cssi/SciSciGPT-SciSciNet huggingface dataset:
Inheritance of three distinct muscle chloride channel gene (CLCN1) mutations in a single recessive myotonia congenita family

Myotonia congenita is an inherited disorder of skeletal muscle membrane excitability that stems from diminished activity of the sarcolemmal voltage-gated chloride channel. The syndrome may be transmitted by either an autosomal dominant (Thomsen's disease) or recessive (recessive generalized myotonia, Becker's myotonia) mode of inheritance, [1] and the molecular genetic basis of both forms is linked to mutations in the skeletal muscle chloride channel gene (CLCN1, 7q35). This gene encodes a member of the ClC family of voltage-gated chloride channels and is believed to form multimeric complexes of subunits each consisting of 10 to 12 transmembrane domains. Although the disease is reported to be rare, there exists striking allelic heterogeneity with more than 25 known mutations in CLCN1. [2] Many patients with recessive generalized myotonia (RGM) exhibit compound heterozygosity with the inheritance of different maternal and paternal alleles. This high degree of genotype variability may help explain individual variability in disease severity. Here we report the unusual occurrence of a single family, segregating three distinct CLCN1 mutations resulting in two distinct compound genotypes in affected offspring. The proband is a 20-year-old woman with western European ancestry, presenting with a lifelong history of muscle stiffness. The patient's mother noted advanced muscular development at …
High Power Interferometric Phase Measurement Limited by Quantum Noise and Application to Detection of Gravitational Waves

Interferometric detection of gravitational waves at levels of astrophysical interest is expected to require measurement of optical phase differences of $\ensuremath{\le}{10}^{\ensuremath{-}10}$ rad. To achieve this sensitivity the measurement must be made at the quantum (shot noise) limit. We have built a laboratory-scale interferometer to investigate limits to sensing the phase at this level, and obtained, with 70 W of circulating power, a phase sensitivity limited by shot noise of $3\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}10}\phantom{\rule{0ex}{0ex}}\mathrm{rad}/\sqrt{\mathrm{Hz}}$ at frequencies above 1.5 kHz. We describe the experiment and discuss the implications for the Laser Interferometer Gravitational-Wave Observatory (LIGO).
Certification of Standard Reference Material 1976b

The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to address specific aspects of the performance of X-ray powder diffraction instruments. This report describes SRM 1976b, the third generation of this powder diffraction SRM. SRM 1976b consists of a sintered alumina disc, approximately 25.6 mm in diameter by 2.2 mm in thickness, intended for use in the calibration of X-ray powder diffraction equipment with respect to line position and intensity as a function of 2θ-angle. The sintered form of the SRM eliminates the effect of sample loading procedures on intensity measurements. Certified data include the lattice parameters and relative peak intensity values from 13 lines in the 2θ region between 20° and 145° using CuKα radiation. A NIST-built diffractometer, incorporating many advanced and unique design features was used to make the certification measurements.
Assessment of Academic, Personal, and Career Development of Alumni from Southeast Missouri State University:

A survey containing institutional and program-specific items examined psychology and other graduates' evaluations of their undergraduate education (1983–1985) at Southeast Missouri State University. Psychology respondents resembled respondents from other majors in their social and personal interests, but differed from other respondents in their educational and career attitudes. Psychology respondents were more likely to be enrolled in graduate coursework than were other respondents and indicated greater agreement that preparation for this coursework was important to them, in contrast, they expressed less agreement than other respondents that career preparation was important. Also, psychology respondents who did not pursue graduate education expressed some dissatisfaction with the career advising and preparation offered in their major. These findings reaffirm the need for psychology departments to develop flexible curricula to meet the diverse needs and interests of their majors and to provide better caree...
Critical illness is associated with elevated parathyroid hormone.

Propofol (Diprivan®, AstraZeneca) is a reliable sedative frequently used in critically ill patients (pts). The modified formulation contains 0.005% disodium edetate (EDTA) as an antimicrobial agent. EDTA is also a chelating agent and may impact calcium balance; therefore, three clinical trials were performed in which ionized calcium (Ca2+) and parathyroid hormone (PTH) levels were assessed. PTH plays a major role in calcium homeostasis but is generally not considered to be a stress hormone.
Severe droughts have occurred in the northeastern United States

People do not usually consider the northeastern United States to be a drought-prone region, but new evidence shows that mega-droughts have occurred there in the past. Dorothy Peteet of Columbia University and NASA's Goddard Institute for Space Studies reported at the AGU Fall Meeting in San Francisco, Calif., on her analysis of sediment cores in marshes in New York State. Different chemicals flow into a marsh from freshwater upriver and from saltwater from the ocean; higher concentrations of bromine and calcium, which are more common in saltwater, indicate a drier period. The data indicate that at least three mega-droughts occurred in the past 6000 years, the longest during what scientists term as the “Medieval warm period,” which lasted from about 850 C.E. to 1350 C.E. “People don't think of this area as threatened by droughts because we've been in a wet period,” Peteet said.
An efficient statistical algorithm for a temporal scan statistic applied to vaccine safety analyses.

In the US, the Vaccine Safety Datalink (VSD) project, sponsored by the Centers for Disease Control and Prevention, conducts near–real-time, population-based, active surveillance for vaccine safety. One of the steps in analyzing signals, if there are enough cases, is to apply temporal scan statistics. The purpose is to determine if the cases clustered in time within an overall a priori defined post-vaccination observation interval. We presented a relatively efficient and accurate algorithm for the purely temporal scan statistic as applied to vaccine safety investigations. It only needs SAS/BASE® software, and the algorithm is simple enough to be programmed in another software languages. Our present work is focused on incorporating the temporal scan statistic algorithm within our previous approach for finding an optimal risk window for studies of vaccine safety.
The Performance of US Corporations: 1981-1994

This study decomposes the performance of US public firms between 1981 and 1994 into year, industry, corporate-focus and firm effects. Performance is measured by Tobin’s q, accounting profitability, and a hybrid measure. The results show that firm effects were more important to performance than industry effects, although industry effects had a large permanent component. Corporate focus was not important. The stylized facts suggest that competitive advantages – that is, differences between direct competitors in the same industry – were at least as important as industry influences on performance. Industry influences were more predictable and sustainable than competitive advantages, however.
Effect of Pasteurization and Cool-Aging on the Salt Balance in Milk

Summary The effects of pasteurization and cool-aging on the distribution of calcium, magnesium, phosphorus, and citric acid in milk into curd and whey were studied by analyzing these constituents in rennet whey from milk after the appropriate treatments. Statistical analysis of the data from ten bulk-milk samples revealed that the differences were not significant, except with respect to magnesium in curd from cool-aged milk. These variations, however, did not reflect any significant change in the Ca:P ratios in the curd. The results were not in harmony with the observations on pure salt solution under similar conditions, and the variations in the behavior of milk are considered partly due to the colloidal systems present in milk. The importance of considering magnesium and citric acid simultaneously is pointed out in any attempt to explain the ionic equilibria regarding calcium phosphate in milk.
Isolation and characterization of a low-molecular weight seed protein from Ricinus communis.

A seed with an apparent molecular weight of 5000 has been isolated and purified from Ricinus communis. This protein has a very high content of glutamine and an unusual ultraviolet absorption spectrum. The amino-terminal sequence of 22 residues determined by automatic Edman degradation is: NH2-Pro-Ser-Gln-Gln-Gly- Cys-Cys-Gly-Gln-Ile-Gln-Glu-Gln-Gln-Asn-Leu-Arg-Gln-Cys-Gln-Glu-Tyr-.
Simvastatin Preserves Cardiac Function in Genetically Determined Cardiomyopathy

Endothelial dysfunction characterizes heart failure (HF). Simvastatin (Sim) increases endothelial nitric oxide (NO) independent of lipid-lowering. We evaluated the effect of Sim on cardiac function, apoptosis, and NO availability in HF. Five-month-old cardiomyopathic (CM) hamsters were divided into 2 groups: Sim (20 mg/kg, 6 weeks, n = 6) and Untreated (n = 6). Age-matched normal hamsters served as controls (n = 6). Serial echocardiograms were performed to measure LV function. Myocardial apoptosis, eNOS, and capillary density were measured at 6 weeks. Cardiomyopathic hamsters had lower LV shortening fraction (SF) compared with controls (17 +/- 3% vs 59 +/- 2%), higher LV end-diastolic volume (30 +/- 3 vs 6 +/- 2 mL/m2), and lower LV mass/volume ratio (0.5 +/- 0.04 vs 0.72 +/- 0.02 mg/ml, P < 0.001). During follow-up, SF decreased (9 +/- 2%) and LV volume increased (38 +/- 1 mL/m2) in untreated hamsters (P < 0.05 from baseline) but did not change significantly in the Sim group (P < 0.05 vs untreated). Myocardial caspase-3 activity was higher and apoptotic nuclear density was lower in Sim compared with untreated CM hamsters (0.072 +/- 0.02% vs 0.107 +/- 0.03%, P < 0.01). Myocardial capillary density was highest in the Sim group (P < 0.05). eNOS expression was not different between groups. Sim retards the progression of HF in CM hamsters. This may be related to an increase in coronary microvasculature, increase in NO availability, and decreased apoptosis.
Treatment of nephrotic hyperlipoproteinemia with gemfibrozil

Hypercholesterolemia is a known complication of the nephrotic syndrome. Patients with persistent proteinuria and prolonged hypercholesterolemia are probably at increased risk for cardiovascular disease. Until recently there has been no safe and effective treatment for this disorder. The effects of gemfibrozil on plasma lipids and lipoproteins in hypercholesterolemic patients with the nephrotic syndrome were therefore studied. Eleven patients with the nephrotic syndrome were studied in a randomized, double-blind placebo-controlled trial with six-week treatment periods. Gemfibrozil 600 mg or placebo was administered twice a day. There was a third unblinded period in which seven patients received gemfibrozil plus the bile acid-binding resin, colestipol, 10 grams twice a day. Gemfibrozil treatment produced a marked reduction in plasma triglyceride (51%, P = 0.001) and a 15% decrease in plasma total cholesterol (P = 0.003). Low density lipoprotein cholesterol decreased 13% (P greater than 0.05), high density lipoprotein cholesterol increased 18% (P = 0.006) and the ratio of low density lipoprotein to high density lipoprotein cholesterol fell 26% (P = 0.01). Apolipoprotein A-l was unchanged while apolipoprotein B decreased 26% (P = 0.006). Four patients were unable to complete period 3 because of gastrointestinal symptoms. The remaining patients had further improvement in plasma lipids and lipoproteins with the combined therapy: total cholesterol further decreased 26%, triglycerides decreased 17%, low-density lipoprotein cholesterol decreased 36%, high-density lipoprotein to high-density lipoprotein cholesterol fell 33%. Gemfibrozil improved lipid and lipoprotein cardiovascular risk factors without major toxicity. Persistent elevations in total plasma and low-density lipoprotein cholesterol during gemfibrozil treatment, however, indicate the need for individualized drug therapy.
■ FEATURED ABSTRACT Biodegradable starch nanoparticles are a novel and potentially effective and safe adjuvant for sonothrombolysis especially for more fibrin rich, aged and rigid clots

Purpose It was postulated that microstreaming produced by ultrasound-induced microbubble (MB) cavitation will propel nanoparticles with sufficient force to help erode clots by a sandblasting-like process. This study tested the plausibility of this hypothesis using biodegradable starch nanoparticles (StNPs) to promote sonothrombolysis (STBL). StNPs were mixed with MBs and/or tPA to determine if these agents interacted synergistically with StNPs to produce more effective lysis of STBL-resistant clots. Materials and Methods Fibrin-rich clots were formed from fresh rabbit blood supplemented with 60 U of thrombin, incubated 24 h at 37 o C, and then cured for 24 h at 4 o C. In vitro STBL of 7.5-12.0 mg pieces of fibrin-rich clot was performed in a flow chamber (37.0 o C) infused with bovine calf serum containing biodegradable starch nanoparticles (StNPs). STBL was performed with pulsed ultrasound (1 MHz or 3 MHz) and intensities of 0.05-2.0 W/cm 2 . STBL efficacy was quantified as % clot mass loss during a 15 min treatment. MBs (1 μm or 3 μm diameter) and/or tPA (0.01 mg/mL) were then combined with the StNPs to determine if they interacted synergistically to improve STBL efficacy. Results StNPs with a mean diameter of 250 nm were two-fold more effective than MBs for STBL of fibrin-rich, and rigid clots at both 1 MHz and 3 MHz. They interacted synergistically with MBs and tPA to provide an additional two- to four-fold more effective STBL. Conclusion Surprisingly, 250 nm StNPs were an effective adjuvant for STBL without MBs or tPA, but interacted synergistically with MBs and/or tPA to provide even more effective STBL, as postulated. StNPs are not destroyed by ultrasound and so provide longer-lasting STBL; plus their biocompatibility and biodegradability (within 2 h) eliminate potential toxicity concerns. Their nm size likely permits StNPs to penetrate deeper through the smaller pores within fibrin-rich clots than MBs. The current model is that as the deeper penetrating StNPs promote clot lysis so that MBs and tPA can then penetrate fibrin-rich clots more readily and interact with the ultrasound to enhance STBL efficacy further.
S&P 500 Trading Strategies and Stock Betas

this paper shows that S&P 500 stock betas are overstated and the non-S&P 500 stock betas are understated because of liquidity price effects caused by the S&P 500 trading strategies. The daily and weekly betas of stocks added to the S&P 500 index during 1985-1989 increase, on average, by 0.211 and 0.130. The difference between monthly betas of otherwise similar S&P 500 and non-S&P 500 stocks also equals 0.125 during this period. Some of these increases can be explained by the reduced nonsynchroneity of S&P 500 stock prices, but the remaining increases are explained by the price pressure or excess volatility caused by the S&P500 trading strategies. I estimate that theprice pressures accountfor 8.5 percent of the total variance of daily returns of a value-weighted portfolio of NYSE/AMEX stocks. The negative own autocorrelations in S&P 500 index returns and the negative cross autocorrelations between S&P 500 stock returns provide further evidence consistent with the price pressure hypothesis.
Changes in the blood and plasma volume of Harris' sparrows during postnuptial molt

Abstract 1. 1. In captive Harris' sparrows ( Zonotrichia querula ), plasma and blood volume increased significantly during stages 2 and 3 of postnuptial molt, when extensive feather replacement was taking place in the wings, tail and body tracts. 2. 2. Erythrocyte number did not increase significantly until molt was essentially complete. 3. 3. Consequently the 6% mean maximum reduction in hematocrit that was observed during molt appeared to be largely the result of plasma volume expansion. 4. 4. This plasma volume expansion was not due to changes in the osmolality or concentration of proteins within the blood plasma since both decreased significantly during intense molt.
How to read a Patent

A patent ordinarily does not presume as much background knowledge on the reader's part as does a technical journal article. Each patent is an exposition of the problem addressed, the solution to the problem, and the opportunities seen by the inventor for the elaboration and practical use of his findings. The patent usually includes a statement of the field of technology, a discussion of the prior art, statements of the benefits of the inventor's discovery, a definition of the invention in technical terms, elaboration of the details of the invention, a description of its usefulness, working examples, and claims. How to interpret these elements in a patent document and how to get through to the technical information sought are the principal subjects of this paper. Also discussed are means for gaining access to patent literature for both current awareness and retrospective searching.
Mechanical features of the r.f. system for the Berkeley 88-inch cyclotron†

Four features are described: the movable-panel drive system, ceramic ball bearings, r.f. hinges, and dee construction. The r.f. tuning is accomplished by varying the volume between the dee stem and six movable panels. Power to move the panels is supplied by four hydraulic cylinders. The hydraulic drive mechanism and control system are described. A special ceramic ball bearing, with alumina balls and stainless steel races, was developed. It operates in the presence of high vacuum, r.f. field, and radiation—and without organic lubrication. Bearing construction and test results are described. The r.f. current-carrying hinges between the movable panels were designed to optimize the hinge thickness and length so that bending stresses and temperature rise were minimized. Graphs showing the relationships between hinge thickness, length bending stress, and temperature rise are presented, together with hinge configuration. The dee-stem and dee structure is approx 14 ft long and weighs 2800 lb. Support for the entire assembly is provided by cantilevering it from the rear of the resonator tank. Materials and fabrication procedure for the dee panel structure are described.
Detection of ocular mucus in normal human conjunctiva and conjunctiva from patients with cicatricial pemphigoid using lectin probes and histochemical techniques.

Conjunctival biopsies from patients with cicatricial pemphigoid affecting the conjunctiva andpatients undergoing cataract surgery (normal conjunctiva) were snap-frozen, cryostat sectioned and incubated with fluorescein-conjugated lectins; peanut agglutinin (PNA), Helix pomatia agglutinin (HPA), soybean agglutinin (SBA), wheat germ agglutinin (WGA) and succinylated wheat germ agglutinin (S-WGA). Controls consisted of preincubating the lectins with the appropriate blocking sugars before applying the lectins to the sections. PNA and HPA stained the mucus granules contained in the conjunctival goblet cells but did not stain mucus or glycocalyx at the ocular surface distal to the goblet cells. Native WGA and S-WGA had high affinities for conjunctival goblet cells and the apical epithelial cell layers. Native WGA stained mucus and glycocalyx at the ocular surface. This staining of the ocular surface by WGA was confirmed at the transmission electron microscopic level using WGA conjugated to ferritin. Cicatricial pemphigoid patients in this study had reduced numbers of goblet cells; however, those goblet cells which were observed in cicatricial pemphigoid conjunctiva stained positively with HPA, PNA, WGA, and SWGA as did goblet cells in normal conjunctiva.
Logical composition of object-oriented interfaces

This paper describes an approach to object-oriented interface design that goes beyond mere object decomposition. In our user interface management system we use logic and filters to declaratively specify and control a space of ways that objects may be composed to create interfaces. A filter is a package of constraints and associated typed objects that express the relationship of data and representation objects.Conceptually our system is completely based on constraints. Filters provide the high bandwidth constraints to maintain the components of the direct-manipulation interface while the logic forms the low bandwidth constraints to combine and provide communication between these components. The use of Horn-clause logic to compose separate interface objects facilitates both the distribution of computation onto multiple processors and the generation of multiple views of data. Intelligent backtracking implemented in the logic allows for user- and system-initiated undo operations to correct errors and/or try alternative approaches to a problem. We illustrate the power and flexibility of this approach by describing a floor layout and design system.
Improving Data Analysis Performance for High-Performance Computing with Integrating Statistical Metadata in Scientific Datasets

Scientific datasets and libraries, such as HDF5, ADIOS, and NetCDF, have been used widely in many data intensive applications. These libraries have their special file formats and I/O functions to provide efficient access to large datasets. When the data size keeps increasing, these high level I/O libraries face new challenges. Recent studies have started to utilize database techniques such as indexing and subsetting, and data reorganization to manage the increasing datasets. In this work, we present a new approach to boost the data analysis performance, namely Fast Analysis with Statistical Metadata (FASM), via data subsetting and integrating a small amount of statistics into the original datasets. The added statistical information illustrates the data shape and provides knowledge of the data distribution; therefore the original I/O libraries can utilize these statistical metadata to perform fast queries and analyses. The proposed FASM approach is currently evaluated with the PnetCDF on Lustre file systems, but can also be implemented with other scientific libraries. The FASM can potentially lead to a new dataset design and can have an impact on big data analysis.
CCD-Digicon Detector System Performance Parameters

We are developing an intensified charge-coupled device (ICCD) detector system, based on the incorporation of a thinned backside-illuminated CCD as the anode of a Hubble Space Telescope design Digicon tube, for particular application to astronomical observations with stringent requirements for accuracy, rapid temporal response, low background, and high two-dimensional resolution. In this paper, images are presented which demonstrate the capability this system provides in achieving sub-CCD-cell resolution, representing a substantial increase in this attribute. These results also indicate that the amount of this increase is at present constrained by the limited extent of the spreading of photoelectron-generated charge evident in the particular thinned CCD used here, and that further increases in resolution remain possible with the use of thicker chips. In connection with this, the potential benefits of magnetic deflection substepping in ensuring excellent uniformity of elemental response in the overall sensor system are shown dramatically in this study. Additionally, we present preliminary results from the fabrication and testing of mesh photocathodes suitable for inclusion in such a system, which may be applied to extend wavelength coverage into the extreme ultraviolet, and from the successful processing and operation of a sealed CCD-Digicon tube.
A HANDBOOK FOR SCRIPTURAL REASONING

The essay includes twelve “rules” to define the nature and goals of the practice of Scriptural Reasoning (SR). These rules are intended for heuristic and pedagogic purposes to introduce Scriptural Reasoning to those who have little experience in and knowledge of the practice of SR. The rules emerged from my observations of SR practice and, taken together, the rules are meant to be a guide or “handbook” for future SR practice.
Death Anxiety Reduction as the Result of Exposure to a Death and Dying Symposium

The purpose of this study was to measure the effect of a three-week death and dying symposium at Colorado State University on attitudes and anxiety related to death, dying, and grief. A prepost control group design was employed using psychology undergraduate students as participants. Because of an overall finding of low participant attendance at the symposium events, participants who attended at least one event were assigned to the treatment group for data analyses. Results indicated lower death anxiety for students in both the treatment and control groups. The findings are discussed in terms of the widespread media coverage and informal discussions which accompany large-scale symposiums. Future research is suggested regarding the dynamic effects of such death and dying symposiums in relation to both attendants and nonattendants.
Search for ligands of neuronal α-bungarotoxin receptors

Extracts of calf brain were analyzed for substances capable of blocking the binding of [125I]-alpha-bungarotoxin to chick brain membrane preparations, and shown to contain blocking activity that was insensitive to heating and trypsin. Fractionation on Sephadex G-25 yielded two components, one representing nonspecific inhibition by inorganic cations, the other identified as choline by co-chromatography experiments and analysis of the purified inhibitor using thin layer chromatography and mass spectrometry. These results support the notion that the alpha-bungarotoxin binding macromolecule in the central nervous system is an acetylcholine receptor.
RNA polymerase of nuclear sap and chromatin fractions of walker tumor

Abstract 1. 1. Walker tumor RNA polymerase II consists of two activities, lIa and IIb, distinguishable by their intranuclear distribution and template preference. 2. 2. RNA polymerase IIa, localized in nuclear sap, preferentially utilizes denatured DNA template, while RNA polymerase IIb, obtained from chromatin (nuclear sap-free nuclei), is more active with native DNA template. 3. 3. The two activities show similarities in response to divalent metal ions, salt concentration, and sensitivity to α-amanitin. 4. 4. The RNA synthesized by the two polymerases show similar nearest neighbor frequences and base ratios. 5. 5. However, RNA product synthesized by RNA polymerase IIa has a much longer average chain length than that synthesized by RNA polymerase IIb, while the RNA product of polymerase IIb shows significantly more self-complementarity than the product of polymerase IIa.
Materials science: Energy storage wrapped up

Cables and wires are used to conduct electricity, but can they also store energy? The answer is a resounding 'yes', if they are encased by a supercapacitor device — a finding that might open up many applications.
Technique for retransplanting heterotopic heart grafts in mice

Removal of a transplanted organ from its original recipient and retransplanting it into a new host is an important method to study the role of the graft in the rejection process. Here we describe a novel technique of heart retransplantation in the mouse. In this technique, a primarily vascularized heart graft is anastomosed to the abdominal aorta and inferior vena cava of a syngeneic or immunodeficient allogeneic mouse, using standard techniques. Either 10 or 70 days later, the same graft is retransplanted into the abdomen of a second mouse by end-to-side anastomosis of the donor (first recipient) aortic and inferior vena cava's cuffs to the second recipient's abdominal aorta and inferior vena cava, respectively. A greater than 90% success rate was achieved by using this microsurgical technique. This method should be useful for studying intragraft factors, such as ischemia-reperfusion injury and donor antigen-presenting cells, on the outcomes of transplantations.
Antegrade, Retrograde, and Combination Strategies for Chronic Total Occlusions

Chronic total occlusion (CTO) represents one of the most challenging lesion subsets faced by the interventional cardiologist. CTO is a common problem, being present in more than 30% of patients undergoing coronary angiography. Over the past 10 years, the success rate of recanalization has increased from approximately 50-85%. Developments in guidewire technology, imaging technique, and coronary devices have contributed to the improved prognosis of patients affected by a CTO lesion. Enhancement in antegrade and retrograde techniques of recanalization also result in improved outcomes. Benefits of CTO recanalization may include symptom relief, decreased need for coronary artery bypass graft surgery, improved left ventricular ejection fraction, and in some cases an improved survival.
Twenty-year trends in emotional and behavioral problems in Dutch children in a changing society.

Objective: Research into changes in the prevalence of children's psychiatric diagnoses has indicated an increase in recent decades. However, methodological problems may have influenced results. This study compared children's emotional and behavioral problem levels across three population samples from different time points across 20 years, assessed with identical methodologies. Method: We compared Child Behavior Checklists and Teacher's Report Forms across three population samples of 6- to 16-year olds, assessed in 1983, 1993, and 2003. Results: We found evidence for small increases in the mean population levels of parent-reported problems, and in the percentages of children with serious problems. These changes concerned mostly internalizing problems. Teacher reports showed less changes. Decreases in scores were found on several areas of competence. Changes were the strongest between 1993 and 2003. Conclusion: We found evidence for small increases in Dutch children's problems. Further developments must be monitored, as this trend may continue and have serious societal consequences.
HUMAN PLACENTAL CYTOPLASMIC 5|[prime]|-NUCLEOTIDASE: PURIFICATION AND MOLECULAR PROPERTIES: 115

Purine nucleotide degradation in human tissues is highly regulated. Dephosphorylation of nucleoside 5'-monophosphates is the first committed and irreversible reaction of purine nucleotide catabolism. Recent studies indicate that cytoplasmic 5'-nucleotidase may have an important role in intracellular nucleotide degradation. We purified cytoplasmic 5'-nucleotidase from human placenta 8075-fold to a specific activity of 58.85 μmol/ min/mg. The enzyme showed absolute requirement for magnesium with a Km of 6 mM and pH optimum from 7.4 to 9.0. CMP and UMP are preferred substrates. A large variety of purine, pyrimidine and pyridine compounds exert an inhibitory effect on enzyme activity. IMP, GMP and NADH produce almost 100% inhibition at 1.0 mM. Nucleoside di- and triphosphates are potent inhibitors. ATP and ADP are competitive inhibitors with respect to AMP and IMP as substrates with Ki values of 100 μM and 15 μM, respectively. Inorganic phosphate is a noncompetitive inhibitor with Ki values of 19 mM and 43 mM. The estimated molecular weight is 143,000 and the stokes radius is 46.1A. The subunit molecular weight is 76,000, suggesting that the enzyme is a dimeric protein. These data elucidate the nature of cytoplasmic 5'-nucleotidase enzyme and its role in purine nucleotide degradation in human tissues.
Recent Shallow-Water Carbonate Sediments: ABSTRACT

The "feedback" from studies of Recent carbonate sediments to studies of ancient carbonate rocks is small. The reason for this unfortunate state of affairs is that the approaches used in the two problems are so different. For example, the materials are different; carbonate sediments are conventionally nearly pure carbonate, whereas carbonate rocks contain up to 50 per cent non-carbonates. Sediment studies usually involve rather elaborate size analyses, mineralogic studies, and individual particle descriptions. For most carbonate rocks diagenetic alteration has made size analysis difficult or meaningless, the minerals have changed, and only a part of the original particles can even be recognized. The best understanding of carbonate rocks comes from conventional isopachous maps, stratigraphic associations, insoluble-residue studies, and fossil content. Only in a few cases can petrographic studies of size or particle type do more than support conclusions based on field relations. The writers do not see any immediate way of changing drastically the methods for studying carbonate rocks. However, new approaches are possible in the study of sediments. By simply enlarging the End_Page 457------------------------------ definition of carbonate sediments to include those containing more than 50 per cent carbonate minerals, many new parameters can be studied and new and useful information can be incorporated in studies of carbonate rocks. It is obvious that, by enlarging the definition, consideration of insoluble residues and stratigraphic associations is possible. Further, the geographic range of carbonate sediments is enlarged, permitting study of a wider variety of environmental conditions. Finally, a greater variation in thickness of Recent carbonate sediments is found, a fact which should allow a better understanding of sedimentation rates. End_of_Article - Last_Page 458------------
A computational model for the AVCN marginal shell with medial olivocochlear feedback: Generation of a wide dynamic range

Abstract Among auditory nerve fibers, sound intensity is best encoded in the responses of low-medium spontaneous rate (LMSR) fibers. Each fiber encodes only a portion of the full dynamic range of hearing because the fibers show saturation at high sound intensities. Despite this saturation, neurons in the marginal shell of the anteroventral cochlear nucleus (AVCN) that receive inputs from LMSR fibers display monotonically increasing firing rates. Feedback to these neurons from medial olivocochlear (MOC) neurons’ collaterals is hypothesized to contribute to the shell neurons’ unusually wide dynamic ranges. A model system incorporating MOC feedback to an AVCN shell neuron was implemented in GENESIS. The rate-intensity function of the model AVCN shell neuron exhibited a wide dynamic range analogous to experimental observations.
Activation of MEK/ERK Signaling Promotes Adipogenesis by Enhancing Peroxisome Proliferator-activated Receptor γ (PPARγ) and C/EBPα Gene Expression during the Differentiation of 3T3-L1 Preadipocytes

We demonstrate that exposure of post-confluent 3T3-L1 preadipocytes to insulin, isobutylmethylxanthine (MIX), dexamethasone (DEX), and fetal bovine serum induces a rapid but transient activation of MEK1 as indicated by extensive phosphorylation of ERK1 and ERK2 during the initial 2 h of adipogenesis. Inhibition of this activity by treating the cells with a MEK1-specific inhibitor (U0126 or PD98059) prior to the induction of differentiation significantly attenuated the expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, perilipin, and adipocyte-specific fatty acid-binding protein (aP2). Treating the preadipocytes with troglitazone, a potent PPARγ ligand, could circumvent the inhibition of adipogenic gene expression by U0126. Fibroblast growth factor-2 (FGF-2), in the presence of dexamethasone, isobutylmethylxanthine, and insulin, induces a prolonged activation of the MEK/ERK signaling pathway, which lasts for at least 12 h post-induction, and this activity is less sensitive to the MEK inhibitors. Consequently, preadipocytes treated with U0126 in the presence of fibroblast growth factor-2 (FGF-2) express normal post-induction levels of MEK activity, and, in so doing, are capable of undergoing adipogenesis. We further show that activation of MEK1 significantly enhances the transactivation of the C/EBPα minimal promoter during the early phase of the differentiation process. Our results suggest that activation of the MEK/ERK signaling pathway during the initial 12 h of adipogenesis enhances the activity of factors that regulate both C/EBPα and PPARγ expression.
Primitive neuroectodermal tumors of the biliary and gastrointestinal tracts: clinicopathologic and molecular diagnostic study of two cases.

Primitive neuroectodermal tumor (PNET) is a prototypic malignant small round cell tumor of childhood that is characterized in most cases by t(11;22) resulting in an EWS-FLI1 gene fusion. Once thought to be uncommon, PNET now accounts for almost 20% of malignant soft tissue tumors in children. Increased recognition of PNET is partly due to advances in immunohistochemistry and molecular diagnostics, which have led to the identification of the tumor in non-classical sites. We report the clinical, histologic, immunohistochemical, and molecular findings of two visceral PNETs of the digestive system—one involving the small intestine and the other involving the hepatic duct. Histologically, each tumor was composed of malignant small cells growing in sheets, nests, and lobules; the tumor cells of both cases showed characteristic immunoreactivity for vimentin and O13 (CD99). Reverse transcription-polymerase chain reaction (RT-PCR) analysis for t(11;22) using nested primers was performed with RNA extracted from paraffin-embedded, formalin-fixed tissue and demonstrated an EWS exon 7 to FLI1 exon 5 fusion in both cases, confirmed by Southern blot hybridization and DNA sequence analysis. These results illustrate the expanded clinicopathologic profile of PNET, and demonstrate that visceral PNETs, despite their unusual sites of presentation, maintain the characteristic immunohistochemical and genetic features of PNETs at more conventional sites.
Escherichia coli Diarrhea

During the 1940s and 1950s, a series of outbreaks of diarrhea in hospital newborn nurseries were reported in which the etiological agent appeared to be Escherichia coli identified by serotype. These strains became known as enteropathogenic E. coli (EPEC). Although it is generally recognized that these strains are responsible for diarrhea among children under 2 years of age, only now are we beginning to understand how they produce disease.
A comparison of the effects of 6-β naltrexol and naltrexone on the consumption of ethanol or sucrose using a limited-access procedure in rats

We recently reported that 6-beta naltrexol, the major metabolite of naltrexone in humans, reduced ethanol consumption in rats. Two new experiments were designed to compare 6-beta naltrexol and naltrexone across three dose levels on an ethanol or sucrose baseline using a limited-access procedure in Wistar rats. The results of Experiment 1 showed that both 6-beta naltrexol and naltrexone reduced ethanol consumption across a range of doses. An in vivo assay showed that naltrexone was approximately 25 times more potent than 6-beta naltrexol at comparable ED50 doses. In addition, there was no indication of systematic development of tolerance to the effect of either drug across the 4 days of drug administration. In Experiment 2, both 6-beta naltrexol and naltrexone reduced the consumption of a sucrose solution using a limited-access procedure. The implications of these data for the development of pharmacotherapeutic agents capable of reducing drinking in recovering alcoholics are discussed.
Anxiety about Foreign Language Learning among High School Women

This study examined the relationship between anxiety and native language skill and foreign language aptitude measures among 154 high school foreign language learners. Three levels of anxiety were identified using the Foreign Language Classroom Anxiety Scale or FLCAS (Horwitz, Horwitz, & Cope, 1986). Low Anxiety (LO-ANX) students were expected to have significantly stronger native language skills and foreign language aptitude than High Anxiety (HI-ANX) students and significantly higher foreign language grades. Average Anxiety (AVE-ANX) students were expected to score somewhere in-between. Findings showed overall significant differences among the groups on nine variables, including measures of native language phonology/orthography, semantics, and verbal memory; foreign language aptitude; eighth-grade English grade; and end-of-year foreign language grade. On measures of phonology/orthography, eighth-grade English, and foreign language grade, LO-ANX and AVE-ANX students outperformed HI-ANX students. On a foreign language aptitude measure and foreign language grade, LO-ANX students outperformed both AVE- and HI-ANX students. On measures of verbal memory and reading comprehension, LO-ANX students outperformed HI-ANX students. Discriminant analysis results showed that all test measures but one were significant in distinguishing the three groups. Among others, implications include the suggestion that skill in one's native language and aptitude for learning a foreign language may affect anxiety level and that the FLCAS may provide an early indicator of basic language problems.
Identification of a Novel Integrin α6β1 Binding Site in the Angiogenic Inducer CCN1 (CYR61)

The angiogenic inducer CCN1 (cysteine-rich 61, CYR61), a secreted matricellular protein of the CCN family, is a ligand of multiple integrins, including alpha 6 beta 1. Previous studies have shown that CCN1 interaction with integrin alpha 6 beta 1 mediates adhesion of fibroblasts, endothelial cells, and smooth muscle cells, as well as migration of smooth muscle cells. Recently, we have reported that CCN1-induced tubule formation of unactivated endothelial cells is also mediated through integrin alpha 6 beta 1. In this study, we demonstrate that human skin fibroblasts adhere specifically to the T1 sequence (GQKCIVQTTSWSQCSKS) within domain III of CCN1, and this process is blocked by anti-alpha 6 and anti-beta 1 monoclonal antibodies. Alanine substitution mutagenesis of the T1 sequence further defines the sequence TTSWSQCSKS as the critical determinant for mediating alpha 6 beta 1-dependent adhesion. Soluble T1 peptide specifically inhibits fibroblast adhesion to CCN1 in a dose-dependent manner. Furthermore, T1 also inhibits cell adhesion to other alpha 6 beta 1 ligands, including CCN2 (CTGF), CCN3 (NOV), and laminin, but not to ligands of other integrins. In addition, T1 specifically inhibits alpha 6 beta 1-dependent tubule formation of unactivated endothelial cells in a CCN1-containing collagen gel matrix. To confirm that T1 binds integrin alpha 6 beta 1 directly, we perform affinity chromatography and show that integrin alpha 6 beta 1 is isolated from an octylglucoside extract of fibroblasts on T1-coupled Affi-gel. Taken together, these findings define the T1 sequence in CCN1 as a novel binding motif for integrin alpha 6 beta 1, providing the basis for the development of peptide mimetics to examine the functional role of alpha 6 beta 1 in angiogenesis.
Why the hadronic multiplicity distributions in e+e− annihilations are so narrow☆

Abstract In the cell theory of hadron production, the final state is partitioned into a set of k cells which emit independently. We use the generalization of our previous formulation for nondiffractive hadron collision multiplicities, which allows the stochastic emission process of each cell to have a coherent component. The e + e − annihilation process is compared to the statistics of photoelectron counting of light from a laser to whose coherent component a small amount of noise is added. This noise, though small, suppresses the peak and widens the tails of the KNO plot. KNO scaling in this reaction is then a consequence of a slowly increasing noise/signal amplitude ratio m (which we find consistent with zero at 15–20 GeV and 0.1–0.2 at 34 GeV). Possible connections with the markovian QCD evolution equations are indicated.
Absolute oral bioavailability of traxoprodil in cytochrome P450 2D6 extensive and poor metabolisers.

Traxoprodil, a substituted 4-phenylpiperidine, is an N-methyl-D-aspartate (NMDA) receptor antagonist that is selective for receptors containing the NR2B subunit. In vivo and in vitro studies examining the disposition of traxoprodil have demonstrated that it is mainly metabolised by cytochrome P450 (CYP) 2D6, a major drug-metabolising enzyme that exhibits a genetic polymorphism. To assess the single-dose absolute oral bioavailability of traxoprodil in healthy male volunteers phenotyped as either CYP2D6 extensive or poor metabolisers. This was an open-label, three-way crossover study. Traxoprodil was administered as a single dose orally in solution of 50, 100 and 300mg and intravenously as a constant rate 2-hour infusion of 50 and 100mg. CYP2D6 phenotype was assigned following single-dose dextromethorphan administration. In poor metabolisers (n = 6), oral bioavailability was ∼80% and was consistent with a liver extraction ratio of ∼20% (plasma clearance of ∼4 mL/min/ kg) indicating near complete absorption. Following intravenous administration, the mean volume of distribution at steady state (Vss) was moderate (∼6.5 L/kg) and the mean elimination half-life (t1/2) was ∼20 hours. Following oral administration the mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinity (AUC∞) increased approximately proportionally with dose. In extensive metabolisers (n = 11), oral bioavailability was dose-dependent and nonlinear. At the 100mg dose, the absolute oral bioavailability was ∼39.5%. Overall, the oral bioavailability ranged from 22.8% to 62.1% and its estimation was confounded by large differences in plasma concentrations at oral doses without equivalent intravenous doses. Following intravenous administration, plasma clearance was high (∼27 mL/min/kg), the Vss was moderate (∼4 L/Kg) and the t1/2 was ∼2–4 hours. Following oral administration the Cmax and AUC∞ increased more than proportionally with dose. Apparent oral clearance decreased with increasing oral dose. However, t1/2 was approximately the same at all doses (∼4 hours). The pharmacokinetics of traxoprodil were quite different in the two phenotypes. In extensive metabolisers, the oral bioavailability was nonlinear and dose-dependent, while in poor metabolisers, oral bioavailability appeared to be linear and dose-independent. Based on the pharmacokinetics in extensive and poor metabolisers, the nonlinear oral bioavailability in extensive metabolisers may be attributed to saturation of hepatic first-pass CYP2D6 metabolism. Thus, at a high oral dose, the impact of CYP2D6 metabolism on traxoprodil pharmacokinetics is minimal.
E-rating Machine Translation

We describe our submissions to the WMT11 shared MT evaluation task: MTeRater and MTeRater-Plus. Both are machine-learned metrics that use features from e-rater®, an automated essay scoring engine designed to assess writing proficiency. Despite using only features from e-rater and without comparing to translations, MTeRater achieves a sentence-level correlation with human rankings equivalent to BLEU. Since MTeRater only assesses fluency, we build a meta-metric, MTeRater-Plus, that incorporates adequacy by combining MTeRater with other MT evaluation metrics and heuristics. This meta-metric has a higher correlation with human rankings than either MTeRater or individual MT metrics alone. However, we also find that e-rater features may not have significant impact on correlation in every case.