cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of the herpes simplex virus thymidine kinase gene transfection in Ltk- cells by potential Z-DNA forming polymers

It has been demonstrated that certain alternating purine and pyrimidine sequences may assume a left-handed Z-DNA conformation. In order to evaluate the possibility that Z-DNA is involved in the modulation of gene expression, we examined the ability of various synthetic DNA polymers to affect the transfection of herpes simplex virus thymidine kinase (HSVtk) gene in Ltk- cells using the DNA-calcium phosphate cotransfection technique. We found that potential Z-DNA forming polymers such as, poly(dG-m5dC) X poly(dG-m5dC) and poly(dG-dC) X poly(dG-dC), cotransfected with the tk gene decreased the level of Tk+ transformed colonies. In contrast, cotransfection of the tk gene with polymers which do not assume Z-conformation such as, poly(dG) X poly(dC) or poly(dA-dT) X poly(dA-dT) showed no effect on the number of colonies formed. About 50% inhibition of the Tk+ colony formation was obtained by 0.4 micrograms of poly(dG-m5dC) X poly(dG-m5dC), or by 2 micrograms of poly(dG-dC) X poly(dG-dC). DNA uptake into Ltk- cells was not significantly affected by any of these polymers. Approximately 20-42 base pairs (bp) long alternating dG-dC sequence linked at either the 5'-end or 3'-end of tk gene were cloned into plasmids. These recombinant plasmids, however, showed no remarkable effect upon the transfection of Ltk- cells. The DNAs of Tk+ colonies obtained by transfecting these recombinant plasmids were digested with BssH II and analyzed by Southern blotting. We demonstrated that the dG-dC sequences proximal to the tk gene were integrated into cellular DNA. All the presented results indicate that only larger polymers with the potential to assume a Z-DNA conformation may affect tk gene transfection either by inhibiting transcription or more probably by affecting the stable integration of the tk gene into the host chromosome.
Evidence from pulse-chase labeling studies that the antiglucocorticoid hormone RU486 stabilizes the nonactivated form of the glucocorticoid receptor in mouse lymphoma cells

Abstract A pulse-chase labeling technique was used to determine the properties of glucocorticoid receptors occupied by the antiglucocorticoid hormone RU486 in S49.1 mouse lymphoma cells. Cells were pulse-labeled with [35S]methionine and then at the beginning of the chase, either no hormone (control), dexamethasone, or RU486 was added to cells. At 4 h into the chase, cytosol was prepared and receptors were immunoadsorbed to protein A-Sepharose using the BuGR2 antireceptor antibody. Immunoadsorbed proteins were resolved by gel electrophoresis and analyzed by autoradiography. The 90kDa heat shock protein (hsp90) coimmunoadsorbed with receptors from control cells when protein A-Sepharose pellets were washed with 250 mM NaCl but not when protein A-Sepharose pellets were washed with 500 mM NaCl, indicating that hsp90-receptor complexes are disrupted by a high concentration of salt in the absence of molybdate. hsp90 coimmunoadsorbed with receptors from RU486-treated cells even when protein A-Sepharose pellets were washed with 500 mM NaCl, indicating that RU486 stabilizes the association of hsp90 with the glucocorticoid receptor. In contrast, hsp90 did not coimmunoadsorb with receptors from dexamethasonetreated cells, consistent with earlier evidence that hsp90 dissociates from the receptor when the receptor binds glucocorticoid hormone. Dexamethasone induced a rapid quantum decrease in the amount of normal receptor recovered from cytosol but did not induce a decrease in the amount of nuclear transfer deficient receptor recovered from cytosol, consistent with tight nuclear binding of normal receptors occupied by dexamethasone. In contrast, RU486 did not induce a quantum decrease in the recovery of normal receptors from cytosol, indicating that receptors occupied by RU486 are not tightly bound in the nuclear fraction. We conclude that the antiglucocorticoid hormone RU486, in contrast to the glucocorticoid hormone dexamethasone, stabilizes the association between the glucocorticoid receptor and hsp90. The decreased affinity of receptors occupied by RU486 for the nuclear fraction may be due to their association with hsp90 and may account for the failure of RU486 to exert agonist activity.
Effect of Striated Muscle Paralysis Induced with Erythroidine upon the Electroencephalogram (E. E. G.)

SummarySo long as proper artificial respiration is given, normal cortical activity, as measured by the E. E. G., persists undisturbed in both the dog and the monkey during complete striated muscular paralysis induced with erythroidine. The difference in results reported here with mammals and that previously reported by other workers in the frog (complete elimination of the E. E. G.) is interpreted to be due to a reduction in the available oxygen necessary for normal cortical metabolism in the latter organism.
Transition state effects in the acid-catalyzed hydrolysis of 5-methoxyacenaphthylene 1,2-oxide : Implications for the mechanism of acid-catalyzed hydrolysis of cyclopenta[cd]pyrene 3,4-oxide

5-Methoxyacenaphthylene 1,2-oxide (5) was synthesized by the reaction of 5-methoxyacenaphthylene with dimethyldioxirane. The rates and products from the acid-catalyzed and pH-independent reactions of 5 in 50:50 dioxane/water have been determined. The half-life of the pH-independent reaction of this very reactive epoxide in 50:50 dioxane/water is only 22 s. Acid-catalyzed hydrolysis of 5 in 50:50 dioxane/water yields 62% of cis diol 6, 37% of trans diol 7, and approximately 1% of 5-methoxy-1,2-dihydroacenaphthylen-1-one (8). The pH-independent reaction of 5 yields mostly ketone 8 (94%), along with minor amounts of cis and trans diols. The relative stabilities of cis and trans diols 6 and 7 were determined by treating either cis or trans diol with perchloric acid in water solutions and following the approach to an equilibrium cis/trans diol mixture as a function of time. At equilibrium, the ratio of cis and trans diols is 19:81, which establishes that trans diol 7 is more stable than cis diol 6. The acid-catalyzed hydrolysis of epoxide 5 therefore yields the less stable cis diol as the major product. It is concluded that transition state effects therefore selectively stabilize the transition state for attack of water on the intermediate carbocation leading to the less stable cis diol. These results suggest that transition state effects are also responsible for formation of the major cis diol in the acid-catalyzed hydrolysis of cyclopenta[cd]pyrene 3,4-oxide, which has a cyclopenta-fused ring similar to that in 5.
Single-neuron RNA-Seq: technical feasibility and reproducibility

Understanding brain function involves improved knowledge about how the genome specifies such a large diversity of neuronal types. Transcriptome analysis of single neurons has been previously described using gene expression microarrays. Using high-throughput transcriptome sequencing (RNA-Seq), we have developed a method to perform single-neuron RNA-Seq. Following electrophysiology recording from an individual neuron, total RNA was extracted by aspirating the cellular contents into a fine glass electrode tip. The mRNAs were reverse transcribed and amplified to construct a single neuron cDNA library, and subsequently subjected to high-throughput sequencing. This approach was applicable to both individual neurons cultured from embryonic mouse hippocampus, as well as neocortical neurons from live brain slices. We found that the average pairwise Spearman’s rank correlation coefficient of gene expression level expressed as RPKM (reads per kilobase of transcript per million mapped reads) was 0.51 between five cultured neuronal cells, whereas the same measure between three cortical layer V neurons in situ was 0.25. The data suggest that there may be greater heterogeneity of the cortical neurons, as compared to neurons in vitro. The results demonstrate the technical feasibility and reproducibility of RNA-Seq in capturing a part of the transcriptome landscape of single neurons, and confirmed that morphologically identical neurons, even from the same region, have distinct gene expression patterns.
TH-D-M100E-04: Evaluation of MVCT Images Containing Lead Alloy Masks for Electron Beam Treatment Planning

Purpose: To evaluate the accuracy of electron beam dose calculations in MVCT images containing lead alloy masks. Method and Materials: A phantom consisting of two 30×30×5‐cm3 slabs of CIRS plastic water® was imaged using kVCT (GE Lightspeed‐RT) and MVCT (TomoTherapy Hi⋅Art). The MVCT scans were taken with nine square masks of Cerrobend® (density = 9.4gcm−3) on top of the phantom. The masks contained square openings of 3×3cm2, 6×6cm2 and 10×10cm2 and had thicknesses of 6mm, 8mm and 10mm. The same collimation was simulated in the kVCT images by creating regions‐of‐interest (ROI) duplicating the sizes, shapes, and density of the masks. Using the Philips Pinnacle3treatment planning system, twelve treatment plans were created using electron energies of 6, 9, 12, and 16 MeV for each opening size. For each plan, the mask thickness appropriate for the electron energy was used and the dose distributions calculated using the kVCT and MVCT images were compared. In uniform dose regions (doses above 90% of maximum) dose differences were calculated; in high‐dose gradient regions (doses below 90% of maximum) distances‐to‐agreement (DTA) were determined. Results: In the uniform dose region, the maximum difference between the doses in the MVCT images and the doses in the kVCT image was greater than or equal to ±5% for all opening and energy combinations. In the high‐dose gradient region, almost half of the maximum DTA values exceeded 2mm. Analysis of the MVCT images showed that DTA differences were largely due to distortions in the phantom CT numbers caused by the masks. Conclusion: Although Cerrobend® produces dramatically less distortion in MVCT images compared to kVCT images,image distortion is still too great for accurate electron beam dose calculations. Supported in part by a research agreement with TomoTherapy, Inc.
Tera-scalable Fourier Spectral Element Code for DNS of Channel Turbulent Flow at High Reynolds Number

Due to the extensive requirement of memory and speed for direct numerical simulation (DNS) of channel turbulence, people can only perform DNS at moderate Reynolds number before. With the fast development of supercomputers, it has become more and more approachable for researchers to perform DNS of turbulence at high Reynolds number. This makes it imperative to consider the development of tera-scalable DNS codes that are capable of fully exploiting these massively parallel machines. In order to achieve this, three parallel models (ID, 2D and 3D domain decompositions) have been implemented and bench-marked. All these models have been successfully ported on BlueGene/L. We have benchmarked these models on BG/L at ANL and BGW at IBM Watson center. Details of these models have been described, discussed and presented in this paper. The optimized model can be used to perform DNS at high Reynolds number in the near future.
Ethylene flooding responses of Rumex species

Enhanced growth of the youngest petiole was observed in Rumex crispus and Rumex palustris in response to submergence. A third species, Rumex acetosa, did not show this “supergrowth” reaction. Evidence is found that ethylene has a regulatory role in the growth responses in relation to submergence of all Rumex species studied. In the course of time variation in endogenous ethylene concentration may be caused by interaction of accumulation, fluctuating production and dilution by increased shoot porosity. The growth responses of the three species are highly correlated to the positions of the plants in the flooding gradient in the field.
Visual Masking and the Schizophrenia Spectrum: Interfacing Clinical and Experimental Methods

The present article reviews and evaluates 20 studies of susceptibility to visual masking among individuals within the schizophrenia spectrum using a neurophysiological framework provided by a multichannel model of masking. Particular emphasis is placed upon methodological considerations within the context of the current experimental visual masking literature. While there is ample evidence to suggest that individuals within the schizophrenia spectrum frequently exhibit a backward masking deficit, very little can be understood about the specific nature of the deficit. To gain increased understanding of the specific nature of this deficit, researchers need to use some contemporary theory of masking and derive a theoretical design rationale that facilitates a priori predictions in addition to the more typical post hoc theorizing.
Pseudo epi-cost reduction approach and a paradigm shift in substrate material

Historically, P/P+ epitaxial wafers have been utilized for CMOS products for more than two decades. The epitaxial wafers have several key characteristics such as latch up immunity, oxygen-free active areas, superior oxide quality, and gettering capability compared to bulk nonepi wafers. The epi wafers, however, are costly. Pseudo epi is an alternative to epi wafers with equivalent device performance and material cost savings of 20%-25%. Pseudo epi or high-temperature hydrogen anneal is expected to save a significant percentage of start material costs over the epi substrate for logic family products where epi wafers have dominated the market.
Uv Laser-Induced Etching of the First-Row Transition Metals

The 248 nm excimer laser-induced etching of Ti, Cr, Fe, Co, Ni, and Cu by Br2 has been studied. The experiment consists of focusing the pulsed UV laser beam at normal incidence onto the surface of a quartz crystal microbalance (QCM) coated with 1μm of polycrystalline metal. Absolute etch rates are determined as a function of the Br2 pressure and the laser fluence. On the basis of the kinetic information, four mechanisms are proposed to explain the etching of these transition metals.
Non-canonical TAF complexes regulate active promoters in human embryonic stem cells

The general transcription factor TFIID comprises the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depleting TAFs that are present or ectopically expressing TAFs that are absent, results in misregulated expression of pluripotency genes and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew. DOI: http://dx.doi.org/10.7554/eLife.00068.001
Tunable mechanical behavior of synthetic organogels as biofidelic tissue simulants.

Abstract Solvent-swollen polymer gels can be utilized as mechanical simulants of biological tissues to evaluate protective systems and assess injury mechanisms. However, a key challenge in this application of synthetic materials is mimicking the rate-dependent mechanical response of complex biological tissues. Here, we characterize the mechanical behavior of tissue simulant gel candidates comprising a chemically crosslinked polydimethylsiloxane (PDMS) network loaded with a non-reactive PDMS solvent, and compare this response with that of tissue from murine heart and liver under comparable loading conditions. We first survey the rheological properties of a library of tissue simulant candidates to investigate the effects of solvent loading percentage, reactive functional group stoichiometry, and solvent molecular weight. We then quantify the impact resistance, energy dissipation capacities, and energy dissipation rates via impact indentation for the tissue simulant candidates, as well as for the murine heart and liver. We demonstrate that by tuning these variables the silicone gels can be engineered to match the impact response of biological tissues. These experiments inform the design principles required for synthetic polymer gels that are optimized to predict the response of specific biological tissues to impact loading, providing insight for further tuning of this gel system to match the impact response of other “soft tissues”.
A test of the singlet oxygen mechanism of cationic dye photosensitization of mitochondrial damage.

Abstract— Aromatic cationic dyes have a potential as photo-chemotherapeutic agents because they are selectively concentrated into the mitochondria of cancerous cells. The mechanism of cytophototoxicity has been proposed to be primarily due to dye sensitized photogeneration of highly toxic singlet oxygen (1O2) at the mitochondria. We tested this hypothesis by measuring the relative phototoxicity of a collection of aromatic cationic dyes towards respiring rat-liver mitochondria (RLM), upon addition of 514 nm laser light. Effectiveness of dye photosensitization towards destruction of RLM function was assayed by its effect on the RLM membrane potential. Three physical parameters of dye phototoxicity were independently measured and a relative phototoxicity calculated assuming adherence of mechanism to the 1O2 hypothesis. Quantum yields of dye sensitized 1O2 production were estimated, either from time-resolved luminescence measurements of photosensitized 1O2 formed, or by comparing rates of photobleaching of 1O2 trap; the relative partition of dye into mitochondrial lipid was determined gravimetrically; and the optical density of dye was determined in a lipid like Triton X-100 micellar environment. Under the assumption of the 1O2 hypothesis, these parameters were used to predict a relative phototoxicity which was compared with that observed. For 12 of the 14 dyes investigated, the observed and predicted phototoxicities were linearly correlated (r=0.85) suggesting support of the 1O2 hypothesis. Carbocyanines DiOC2(3) and DiSC2(3) did not correlate and were found to be 10 and 1000 times more potent than predicted, suggesting an additional factor at play in their phototoxicity.
The Impact of a Strategy-Based Intervention on the Comprehension and Strategy Use of Struggling Adolescent Readers.

This study examines the impact of the Learning Strategies Curriculum (LSC), an adolescent reading intervention program, on 6th- and 9th-grade students' reading comprehension and strategy use. Using a randomized treatment-control group design, the study compared student outcomes for these constructs for 365 students who received daily instruction in 6 LSC strategies and 290 students who did not receive intervention instruction. After 1 school year, 6th-grade students who received intervention instruction significantly outperformed students in the control group on a standardized measure of reading comprehension and reported using problem-solving strategies in reading to a greater extent than students in the control group. There were no significant differences between 9th grade intervention and control groups in reading comprehension or strategy use.
Average Cost-Effectiveness Ratio with Censored Data

In cost-effectiveness analysis, interest could lie foremost in the incremental cost-effectiveness ratio (ICER), which is the ratio of the incremental cost to the incremental benefit of two competing interventions. The average cost-effectiveness ratio (ACER) is the ratio of the cost to benefit of an intervention without reference to a comparator. A vast literature is available for statistical inference of the ICERs, but limited methods have been developed for the ACERs, particularly in the presence of censoring. Censoring is a common feature in prospective studies, and valid analyses should properly adjust for censoring in cost as well as in effectiveness. In this article, we propose statistical methods for constructing a confidence interval for the ACER from censored data. Different methods-Fieller, Taylor, bootstrap-are proposed, and through simulation studies and data analysis, we address the performance characteristics of these methods.
Delivering Biodefense Continuing Education to Military Medical Providers by Allowing a Biodefense Educational Curriculum to Unfold in Practice

ABSTRACT A challenge today is how to deliver initial and continuing education on biodefense to military medical providers in a manner that can be integrated into their workflow and lifestyle. A summative evaluation of a prototypical biodefense digital library (BDL) and learning collaboratory was performed. The BDL posted daily links to biodefense news stories from January 2004 to December 2005. Four evaluations were completed, that is, content evaluation, curriculum comparison with a biodefense graduate program, usage evaluation, and impact factor analysis. News stories (N = 678) came from a broad range of authoritative national and international news sources (N = 178). News stories covered all of the categories in the required and elective formal biodefense graduate program courses. The BDL was consistently displayed on the first page of the top three Internet search engines, meaning that it was among the top 10 authoritative Internet sites on biodefense. Presenting biodefense news stories to busy milita...
Nutrient Demand Interacts with Forage Family to Affect Intake and Digestion Responses in Dairy Cows

The effect of feed intake in the preliminary period on responses to diets containing alfalfa silage or orchardgrass silage was evaluated using 8 ruminally and duodenally cannulated Holstein cows in a crossover design experiment with a 14-d preliminary period and two 15-d treatment periods. Responses measured were DMI, rates of fiber digestion and passage, and milk production. Cows were 139 +/- 83 (mean +/- SD) d in milk at the beginning of the preliminary period. During the preliminary period, 3.5% fat-corrected milk yield ranged from 23.9 to 47.6 kg/d (mean = 36.9 kg/d) and preliminary voluntary DMI (pVDMI) ranged from 14.2 to 21.3 kg/d (mean = 18.6 kg/d). The 2 treatments were a diet containing alfalfa silage as the sole forage (AL) and a diet containing orchardgrass silage as the sole forage (OG). Alfalfa silage contained 43% neutral detergent fiber (NDF; dry-matter basis) and orchardgrass silage contained 48% NDF; diets contained approximately 23% forage NDF and 27% total NDF, so forage-to-concentrate ratio was 53:47 for AL and 48:52 for OG. Digestibility of NDF was lower for AL in the rumen and whole tract compared with OG, and milk fat concentration tended to be greater for OG than for AL. Mean 3.5% fat-corrected milk yield and DMI were not different between AL and OG. Response of DMI to forage family depended on pVDMI, as indicated by a significant interaction between treatment and pVDMI in predicting DMI. As pVDMI increased, DMI increased when cows were fed AL but not when they were fed OG. That is, as appetite increased, intake was more restricted for the more physically filling OG than for the less physically filling AL. This more positive DMI response to AL over OG among high-pVDMI cows is corroborated by interactions between treatments and pVDMI for both ruminal NDF turnover rate and indigestible NDF passage rate response. Therefore, the effects of alfalfa and orchardgrass forages on intake and fiber digestion depended on the extent to which fill limited feed intake of an individual cow.
Cryptic impacts of temperature variability on amphibian immune function

SUMMARY Ectothermic species living in temperate regions can experience rapid and potentially stressful changes in body temperature driven by abrupt weather changes. Yet, among amphibians, the physiological impacts of short-term temperature variation are largely unknown. Using an ex situ population of Cryptobranchus alleganiensis , an aquatic North American salamander, we tested the hypothesis that naturally occurring periods of temperature variation negatively impact amphibian health, either through direct effects on immune function or by increasing physiological stress. We exposed captive salamanders to repeated cycles of temperature fluctuations recorded in the population9s natal stream and evaluated behavioral and physiological responses, including plasma complement activity (i.e. bacteria killing) against Pseudomonas aeruginosa , Escherichia coli and Aeromonas hydrophila . The best-fit model (ΔAIC c =0, w i =0.9992) revealed 70% greater P. aeruginosa killing after exposure to variable temperatures and no evidence of thermal acclimation. The same model predicted 50% increased E. coli killing, but had weaker support (ΔAIC c =1.8, w i =0.2882). In contrast, plasma defenses were ineffective against A. hydrophila , and other health indicators (leukocyte ratios, growth rates and behavioral patterns) were maintained at baseline values. Our data suggest that amphibians can tolerate, and even benefit from, natural patterns of rapid warming/cooling. Specifically, temperature variation can elicit increased activity of the innate immune system. This immune response may be adaptive in an unpredictable environment, and is undetectable by conventional health indicators (and hence considered cryptic). Our findings highlight the need to consider naturalistic patterns of temperature variation when predicting species9 susceptibility to climate change.
Vitamin E supplementation suppresses macrophage accumulation and endothelial cell expression of adhesion molecules in the aorta of hypercholesterolemic rabbits

Suppression of cell adhesion molecule expression and macrophage accumulation by the endothelium is believed to play an important role in preventing the development of atherosclerosis. Earlier, we have shown that in vitro supplementation of human aortic endothelial cells with Vitamin E dose-dependently reduced expression of adhesion molecules and monocyte adhesion. Here, we report the in vivo down-regulation of endothelial cell adhesion molecules expression and macrophage accumulation in the aortas of hypercholesterolemic rabbits supplemented with Vitamin E. To this end, New Zealand White rabbits were fed a semi-purified diet containing 30 (control) or 1000 IU/kg Vitamin E. After 4 weeks, both groups' diets were switched to an atherogenic diet (0.3% cholesterol, 9% hydrogenated coconut oil, and 1% corn oil) containing the respective levels of Vitamin E and fed for 2, 4, and 6 weeks. Vitamin E supplemented rabbits had significantly higher levels of Vitamin E in their plasma and aortas. Frozen aorta sections were fixed and stained by an avidin-biotin complex method using Rb2/3 and Rb1/9 monoclonal antibodies against rabbit ICAM-1 and VCAM-1, respectively, and with RAM-11 for macrophage and von Willebrand factor for endothelial cells, followed by staining with secondary antibodies and counterstaining and evaluation under the microscope. At 6 weeks on atherogenic diet treatment, a trend (P = 0.08) toward a lower score of ICAM-1 expression by endothelial cells was observed in the aorta of Vitamin E treated rabbits compared to the control. However, a decrease in the score of VCAM-1 expression by endothelial cells in Vitamin E treated rabbits did not reach to a statistical significance. At 4 and 6 weeks on atherogenic diet, Vitamin E supplementation also significantly (P = 0.003) inhibited the accumulation of macrophages in the aorta. These results support the concept that down-regulation of adhesion molecule expression and suppression of monocyte/macrophage activation by Vitamin E in vivo is one of the potential mechanisms by which Vitamin E may suppress the development of aortic lesions in a rabbit model of atherosclerosis.
ON THE INVERSE SCATTERING AND DIRECT LINEARIZING TRANSFORMS FOR THE KADOMTSEV-PETVIASHVILI EQUATION

Abstract The existing formalism for solving the initial-value problem associated with the Kadomtsev-Petviashvili equation, a physically significant two-spatial dimensional analogue of the Korteweg-de Vries equation, is both simplified and extended. The lump solutions, algebraically decaying solitons, are naturally incorporated and given a spectral characterization in the new scheme. In addition, a very general linearization of the Kadomtsev-Petviashvili equation is presented.
Interaction with Polyglutamine Aggregates Reveals a Q/N-rich Domain in TDP-43

The identification of pathologic TDP-43 aggregates in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, followed by the discovery of dominantly inherited point mutations in TDP-43 in familial ALS, have been critical insights into the mechanism of these untreatable neurodegenerative diseases. However, the biochemical basis of TDP-43 aggregation and the mechanism of how mutations in TDP-43 lead to disease remain enigmatic. In efforts to understand how TDP-43 alters its cellular localization in response to proteotoxic stress, we found that TDP-43 is sequestered into polyglutamine aggregates. Furthermore, we found that binding to polyglutamine aggregates requires a previously uncharacterized glutamine/asparagine (Q/N)-rich region in the C-terminal domain of TDP-43. Sequestration into polyglutamine aggregates causes TDP-43 to be cleared from the nucleus and become detergent-insoluble. Finally, we observed that sequestration into polyglutamine aggregates led to loss of TDP-43-mediated splicing in the nucleus and that polyglutamine toxicity could be partially rescued by increasing expression of TDP-43. These data indicate pathologic sequestration into polyglutamine aggregates, and loss of nuclear TDP-43 function may play an unexpected role in polyglutamine disease pathogenesis. Furthermore, as Q/N domains have a strong tendency to self-aggregate and in some cases can function as prions, the identification of a Q/N domain in TDP-43 has important implications for the mechanism of pathologic aggregation of TDP-43 in ALS and other neurodegenerative diseases.
Cost Impacts, Scheduling Impacts, and the Claims Process during Construction

Construction mismanagement results in multiple problems that can cascade throughout the work force chain, affecting the schedule and leading to damages to multiple parties. Although the problem may start with a single subcontractor, it can result in all contractors feeling some impact to their work. In this paper, a case study is presented of a project with seven different mismanagement scenarios. A description of each scenario is provided as well as a quantification of the damages that result from the problem. A construction claims section is also included that addresses many of the issues that could result from a claim for each of the seven scenarios. A discussion is presented outlining possible preventative steps to minimize the damages from the problems presented.
Evolution at protein ends: major contribution of alternative transcription initiation and termination to the transcriptome and proteome diversity in mammals

Alternativesplicing(AS),alternativetranscriptioninitiation (ATI) and alternative transcription termination (ATT) create the extraordinary complexity of transcriptomes and make key contributions to the structural and functional diversity of mammalian proteomes. Analysis of mammalian genomic and transcriptomic data shows that contrary to the traditional view, the joint contribution of ATI and ATT to the transcriptome and proteome diversity is quantitatively greater than the contribution of AS. Although the mean numbers of protein-coding constitutive and alternative nucleotides in gene loci are nearly identical, their distribution along the transcripts is highly non-uniform. On average, coding exons in the variable 5 � and 3 � transcript ends that are created by ATI
Novice teachers learning through participation in a teacher study group

Abstract Using Lave and Wenger’s framework of legitimate peripheral participation in communities of practice, this case study explores the experiences of three novice teachers engaged with more experienced teachers in a teacher study group during their first year of teaching. The study illustrates how, over time, the novices moved from more peripheral to more central participation as revealed through changes in their talk and feelings about participating. The study highlights the importance of legitimacy and peripherality provided by the more experienced teachers and identifies the ways in which the facilitator scaffolded and mediated the novices’ participation and learning.
DOCK8 Immune Deficiency as a Model for Primary Cytoskeletal Dysfunction

DOCK8 deficiency is a newly described primary immune deficiency resulting in profound susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia, but lacking in the skeletal manifestations commonly seen in hyper IgE syndrome, which it otherwise resembles. Although little is known about the DOCK8 protein, it resembles other atypical guanine exchange factors in the DOCK family, and is known to bind to CDC42. This suggests that a likely role for DOCK8 is in modulating signals that trigger cytoskeletal reorganization. As a result, DOCK8 may also be related to other immune deficiencies that involve the cytoskeleton and Rho GTPase signaling pathways, such as Wiskott-Aldrich syndrome and Rac2 deficiency.
The role of arteriovenous shunts in the pathogenesis of varicose veins

Abstract Varicose veins and venous insufficiency are causes of significant morbidity. In North America 10% to 17% of the adult population is affected, an incidence 10 times that of arterial disease. Despite this, origin and mechanism of disease remain obscure. This study was designed to illustrate the presence of patent arteriovenous shunts in the varicosed limb and to assess their role. Twenty-eight women and twenty-one men with primary varicose veins were studied. Thirty-six men and seven women without venous disease served as a control group. Blood samples were collected from an arm vein and a limb varicosity in the study group along with an arterial blood sample. Blood samples were also drawn from an arm vein and the femoral vein in the control group along with an arterial blood sample. Venous partial oxygen pressure (PVO 2 ) and hemoglobin saturation (HbSat) were measured and venous oxygen content (CVO 2 ) calculated. Mean values were then obtained and statistical comparisons made between each group. A statistically significant increase (p 2 , HbSat, and CVO 2 —was demonstrated in the patients' limbs with varicose veins, consistent with a functioning arteriovenous shunt. (J VASC SURG 1986;4:124-8.)
Narrowteuthis nesisi, a new genus and new species of the squid family Neoteuthidae (Mollusca: Cephalopoda)

A new neoteuthid genus and species, Narrowteuthis nesisi, is described on the basis of two specimens with the following characters that are unique within the family: laterally compressed proximal manal suckers, short tentacular clubs relative to mantle length, and smooth sucker rings on arm suckers. It is also the only neoteuthid in which the proximal and distal manus regions of the club are approximately equal in length.
Chaotic quantum cryptography: The ultimate for network security

As the sophistication of intruders' increases, so does the incidents of information integrity breaches and network attacks. In response, very complex cryptographic processes have started being employed, such as chaos theory and quantum theory, in an effort to create the “holy grail” of cryptographic systems and network security. Quantum theory defines the non-classical qubit, which is the superposition of quantum states having no classical analog. It is also based on the “no cloning” and “no copying” theorem and on the Heisenberg's uncertainty. The quanto-mechanical properties of photons and the quantum mechanics provide a superb platform for communications security and particularly in secure optical communication networks, known as quantum cryptography and quantum networks, respectively. Chaos is based on the particular behavior of certain non-linear functions, which for a minute change of parameters produce a huge and unstable output, known as the “chaotic regime”. However, this chaos can be reproducible, which makes it attractive to secure communications. Thus, the combined Chaos and Quantum theories play a synergistic role in the quest for the “holy grail” in communications security. In this talk we explain with simple examples quantum cryptography and protocols, as well as chaos and chaotic processes. We also describe the synergy of chaos and quantum theories as well as the increased efficiency and speed of the quantum key establishment.
A Longitudinal Assessment of Consumers' Attitudes Toward Accounting Advertising

This study investigates current attitudes and opinions toward accounting advertising and compares them to the attitudes expressed 10 years ago. It replicates a survey administered in 2004 and uses the same questionnaire and the same population to compare responses longitudinally. Both the 2004 and 2014 respondents agreed the public would be provided useful information through advertising by accountants, and both groups also believed it is proper for accountants to advertise. The study seems to confirm the belief of many marketing professionals that advertising and marketing clearly have a place in the future of accounting services.
Has Conduct in Iraq Confirmed the Moral Inadequacy of International Humanitarian Law? Examining the Confluence between Contract Theory and the Scope of Civilian Immunity

For decades, it has been established that a resistance movement operating in an occupied territory that complies with International Humanitarian Law (IHL) may be accorded lawful combatant status, rather than branded war criminals. The justification for protecting these resistance movements emanates principally from two rationales. First, that granting them combatant status will incite their increased compliance with IHL. Second, that a resistance movement's compliance with IHL will better enable an occupying force to distinguish them from the peaceful civilian populace during military operations. The underlying goal or justification uniting the two rationalizations is the safeguarding of the peaceful civilian populace from the tragedies of armed conflict. This article explains how these rationalizations inform the juridical constructs, institutional elements and doctrinal precepts that comprise IHL when evaluated against the conditions imposed by insurgents in present day Iraq. In so doing, the article broadly explores the degree to which these jurisprudential modules produce coherency between the juridical constructs governing hostile conduct and the desired outcome of safeguarding innocent civilians. By examining the empirical dimensions of civilian immunity, the military necessity doctrine and the socio-contractarian aspects of armed conflict, this article demonstrates the reformative value of coherency theory and its empirical impact on civilian safety. The need for this analysis regarding civilian protectionism is crucial to IHL and the values imbued in its justification. The reported number of innocent Iraqi civilian deaths lies between 24,000 and approximately 100,000, at least ten times the amount of deaths suffered by the U.S. led coalition force reportedly on Iraqi soil to protect civilians from an obviously vibrant and ever evasive insurgency. Simply stated, the statistic represents a gapping indictment against the effectiveness of those juridical constructs designed to protect civilians.
The Efficacy of Bisphosphonates with Core Decompression and Mesenchymal Stem Cells Compared with Bisphosphonates Alone in the Treatment of Osteonecrosis of the Hip: A Retrospective Study:

IntroductionOsteonecrosis of the femoral head (ONFH) is a devastating disease with complete collapse of the femoral head often reported in greater than 70% of patients within 3 to 4 years of diagno...
New age roles: Are we preparing girls and boys for personal and social change?

This paper suggests that changes in society, particularly Western nations, require us to look at male and female development and youth preparation for future roles from a systems perspective. As indicators of need to use different methods of career guidance, the author cites 1) the narrow range of possibilities from which girls and boys choose; 2) the gap between perceptions and reality; 3) the pervasiveness of sex-role stereotyping and its limiting effects; 4) the growing linkage between work and family roles; and 5) the lack of communication between the sexes about future roles and goals. She suggests that the reality of social change, difficult though it is for some to accept, requires us to more adequately prepare youth for the exponential change which is occurring around the world. She analyzes some of the changes which have occurred and discusses possible consequences for individuals, work, and family.
Amending the Americans with Disabilities Act Shifting Equal Employment Opportunity Obligations in Public Human Resource Management

This research examines changing public human resources obligations under the Americans with Disabilities Act (ADA). During the first 12 years after ADA implementation, the U.S. Supreme Court issued...
The Differential Response of Meristems of Vicia Faba to Colchicine

SUMMARYThe response of primordia and lateral root meristems to short treatments with colchicine (2–3 hours) is described. Evidence is presented that anaphase continues to occur in large primordia after it has been suppressed in lateral roots. Since the anaphases occur together with c-metaphases and restitution nuclei it is clear that colchicine reaches the primordia. The differential response of large primordia to colchicine is also demonstrated by the extent of other changes: accumulation of metaphases, prophase: metaphase ratios and M.I. The response of primordia and lateral roots to 0.05, 0.025, 0.0125 and 0.001% colchicine is compared and additional evidence is presented that large primordia show a differential response.
Small dim object tracking using frequency and spatial domain information

Small dim target tracking is an active and important research area in image processing and pattern recognition. Recently, there has been an emphasis on the development of algorithms based on spatial domain Constant False Alarm Rate (CFAR) detection. This paper presents a novel algorithm for detecting and tracking small dim targets in Infrared (IR) image sequences with low Signal to Noise Ratio (SNR) based on the frequency and spatial domain information. Using a Dual-Tree Complex Wavelet Transform (DT-CWT), a CFAR detector is applied in the frequency domain to find potential positions of objects in a frame. Following this step, a Support Vector Machine (SVM) classification is applied to accept or reject each potential point based on the spatial domain information of the frame. The combination of the frequency and spatial domain information demonstrates the high efficiency and accuracy of the proposed method which is supported by the experimental results. A novel algorithm for detecting and tracking small dim targets in Infrared (IR) image sequences is presented.Using a Dual-Tree Complex Wavelet Transform, a CFAR detector is applied to find potential targets.A Support Vector Machine (SVM) classification is applied to refine potential targets.The combination of the frequency and spatial domain information can accurately provide moving object trajectories.
ATP-dependent regulation of a G protein-coupled K+ channel (GIRK1/GIRK4) expressed in oocytes

Recent studies suggest that activation of the atrial muscarinic K+ current by acetylcholine (ACh) involves an ATP-dependent process that is then inhibited by a cytosolic protein to result in the rapid desensitization. To obtain further evidence in support of such a dually regulated process, we studied the properties of GIRK1 and GIRK4, which, when coexpressed in oocytes, form a heteromultimer that closely resembles the muscarinic K+ channel. ACh activated an inwardly rectifying K+ current that desensitized slowly. In cell-attached patches with ACh in the pipette, the mean open times (tau zero) of GIRK1/GIRK4 were 1.2 +/- 0.1 (28%) and 6.7 +/- 0.8 ms (72%) and did not change significantly with time. However, in inside-out patches, the tau zero of GIRK1/GIRK4 activated with guanosine 5'-O-(3-thiotriphosphate) was 1.3 +/- 0.1 ms (100%), and the channel activity (NP0) was almost fivefold lower. These changes in channel kinetics did not occur in the presence of sodium orthovanadate (3 mM), an inhibitor of phosphatase. Addition of 1 mM ATP, but not adenylimidodiphosphate, to inside-out patches resulted in increases in NP zero (4.8-fold) and the open-time duration of GIRK1/GIRK4, such that tau zero were 1.2 +/- 0.2 (32%) and 6.2 +/- 0.6 ms (68%). Single channel conductances were unchanged (34 +/- 1 pS). Cytosolic extract from atria, but not oocytes, could reverse these effects of ATP. These results provide further evidence that the antagonistic modulation of G protein-gated K+ channels by ATP and the atrial cytosolic protein produces the early rapid desensitization in atrial cells. In oocytes the ATP-dependent step is dominant and thus provides a major component of the total GIRK1/GIRK4 current activated by ACh.
Current status of biological indicators to detect and quantify previous exposures to radiation

Hematologic changes following whole-body exposure to γ or x-ray radiation have been used to estimate dose. The usefulness of this biological indicator is limited because of the recovery of these cells with time, thus making it unsuitable for estimation of dose years after exposure. The same is true for spermatogenic indicators; As noted in the text of the report, immunological concepts are in a state of rapid development, and it is possible that improved methods for applying immunologic procedures as biological indicators of radiation may be developed in the future. There is good agreement that ionizing radiation causes biochemical changes in the body; however, attempts to apply these changes to provide a reliable biological dosimetry system have not been particularly successful
Leader/Teacher Credibility and Bias in the Classroom and Workplace

Teachers are the leaders of their multiple, semester-length, organizational microcosms, and just as leader credibility is paramount for practitioner leaders, so too do teachers prove their “cred” i...
Mean Squared Error Based Excitation Pattern Design for Parallel Transmit and Receive SENSE MRI Image Reconstruction

Parallel coils at both the transmitter and receiver can be used to offer more control over the magnetic resonance imaging (MRI) system, and this implementation has potential to improve the performance in high-field MRI. A new MSE-based EXcitation Pattern (MSE-EXP) design for image reconstruction in parallel transmit and receive SENSitivity Encoding (pTxRx SENSE) MRI is presented in this paper to maximize the performance of an MRI using an array of transmit and receive coils. In the the small-tip-angle regime, we derive theoretically effective excitation patterns for fully-sampled k -space data (with no SNR assumption) and for under-sampled k -space data under both low and high SNR assumptions. The proposed MSE-EXP-encoded pTxRx SENSE MRI has two main advantages for high-field MRI, one is the specific absorption rate (SAR) management through prespecification of the global SAR regulatory limit in the excitation pattern design weight constraint and an another is the imaging acceleration by effective reduction of aliasing artifacts, particularly for advanced image reconstruction in highly under-sampled pTxRx SENSE MRI in the high-SNR regime. Numerical experiments demonstrate that reconstruction accuracy in pTxRx SENSE MRI is significantly improved by the proposed MSE-EXP design, but our study also identifies several practical challenges associated with generation of the proposed MSE-EXP.