE2) and its antagonists were tested for their effects on the chronotropic responses induced by electrical stimulation of autonomic nerve fibers in the isolated, spontaneously beating, rabbit sino-atrial node. PGE2 (8 × 10−7M) almost completely blocked positive chronotropic responses induced by stimulation of intrandal sympathetic fibers at low frequencies (2 – 5 Hz), while it had no effect at high frequencies of stimulation (20 – 100 Hz). Negative chronotropic responses induced by stimulation of intranodal parasympathetic fibers were only slightly and insignificantly reduced by PGE2 at low frequencies (2 – 20 Hz), and were increased at high frequencies (50 – 100 Hz). Three prostaglandin antagonists, polyphloretin phosphate (PPP), 7-oxa-13-prostynoic acid (EC-I-148) and 1-acetyl-2-(8-chloro-10,11-dihydrodibenz(b,f)(1,4)oxazepine-10-carbonyl) hydrazine (SC-19220), failed to antagonize the inhibitory effects of PGE2 on the chronotropic response induced by stimulation of intranodal fibers in the isolated sino-atrial node.
1538 GROWTH FAILURE DURING DEXAMETHASONE THERAPY IN PRETERM NEONATES

Recent reports suggest that steroid treatment may improve lung function in infants with chronic lung failure. Glucocorticoid therapy has many potential toxicities, including growth failure. Growth retarding effects have been reported with 200 mg/kg of cortisol. Suggested mechanisms include inhibition of cell mitosis, loss of thymic growth factor, and increased consumption of amino acids by liver. We have noted that growth cruves of ventilator dependent infants were flat during dexamethasone (D) therapy; we retrospectively evaluated 13 such infants 27±2 wks GA, 1057±251 gms b.wt. with chronic lung failure. Parenteral D was started at mean age of 6±2 wks at a dose of 1 mg/kg/day for 4 days and 0.5 mg/kg/day for 6 days. The mean weight of the infants the week prior to treatment was 1346 gms ± 474 and 1420 gm ± 464 at the time D was started. The median daily weight change (gms) prior to and during D therapy are plotted below. This pattern was not related to differences in mean fluid intake or output for the 2 periods. These preliminary data suggest that growth during D may be impaired. Further research is needed to determine if this is a transient or long term effect.
Activation of protein kinase C-mitogen-activated protein kinase signaling in response to inositol starvation triggers Sir2p-dependent telomeric silencing in yeast.

Depriving wild type yeast of inositol, a soluble precursor for phospholipid, phosphoinositide, and complex sphingolipid synthesis, activates the protein kinase C (PKC)-MAPK signaling pathway, which plays a key role in the activation of NAD+-dependent telomeric silencing. We now report that triggering PKC-MAPK signaling by inositol deprivation or by blocking inositol-containing sphingolipid synthesis with aureobasidin A results in increased telomeric silencing regulated by the MAPK, Slt2p, and the NAD+-dependent deacetylase, Sir2p. Consistent with the dependence on NAD+ in Sir2p-regulated silencing, we found that inositol depletion induces the expression of BNA2, which is required for the de novo synthesis of NAD+. Moreover, telomeric silencing is greatly reduced in bna2Δ and npt1Δ mutants, which are defective in de novo and salvage pathways for NAD+ synthesis, respectively. Surprisingly, however, omitting nicotinic acid from the growth medium, which reduces cellular NAD+ levels, leads to increased telomeric silencing in the absence of inositol and/or at high temperature. This increase in telomeric silencing in response to inositol starvation is correlated to chronological life span extension but is Sir2p-independent. We conclude that activation of the PKC-MAPK signaling by interruption of inositol sphingolipid synthesis leads to increased Sir2p-dependent silencing and is dependent upon the de novo and salvage pathways for NAD+ synthesis but is not correlated with cellular NAD+ levels. Background: Inhibition of complex sphingolipid synthesis by inositol starvation activates the PKC-MAPK signaling pathway. Results: Sir2p-dependent telomeric silencing is activated by interrupting sphingolipid synthesis and requires the MAPK, Slt2p. Conclusion: Telomeric silencing is regulated by PKC-MAPK signaling in response to interruption of sphingolipid synthesis. Significance: Sphingolipid metabolism plays an important role in regulating silencing and chronological life span.
Hemodynamic consequences of afterload reduction in patients with valvular abnormalities

Abstract Ten patients with mitral insufficiency, eight patients with aortic insufficiency and eight patients with mitral stenosis were studied by right- and left-heart catheterization. Hemodynamic observations were made during a control period and during the infusion of phentolamine at a rate of 0.3 mg/min. The patients with mitral insufficiency and aortic insufficiency responded to phentolamine with a significant decline in the right and left ventricular filling pressures, pulmonary-artery mean pressure, peripheral resistance and arteriovenous oxygen difference. A significant increase in the cardiac index was seen in both groups. The patients with mitral stenosis did not show any hemodynamic improvement with the phentolamine infusion.
Determination of Dopa in Pharmaceutical Dosage Forms Based on Oxidation at Tubular Carbon Electrode

Abstract: A method for the determination of dopa [3-(3,4-di-hydroxyphenyl)alanine] in pharmaceutical dosage forms based on electrochemical oxidation at the tubular carbon electrode is presented. A comparison with a colorimetric method shows this new method to be considerably faster and simpler without a significant loss in precision or accuracy. Between 25 and 30 samples may be determined each hour, for which the variance due to the method results in a standard deviation no greater than ± 0.9%.
Mechanical properties of metal hydrides

Abstract The role of metal hydrides in the hydrogen embrittlement of a number of metal-hydrogen systems is reviewed. The stress-induced formation and cleavage of hydrides at crack tips and the thermodynamics of the hydrides in the stress field of the crack tip are discussed. The mechanical response of the hydrides to applied stresses is described. Many of the hydrides exhibit some plastic deformation under favorable stress systems with the amount of this deformation increasing as the temperature of testing is increased. Phonon properties and the elastic moduli of the hydrides are briefly discussed and it is suggested that these parameters do not provide a basis for understanding the mechanical properties of the hydrides. The deformation response of the hydrides is consistent with the expected behavior of dislocations in the ordered hydride structures.
Enzymatic conversion of vitamin B12a to adenosyl-B12: Evidence for the existence of two separate reducing systems

Abstract The reduction of vitamin B 12 a , (Co III ) to B 12 s (Co I ) appears to be carried out by two separate enzyme systems in extracts of Clostridium tetanomorphum . The reduction of B 12 a to B 12 r (Co II ) occurs at a relatively rapid rate and is catalyzed by a DPNH-dependent flavoprotein (B 12 a reductase) that utilizes PAD better than FMN. Trapping experiments suggest that B 12 a is not an intermediate in this reaction. The reduction of B 12 r to B 12 s , a reaction characterized by an unfavorable equilibrium, requires a second DPNH-dependent flavoprotein (B 12 r reductase) that is stimulated equally well by FAD or FMN. In addition to their different responses to added flavins, these systems are also distinguished by other characteristics: ( a ) B 12 a reductase is considerably more labile than the B 12 r reductase; and ( b ) Dithioerythritol can replace DPNH as the reductant for the B 12 r reductase but not for the B 12 a reductase.
Polymerization of Vinylpyridinium Salts. XI. Charge-Transfer Polymerization of 4-Vinylpyridinium p-Styrenesulfonate

Abstract The spontaneous polymerization of 4-vinylpyridinium p-styrene-sulfonate or 4-vinylpyridinium chloride with sodium p-styrenesuifonate or of 4-vinylpyridinium 2-acrylamido-2-methylpro-panesulfonate with sodium p-styrenesuifonate produces an amphoteric, equimolar copolymer. An UV study on the interaction between 4-vinylpyridinium chloride and sodium p-styrenesulfonate indicates an absorption maximum corresponding to 1:1 charge transfer complex. From the observed results, a charge-transfer polymerization of 4-vinylpyridinium salts with electron-donating monomers is elucidated.
Re-entrant solidification in polymer–colloid mixtures as a consequence of competing entropic and enthalpic attractions

In polymer-colloid mixtures, non-adsorbing polymers dispersed with much larger colloids provide a universal yet specific entropic attraction between the colloids. Such so-called depletion interaction arises from an osmotic-pressure imbalance caused by the polymers and is considered to be independent of temperature. Here we show that, for the most commonly used polymer-colloid depletion systems, the polymer undergoes a crossover from non-adsorbing to adsorbing and that, consequently, the effective colloidal interactions depend on temperature. We also find that a combination of the enthalpic (polymer bridging) and entropic (polymer exclusion) interactions, both attractive, leads to a re-entrant regime where the colloids are dispersed and form solids both on heating and on cooling. We provide a simple model to explain the observed transitions and to fill the theoretical gap at the polymer-adsorption crossover. Our findings open possibilities for colloidal self-assembly, the formation of colloidal crystals and glasses, and the behaviour of temperature-controlled viscoelastic materials.
Comparative growth rates and oxygen consumption in young Galliformes

Abstract 1. 1. The high correlation between growth rate and adult body weight has been much more thoroughly documented for altricial birds than for precocial species. 2. 2. This paper gathers data from the literature for precocial Galliformes and also reports new growth data on six galliform species for analysis. 3. 3. The onset of homeothermic ability is investigated in Galliformes over a range of body size. 4. 4. The results confirm that (1) large species' chicks grow at a slower rate than those of smaller species, and (2) larger species' chicks can thermoregulate earlier than smaller species' chicks under cold stress situations. 5. 5. Published embryonic body weights are also analysed to determine when growth rate differences appear in the development of precocial species. 6. 6. No interspecific differences appeared in the relative growth rates of embryos, and therefore species body size does not appear to influence growth rate before hatching.
Further evidence of an inverse genetic relationship between innate differences in alcohol preference and alcohol withdrawal magnitude in multiple selectively bred rat lines.

Background: We have previously shown that a genetic association exists between low alcohol drinking and high alcohol withdrawal magnitude after acute alcohol exposure in alcohol-naive rats. However, the behavioral rating scale used in this prior study was not optimal for assessing the magnitude of mild alcohol withdrawal. The present study examined whether a genetic relationship is again found between alcohol preference and alcohol withdrawal magnitude when a sensitive measure is used to index mild alcohol withdrawal in rats. Methods: Alcohol-naive, male rats selectively bred for alcohol preference (P, HAD1, HAD2) or nonpreference (NP, LAD1, LAD2) received a single intragastric infusion of alcohol (4.0 g/20.3 ml/kg body weight; 25% v/v) or water followed by acoustic startle testing. Results: Startle probability and magnitude was greater in water-treated P than in water-treated NP rats. During alcohol withdrawal, startle probability and magnitude was suppressed in P rats and elevated in NP rats relative to water-treated controls. Startle probability and magnitude was greater in water-treated LAD1 rats than in water-treated HAD1 rats. During alcohol withdrawal, startle probability and magnitude was suppressed in HAD1 and elevated in LAD1 rats relative to water-treated controls at 20 hr after acute alcohol exposure. Startle probability and magnitude did not differ between water-treated HAD2 and water-treated LAD2 rats. During alcohol withdrawal, there was a trend toward decreased startle probability and magnitude in HAD2 rats compared with water-treated controls. Conclusions: The acoustic startle response to a tone stimulus is a sensitive measure of mild alcohol withdrawal in rats. Rats selectively bred for low alcohol intake showed greater alcohol withdrawal magnitude than did rats selectively bred for high alcohol intake. These results provide further evidence that an inverse genetic association exists between alcohol withdrawal magnitude and propensity toward alcohol drinking in rats.
Transcriptional responses of tolerant and susceptible soybeans to soybean aphid (Aphis glycines Matsumura) herbivory

The soybean aphid, Aphis glycines Matsumura, was introduced in 2000 to North America and has become one of the most significant pests to soybean, Glycine max (L.) Merrill, production. Possible solutions to this problem are the use of resistant plants and the understanding of the genes involved in plant resistance. In this study, we sought to better understand the genes involved in the tolerance response of soybean plants to the soybean aphid, utilizing tolerant (KS4202) and susceptible (K-03-4686) plants. Studies were conducted under greenhouse conditions. Leaf samples of both tolerant and susceptible plants were collected at day 5 and day 15 after infestation and analyzed by sequencing-by-synthesis on an Illumina GA II X instrument. In the tolerant genotype, 3 and 36 genes were found to be differentially expressed in the infested plants compared to the control treatments at day 5 and day 15, respectively. A similar comparison in the susceptible genotype revealed 0 and 11 genes to be differentially expressed at day 5 and day 15, respectively. Predominately, genes related to plant defense, such as WRKY transcription factors, peroxidases, and cytochrome p450s, were up-regulated in the tolerant genotype 15 days post-infestation by aphids. In contrast, none of these genes were similarly up-regulated in the susceptible plants, suggesting that consistent elevation of defense responses is important to plant tolerance. However, significant genotypic differences in global gene expression were also found when transcriptomes from control uninfested plants were compared at both day 5 and 15. qPCR validation of select genes confirmed our RNA-seq data. These comparisons indicate that potentially broader regulation of transcriptomes also contributes to the tolerance response and provides data that the tolerant genotype (KS4202) could be useful in soybean breeding programs trying to minimize production losses accruing from soybean aphid feeding.
Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4 + T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.
Graphical Approach to Model Reduction for Nonlinear Biochemical Networks

Model reduction is a central challenge to the development and analysis of multiscale physiology models. Advances in model reduction are needed not only for computational feasibility but also for obtaining conceptual insights from complex systems. Here, we introduce an intuitive graphical approach to model reduction based on phase plane analysis. Timescale separation is identified by the degree of hysteresis observed in phase-loops, which guides a "concentration-clamp" procedure for estimating explicit algebraic relationships between species equilibrating on fast timescales. The primary advantages of this approach over Jacobian-based timescale decomposition are that: 1) it incorporates nonlinear system dynamics, and 2) it can be easily visualized, even directly from experimental data. We tested this graphical model reduction approach using a 25-variable model of cardiac β(1)-adrenergic signaling, obtaining 6- and 4-variable reduced models that retain good predictive capabilities even in response to new perturbations. These 6 signaling species appear to be optimal "kinetic biomarkers" of the overall β(1)-adrenergic pathway. The 6-variable reduced model is well suited for integration into multiscale models of heart function, and more generally, this graphical model reduction approach is readily applicable to a variety of other complex biological systems.
A literature review of indirect costs associated with stroke.

Background Stroke is a leading cause of mortality and long-term disability. However, the indirect costs of stroke, such as productivity loss and costs of informal care, have not been well studied. To better understand this, we conducted a literature review of the indirect costs of stroke. Methods A literature search using PubMed, MEDLINE, and EconLit, with the key words stroke, cerebrovascular disease, subarachnoid hemorrhage, intracerebral hemorrhage, cost-of-illness, productivity loss, indirect cost, economic burden, and informal caregiving was conducted. We identified original research articles published during 1990-2012 in English-language peer-reviewed journals. We summarized indirect costs by study type, cost categories, and study settings. Results We found 31 original research articles that investigated the indirect cost of stroke. Six of these investigated indirect costs only; the other 25 studies were cost-of-illness studies that included indirect costs as a component. Of the 31 articles, 6 examined indirect costs in the United States, with 2 of these focused solely on indirect costs. Because of diverse methods, kinds of data, and definitions of cost used in the studies, the literature indicated a very wide range internationally in the proportion of the total cost of stroke that is represented by indirect costs (from 3% to 71%). Conclusions Most of the literature indicates that indirect costs account for a significant portion of the economic burden of stroke, and there is a pressing need to develop proper approaches to analyze these costs and to make better use of relevant data sources for such studies or establish new ones.
Coup-TFII is up-regulated in adenovirus type 12 tumorigenic cells and is a repressor of MHC class I transcription.

Abstract Down-regulation of the MHC class I enhancer in tumorigenic Ad12 cells is associated with strong binding of COUP-TF and negligible binding of activator NF-κB. By comparison, in nontumorigenic Ad5 cells, class I expression is high due to negligible binding of COUP-TF and strong binding of NF-κB. Here, we show that COUP-TFII, but not COUP-TFI, is expressed in Ad12-transformed cells. The dramatically stronger DNA binding of COUP-TFII to the class I enhancer in Ad12- compared to Ad5-transformed cells correlates with higher COUP-TFII promoter activity and higher levels of COUP-TFII mRNA and protein. Significantly, NF-κB p50/p52 double-knockout cells enabled us to demonstrate directly that COUP-TFII can completely repress both nonactivated and NF-κB-activated MHC class I transcription.
A Dynamic Spatial Analysis of Changes in Aesthetic Responses

Models of evaluative judgment in applied aesthetics generally assume that movements of objects' positions in a multidimensional perceptual space will produce corresponding changes in preferences. However, such spatial representations have usually been tested using static designs or, at best, longitudinal studies that fail to tie perceptual movements to shifts in affective response. This study reports what we believe to be a first dynamic analysis of changes in aesthetic responses. Specifically, twenty-nine aesthetically naive subjects supplied perceptual and affective ratings of twenty art prints on four occasions spaced a week apart. Multiple discriminant analysis (MDA) of the perception data created an MDA space representing each person's perceptions of each print at the beginning and end of the period. We then constructed each individual's preference function based on the MDA space, used beginning and ending perceived positions to compute changes in that preference function, regarded these as predictio...
Microscopic properties of H2 in Si from the dependence of the 3618.4cm−1 line on temperature and stress

Abstract The dependence of the 3618.4 cm −1 line assigned to interstitial H 2 in Si on temperature and stress has been studied to probe the structure and microscopic properties of this defect. The H 2 (and D 2 ) stretching lines broaden and shift to lower frequency with increasing temperature while the integrated intensity remains approximately constant. Uniaxial stress results are consistent with triclinic (C 1 ) symmetry and suggest a near 〈1 0 0〉 orientation for the H 2 molecular axis.
Causes of damage to brachiopods from the Middle Pennsylvanian Naco Formation, central Arizona

The Kohl Ranch locality in the Naco Formation of central Arizona has yielded an abundant and diverse fauna including eight genera of brachiopods and four of sharks including Cochliodus. The most abundant brachiopod, Composita subtilita, was analyzed for predation damage and of 935 specimens 503 (53.7%) were found to show the type of unrepaired crushing previously attributed to shark predation. Reconstruction of the jaw of Cochliodus, however, suggests that it may have been a selective feeder similar to the modern Heterodontus and unlikely therefore to have left so many damaged but uningested specimens. Evidence from specimens collected in situ suggests that the damage mostly occurred post-mortem due to the compaction of the sediments and was not due to the sharks who would have comminuted any prey items taken.
A quantitative analysis of tension band plating of the femur diaphysis.

To measure quantitatively the strains in the concave and convex sides of a femur to substantiate the Arbeitsgemeinschaft fur Osteosynthesefragen (AO) tension band principle. Eight cadaveric fresh-frozen femurs were cleaned of soft tissue and prepared for mounting the strain gages (Vishay, Raleigh, NC). The student strain gages were mounted at the anterior, lateral and medial surfaces of a femur. They were loaded at 100, 250, 500, 1,000 and 1,500 N axial forces in a mechanical testing machine (Instron Model 4202, Norwood, MA) and the micro strains were measured for intact and after fixation of a simulated fracture by an eight hole broad 4.5 mm stainless steel compression plate (Synthes LCP). In order to simulate the fracture conditions, where all eight screw holes might not be filled, three different arrangements were tested: 8 screws, 4 screws and 2 screws. The microstrains under different loads were analyzed by Analysis of Variance (ANOVA) with Holm-Sidak multiple comparison method. At the same gage location micro strains were not significantly different between the intact, and the femur fixated by 8, 4 and 2 screws. For intact bones at 1,500 N the strain ratio between the tension to compression sides was −0.21 proximally and −0.04 distally. The comparison of these strain ratios at different loads did not show any significant differences at p = 0.05 and power of 0.8. The data showed a trend validating the tension band principle as tensile strains lowered and compressive strains increased after placement of the plate.
Personal and Situational Determinants of Referent Choice

This review examines the personal and situational variables that influence an individual's choice of comparative referent. Earlier models (Goodman, 1974; Levine & Moreland, 1987) are considered, which predict referent choice based on the availability of referent information and the relevance of the referent. These models are then expanded to consider situational and personal variables that may influence availability and relevance. Hypotheses detailing the effects of these personal and situational variables on referent choice are presented, and the potential impact of these choices for organizations is explored.
Cancer Therapy with a Replicating Oncolytic Adenovirus Targeting the Hypoxic Microenvironment of Tumors

Hypoxia plays a critical role in driving tumor malignancy and is associated with poor patient survival in many human cancers. Novel therapies targeting hypoxic tumor cells are urgently needed, because these cells hinder tumor eradication. Here we demonstrate than an anticancer strategy based on intratumoral delivery of a novel type of oncolytic adenovirus targeting tumor hypoxia is therapeutically efficient and can augment standard chemotherapy. We used a conditionally replicative adenovirus (HYPR-Ad) to specifically kill hypoxic tumor cells. Viral infection and conditional replication occurred efficiently in hypoxic/hypoxia-inducible factor-active cells in culture and in vivo, prevented tumor formation, and reduced the growth of established tumors. Combining HYPR-Ad with chemotherapy effective against normoxic cells resulted in strongly enhanced antitumor efficacy. These studies demonstrate that targeting the hypoxic microenvironment of tumors rather than an intrinsic gene expression defect is a viable and novel antitumor therapeutic strategy that can be used in combination with existing treatment regimens. The replication and oncolytic potential of this virus was made dependent on hypoxic/hypoxia-inducible factor, a transcription factor activated in the tumor hypoxic microenvironment, broadening its therapeutic use to solid tumors of any genetic make-up or tissue of origin.
Forskolin induces preproenkephalin and preprodynorphin mRNA in rat striatum as demonstrated by in situ hybridization histochemistry.

Cyclase response elements (CREs) are located in the promoter regions of several neuropeptide and immediate early genes. Activation of the adenylate cyclase/ cAMP second messenger cascade leads to phosphorylation of CRE-binding proteins (PCREBs) which bind to CREs in the promoter region of these genes and alter their rate of transcription. We have previously reported an increase in striatal immunoreactivity for P-CREB (phosphorylated on Ser-133) and Fos following intracerebroventricular (ICV) injection of H2O-soluble forskolin, a direct activator of adenylate cyclase. Because CREs are located in the promoter regions of the opioid peptide genes, preproenkephalin (PPE) and preprodynorphin (PPD), we investigated what effect continuous ICV infusion of H2O-soluble forskolin has on striatal PPE and PPD mRNA levels. Quantitative in situ hybridization histochemistry demonstrated that continuous activation of the adenylate cyclase/cAMP second messenger cascade results in a significant induction of striatal PPE and PPD mRNA at 6, 24, and 72 h. The sustained induction of striatal PPE and PPD mRNA indicates that pro-opioid gene transcription is not desensitized following 72 h of continuous adenylate cyclase activation. Continuous ICV infusion of 1,9-dideoxyforskolin, a forskolin analog which does not activate adenylate cyclase, did not induce striatal PPE and PPD mRNA. These data are consistent with cAMP-dependent protein kinaseinduced phosphorylation and binding of CREBs to CREs in the promoter regions of pro-opioid genes during sustained activation of adenylate cyclase. © 1995 Wiley-Liss, Inc.
Tri-gate bulk CMOS technology for improved SRAM scalability

A simple approach for manufacturing quasi-planar tri-gate bulk MOSFET structures is demonstrated and shown to be effective for reducing variation in 6T-SRAM read and write margins, in an early 28nm CMOS technology. With optimization of the pocket implant doses, quasi-planar bulk CMOS technology can facilitate voltage scaling. It also provides a means to achieve high yield with a notch-less 6T-SRAM cell layout, to facilitate area scaling.
An application of goal programming technique in metal cutting

This paper outlines the use of the goal programming technique in selecting levels of machining parameters in a fine turning operation on A1S1 4140 steel using cemented tungsten carbide tools. Goals that are proposed to be achieved are: (i) to finish turning the required depth in one pass, mid (ii) to finish turning within a stipulated time. Constraints used are: R.M.S. surface finish values, cutting horse power of the machine, ranges for cutting speed, feed and depth of cut. A predictive equation to predict the R.M.S. Surface roughness values from the machining variables, cutting speed, feed, depth of cut, and time of cut was used. This mathematical model was developed using stepwise regression analysis on the experimental data for 1/64 in. nose radius cemented tungsten carbide cutting tool. Experiment with the machining variables at different levels were performed to obtain the data. A statistically designed experiment called the rotatable design was used for the experimental design
Are Newcomb problems really decisions

Richard Jeffrey long held that decision theory should be formulated without recourse to explicitly causal notions. Newcomb problems stand out as putative counterexamples to this ‘evidential’ decision theory. Jeffrey initially sought to defuse Newcomb problems via recourse to the doctrine of ratificationism, but later came to see this as problematic. We will see that Jeffrey’s worries about ratificationism were not compelling, but that valid ratificationist arguments implicitly presuppose causal decision theory. In later work, Jeffrey argued that Newcomb problems are not decisions at all because agents who face them possess so much evidence about correlations between their actions and states of the world that they are unable to regard their deliberate choices as causes of outcomes, and so cannot see themselves as making free choices. Jeffrey’s reasoning goes wrong because it fails to recognize that an agent’s beliefs about her immediately available acts are so closely tied to the immediate causes of these actions that she can create evidence that outweighs any antecedent correlations between acts and states. Once we recognize that deliberating agents are free to believe what they want about their own actions, it will be clear that Newcomb problems are indeed counterexamples to evidential decision theory.
A Cash Flow Model of Rational Housing Tenure Choice

This paper develops a model of housing costs in a cash flow framework. The cash flow approach allows both the consumption and investment aspects of tenure choice to be analyzed. By solving the model for the rental flow equivalent to any owning situation, we can determine whether or not a household would buy or rent from an economic perspective. The results are very sensitive to the household's income, the expected duration of occupancy, the mortgage interest rate, and inflation expectations. The results suggest that “rule-of-thumb” generalizations about tenure choice are often ill-founded, and that studies of tenure choice need to explicitly consider the interaction of income, taxes, length of occupancy and expectations.
Miniprobe transducer for tissue characterization

A design for PVDF transducers in which ultrasound transducers are fabricated at the tips of calipers (analog and digital) as miniprobes is proposed. A goal was to design a miniprobe transducer that is convenient to use during surgical operation. This probe will be able to estimate the speed and attenuation of sound, as well as backscattering from small regions. Measurement techniques for this purpose are suggested. Several prototype ultrasonic miniprobes are presented and discussed. The feasibility of this miniprobe was verified by using measurements of liquids and phantoms. The proposed technique will provide in vivo data, which is of major importance in the evaluation of tissue characterization. Measuring tissue properties in vivo is highly desirable to obviate concerns about changes of tissue properties following blood stains and coagulation, autolysis, temperature change, or fixation. >
A probabilistic mispointing analysis for land mobile satellite communications systems with directive antennas

A probabilistic analysis of the antenna mispointing phenomenon observed in many land mobile satellite communications systems is presented. Specifically, the PDF of the total mispointing error is derived under the assumption of Gaussian distributed azimuth and elevation mispointing. Both equal and unequal variances with respect to azimuth and elevation mispointing are considered. Moreover, the effect of mispointing on average bit error rate is also determined analytically. The analysis is applicable to a wide range of pointing systems and antenna types.
Concurrent application of tretinoin (retinoic acid) partially protects against corticosteroid-induced epidermal atrophy

Summary Cutaneous atrophy arising from prolonged use of potent topical corticosteroids has long been a concern. Thus, it would be advantageous to find an agent which protects against atrophy produced by corticosteroids but at the same time does not impair their anti-inflammatory effects. Recent work shows that topical all-trans retinoic acid (tretinoin) prevents skin atrophy in mice treated with topical corticosteroids, but such studies have not been performed in humans. We performed an 8-week clinical, histological and biochemical study to test the ability of tretinoin to enhance efficacy and inhibit atrophogenicity of topical corticosteroids, when used in the treatment of psoriasis. In each of 20 psoriasis patients, one plaque, and its perilesional skin, was treated once daily with betamethasone dipropionate and tretinoin 0·1%, and one plaque, and its perilesional skin, treated with once daily betamethasone dipropionate and tretinoin vehicle. There was no difference in the speed or degree of improvement in plaques treated with either the topical corticosteroid/tretinoin combination or with corticosteroid alone. Light microscopy revealed a 19% reduction in epidermal thickness, in corticosteroid-treated perilesional skin, as compared with a slight (1%) increase in corticosteroid/ tretinoin-treated perilesional areas (P= 0.067). Western blot analysis showed a 55% reduction in procollagen I aminopropeptide in perilesional skin treated with corticosteroid alone, as compared with a 45% reduction in corticosteroid/tretinoin-treated perilesional skin. These data indicate that the addition of tretinoin does not impair the efficacy of a topical corticosteroid, in the treatment of psoriasis, and partially ameliorates epidermal atrophy produced by the topical corticosteroid.
Unadjusted Differences: They Won't Just Affect Auditors

Recent changes mean heavier responsibilities for auditors of public companies' financial statements. But will they also mean new headaches for top management and audit committees? © 2001 John Wiley & Sons, Inc.
DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling

DNA methylation is a major epigenetic factor that has been postulated to regulate cell lineage differentiation. We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation. The developmentally regulated demethylation of astrocyte marker genes as well as genes encoding the crucial components of the gliogenic JAK-STAT pathway is accelerated in Dnmt1 –/– NPCs. Through a chromatin remodeling process, demethylation of genes in the JAK-STAT pathway leads to an enhanced activation of STATs, which in turn triggers astrocyte differentiation. Our study suggests that during the neurogenic period, DNA methylation inhibits not only astroglial marker genes but also genes that are essential for JAK-STAT signaling. Thus, demethylation of these two groups of genes and subsequent elevation of STAT activity are key mechanisms that control the timing and magnitude of astroglial differentiation.
Estimating Jakes' Doppler power spectrum parameters using the whittle approximation

We derive methods for asymptotic maximum likelihood (ML) estimation of Jakes' Doppler power spectrum parameters from complex noisy estimates of the fading channel. We consider both single-input single-output (SISO) and smart-antenna scenarios and utilize the Whittle approximation to the likelihood to estimate the Doppler spread, noise variance, and channel covariance parameters. Asymptotic Crame/spl acute/r-Rao bounds (CRBs) for the unknown parameters are derived. We also discuss the initialization of the proposed methods and their generalization to the Ricean-fading scenario. Numerical simulations demonstrate the performance of the proposed methods.
OSSICULAR SCULPTING FOR CONDUCTIVE HEARING LOSS

Abstract Although declining in popularity, autograft bone and cartilage provide the surgeon with a predictable and well-established option for ossicular reconstruction. This article reviews the indications, advantages, techniques, and complications of sculpted autograft ossiculoplasty. Reconstructive procedures using bone and cartilage grafts are illustrated.
A revision of Martin's seed classification system, with particular reference to his dwarf-seed type

Martin's (1946) seed classification system has 10 types based on embryo and endosperm characteristics and two additional types based on seed size: dwarf (0.3–2.0 mm) and micro ( ≤ 0.2 mm). He listed 17 families and 12 genera (in five other families) as having dwarf seeds. Our recent discovery of morphophysiological dormancy in dwarf seeds of several taxa of Campanulaceae and one of Gentianaceae prompted an evaluation of dwarf seeds. Martin's paper contains 37 families with one to several small (0.3–2.0 mm) seeded species that he did not list as being dwarf. Comparison of Martin's dwarf families and the 37 small-seeded non-dwarf families revealed no consistent differences between the two groups in endosperm texture, seed-coat anatomy, embryo morphology, class of seed dormancy or phylogenetic position. Also, Martin's dwarf seeds include a variety of embryo morphologies. Consequently, we have revised Martin's key to seed types. The dwarf category has been removed and the micro category replaced by ‘undifferentiated’ to reflect the state of the embryo in fresh seeds. Further, the key now includes linear fully developed, linear underdeveloped, spatulate fully developed and spatulate underdeveloped seed types, which Martin illustrated but did not include in his key. In the revised key, all seeds are distinguished on the basis of embryo and endosperm characteristics.
Treaty Compliance and Violation

International law has enjoyed a recent renaissance as an important subfield of study within international relations. Two trends are evident in the recent literature. First, the obsession with theoretical labels is on the decline. Second, empirical, especially quantitative, work is burgeoning. This article reviews the literature in four issues areas—security, war, and peace; international trade; protection of the environment; and human rights—and concludes we have a much stronger basis for assessing claims about compliance and violation now than was the case only a few years ago. Still, the literature suffers from a few weaknesses, including problems of selection and endogeneity of treaties themselves and an enduring state-centric focus, despite the fact that researchers recognize that nonstate and substate actors influence treaty behavior. Nonetheless, the quality and quantity of new work demonstrates that international law has regained an important place in the study of international politics.