cssi/SciSciGPT-SciSciNet huggingface dataset:
Nicotine and amyloid formation

The major protein constituents of amyloid deposits in Alzheimer's disease (AD) are the 40-residue beta-amyloid (Abeta) (1-40) peptide and the 42-residue Abeta(1-42) peptide. The Abeta(1-42) is more pathogenic and produced in greater quantities in familial forms of AD. A major goal of research is to uncover a suitable inhibitor that either slows down or inhibits Abeta formation (beta-amyloidosis). During beta-amyloidosis, structural changes associated with the conversion of monomeric Abeta peptide building blocks into the aggregated fibrillar beta-sheet structures occur (alpha-helix-->beta-sheet or random, extended chain-->beta-sheet). In previous work, we and others established that nicotine, a major component of cigarette smoke, inhibits beta-amyloidosis of the Abeta(1-42), which may result from nicotine binding to the alpha-helical structure. These conclusions were based on solution nuclear magnetic resonance (NMR) spectroscopic studies with the nonnative 28-residue Abeta(1-28). This information suggests that, when administered therapeutically to AD patients, nicotine may not only affect cholinergic activation, but could also conceivably alter amyloid deposition. In this report, NMR studies were augmented with the naturally occurring Abeta(1-42), under conditions where the peptide folds into a predominantly alpha-helical or random, extended chain structure. The major result is that nicotine shows only modest binding to these conformations, indicating that the nicotine inhibition to beta-amyloidosis probably results from binding to a small, soluble beta-sheet aggregate that is NMR invisible.
Long range planning in the process industries: a projection approach

Abstract The problem of selecting processes and capacity expansion policies for a chemical complex can be formulated as a multiperiod, mixed-integer linear program (MILP). This MILP can be reformulated by exploiting lot sizing substructures. The reformulation produces a tight linear programming relaxation but also introduces a large number of variables and constraints. To avoid unnecessary additional variables and contraints, a polyhedral approach is developed. The reformulation variables are projected out giving rise to a larger constraint system. The new model is solved using a strong cutting plane approach. The separation problem is solved exactly in polynomial time. Computational experiments are performed to compare the conventional MILP formulation with the nonconventional formulations after variable disaggregation and projection. It is found that only a few of the constraints of the projection model suffice to substantially reduce the relaxation gap of the conventional model. This property leads to more robust and faster solution algorithms for large scale problems. Computational results are presented for planning problems with up to 38 processes, 25 products and 8 time periods. The corresponding MILPs included up to 300 binary variables and a few thousand continuous variables and constraints.
Effect of diazepam on gabaergic cuneate neurons

Abstract Diazepam may act as a γ-aminobutyric acid (GABA) agonist in the CNS, but the evidence is conflicting. This study done with iontophoresis demonstrated that diazepam inhibited the spontaneously firing neurons in the cuneate nucleus, also inhibited by GABA. Non-spontaneous neurons, excited by iontophoresis of glutamate, were inhibited by GABA and by diazepam. When diazepam and GABA were applied simultaneously, only inhibition was seen. The inhibition of spontaneously firing neurons by GABA or diazepam was blocked by the concurrent iontophoresis of bicuculline or picrotoxin, both known GABA antagonists. No evidence was found for GABA and diazepam being antagonistic in action.
In search of the Phillips curve for India

Abstract The economics literature suggests that the Phillips curve is nonexistent in India. This study finds that supply shocks, namely droughts and oil crises, and the liberalization-policy shock of the early 1990s are the main reasons for the absence of the Phillips curve in India. Once I account for these shocks by reconstructing the data of inflation and the output gap in crop year instead of fiscal year, and move to the industrial sector, the Phillips curve emerges in the conventional fashion. Thus, the short-run tradeoff between inflation and industrial output is still possible in India, as it is in other developed economies.
Integrated optic gaseous NH3 sensor for agricultural applications

An integrated optic sensor for monitoring NH3 volatization as related to agricultural fertilizer applications is described. The sensor is capable of monitoring NH3 levels over a range from less than 100 parts per billion by volume to levels approaching 1000 parts per million by volume. The sensor is based on a planar waveguide operating in an interferometric mode. The device functions by monitoring a refractive index change resulting from a reversible chemical reaction occurring on the waveguide surface.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Velocity and myosin phosphorylation transients in arterial smooth muscle: effects of agonist diffusion.

Transients in myoplasmic [Ca2+] and in phosphorylation of the 20,000 dalton light chain of myosin have been reported following stimulation of vascular smooth muscle by various agonists. Since these transients are rapid compared with the time required to attain a steady-state stress, agonist diffusion rates may be a significant limitation in activation. The purpose of this study was to estimate the effect of agonist diffusion rates on the time course of activation as assessed by mechanical measurements of stress development and isotonic shortening velocities and by determinations of the time course of myosin phosphorylation. The approach was to measure these parameters in K+-stimulated preparations of the swine carotid media of varying thicknesses and to estimate the theoretical contributions imposed by diffusion rates and the presence of a diffusion boundary layer surrounding the tissue. The results show that the time course of parameters which are tissue averages such as stiffness, active stress, and myosin phosphorylation is dominated by agonist diffusion rates. The sequence of events involved in excitation-contraction coupling including agonist actions on the cell membrane, Ca2+ release, activation of myosin light chain kinase, and cross-bridge phosphorylation appear to be very rapid events compared with stress development. Estimates of unloaded or lightly loaded shortening velocities which are not simple tissue averages appear to provide an imporoved estimate of activation rates.
Sleep. Sleep the beloved teacher

Recent studies of humans and rats show that neuronal firing patterns initiated by prior sensory stimulation, and even learning, can occur during sleep. But what they tell us about the functions of sleep remains unclear.
Length dependence of the kinetic complexity of mouse satellite DNA.

Abstract Treatment of renatured mouse satellite DNA with the single stranded DNA specific endonuclease Sl leads to the isolation, with no losses, of regions of length, L ≤ 56±28, from molecules containing several such regions. The rate of renaturation is observed to be an unusual function of length, extrapolating to an apparent complexity, N ≤ 36±9. The results are consistent with a model of tandem, spaced, repetitions where multiple nucleations may occur between two strands containing the complementary repetition units.
Toxicity and Metabolism of 2-CyanopropyIamine in Rats, Chicks, and Turkeys.

SummaryLathyrogenic activity of 2-cyanopropylamine (CPA), a methyl analog of BAPN, was studied in chicks, turkey poults and weanling rats. Dissecting aneurisms of the aortae resulted in all 3 species. Although characteristic deformities of leg bones appeared in chicks and turkeys, lathyritic osseous changes were not produced in rats. A toxic symptom produced in all rats by CPA was male priapism. A level of 0.216% CPA in the diet of turkey poults was at least as toxic as 0.079% of BAPN-fumarate. CPA was excreted in urine of rats as unchanged CPA and as 2-cyanopropionic acid.
NEW CONSISTENCY CONDITIONS ON PION--PION AMPLITUDES AND THEIR DETERMINATION TO FOURTH ORDER IN EXTERNAL MOMENTA.

We derive a set of new consistency conditions for the pion-pion scattering amplitude. These conditions hold for any $s$, $t$, $u$ in the cube $0\ensuremath{\le}s,t,u\ensuremath{\le}{\ensuremath{\mu}}^{2}$, with the four external mass variables off the mass shell and restricted so that ${{q}_{1}}^{2}=0$, ${{q}_{2}}^{2}=s$, ${{q}_{3}}^{2}=t$, and ${{q}_{4}}^{2}=u$. Using these consistency conditions, we determine the coefficients of the power-series expansion of the pion-pion amplitude up to and including second-order terms in the variables $s$, $t$, $u$, and ${{q}_{i}}^{2}$. We use this expansion to calculate the pion-pion $S$-wave scattering lengths and thus check the consistency of Weinberg's recent calculation of these numbers to the next higher order. The final result is within 10% of that obtained by Weinberg.
Cryogenic adhesive properties of bisphenol‐A epoxy resins

This article includes a comparison of the adhesive properties of bisphenol-A expoxides at 300°K and 76°K with respect to the molecular weight of the uncured resins. Joints of 2024 aluminum were tested at 300°K and 76°K in tensile-shear and in impact-shear, and total linear thermal contraction of the cured resins was measured between the two temperatures. Results are discussed with respect to residual joint stresses and adsorptive properties of the resins.
Multimodal imaging of mouse development: Tools for the postgenomic era

With the sequence of the mouse genome known, it is now possible to create or identify mutations in every gene to determine the molecules necessary for normal development. Consequently, there is a growing need for advanced phenotyping tools to best understand defects produced by altering gene function. Perhaps nothing is more satisfying than to directly observe a process in action; to disturb it and see for ourselves how the process changes before our very eyes. No doubt, this desire is what drove the invention of the very first microscopes and continues to this day to fuel progress in the field of biological imaging. Because mouse embryos are small and develop embedded within many tissue layers within the nurturing environment of the mother, directly observing the dynamic, micro- and nanoscopic events of early mammalian development has proven to be one of the greater challenges for imaging scientists. Here, I will review some of the imaging methods being used to study mouse development, highlighting the results obtained from imaging.
XML-based resources for simulation

As simulations and the machines they run on become larger and more complex the inputs and outputs become more unwieldy. Increased complexity makes the setup of simulation problems difficult. It also contributes to the burden of handling and analyzing large amounts of output results. Another problem is that among a class of simulation codes (such as those for physical system simulation) there is often no single standard format or resource for input data. To run the same problem on different simulations requires a different setup for each simulation code. The eXtensible Markup Language (XML) is used to represent a general set of data resources including physical system problems, materials, and test results. These resources provide a "plug and play" approach to simulation setup. For example, a particular material for a physical system can be selected from a material database. The XML-based representation of the selected material is then converted to the native format of the simulation being run and plugged into the simulation input file. In this manner a user can quickly and more easily put together a simulation setup. In the case of output data, an XML approach to regression testing includes tests and test results with XML-based representations. This facilitates the ability to query for specific tests and make comparisons between results. Also, output results can easily be converted to other formats for publishing online or on paper.
A Rejoinder: Building 'Positive, Cooperative and Comprehensive’ China-US Relations

The US-China relationship is one of the most important bilateral relationships in the world. As two of the world's largest economies, there can be no solution to the global economic crisis if the two work at cross purposes and many of the region's most complex security challenges - North Korean denuclearisation first among them - require Sino-US cooperation. The good news is that both US President Barrack Obama and Chinese President Hu Jintao are aware of and accept the shared responsibility and necessity for a cooperative approach toward dealing with the global financial crisis and regional security challenges; both have pledged to develop a "positive, cooperative and comprehensive" relationship and build mutual trust in a way that encourages, rather than worries, friends and allies in the Asia Pacific.
A study on diazepam and postwithdrawal drinking of ethanol solution in rats.

Abstract A 10-day ethanol inhalation procedure without the use of pyrazole was used to produce physical dependence on ethanol in Sprague-Dawley rats. During this 10-day period, weight changes in the control animals reflected the weight changes in the ethanoltreated animals. At the end of the inhalation procedure the rate of ethanol clearance from the blood was 0.44 ± 0.2 mg/ml/hr in the dependent animals; also, signs of withdrawal were manifested in all ethanol vapor-treated animals, but not in control animals. Twenty-four hours after removal from the chamber, a 5-day drinking study was started. Control animals and physically dependent animals were each divided into two groups, one for diazepam (5 mg/ kg, orally) administration and one for vehicle administration. The results from the free-choice drinking study (water and ethanol solution, 7%) indicated that diazepam did not enhance ethanol consumption in animals which were physically dependent on ethanol but significantly suppressed ethanol drinking in nondependent animals. Also when examining the effect of physical dependence alone on postwithdrawal drinking, it appeared that no increase in ethanol preference was observed with animals under our experimental design.
Repeated magnitude estimations with a variable standard: Sequential effects and other properties

Twelve Ss made magnitude estimations of the loudness of each one of a sequence of pure tones according to the rule R(N) = R(N - 1) · [S(N)/S(N - 1)], where R(N) is the response on Trial N, R(N - 1) is the response on Trial N - 1, and S(N)/S(N - 1) is the judged ratio of the “loudness” of the pure tone presented on Trial N to that of the pure tone presented on Trial N - 1. It was found that these magnitude estimations were assimilated toward the immediately preceding stimuli as far as five trials back in the sequence of stimuli. In addition, ratio judgments were consistently asymmetric and the data displayed a form of “time order error.” In all cases, there are similar effects displayed in category judgment data. These and other data imply that at least some kinds of magnitude estimations may involve a judgment of the “difference” or “distance” between pairs of stimuli as a first step in the production of the response required by the judgment situation.
Reef fish structure and cascading effects in response to artisanal fishing pressure

This paper is the first of its kind in Indonesia where effects of artisanal fishing pressure from particular gear types shows an influence on the biomass of reef fish families measured by visual census. Surveys of reef fish communities and benthic variables at 36 fishing grounds, of varying fishing pressure, showed that Scaridae abundance was the factor most influencing fish community structure. The positive relationships between algal turf and reef fish variables and the negative relationships between hard coral cover and three reef fish variables (Scaridae biomass, herbivore biomass and fish species richness) suggests that substrate variables may be used to predict reef fish community variables and that herbivorous fish promote algal turfs at the expense of other benthos. Relationships between reef fish guilds and fishing pressure showed a strong negative impact of muro-ami and gill netting on seven families of reef fish. The strong influence of netting on Caesonidae and Lethrinidae biomass was consistent with the targeting of these families by these fishing methods in Karimunjawa. Both gillnets and muro-ami netting were also negatively correlated with invertivores, a trophic group consisting of a range of reef fish families in Karimunjawa. Although the low biomass of fish populations is likely associated with past and existing fishing practices, negative relationships between fishing pressure indices and reef fish biomass were consistent with the selectivity of families by different fishing gears in Karimunjawa. The implication for management is that both non-selective gears (netting) and selective fishing practices (e.g., handspear and speargun) are capable of modifying the structure of reef fish populations and require active management controls.
Trade liberalization and the environment: The case of intra-industry trade

Abstract While a large body of literature examines the environmental impact of trade on the environment, this discussion focuses largely on the context of inter-industry trade. Empirical evidence has long suggested that an increasing share of international trade takes the form of intra- rather than inter-industry trade. In an attempt to fill this gap, the present paper uses a price-setting duopoly model of intra-industry trade to highlight the environmental consequences of trade liberalization when oligopolistic rivalry rather than comparative advantage drives international trade. We find that the environmental impact of trade liberalization depends mostly on two factors, namely, on the nature of pollution (i.e. whether it is local, transboundary or global) and on which country liberalizes trade (i.e. whether it is the ‘clean’ country or the ‘dirty’ country).
Who Uses Formal, Early Child Care in California? A Comparative Study of Children from Immigrant and Nonimmigrant Families

The purpose of this study is to examine the predictors of formal, early child care usage and to study the differences between immigrant and nonimmigrant families in their use of formal (center-based, preschool, Head Start, and family child care) and informal child care arrangements (grandparent and nanny) among California’s children. Since the California Health Interview Survey (CHIS) had children from California’s immigrant and nonimmigrant families, the data for 897 preschool age children who attended child care for 10 h or more were retrieved from the CHIS 2005 Child Survey. This study found that immigrants are twice more likely (OR = 2.006; p < 0.005) to use formal child care than nonimmigrant families in California. The study concludes with implications for social work.
EPOCH TIME SYNCHRONIZATION METHOD WITH CONTINUOUS UPDATE FOR DISTRIBUTED SIMULATION

Abstract A new time synchronization method for distributed simulations is proposed. In this approach, each federate estimates its potential synchronization point (PSP) ). The coordinator, after receiving PSPs, selects the minimum of them ( synchronization point (SP) ). Each federate then advances its time to SP. While each federates advances its time, it re-calculates its PSP whenever the certain system status changes, and sends it to the coordinator. The coordinator updates SP when the updated PSPs affect it, and notifies its new SP to the federates. When a federate reaches close to the actual epoch event, the synchronization method switches to the conservative phase.
Positive direct Coombs tests with anti-IgA antiserum.

Abstract. Six patients with hemolytic anemia were found to have positive direct antiglobulin tests with antisera to IgA, in addition to positive reactions with anti-IgG, -IgM or C3 antisera. Absorption studies suggest that IgA exists as a complex with other immunoglobulins. IgA found on such erythrocytes may be a true auto-antibody but may represent absorption of this immunoglobulin by antigen-antibody complexes.
Suppression of converter introduced harmonic currents using a forced-commutated cycloconverter

A method of current harmonic suppression through application of a modified forced-commutated cycloconverter is described. The cycloconverter is operated using current-error control with hysteresis. Advantage is taken of the multiple source voltage switching choices available with the cycloconverter to produce corrective harmonic current injection that tracks the command with minimum error. A numerical simulation of the filter is made with a three-phase, six-pulse rectifier load. The results are presented in the forms of both harmonic residual components and Fourier spectra. >
Morality, Rationality and Academic Dishonesty: A Partial Test of Situational Action Theory

This study uses self-report survey data from a sample of college students to provide a partial test of WikstrO§mâ€™s situational action theory (2010a) by examining the extent, if any, to which the effects of perceptual deterrence on academic dishonesty are moderated by personal morality. The findings show that both personal morality and perceived certainty of formal sanctions are inversely associated with cheating; however, the deterrent effect of high perceived certainty of formal sanctions is not greater among those with weak moral prohibitions against cheating as predicted by WikstrO§m and observed by Svensson (2015) in an earlier test of WikstrO§mâ€™s situational action theory.
Monitoring the Longitudinal Intra-tumor Physiological Impulse Response to VEGFR2 Blockade in Breast Tumors Using DCE-CT

The purpose of this study was to quantify and model the longitudinal intra-tumor physiological response to a single dose of a monoclonal antibody specific to the VEGFR2 using dynamic contrast-enhanced CT. Dynamic contrast-enhanced CT imaging was performed on athymic nude mice bearing xenograft VEGF-transfected MCF-7 tumors (MCF7VEGF) to quantify intra-tumor physiology pre- and post-injection (days 2, 7, and 14) of a nonspecific (IgG1, controls) and specific (DC101, treated) monoclonal antibody targeting VEGFR2. Parametrical maps of tumor physiology—perfusion (F), permeability surface area (PS), fractional plasma (f p), and interstitial space (f is)—were obtained at four time points over a 2-week period. A temporal multistage recovery process whereby a decoupling of the fractional change in physiological parameters (f p, F) was observed when comparing treated to control tumors: f p and perfusion decreased by a combined 27% (P < 0.01) and 65% (P < 0.01) on day 2, while only perfusion remained reduced by 46% (P < 0.01) on day 7. Intra-tumor heterogeneity defined by the change in variance of perfusion decreased on days 2 and 7; no change in the variance of f p was observed. Analysis based on a mathematical model linking perfusion and vascular morphology indicates that a decrease in f p and perfusion was consistent with a reduction in blood vessel radius, followed by an increase in the vascular radius and tortuosity resulting in the decoupling of f p and perfusion before returning to control levels. Inhibiting VEGFR2 activity results in a temporal decoupling of physiological parameters, which can be explained by a combination of morphological changes influencing perfusion. Such a decoupling has the potential to significantly impact the delivery of pharmaceuticals and oxygen within solid tumors, critical factors in combined anti-angiogenic and radio- and chemotherapies.
Widespread N-Acetyl-d-Glucosamine Uptake among Pelagic Marine Bacteria and Its Ecological Implications

Dissolved free and combined N-acetyl-D-glucosamine (NAG) is among the largest pools of amino sugars in the ocean. NAG is a main structural component in chitin and a substantial constituent of bacterial peptidoglycan and lipopolysaccharides. We studied the distribution and kinetics of NAG uptake by the phosphoenolpyruvate:NAG phosphotransferase systems (PTS) in marine bacterial isolates and natural bacterial assemblages in near-shore waters. Of 78 bacterial isolates examined, 60 took up 3H-NAG, while 18 showed no uptake. No systematic pattern in NAG uptake capability relative to phylogenetic affiliation was found, except that all isolates within Vibrionaceae took up NAG. Among 12 isolates, some showed large differences in the relationship between polymer hydrolysis (measured as chitobiase activity) and uptake of the NAG, the hydrolysis product. Pool turnover time and estimated maximum ambient concentration of dissolved NAG in samples off Scripps Pier (La Jolla, Calif.) were 5.9 +/- 3.0 days (n = 10) and 5.2 +/- 0.9 nM (n = 3), respectively. Carbohydrate competition experiments indicated that glucose, glucosamine, mannose, and fructose were taken up by the same system as NAG. Sensitivity to the antibiotic and NAG structural analog streptozotocin (STZ) was developed into a culture-independent approach, which demonstrated that approximately one-third of bacteria in natural marine assemblages that were synthesizing DNA took up NAG. Isolates possessing a NAG PTS system were found to be predominantly facultative anaerobes. These results suggest the hypothesis that a substantial fraction of bacteria in natural pelagic assemblages are facultative anaerobes. The adaptive value of fermentative metabolism in the pelagic environment is potentially significant, e.g., to bacteria colonizing microenvironments such as marine snow that may experience periodic O2-limitation.
Comparison of manual and autopilot breakout maneuvers with three closely spaced parallel runway approaches

This study used a high-fidelity flight simulator to explore approach operations for three closely-spaced parallel runways using autopilot and manually flown breakout procedures. An initial study investigated the concept under manual control mode only. The concept aimed to achieve visual meteorological conditions capacities under instrument meteorological conditions when landing aircraft on runways as close as 750 ft apart. This investigation studied procedures related to autopilot breakout maneuvers for triple parallel aircraft flying in an echelon formation and compared them to the manual procedures investigated earlier. All of the data collection runs had an off-nominal situation, which was either caused by the wake of the lead aircraft drifting too close to the center and trailing aircraft, or the lead aircraft deviating from its course and blundering towards the center and trailing aircraft. The location of the off-nominal situation (high/low altitude) and the position of the ownship (center or right runway) were also manipulated. Statistically significant results showed that autopilot breakout maneuvers were flown more accurately than manual breakout maneuvers. Some improved lateral separation was also observed between the paired aircraft while the autopilot was used, which could be attributed to the improved accuracies with which the breakout maneuver was flown using autopilot. On the subjective ratings, pilots experienced reduced workload, a similar level of situation awareness, and a reduced level of situational demands under the autopilot condition. Objective and subjective data from the current study extends the results from the previous research [1], with some evidence to suggest further improvement in these factors when autopilot breakout procedures are used.
High-repetition cyclic loading is a risk factor for a lumbar disorder.

Epidemiological data suggest that prolonged exposure to cyclic lumbar flexion elicits a chronic neuromuscular disorder and disability in workers. This study provides a physiological and biomechanical assessment of various repetitions of cyclic lumbar flexion sessions as a risk factor for development of an acute neuromuscular disorder. An in vivo feline model was subjected to 10 minutes of cyclic (0.25-HZ) loading, followed by a 10-minute rest period, re- peated three times in one experimental group, six times in a second group, and nine times in the third group, followed by rest for 7 hours. Displacement of the lumbar viscoelastic tissue and reflex electromyographic (EMG) activity from the lumbar multifidus muscle were monitored. Creep developed and accumulated during each load/rest period and partially recovered during the subsequent rest. Loading periods were characterized by a decrease in reflex EMG activity with superimposed spasms. In the 7-hour recovery period, initial hyperexcitability was present in all groups, whereas only the six- and nine-repetition groups displayed significant delayed hyperexcitability, indicating the presence of acute inflammation. The mathematical model developed fit the data reasonably well, as the R 2 values were generally near 0.90. It was concluded that the resulting delayed muscular hyperexcitability constitutes an acute neuromuscular disorder associated with exposure to many repetitions of cyclic lumbar flexion. The acute disorder can become chronic if not allowed sufficient rest to resolve itself. Workers engaged in cyclic lumbar flexion (e.g., loading/unloading, assembly workers) should avoid long-term exposure in order to prevent the development of a chronic neuromuscular condition known as cumulative trauma disorder. Muscle Nerve 34: 614-622, 2006
Prologue to the volume: Endocrine tumors and their genetics, a perspective.

Although endocrine tumors (or their consequences) have been known since the beginning of history (1, 2), familial predisposition to these lesions was described only in the last 70 years (3). The term "multiple endocrine neoplasia" (MEN) was introduced only relatively recently, in 1968, although Dr. Wermer had suggested the term multiple endocrine adenoma in 1954 (3). A series of meetings on multiple endocrine neoplasias (MEN) have documented the extraordinary progress of the field in the modern era (4–6). We got a glimpse of what modern genetics is able to do when Neumann et al. described one of the classic RET oncogene mutations in a family afflicted by inherited pheochromocytoma since the 1890’s (7). Certainly, multiple endocrine neoplasia type-2 (MEN 2) syndromes are not novices to being pioneers in the modern era of (genetic) medicine: RET, along with the gsp (now GNAS) oncogene, were the first oncogenes to be found mutated in any genetic disorder predisposing to tumor formation (amazingly, both to endocrine tumors). The present volume is an extraordinary compilation of articles from some of the leading scientists and clinicians in the field of familial endocrine neoplasias, extending the field from the “classic” MENs, MEN 1 (8) and MEN 2 (9), to other syndromes predisposing to endocrine neoplasms among many other lesions, such as Carney complex (10), Von Hippel-Lindau disease (11), tumors associated with mutations of the succinate dehydrogenase enzyme (12), MEN 4 (13), and the neurofibromatosis and tuberous sclerosis syndromes (14). This presentation on MENs and MEN-related disorders is enhanced by an article on mouse models of endocrine tumors by Jones et al. (15). Finally, the last four articles of the volume present the significant advances in our understanding of the genetics of pituitary, adrenal, parathyroid and testicular (germ cell) tumors (16–19). One might ask why these four articles are included in a volume on “familial” endocrine neoplasias. The answer is clear: as we understand more about the genes that are involved in endocrine tumor formation, we find even more about genetic predisposition not only to the rare MENs and MEN-related syndromes, but also to common tumors. For example, a recent study found that as many as half of growth-hormone producing pituitary tumors in children and adolescents are caused by “mild” genetic defects in the germline, in genes such as AIP and menin (20). The clinician reader will find these articles a useful update on one of the most active areas of endocrinology, and one that is a leading field of translational Medicine. Researchers in the audience will find in this volume a guide to endocrine disease associated with aberrant signaling; understanding the complex interactions of genes that lead to endocrine tumors are essential for the current approach to cancer research, as well as for directing the development of molecularly designed drugs.
On-Chip I/sub DDQ/ testability schemes for detecting multiple faults in CMOS ICs

In this paper we present two on-chip design-for-testability (DFT) schemes for CMOS ICs. One is for small circuits and the other for large circuits. Both schemes identify a faulty area on a chip with only a small area overhead for the additional circuitry and at most two extra pins. Moreover, if faults occur in different areas, multiple faults can also be detected with the proposed schemes. To demonstrate the ideas, DFT is incorporated in a 4-bit carry look ahead adder/subtractor (CLAAS) as well as a 16-bit arithmetic logic unit (ALU). Simulation results are given.
Effects of cytochalasin B on the response of toad urinary bladder to vasopressin.

A combined physiological and morphological study of the effects of cytochalasin B (CB) on the toad urinary bladder has been carried out. CB inhibits the hydro-osmotic response to vasopressin without altering basal water permeability or diffusion, or the increase in 3H2O diffusion observed after hormone addition. Although CB increases [22Na]-, [36Cl]-, and [14C]urea fluxes, and decreases transepithelial potential, no alteration in basal short-circuit current, the vasopressin-induced increase in this parameter, or [14C]inulin permeability occurs. In the absence of hormone, CB does not markedly alter the structure of the toad bladder. However, in the presence of vasopressin, CB induces the formation of large intracellular vacuoles. These results suggest a possible coupling of solute and water movement across the tissue.
A divide-and-conquer approach to fragment assembly

Motivation: One of the major problems in DNA sequencing is assembling the fragments obtained by shotgun sequencing. Most existing fragment assembly techniques follow the overlap—layout—consensus approach. This framework requires extensive computation in each phase and becomes inefficient with increasing number of fragments. Results: We propose a new algorithm which solves the overlap, layout, and consensus phases simultaneously. The fragments are clustered with respect to their Average Mutual Information (AMI) profiles using the k-means algorithm. This removes the unnecessary burden of considering the collection of fragments as a whole. Instead, the orientation and overlap detection are solved efficiently, within the clusters. The algorithm has successfully reconstructed both artificial and real data. Availability: Available on request from the authors.
Guest Column: correlation bounds for polynomials over {0 1}

This article is a unified treatment of the state-of-the-art on the fundamental challenge of exhibiting explicit functions that have small correlation with low-degree polynomials over {0 1 }. It discusses long-standing results and recent developments, related proof techniques, and connections with pseudorandom generators. It also suggests several research directions.
Calpain-1 cleaves Rad21 to promote sister chromatid separation

Defining the mechanisms of chromosomal cohesion and dissolution of the cohesin complex from chromatids is important for understanding the chromosomal missegregation seen in many tumor cells. Here we report the identification of a novel cohesin-resolving protease and describe its role in chromosomal segregation. Sister chromatids are held together by cohesin, a multiprotein ring-like complex comprised of Rad21, Smc1, Smc3, and SA2 (or SA1). Cohesin is known to be removed from vertebrate chromosomes by two distinct mechanisms, namely, the prophase and anaphase pathways. First, PLK1-mediated phosphorylation of SA2 in prophase leads to release of cohesin from chromosome arms, leaving behind centromeric cohesins that continue to hold the sisters together. Then, at the onset of anaphase, activated separase cleaves the centromeric cohesin Rad21, thereby opening the cohesin ring and allowing the sister chromatids to separate. We report here that the calcium-dependent cysteine endopeptidase calpain-1 is a Rad21 peptidase and normally localizes to the interphase nuclei and chromatin. Calpain-1 cleaves Rad21 at L192, in a calcium-dependent manner. We further show that Rad21 cleavage by calpain-1 promotes separation of chromosome arms, which coincides with a calcium-induced partial loss of cohesin at several chromosomal loci. Engineered cleavage of Rad21 at the calpain-cleavable site without activation of calpain-1 can lead to a loss of sister chromatid cohesion. Collectively, our work reveals a novel function of calpain-1 and describes an additional pathway for sister chromatid separation in humans.
The Methanol Dehydrogenase Gene, mxaF, as a Functional and Phylogenetic Marker for Proteobacterial Methanotrophs in Natural Environments

The mxaF gene, coding for the large (α) subunit of methanol dehydrogenase, is highly conserved among distantly related methylotrophic species in the Alpha-, Beta- and Gammaproteobacteria. It is ubiquitous in methanotrophs, in contrast to other methanotroph-specific genes such as the pmoA and mmoX genes, which are absent in some methanotrophic proteobacterial genera. This study examined the potential for using the mxaF gene as a functional and phylogenetic marker for methanotrophs. mxaF and 16S rRNA gene phylogenies were constructed based on over 100 database sequences of known proteobacterial methanotrophs and other methylotrophs to assess their evolutionary histories. Topology tests revealed that mxaF and 16S rDNA genes of methanotrophs do not show congruent evolutionary histories, with incongruencies in methanotrophic taxa in the Methylococcaceae, Methylocystaceae, and Beijerinckiacea. However, known methanotrophs generally formed coherent clades based on mxaF gene sequences, allowing for phylogenetic discrimination of major taxa. This feature highlights the mxaF gene’s usefulness as a biomarker in studying the molecular diversity of proteobacterial methanotrophs in nature. To verify this, PCR-directed assays targeting this gene were used to detect novel methanotrophs from diverse environments including soil, peatland, hydrothermal vent mussel tissues, and methanotroph isolates. The placement of the majority of environmental mxaF gene sequences in distinct methanotroph-specific clades (Methylocystaceae and Methylococcaceae) detected in this study supports the use of mxaF as a biomarker for methanotrophic proteobacteria.
Sex reassignment. Follow-up.

• Although medical interest in individuals adopting the dress and life-style of the opposite sex goes back to antiquity, surgical intervention is a product of the last 50 years. In the last 15 years, evaluation procedures and surgical techniques have been worked out. Extended evaluation, with a one- to two-year trial period prior to formal consideration of surgery, is accepted practice at reputable centers. Cosmetically satisfactory, and often functional, genitalia can be constructed. Less clear-cut, however, are the characteristics of the applicants for sex reassignment, the natural history of the compulsion toward surgery, and surgery's long-term effects. The characteristics of 50 applicants for sex reassignment, both operated and unoperated, are reviewed. The results of long-term follow-up are reported in terms of such indices as job, educational, marital, and domiciliary stability. Outcome data are discussed in terms of the adjustments of operated and unoperated patients.
Modeling Autoignition and Engine Knock Under Spark Ignition Conditions

A computer model that is able to predict the occurrence of knock in spark ignition engines has been developed and implemented into the KIVA-3V code. Three major sub-models were used to simulate the overall process, namelythe spark ignition model, combustion model, and end-gas autoignition models. The spark ignition and early flame development is modeled by a particle marker technique to locate the flame kernel. The characteristic-time combustion model is applied to simulate the propagation of the regular flame. The autoignition chemistry in the end-gas was modeled by a reduced chemical kinetics mechanism that is based on the Shell model. The present model was validated by simulating the experimental data in three different engines. The spark ignition and the combustion models were first validated by simulating a premixed Caterpillar engine that was converted to run on propane. Computed cylinder pressure agrees well with the experimental data. To test the performance of the autoignition model, simulations were compared to experimental data of the Sandia Optical Engine, a research engine equipped with four spark plugs and operated with n-butane. The model predicted the pressure history and ignition delay times in the end gas reasonably well. Finally the model was applied to simulate a single cylinder spark-ignition Kohler utility engine that was run at various conditions, including intentional knocking conditions. Different engine speeds were studied and the occurrence of knock was predicted correctly. Furthermore, resonant pressure oscillations in the combustion chamber under knocking conditions were investigated for this engine.
P3H-6 An Integrated Circuit with Transmit Beamforming and Parallel Receive Channels for Real-Time Three-Dimensional Ultrasound Imaging

We present the design of an integrated circuit (IC) that will be flip-chip bonded to a 16times16-element CMUT array. The IC provides 16 receive channels which can be configured to receive along either of the array diagonals or on any single row of the array. On transmit, all 256 elements can be used to transmit arbitrarily focused beams. Focused transmission with the full array is made possible by on-chip pulsers and memory. A 25-V pulser and 8-bit shift register is provided for each element of the array. Prior to each transmit, new values are loaded into the shift registers. Current-controlled one-shots control the transmit pulse widths. Circuit simulations and the IC layout are presented. Simulations predict that delay values can be loaded in less than 1.3 mus and show the generation of precisely timed pulses. The IC is being prepared for submission to National Semiconductor for fabrication in a high-voltage BiCMOS process
Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflammatory musculoskeletal disorders

Objectives Herpes zoster (HZ) is a common disorder that causes substantial pain and morbidity. We examined its rate and predictors in rheumatoid arthritis (RA) and non-inflammatory musculoskeletal (MSK) disorders to determine if HZ was increased in RA and whether treatment contributed to the risk of HZ. Methods After excluding patients witzh prior HZ, we assessed 10 614 RA and 1721 MSK patients by semi-annual questionnaires during 33 825 patient-years of follow-up. Predictors of HZ were determined by Cox regression and expressed as hazard ratios (HR) and 95% confidence intervals (CI). Results The annualized incidence rate per 1000 patient-years was 13.2 (95% CI 11.9-14.5) in RA and 14.6 (95% CI 11.2-18.1) in MSK, and did not differ significantly after adjustment for age and sex. HZ was predicted by impaired functional status, as measured by the Health Assessment Questionnaire (HAQ), [HR 1.3 (95% CI 1.1-1.5)] and by the use of COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs) [HR 1.3 (95% CI 1.1-1.6)] in RA and MSK. In multivariable analyses in patients with RA, cyclophosphamide HR 4.2 (95% CI 1.6-11.5), azathioprine HR 2.0 (1.2-3.3), prednisone HR 1.5 (1.2-1.8), leflunomide HR 1.4 (1.1-1.8) and COX-2 NSAIDs HR 1.3 (95% CI 1.1-1.6) were significant predictors of HZ. Conclusion The incidence of HZ is increased in RA and MSK compared with population-based rates. However, the rate of HZ in RA is not increased compared with MSK. After adjustment for severity, various treatments, but not methotrexate or biologics, were risk factors for HZ.
Yolk Testosterone Levels are Not Consistently Higher in the Eggs of Obligate Brood Parasites Than Their Hosts

Abstract The survival of obligate brood parasitic nestlings depends on their ability to exploit hosts' parental care, mostly at the expense of the unrelated nestmates. Foster parents are characteristically manipulated by parasitic young through more intensive begging displays. For example, young of parasitic brown-headed cowbirds (Molothrus ater) beg more loudly and elevate their head higher than the chicks of most host species. What is the developmental basis of this difference between parasite and its host species? Previous studies showed that intraspecific differences in some maternally deposited egg-yolk steroid hormone concentrations were related to differences in the begging behaviors and growth of hatchling birds. The prediction was tested that interspecific variation in yolk testosterone concentrations was related to consistent differences in the begging of hosts vs. parasites. Contrary to this prediction, yolk testosterone levels in the eggs of brown-headed cowbirds were not consistently higher t...
Combined Radiometer-Radar Microphysical Profile Estimations with Emphasis on High Frequency Brightness Temperature Observations

Information about the vertical microphysical cloud structure is useful in many modeling and predictive practices. Radiometers and radars are used to observe hydrometeor properties. This paper describes an iterative retrieval algorithm that combines the use of airborne active and wideband (10 to 340 GHz) passive observations to estimate the vertical content and particle size distributions of liquid and frozen hydrometeors. The physically-based retrieval algorithm relies on the high frequencies (greater than 89 GHz) to provide details on the frozen hydrometeors. Neglecting the high frequencies yielded acceptable estimates of the liquid profiles, but the ice profiles were poorly retrieved. Airborne radar and radiometer observations from the third Convection and Moisture EXperiment (CAMEX-3) were used in the retrieval algorithm as constraints. Nadir profiles were estimated for a minute each of flight time (approximately 12.5 km along track) from an anvil, convection, and quasi- stratiform rain. The complex structure of the frozen hydrometeors required the most iterations for convergence for the anvil cloud type. The wideband observations were found to more than double the estimated frozen hydrometeor content as compared to retrievals using only 90-GHz and below. The convective and quasi-stratiform quickly reached convergence (minimized difference between observations and calculations using the estimated profiles). A qualitative validation using coincident in situ CAMEX-3 observations shows that the retrieved particle size distributions are well corroborated with independent measurements.
Tertiary Structure of Proteins

In Chapter 4, we gave a brief introduction to proteins. The structures of a very large number of proteins have been determined and it is possible to ask fundamental questions: Given the primary sequence, what is tertiary structure? How does the protein fold into the final structure? This “folding problem” has attracted a great deal of attention, and it has become an industry. (One of the Web search engines has more than 106 entries.) We will not treat the folding problem here, but refer to review articles for more information [1]–[7]. Here we discuss a simpler problem, how the main secondary structures, ?-helices and ? pleated sheets , combine to form globular proteins. The folding problem is also treated in Section 17.3.