cssi/SciSciGPT-SciSciNet huggingface dataset:
Experiments on the protection of the thioether in methionine

The decrease in the solubility of peptides when their methionine residues are replaced by methionine sulfoxides prompted the exploration of an alternative approach to the protection of the thioether in methionine side chains. Alkylation of tert.-butyloxycarbonyl methionine p-nitrophenyl ester with methyl p-toluenesulfonate yielded the crystalline derivative of methionine S-methyl p-toluenesulfonate which could be incorporated into peptide chains. Alternatively, methionine S-methyl p-toluenesulfonate (Mmt) residues could be generated by the action of methyl p-toulensulfonate on methionine containing peptides. The protecting group remained intact under the conditions of aminolysis and ammonolysis commonly used in peptide synthesis, and it was unchanged after the removal of other blocking groups with trifluoroacetic acid or diethylamine. On treatment with hydrobromic acid in acetic acid the toluenesulfonate anion was replaced by bromide ion, while hydrogenation resulted in the decomposition of the modified methionine side chain. In the process of deprotection Mmt residues could be smoothly converted to methionine residues by thiolysis. Thus, the protecting group functioned well in several respects but an increase in solubility (in dimethylformamide) on alkylation was observed only in a part of the peptide derivatives tested. Therefore, the value of the new approach for the protection of the methionine side chain in peptide synthesis remains to be established.
Organizational issues of flexible manufacturing systems

Abstract In the last two decades, flexible manufacturing systems (FMS) have emerged as an offspring of technological innovations in computer and numerical control techniques. These systems have brought about significant changes in the ways in which manufacturing organizations compete. This paper examines the organizational impact of FMSs and the resulting implications for management in terms of feasibility, design and implementation activities.
Modelling flower development in navel oranges

Abstract Two models utilizing physiological (degree-day) time-scales were used to describe flower development data in ‘Washington’ navel orange in California. A differential equation model with linear structure and constant coefficients provided a smooth description of flower development, with overall R 2 values ranging from 86 to 92%. Regular trends of underestimation early in the season and overestimation late in the season, however, indicated a non-constancy in rates of flower development. The second model incorporated distributed developmental times and stage-specific loss rates into a discrete time-equation model. This model provided an improved description of field data. Applications of models of flower development to citrus pest management are discussed.
Design of smart photodetector arrays for page-oriented optical memories

Parallel optical memoirs offer the capability for storage and retrieval of optical data in 2D pages resulting in high throughput data rates. The optical data page can be received by 2D arrays of 'smart' photodetector elements that perform fast parallel data decoding and error control, thereby providing an efficient optoelectronic interface between the memory and the electronic computer. In this paper, ewe consider the design of smart photodetector arrays in terms of hardware complexity, optical power requirements, and electrical power dissipation. Scalability and throughput are discussed with respect to these parameters.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Eleventh Amendment Immunity in Contemporary Practice: Revisiting the Legal Liability of Local Government in the United States

Sovereign immunity is deeply rooted in the American system of government, and its role in balancing individual rights with democratic rule is crucial in litigation still today. This research highlights the fundamental principle of sovereignty and reviews relevant cases as it examines the legal liability of local governments in the twenty-first century. While the U.S. Supreme Court continues to reject immunity below the state level, the lower courts have extended Eleventh Amendment immunity to local government entities in some cases. The author posits that the modernization and delegation of powers to cities, counties, and other local political subdivisions warrant a more contemporary and explicit interpretation of sovereignty by the U.S. judicial system. La inmunidad soberana estatal esta profundamente arraigada en el sistema americano de gobierno, y su papel en ajustar el gobierno democratico a los derechos individuales es crucial en la litigacion aun hoy. Esta investigacion destaca el principio fundamental de la soberania y revisa casos relevantes mientras examina la responsabilidad legal de los gobiernos locales en el siglo XXI. Mientras la Suprema Corte de Justicia continua rechazando la inmunidad del nivel estatal para abajo, en algunos casos las cortes estatales han ampliado la inmunidad de la Onceava Enmienda a las entidades de los gobiernos locales. El autor propone que la modernizacion y la delegacion de poderes a las ciudades, condados, y otras subdivisiones politicas locales garantizan una interpretacion mas contemporanea y explicita de la soberania del sistema judicial de los Estados Unidos.
Role Strain, Emotion Management, and Burnout: Homeschooling Mothers' Adjustment to the Teacher Role

Drawing from three years of field research with a homeschooling support group in the Pacific Northwest, I present the emotional stages mothers passed through as they tried to integrate the teacher role into their busy lives. In most cases, mothers found teaching more demanding than they had expected, straining their other roles as mothers and homemakers, as well as causing emotional burnout. To manage their insecurity, anxiety, and stress, mothers employed a variety of emotion management techniques. Mothers who successfully overcame burnout prioritized some roles, combined others, and received significant support from their husbands. I conclude by discussing the implications for theories of burnout.
Excitation of an Open Cavity via HE11 Excited Single Mode Optical Fiber for a Fabry-Perot Interferometer

Fabry-Perot interferometer configuration consisting of a single mode optical fiber end coupled to an open cavity has been studied. The established fields inside the open cavity due to excited HE11 mode, transmission and reflection coefficients incorporating diffraction effects from the fiber end were formulated using the mode matching method. A semi-analytical algorithm that accounts for the vector nature of the fields was developed and evaluated. Numerical simulations were verified against experimental measurements.
A new method for determining optical purity, using circular polarization of luminescence

Abstract A new method for determining optical purity is proposed which utilizes circular polarization of luminescence. The calculational method is derived.
Design of PH-based accelerated life testing plans under multiple-stress-type

Accelerated life testing (ALT) is used to obtain failure time data quickly under high stress levels in order to predict product life performance under design stress conditions. Most of the previous work on designing ALT plans is focused on the application of a single stress. However, as components or products become more reliable due to technological advances, it becomes more difficult to obtain significant amount of failure data within reasonable amount of time using single stress only. Multiple-stress-type ALTs have been employed as a means of overcoming such difficulties. In this paper, we design optimum multiple-stress-type ALT plans based on the proportional hazards model. The optimum combinations of stresses and their levels are determined such that the variance of the reliability estimate of the product over a specified period of time is minimized. The use of the model is illustrated using numerical example, and sensitivity analysis shows that the resultant optimum ALT plan is robust to the deviation in model parameters.
Formation and Catalytic Application of Electrically Conductive Pt Nanowires

Pt nanowires with variable lengths have been synthesized by the reduction of Pt(IV) ions using alkaline 2,7-DHN in CTAB micellar media under 3 h of UV photoirradiation. The synthesized Pt nanowires are stable for more than 3 months in ambient conditions. The particles’ morphology can be tuned by simply changing the surfactant-to-metal ion molar ratios and other reaction parameters. The mechanisms of the nanowire formation and effects of different reaction parameters are studied in detail. The resulting nanowires are found to be electrically conductive and maintain Ohm’s law with the electrodes. Moreover, they serve as a good catalyst for the reduction of organic dye molecules in the presence of NaBH4. The catalysis rate was compared by considering the electron-transfer process during reduction. The present method would lead to a quick process for the synthesis of other monometallic and composite nanowires with variable lengths. The Pt nanowires offer promising applications in different types of organic an...
Maintenance loses its innocence

In this issue of Blood, Schmiegelow and colleagues on behalf of the Nordic Society for Paediatric Haematology and Oncology (NOPHO) present convincing evidence of a link between maintenance therapy with 6-mercaptopurine/methotrexate and the development of SMNs after treatment for pediatric ALL.
The ultrastructure of precocene-induced effects on the corpora allata of the adult milkweed bug, Oncopeltus fasciatus.

Abstract If Oncopeltus fasciatus are exposed to precocene during the first 7 days following adult emergence, the corpora allata fail to completely mature or secrete juvenile hormone. The ultrastructure of these treated gland cells resembles that of inactive cells; i.e., they contain vast accumulations of the vesicles typically seen in immature gland cells.
Hyperamino aciduria induced in rats by O,O,S-trimethyl phosphorothioate

Abstract A single oral dose of the malathion impurity, O,O,S -trimethyl phosphorothioate (OOS-Me) resulted in a substantial increase in the amount of amino acids excreted in rat urine over a 10-day period as estimated by the ninhydrin method. Levels of amino acids in the urine of treated rats increased as high as 13-fold compared to levels found in untreated rats. The effects of OOS-Me was dose dependent, notable amino aciduria being observed at 20–60 mg/kg and no effect observed at 10 mg/kg. Animals receiving 40 and 60 mg/kg OOS-Me manifested typical signs of delayed toxicity, e.g., weight loss and refusal of food and water. Moreover, the amino acid content in the urine of rats treated with 60 mg/kg OOS-Me adulterated with 3 mg/kg OOO-Me (5% antagonist) was comparable to that found with control rats. In contrast to the urine study, the results reveal essentially no difference in amino acid levels in the blood of control rats and rats treated with the various dosages of OOS-Me. This finding, coupled with evidence of the occurrence of oliguria, diuresis, and reduction in blood urea nitrogen-creatinine ratios, suggests that OOS-Me may cause acute kidney tubular damage.
Mechanism of portal venous tolerant long-term MHC Class I Ld-specific skin graft survival in transgenic 2CF1 mice

Abstract Background: Administration of alloantigen via the portal vein (PV) in non-transgenic animals has been shown to promote immunologic tolerance and enhance transplant allograft survival. The underlying mechanisms remain unclear. In 2C×dm2 F1 (2CF1) transgenic mice, the monoclonal antibody, 1B2, identifies specific 2C TCR transgenic CD8+ T cells that are cytotoxic against Class I MHC Ld. In these mice, the specific response by these cells to Ld+ skin grafts after PV administration of Ld+ antigen was determined. Materials and Methods: Saline (control) or allogeneic C57BL/6×BALB/c F1 (CB6F1) spleen cells (25×106), which differ from 2CF1 only at Ld, were injected PV into 2CF1 mice. One week later, CB6F1 tail skin was transplanted onto the dorsum of these 2CF1 mice. Skin graft rejection was defined as >50% loss of the graft. Parallel experiments were performed in non-transgenic littermates [B6F1 (C57BL/6×dm2)]. FACS analysis of 2CF1 peripheral blood for 1B2+, CD4+, and CD8+ T cells was performed 2 days before PV injection (9 days prior to skin grafting), 5 days after PV injection (2 days prior to skin grafting), and 7, 14, 21, 28, and 60 days after skin grafting. FACS analysis of naive, saline control, and CB6F1 PV-treated 2CF1 thymocytes was also performed. Responsiveness of saline (control)-treated and PV-treated 2CF1 splenocytes was measured by in vitro cytotoxic T lymphocyte (CTL). Results: All CB6F1 skin grafts were rejected in
Stability Analysis of Semicohesive Streambanks with CONCEPTS : Coupling Field and Laboratory Investigations to Quantify the Onset of Fluvial Erosion and Mass Failure

AbstractThe overarching goal of this study is to perform a comprehensive bank stability analysis that is phenomenologically sound by considering both mass failure and fluvial erosion. The nature of this study is twofold. First, field and experimental analyses are conducted to generate data for channel cross-section properties, soil index properties, and mechanical and erosional strengths at two sites in a representative, midsize, midwestern stream in southeastern Iowa that is subjected to frequent flash floods and characterized by active fluvial erosion and cantilever failure. Second, the channel surveys and data obtained from the field and laboratory analyses are used as input parameters for an established one-dimensional, channel evolution model, namely, the conservational channel evolution and pollutant transport system (CONCEPTS, version 2.0, Langendoen and Alonso 2008), to estimate the factor of safety for mass failure (FSm) and fluvial erosion (FSf) and simulate the bank retreat as a result of eithe...
The spreading of liquids on low-energy surfaces. II. Modified tetrafluoroethylene polymers

Abstract 1. 1. Data are presented on the equilibrium contact angles of a wide variety of liquids on specially prepared surfaces of halogenated derivatives of polyethylene. The free energy decrease of immersion (fSL), the work of adhesion (WA), and the spreading coefficients have been calculated for the liquids which do not spread. The free energy decrease on immersion of these solids in the saturated vapor of most of the liquids of this study is shown to be negligible. 2. 2. For each solid surface the contact angle and spreading coefficient follow the relation to liquid surface tension reported previously for polytetrafluoroethylene, i.e., as the liquid surface tension increases, the contact angle increases and the spreading coefficient decreases. 3. 3. Substitution of chlorine or hydrogen for fluorine in these polymers increases WA, fSL, and the spreading coefficient with respect to a given liquid, the increase depending on the proportion of nonfluorine substituent. Substitution of hydrogen for fluorine has a smaller effect in this respect than substitution of chlorine for fluorine. 4. 4. It is shown that when fSL for a given solid in a series of liquids is constant, the plots of WA υs. surface tension and spreading coefficient υs. surface tension should be straight lines with positive and negative 45° slopes, respectively. The data presented for the fluorinated polymers and the liquid n-alkanes and di-n-alkyl ethers fall on such lines. The values of fSL for the fluorinated polymers plot as a straight line against mole per cent fluorine substitution. 5. 5. There appears to be a maximum value of WA characteristic of the polymer, which is identical with the work of adhesion given by the liquid having a contact angle of 90° on the given solid. 6. 6. It is shown experimentally that there are many exceptions to the “rule” that nonpolar liquids wet nonpolar solids. 7. 7. From the data it is shown that recent attempts to measure the surface tension of solids by contact angle measurements alone involve unjustifiable assumptions.
Velocity compression in cylindrical capacitor electrospray of methanol-water mixtures

Phase Doppler anemometry was utilized to measure the >0.5-μm portion of the size distributions and the corresponding velocity distributions of methanol−water droplets generated by a miniature cylindrical capacitor electrospray (CCES) source. Droplets exceeding 1 μm in diameter were observed with the tail of the size distributions extending up to 5 μm. Droplets produced by this source displayed significantly narrower velocity distributions and smaller mean axial velocities relative to those generated by forced flow electrospray. In terms of flow rate, spraying voltage, droplet size, and axial velocity distributions, the CCES source represents a transition between conventional electrospray and nanospray sources. The CCES is quasi-monodisperse, and the droplets have close to uniform velocities. There is a significant effect of the spraying voltage on the width and mean values of the droplet size and velocity distributions for methanol solutions. Both mean diameters and average axial velocities are shifted to...
Can treating depression improve disease outcomes

Although treating depression may not improve the outcome of comorbid illnesses, as a study in this issue suggests, it may dramatically improve the quality of life for patients and their families. C...
Molecular Motion and Environmental Rigidity in the Framework and Ionic Interface Regions of Mesostructured Silica Thin Films

The rigidochromic probe molecule ClRe(CO)3-2,2‘-bipyridine is used to study the properties of mesostructured silica thin films. The probe serves dual functions: its emission band maximum shifts to higher energy with increasing rigidity of its environment and simultaneously the fluorescence depolarization measures the mobility of the probe molecule itself. Dip-coated, mesostructured 2-d hexagonal thin films doped with ClRe(CO)3-2,2‘-bipyridine are prepared by a one-step, one-pot synthesis procedure using tetraethoxysilane as the silicon source and cetyltrimethylammonium bromide as the structure directing agent. Amorphous silicate films prepared without the surfactant are used as controls. In the freshly prepared mesostructured films, the probe molecules reside in both the silica framework (in a rigid environment) and the ionic interface region near the surfactant headgroups (in a nonrigid environment) as shown by the rigidochromic shift. The fluorescence depolarization confirms the rigidity; the molecule ...
Microbial population of shredded carrot in modified atmosphere packaging as related to irradiation treatment.

Shredded carrots in modified atmosphere packaging were treated with low-dose irradiation of 0.5 kGy in order to determine whether additional reduction of microbial population would be achieved for carrots previously treated with chlorine. Commercially prepared shredded carrots treated with irradiation had a mean microbial population of 1300 CFU/g at the expiration date (9 days after irradiation) compared with 87,000 CFU/g for nonirradiated, chlorinated controls. Oxygen content of the headspace gas and ethanol content of the carrots were not significantly affected. Irradiation appears to be a suitable technology for shredded carrots.
A study of the surface texture of composite drilled holes

Abstract An investigation of the surface texture of composite drilled holes was conducted by drilling experiments at constant speed with two different PCD tipped drill geometries at varying feed rates. Surface profilometry was used to measure the surface roughness profiles of machined graphite/epoxy holes and roughness characteristics were evaluated using average roughness heights, statistical methods, and random process methods. It was found that the width of damage in a composite material is a function of the drill geometry and the feed rate. All the surfaces studied were found to be non-Gaussian, negatively skewed, leptokurtic, and produced a good bearing surface. The use of maximal roughness height parameters, power spectral density function, and cumulative height density plotted on a probit scale allows characterization of the texture of the surfaces of the drilled holes.
Post-Treatment with Voltage-Gated Na+ Channel Blocker Attenuates Kainic Acid-Induced Apoptosis in Rat Primary Hippocampal Neurons

Injection of rats with kainic acid (KA), a non-N-methyl-d-aspartate (NMDA) type glutamate receptor agonist, induces recurrent (delayed) convulsive seizures and subsequently hippocampal neurodegeneration, which is reminiscent of human epilepsy. The protective effect of anti-epileptic drugs on seizure-induced neuronal injury is well known; however, molecular basis of this protective effect has not yet been elucidated. In this study, we investigated the effect and signaling mediators of voltage-gated Na+ channel blockers (Lamotrigine, Rufinamide, Oxcarbazepine, Valproic Acid, and Zonisamide) on KA-induced apoptosis in rat primary hippocampal neurons. Exposure of hippocampal neurons to 10 μM KA for 24 h caused significant increases in morphological and biochemical features of apoptosis, as determined by Wright staining and ApopTag assay, respectively. Analyses showed increases in expression and activity of cysteine proteases, production of reactive oxygen species (ROS), intracellular free [Ca2+], and Bax:Bcl-2 ratio during apoptosis. Cells exposed to KA for 15 min were then treated with Lamotrigine, Rufinamide, Oxcarbazepine, Valproic Acid, or Zonisamide. Post-treatment with one of these anti-epileptic drugs (500 nM) attenuated production of ROS and prevented apoptosis in hippocampal neurons. Lamotrigine, Rufinamide, and Oxcarbazepine appeared to be less protective when compared with Valproic Acid or Zonisamide. This difference may be due to blockade of T-type Ca2+ channels also by Valproic Acid and Zonisamide. Our findings thus suggest that the anti-epileptic drugs that block both Na+ channels and Ca2+ channels are significantly more effective than agents that block only Na+ channels for attenuating seizure-induced hippocampal neurodegeneration.
MTA family of coregulators in nuclear receptor biology and pathology

Nuclear receptors (NRs) rely on coregulators (coactivators and corepressors) to modulate the transcription of target genes. By interacting with nucleosome remodeling complexes, NR coactivators potentiate transcription, whereas corepressors inhibit transcription of the target genes. Metastasis-associated proteins (MTA) represent an emerging family of novel NR coregulators. In general, MTA family members form independent nucleosome remodeling and deacetylation (NuRD) complexes and repress the transcription of different genes by recruiting histone deacetylases onto their target genes. However, MTA1 also acts as a coactivator in a promoter-context dependent manner. Recent findings that repression of estrogen receptor transactivation functions by MTA1, MTA1s, and MTA2 and regulation of MTA3 by estrogen signaling have indicated the significance of these proteins in NR signaling. Here, we highlight the action of MTA proteins on NR signaling and their roles in pathophysiological conditions.
Decreased endothelium-dependent vascular relaxation following subtotal coronary artery occlusion in dogs.

Abstract Total coronary artery occlusion followed by reperfusion leads to neutrophil accumulation in the reperfused myocardium and a reduction in endothelium-dependent coronary artery relaxation. Attenuated coronary artery relaxation in the affected regions is thought to be related to breakdown of endothelium-derived relaxing factor (EDRF) by free oxygen radicals released during reperfusion. To determine if temporary subtotal coronary artery narrowing leads to similar alteration in vascular reactivity, eight open-chest dogs were subjected to 1 h of left anterior descending (LAD) coronary artery narrowing (70% reduction in basal flow) and pacing-induced increase in heart rate (30% above baseline) followed by reperfusion for 1 h. Thereafter reactivity of ischemic-reperfused LAD and nonischemic circumflex (Cx) coronary aftery rings to the thromboxane A2 analog U46,619 and EDRF-dependent vasorelaxants acetylcholine (ACh), thrombin, and adenosine diphosphate (ADP), as well as to EDRF-independent vasorelaxant nitroglycerin (NTG), was examined. Unlike in the setting of total coronary artery occlusion, reperfused myocardium or LAD did not reveal neutrophil infiltration. However, contraction in response to U46,619 was markedly (P
Prospective evaluation of serum amiodarone concentrations when administered via a nasogastric tube into the stomach conduit after transthoracic esophagectomy

Abstract Background: Atrial fibrillation occurs in up to 46% of patients following esophagectomy; amiodarone may be used for prophylaxis or treatment in these patients. There are few data regarding drug absorption following esophagectomy. Objective: The aim of this study was to determine serum amiodarone concentrations when the drug is administered into the stomach conduit following esophagectomy. Methods: Patients who underwent noncardiac thoracic surgery were enrolled in this prospective, controlled study. One group of patients underwent esophagectomy, and a second group of patients comprised a control group who underwent pulmonary resection (PR). A continuous IV amiodarone infusion (0.73 mg/min) was initiated at anesthesia induction and continued for 24 hours (total IV dose 1050 mg), ollowed by 400 mg via a nasogastric tube (in the esophagectomy group) or orally (in the PR group) every 12 hours for 6 days. Blood samples for determination of serum amiodarone concentrations were obtained at completion of the infusion (postoperative day [POD] 1), and before the third (POD 2) and seventh (POD 4) enteral doses. Results: A total of 27 patients were enrolled (esophagectomy group, 13 patients; PR group, 14 patients). Patients in the 2 groups had statistically similar ages (mean [SD], 60 [10] vs 53 [10] years; P=0.07) and proportions of men (12/13 [92%] vs 8/14 [57%]; P=0.08). Patients in the 2 groups were statistically similar with respect to race (white, 13/13 [100%] vs 13/14 [93%]) and preoperative weight (mean [SD], 83.3 [11.5] vs 77.7 [18.6] kg). On POD 1, age-adjusted and sex-adjusted serum amiodarone concentrations were not significantly different in the esophagectomy group versus the PR group (mean [SD] 0.65 [0.22] vs 0.84 [0.20] μg/mL). Mean (SD) serum amiodarone concentrations were significantly lower in the esophagectomy group on POD 2 (0.35 [0.27] vs 0.60 [0.18] μg/mL; P=0.02) and on POD 4 (0.30 [0.34] vs 0.87 [0.16] µg/mL; P Conclusions: Serum amiodarone concentrations were significantly lower (and in some cases undetectable) when the drug was administered via a nasogastric tube into the stomach conduit in patients after esophagectomy compared with those concentrations after oral administration in a PR population. These data were presented as a poster presentation at the Spring Practice and Research Forum, American College of Clinical Pharmacy, April 9, 2006, Monterey, California.
Circuit simulation-the early years

A personal perspective on circuit simulation from the mid-1960s through the mid-1970s is given. Attempts to use an optimization-based approach to design are described. The development of circuit simulation programs is chronicled, and the manipulation of sparse matrices is discussed. Commercialization of simulation programs is addressed, with particular attention to SPICE, illuminating its strengths, uncovering its weaknesses, and projecting its future. >
Probing the non-native H helix translocation in apomyoglobin folding intermediates.

Apomyoglobin folds via sequential helical intermediates that are formed by rapid collapse of the A, B, G, and H helix regions. An equilibrium molten globule with a similar structure is formed near pH 4. Previous studies suggested that the folding intermediates are kinetically trapped states in which folding is impeded by non-native packing of the G and H helices. Fluorescence spectra of mutant proteins in which cysteine residues were introduced at several positions in the G and H helices show differential quenching of W14 fluorescence, providing direct evidence of translocation of the H helix relative to helices A and G in both the kinetic and equilibrium intermediates. Forster resonance energy transfer measurements show that a 5-({2-[(acetyl)amino]ethyl}amino)naphthalene-1-sulfonic acid acceptor coupled to K140C (helix H) is closer to Trp14 (helix A) in the equilibrium molten globule than in the native state, by a distance that is consistent with sliding of the H helix in an N-terminal direction by approximately one helical turn. Formation of an S108C–L135C disulfide prevents H helix translocation in the equilibrium molten globule by locking the G and H helices into their native register. By enforcing nativelike packing of the A, G, and H helices, the disulfide resolves local energetic frustration and facilitates transient docking of the E helix region onto the hydrophobic core but has only a small effect on the refolding rate. The apomyoglobin folding landscape is highly rugged, with several energetic bottlenecks that frustrate folding; relief of any one of the major identified bottlenecks is insufficient to speed progression to the transition state.
Radioiodinated (+)‐4‐[(αR)‐α‐[(2S5R)‐4‐(iodopropen‐2‐yl)‐2,5‐dimethyl‐1‐piperazinyl]‐3‐hydroxybenzyl]‐N,N‐diethylbenzamide: a potential ligand for in vitro and in vivo investigations of δ‐opioid receptors

(+)-4-[(αR)-α-[(2S, 5R)-4-(iodopropen-2-yl)-2,5-dimethyl-1-piperazinyl]]-3-hydroxybenzyl]-N, N-diethylbenzamide (1), a novel radioiodinated derivative of the selective δ-opioid antagonist (+)-BW373U86, was synthesized and evaluated in vitro for binding to opioid receptor subtypes. This new compound was found to have high affinity (Ki = 0.57 ± 0.10 nM) and good selectivity for delta (δ) opioid receptors over mu (μ) (Ki μ/δ = 13.6) and kappa (K) (Ki K/6 = 175) receptors. The corresponding 123 I and 125 I derivatives were prepared by oxidative radioiododestannylation from a trans-vinyltributyltin precursor. The radiochemical yield was 72-78% EOS (74.3 ± 2.6%, n = 3) for 125 I-1 and 40-62% EOS (53.9 ± 9.8%, n = 3) for 123 I-1. The specific activities were 200-300 mCi/μmol and >5,000 mCi/μmol for the 125 I and 123 I-labeled tracers, respectively.
Reciprocal identities and integral formulations for diffusive scalar transport and Stokes flow with position-dependent diffusivity or viscosity

Reciprocal relations between any two solutions of the equations of diffusive scalar transport with position-dependent diffusivity are derived, and integral representations involving the Green’s function of Laplace’s equation and accompanying integral equations are developed. When the diffusivity exhibits mild variations over the solution domain, the rate of transport across an isoscalar surface can be predicted from the solution for uniform diffusivity. A corresponding analysis is presented for the equations of Stokes flow with position-dependent fluid viscosity. When the viscosity exhibits mild variations, the force and torque exerted on a surface moving as a rigid body can be predicted from the solution for constant viscosity. Numerical methods for solving the integral equations based on boundary-element and domain discretizations into triangular elements are developed in two dimensions.
Systemic Therapy for Hepatocellular Carcinoma and Cholangiocarcinoma

Understanding core signaling pathways in hepatic carcinogenesis has brought about a new era in the management of hepatocellular carcinoma. Sorafenib was the first molecular targeted therapy to be approved for advanced hepatocellular carcinoma and is the benchmark for all other therapies. Cytotoxic chemotherapy remains the mainstay treatment of advanced cholangiocarcinoma and there are no US Food and Drug Administration-approved molecular targeted therapies. If clinicians are able to minimize the toxicity of therapy by targeting the driving mechanism of cell proliferation, they will be able to significantly improve the survival and quality of life of patients.
Performance of multiple-ring networks for real-time communications

The results of a simulation study in which the real-time performances of a high-speed token ring network and a multiple-ring network were compared are described. The medium access protocols and the interconnection topologies of the multiple-ring network evaluated are discussed. The characteristic of the workload used in this simulation experiment is described. The simulation results are given. >
Full-Length Dimeric MCAK Is a More Efficient Microtubule Depolymerase than Minimal Domain Monomeric MCAK

MCAK belongs to the Kinesin-13 family, whose members depolymerize microtubules rather than translocate along them. We defined the minimal functional unit of MCAK as the catalytic domain plus the class specific neck (MD-MCAK), which is consistent with previous reports. We used steady-state ATPase kinetics, microtubule depolymerization assays, and microtubule.MCAK cosedimentation assays to compare the activity of full-length MCAK, which is a dimer, with MD-MCAK, which is a monomer. Full-length MCAK exhibits higher ATPase activity, more efficient microtubule end binding, and reduced affinity for the tubulin heterodimer. Our studies suggest that MCAK dimerization is important for its catalytic cycle by promoting MCAK binding to microtubule ends, enhancing the ability of MCAK to recycle for multiple rounds of microtubule depolymerization, and preventing MCAK from being sequestered by tubulin heterodimers.
Effect of low meter impedance on loop-antenna based measurements of magnetic fields

In using a simple loop-antenna for the measurement of low-frequency magnetic fields, systematic errors (of the order of 20%) could arise if a low impedance (50 Omega ) meter is substituted in lieu of a high-impedance type. Nonconsideration of this error in recommended measurement practices and procedures (such as the SAE specification) for radiated emissions is indicated. Theoretical results indicating the systematic error computed over a frequency range of 30 Hz to 25 KHz are presented. Supporting experimental data concerning the loop impedance measurements and the difference in loop-antenna output voltage noticed with low and high impedance meters confirm the theoretical elucidations. >
How much medical care do the uninsured use, and who pays for it?

With the number of uninsured exceeding 41 million people in 2001, insuring the uninsured is again a major policy issue. This analysis establishes benchmarks for the inevitable debate over the cost of expanding coverage: how much is currently spent on care for the uninsured and where does the money come from? This information is essential for assessing how much new money will be required for expanded coverage, how much can be reallocated from existing sources, and how a new financing system would redistribute the burden of subsidizing care for the uninsured from private to public sources (Health Affairs,/i> Web Exclusive, February 2003).
Probabilistic fracture mechanics: J-estimation and finite element methods

Abstract The objective of this study was to evaluate the adequacy of current J-estimation models commonly used in probabilistic elastic–plastic analysis of ductile cracked structures. A newly developed probabilistic model based on elastic–plastic finite element method was used to evaluate the J-estimation model. In both models, the analyses involve elastic–plastic fracture mechanics for underlying deterministic calculations, statistical representation of uncertainties in loads, crack size, and material properties involving both tensile and fracture toughness characteristics, and standard computational methods of structural reliability theory. Numerical examples are presented for two- and three-dimensional cracked structures. The results show that the probabilistic analysis based on J-estimation model provides accurate estimates of failure probability when compared with those predicted by generally more accurate finite element model. The uncertainty in the crack size, if exists, can have a significant effect on the probability of failure, particularly when the crack size has a large coefficient of variation. A finite element-based probabilistic fracture-mechanics model is useful in benchmarking approximate results of J-estimation analysis.
The widening spectrum of celiac disease

Celiac disease is a permanent intolerance to ingested gluten that results in immunologically mediated inflammatory damage to the small-intestinal mucosa. Celiac disease is associated with both human leukocyte antigen (HLA) and non-HLA genes and with other immune disorders, notably juvenile diabetes and thyroid disease. The classic sprue syndrome of steatorrhea and malnutrition coupled with multiple deficiency states may be less common than more subtle and often monosymptomatic presentations of the disease. Diverse problems such as dental anomalies, short stature, osteopenic bone disease, lactose intolerance, infertility, and nonspecific abdominal pain among many others may be the only manifestations of celiac disease. The rate at which celiac disease is diagnosed depends on the level of suspicion for the disease. Although diagnosis relies on intestinal biopsy findings, serologic tests are useful as screening tools and as an adjunct to diagnosis. The treatment of celiac disease is lifelong avoidance of dietary gluten. Gluten-free diets are now readily achievable with appropriate professional instruction and community support. Both benign and malignant complications of celiac disease occur but these can often be avoided by early diagnosis and compliance with a gluten-free diet.
Traits, trees and taxa: global dimensions of biodiversity in mammals

Measures of biodiversity encompass variation along several dimensions such as species richness (SR), phylogenetic diversity (PD) and functional/trait diversity (TD). At the global scale, it is widely recognized that SR and PD are strongly correlated, but the extent to which either tends to capture variation in TD is unclear. Here, we assess relationships among PD, SR and TD for a number of traits both across clades and regional assemblages of mammals. We also contrast results using two different measures of TD, trait variance and a new measure we refer to as trait bin filling (the number of orders of magnitude of variation that contain at least one species). When TD is defined as trait variance, PD is a much stronger correlate of TD than SR across clades, consistent with hypotheses about the conservation value of PD. However, when TD is defined as bin filling, PD and SR show similar correlations with TD across clades and space. We also investigate potential losses of SR, PD and TD if species that are currently threatened were to go extinct, and find that threatened PD is often a similar predictor of threatened TD as SR.
Targeting β-Cell Mass in Type 2 Diabetes : Promise and Limitations of New Drugs Based on Incretins

Progressive insulin secretory defects, due to either functional abnormalities of the pancreatic β-cells or a reduction in β-cell mass, are the cornerstone of type 2 diabetes. Incretin-based drugs hold the potential to improve glucose tolerance by immediate favorable effect on β-cell physiology as well as by expanding or at least maintaining β-cell mass, which may delay the progression of the disease. Long-term studies in humans are needed to elaborate on these effects.
Effects of mechanical stress and growth on the velocity of tooth movement

Introduction In this study, we investigated the effects of the magnitudes of applied stress and growth status on the speed of tooth movement. Methods Eighty-two maxillary canines in 41 subjects were retracted for 84 days by estimated stresses of 4, 13, 26, 52, or 78 kPa applied continuously via segmental mechanics. Dental impressions made at intervals of 1 to 14 days resulted in 9 or 10 dental casts per subject. Three-dimensional tooth movements were quantified using these casts, custom reference templates, and a measuring microscope. Serial height and cephalometric measurements determined growth status. Results Distal tooth movement was linear with no lag phase in 96% of the teeth. Speeds averaged 0.028, 0.040, 0.050, 0.054, and 0.061 mm per day (standard errors, ± 0.004) for 4, 13, 26, 52, and 78 kPa, respectively. The maximum difference in speed between teeth was 9:1. Teeth moved significantly faster (P Conclusions The speed of retraction was logarithmically related to the applied stress and was significantly faster in actively growing subjects compared with those who were not growing.
Science knowledge and cognitive strategy use among culturally and linguistically diverse students

Science performance is determined, to a large extent, by what students already know about science (i.e., science knowledge) and what techniques or methods students use in performing science tasks (i.e., cognitive strategies). This study describes and compares science knowledge, science vocabulary, and cognitive strategy use among four diverse groups of elementary students: (a) monolingual English Caucasian, (b) African-American, (c) bilingual Spanish, and (d) bilingual Haitian Creole. To facilitate science performance in culturally and linguistically congruent settings, the study included student dyads and teachers of the same language, culture, and gender. Science performance was observed using three science tasks: weather phenomena, simple machines, and buoyancy. Data analysis involved a range of qualitative methods focusing on major themes and patterns, and quantitative methods using coding systems to summarize frequencies and total scores. The findings reveal distinct patterns of science knowledge, science vocabulary, and cognitive strategy use among the four language and culture groups. The findings also indicate relationships among science knowledge, science vocabulary, and cognitive strategy use. These findings raise important issues about science instruction for culturally and linguistically diverse groups of students.
Phase I and Pharmacokinetic Study of the Ribonucleotide Reductase Inhibitor, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, Administered by 96-Hour Intravenous Continuous Infusion

Purpose 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP; Triapine; Vion Pharmaceuticals Inc, New Haven, CT) is a potent inhibitor of ribonucleotide reductase, with activity in preclinical tumor model systems. A phase I trial was initiated to determine the dose-limiting toxicities, maximum-tolerated dose, and pharmacokinetics of a 96-hour intravenous (IV) continuous infusion in patients with advanced cancer. Patients and Methods Initially, courses were administered every 3 weeks, using an accelerated titration design. Subsequently, courses were administered every 2 weeks, and the dose was escalated in cohorts of three to six patients. Results Twenty-one patients were enrolled, seven on the every-3-week schedule and 14 on the every-other-week schedule. Three of six patients at 160 mg/m2/d developed dose-limiting toxicities including neutropenia, hyperbilirubinemia, and nausea or vomiting. Based on these initial results, the dose for 3-AP was re-escalated beginning at 80 mg/m2/d but administered eve...
The Impact of Obesity on Overall and Cancer Specific Survival in Men With Prostate Cancer

Purpose: We examined the impact of obesity on disease specific and overall survival in patients with prostate cancer.Materials and Methods: We identified 7,274 men from the Cancer of the Prostate Strategic Urological Research Endeavor database with clinically localized prostate cancer, known body mass index and clinicopathological disease characteristics. Patients were classified by body mass index as normal (less than 25 kg/m2), overweight (25 to 29.9 kg/m2), obese (30 to 34.9 kg/m2) and severely obese (35 kg/m2 or greater). Associations between body mass index and need for secondary treatment, disease specific survival and overall survival were analyzed using univariate and multivariate models.Results: Patients were classified by body mass index category as normal (28.8%), overweight (50%), obese (16.4%) and very obese (4.8%). Mean followup was 51.3 ± 38.5 months. During followup there were 1,044 deaths with 220 (21.1%) from prostate cancer. Stratified by body mass index category the groups differed wit...
Integrins in Slow-Cycling Corneal Epithelial Cells at the Limbus in the Mouse

Adult corneal epithelial stem cells (CESCs) have been shown to reside at the periphery of the cornea at a site called the corneoscleral junction or limbus. Although studies have shown that these cells are slow cycling, their molecular characteristics are not well understood. Using a whole-mount procedure, we show that whereas alpha9-integrin is present in a subset of the basal cells at the corneal limbus and absent in the central cornea, beta1-, beta4-, alpha3-, and alpha6-integrins are more highly expressed overall in central corneal basal cells. To characterize CESCs based on their slow-cycling nature, we simultaneously evaluated 5-bromo-2-deoxyuridine (BrdU) label-retaining cells (LRCs) and integrin expression (alpha9, beta1, and beta4) in a total of 1,889 cells at the limbus of adult mice that had been injected as neonates with BrdU. Whereas the LRCs were usually observed adjacent to alpha9-integrin-positive cells, most LRCs were alpha9-integrin-negative and expressed high levels of beta1- and beta4-integrin. In addition, we observed more BrdU-positive LRCs at the superior and inferior quadrants of adult mouse corneas than at the nasal and temporal quadrants, and determined that 0.94 to 3.6% of the limbal basal cells were slow cycling. We conclude from these data that the slow-cycling LRCs in the adult mouse cornea are enriched in cells that express high levels of beta1- and beta4-integrin and little alpha9-integrin.
Reprogramming of vascular smooth muscle α-actin gene expression as an early indicator of dysfunctional remodeling following heart transplant

Objective: Chronic rejection in cardiac allografts depletes vascular smooth muscle (VSM) α-actin from the coronary arterial smooth muscle bed while promoting its abnormal accumulation in cardiomyocytes and myofibroblasts. The objective was to determine if the newly discovered TEF1, MSY1, Purα and Purβ VSM α-actin transcriptional reprogramming proteins (TRPs) were associated with development of chronic rejection histopathology in accepted murine cardiac allografts. Methods: A mouse heterotopic cardiac transplant model was employed using H2 locus-mismatched mouse strains (DBA/2 or FVB/N to C57BL/6). Recipients were immunosuppressed to promote long-term allograft acceptance and emergence of chronic rejection. Explanted grafts and isolated heart cells were evaluated for changes in the DNA-binding activity and subcellular distribution of VSM α-actin transcriptional regulatory proteins. Results: The DNA-binding activity of all four TRPs was high in the developing mouse ventricle, minimal in adult donor hearts and increased substantially within 30 days after transplantation. Immunohistologic analysis revealed nuclear localization of Purβ and MSY1 particularly in fibrotic areas of the allograft myocardium demonstrating extravascular accumulation of VSM α-actin. Cardiomyocytes isolated from adult, non-transplanted mouse hearts not only exhibited less VSM α-actin expression and lower levels of TRPs compared to isolated cardiac fibroblasts or neonatal cardiomyocytes, but also contained a novel size variant of the MSY1 protein. Conclusion: Accumulation of TRPs in cardiac allografts, particularly within the fibroblast-enriched myocardial interstitium, was consistent with their potential role in VSM α-actin gene reprogramming, fibrosis and dysfunctional remodeling following transplant. These nuclear protein markers could help stage peri-transplant cellular events that precede formation of graft-destructive fibrosis and coronary vasculopathy during chronic rejection.