cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1754: A pharmacokinetics/pharmacodynamics study of sequence specificity of the PARP inhibitor, olaparib (O) with carboplatin (C) in recurrent women's cancers NCT01237067

Background: C, O, and C+O have documented activity in BRCA1/2 mut+ or BRCA-like breast and ovarian cancers (Br/OvCa). The effect of drug sequence on DNA damage and cell death is unknown. Our in vitro modeling suggests that exposure to O prior to C (O>C) reduced double stranded DNA damage and cell loss. Our trial tests the hypothesis that C>O causes more cellular injury. Methods: Eligible pts have recurrent women9s cancers, good end organ function, and evaluable disease. A 3+3 dose escalation run-in defined the O tablet dose in combination with C (AUC 4). The study will now randomize pts to schedule A or B (below), allowing intra-pt and inter-cohort analysis of PK/PD endpoints. PBMCs will be collected C1/2 for measurement of platination and DNA damage/repair; DNA repair protein integrity will be assessed on archival tissues. Clinical benefit, response frequency and duration, and toxicity will be ascertained. Mutation carriers will undergo progression biopsy for analysis of BRCA1/2 re-expression mutations. Results: The phase I portion is complete. 12 women (8Ov/3Br/1Endometrial[En]) have been accrued on 3 dose levels (DLs). Median prior number of regimens was 5. No DLT have been seen in 5 evaluable pts on DL3 (O tablet 200mg q12h/C AUC4 [1 pt pending]). Gr3 AEs included neutropenia (44%), and gr2 were anemia (56%), fatigue (22 %), C hypersensitivity (22%), thrombocytopenia (11%), and nausea (11%). 1 pt (DL2; stable disease) died of unrelated bleeding during C4. Clinical benefit has been observed in 8 evaluable pts with PR in 2 BRCA1 mut+ OvCa (9 + , 11 + mo), stabilization > 4mo in 6 pts (4OvCa,1BrCa, 1EnCa), and 3 are TETE. Conclusions: O in tablet formulation at 200mg q12h x 7d with C AUC4 q21d is active and tolerable, with observed interactive marrow suppression. Subsequent women will be randomized to examine schedule dependence of activity and toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1754. doi:1538-7445.AM2012-1754
The Mre11-Rad50-Nbs1 complex acts both upstream and downstream of ataxia telangiectasia mutated and Rad3-related protein (ATR) to regulate the S-phase checkpoint following UV treatment.

The Mre11-Rad50-Nbs1 (MRN) complex is required for mediating the S-phase checkpoint following UV treatment, but the underlying mechanism is not clear. Here we demonstrate that at least two mechanisms are involved in regulating the S-phase checkpoint in an MRN-dependent manner following UV treatment. First, when replication forks are stalled, MRN is required upstream of ataxia telangiectasia mutated and Rad3related protein (ATR) to facilitate ATR activation in a substrate and dosage-dependent manner. In particular, MRN is required for ATR-directed phosphorylation of RPA2, a critical event in mediating the S-phase checkpoint following UV treatment. Second, MRN is a downstream substrate of ATR. Nbs1 is phosphorylated by ATR at Ser-343 when replication forks are stalled, and this phosphorylation event is also important for down-regulating DNA replication following UV treatment. Moreover, we demonstrate that MRN and ATR/ATR-interacting protein (TRIP) interact with each other, and the forkhead-associated/breast cancer C-terminal domains (FHA/BRCT) of Nbs1 play a significant role in mediating this interaction. Mutations in the FHA/BRCT domains do not prevent ATR activation but specifically impair ATR-mediated Nbs1 phosphorylation at Ser-343, which results in a defect in the S-phase checkpoint. These data suggest that MRN plays critical roles both upstream and downstream of ATR to regulate the S-phase checkpoint when replication forks are stalled.
RANDOM WALKS WITH HEAVY TAILS AND LIMIT THEOREMS FOR BRANCHING PROCESSES WITH MIGRATION AND IMMIGRATION

The central result of this paper is the existence of limiting distributions for two classes of critical homogeneous-in-space branching processes with heavy tails spatial dynamics in dimension d = 2. In dimension d ≥ 3, the same results are true without any special assumptions on the underlying (non-degenerated) stochastic dynamics.
Cryopreservation of Preimplantation Embryos of Cattle, Sheep, and Goats

Preimplantation embryos from cattle, sheep, and goats may be cryopreserved for short- or long-term storage. Preimplantation embryos consist predominantly of water, and the avoidance of intracellular ice crystal formation during the cryopreservation process is of paramount importance to maintain embryo viability. Embryos are placed into a hypertonic solution (1.4 – 1.5 M) of a cryoprotective agent (CPA) such as ethylene glycol (EG) or glycerol (GLYC) to create an osmotic gradient that facilitates cellular dehydration. After embryos reach osmotic equilibrium in the CPA solution, they are individually loaded in the hypertonic CPA solution into 0.25 ml plastic straws for freezing. Embryos are placed into a controlled rate freezer at a temperature of -6°C. Ice crystal formation is induced in the CPA solution surrounding the embryo, and crystallization causes an increase in the concentration of CPA outside of the embryo, causing further cellular dehydration. Embryos are cooled at a rate of 0.5°C/min, enabling further dehydration, to a temperature of -34°C before being plunged into liquid nitrogen (-196°C). Cryopreserved embryos must be thawed prior to transfer to a recipient (surrogate) female. Straws containing the embryos are removed from the liquid nitrogen dewar, held in room temperature air for 3 to 5 sec, and placed into a 37°C water bath for 25 to 30 sec. Embryos cryopreserved in GLYC are placed into a 1 M solution of sucrose for 10 min for removal of the CPA before transfer to a recipient (surrogate) female. Embryos cryopreserved in EG, however, may be directly transferred to the uterus of a recipient.
The Social Context of Law in the Second Temple Period

In this study, cultural expectation, situational expedience, and adaptation to new social norms will be the guide for the examination of legal statements. It will be determined that in the post-exilic period, legal pronouncement blended with political expediency and religious zeal to shape the social context. Concerns over defensive posture within disputed regions, maintenance of protocol and recognition of the rights of posted garrisons in conquered territories (as at Elephantine), and the general sense that people who can be defined as identifiable groups and set in fixed patterns are easier to control may have separately or together driven Persian policy. The reforms imposed by Nehemiah and Ezra suggest both imperial meddling as well as cultural incursion by the advocates of Diasporic Judaism and its more rigid concept of law and ethnic identity.
Selective stimulation of venous prostaglandin E 9-ketoreductase by bradykinin.

Abstract The effects of bradykin on prostaglandin metabolism in canine mesenteric vessels were examined. Bradykinin stimulated microsomal prostaglandin synthesis in both artery and vein; this stimulation was more pronounced when [ 14 C]phosphatidylcholine rather than [ 14 C]arachidonate was used as the substrate for prostaglandin synthetase. This suggested that bradykinin enhanced a membrane phospholipase. In addition, bradykinin selectively stimulated prostaglandin E 9-ketoreductase activity from veins but not arteries. This may explain the finding that bradykinin induces the release of prostaglandin E compounds from arteries but prostaglandin F compounds from veins.
On the isbell and marlow fire programming problem

A complete solution is derived to the Isbell and Marlow fire programming problem. The original work of Isbell and Marlow has been extended by determining the regions of the initial state space from which optimal paths lead to each of the terminal states of combat. The solution process has involved determining the domain of controllability for each of the terminal states of combat and the determination of dispersal surfaces. This solution process suggests a solution procedure applicable to a wider class of tactical allocation problems, terminal control attrition differential games. The structure of optimal target engagement policies in “fights to the finish” is discussed.
Involvement of Arginine 120, Glutamate 524, and Tyrosine 355 in the Binding of Arachidonate and 2-Phenylpropionic Acid Inhibitors to the Cyclooxygenase Active Site of Ovine Prostaglandin Endoperoxide H Synthase-1

Examination of the crystal structure of the ovine prostaglandin endoperoxide synthase-1 (PGHS-1)/S-flurbiprofen complex (Picot, D., Loll, P. J., and Garavito, R. M.(1994) Nature 367, 243-2491) suggests (a) that the carboxyl group of arachidonic acid interacts with the arginino group of Arg120; (b) that Arg120 forms an important salt bridge with Glu524; and (c) that Tyr355, which is in close proximity to Arg120, could determine the stereochemical specificity of PGHS-1 toward 2-phenylpropionic acid inhibitors. To test these concepts, we used site-directed mutagenesis to prepare ovine PGHS-1 mutants having modifications of Arg120 (R120K, R120Q, R120E), Glu524 (E524D, E524Q, E524K), and Tyr355 (Y355F) and examined the properties of the mutant enzymes expressed in COS-1 cells. All of the mutants retained at least part of their cyclooxygenase and peroxidase activities except the R120E mutant, which had no detectable activity. The Km values of the R120K and R120Q mutants with arachidonic acid were 87 and 3300 μM, respectively, versus 4 μM for native PGHS-1. The R120Q mutant failed to undergo suicide inactivation during catalysis or time-dependent inhibition by flurbiprofen. These results are consistent with Arg120 binding the carboxylate group of arachidonate and suggest that interaction of the carboxylate group of substrates and inhibitors with Arg120 is necessary for suicide inactivation and time-dependent inhibition, respectively. The Km values for the E524D, E524Q, and E524K mutants were not significantly different from values obtained for the native PGHS-1, suggesting that this residue is not importantly involved in catalysis or substrate binding. The effect of modifications of Arg120 and Tyr355 on the stereospecificity of inhibitor binding were determined. Ratios of IC50 values for cyclooxygenase inhibition by D- and L-ibuprofen, a competitive cyclooxygenase inhibitor, were 32, 67, and 7.1 for native PGHS-1, R120Q PGHS-1, and Y355F PGHS-1, respectively. The decreased stereochemical specificity observed with the Y355F PGHS-1 mutant suggests that Tyr355 is a determinant of the stereospecificity of PGHS-1 toward inhibitors of the 2-phenylpropionic acid class.
Estrogen use — Risk of endometrial carcinoma

Abstract A retrospective analysis was carried out to determine the prior usage rate of exogenous estrogens in all patients treated for adenocarcinoma of the endometrium in our institution from 1960 to 1974, and in a series of matched controls. Hospital records were reviewed, and patients were matched with controls who had a different gynecologic malignancy. The crude usage rate for all patients with endometrial carcinoma was 18.4% compared with 9.2% of controls yielding a relative risk of 2.2. There was a statistically significant increase in estrogen exposure since 1970, but the risk did not change. Hypertension, diabetes mellitus, and obesity were significant risk factors by themselves, but estrogen exposure in these patients did not appear to put them at further increased risk. There was no significant difference between the exposed and nonexposed groups in respect to grade or stage. In spite of a low exposure rate in this area, the relative risk for estrogen exposure was significant, independent of other variables.
Relevance and Avoidance of Skin-Care Product Allergens: Pearls and Pitfalls

Patch testing can be particularly rewarding when skin-care product allergens are identified. Careful determination of relevance, followed by careful education regarding allergen avoidance, can result in dramatic clinical improvement. Several common clinical scenarios are reviewed with a focus on pragmatic solutions to heighten positive patient outcomes.
Congressional Response to Mandate Elections

Elections from time to time are widely believed to carry a mandate, to express a message about changed policy preferences of the electorate. Whatever the accuracy of such beliefs—a matter about which we are skeptical—perceptions of a mandate should affect the behavior of actors in government. Politicians lack the scholarly luxury of waiting for careful analyses. They must act in the months following elections. We postulate that many will act as if the mandate perceptions were true, veering away from their normal voting patterns. This is driven by election results and interpretations that undermine old calculations about what voters want. As the flow of information gradually changes these perceptions, and the election becomes more distant, members of Congress return to their normal position. We first ask, how would members observe an emerging consensus of mandate? And then we model the duration of the change in behavior in an event-history framework. That permits a depiction of important movements of the median member and, from this, inferences about policy impact.
MITOMAP: A Human Mitochondrial Genome Database

We have developed a comprehensive database (MITOMAP) for the human mitochondrial DNA (mtDNA), the first component of the human genome to be completely sequenced [Anderson et al. (1981) Nature 290, 457-465]. MITOMAP uses the mtDNA sequence as the unifying element for bringing together information on mitochondrial genome structure and function, pathogenic mutations and their clinical characteristics, population associated variation, and gene- gene interactions. As increasingly larger regions of the human genome are sequenced and characterized, the need for integrating such information will grow. Consequently, MITOMAP not only provides a valuable reference for the mitochondrial biologist, it may also provide a model for the development of information storage and retrieval systems for other components of the human genome.
Inhibition of Ca2+/Calmodulin-dependent Protein Kinase Blocks Morphological Differentiation of Plasmodium gallinaceum Zygotes to Ookinetes

Abstract Once ingested by mosquitoes, malaria parasites undergo complex cellular changes. These include zygote formation, transformation of zygote to ookinete, and differentiation from ookinete to oocyst. Within the oocyst, the parasite multiplies into numerous sporozoites. Modulators of intracellular calcium homeostasis A23187, MAPTAM, and TMB-8 blocked ookinete development as did the calmodulin (CaM) antagonists W-7 and calmidazolium. Ca2+/CaM-dependent protein kinase inhibitor KN-93 also blocked zygote elongation, while its ineffective analog KN-92 did not have such effect. In vitro both zygote and ookinete extracts efficiently phosphorylated autocamtide-2, a classic CaM kinase substrate, which could be blocked by calmodulin antagonists W-7 and calmidazolium and CaM kinase inhibitor KN-93. These results demonstrated the presence of calmodulin-dependent CaM kinase activity in the parasite. KN-93-treated parasites, however, expressed the ookinete-specific enzyme chitinase and the ookinete surface antigen Pgs28 normally, suggesting that the morphologically untransformed parasites are biochemically mature ookinetes. In mosquitoes, KN-93-treated parasites did not develop as oocysts, while KN-92-treated parasites produced similar numbers of oocysts as controls. These data suggested that inPlasmodium gallinaceum morphological development of zygote to ookinete, but not its biochemical maturation, relies on Ca2+/CaM-dependent protein kinase activity and demonstrated that the morphological differentiation is essential for the further development of the parasite in infected blood-fed mosquitoes.
The political economy of economic underdevelopment and external migration in Nepal

Abstract This study provides a political-economic analysis of the roots of, and the relationship between, the process of underdevelopment and external migration in Nepal. While the internal institutional policies were responsible for initiating these two economic and demographic processes, British India's Gorkha recruitment policy contributed to their perpetuation. Today, Nepal's economy is trapped in a negative feedback cycle in which underdevelopment fuels outmigration which, in turn, propagates underdevelopment. Regardless of the nature of its socioeconomic impact, outmigration from the hills has emerged as a major economic survival factor for many migrant households and local economies.
Demonstration of Na+-dependent Ca2+ efflux using low concentrations of fluorometric Ca2+ probes.

The effects of different concentrations of the fluorometric Ca2+ probes, fura-2 and indo-1, on Ca2+ transients in cultured rat aortic smooth muscle cells were examined. When stimulated with the agonists, angiotensin II and arginine vasopressin, cells incubated with low concentrations of fura-2 or indo-1 (< 1 μM) produced Ca2+ transients characterized by a small increase followed by a dramatic decrease in fluorescence below the original baseline. This effect of agonists was concentration-dependent, reversible, and blocked by receptor antagonists. In contrast to the agonists, stimulation of Ca2+ transients with depolarizing concentrations of K+ or with caffeine did not produce decreases in fluorescence and Ca2+ levels at any loading concentration of probe. The decrease in Ca2+ observed with agonists was dependent on the presence of extracellular Na+. These data suggest that under certain loading conditions, fluorescent Ca2+ indicators measure agonist-stimulated Ca2+ efflux mediated by a Na+Ca2+ exchange mechanism.
FEMINISM AND A FEMALE TRINITY IN DENISE BOUCHER'S LES FÉES ONT SOIF

(1984). FEMINISM AND A FEMALE TRINITY IN DENISE BOUCHER'S LES FEES ONT SOIF. American Review of Canadian Studies: Vol. 14, No. 1, pp. 63-71.
The effect of information scent on searching information: visualizations of large tree structures

Focus + context information visualizations have sought to amplify human cognition by increasing the amount of information immediately available to the user. We study how the focus + context distortion of the Hyperbolic Tree browser affects information foraging behavior in a task similar to the CHI '97 Browse Off. In comparison to a more conventional browser, Hyperbolic users searched more nodes, searched at a faster rate, and showed more learning. However, the performance of the Hyperbolic was found to be highly affected by “information scent”, proximal cues to the value of distal information. Strong information scent made hyperbolic search faster than with a conventional browser. Conversely, weak scent put the hyperbolic tree at a disadvantage. There appears to be two countervailing processes affecting visual attention in these displays: strong information scent expands the spotlight of attention whereas crowding of targets in the compressed region of the Hyperbolic narrows it. The results suggest design improvements.
Degradation of the Peroxisome Proliferator-activated Receptor γ Is Linked to Ligand-dependent Activation

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated transcription factor that regulates several crucial biological processes such as adipogenesis, glucose homeostasis, and cell growth. It is also the functional receptor for a new class of insulin-sensitizing drugs, the thiazolidinediones, now widely used in the treatment of type 2 diabetes mellitus. Here we report that PPARgamma protein levels are significantly reduced in adipose cells and fibroblasts in response to specific ligands such as thiazolidinediones. Studies with several doses of different ligands illustrate that degradation of PPARgamma correlates well with the ability of ligands to activate this receptor. However, analyses of PPARgamma mutants show that, although degradation does not strictly depend on the transcriptional activity of the receptor, it is dependent upon the ligand-gated activation function 2 (AF2) domain. Proteasome inhibitors inhibited the down-regulation of PPARgamma and ligand activation enhanced the ubiquitination of this receptor. These data indicate that, although ligand binding and activation of the AF2 domain increase the transcriptional function of PPARgamma, these same processes also induce ubiquitination and subsequent degradation of this receptor by the proteasome.
Further studies on the urinary excretion of thiamin in children

T HIAMIN excretion in the urine has been used as an indication of thiamin tissue saturation and unsaturation. There are various degrees of tissue unsaturation. For practical purposes, two groups are considered: (1) tissue unsaturation with clinical signs or symptoms; (2) tissue unsaturation without clinical signs or symptoms. The latter group can be recognized only by laboratory means. We have reported 1 on the urinary thiamin excretion of "healthy" children from 4 to 11 years of age who were hospitalized and so could be kept under close observation. These children were free to eat what they wished of the routine hospital diet. Their daily thiamin intake'was found to average 990 ~g, and it was significant that each child constantly approximated that figure. The thiamin excretion for the group averaged 268 /~g per day. The lowest daily excretion for any child was found to be more than 100/~g. The average excretion was 27.2 per cent of the thiamin ingested in the diet. The figures for each child in this "hea l t hy" group are given in Table I. No child excreted less than 20 per cent of the thiamin intake. A study of ill children (acute, chronic, and convalescent) was then undertaken. The results were compared to and interpreted with those of the healthy children. The factors which operate to produce low urinary excretions were further studied. Ea, ch patient was hospitalized and observed for from ten days to two months. Each child received a careful study, including history, physical examination, and indicated laboratory examinations. The daily dietary intake of carbohydrate, protein, fat, total calories and thiamin 2 was computed, and the daily urinary thiamin excretion was determined by a thiochrome '~ method. Fifty-five children received test doses in an attempt to find a serviceable saturation test.
Geometric Brownian distribution of solar radiation with an economic application

Abstract This paper presents the results of a recent model by Hamlen and Hamlen[1] which uses a distributed lag model to predict local levels of incoming solar radiation. The results indicate that the daily levels display a geometric Brownian motion. This distribution was introduced by Professor Samuelson[2] to explain the movement in stock prices over time. It modifies the more familiar arithmetic Brownian motion to eliminate the problem of negative values of the predicted stock prices with a high probability. Solar radiation, kike stock prices, cannot take on negative values and requires the geometric Brownian motion. The distribution is introduced and parameters of the distribution are given for twenty-two cities in the U.S. The results are then applied to the problem of determining economically efficient combinations of heating technologies given a solar heating system and a conventional backup system. A production function for heat is developed that results in a stochastic function with two random variables: available solar radiation and outside temperature. This, in turn, results in a chance constrained cost minimization problem.
A neutral thiol proteinase in normal and dystrophic human muscle

Abstract Human skeletal muscle homogenates were found to contain a neutral proteinase that catalyzes the hydrolysis of benzyloxycarbonyl- l -alanyl- l -alanyl- l -lysine 4-methoxynaphthylamine. The proteinase was inhibited by sulfhydryl blocking reagents, tosylphenylalanine chloromethyl ketone, tosyllysine chloromethyl ketone, and benzamidine but not by phenylmethanesulfonyl fluoride and metal chelating agents. It was not thiol dependent but its sensitivity to thiol blocking reagents suggests that the enzyme probably is a thiol proteinase. When the levels in patients were compared with controls, significant increases in muscle proteinase levels were observed in patients with major forms of muscular dystrophies and certain denervating diseases. These results suggest the possibility that this neutral proteinase may be involved in some way in the muscle wasting process in these muscle diseases.
Effects of a single omission of reinforcement.

34, p < ,001) while the number of responses during the next two intervals was significantly lower (t = 2.74, df = 34. p < .001). To be consistent with the theoretical assumprions outlined above these data could be explained in the following manner. The immediate increase in number of responses in the first interval following frustration would be due to the energization characteristics of frustration and the significant decrease in number of responses immediately afterward would be due to the aversive aspects of frustrarion which tend to act as a punishment and suppress responses. We would have to assume an interaction of the aversive and energizing parameters from the moment of frustration, with a larger algebraic sum of ener,:ization immediately following frustration; however, dissipation of this temporary incr-e reveals the aversive, and thus suppressive, characteristics. The return of the behavior to baseline level would be due to the effects of the repeated reinforcements after the frustrarion.
Backwards uniqueness of the C_0-semigroup associated with a parabolic-hyperbolic Stokes-Lamé partial differential equation system

In this paper the "backward-uniqueness property" is ascertained for a two- or three-dimensional, fluid-structure interactive partial differential equation (PDE) system, for which an explicit Co-semigroup formulation was recently given by Avalos and Triggiani (2007) on the natural finite energy space H. (See also their Contemporary Mathematics article of 2007 for a preliminary, simplified, canonical model.) This system of coupled PDEs comprises the parabolic Stokes equations and the hyperbolic Lame system of dynamic elasticity. Each dynamic evolves within its respective domain, while being coupled on the boundary interface between fluid and structure. In terms of said fluid-structure semigroup {e At }, posed on the associated finite energy space H, the backward-uniqueness property can be stated in this way: If for given initial data y 0 ∈ H, e AT y 0 = 0 for some T > 0, then necessarily y 0 = 0. The proof of this property hinges on establishing necessary PDE estimates for a certain static fluid-structure equation in order to invoke the abstract backward-uniqueness resolvent-based criterion by Lasiecka, Renardy, and Triggiani (2001). The backward-uniqueness property for the coupled Stokes-Lame PDE is motivated by, and has positive implications to, the problem of exact controllability (in the hyperbolic state variables {w, w t }) and, simultaneously, approximate controllability (in the parabolic state variable u) of the present coupled PDE model, under boundary control. A similar situation occurred for thermoelastic models as shown in papers by M. Eller, V. Isakov, I. Lasiecka, M. Renardy, and R. Triggiani.
Perspective on ATR evaluation technology

A historical perspective on the evolution of performance evaluation technology for automatic target recognition (ATR) systems is presented. It is shown that the ad hoc and artistic evaluation techniques of the past are now evolving into scientific approaches. The most perspective areas of this technology include: (1) first principle coupled, multi-sensor modeling of objects, environment, atmosphere, and vegetation; (2) integration of models with the task of ATR algorithm development; (3) integration of a new generation of parallel processor that can process every pixel of an image without the need for data reduction; (4) extending the instrumentation control of ATR to include sensor selection and sensor fusion; and (5) development of signal metrics for radar, acoustic and ladar, and linking these metrics to phenomenological sources.© (1990) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
MinK Endows the IKs Potassium Channel Pore with Sensitivity to Internal Tetraethylammonium

I(Ks) channels are heteromeric complexes of pore-forming KvLQT1 subunits and pore-associated MinK subunits. Channels formed only of KvLQT1 subunits vary from I(Ks) channels in their gating kinetics, single-channel conductance, and ion selectivity. Here we show that I(Ks) channels are more sensitive to blockade by internal tetraethylammonium ion (TEA) than KvLQT1 channels. Inhibition by internal TEA is shown to proceed by a simple bimolecular interaction in the I(Ks) conduction pathway. Application of a noise-variance strategy suggests that MinK enhances blockade by increasing the dwell time of TEA on its pore site from approximately 70 to 370 micros. Mutation of consecutive residues across the single transmembrane segment of MinK identifies positions that alter TEA blockade of I(Ks) channels. MinK is seen to determine the pharmacology of I(Ks) channels in addition to establishing their biophysical attributes.
Predictors of suicide ideation and risk for HIV among juvenile offenders in Georgia

The purpose of this study was to examine self-reported thoughts of suicide, HIV risk behaviors and history of sexually transmitted infections (STIs) in a sample of adolescent juvenile offenders in Georgia [USA]. Participants were 2260 juvenile offenders housed at selected youth development campuses (YDCs) in the state of Georgia. Self-reported measures of suicide ideation, HIV risk, and past occurrence of STIs were collected. Significance tests were conducted using univariate logistic regressions to examine the independent associations of lifetime self-reported thoughts of suicide and dichotomized HIV risk behaviour correlates prior to incarceration. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Significant differences were observed between juveniles in several factors for increased risk, including having been previously incarcerated (p Language: en
Catabolism of Glucose Dissolved in Sea Water by Mysis and Postlarvae of Two Species of Penaeid Shrimp1

Respiration rates were determined in mysis and early postlarval stages in the shrimp species Penaeus aztecus and Penaeus setiferus. Rates in the same stages differed somewhat between the two species, being higher in Penaeus setiferus at the experimental temperature of 28 C and salinity of 32 ppt. On the basis of oxygen consumption per unit dry weight, rates were highest in the youngest stages and lower in the older stages. The ability of these organisms to catabolize D-glucose dissolved in seawater was studied, using uniformly labeled 14C-D-glucose. Respiratory CO2 was collected, and the radioactivity determined by liquid scintillation counting. Catabolism of the dissolved D-glucose on a per unit dry weight basis was not different between the two species at the same stage of development and was highest in the earlier stages, decreasing with increasing animal size. The results indicate that dissolved D-glucose contributes to the total catabolic requirements in these animals. The contribution to total respiration made by dissolved glucose was very small. The potential for this contribution needs further study.
Dissolution behavior of phenolic resins and resists as studied by quartz crystal microbalance

The thin film dissolution behavior of phenolic resins such as poly(4-hydroxystyrene) and poly(4-hydroxystyrene-co-t-butyl acrylate), the dissolution inhibition effect of acid generators, and the development kinetics of the ESCAP resist are reported. All the dissolution rate measurements were carried out using a quartz crystal microbalance (QCM), which can provide valuable information on the time-dependent dissolution behavior even for an extremely fast rate of 30,000 angstroms/sec. Poly(4-hydroxystyrene)s with a wide range of molecular weights (M n equals 2,300 - 26,000) and molecular weight distributions (1.2 - 5.5) have been found to dissolve linearly with time in a 0.21 N tetramethylammonium hydroxide (TMAH) aqueous solution. The dissolution rate of the copolymers decreases exponentially with an increase in the acrylate concentration, accompanied by an increase in an induction period. The dissolution inhibition effect of acid generators varies widely. Onium salts are excellent dissolution inhibitors, even stronger than so-called dissolution inhibitors such as t-butoxycarbonyl-protected bisphenol A. A higher loading of triphenylsulfonium triflate in the copolymer film results in a longer induction period and an exponentially slower dissolution rate. The ESCAP resist based on the copolymer begins to dissolve in a 0.26 N TMAH solution at only ca. 5% conversion of the t-butyl ester to carboxylic acid and reaches its maximum dissolution rate of 30,000 angstroms/sec at the dose to clear with ca. 60% conversion, which corresponds to the developer selectivity of greater than 15. Although the dissolution rate does not change much above the dose to clear, the induction period becomes shorter at a higher dose, which can be observed by QCM even when the full development time is less than 1 sec.
Distributed access control of volatile renewable energy resources

In this paper, we develop a general framework of distributed access control which allows for anytime connections and disconnections of volatile renewable energy resources in the power grid. We formally prove that the hard state constraints are satisfied all the time and the asymptotic stability is reached if connections and disconnections only happen for a finite number of times. Our framework and analysis leverage the tools of input-to-state stability and small gain theorems in nonlinear systems. The performance of our framework is illustrated by a case study on frequency control with wind integration.
Differential RNA metabolism in rat brain cells fractionated by zonal centrifugation.

Abstract Combined fractionation and RNA metabolism studies were made on homologous cell types (neurons and glia) banded from rat brain cerebral cortex and hippocampus tissue at 40, 000 rev/min for 50 minutes in a Beckman Ti 14 zonal rotor loaded with a discontinuous methyl cellulose (Methocel) and sucrose density gradient. Comparisons were made on the cellular fractions recovered from animals intracisternally injected with 15 μCi tritiated cytidine (3HCR) RNA precursor one hour before sacrifice and tissue cellular filtrate preparation. Immediate3H pool-correction of extracted3HRNA from the three cellular Bands recovered made possible a mathematically valid measure of3HCR-precursor incorporation into RNA of the different cell types. Comparison of the cellular3HRNA data by analysis of variance revealed the occurrence of differential tritium labelling of RNA in the same cell types banded from different brain regions. In particular, an important advance was demonstrated by the procedures developed in these st...
The abundance of Rad51 protein in mouse embryonic stem cells is regulated at multiple levels

DNA double-strand breaks (DSBs) in embryonic stem (ES) cells are repaired primarily by homologous recombination (HR). The mechanism by which HR is regulated in these cells, however, remains enigmatic. To gain insight into such regulatory mechanisms, we have asked how protein levels of Rad51, a key component of HR, are controlled in mouse ES cells and mouse embryo fibroblasts (MEFs). The Rad51 protein level is about 15-fold higher in ES cells than in MEFs. The level of Rad51 mRNA, however, is only ~2-fold higher, indicating that the differences in mRNA levels due to rates of transcription or mRNA stability are not sufficient to account for the large difference in the abundance of Rad51 protein. Comparison of Rad51 half-lives between ES cells and MEFs also did not explain the elevated level of Rad51 protein in the ES cells. A comparative assessment of the Rad51 translation level demonstrated that it is translated with much greater efficacy in ES cells than in MEFs. To determine whether this high level of translation in ES cells is a general phenomenon in these cells or whether it is a characteristic of specific proteins, such as those involved with recombination and cell cycle progression, we compared mechanisms that regulate the level of Pcna in ES cells with those that regulate Rad51. The half-life of Pcna and its rate of synthesis were considerably different from those of Rad51 in ES cells, demonstrating that regulation of Rad51 abundance cannot be generalized to other ES cell proteins and not to proteins involved in DNA replication and cell cycle control. Finally, we show that only a small proportion of the abundant Rad51 protein population is activated under basal conditions in ES cells and recruited to DNA DSBs and/or stalled replication forks.
Vibratory Thresholds Correlation With Systolic Blood Pressure in Diabetic Women

Abstract Previous studies have suggested a potential association of elevated blood pressure (BP) and the development of diabetic neuropathy for individuals with insulin-dependent diabetes mellitus. In this study, we examined an association between BP and vibratory thresholds (assessment modality of large sensory nerve fiber function) for 33 participants with non–insulin-dependent diabetes mellitus. There were 19 women and 14 men aged 58 ± 7 (mean ± SD) years, with diabetes duration of 7 ± 6 years and a body mass index of 29 ± 5 kg/m2. None of the individuals were taking any medications that lower BP and all were negative for the presence of microalbuminuria. Vibratory thresholds were determined at three visits using a two-alternative, forced-choice procedure. BP was assessed by 24-h ambulatory BP monitoring. As expected, vibratory thresholds were higher for men than for women (6.3 ± 4 v 4.2 ± 3 vibration units) but there was no statistical difference after controlling for height. In multivariate analyses with vibratory thresholds as the dependent variable, duration of diabetes (P 90 mm Hg) for day DBP was found to be independently associated with vibratory thresholds for women. The association of BP and large sensory nerve fiber dysfunction for nonnephropathic diabetic women found in this cross-sectional study warrants further investigation.
Determination of native zinc content of alpha-2-macroglobulin in normal, hyperzincemic and hypozincemic sera by sucrose density gradient centrifugation.

Abstract Fractions of human serum proteins obtained by sucrose density gradient centrifugation were analyzed for zinc content by atomic absorption spectrophotometry and colorimetry. Zinc was found in two distinct fractions: one fraction appeared at the albumin sedimenting area, and the second fraction appeared with alpha-2-macroglobulin (alpha-2-M). Approximately 30% of total serum zinc was associated with the alpha-2-M fraction. The high purity of this alpha-2-M containing fraction was reflected by the excellent correlation of results obtained from the determination of the protein content of these fractions by Bradford method and radial immunodiffusion analysis. Further evidence of the purity of alpha-2-M in these fractions was obtained by immunoelectrophoresis. Moreover, these alpha-2-M containing fractions did not have any significant amount of trace elements that could possibly interfere with zinc determination by the dithizone method. The suitability and reliability of this method for the determination of the native zinc content of serum alpha-2-M is supported by the experimental findings that this procedure does not cause exogenous zinc contamination and is not disruptive to protein-metal interaction. Our results also indicate that native alpha-2-M contains approximately 80–100 μg Zn/g protein and that the molar ratio between zinc and alpha-2-M is approximately 1.0. This ratio was also maintained in hypo- and hyper-zincemic sera obtained from patients with multiple myeloma and lymphocytic lymphoma.
The Louisville Burlesque War: Empire Circuit Company vs. Columbia Amusement

The Louisville burlesque war began in July of 1908 and ended in late August, 1909, with the opening of the Columbia Amusement Company's Gayety Theatre. In all, there were over ten court cases and thousands of dollars expended by both sides. It was a conflict which, with the help of the press, moved from a private business matter to embroil the whole community. Beyond its local significance, however, the “Gayety Theatre war” foreshadowed a revolution in national burlesque business.
SU‐FF‐T‐134: Delivery Outcome‐Driven Adaptive Re‐Planning Strategy

Purpose: With increasing availability of imaging and dosimetric information during a treatment course, it is now possible to consider whether the plan should be altered during the treatment course in order to tailor treatment delivery outcomes or control them in the presence of pretreatment model variations and delivery errors. In this study, a general offline re‐planning framework based on multiple planning metrics is investigated for IMRTtreatments. The framework was designed to explicitly handle nonlinear constraints and goals including gEUD, and NTCP. Method and Materials: Use of the re‐planning strategy is demonstrated using an optimization technique (called MIGA) that accounts for inter‐fraction setup variations. While an initial plan is generated by MIGA incorporating a population‐based setup variation (assumed statistically Gaussian), the population model is individualized into a patient‐specific posterior distribution through Bayesian learning with daily setup measurements. The individualized distribution is fed back into the TPS, tracking the delivery outcomes. Re‐planning is triggered to restore the original delivery outcomes when results deviate significantly beyond the tolerable limits. In each re‐planning, a non‐linear constrained optimization problem is solved. Results: With the adaptation of a patient‐specific setup distribution, the plan outcomes of MIGA are improved in terms of accuracy and robustness to individual errors. With an assumption of the normal‐gamma distribution for the prospective mean and standard deviation, the individual setup is quickly learned through Bayesian inference with a limited number of measurements (e.g., ∼10 or less). This helps reducing a frequent need for resource‐intensive re‐planning. Conclusion: A re‐planning framework driven by multiple delivery outcomes facilitates direct prediction and control of consequences brought by newly available treatment models (patient setup in this study of MIGA planning) or treatment errors. Explicit handling of planning constraints allows an intuitive allocation of planning and QA resources as the fractionated treatment proceeds over time.
Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase

Obesity is an increasingly prevalent problem, and long-term maintenance of the weight-reduced state is difficult for the obese individual. Following weight reduction, many metabolic changes occur. Among these is an increase in adipose tissue lipoprotein lipase (ATLPL), which predicts an alteration in lipid fuel partitioning which may then contribute to resumption of the obese state. The purpose of this study was to test whether changes in skeletal muscle LPL (SMLPL) and its response to insulin/glucose after sustained weight reduction also indicate a potential altered partitioning of lipid fuels away from oxidative pathways in muscle to storage in adipose tissue. Biopsies of vastus lateralis muscle were carried out in premenopausal obese women (n = 11, 94 +/- 4 kg, mean +/- SEM) before and after consumption of a 900 kcal day-1 diet for 3 months followed by 3 months of isocaloric maintenance of the reduced weight (n = 11, 82 +/- 4 kg). SMLPL activity was measured in the fasted state and after 6 h insulin/glucose infusion, before and after sustained weight loss. SMLPL activities were also measured in six normal weight women. Fasting SMLPL activity in obese women (3.9 +/- 0.3 nmol FFA min-1 g-1) was similar to that measured in normal weight control women (4.4 +/- 0.5). Unlike normal weight controls in whom a 6 h insulin/glucose infusion decreased SMLPL activity, in obese women the response of SMLPL was positive (normal weight vs. obese: delta -0.8 +/- 0.3 vs. delta 1.6 +/- 0.5, P = 0.002). Following maintained weight reduction, fasting SMLPL in the obese group was reduced to 1.2 +/- 0.3 (obese before weight loss vs. obese after: P = 0.0001). This change in fasting SMLPL activity following weight loss/maintenance correlated with the resultant change in percent body fat (r s = 0.663, P = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)
Nickel-induced defects and their role in governing chlorine chemistry on the Si(100) surface

Abstract The effect on chlorine surface chemistry of surface defects (split-off dimers) induced by controlled nickel contamination of Si(100) surfaces has been studied. It is shown that the mechanism of chlorine surface etching changes significantly with the presence of a small amount of split-off dimer defects ( 2 desorption peak is observed at ∼550 K, and the shape of the major SiCl 2 desorption peak at ∼950 K is changed. The presence of the low temperature SiCl 2 desorption is attributed to the existence of SiCl 2 surface species on the split-off dimer defects. The chlorine saturation coverage increases by up to ∼10% in the studied range of defect densities. It is estimated that each split-off dimer defect contains 4.3±0.6 extra chlorine atoms compared to the ideal chlorine-saturated Si(100) surface. On non-defective Cl-dosed Si(100) surfaces, the electron stimulated desorption ion angular distribution (ESDIAD) images show only four off-normal Cl + beams. With increasing defect density a new Cl + beam develops in the normal 〈100〉 direction. This feature is associated with the Cl bonding on the split-off dimer defects, and is similar to that produced on a Si(100) surface containing point defects created in other ways.
Closed irregularity sets of linear differential systems with a parameter multiplying the derivative

For any closed subset M of the real line that does not contain zero, we construct a linear differential system with bounded piecewise continuous coefficient matrix A(·) such that the corresponding system with coefficient matrix µA(·) linearly depending on a real parameter µ is Lyapunov irregular for all µ in M and Lyapunov regular for all other parameter values.
Homotopies for computation of fixed points

Given a point to set mapf on a simplex with certain conditions, an algorithm for computing fixed points is described. The algorithm operates by following the fixed point as an initially affine function is deformed towardsf.
TREATMENT OF PSORIASIS WITH TOPICAL NITROGEN MUSTARD

With the advent of various new methods of treating psoriasis, it is necessary to remind physicians to consider an agent that is easy to administer, locally effective, relatively inexpensive, not time-consuming and without systemic toxic effects. Nineteen patients were treated with topical nitrogen mustard between 1972 and 1976, and only five developed sufficient contact sensitization to warrant stopping medication.