cssi/SciSciGPT-SciSciNet huggingface dataset:
Biologic basis for combining drugs with radiation.

Concurrent administration of radiation and chemotherapy has emerged as a dominant form of cancer treatment. Nevertheless, our understanding of the specific mechanisms of interaction between radiation and chemotherapy is still evolving. Biological evidence gained in experimental cell lines and tumors suggests that cisplatin lesions cause repair inhibition of radiation-induced DNA damage affecting both homologous recombination and nonhomologous end joining. In the case of 5-fluorouracil (5-FU), the crucial event in the radiosensitisation process appears to be inappropriate progression through S-phase in the presence of bound drug affecting both DNA repair and cell cycle. In similar fashion, data with gemcitabine suggest that radiosensitization arises through progression into S-phase causing depletion of 2′-deoxyadenosine 5′-triphosphate pools, which leads to misincorporation and misrepair of incorrect bases in irradiated cells. As the new molecular-targeted agents become increasingly available to complement established radiation and chemoradiation treatment regimens, new concepts of drug-radiation interaction are evolving that require innovative thinking regarding the manner in which radiation and drugs cooperate and how clinical trials are best performed.
Long-latency evoked potentials to irrelevant, deviant stimuli.

Occasional shifts of loudness in a repetitive train of clicks elicited a late-positive wave (P3a) in nonattending subjects which peaked at a mean latency of 258 msec and had a frontocentral scalp distribution; P3a was typically preceded by an 'N2' component at 196 msec. The P3a wave was distinguishable from the longer-latency (378 msec) parietocentrally distributed 'P3b' wave that was evoked by the same stimulus in an actively attending subject, thus confirming the findings of Squires et al. (1975). Infrequently presented single sounds did not produce large or consistent N2-P3a components; the critical condition for the generation of an N2-P3a wave seemed to be that the infrequent sounds represent a deviation (intensity increment or decrement) from a repetitive background. Furthermore, increasing the repetition rate of the background clicks drastically reduced N1-P2 amplitude but had little effect on the amplitude of N2-P3a. This suggests that N2-P3a is not simply a delayed N1-P2 'vertex potential', but rather reflects the operation of a 'mismatch' detector, which registers deviations from an ongoing auditory background.
Polymyxin B and Colistin: Activity, Resistance and Crossresistance in vitro.∗

Summary and ConclusionsPolymyxin B and colistin. 2 closely related polypeptide antibiotics, had similar antibacterial activity against a large number of pathogenic bacteria. Polymyxin was somewhat more active than colistin against 55% of susceptible strains. on the average 3.4 and 4 times as active against most strains of N. gonorrhoeae and H. influenzae, respectively. Highly resistant variants developed on repeated subculture of a strain of A. aerogenes and one of Ps. aeruginosa on agar containing either of these antibiotics; complete crossresistance to the other antibiotic developed in each instance. Single-step mutants of the same strain of A. aerogenes, highly resistant to each antibiotic, were readily obtained by seeding a large inoculum on the surface of agar containing 100 or 200 μg/ ml of that antibiotic; these mutants were completely cross-resistant to the heterologous antibiotic. Antibiotic-dependent variants were not encountered.
The pH dependent accumulation of PCP in aquatic microcosms with sediment

Abstract The fate of pentachlorophenol in aquatic microcosms, consisting of three trophic levels and held under varying conditions of pH and sediment type, was assessed. The pH was set at 4, 6, or 8, with an organic sediment (3% organic carbon) or an inorganic sediment (0% organic carbon) as a substrate. The distribution of PCP in the microcosm media and organisms varied significantly as environmental conditions changed. There was significantly more PCP (or phenate ion) in the water at pH 8 than pH 6 or 4 in both the organic and inorganic systems. However, accumulation of PCP in most of the microcosm organisms was significantly greater at pH 4, followed by 6 and then 8. Partitioning of PCP into organic sediment followed the same trend with the highest amounts of PCP appearing in sediment at pH 4. The organic carbon content of sediment was important in determining partitioning into sediment; the 3% organic carbon sediment sorbed significantly more PCP than the 0% organic carbon sediment. In addition, the organisms in the 3% organic carbon sediment microcosms accumulated significantly less PCP then did those in the 0% organic carbon systems. The 3% organic carbon sediment also appeared to facilitate the breakdown of PCP in sediment and water. Among others these data indicate that hazard assessments should not be based on aqueous levels of PCP unless pH is considered.
Induction of the heme oxygenase-1 gene by metalloporphyrins.

Induction of expression of heme oxygenase-1 (HO-1) has been studied in primary cultures of chick embryo liver cells and in the LMH line of avian hepatoma cells. Cells were transiently transfected with selected constructs containing portions of the 5′-untranslated (promoter) region of the HO-1 gene linked to luciferase as reporter gene. LMH cells that had been stably transfected with selected wild type or mutant constructs were also studied. Metalloporphyrins, especially Fe protoporphyrin (heme) and Co protoporphyrin strongly induced luciferase expression in both types of transfected cells. Low concentrations of Zn mesoporphyrin, an inhibitor of HO activity, exerted a synergistic effect on heme-, but not Co protoporphyrin-dependent induction. The antioxidant and SH donor N-acetyl cysteine had little effect on the metalloporphyrin-dependent inductions of HO-1, in contrast to its marked inhibitory effect on the sodium arsenite-dependent induction of the HO-1 gene. Deletional analysis showed that the key element(s) required for the metalloporphyrin-dependent induction of HO-1 is located between −3.6 and −5.6 kb upstream of the transcription starting point. Data from electrophoretic mobility shift and site-directed mutagenesis experiments excluded a role for consensus AP-1 binding elements at −1576, −3647, or −4578 in the inductions produced by heme or Co protoporphyrin.
Cardiac rehabilitation after myocardial infarction. Combined experience of randomized clinical trials.

Randomized clinical trials of cardiac rehabilitation following myocardial infarction have typically demonstrated a lower mortality in treated patients, but with a statistically significant reduction in only one trial. To overcome the problem of not being able to detect small but clinically important benefits in mortality in randomized clinical trials of exercise and risk factor rehabilitation after myocardial infarction with small numbers of patients, we carried out a meta-analysis on the combined results of ten randomized clinical trials that included 4347 patients (control, 2145 patients; rehabilitation, 2202 patients). The pooled odds ratios of 0.76 (95% confidence intervals, 0.63 to 0.92) for all-cause death and of 0.75 (95% confidence intervals, 0.62 to 0.93) for cardiovascular death were significantly lower in the rehabilitation group than in the control group, with no significant difference for nonfatal recurrent myocardial infarction. These results suggest that, for appropriately selected patients, comprehensive cardiac rehabilitation has a beneficial effect on mortality but not on nonfatal recurrent myocardial infarction. ( JAMA 1988;260:945-950)
Xylem vascular anatomy and water transport of Salicornia europaea

Abstract The xylem anatomy, changes in vessel member diameter at stem nodes and branch junctions, and effects of these changes on water flow rates and water potential in greenhouse and field grown Salicornia europaea L. (Chenopodiaceae) have been investigated. There was a two-fold decrease in vessel diameter at branch junctions and stem nodes. In greenhouse grown plants, this decrease resulted in a 1000-fold decrease in water flow rates, and a four-to eight-fold increase in resistance to water flow across branch junctions and stem nodes relative to within-internode flow rates. However, in field grown plants, there were no differences in water flow across branch junctions and stem nodes compared with water flow within internodes. Water potentials in field plants were 3–15 times lower than in greenhouse plants. Under field conditions, hypersalinity is probably the key determinant of Salicornia water relations. Localized reductions in vessel member diameter in Salicornia appear to result from developmental changes in vasculature attending axillary bud growth. Reductions in Salicornia vessel diameter, therefore, may not be hydraulically functional adaptations per se. Rather, they may reflect a consequence of developmental branching.
An analogous model for slabs using a truss element

Abstract Restrained reinforced concrete slabs have load-deflection curves which are similar to those for shallow shells. These curves have a distinct instability following an initial peak. However, most analytical procedures for slabs do not take into consideration the effects of nonlinear geometry, but attribute the instability to material nonlinearity. In this paper, a simple truss element model which is typically used in the stability analysis of thin shells is shown to predict the total load-deflection curve for a restrained slab. The element is formulated with a small initial angle of inclination which is related to the height of the internal arch formed in the slab during early deflections. Solution of the nonlinear equation is accomplished with the Newton-Raphson method. Results of analyses demonstrate a reasonable similarity with recent experimental data.
Elevated Temperature Fatigue Prediction Model for AISI 4340 Gun Steel

Cannon barrel life can be maximized by fully understanding the correlation between temperature and hoop stress and their relation to crack growth. Use of elevated temperature fatigue to predict failure of a gun barrel based on the number and type of rounds along with temperature data will both maximize the usable life of a cannon barrel and maintain a safe operating environment the men and women using these cannons. This analysis will help increase the usable life of large caliber cannon barrels; round data that is collected throughout the life of a cannon barrel will be used to determine the proper time to decommission the barrel. Experimental data was collected utilizing an MTS 858 fatigue system applying low cycle fatigue analysis. Numerous operating temperatures and stresses were calculated from various cannon round types and used to determine test parameters. From this data, a correlation was generated between stress and temperature to predict life expectancy of the test specimens. Several specimens were then cycled for various temperature and pressure combinations, thereby verifying the accuracy of the prediction model. Data was collected using methods set forth in ASTM E466-07 which dictates the standard practice for force-controlled fatigue testing. Data was analyzed using Minitab for development of the life cycle prediction model. Since the accuracy of the model dictates its reliability, this was used to provide a safety cushion to ensure that failure does not occur prior to the expected time.Copyright © 2008 by ASME
Differential Integration of DPLP Protein Variants Regulates Inactivation Kinetics of Neuronal A-Type Current

Voltage-sensitive potassium channel complexes consisting of Kv4 pore-forming subunits and modulatory subunits mediate the neuronal subthreshold A-type current (ISA), a regulator of membrane excitability and action potential firing patterns. Both the KChIP (Kv channel-interacting proteins) and DPLP (dipeptidyl peptidase-like protein) modulatory subunits are expressed as N-terminal variants, and two DPLP variants (DPP10a, DPP6a) possess the unusual property of inducing similar fast inactivation kinetics of Kv4 channels in reconstitution studies. To investigate whether their effects are similar on native ISA, we characterized ISA from DPP10a-expressing cortical layer II/III pyramidal neurons (CtxPN) and DPP6a-expressing cerebellar granule neurons (CbGN) in rat brain slices. Surprisingly, CtxPN ISA and CbGN ISA differ significantly in their inactivation kinetics. CtxPN ISA undergo mono-exponential decay (τ = ∼8 ms); CbGN ISA, bi-exponential decay (at +36 mV: τ-1 = ∼11 ms, τ-2 = ∼120 ms). While CtxPN ISA resembles heterologously expressed Kv4.2+KChIP3a+DPP10a current, CbGN ISA is not recapitulated by the Kv4.2+KChIP3a+DPP6a current. Since CbGN reportedly also express robust levels of other DPP6 variants competing for Kv4 channels, we quantitated the levels of different DPP6 isoforms by qRT-PCR and determined their percentage contributions: DPP6a (DPP6-E) = ∼32%, DPP6b (DPP6-K) = ∼42%, DPP6c (DPP6-L) = ∼8%, and DPP6d (DPP6-S) = ∼18%. Since DPP6a and DPP6b variants together constitute the majority of the CbGN DPP6 species, we performed coexpression studies to investigate whether CbGN ISA is mediated by ternary complex channels with these DPP6 variants. We propose that relative ratios of DPLP auxiliary subunit isoforms likely contribute to the variability of ISA inactivation kinetics between neuronal populations.
The impact of OECD biofuels policies on developing countries.

OECD countries’ biofuels policies, derived from energy and environmental legislation and activated by high oil prices, were the primary cause of not only the sudden spike in grain and oilseed prices in 2007–2008 but also of the ensuing price volatility. Even though developing countries have a comparative advantage in biofuels production, they were shut out of rich countries’ biofuel markets by trade discriminating biofuels policies. Developing countries would not have been able to take full advantage of the price spike in the short run anyway given the low supply elasticities and the long time required for biofuel production to come online, unlike for corn-ethanol. The controversy over the right price of food is misplaced and policy makers should instead focus on improving biofuels policies, which like their counterpart agricultural policies in previous decades, have damaged the welfare of developing countries.
Benzoylecgonine Hydrazides: Synthesis, Coupling to Horseradish Peroxidase, and Characterization of the Conjugates

Benzoylecgonine-horseradish peroxidase conjugate (BE-HRP) can be used as a diagnostic reagent for the detection of cocaine in illicit drug samples and in biological fluids. This paper describes the preparation and characterization of BE-HRP. Two hydrazide derivatives of benzoylecgonine, N-2-(tert-butyloxycarbonyl)benzoylecgonine hydrazide and mono(N-2'-benzoylecgoninoyl)adipic dihydrazide, were synthesized by carbodiimide-activated coupling of benzoylecgonine to N-2-(tert-butyloxycarbonyl) hydrazide and adipic dihydrazide, respectively. Removal of the tert-butyloxycarbonyl protecting group in N-2-(tert-butyloxycarbonyl)benzoylecgonine hydrazide with anhydrous HCl yielded benzoylecgonine hydrazide hydrochloride. NMR and high-resolution mass spectral analyses demonstrated that the benzoyl group of benzoylecgonine remained intact under the conditions of both carbodiimide coupling and anhydrous HCl treatment. By aldehyde-hydrazide condensation, the hydrazides were covalently conjugated to the carbohydrate residues of horseradish peroxidase (HRP). Dot blot analysis of the conjugates employing antibodies specific to benzoylecgonine demonstrated the presence of bound benzoylecgonine in HRP. The stoichiometry of benzoylecgonine residues to HRP was determined by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Mono(N-2'-benzoylecgoninoyl)adipic dihydrazide gave a 2.5-3-fold higher coupling compared with benzoylecgonine hydrazide. Conjugates were also prepared by the coupling of the carbodiimide-activated benzoylecgonine to HRP that was derivatized with adipic dihydrazide.
Quantifying faculty teaching time in a department of obstetrics and gynecology.

Abstract Objective: The goal of this project was to develop a reproducible system that measures quantity and quality of teaching in unduplicated hours, such that comparisons of teaching activities could be drawn within and across departments. Such a system could be used for allocating teaching monies and for assessing teaching as part of the promotion and tenure process. Methods: Various teaching activities, including time spent in clinic, rounds, and doing procedures, were enumerated. The faculty were surveyed about their opinions on the proportion of clinical time spent in teaching. The literature also was reviewed. Results: Based on analysis of the faculty survey and the literature, a series of calculations were developed to divide clinical time among resident teaching, medical student teaching, and patient care. The only input needed was total time spent in the various clinical activities, time spent in didactic activities, and the resident procedure database. Conclusion: This article describes a simple and fair database system to calculate time spent teaching from activities such as clinic, ward rounds, labor and delivery, and surgery. The teaching portfolio database calculates teaching as a proportion of the faculty member’s total activities. The end product is a report that provides a reproducible yearly summary of faculty teaching time per activity and per type of learner.
Choline acetyltransferase immunoreactivity in the human vestibular end-organs.

Abstract Acetylcholine (ACh) is believed to play a major role in the efferent vestibular system in several animal models, however no information regarding the role of ACh in the human efferent vestibular system has been published. Post-embedding immunohistochemistry in a hydrophilic resin was used to investigate the choline acetyltransferase immunoreactivity (ChATi) and acetylcholinesterase (ACHE) histochemistry in human vestibular end-organs. ChATi and AChE activity was found in numerous bouton-type terminals at the basal area of the vestibular hair cells. These terminals were found to contact type II vestibular hair cells and the afferent chalices surrounding type I hair cells. This study provides the first evidence that the human efferent vestibular axons and terminals are cholinergic.
The hidden observer, hypnotic dreams, and age regression: clinical implications.

This article summarizes data from three studies (Mare, Lynn, Kvaal, Segal, & Sivec, in press; Lynn, Mare, Kvaal, Segal, & Sivec, 1993) designed to extend research on the "hidden observer" to two phenomena of clinical relevance: hypnotic dreams and suggested age regression. Subjects received suggestions for a hypnotic dream or age regression and then received suggestions for a "hidden observer" (i.e., the subject possesses a part of the self that is aware of images and ideas that the conscious mind is unaware of) with respect to the dream or age-regression experience. Hidden reports contained more personally relevant information than the target suggestions (i.e., dream, age regression). Subjectives were also less likely to recall hidden reports. The high rate of hidden-observer responding (> 80%) was also evident in nonhypnotized simulating and relaxed subjects, although they did not exhibit as much primary process thinking in their dream reports as hypnotized subjects. Case studies of a trauma client and a forensic client are used to illustrate the clinical potential of hidden-observer suggestions.
Dexmedetomidine for Acute Baclofen Withdrawal

Intrathecal baclofen is widely accepted as a treatment option for severe spasticity through its γ-Aminobutyric acid-B (GABAB ) agonist properties. Abrupt cessation can lead to severe and life-threatening withdrawal characterized by altered mental status, autonomic dysreflexia, rigidity, and seizures. This symptomatic presentation is similar to alcohol withdrawal, which is mediated by modification of GABAA expression. Use of the α2-adrenergic agonist dexmedetomidine for the treatment of ethanol withdrawal has been widely reported, raising the question of its potential role in baclofen withdrawal. We present a case of the successful treatment of acute severe baclofen withdrawal with a dexmedetomidine infusion. A 15-year-old patient with spastic quadriparesis and cerebral palsy underwent unexpected removal of his baclofen pump due to an infection that was encountered during a planned pump revision. Following removal, he was placed on high dose enteral baclofen every 6 h. Despite further benzodiazepine supplementation, he had progressive hemodynamic instability, severe rebound spasticity, and intermittent spontaneous clonus consistent with baclofen withdrawal. A dexmedetomidine infusion was titrated to a peak dose of 16 mcg per hour with successful treatment of withdrawal symptoms. The patient became normotensive without tachycardia. Tone and agitation improved. Dexmedetomidine is to our knowledge a previously unreported option for treatment of acute severe baclofen withdrawal. We report a case of safe and efficacious use in a patient with spastic quadriparesis on chronic intrathecal baclofen. Scientifically rigorous comparison with other options remains to be performed.
Trinocular stereo: a real-time algorithm and its evaluation

In telepresence applications each user is immersed in a rendered 3D-world composed from representations transmitted from remote sites. The challenge is to compute dense range data at high frame rates, since participants cannot easily communicate if the processing cycle or network latencies are long. Moreover errors in new stereoscopic views of the remote 3D-world should be hardly perceptible. To achieve the required speed and accuracy, we use trinocular stereo, a matching algorithm based on the sum of modified normalized cross-correlations, and subpixel disparity interpolation. To increase speed we use Intel IPL functions in the pre-processing steps of background subtraction and image rectification as well as a four-processor parallelization. To evaluate our system we have developed a testbed which provides a set of registered dense "ground-truth" laser data and image data from multiple views.
Displacement Energies for Nanorods

The geometries have been optimized and harmonic frequencies computed for three small hydrocarbon rods. The two lowest unique frequencies correspond to a torsion and a bend of the rods. The energy to bend or twist the rods has been computed by adding a fraction of the normal coordinate corresponding to these two modes to the equilibrium geometry. The density functional theory (using B3LYP) and self-consistent field (SCF) results are very similar for all properties considered.
Evaluating software design processes by analyzing change data over time

An analysis is presented of early design and code change data from the software cost reduction (SCR) project, a well-reported effort conducted at the US Naval Research Laboratory from 1978 to 1988. The analyses are mostly time-based studies of the change data and relationships between the data and SCR personnel activity data. Some analyses of the change data show patterns consistent with a major goal of the SCR project: the design and development of easy-to-change software. Specifically, most changes took a day or less to uncover and resolve; the majority of changes updated at most one module. Moreover, these percentages remained fairly stable. No positive relationship appeared between error-correction effort and the number of days that an error remained in the SCR design documentation. Other analyses suggest that consistency may have been temporary. For example, the analyses suggest a stepwise growth in average change effort, and an increasing percentage of changes resulted in module interface updates. Certain specific ratios between SCR change data and personnel activity data may be possible indicators of design incompleteness. >
Roller coaster marathon: being a live liver donor.

The purpose of this phenomenological study was to examine the meaning of being a live liver donor. Six people between ages 27 and 53 years participated. A qualitative, in-depth, semistructured interview format was used to explore donors' thoughts and feelings about being an organ donor. Five themes were identified: (1) no turning back—how do I live without you? (2) roller coaster marathon, (3) donor network, (4) the scar, and (5) reflections—time to think. At the center of the experience was the donor's commitment to the recipient. Once donors began the process, they were determined to see it through. The process was complex, and donors received various levels of support from family, friends, health care professionals, and others. After donation, as donors recovered and were able to resume their usual daily responsibilities, they reflected on the impact of the experience and how it changed their view of life.
Use of melatonin for sleep and circadian rhythm disorders

Although not licensed as a drug, melatonin is widely sold as a nutritional supplement in the USA for its purported sleep-promoting and antiageing properties. In this article, we provide some guidelines for its use in sleep disorders medicine. In brief, melatonin appears to promote sleep by producing corrective circadian phase shifts, thereby improving the alignment of the endogenous sleep propensity rhythm with the desired sleep schedule. Melatonin may also have a direct soporific effect, especially when administered during the day. We suggest that the direct soporific action results from the release of accumulated sleep drive by melatonin's attenuation of the circadian alerting signal. Melatonin has not been proven safe by the usual clinical trial criteria, but to date no catastrophes have been related to its use. Also, there is little information about the safety and efficacy of chronic administration.
The Radical Promise of Reformist Zeal: What Makes “Inquiry for Equity” Plausible?

Education reform movements often promise more than they deliver. Why are such promises plausible in light of seemingly perpetual education reform? Drawing on ethnographic fieldwork based in a nonprofit education reform organization, this article explores the appeal of popular notions about “using data to close the racial achievement gap.” It focuses on training institutes wherein passionate reformers made complex claims about the power of a program called Inquiry for Equity. It argues that zealous performances of faith in the program raise expectations for social—not just educational—transformation. Because such radical claims cannot be pinned down in either public documents or daily discourse, they elude critical assessment.[education reform, affect, equity, progressive politics, inquiry]
Use of daily vitamin K supplementation in patients on warfarin with a history of frequent dose changes or variable INRs

Variation in dietary intake of vitamin K is known to lead to international normalized ratio (INR) instability in patients on warfarin. Additionally, patients with a history of unstable INRs have lower dietary intake of vitamin K than patients with stable INRs. It is not known if daily supplementation with vitamin K leads to INR stabilization in patients with a history of variable INRs. We performed a prospective open-label crossover study of patients on warfarin with a history of fluctuating INRs to determine whether vitamin K supplementation leads to a decrease INR variability, how soon the INR decreases after vitamin K therapy is initiated, the time to reach a therapeutic INR after vitamin K initiation, and how much of an increase in warfarin dose is needed to maintain the INR in the desired range. Patients completed a 9 week observation phase in which patients remained on warfarin alone followed by an 8 week period with patients receiving vitamin K 500 lg daily. INRs were determined once weekly with a home point of care monitoring instrument. INR variability decreased with vitamin K supplementation in five of the nine patients studied. INR decreased 2–7 days after vitamin K was initiated and it took 2–35 days for INRs to return to the therapeutic range. Warfarin dose increases ranging from 6% to 95% were required to bring the INR back into the therapeutic range. INR fluctuations may decrease in selected patients with unstable INRs who receive vitamin K supplementation, but further large studies are needed to determine the true effects.
Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase

ATP-sensitive potassium channels (KATP channels) regulate cell excitability in response to metabolic changes. KATP channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K+ channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), activate KATP channels and antagonize ATP inhibition of KATP channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP2 levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed KATP channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K1/2, the half maximal inhibitory concentration, ≈ 60 μM) than the sensitivities from control cells (K1/2 ≈ 10 μM). An inactive form of the PIP5K had little effect on the K1/2 of wild-type channels but increased the ATP-sensitivity of a mutant KATP channel that has an intrinsically lower ATP sensitivity (from K1/2 ≈ 450 μM to K1/2 ≈ 100 μM), suggesting a decrease in membrane PIP2 levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP2 and PI-3,4,5-P3 levels, is a significant determinant of the physiological nucleotide sensitivity of KATP channels.
When silence is golden Ostracism as resource conservation during aversive interactions

This investigation examined whether the strain of ignoring another depends on the other’s desirability as a relationship partner. Participants were asked to ignore or converse with highly likeable (polite and egalitarian) or highly unlikeable (rude and bigoted) acquaintance. They then completed a task in which good performance hinged on successful thought regulation. Study 1 revealed that participants performed worse in the self-regulatory task after conversing with (compared to ignoring) the unlikeable person but performed slightly better after conversing with (compared to ignoring) the likeable person. Study 2 replicated this crossover interaction using an alternative measure of self-regulation. The findings suggest that the use of silent treatment may allow one to conserve regulatory resources during aversive social interactions.
MMST development for HgCdTe FPA manufacture

The Microelectronics Manufacturing Science and Technology (MMST) program at Texas Instruments is developing a generic semiconductor device manufacturing technology for the mid-1990s. In-situ vacuum processing, modular cluster tool equipment, sensor-based real time process control and computer integrated manufacturing are key components of this activity. Although the program goal is to develop and demonstrate low volume, fast cycle time, cost effective silicon microelectronic manufacturing, the technology also is applicable to HgCdTe, GaAs and other materials. The extension and evolution of MMST concepts and technologies to HgCdTe focal plane array production at TI are discussed. The use of generic process modules, sensors, and energy sources are outlined and compared for silicon integrated circuit and HgCdTe FPA applications. Generic modules and those tailored to specific HgCdTe process requirements are discussed.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Preclinical Pharmacokinetics and Tissue Distribution of Long-Acting Nanoformulated Antiretroviral Therapy

Long-acting injectable nanoformulated antiretroviral therapy (nanoART) was developed with the explicit goal of improving medicine compliance and for drug targeting of viral tissue reservoirs. Prior nanoART studies completed in humanized virus-infected mice demonstrated sustained antiretroviral responses. However, the pharmacokinetics (PK) and tissue distribution of nanoART were not characterized. To this end, the PK and tissue distribution of nanoformulated atazanavir (ATV) and ritonavir (RTV) injected subcutaneously or intramuscularly in mice and monkeys were evaluated. Fourteen days after injection, ATV and RTV levels were up to 13-, 41-, and 4,500-fold higher than those resulting from native-drug administration in plasma, tissues, and at the site of injection, respectively. At nanoART doses of 10, 50, 100, and 250 mg/kg of body weight, relationships of more- and less-than-proportional increases in plasma and tissue levels with dose increases were demonstrated with ATV and RTV. Multiple-dose regimens showed serum and tissue concentrations up to 270-fold higher than native-drug concentrations throughout 8 weeks of study. Importantly, nanoART was localized in nonlysosomal compartments in tissue macrophages, creating intracellular depot sites. Reflective data were obtained in representative rhesus macaque studies. We conclude that nanoART demonstrates blood and tissue antiretroviral drug levels that are enhanced compared to those of native drugs. The sustained and enhanced PK profile of nanoART is, at least in part, the result of the sustained release of ATV and RTV from tissue macrophases and at the site of injection.
Cek5, a Membrane Receptor-Type Tyrosine Kinase, Is in Neurons of the Embryonic and Postnatal Avian Brain

Cek5 is a recently identified receptor-type tyrosine kinase of the Eph subclass that is nearly ubiquitously expressed during embryonic development (Pasquale, 1991). Cek5 is predominantly expressed in the avian CNS throughout development, and high levels remain apparent in adult neurons. By means of immunofluorescence microscopy and high-resolution immunoelectron microscopy, Cek5 was found to be expressed in many regions of the chicken brain at various developmental stages, most notably in the hippocampus and cerebellum. The highest concentration of Cek5 was observed in the molecular layer of the cerebellum, associated within the axons of mature granule cells (parallel fibers) and with the cell bodies of immature granule cells. In the axons of parallel fibers, Cek5 was concentrated in the fasciculated nonsynaptic portions. This localization, together with the "adhesion" motifs present in the Cek5 extracellular region suggest that Cek5 may interact with other cell surface-associated molecules and be involved in the growth, guidance, and/or bundling of certain unmyelinated axonal processes. Alternatively (or in addition), Cek5 may represent the receptor for a neurotrophic substance, similar to several other neuronal transmembrane tyrosine kinases.
Transfer learning in real-time strategy games using hybrid CBR/RL

The goal of transfer learning is to use the knowledge acquired in a set of source tasks to improve performance in a related but previously unseen target task. In this paper, we present a multilayered architecture named CAse-Based Reinforcement Learner (CARL). It uses a novel combination of Case-Based Reasoning (CBR) and Reinforcement Learning (RL) to achieve transfer while playing against the Game AI across a variety of scenarios in MadRTSTM, a commercial Real Time Strategy game. Our experiments demonstrate that CARL not only performs well on individual tasks but also exhibits significant performance gains when allowed to transfer knowledge from previous tasks.
The Problem of Organizational Purpose

(1965). The Problem of Organizational Purpose. The Sociological Quarterly: Vol. 6, No. 2, pp. 139-146.
Heifer Performance Under Two Stocking Rates on Fourwing Saltbush-Dominated Rangeland

The efficiency of livestock production in shortgrass steppe may be increased by grazing fourwing saltbush (Atriplex canescens [Pursh] Nutt)-dominated rangeland in late fall and/or early spring, but there is a paucity of information concerning stocking rates and animal gains. The objective of this study was to compare the effects of light and moderate stocking rates on weight gains of heifers grazing twice-replicated 16-ha pastures in late fall (November to mid-January) from 1996 to 1998, and in early spring (April to mid-May) from 1996 to 1999. Stocking rates for late fall (light: 1.3‐1.5 ha � animal unit month � 1 [AUM � 1 ] vs. moderate: 0.8‐1.0 ha � AUM � 1 ) and early spring (light: 3.7‐4.0 ha � AUM � 1 vs. moderate: 2.3‐2.5 ha � AUM � 1 ) were achieved using 5 (for light grazing) and 8 (for moderate grazing) Hereford heifers, with initial average weights of 405 6 5.7 (mean 6 1 SE) kg for the late fall grazing period and 267 6 3.8 kg for the early spring grazing period across the study years. Average daily gain was 58% greater for light (0.65 6 0.06 kg � head � 1 � d � 1 ) compared to moderate (0.41 6 0.05 kg � head � 1 � d � 1 ) stocking rates in the late fall grazing period, and 115% greater with light (0.59 6 0.06 kg � head � 1 � d � 1 ) than with moderate (0.27 6 0.07 kg � head � 1 � d � 1 ) stocking rates in the early spring grazing period. Beef production did not differ between stocking � � ha � 1 ) grazing periods. We suggest that land managers employ light stocking rates during both grazing periods to obtain adequate individual animal gains without sacrificing gains per unit land area. Lengthening the grazing season in the shortgrass steppe should be economically desirable to land managers because feed costs could be lowered and animal gains obtained through minimal input.
Abstract 886: Genetic polymorphisms in telomere pathway genes may potentially impact breast cancer survival

Genetic polymorphisms are not only responsible for disease susceptibility, but may also play a role in determining cancer survival. We examined the associations between genetic variants of 9 genes involved in the telomere pathway in peripheral blood leucocytes (PBLs) and survival among breast cancer cases obtained from a population-based study – the Long Island Breast Cancer Study Project (LIBCSP). Fifty-two genetic variants were analyzed in the current study. Univariate and multivariate Cox regression analysis were used to test telomere length, genotyping and survival relationships. Telomere length had no significant relationship with overall and breast cancer specific mortality. Carrying genetic variants of the POT1 (rs7784168) A-allele and the TERT (rs2853677) TT genotype were significantly associated with increased all-cause mortality. The HRs were, respectively, 2.17 (95%CI: 1.01-4.66) and 1.73 (95%CI: 1.21-2.45) after adjusting for age at diagnosis (continuous), BMI ( Acknowledgments Grant support: National Cancer Institute and National Institute of Environmental Health Sciences grants R03CA125768, U01CA/ES66572, P30ES009089 and P30ES10126; and awards from the Breast Cancer Research Foundation, and Women At Risk (WAR). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 886.
Analysis of Transurethral Resection of the Prostate Costs across New York State Hospitals Using Severity of Illness Score

Abstract Introduction Using data on surgical treatment for benign prostatic hyperplasia we evaluated the effect of beneficiary health status on hospital reported costs. Methods We examined the records of 9,895 patients in the New York State Hospital Inpatient Cost Transparency database who underwent surgical treatment for benign prostatic hyperplasia, including laser prostatectomy and traditional transurethral resection of the prostate, in New York State from 2009 to 2011. Results Using the 3M™ APR-DRG (All Patient Refined Diagnosis Related Group) severity of illness index as a measure of patient preoperative health we found a significant increase in the cost of transurethral resection of the prostate for patients with higher severity of illness scores. We confirmed an increase in the cost and the cost variability of transurethral resection of the prostate for patients with higher severity of illness scores. Conclusions Our findings illustrate the inherent unpredictability of cost forecasting and budgeting for these patients.
Influence of Benzyl-Imidazoline on the Peripheral Circulation of Man.*

SummaryBenzyl-imidazoline given intravenously effectively increased the rate of blood flow to the periphery in normal individuals and in certain patients with arteriosclerotic obliterative disease. The volume change of the digits following venous occlusion and the skin temperatures were augmented to a greater degree in the lower estremities than in the upper. The amplitude of pulsation showed less change than did the skin temperature or volume changes of the digits.The greatest rise in temperature was seen in the toes. The temperature of the skin of the calf, subcutaneous tissues, and deep muscle of the calf showed a decreasing temperature effect in the order shown. The rectal temperature and temperature of the forehead showed the least change.Benzyl-imidazoline was not effective in raising the skin temperature of the foot, forehead, or hand after indirect heating of one arm.Benzyl-imidazoline shock was seen on 2 occasions.The action of benzyl-imidazoline is complex, and the increased flow to the extremit...
18F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy

Purpose We sought to investigate the ability of mid-treatment 18 F-fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. Methods and Materials This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized 18 F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region ( Results Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion. Symptom progression was predicted with an AUC of 0.75. Dose metrics performed poorly at classifying esophagitis (AUC of 0.52, grade 2 or higher mid treatment) or predicting symptom progression (AUC of 0.67). Conclusions Normalized uptake can objectively, locally, and noninvasively quantify esophagitis during radiation therapy and predict eventual symptoms from asymptomatic patients. Normalized uptake may provide patient-specific dose-response information not discernible from dose.
PATIENT-CUSTOMISABLE KNEE MODEL FOR INTRA-OPERATIVE PLANNING OF UNI- AND BI-COMPARTMENTAL ARTHROPLASTY

Tibial and femoral component malalignment is poorly tolerated in uni- and bi-compartmental knee replacement. Poor outcomes may still occur while using navigation or robotic-assisted bone preparation, which currently require surgeon assessment to establish a preoperative plan for implant placement. Choosing where to place partial knee replacement components is a challenging task that depends on complicated interactions between patient variability and implant design. We developed a patient-customizable knee model that can assist surgeons by providing a quantitative measure of knee laxity. In order to build upon previous knee modeling efforts and to demonstrate the technique, three-dimensional femur and tibia bone and articular cartilage geometries were obtained from the OpenKnee finite element repository (https://simtk.org/home/openknee). Generic, patient-customizable transversely isotropic, fibril-reinforced cruciate and collateral ligament models, which allow for bone-to-ligament, cartilage-to-ligament, ligament-to-ligament interaction, were substituted into the model (Figure 1). This reduces the dependency on expensive and time-consuming MRI segmentation required to recreate soft-tissue geometries. Ligament pre-tensioning and insertion and origin sites (approximated as elliptical regions fit to the bone surface) can be tuned to match a patient9s passive knee kinematics. The model was run through a series of simulated passive flexion paths. At each degree of flexion, combinations of anterior-posterior and medial-lateral forces as well as internal-external and varus/valgus moments were applied and the resulting joint kinematics were recorded. These results represent the passive envelope of knee motion, which is used to characterize knee laxity. An optimization framework was developed to iteratively tune the cruciate ligament model to match a virtual set of passive loading conditions. A majority of preoperative planning techniques only monitor geometric targets such as flexion and extension gaps, limb alignment, restoration of the joint line, and tibial component slope. Patient-customized knee models can be tuned to quantify post-operative knee laxity and identify the range of tolerable alignment of partial knee replacement components. Future work will employ in-vitro testing to validate the capability of the model to identify patient-specific cruciate ligament parameters.
101 – Hodograph Transformation

Publisher Summary This chapter discusses the different aspects of hodograph transformation. The hodograph transformation is applicable to quasi-linear partial differential equations, a single equation, or a system of equations. It yields a new formulation of the original equations. In a partial differential equation it may be easier to solve the equation with the dependent and independent variables switched. This procedure works on a quasi-linear equation or a system of such equations. Every term of each equation must have one, and only one first derivative term, and there can be no higher order derivative terms in the equations. The solution obtained will, in general, be implicit. It is suggested that after the solution is obtained in the hodograph plane, the transformation must be checked to ensure that it is not singular. It is found that because the original equations were quasi-linear, the Jacobian factors out of the equations and does not appear.
Incident Heart Failure and Cognitive Decline: The Atherosclerosis Risk in Communities Study

Abstract Background Cognitive impairment is found in a significant proportion of patients with heart failure (HF). Although cognitive impairment may be a consequence of HF, early signs of cognitive impairment may also indicate subclinical vascular disease, and thus a risk factor for future cardiovascular events. Methods and Results The Atherosclerosis Risk in Communities Study is a prospective cohort study of the development of atherosclerosis. Cox proportional hazards regression was used to examine the association between mean 6-year change in cognitive function and incident HF in 7962 white and 1933 African-American men and women aged 46 to 70 years and free of clinical stroke. Scores were obtained for the Delayed Word Recall Test, the Digit Symbol Substitution Test (DSST), and the Word Fluency Test. There was a significantly increased risk of developing HF during the mean 12.6-year follow-up period after adjustment for age, gender, race, and education for those in the quartile with the greatest decline in DSST scores (hazard ratio [HR] = 1.17, P = .009), and in the quartile with the lowest baseline DSST scores (HR = 1.43, P Conclusions The results suggest that relatively low performance on a test of information processing speed may serve as an indicator of HF risk in middle age.