cssi/SciSciGPT-SciSciNet huggingface dataset:
Adenovirus-mediated Heat-activated Antisense Ku70 Expression Radiosensitizes Tumor Cells in Vitro and in Vivo

Ku70 is one component of a protein complex, Ku70 and Ku80, that functions as a heterodimer to bind DNA double-strand breaks and activates DNA-dependent protein kinase. Our previous study with Ku70−/− and Ku80−/− mice, and cell lines has shown that Ku70- and Ku80-deficiency compromises the ability of cells to repair DNA double-strand breaks, increases radiosensitivity of cells, and enhances radiation-induced apoptosis. In this study, we examined the feasibility of using adenovirus-mediated, heat-activated expression of antisense Ku70 RNA as a gene therapy paradigm to sensitize cells and tumors to ionizing radiation. First, we performed experiments to test the heat inducibility of heat shock protein (hsp) 70 promoter and the efficiency of adenovirus-mediated gene transfer in rodent and human cells. Replication-defective adenovirus vectors were used to introduce a recombinant DNA construct, containing the enhanced green fluorescent protein (EGFP) under the control of an inducible hsp70 promoter, into exponentially growing cells. At 24 h after infection, cells were exposed to heat treatment, and heat-induced EGFP expression at different times was determined by flow cytometry. Our data clearly show that heat shock at 42°C, 43°C, or 44°C appears to be equally effective in activating the hsp70 promoter-driven EGFP expression (>300-fold) in various tumor cells. Second, we have generated adenovirus vectors containing antisense Ku70 under the control of an inducible hsp70 promoter. Exponentially growing cells were infected with the adenovirus vector, heat shocked 24 h later, and the radiosensitivity determined 12 h after heat shock. Our data show that heat shock induces antisense Ku70 RNA, reduces the endogenous Ku70 level, and significantly increases the radiosensitivity of the cells. Third, we have performed studies to test whether Ku70 protein level can be down-regulated in a solid mouse tumor (FSa-II), and whether this results in enhanced radiosensitivity in vivo, as assessed by in vivo/in vitro colony formation and by the tumor growth delay. Our data demonstrate that heat-shock-induced expression of antisense Ku70 RNA attenuates Ku70 protein expression in FSa-II tumors, and significantly sensitizes the FSa-II tumors to ionizing radiation. Taken together, our results suggest that adenovirus-mediated, heat-activated antisense Ku70 expression may provide a novel approach to radiosensitize human tumors.
Catheptic Enzymes and Meat Tenderization.

SUMMARY— A cathepsin has been purified from chicken leg muscle by ammonium sulfate fractionation and by chromatography on carboxy methyl- and diethylaminoethylcellulose. With respect to the specific activity of the initial 2% potassium chloride extract the cathepsin was purified 580. fold. The purified cathepsin hydrolyzed urea-denatured hemoglobin readily at pH 4.40, but it had no activity on a-N-benzyloxy-carbonyl-L-glutamyl-L-tyrosine, a-N-benzoyl-L-argininamide and a-N-acetyl-L-tyrosinamide. The data indicate the preparation was cathepsin D and that it did not contain cathepsins A, B, and C. The cathepsin preparation had no activity on actomyosin at pH 4.95 and 5.90 as measured by viscosity and gel-filtration methods. On the other hand trypsin, with 0.014 the potential activity of the cathepsin used and at pH 7.9, hydrolyzed actomyosin readily. While the cathepsin prepared here, probably cathepsin D, did not hydrolyze actomyosin, the data do not exclude the possibility of hydrolysis of actomyosin by other cathepsins or by cathepsin D in combination with other cathepsins.
Near-Field ETAS Constraints and Applications to Seismic Hazard Assessment

The epidemic type aftershock sequence (ETAS) statistical model of aftershock seismicity combines various earthquake scaling relations to produce synthetic earthquake catalogs, or estimates of aftershock seismicity rates, based on recent earthquake activity. One challenge to ETAS-based hazard assessment is the large number of free parameters involved. In this paper, we introduce an approach to constrain this parameter space from canonical scaling relations, empirical observations, and fundamental physics. We show that ETAS parameters can be estimated as a function of an earthquake’s magnitude m based on the finite temporal and spatial extents of the rupture area. This approach facilitates fast ETAS-based estimates of seismicity from large “seed” catalogs, and it is particularly well suited to web-based deployment and otherwise automated implementations. It constitutes a significant improvement over contemporary ETAS by mitigating variability related to instrumentation and subjective catalog selection.
Sodium Ion Binding Pocket Mutations and Adenosine A2A Receptor Function

Recently we identified a sodium ion binding pocket in a high-resolution structure of the human adenosine A2A receptor. In the present study we explored this binding site through site-directed mutagenesis and molecular dynamics simulations. Amino acids in the pocket were mutated to alanine, and their influence on agonist and antagonist affinity, allosterism by sodium ions and amilorides, and receptor functionality was explored. Mutation of the polar residues in the Na(+) pocket were shown to either abrogate (D52A(2.50) and N284A(7.49)) or reduce (S91A(3.39), W246A(6.48), and N280A(7.45)) the negative allosteric effect of sodium ions on agonist binding. Mutations D52A(2.50) and N284A(7.49) completely abolished receptor signaling, whereas mutations S91A(3.39) and N280A(7.45) elevated basal activity and mutations S91A(3.39), W246A(6.48), and N280A(7.45) decreased agonist-stimulated receptor signaling. In molecular dynamics simulations D52A(2.50) directly affected the mobility of sodium ions, which readily migrated to another pocket formed by Glu13(1.39) and His278(7.43). The D52A(2.50) mutation also decreased the potency of amiloride with respect to ligand displacement but did not change orthosteric ligand affinity. In contrast, W246A(6.48) increased some of the allosteric effects of sodium ions and amiloride, whereas orthosteric ligand binding was decreased. These new findings suggest that the sodium ion in the allosteric binding pocket not only impacts ligand affinity but also plays a vital role in receptor signaling. Because the sodium ion binding pocket is highly conserved in other class A G protein-coupled receptors, our findings may have a general relevance for these receptors and may guide the design of novel synthetic allosteric modulators or bitopic ligands.
ION PERMEATION IN NORMAL AND BATRACHOTOXIN-MODIFIED NA+ CHANNELS IN THE SQUID GIANT AXON

Na+ permeation through normal and batrachotoxin (BTX)-modified squid axon Na+ channels was characterized. Unmodified and toxin-modified Na+ channels were studied simultaneously in outside-out membrane patches using the cut-open axon technique. Current-voltage relations for both normal and BTX-modified channels were measured over a wide range of Na+ concentrations and voltages. Channel conductance as a function of Na+ concentration curves showed that within the range 0.015-1 M Na+ the normal channel conductance is 1.7-2.5-fold larger than the BTX-modified conductance. These relations cannot be fitted by a simple Langmuir isotherm. Channel conductance at low concentrations was larger than expected from a Michaelis-Menten behavior. The deviations from the simple case were accounted for by fixed negative charges located in the vicinity of the channel entrances. Fixed negative charges near the pore mouths would have the effect of increasing the local Na+ concentration. The results are discussed in terms of energy profiles with three barriers and two sites, taking into consideration the effect of the fixed negative charges. Either single- or multi-ion pore models can account for all the permeation data obtained in both symmetric and asymmetric conditions. In a temperature range of 5-15 degrees C, the estimated Q10 for the conductance of the BTX-modified Na+ channel was 1.53. BTX appears not to change the Na+ channel ion selectively (for the conditions used) or the surface charge located near the channel entrances.
Breached Initiations: Sociopolitical Resources and Conflicts in Emergent Adulthood*

Work theorizing youth subcultures, especially of the spectacular kind, has provided an influential approach for understanding the lives of young people for the past 40 years in anthropology and sociology. In this review, we frame current literature through a lens we call “breached initiations.” We motivate our organization of the literature into processes we term “delaying,” “hopscotching,” and “opting out,” referring to ways in which youth engage sociopolitical resources and chronotopes to alter the sequencing and clustering of their expected progress through milestones of adulthood. In many cases, youth delay or refuse entry into a world that is considered “normal” and demand a reconsideration of its very premises. We highlight symbolic, material, and networked resources; by considering the commonalities in the structural situations of different youth groups, we do not view them as islands, but instead assert their embeddedness in common change.
The voluntariness of virtue – and belief

This paper examines the relative voluntariness of three types of virtue: ‘epistemic’ virtues like open-mindedness; ‘motivational’ virtues like courage, and more robustly ‘moral’ virtues like justice. A somewhat novel conception of the voluntariness of belief is offered in terms of the limited, but quite real, voluntariness of certain epistemic virtues.
Does radiotherapy still have a place in Hodgkin lymphoma

Over half a century, radiation therapy (RT) for Hodgkin lymphoma has been transformed from a radical, extensive, high-dose therapy (which alone cured most patients) into an essential component of a comprehensive combined-modality program. RT is now used in a “mini” version that encompasses only the clinically involved sites following chemotherapy and is administered in a markedly reduced dose. This change has considerably reduced the long-term complications that were associated with the now-outdated radical RT approach. The use of RT also allows a shorter and safer course of chemotherapy. The combination of reduced chemotherapy followed by mini-RT has produced disease control and even overall results that are significantly superior to those achieved with chemotherapy alone. This review discusses controversial issues regarding RT, the studies that have addressed them, the new indications for integrating RT, and the safety of minimizing the radiation field and dose.
Metabolic chemistry of pyrethroid insecticides

This review of studies on 20 pyrethroids with nine different acid moieties and ten different alcohol moieties reveals a diversity of functional groups undergoing metabolism in mammals, insects, other organisms, and microsomal esterase and oxidase systems. Seventy-nine metabolites are identified from the cis-isomer of permethrin and transpermethrin but fewer from other pyrethroids examined in less detail. The sites and rates of metabolic attack on each pyrethroid depend on the organism or system. Metabolism of pyrethoids by esterase and oxidase action usually limits their toxicity to mammals more than to insects, thereby conferring useful selective toxicity properties.
Gender-based differences in birdwatchers' participation and commitment.

This study explored possible gender-based differences in birdwatching participation and commitment using a sample of North Carolina birding organization members. Within the theoretical contexts of ...
Does the microbiota regulate immune responses outside the gut

Perturbations in the gastrointestinal (GI) microbiota composition that occur as a result of antibiotics and diet in ‘westernized’ countries are strongly associated with allergies and asthma (‘hygiene hypothesis’). The microbiota (‘microflora’) plays a crucial role in the development of mucosal tolerance, including the airways. Significant attention has been focused on the role of the microbiota in GI development, immune adaptation and initiation of GI inflammatory diseases. This review covers the post-developmental functions that the microbiota plays in regulating immunological tolerance to allergen exposure outside the GI tract and proposes the question: is the microbiota a major regulator of the immune system?
Power Calculations for Two-Wave, Change from Baseline to Follow-Up Study Designs

Change in a quantitative trait is commonly employed as an endpoint in two-wave longitudinal studies. For example, early phase clinical trials often use two-wave designs with biomarker endpoints to confirm that a treatment affects the putative target treatment pathway before proceeding to larger scale clinical efficacy trials. Power calculations for such designs are straightforward if pilot data from longitudinal investigations of similar duration to the proposed study are available. Often longitudinal pilot data of similar duration are not available, and simplifying assumptions are used to calculate sample size from cross-sectional data, one standard approach being to use a formula based on variance estimated from cross sectional data and correlation estimates abstracted from the literature or inferred from experience with similar endpoints. An implicit assumption of this standard approach is that the variance of the quantitative trait is the same at baseline and follow-up. In practice, this assumption rarely holds, and sample size estimates by this standard formula can be dramatically anti-conservative. Even when longitudinal pilot data for estimating parameters required in sample size calculations are available, sample size calculations will be biased if the interval from baseline to follow-up is not of similar duration to that proposed for the study being designed. In this paper we characterize the magnitude of bias in sample size estimates when formula assumptions do not hold and derive alternative conservative formulas for sample size required to achieve nominal power.
The most dangerous code in the world: validating SSL certificates in non-browser software

SSL (Secure Sockets Layer) is the de facto standard for secure Internet communications. Security of SSL connections against an active network attacker depends on correctly validating public-key certificates presented when the connection is established.We demonstrate that SSL certificate validation is completely broken in many security-critical applications and libraries. Vulnerable software includes Amazon's EC2 Java library and all cloud clients based on it; Amazon's and PayPal's merchant SDKs responsible for transmitting payment details from e-commerce sites to payment gateways; integrated shopping carts such as osCommerce, ZenCart, Ubercart, and PrestaShop; AdMob code used by mobile websites; Chase mobile banking and several other Android apps and libraries; Java Web-services middleware including Apache Axis, Axis 2, Codehaus XFire, and Pusher library for Android and all applications employing this middleware. Any SSL connection from any of these programs is insecure against a man-in-the-middle attack.The root causes of these vulnerabilities are badly designed APIs of SSL implementations (such as JSSE, OpenSSL, and GnuTLS) and data-transport libraries (such as cURL) which present developers with a confusing array of settings and options. We analyze perils and pitfalls of SSL certificate validation in software based on these APIs and present our recommendations.
Organizational size and IT innovation adoption: A meta-analysis

Organizational size has long been considered to be an important predictor of IT innovation adoption. However, empirical results on the relationship between them have been disturbingly mixed and inconsistent. Through a meta-analysis of 54 correlations derived from 21 empirical studies, we attempted to explain and resolve these mixed results by synthesizing across studies the effects of organizational size on IT innovation adoption and by examining the effects of six moderators on the relationship. The results suggested that, although a positive relationship generally existed between them, the relationship was moderated by five variables: type of IT innovation, type of organization, stage of adoption, scope of size, and type of size measure. This suggested that the mixed empirical results from previous studies can be explained by a lack of consideration of moderators.
Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenzae era.

Context. Children with meningitis are routinely admitted to the hospital and administered broad-spectrum antibiotics pending culture results be- cause distinguishing bacterial meningitis from aseptic meningitis is often difficult. Objective. To develop and validate a simple multiva- riable model to distinguish bacterial meningitis from aseptic meningitis in children using objective parameters available at the time of patient presentation. Design. Retrospective cohort study of all children with meningitis admitted to 1 urban children's hospital from July 1992 through June 2000, randomly divided into derivation (66%) and validation sets (34%). Patients. Six hundred ninety-six previously healthy children aged 29 days to 19 years, of whom 125 (18%) had bacterial meningitis and 571 (82%) had aseptic meningi- tis. Intervention. Multivariable logistic regression and recursive partitioning analyses identified the following predictors of bacterial meningitis from the derivation set: Gram stain of cerebrospinal fluid (CSF) showing bacte- ria, CSF protein >80 mg/dL, peripheral absolute neutro- phil count >10 000 cells/mm 3 , seizure before or at time of presentation, and CSF absolute neutrophil count >1000 cells/mm 3 . A Bacterial Meningitis Score (BMS) was de- veloped on the derivation set by attributing 2 points for a positive Gram stain and 1 point for each of the other variables. Main Outcome Measure. The accuracy of the BMS when applied to the validation set. Results. A BMS of 0 accurately identified patients with aseptic meningitis without misclassifying any child with bacterial meningitis in the validation set. The neg- ative predictive value of a score of 0 for bacterial menin- gitis was 100% (95% confidence interval: 97%-100%). A BMS >2 predicted bacterial meningitis with a sensitivity of 87% (95% confidence interval: 72%-96%). Conclusions. The BMS accurately identifies children at low (BMS 0) or high (BMS >2) risk of bacterial meningitis. Outpatient management may be considered for children in the low-risk group. Pediatrics 2002;110: 712-719; prediction model, bacterial meningitis, aseptic meningitis. ABBREVIATIONS. CSF, cerebrospinal fluid; WBC, white blood cell count; Hib, Haemophilus influenzae type b; ANC, absolute neutrophil count; RBC, red blood cells; ROC, receiver operating characteristic; BMS, Bacterial Meningitis Score; NPV, negative pre- dictive value; CI, confidence interval; PPV, positive predictive value.
Achieving tensile superplasticity in 8 mol% Y2O3 cubic stabilized ZrO2 through the addition of intergranular silica

Abstract The addition of 5 wt.% SiO2, a viscous second phase, to 8 mol% Y2O3 cubic stabilized ZrO2 (8Y-CSZ) made superplastic 8Y-CSZ. This material had a fine grain size of 0.4 μm and exhibited deformations in tension as large as 520% at 1430 °C with a strain rate of 1.0 × 10−4 s−1.
Aspects of Isolated Power System s for Hospital Operating Rooms

In general, electric power systems for hospitals will be designed following the well-established principles of commercial building power system design. In particular, they include one new power system design situation. For safety in the explosive atmospheres of anesthetizing and anesthetic storage areas, an isolated power system (no solid system grounding) is mandatory, although the rest of the system will be solidly grounded at the service entrance.
Variable-ratio conditioning history produces high- and low-rate fixed-interval performance in rats.

Four rats were exposed to an A-B-A-B series of 30 sessions each of variable-ratio 20 (A) and fixed-interval 30-s (B) schedules. Four other rats received 120 sessions of fixed-interval 30 s. The rats with a history of variable-ratio responding subsequently showed primarily high or low response-rate patterns on the fixed-interval schedule without evidence of classical scalloping (i.e., increased rates of responding throughout the interreinforcement interval), except infrequently in 1 rat. The rats exposed to only the fixed-interval 30-s schedule displayed the expected sequence of scalloping giving way to lower rate break-run or simply low-rate responding over time. This experiment shows that when naive rats are exposed to even a simple history of reinforcement (in this case, a variable-ratio 20), their subsequent fixed-interval performance is very different from comparable performance in naive rats, and might be said to be more similar to the responding of adult humans. The argument is made that care should be taken in comparing the fixed-interval performance of humans and nonhumans because humans have a complex history of reinforcement, whereas laboratory nonhumans are typically naive.
Linear turbo equalization for parallel ISI channels

We propose a method for exploiting transmit diversity using parallel independent intersymbol interference channels together with an iterative equalizing receiver. Linear iterative turbo equalization (LITE) employs an interleaver in the transmitter and passes a priori information on the transmitted symbols between multiple soft-input/soft-output minimum mean-square error linear equalizers in the receiver. We describe the LITE algorithm, present simulations for both stationary and fading channels, and develop a framework for analyzing the evolution of the a priori information as the algorithm iterates.
Synthesis of Tetraalkenylmethane: Building Blocks for Three-Dimensional Hydrocarbon Networks

In this paper, we show a common strategy to synthesize tetraalkenylmethanes, a cross-linker series for building three-dimensional hydrocarbon networks. To demonstrate the feasibility of this method, we have synthesized tetrapentenylmethane. Attempts to synthesize this cross-linker from pentaerythrityl tetrabromide using substitution reactions resulted in the formation of a spiro compound due to intramolecular cyclization. We also show that the difficulty in reactions at the neopentyl carbon site is due to the neopentyl carbanion stability, not the sterics.
Near infrared muscle spectroscopy in patients with Friedreich's ataxia.

Friedreich's ataxia is a progressive neurodegenerative disorder of the afferent cerebellar pathways associated with mitochondrial dysfunction at the cellular level. We have used noninvasive continuous near infrared muscle spectroscopy (NIRS) to investigate the delivery and utilization of oxygen in response to exercise in this disorder. Patients performed an incremental treadmill walking protocol in which levels of muscle deoxygenation or oxygenation were continuously measured in the medial calf muscle. The kinetics of recovery from exercise-induced deoxygenation, called the half-time of recovery (t(1/2)) were determined. The t(1/2) was prolonged in patients with Friedreich's ataxia compared with controls, and the degree of prolongation correlated with the length of the shorter GAA repeat, a genetic measure that correlates with the age of onset of disease. The t(1/2) also correlated inversely with patient age and with the maximum treadmill speed attained. Several patients also displayed features consistent with inadequate oxygen utilization by muscle. These results suggest that NIRS may be an effective tool for monitoring the biochemical and functional features of Friedreich's ataxia in parallel.
Impact of antimicrobial stewardship programme changes on unnecessary double anaerobic coverage therapy

BACKGROUND Concern has been raised over the practice of unnecessary double anaerobic coverage therapy (DACT) in the hospital setting. However, the incidence of and risk factors for unnecessary DACT are not well studied. On 8 September 2008, the antimicrobial stewardship programme (ASP) at our institution was modified such that several antibiotics, including ampicillin/sulbactam and metronidazole, no longer required pre-approval. We anticipated that this change would increase both unnecessary DACT and target antibiotic consumption. METHODS A nested case-control study was conducted to determine the cumulative incidence of and risk factors for unnecessary DACT. Cases were subjects who received unnecessary DACT while controls were subjects who did not receive DACT or who received necessary DACT. Segmented regression analysis was subsequently performed to evaluate the impact of ASP changes on unnecessary DACT and consumption of target antibiotics. RESULTS From October 2007 to September 2009, the cumulative incidence of unnecessary DACT was 2.3% [95% confidence interval (CI) 1.7-3.1]. Independent risk factors for unnecessary DACT [adjusted odds ratio (95% CI); P value] included hospitalization on a surgical ward [3.51 (1.03-12.02); P = 0.002], hospitalization on an obstetrics and gynaecology ward [9.07 (2.54-32.40); P = 0.002] and underlying metastatic malignancy [3.18 (1.38-7.09); P = 0.006]. The ASP change was associated with an increase in ampicillin/sulbactam and metronidazole consumption. However, there was no significant impact on unnecessary DACT prescribing. CONCLUSIONS Although uncommon, unnecessary DACT is more prevalent in specific services. Future qualitative studies focusing on these specific subgroups would be useful in elucidating this problem more clearly. The ASP changes were not associated with increases in unnecessary DACT.
Characterization of Racemic α-Hydroxy- and β-Hydroxysuccinanilic Acids

Alkaline hydrolysis of racemic malic acid phenylimide (malanil) yielded two products corresponding to the two possible directions of cleavage. These were shown to be racemic α -hydroxy- and β -hydroxysuccinanilic acid present in the ratio 5:1, the proportion being essentially as expected on the basis of the relative electrophilicities of the respective carbonyl centers.
Control of Mars global atmospheric loss by the continuous rotation of the crustal magnetic field: A time‐dependent MHD study

We present a time-dependent MHD study of the controlling effects of the Mars crustal field on atmospheric escape. We calculate globally integrated planetary ion loss rates under quiet solar conditions considering the continuous rotation of crustal anomalies with the planet. It is found that the rotating crustal field plays an important role in controlling atmospheric escape. Significant time variation of ∼20% and ∼50% is observed during the entire rotation period for O+ and for O2+ and CO2+, respectively. The control is exerted mainly through two processes. First, the crustal magnetic pressure over the subsolar regime controls solar wind penetration and mass loading and therefore the escaping planetary ion source. There is a strong negative correlation between the magnetic pressure and ion loss, with a time lag of <1 h for O+ and ∼2.5 h for O2+ and CO2+. Second, the crustal magnetic pressure near the terminator region controls the cross-section area between the induced magnetospheric boundary and 100 km altitude at the terminator. The change in day-night connection regulates the extent to which planetary ions created on the dayside can be ultimately carried away by the solar wind and escape Mars. There is a strong positive correlation between the cross-section area and ion loss, with no significant time lag. As the planet rotates, the dayside process and the terminator process work together to control the total amount of escaping planetary ions. However, their relative importance changes with the local time of the strong crustal field region.
17. – OPIATES AND CYCLIC AMP

Laboratory of General and Comparative Biochemistry, National Institute of Mental Health, Bethesda, Maryland, 20014. Cyclic nucleotides, and particularly cyclic AMP, are believed to play important roles in the nervous system as second messengers of synaptic communication (1-4). Thus, catecholamines functioning through 8-adrenergic receptors, dopamine, histamine, adenosine, E prostaglandins and some other putative neurotransmitters and neuromodulators are believed to function as substances which stimulate adenylate cyclase and thus raise cyclic AMP levels in cells with the appropriate receptors. Morphine and the other opiate-like substances have been shown to interact, directly or indirectly, with Many of these transmitter and modulator substances (5-7), and it was therefore natural to ask whether the opiates might not also function via the adenylate cyclase system.
Directions for Bipartisan Medicare Reform

Although meaningful Medicare reform is not likely to occur until after the 2012 elections, some Republicans and Democrats appear to be in substantial agreement about some changes that might make Medicare more efficient, effective, and fiscally sustainable.
Cellular bioavailability of natural hormones and environmental contaminants as a function of serum and cytosolic binding factors.

Environmental contaminants have been reported to function as hormone mimics in various wildlife species. To investigate a potential mechanism for the interaction of contaminants with the endocrine system, we evaluated the cellular bioavailability of numerous chemicals. Hormone binding proteins from oviductal cytosol of the American alligator (Alligator mississippiensis) and yellow-bellied turtle (Trachemys scripta) were used in competitive binding assays with [3H] 17β-estradiol. Most of the environmental contaminants, and the potent, synthetic estrogen diethylstilbestrol (DES), did not interact with the cytosolic binding proteins. Among the compounds tested, o,p'-DDT and toxaphene exhibited the greatest affinity for the binding proteins. The functional consequence of the apparent lack of interaction of most contaminants with binding proteins was studied in a strain of yeast containing the human estrogen receptor (YES assay). The activation of YES with estradiol was reduced 30% in the presence of a physiol...
Bilingual Language Acquisition: The development of verb morphology

Introduction Previous research (e.g., Lipski 1993; Montrul 2009; Silva-Corvalan 1994; Zentella 1997) has shown that in situations of societal bilingualism a functionally restricted language evidences grammatical simplification, among other phenomena. The question that arises is whether this stage of grammatical simplification is due to imperfect or incomplete acquisition in the early years of a bilingual’s life, or is a result of processes of attrition or loss of acquired knowledge of the underused language (Cuza 2010; Montrul 2002, 2005). I explore this question in this chapter, in addition to the issue that underlies the various chapters of the book, namely, the effect that differing levels of proficiency have on bilingual development. The empirical study is conducted on data from the two developing bilingual siblings (Nico and Brennan), from the very first production of what in adult language would be considered to be “a verb” until age 5;11, when the siblings began to attend kindergarten in the Spanish-immersion track of a dual-language school (see Chapter 2). In this case, the central question of what effect reduced exposure to a language may have is explored in the development of tense, mood, and aspect markers (TMA) in English and Spanish. To this end, the chapter presents a description of the path of development of verb inflections in the two languages. It also gives information about the siblings’ verb lexicon in the early age stages. Although the study is centered on the siblings’ productive abilities, it is assumed that their comprehension abilities are at least equally developed. There is no evidence of misunderstandings in the early stages, but some instances of misunderstood conditionals in Spanish are attested in the later years, when communication includes reference to hypothetical situations and the language addressed to the children is more complex linguistically and in terms of content.
The diversified examination methods in the reform of database courses

Through analyzing the significance of diversified examination methods and learning from other advanced countries,the authors try the reform in the "Database System Essentials",and design several special ways of examination.The authors also have some proposals in various types of courses for reference.
Protoplast Preparation of Barnyardgrass (Echinochloa sp.) Pathogenic fungus Curvularia lunata

The effects of factors, such as mycelia growth stage, lytic enzyme concentration, osmotic presure of stabilizer, pH value of buffer solution and digesting temperature, on the formation of protoplast of Barnyard grass (Echmochloa sp. ) pathogenic fungus Curvularia lunata were studied. Maximum yield of C. lunata protoplast could be obtained with mycelia cultured for 18 h by using 2％ Lywallzyme and 4％ Cellulase (pH5.8) containing 0.7 mol·L~(-1) K Cl as osmotic stabilizer and digesting for 4 h at 30℃. Theregeneration of the protoplast of C. lunata was tested on the solid media containing osmotic stabilizer and the regeneration rate reached 0.76％.
Diagnostic considerations in the medical setting.

The diagnostic models traditionally used by the psychiatrist do not lend themselves to the assessment of many of the problems that confront the nonpsychiatric physician on a day-to-day basis. Ways in which the psychiatrist might contribute to the resolution of these issues and expand his role in the medical setting are explored.
Design, Synthesis, and In Vitro and In Vivo Evaluation of an (18)F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer.

Sphingosine 1-phosphate receptor 1 (S1P1) plays a pivotal signaling role in inflammatory response; because S1P1 modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P1 would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P1 (S1P1 IC50 100-fold selectivity for S1P1 over S1P2 and S1P3). The most potent ligand, 28c (IC50 = 2.63 nM for S1P1) was (18)F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P1-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [(18)F]28c accumulation in the liver of LPS-treated mice than controls. Increased expression of S1P1 in the LPS model was confirmed by immunohistochemical analysis (IHC). These data suggest that [(18)F]28c is a S1P1 PET tracer with high potential for imaging S1P1 in vivo.
Reaching Closure on Health-Related Controversies

… Science cannot tell us how many potential human cancers swim in a can of diet soda, though it has made some guesses. What can be shown is that a weak cancer can be induced by saccharin in rats, but only under unusual conditions whose relevance to human risk is obscure. From epidemiology we learned that the number of human bladder cancer cases that might currently be caused by past patterns of saccharin use is certainly small, and perhaps zero. We know, on the other hand, that it is at least plausible that saccharin offers substantial health benefits to certain groups of people, that these benefits need not be large in order to offset saccharin’s slight risk, and that, unless we know for sure that the benefits are imaginary, it would be reckless to gamble with the public’s health to compel a ban on diet food products. We know that a simple program of informing the public would accomplish by itself most or all af the aims of wise policy. And we know that the impetus for a ban does not issue from a proven public injury but from a well-intentioned legalism whose full consequences probably were not foreseen. Finally, we know that the public has spoken against a ban not just patiently and politely, but with a mass roar ([3], p. 24).
The Disproportionate Effect of Perioperative Complications on Mortality within 1 Year After Colorectal Cancer Resection in Octogenarians

Risks and benefits of colorectal cancer resection in octogenarians are not clearly defined. This study aimed to assess the relationship between morbidity and mortality within 1 year after colorectal cancer resection in octogenarians compared with other age groups. A single-institution, prospectively maintained database was queried to identify patients with sporadic, pathological stages I–III colorectal adenocarcinoma, electively undergoing radical resection with curative intent between 2000 and 2012. Patients were divided into three age groups: ‘octogenarians’ if ≥80 years of age; ‘intermediate’ if ≥65 and <80 years of age; and ‘younger’ if <65 years of age. Overall, 2485 patients fulfilled the inclusion criteria—326 in the octogenarian age group, 949 in the intermediate age group, and 1210 in the younger age group. Postoperative morbidity disproportionally increased 1-year mortality in octogenarians when compared with the younger age group (37 vs. 6.5 %; p < 0.001). Anastomotic leak, abdominopelvic abscess, reoperation, and readmission rates were comparable among different age groups, but were associated with a disproportionate risk of 1-year mortality in octogenarians (67, 43, 33, and 41 %, respectively). Multivariate analysis indicated that older age and postoperative complications were the only two independent variables associated with 30- and 90-day mortality. Besides these, American Society of Anesthesiologists (ASA) and pathological stage III were additional independent variables associated with 1-year mortality. An interaction test confirmed that age and postoperative complications were independent variables, with additive effect on 30-day, 90-day, and 1-year mortality. Age plays an important and independent role in affecting mortality when complications occur following surgery for colorectal cancer. The full magnitude of postoperative risks should be taken into consideration when discussing colorectal cancer surgery in octogenarians.
Forestland owners' willingness to plant pine on non-forested land for woody bioenergy in Virginia

Woody bioenergy provides an opportunity for new source of revenue, which forestland owners can respond to either by supplying biomass from an existing stand or by establishing feedstock plantations on currently non-forested land. Using survey data sent out to 900 randomly selected participants in Virginia, we assess if forestland owners would allocate parts of their currently non-forested land, such as cropland and pasture/grazing land, to growing loblolly pine for bioenergy production purposes. Using recursive partitioning based logistic regression, we show that the decision to plant pine on non-forested land depends both on economic and non-economic factors, including price, demographic attributes of the forestland owner, mode of land acquisition and their respective threshold values, providing profile types policies encouraging biomass supply can use in tailoring their efforts. Using bid values, expected landowner revenue from growing pine, we also find a mean willingness to accept value of $1424/acre. Our results also show that the choice among land use types follows economies of scale while the choice among land covers for a given land use type follows species diversification.
Reinforcement learning with a hierarchy of abstract models

Reinforcement learning (RL) algorithms have traditionally been thought of as trial and error learning methods that use actual control experience to incrementally improve a control policy. Sutton's DYNA architecture demonstrated that RL algorithms can work as well using simulated experience from an environment model, and that the resulting computation was similar to doing one-step lookahead planning. Inspired by the literature on hierarchical planning, I propose learning a hierarchy of models of the environment that abstract temporal detail as a means of improving the scalability of RL algorithms. I present H-DYNA (Hierarchical DYNA), an extension to Sutton's DYNA architecture that is able to learn such a hierarchy of abstract models. H-DYNA differs from hierarchical planners in two ways: first, the abstract models are learned using experience gained while learning to solve other tasks in the same environment, and second, the abstract models can be used to solve stochastic control tasks. Simulations on a set of compositionally-structured navigation tasks show that H-DYNA can learn to solve them faster than conventional RL algorithms. The abstract models also serve as mechanisms for achieving transfer of learning across multiple tasks.
Circadian Clock and Photoperiodic Flowering in Arabidopsis: CONSTANS Is a Hub for Signal Integration

The circadian clock and light signaling regulate CONSTANS function through intricate mechanisms that reside in phloem companion cells of leaves for controlling photoperiodic flowering in Arabidopsis.
Long-term vital sign measurement using a non-contact vital sign sensor inside an office cubicle setting

Heart and respiration rates can be wirelessly measured by extracting the phase shift caused by the periodic displacement of a patient's chest wall. We have developed a phased-array Doppler-based non-contact vital sign (NCVS) sensor capable of long-term vital signs monitoring using an automatic patient tracking and movement detection algorithm. Our NCVS sensor achieves non-contact heart rate monitoring with accuracies of over 90% (i.e, within ±5 Beats-Per-Minute vs. a reference sensor) across a large number of data points collected over various days of the week inside a typical office cubicle setting at a distance of 1.5 meters.
Red flags in the clinical interview may forecast invalid neuropsychological testing.

AbstractObjective: Evaluating assessment validity is expected in neuropsychological evaluation, particularly in cases with identified secondary gain, where malingering or somatization may be present. Assessed with standalone measures and embedded indices, all within the testing portion of the examination, research on validity of self-report in the clinical interview is limited. Based on experience with litigation-involved examinees recovering from mild traumatic brain injury (mTBI), it was hypothesized that inconsistently reported date of injury (DOI) and/or loss of consciousness (LOC) might predict invalid performance on neurocognitive testing. Method: This archival study examined cases of litigation-involved mTBI patients seen at an outpatient neuropsychological practice in Philadelphia, PA. Coded data included demographic variables, performance validity measures, and consistency between self-report and medicolegal records. Results: A significant relationship was found between the consistency of examine...
Associations Between β-Amyloid Kinetics and the β-Amyloid Diurnal Pattern in the Central Nervous System.

Importance Recent studies found that the concentration of amyloid-β (Aβ) fluctuates with the sleep-wake cycle. Although the amplitude of this day/night pattern attenuates with age and amyloid deposition, to our knowledge, the association of Aβ kinetics (ie, production, turnover, and clearance) with this oscillation has not been studied. Objective To determine the association between Aβ kinetics, age, amyloid levels, and the Aβ day/night pattern in humans. Design, Setting, and Participants We measured Aβ concentrations and kinetics in 77 adults aged 60 to 87 years with and without amyloid deposition by a novel precise mass spectrometry method at the Washington University School of Medicine in St Louis, Missouri. We compared findings of 2 orthogonal methods, enzyme-linked immunosorbent assay and mass spectrometry, to validate the day/night patterns and determine more precise estimates of the cosinor parameters. In vivo labeling of central nervous system proteins with stable isotopically labeled leucine was performed, and kinetics of Aβ40 and Aβ42 were measured. Interventions Serial cerebrospinal fluid collection via indwelling lumbar catheter over 36 to 48 hours before, during, and after in vivo labeling, with a 9-hour primed constant infusion of 13 C 6 -leucine. Main Outcomes and Measures The amplitude, linear increase, and other cosinor measures of each participant’s serial cerebrospinal fluid Aβ concentrations and Aβ turnover rates. Results Of the 77 participants studied, 46 (59.7%) were men, and the mean (range) age was 72.6 (60.4-87.7) years. Day/night patterns in Aβ concentrations were more sharply defined by the precise mass spectrometry method than by enzyme-linked immunosorbent assay (mean difference of SD of residuals: Aβ40, −7.42 pM; P P r = 0.42; P r = 0.28; P r = −0.38; P r = 0.238; P Conclusions and Relevance Amyloid deposition is associated with premature loss of normal Aβ42 day/night patterns in older adults, suggesting the previously reported effects of age and amyloid on Aβ42 amplitude at least partially affect each other. Production and turnover rates suggest that day/night Aβ patterns are modulated by both production and clearance mechanisms active in sleep-wake cycles and that amyloid deposition may impair normal circadian patterns. These findings may be important for the designs of future secondary prevention trials for Alzheimer disease.
In vitro characterization of electronically stimulated ionic electroactive polymers with application to muscle prosthesis

Towards the development of new classes of subcutaneous muscle prosthesis, this paper presents and discusses results of in vitro characterization of biocompatible ionic electro-active polymers (iEAPs) under different electrical stimulation scenarios. The electrical stimulation is provided via a low-dropout regulator (LDO). The functionality of electrically stimulated iEAPs is evaluated under steady-state and transient conditions. Electrical characteristics of iEAPs in terms of conductance, and movement characteristics of iEAPs in terms of changes in the bending angle during fixed and transient stimulation are evaluated. Measured results suggest that iEAPs in combination with LDO-based stimulator have great potentials for the realization of the next generation muscle prosthesis that are flexible, and can enable immediate movement restoration, upon implantation.