cssi/SciSciGPT-SciSciNet huggingface dataset:
Detection of four novel mutations in the iduronate-2-sulphatase gene by single-strand conformation polymorphism analysis of genomic amplicons

Hunter syndrome (mucopolysaccharidosis type II, MPS II; McKusick 309900) is caused by the deficiency of iduronate-2-sulphatase (IDS, EC 3.1.6.13) enzyme activity (Bach et al 1973). The X-linked IDS gene comprises nine exons and eight introns and encodes a polypeptide of 550 amino acids (Wilson et al 1993). About 50 small mutations in the IDS gene have been detected by an approach using reverse transcription-linked polymerase chain reaction (RT-PCR) (Jonsson et al 1995). In the present investigation, an alternative approach which combined exon-by-exon PCR amplification of the IDS genomic sequence with single-strand conformation polymorphism (SSCP) analysis was developed for screening mutations in the IDS gene. Five unrelated patients, designated patients 1-5, with the severe type of Hunter syndrome were investigated. All five patients were diagnosed by the demonstration of the IDS enzyme deficiency in serum or cultured fibroblasts. For mutation analysis, nine pairs of IDS exon-specific primers, designated ElL, R; E2L, R; E3L, R; E4L, R; E5L, R; E6L, R; E7L, R; ESL, R; and E9L, R, were designed from the IDS genomic 5' and 3' non-coding regions and exon/intron boundary sequences (Wilson et al 1993). The synthesized primer pairs were used in a standard PCR to generate IDS exon I to IX specific amplicons with size ranging from 129bp to 595bp. The IDS exon-specific amplicons were subjected to SSCP analysis in order to identify an alteration in mobility by MDE gel electrophoresis (AT Biochem). The amplicons with altered mobility were directly sequenced using a ATaq cycle sequencing kit (United States Biochemical). Two unique missense mutations in exon VII were identified: D334G (GAT to GGT, At°°I--~G) in patient 3 and Gl°°6--~A (TGgt to TAgt; italic denotes intron sequence) in patient 4. A previously reported mutation, $333L (TCG to TTG, C99s--~T in exon VII), was found in patient 2. Two novel nonsense mutations were defined: Y234X (TAC to TAA, C7°2-~A in exon V) in patient 1 and Q465X (CAG to TAG, C1393---)T in exon IX) in patient 5. The GI°°6~A mutation eliminates a NlaIII recognition site and the Q465X mutation introduces an AluI recognition site, which allow a convenient PCR-based restriction enzyme assay for carrier detection. The $333L mutation was defined as one of the several CpG dinucleotide 'hot spots' in the IDS gene (Jonsson et al 1995). The identification of four novel mutations in the IDS gene provides further evidence of mutational heterogeneity in Hunter syndrome.
Analog Test Technology: Stable and Grounded, or Open Loop and Spurious?

The op-amp test loop used in the 1970s is still in use today. In the early 1980s, Matt Mahoney won best paper and honorable mention awards at this conference for ground breaking work in the area of analog and DSP based testing. While devices have evolved over the years in terms of speed, precision, and integration on SOC chips, almost all of the test techniques created by the early leaders are still in use today.
Catecholamine uptake into isolated adrenal chromaffin cells: Inhibition of uptake by acetylcholine

Abstract We have investigated the process of catecholamine uptake in guinea-pig chromaffin cells. Isolated guinea-pig chromaffin cells accumulate [3H]norepinephrine and [3H]epinephrine by a saturable transport system. Catecholamine uptake is dependent upon temperature, energy, and extracellular Na+. The apparentKms for norepinephrine and epinephrine transport are approximately 1 and 3.5 μM, respectively; the transport maximum (Vmax) for both compounds is about 100p mol/min/mg protein. The uptake of norepinephrine into chromaffin cells is inhibited by imipramine (Ki = 50 nM) and by desmethylimipramine (IC50 = 20 nM). In both its substrate specificity and its sensitivity to pharmacological inhibition, the catecholamine uptake system in chromaffin cells is similar to the catecholamine transport system previously described in sympathetic neurons. Decreasing external Na+ from 130 to 19 mM increases the apparentKm for norepinephrine to 2.8 μM. Decreasing external norepinephrine increases the Na+ concentration required for half-maximal transport. Agents that depolarize chromaffin cells, such as acetylcholine and veratridine, significantly inhibit [3H]norepinephrine uptake. This decrease in uptake is due to an increase in the apparentKm for norepinephrine. The inhibition of [3H]norepinephrine uptake by depolarizing agents cannot be accounted for by the preferential release of newly-accumulated [3H]norepinephrine, or by the competitive inhibition of [3H]norepinephrine uptake by secreted catecholamines. The inhibition of catecholamine uptake by depolarizing agents suggests that the transport system may be regulated by the membrane potential. Norepinephrine and epinephrine that are spontaneously released from the adrenal medulla may be recapturedin vivo. The inhibition of transport by acetylcholine may prevent the re-uptake of catecholamine released during the physiological stimulation of secretion.
ELASTIC-PLASTIC CONSTITUTIVE RELATIONS AT LARGE STRAIN

Most computer codes intended for the solution of dynamic mechanics problems use classical infinitesimal plasticity relations together with the Jaumann stress rate to account for finite rotations. Use of the Jaumann stress rate is known to lead to oscillating stress-strain response in simple shear at large deformations for some elastic and plastic relations, and is limited to isotropic material functions. Formulations of finite deformation plasticity based on the Lagrangian reference configuration and an unrotated configuration have been proposed which, in principle, should overcome these limitations. The latter has been implemented in a finite element computer code. In this paper, it is shown how a Lagrangian description based on the reference configuration may be implemented in computer codes, and how it may be translated into corresponding Eulerian and unrotated descriptions for comparison with currently used descriptions.
The impact of emergence of Chinese international corn markets on Chinese and US corn prices

Because of reduced stockholding, Chinese domestic corn markets are becoming much more interdependent with the rest of the world. As China's economy continues to transition from centrally planned to market oriented, internal pressure for increased use of market mechanisms in trading corn and other commodities is continuous. Moreover, there is also external pressure for increased use of market mechanisms because of the accession of China to the World Trade Organization (WTO). The objective of this article is to evaluate the dynamic interrelationships between Chinese corn prices in producing, consuming and export/import locations and the US Chicago Board of Trade (CBOT) price. A novel dataset including daily prices from dominant cash markets at producing regions, at export/import ports and at major consuming regions within China, as well as prices at Chicago is used in the analysis. Based on results of Vector Error Correction (VEC) model, prices in these markets are correlated in short run while error correc...
A Duel Involving False Targets

A duel is initated by an attacker at some time t in [-T, 0]. The defender possesses weapons at -T and encounters "false" targets that occur at time t with probability density λt and are classified as "real" with probability cfa. At the time of attack, the probabilities that the attacker is detected and classified as real are D and caaD, caa, cfa are constant. If the defender responds with one of his k weapons at the time of attack, he survives with probability pk, and, if he does not respond, he survives with probability qk; qk <pk, pk â¦ pk+1, qk â¦ qk+1 for k = 0, 1, 2, '. The payoff is the defender's survival probability. Both players are informed of the current time, the defender's weapon level, λ, D, caa, Cfa, pk and qkk = 0, 1, 2, '. The attacker selects a time of attack to minimize the payoff. He may change the attack time as the defender expends weapons against false targets. The defender responds to classifications so as to maximize the payoff. This paper derives an iterative system of first-order differential equations whose unique solution V1t, V2t, ', Vkt, ' at time t is the value of the game when the defender has 1, 2, ', k, ' weapons, respectively, at time t. It expresses the optimal strategies in terms of the values, and determines the limit of Vkt as k â ∞ with k / â«t0λsds held constant.
Crystal structure of phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with amodiaquine.

Phosphoethanolamine N-methyltransferase (PMT) is essential for phospholipid biogenesis in the malarial parasite Plasmodium falciparum. PfPMT catalyzes the triple methylation of phosphoethanolamine to produce phosphocholine, which is then used for phosphatidylcholine synthesis. Here we describe the 2.0 {angstrom} resolution X-ray crystal structure of PfPMT in complex with amodiaquine. To better characterize inhibition of PfPMT by amodiaquine, we determined the IC{sub 50} values of a series of aminoquinolines using a direct radiochemical assay. Both structural and functional analyses provide a possible approach for the development of new small molecule inhibitors of PfPMT.
Planetary protection issues and the future exploration of Mars.

The results of a workshop are presented in which the issues of planetary protection and biological cross-contamination between the earth and Mars were addressed. A detailed proposal is given regarding strategies for the implementation of the conclusions of the workshop. The significant findings include: (1) the need for evaluating protection issues via unmanned precursor missions; (2) the consideration of all Martian samples as hazardous; and (3) the strategy to avoid Martian landings until it is shown that Martian materials are safe for human contact. The resulting strategy is based on preventing the forward contamination of orbiters and landers by following Mars Observer and Viking planetary-protection procedures. The strategy also allows for back-contamination prevention by means of sample sealing, containment, and quarantine analysis.
The Metabolism of 14 C‐Disulfiram by the Rat

After administration of 14C-disulfiram to rats by stomach tube, we found that 87% of the radioactivity was excreted in urine and 7% in feces. Greater than 80% of the radioactivity was excreted by 48 hr. Small but measurable radioactivity was excreted in urine up to 144 hr after administration. Total recovery of radioactivity at 144 hr was 95% of the ingested dose with less than 1% in organs, blood, and carcass; the remainder was in urine and feces. Studies on specific radioactivity showed that diethylamine, a major urinary metabolite of disulfiram, is excreted in the urine undiluted with endogenous diethylamine. Pretreatment of rats with unlabeled disulfiram leads to a more rapid catabolism of the radioactive drug and more rapid excretion of radioactivity in the urine. Further, pretreatment appears to induce formation of a glucuronide conjugate of a disulfiram metabolite.
Business process management (BPM) in a day

Keeping an organization agile is a means of survival today. This hands-on workshop demonstrated how business process management (BPM) is one avenue that can bring flexibility and adaptability to even very large enterprises.
The phase behavior of fluorinated diols, divinyl adipate and a fluorinated polyester in supercritical carbon dioxide

Abstract The use of supercritical carbon dioxide as a reaction medium for polyester synthesis is hindered by the low solubility of diols in CO2. However, it has been previously demonstrated that fluorinated compounds can exhibit greater miscibility with carbon dioxide than their hydrocarbon analogs. Therefore, the phase behavior of fluorinated diols and divinyl adipate (DVA), an activated diester, in supercritical carbon dioxide has been investigated at 323 K. The phase behavior of equimolar mixtures of DVA with the most carbon dioxide-soluble diol, 3,3,4,4,5,5,6,6-octafluorooctan-1,8-diol (OFOD), was also determined. The solubility of a polyester synthesized from DVA and 2,2,3,3-tetrafluoro-1,4-butanediol (TFBD) was found to be less CO2-soluble than its monomers. DVA was much more soluble in CO2 than any of the fluorinated diols, therefore, no attempt was made to fluorinate the DVA structure. Because both substrates and polyester product were soluble in carbon dioxide, the enzymatic synthesis of a fluorinated polyester from DVA and octafluorooctandiol was performed in supercritical carbon dioxide, resulting in a polymer with a weight average molecular weight of 8232 Da.
Fiber optic infrared reflectance probe for detection of hydrocarbon fuels in soil

The acquisition of fiber optic reflectance spectra of diesel fuel marine (DFM) dispersed on sea sand is described. Reflectance spectra are acquired by collection of the diffusely scattered light from a black body source imaged onto a specially designed sample cell. Samples of DFM were prepared by diluting a stock standard containing 10 wt% DFM on sea sand. Interactive band analysis is used to remove the background absorption due to residual water on the sand. Results indicate a linear relationship between the band depth at 3.68 microns and the concentration of DFM. Statistical analysis of ten replicate measurements of a 0.02 wt% DFM on sea sand gives the average band depth and 95% confidence interval of 0.02875 +/- 0.000654. An instrumental detection limit of 0.0033 percent reflectance is calculated from the standard deviation of the replicate measurements.
Osmotic Shock Inhibits Auxin-stimulated Acidification and Growth

Cells of oat coleoptiles (Avena sativa L. cv. “Garry”) have been osmotically shocked in order to observe the effect of alterations of the plasma membrane on some auxin responses. When coleoptile sections were treated sequentially with 0.5 m mannitol and 1 mm Na-phosphate (pH 6.4) at 4 C, polar auxin transport and acidification by 1 mM CaCl2 were unaffected, but auxin-stimulated acidification and growth were eliminated. Shock treatment also had no effect on acid-stimulated growth or on freezing point depression by the cytoplasm. It is suggested that osmotic shock modifies a portion of the plasma membrane which interacts with auxin and eventually leads to growth.
Bariatric Surgery: Low Mortality at a High-Volume Center

The American Society of Bariatric Surgery has initiated a Bariatric Surgery Center of Excellence Program and the American College of Surgeons has followed with their Bariatric Surgery Center Network Accreditation Program. These programs postulate that concentration of weight loss operations in high-volume centers will decrease surgical mortality and improve outcomes. The purpose of this study was to calculate the in-hospital mortality for bariatric operations accomplished at the highest volume bariatric surgery center in the state of New Jersey. After receiving Institutional Revew Board approval, the revised surgical schedule was used to identify all patients undergoing weight loss surgery (WLS) at Hackensack University Medical Center from 1998 through June, 2006. Data for these patients were then harvested from the hospital’s electronic medical record. Step-wise and univariate logistic regression analysis tested the impact of various factors on hospital length of stay and in-hospital mortality. Between 1998 and June, 2006, 5,365 patients underwent WLS surgery: 2,099 open vertical banded gastroplasty–Roux en Y gastric bypass (VBG–RYGB); 2,177 laparoscopic Roux en Y gastric bypass (LRYGB); and 1,089 laparoscopic adjustable gastric banding (LAGB). 75.5% of patients were women. Median age was 41 years old (13–79), median weight 128 kg (81.2–290.3), and median body mass index 46.1 kg/m2 (35.0–92.6). Median total operating room time for VBG–RYGB was 115 min (33–328); LRYGB 155 min (53–493), and LAGB 92 min (33–274). Median length of stay for VBG–RYGB was 3 days (1–39 days), LRYGB 2 days (1–46 days), and LAGB 1 day (1–20). Seven patients died in hospital after the 5,365 WLS operations (0.13%): four after VBG–RYGB (0.19%); three after LRYGB (0.14%); and none after LAGB (0%). The characteristics of the patients who died did not significantly differ from the group as a whole. Surgeons at Hackensack University Medical Center, a high volume, accredited 1A American College of Surgeons Bariatric Surgery Center, achieved a 0.13% mortality among 5,365 patients undergoing weight loss operations between 1998 and June, 2006. This study supports the concept that high-volume centers perform bariatric operations with low mortalities.
Flow to a Well in a Water‐Table Aquifer: An Improved Laplace Transform Solution

An alternative Laplace transform solution for the problem, originally solved by Neuman, of constant discharge from a partially penetrating well in a water-table aquifer was obtained. The solution differs from existing solutions in that it is simpler in form and can be numerically inverted without the need for time-consuming numerical integration. The derivation involves the use of the Laplace transform and a finite Fourier cosine series and avoids the Hankel transform used in prior derivations. The solution allows for water in the overlying unsaturated zone to be released either instantaneously in response to a declining water table as assumed by Neuman, or gradually as approximated by Boulton's convolution integral. Numerical evaluation yields results identical with results obtained by previously published methods with the advantage, under most well-aquifer configurations, of much reduced computation time.
Nitrogen mustard exposure of murine skin induces DNA damage, oxidative stress and activation of MAPK/Akt-AP1 pathway leading to induction of inflammatory and proteolytic mediators

Our recent studies in SKH-1 hairless mice have demonstrated that topical exposure to nitrogen mustard (NM), an analog of sulfur mustard (SM), triggers the inflammatory response, microvesication and apoptotic cell death. Here, we sought to identify the mechanism/s involved in these NM-induced injury responses. Results obtained show that NM exposure of SKH-1 hairless mouse skin caused H2A.X and p53 phosphorylation and increased p53 accumulation, indicating DNA damage. In addition, NM also induced the activation of MAPKs/ERK1/2, JNK1/2 and p38 as well as that of Akt together with the activation of transcription factor AP1. Also, NM exposure induced robust expression of pro-inflammatory mediators namely cyclooxygenase 2 and inducible nitric oxide synthase and cytokine tumor necrosis factor alpha, and increased the levels of proteolytic mediator matrix metalloproteinase 9. NM exposure of skin also increased lipid peroxidation, 5,5-dimethyl-2-(8-octanoic acid)-1-pyrroline N-oxide protein adduct formation, protein and DNA oxidation indicating an elevated oxidative stress. We also found NM-induced increase in the homologous recombinant repair pathway, suggesting its involvement in the repair of NM-induced DNA damage. Collectively, these results indicate that NM induces oxidative stress, mainly a bi-phasic response in DNA damage and activation of MAPK and Akt pathways, which activate transcription factor AP1 and induce the expression of inflammatory and proteolytic mediators, contributing to the skin injury response by NM. In conclusion, this study for the first time links NM-induced mechanistic changes with our earlier reported murine skin injury lesions with NM, which could be valuable to identify potential therapeutic targets and rescue agents.
Ligand interactions with E-selectin. Identification of a new binding site for recognition of N-acyl aromatic glucosamine substituents of sialyl Lewis X.

Several N-acylglucosamine derivatives of sialyl Lewis X (1−3) were prepared using a combined chemical enzymatic approach and evaluated as an inhibitor of E-selectin-mediated cellular adhesion. Compounds with aromatic functionality, 1 and 2, were found to be 3−10 times more potent than the N-acetyl derivative (14) in an ELISA E-selectin cell adhesion assay. Conformational analysis with NMR indicated that the sialyl Lewis x domain of 1 retained the conformation of the N-acetyl derivative (14) despite the presence of the N-naphthamido group. The dramatic order of magnitude increase in potency of these monovalent structures can be utilized to design more potent selectin-based cell adhesion inhibitors.
The semigroup approach to first order quasilinear equations in several space variables

The Cauchy problem for ut + Σi = 1n (φi(u))xi = 0 is treated via the theory of semigroups of nonlinear transformations. This treatment requires the development of results concerning the time-independent equation u + Σi = 1n (φi(u))xi = h for h∈L1(Rn), which in turn is studied via the regularized equation $$ u + \sum\nolimits_{i = 1}^n {\left( {\phi _i \left( u \right)} \right)} _{xi} - \varepsilon \Delta u = h $$ .
Distributed control for the smart grid: The case of economic dispatch

We describe and summarize our recent results on designing distributed control algorithms for the smart grid that are designed to interact intelligently with traditional control mechanisms in the existing electric grid. We illustrate our approach using our recent work on a novel approach to the classical problem of economic dispatch i.e. the problem of allocating power generation among multiple generating units in such a way as to minimize the total cost of generation while satisfying a set of constraints. Our approach is based on a simple distributed algorithm in which each generator independently adjusts its power-frequency set-points to correct for generation and load fluctuations using only the aggregate power imbalance in the network. We show that the algorithm eventually achieves the condition of optimal economic dispatch under mild assumptions. Our algorithm exploits the power-frequency droop curve, which is a mechanism developed over many decades by power systems engineers to ensure stability in the presence of load fluctuations. Specifically the droop curve allows each generator to measure the aggregate power imbalance in the network in a distributed fashion simply by measuring frequency deviations on the grid. While our approach achieves optimal dispatch using only the implicit communication signal from the droop curve, without requiring any explicit communication whatsoever between the generating units, our recent work also shows that additional communication links can be exploited to improve the rate of convergence to optimality.
Accelerated Alkali-Silica Reactivity Testing of Recycled Concrete Pavement

Techniques and procedures are investigated for assessing the alkali-silica reactivity (ASR) expansion potential of concrete that was made from recycled concrete aggregate, was known to have ASR, or was capable of ASR under conditions of increased alkalinity. Laboratory tests included evaluating prisms characterized by variable surface-to-volume ratios, increased temperature, microwave energy, increased alkali content, and ultrasonic energy. Standard 280-mm (11-in.) prisms with 76.2-mm (3-in.) faces, which were cast with four 6.35-mm (0.5-in.) parallel longitudinal holes, were shown to accelerate ASR and to lower the coefficient of variation of the expansion data. The expansions of 76.2-mm (3-in.) concrete cubes were found to be greatly accelerated, compared with standard prisms. Concrete prisms were subjected to AASHTO T303 and ASTM 1293 conditions and were compared to modified versions of the same tests. Modified AASHTO T303 and modified ASTM 1293 conditions were found to effectively accelerate ASR in concrete prisms cast with holes. Prisms that were sealed in evacuated plastic bags with water were found to effectively accelerate ASR expansion. Testing to date has eliminated the use of ultrasonic energy because it was shown to have no effect on ASR acceleration.
The Use of Remote Sensing for Predictive Modeling of Schistosomiasis in China

The development of predictive models of the spatial distribution of schistosomiasis are hampered by the existence of different regional subspecies of the Oncomelania hupensis snail that serve as intermediate hosts for the disease in China. The habitats associated with these different subspecies vary considerably, with mountainous habitats in the west and floodplain habitats in the east. Despite these challenges, con tin uing environmental change resulting from the construction of the Three Gorges Dam and global warming that threaten to increase snail habitat, as well as limited public health resources, require the ability to accurately map and prioritize areas at risk for schistosomiasis. This paper describes a series of ongoing studies that rely on remotely sensed data to predict schistosomiasis risk in two regions of China. The first study is a classification of Landsat TM image~y to identify snail habitats in mountainous regions of Sichuan Province. The accuracy of this classification was assessed in an independent field study, which revealed that seasonal flooding may have contributed to misclassification, and that the incorporation of soil maps may greatly improve classification accuracy A second study presents the use of Landsat TM and water level data to understand seasonal differences in Oncomelania hupensis habitat in the lower Yangtze River
Surface plasmon resonance imaging (SPRi) for multiplexed evaluation of bacterial adhesion onto surface coatings

Surface plasmon resonance imaging (SPRi) provides continuous, label-free, high-spatial-resolution monitoring of physical changes that occur on surfaces that are up to one square centimeter in area. Here, we utilize SPRi technology to address the challenge of quantitatively evaluating the efficacy of multiple materials to prevent biofilm formation when exposed to flowing fluids. A multiplexed analysis format is particularly important in bacterial attachment studies as adhesion events are very sensitive to their local micro-environment, which are difficult to reproduce and control between experiments. In this study, the effectiveness of bovine serum albumin (BSA), casein, and penicillin/streptomycin surface coatings to prevent Pseudomonas aeruginosa and Staphylococcus aureus adhesion is investigated with SPRi. The coatings were deposited on different sections of a single gold SPRi sensing surface and monitored for 24 hours while being exposed to a continuous flow of growth medium containing bacterial cells. We found that casein most effectively inhibits attachment of cells to the gold surface over a 24 hour period, with an 80% decrease in adhesion versus a bare gold surface for P. aeruginosa and a 60% decrease for S. aureus.
Building an Effective Competitive Intelligence System for Health Care Service Providers

With the increasing competitiveness of the health care marketplace, the need for information by service providers has increased concomitantly. In response to this need, strategic and competitive intelligence systems have emerged as a vital source of information. This article established a basis for the development and operation of a competitive intelligence system. Initially, strategic and competitive intelligence systems are conceptualized, then followed by a discussion of the areas which are candidates for inclusion in the intelligence system. The remainder of the article focuses on system development and operation. Attention also is directed toward information utilization and integration.
A New Design Framework for Sparse FIR MIMO Equalizers

In this paper, we propose a new framework for the design of sparse finite impulse response (FIR) equalizers. We start by formulating greedy and convex-optimization-based solutions for sparse FIR linear equalizer tap vectors given a maximum allowable loss in the decision-point signal-to-noise ratio. Then, we extend our formulation to decision feedback equalizers and multiple-antenna systems. This is followed by further generalization to the channel shortening setup which is important for communication systems operating over broadband channels with long channel impulse responses. We propose a novel approach to design a sparse target impulse response. Finally, as an application of current practical interest, we consider self far-end crosstalk cancellation on vectored very high-speed digital subscriber line systems for cellular backhaul networks.
Sigma receptors as novel target structures for cancer chemotherapeutics

Sigma receptors bind several important classes of psychotropic drugs. Two pharmacologically defined subtypes exist, termed sigma-1 and sigma-2. Sigma receptors are widely distributed across tissues. Both subtypes are highly expressed in tumor cell lines, including breast, lung, and prostate tumor cellines as well as neuroblastomas, gliomas, and melanomas. Furthermore, sigma-2 receptors become more upregulated in rapidly dividing cells. Activation of sigma-2 receptors results in apoptotic cell death. The signaling pathway involves changes in intracellular calcium levels as well as increases in the cellular sphingolipids ceramide and sphingosylphosphorylcholine. The apoptotic effect of sigma-2 agonists is not affected by the p53 status of the cells and is independent of caspase activity. Subtoxic doses of sigma-2 receptor agonists markedly potentiate the cytotoxic effect of doxorubicin and actinomycin-D in breast tumor cellines, indicating a chemosensitizing effect. The very high density of Sigma receptors in tumor cells indicates that they may also be useful targets for development of non-invasive tumor imaging agents. Several radiolabeled sigma ligands show favorable biodistribution and tumor uptake, and melanoma cell tumor xenografts have been successfully imaged in nude mice. Taken together, these results suggest that sigma-2 receptors are involved in the regulation of cell proliferation and survival and activate a novel pathway of programmed cell death. It may be possible to exploit this pathway and the high tumor expression of sigma-2 receptors to develop agents for the treatment and diagnosis of drug-resistant tumors.
Tissue-specific regulation of Ca2+ channel protein expression by sex hormones

The L-type Ca(2+) channel pore-forming alpha subunit, alpha(1C) can be detected in brain and heart as two proteins with molecular masses of approximately 240 kDa and approximately 190 kDa known as alpha(1C-long) and alpha(1C-short), respectively. In brain, the alpha(1C-short) is thought to be the product of a approximately 50 kDa C-terminus calpain-mediated proteolytic deletion. We now show that uterine smooth muscle also possesses alpha(1C-long) and alpha(1C-short) isoforms, and that the relative expression of these two forms is regulated by sex hormones in a tissue-specific manner. Protein expression of alpha(1C) L-type Ca(2+) channels was examined in uterine smooth muscle, brain and heart, comparing non-pregnant (NP) estrus vs. late-pregnant (21 days) rats. The two forms of alpha(1C) were detected in all studied tissues. In late-pregnant uterus, alpha(1C-long) doubled the expression of alpha(1C-short); in NP uterus the opposite occurred. However, these changes were restricted to the uterine muscle, with no changes in brain and heart. To investigate the mechanism of such regulation, ovariectomized rats were treated with sex hormones, progesterone (P4) and/or 17beta-estradiol (estrogen, E2). P4 treatment, which yielded P4 plasma levels of 5 +/- 1 ng/ml and a high P4/E2 ratio (3 +/- 1.5 x 10(3)) similar to the ratio in late-pregnant uterus (1.5 +/- 0.3 x10(3)), facilitated alpha(1C-long) expression. In contrast, E2 or E2+P4 treatment that increased E2 plasma levels to 60 +/- 8 pg/ml and 75 +/- 24 pg/ml, produced low P4/E2 ratios of 0.03 +/- 0.006 and 0.2 +/- 0.1, respectively. These low P4/E2 ratios also found in NP rats at estrus (0.3 +/- 0.1) favored the expression of alpha(1C-short) form in myometrium. Neither hormone treatment altered alpha(1C) expression in brain or heart. Our results indicate that expression of alpha(1C) isoforms depends on P4/E2 ratios. Plasma P4/E2 ratios 1 x 10(3) facilitate the expression of the alpha(1C-long) form. This regulation is tissue-specific for myometrium since it did not occur in heart and brain tissues.
Use of spirometry in the diagnosis of chronic obstructive pulmonary disease and efforts to improve quality of care.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible. In a patient presenting with respiratory symptoms and risk factors, the recommendation is to perform spirometry to determine the presence of airflow obstruction. However, only about a third of patients with a diagnosis of COPD have spirometry along with their diagnosis, although studies have shown that history and physical examination alone are neither sensitive nor specific for diagnosing COPD. Thus, in current practice, many health care providers continue to diagnose and manage COPD without an accurate diagnosis and assessment of severity based on spirometry. This can contribute to inconsistent care and outcomes, as evidenced by findings of variation in spirometry use and acute exacerbation rates of COPD across geographic regions. As there is increasing evidence that pharmacotherapy for COPD has associated risks, including poor cardiovascular outcomes and pneumonia, it is pertinent to obtain an accurate diagnosis to determine appropriate risk–benefit ratios. Previous studies have shown that spirometry has an impact on COPD management; however, there seem to be barriers to the use of spirometry at the patient, provider, and health system level. Innovative quality improvement approaches, such as the application of the various components of the Chronic Care Model, could improve spirometry use in COPD. Only with accurate diagnosis can appropriate management and evidence-based treatment strategies be applied in practice. Therefore, it is important that we continue efforts to increase the use of spirometry in the diagnosis of COPD.
The Rab Protein Family: Genetic Mapping of Six Rab Genes in the Mouse

Rab proteins constitute a family of GTP-binding proteins that are located in distinct intracellular compartments and play a role in the regulation of vesicular trafficking. Yeast mutations in Rab gene homologs cause defects in vesicular transport similar to those observed in beige (bg) mice. To investigate Rab genes as candidates for mouse mutations characterized by defects in vesicular trafficking, we utilized an inter-subspecific backcross [C57BL/6J-bgJ x (C57BL/6J-bgJ x CAST/Ei)F1] segregating for the bg locus. Restriction fragment length polymorphisms (RFLPs) were obtained through Southern hybridization of F1 and C57BL/6J chromosomal DNA with the coding sequences of Rab genes. These RFLPs and 12 polymorphic microsatellites were used to determine the segregation of the Rab genes in 93 backcross mice. Rab4a, Rab4b, Rab7, Rab10, Rab22, and Rab24 were localized on mouse chromosomes 8, 7, 9, 12, 2, and 13, respectively. Although the results exclude these loci as candidates for bg, they demonstrate a wide dispersion of Rab genes throughout the mouse genome and reveal that Rab4b and Rab24 are possible candidates for the mouse mutations reduced pigmentation (rp) and purkinje cell degeneration (pcd), respectively.
Mechanism of extracellular potassium stimulation of protein synthesis in the in vitro hippocampus.

Transverse slices of guinea-pig hippocampus respond to small increases in extracellular potassium concentration [K +] by showing a marked augmentation in the rate of incorporation of labelled precursor amino acid into protein. We find that this augmentation is manifested equally in superfusing solutions containing low specific activity/high concentration precursor and high specific activity/low concentration precursor. This provides additional evidence that the effect of extracellular [K +] is on the rate of protein synthesis and not on the precursor pool. Extracellular [K +] augments amino acid incorporation normally in the presence of concentrations of α-amanatin and actinomycin D which are inhibiting RNA synthesis by over 97%. This suggests the effect is exerted post-transcriptionally. Extracellular [K +] causes an unattenuated increase in protein synthesis in the presence of high Mg2+ (20mm) or low Ca2+ (0 mm) in the superfusate–suggesting this effect of [K +] does not result from an effect on neurotransmitter release. Increases in extracellular [K+] which increase protein synthesis threefold (1.3-6.4mm-K +) increase the intracellular [K +]/[Na +] 2-fold. 3 x 10-7m-Ouabain. which lowers incorporation by 40-50% lowers [K +]/[Na +] by about 50% while having no effect on the uptake of labelled precursor or on the cell concentrations of ATP. These results suggest that protein synthesis in the cell is sensitive to [K. +]/[Na +] and that an alteration in this ratio is the mechanism by which the concentration of extracellular [K +] affects the rate of in vitro hippocampal protein synthesis. This effect of extracellular [K +] on synthesis is not observed in slices from non-cerebral organs of the guinea pig.
Gallium Removal from Weapons-Grade Plutonium and Cerium Oxide Surrogate by a Thermal Technique

Currently, there is interest in fissioning weapons-grade plutonium in nuclear reactors, making use of its valuable energy while at the same time reducing certain dangers associated with its potential for nuclear weapons proliferation. In the process of dismantling nuclear weapons, the US intends to convert much of the Pu metal to oxide. This process yields a PuO{sub 2{minus}x} powder that potentially can be incorporated into mixed oxide nuclear fuel (MOX), a mixture of PuO{sub 2} and UO{sub 2}. This paper describes the process of gallium removal from Ga{sub 2}O{sub 3}-doped CeO{sub 2{minus}x}, a surrogate for weapons-grade PuO{sub 2{minus}x}. Gallium is removed from the surrogate feedstock material using thermal techniques. An Ar-6% H{sub 2} gas was used in order to reduce the oxide to gaseous Ga{sub 2}O. Experimental results were shown in the temperature range of 600 C to 1,200 C as a function of time and sample geometry. The results to date have shown that CeO{sub 2{minus}x} is a very good surrogate for PuO{sub 2{minus}x}.
THE PRICING OF DELIVERY SERVICES

Due to spatial separation between points of distribution and consumption, a vital feature of retailing is the provision of delivery services by customers, retailers, or transport intermediaries. Some store retailers, many Internet retailers, and most transport intermediaries use a multizone pricing plan or a generalized N-zone menu plan. We extend spatial pricing theory to encompass multizone plans. We prove that the optimal number of zones varies with the level of demand relative to the spatial dispersion of customers, and with the cost of implementing a zonal plan. We show that a small number of zones capture almost all the profit attainable with a spatially discriminatory plan.
Characterization of Thermoelectric Modules for Powering Autonomous Sensors

The characterization of three commercial thermoelectric modules, designed for cooling/heating applications, is presented in order to employ the devices for power conversion, i.e as thermoelectric generators (TEG). The thermoelectric theory is briefly described at first, also taking into account the relationship between effective temperature difference across the TEG junctions and temperature difference applied externally, when insulating ceramic plates have a finite thermal conductance. Performances of thermoelectric modules are evaluated in terms of open-circuit output voltage and output power density for different temperature gradients and load conditions. Measurement techniques and experimental data are reported, showing the possibility of use thermoelectric devices for waste heat recover. A TEG was then used to supply an autonomous system that interfaces with a temperature sensor and periodically transmits the measurement information via a radiofrequency (RF) link. Experimental data show that the system works correctly and sends the RF signal when temperature difference applied across TEG is high enough.
Histories of Bayezid I, historians of Bayezid II: Rethinking late fifteenth-century Ottoman historiography

Current scholarship often describes early Ottoman historiography as a phenomenon initiated and conducted by the Ottoman state. In particular, the unprecedented growth in the number of Ottoman history books composed during the reign of Bayezid II (1481–1512) is viewed as such. Modern historians commonly argue that in the aftermath of the Kilia and Akkerman victories (1484), Bayezid II decided to propagate a new Ottoman ideology and commissioned Ottoman history books to be written for this purpose. This article argues that there is not enough evidence to suggest that Bayezid II orchestrated or directed this upsurge in history production. The premises of Halil Inalcik's earlier studies in particular, upon which much of our understanding of the subject was built, do not hold.
Body Image Dissatisfaction in Women Seeking Rhytidectomy or Blepharoplasty

Ninety-seven women seeking rhytidectomy, blepharoplasty, or both completed two measurements of body image prior to their initial consultation. Results were compared with the normal scores for each of the measurements and with a sample of 32 women seeking rhinoplasty. Results indicated that women seeking rhytidectomy, blepharoplasty, or both to improve aging facial features reported a greater investment in and satisfaction with their overall appearance than women in a normattive sample. As was consistent with the findings of previous investigations, when asked about the specific body feature for which they were considering surgery, patients who wished to improve the appearance of aging facial features reported significantly greater dissatisfaction with their appearance feature than the normative sample but significantly less dissatisfaction than patients undergoing rhinoplasty. Patients wishing to improve the appearance of aging facial features seem to present for cosmetic surgery with different body image concerns than patients undergoing other types of cosmetic surgery.
The long and short of it: anterior vaginal wall length before and after anterior repair

Anterior vaginal wall length (AVL) is on average 6.1 ± 1.3 cm in women with normal support and lengthened in women with cystocele. We hypothesize that AVL is reduced after anterior repair and that women with larger cystoceles will have greater reduction in AVL. Demographic, clinical, and surgical data were collected for women undergoing hysterectomy and anterior repair in whom intraoperative vaginal wall measurements had been made between November 2009 and April 2014. In the operating room, AVL was defined preoperatively as the distance from the hymenal ring to the anterior cervicovaginal junction at the hysterectomy incision site, and postoperatively, from the hymenal ring to the same location on the anterior cuff. During the anterior repair the fibromuscular tissues were plicated using an interrupted technique. Measurements were available for 40 women. Average age was 61.7 ± 10 years, median parity was 2.5 and median preoperative Pelvic Organ Prolapse Quantification System (POP-Q) point Ba was 3 cm distal to the hymen. On average, AVL was reduced after surgery by 2.5 cm. Mean postoperative AVL was similar to mean AVL in women with normal pelvic support (6.4 ± 0.8 cm vs 6.1 ± 1.3 cm, p = 0.15). Longer preoperative AVLs had greater AVL change (R 2 = 0.78, p = <0.0001). In women undergoing anterior repair, mean AVL was reduced by 28 % and returned to the normal range after surgery. These data highlight a rarely discussed effect of anterior repair, which is restoration of normal anterior vaginal wall length.
Closed-Loop Control of MBE Using an Integrated Multi-Sensor System

The use of in situ sensors to achieve real-time control of molecular beam epitaxy (MBE) is a rapidly evolving technology that promises to revolutionize MBE in terms of process repeatability and first-pass success, and consequently to improve the overall yield and reduce the cost of the process. To achieve robust real-time control of MBE, we have constructed a multiple-sensor control system comprising in situ sensors for substrate temperature, for effusion cell fluxes, and for the epitaxial layer composition and thickness, along with advanced software to manage the sensor information and execute sensor-feedback control algorithms. This system has been used to grow a number of different III-V semiconductor materials and device structures, including heterojunction bipolar transistors, resonant tunneling devices, and mid-IR lasers. In the present paper, we present results demonstrating control and regulation of substrate temperature and epitaxial layer composition during the growth of lattice-matched InGaAs and InA1As on InP. The control algorithms and software used in the system are described, and we discuss how the synergistic application of multiple sensors allows the regime of composition control to be expanded beyond what would be possible with only a single composition sensor.
Performance Analysis for a Suboptimum ML Receiver in Decode-and-Forward Communications

In this paper, a closed-form bit-error-rate (BER) performance analysis is presented for a suboptimum maximum- likelihood (ML) receiver in decode-and-forward (DF) cooperative wireless communications. The suboptimum ML receiver assumes that an average probability of decoding error at the relay is available at the destination, which depends only on the variance of the source-relay channel link. A by-product of the analysis is that we can obtain a BER analytical result for the DF cooperative protocol using an equal-gain-combining receiver at the destination. Simulation results are presented to validate the theoretical analvsis.
Solution-Dispersible Metal Nanorings with Deliberately Controllable Compositions and Architectural Parameters for Tunable Plasmonic Response

We report a template-based technique for the preparation of solution-dispersible nanorings composed of Au, Ag, Pt, Ni, and Pd with control over outer diameter (60–400 nm), inner diameter (25–230 nm), and height (40 nm to a few microns). Systematic and independent control of these parameters enables fine-tuning of the three characteristic localized surface plasmon resonance modes of Au nanorings and the resulting solution-based extinction spectra from the visible to the near-infrared. This synthetic approach provides a new pathway for solution-based investigations of surfaces with negative curvature.
Kentucky’s Medicaid Expansion Showing Early Promise On Coverage And Access To Care

Kentucky is one of only two southern states, at the time of this writing, to have expanded Medicaid under the Affordable Care Act. The expansion raised Medicaid eligibility levels as a means to mak...
The Effect of Government Control Over Health Care Expenditures on Health Care System Efficiency in the U.S. and Other OECD Countries, 1972-2009

This paper focuses on the question: Does public or private control of health care lead to greater healthcare system efficiency? The data analysis demonstrates a curvilinear relationship between government control over health care and health care system inefficiency and that, as a result, a hybrid approach to health care which takes advantage of a mixture of both government monopsy and private market forces will be the most efficient. In addition, analysis of the data indicates that health risk factors such as obesity play a much larger role in health care costs than assumed by most models.