cssi/SciSciGPT-SciSciNet huggingface dataset:
Tim-Tipin dysfunction creates an indispensible reliance on the ATR-Chk1 pathway for continued DNA synthesis.

The Tim (Timeless)–Tipin complex has been proposed to maintain genome stability by facilitating ATR-mediated Chk1 activation. However, as a replisome component, Tim–Tipin has also been suggested to couple DNA unwinding to synthesis, an activity expected to suppress single-stranded DNA (ssDNA) accumulation and limit ATR–Chk1 pathway engagement. We now demonstrate that Tim–Tipin depletion is sufficient to increase ssDNA accumulation at replication forks and stimulate ATR activity during otherwise unperturbed DNA replication. Notably, suppression of the ATR–Chk1 pathway in Tim–Tipin-deficient cells completely abrogates nucleotide incorporation in S phase, indicating that the ATR-dependent response to Tim–Tipin depletion is indispensible for continued DNA synthesis. Replication failure in ATR/Tim-deficient cells is strongly associated with synergistic increases in H2AX phosphorylation and DNA double-strand breaks, suggesting that ATR pathway activation preserves fork stability in instances of Tim–Tipin dysfunction. Together, these experiments indicate that the Tim–Tipin complex stabilizes replication forks both by preventing the accumulation of ssDNA upstream of ATR–Chk1 function and by facilitating phosphorylation of Chk1 by ATR.
Ahomocysteinemia in molybdenum cofactor deficiency

We report an infant with molybdenum cofactor deficiency (MCD) and a unique clinical presentation of hemiplegia, hypotonia, dystonia, and bilateral basal ganglia changes. Biochemistry revealed absent serum homocysteine, low concentrations of plasma cystine, high levels of urinary S-sulfocysteine and sulfite, and high levels of oxypurines in serum and urine. The depletion of cysteine and cystine through reaction with sulfite suggests that other thiols and thiol-dependent proteins may be similarly depleted. Ahomocysteinemia may be a clue to the mechanism of cytotoxicity in MCD.
New method for determining internal temperature of cooking meat via NMR spectroscopy

NMR spectroscopy is used to determine fat content and internal temperature of hamburger, pork sausage, and various cuts of chicken during cooking. The temperature is determined by the frequency difference of the water and fat lines within the NMR spectrum. This method is more accurate than the absolute measurement of either peak alone. Furthermore, because the measurement relies on a frequency difference, precise control of the magnetic field is unnecessary. The hamburger and sausage data indicate an accuracy of ± 1C. The temperature accuracy for chicken is ± 5C. The difference in accuracy is due to the lower fat content of chicken. Chicken bone marrow, however, has a high fat content which could be used to measure its temperature. The speed and accuracy of this technique admits the possibility of using NMR spectroscopy on the process line to determine when these cuts of meat are sufficiently cooked and thus safe.
Uv photooxidation and photopatterning of alkanethiolate self-assembled monolayers (SAMs) on GaAs (001)

We have investigated the photooxidation of alkanethiolate self-assembled monoalyers (SAMs) adsorbed on GaAs (001) using time-of-flight secondary ion mass spectrometry. Both -CH3- and -COOH-terminated SAMs undergo photoreaction to form sulfonated species upon exposure to UV light from a 500 W Hg arc lamp (lambda = 280-440 nm) in the presence of oxygen. In contrast to SAMs adsorbed on metals, the photooxidation of octadecanethiol adsorbed on GaAs can be fit to two first-order reactions: a fast initial reaction followed by a second slower reaction ( approximately 6 times slower). For SAMs with shorter alkyl chain lengths, the photooxidation process is can be fit to a single first-order reaction. Using the optimal photooxidation time, we also demonstrate that SAMs can be successfully UV photopatterned on GaAs substrates producing sharp, well-defined patterns.
IDENTIFICATION AND MEASUREMENT OF THE RESISTANCES TO ABSCISSION OF INTACT OR UNIT KERNELS OF SWEET CORN

The successful detachment of sweet corn kernels as intact kernels promises large yield and effluent advantages over cut kernels during processing but requires a low strength of kernel attachment to the cob. This work describes the development of a test method for measuring the strength of kernel attachment and applies it to the identification of %varietal differences. Two components resisting detachment were identified: a base or abscission component and a side or frictional component. Base components as low as 1.3 Newton (N) (Golden Happiness) and as high as 5.5N (Illini Xtra Sweet) and side components as low as 1.3N (Vanguard) and as high as 4.0N (Golden Happiness) were observed. Abscission strength was found to correlate with prototype machine processing variables such as kernel mass production rates and the completeness of kernel removal from the cob.
Pubertal maturation and cortisol level in response to a novel social environment among female adolescents.

Abstract Research indicates changes in HPA-axis activity across puberty. The current study extends existing work by evaluating pubertal status and cortisol level in a novel social environment (research laboratory) while controlling for several important biological, behavioral, and psychological variables. Participants were 30 girls (ages 9–16 years) from the United States. Pubertal status was assessed via the Pubertal Development Scale. Salivary samples were collected at laboratory-introduction and a matched at-home period; laboratory-introduction levels were regressed on basal cortisol levels to create standardized residual scores. After controlling for covariates, pubertal status was positively associated with residualized cortisol values. Findings indicate more advanced puberty related to greater cortisol response to the laboratory; data are discussed in terms of future research and building biopsychosocial models of the puberty-psychopathology linkage.
Sigma-1 Receptor Regulation of Voltage-Gated Calcium Channels Involves a Direct Interaction

Purpose The sigma-1 receptor belongs to a recently discovered family of transmembrane proteins expressed in the central nervous system, including the eye, and mediates the regulation of ion channels. The exact function of sigma receptors remains to be elucidated. The purpose of this study was to investigate the effect of sigma-1 receptor ligands on calcium homeostasis in a retinal ganglion cell line (RGC)-5 and rat primary RGCs. Methods Calcium imaging was used to assess the effect of sigma-1 receptor agonist (+)-N-allylnormetazocine ((+)-SKF10047) on potassium chloride (KCl)-induced calcium influx in RGC-5. The whole-cell patch clamp technique was used to analyze the effect of (+)-SKF10047 on calcium currents in primary RGCs. Coimmunoprecipitation assessed the interaction between the sigma-1 receptor and the L-type voltage-gated calcium channel. Results The sigma-1 receptor agonist (+)-SKF10047 inhibited potassium chloride (KCl)-induced calcium influx. The sigma-1 receptor antagonist, BD1047, reversed the inhibitory effect of (+)-SKF10047. Whole-cell patch clamp recordings of rat cultured primary RGCs demonstrated that (+)-SKF10047 inhibited calcium currents. Coimmunoprecipitation studies demonstrated an association between L-type calcium channels and the sigma-1 receptors. Conclusions These results suggest that sigma-1 receptor activation can regulate calcium homeostasis and signaling in RGCs, likely by directly influencing the activity of L-type voltage-gated calcium channels. Regulation of calcium influx in RGCs by sigma-1 receptor ligands may represent in part the neuroprotective effect of sigma-1 receptors.
Transepithelial electrical responses to sodium and potassium of nonsensory region of gerbil utricle.

Abstract Sheets of utricular epithelium from gerbil were mounted in a micro-Ussing chamber. Step changes in [Na] and [K] on each side of the epithelium led to changes in transepithelial potential difference (Vt) and resistance (Rt) which were consistent with the presence of ionic conductances for these two ions. Responses of Vt, to 20 mM Rb steps were similar to those to 20 mM K steps. Several common Na and K channel blockers were applied: No evidence for the presence of amiloride-sensitive Na channels was found. At 10−6 M, amiloride caused no significant changes in Vt but at 10−3 M it initially decreased or increased Vt when applied from the apical or the basolateral side, respectively. Ba and quinidine each reduced Vt, quinidine more strongly from the basolateral than from the apical side. Tetraethylammonium, another K channel blocker, had no significant effect from either side. These data suggest that in spite of the low value of (Rt), the cellular pathway contributes significantly to the voltage response to cation concentration steps in this epithelium. The mode of action of 10−3 M amiloride and the K channel blockers remains uncertain.
Invertebrates associated with the marine wood boring isopod, Limnoria tripunctata.

Untreated wood submerged for 4–6 months and infested with the marine wood boring isopod, Limnoria tripunctata Menzies, was analyzed for the associated invertebrate community. Associated with Limnoria were acoelous turbellarians, nematodes, the archiannelid Dinophilus sp., the tubicolous polychaete, Polydora sp., 4 harpacticoid copepods, 2 amphipods and the tanaid, Leptochelia savignyi. Limnoria ecto-commensals included ciliated and diatoms.
Phase equilibria in gas mixtures at high pressures: Implications for planetary structures

Abstract An understanding of phase equilibria in gas mixtures under pressure is essential to the study of the deep-atmosphere and interior structures of the outer planets. The results of experiments on phase equilibria in mixtures of He with Ar and N 2 , at pressures up to 10 000 atm, are presented, and serve as the basis for a discussion of the characteristics of phase diagrams for two-component gas mixtures at high pressures. The application of these results to problems of planetary interiors is briefly discussed. A brief description of the experimental method is included.
Experimental analysis of arsenic precipitation during microbial sulfate and iron reduction in model aquifer sediment reactors

Abstract Microbial SO42− reduction limits accumulation of aqueous As in reducing aquifers where the sulfide that is produced forms minerals that sequester As. We examined the potential for As partitioning into As- and Fe-sulfide minerals in anaerobic, semi-continuous flow bioreactors inoculated with 0.5% (g mL−1) fine-grained alluvial aquifer sediment. A fluid residence time of three weeks was maintained over a ca. 300-d incubation period by replacing one-third of the aqueous phase volume of the reactors with fresh medium every seven days. The medium had a composition comparable to natural As-contaminated groundwater with slightly basic pH (7.3) and 7.5 μM aqueous As(V) and also contained 0.8 mM acetate to stimulate microbial activity. Medium was delivered to a reactor system with and without 10 mmol L−1 synthetic goethite (α-FeOOH). In both reactors, influent As(V) was almost completely reduced to As(III). Pure As-sulfide minerals did not form in the Fe-limited reactor. Realgar (As4S4) and As2S3(am) were undersaturated throughout the experiment. Orpiment (As2S3) was saturated while sulfide content was low (∼50 to 150 μM), but precipitation was likely limited by slow kinetics. Reaction-path modeling suggests that, even if these minerals had formed, the dissolved As content of the reactor would have remained at hazardous levels. Mackinawite (Fe1 + xS; x ⩽ 0.07) formed readily in the Fe-bearing reactor and held dissolved sulfide at levels below saturation for orpiment and realgar. The mackinawite sequestered little As (
Functional characterization and NMR spectroscopy on full-length Vpu from HIV-1 prepared by total chemical synthesis

Vpu is an 81-residue integral membrane protein encoded in the HIV-1 genome that is of considerable interest because it plays important roles in the release of virus particles from infected cells and in the degradation of the cellular receptor. We report here the total chemical synthesis of full-length Vpu(1−81) as well as a site-specifically 15N-labeled analogue, Vpu(2−81), using native chemical ligation methodologies and also report a structural and functional comparison of these constructs with recombinant protein obtained via bacterial expression. The structures of the synthetic and expressed polypeptides were similar in lipid micelles using solution NMR spectroscopy. Solid-state NMR spectra of the polypeptides in aligned hydrated lipid bilayers indicated that their overall topologies were also very comparable. Further, the channel activity of the synthetic protein was found to be analogous to that previously characterized for the recombinant protein. We have thus demonstrated that using solid phase pe...
The heterogeneous character of the dilute acid hydrolysis of crystalline cellulose. II. Hydrolysis in sulfuric acid

Nine prehydrolyzed cellulose samples, including native, mercerized, and regenerated celluloses were hydrolyzed in 2% sulfuric acid at 150, 160, and 170°C. The first-order rate constants and the weight average degrees of polymerization (by size exclusion chromatography) were determined for each sample. The results indicate that Sharples' end-attack model [Trans. Faraday Soc., 53, 1003 (1957)] is consistent with kinetic data for cellulose II samples, but is not appropriate for characterizing the reactions of cellulose I samples.
Preparation of self-organized niobium oxide microstructures via potentiostatic anodization

Abstract Self-organized niobium oxide microcones were prepared in an electrolyte (0.25–2.5 wt% HF) via anodization and observed with scanning electron microscopy. The nano and mesoscale tips ranged between 40 and 300 nm in size. The dimensions and integrity of the bulk microstructures were found to be strongly dependent on potential, temperature, electrolyte composition, and anodization time. Microcone texture revealed nano and mesoscale grooves, gaps, and roughness. Growth rates were investigated and possible explanations for the conical formations are discussed.
Interannual atmospheric angular momentum variability 1963-1973 and the Southern Oscillation

The Oort (1981) data set is used to determine the total angular momentum variability of the atmosphere below 75 mbar over the 120-month period from May 1963 to April 1973. These results are in turn compared with the observed length of day variations of the same period. When the mean, annual and semi-annual cycles are removed, the angular momentum displays an irregular oscillation with periods of three to four years and a corresponding relative change in the length of day of about + or - 0.2 x 10 to the -8th. This oscillation, which agrees with the observed interannual length of day variations for the period, appears to be related to the oscillation in tropical air and sea surface temperatures which lags behind the temperature oscillation by a few months. A relative change in the rotation of the earth on the order of 0.2 x 10 to the -8th can be produced by an observed tropical temperature oscillation of 1.0 C, according to a thermal wind argument.
Hormonally active agents in the environment and children's behavior: assessing effects on children's gender-dimorphic outcomes.

Background Early sex hormone exposure contributes to gender-dimorphic behavioral development in mammals, including humans. Environmental toxicants concentrated in contaminated sport fish can interfere with the actions of sex steroids. Methods This study developed an outcome variable by combining gender-dimorphic behaviors that differentiates boys and girls. Offspring of participants in the New York State Angler Cohort Study (NYSACS) were targeted in a parent-report postal survey. Instruments were selected based on findings of gender differences in the general population. Results A linear discriminant function model incorporating three gender behavior scales correctly classified the sex of 97.7% of children (252 boys and 234 girls) from a random NYSACS sample. The discriminant function was cross-validated by correctly classifying the sex of 98.4% of children (457 boys and 425 girls) from the remaining NYSACS cases and 97.6% of children (154 boys and 142 girls) from an independent school sample. Within-sex stepwise multiple regression analyses revealed that masculine behavior increased among boys with age and with the number of years of maternal sport fish consumption. In girls, older age and previous live-born siblings were associated with more masculine behavior, whereas feminine behavior increased with the duration of breast feeding. These associations were replicated in an independent sample. Conclusions A linear discriminant function effectively transformed the binary classification of sex (male-female) to a bipolar continuum of gender (masculinity-femininity). Findings from this study are consistent with the hypothesis that environmental contaminants contribute to shifts in gender-role behavior. Future investigations will need to account for competing explanations of this effect.
Remodeling of Carotid Artery Is Associated With Increased Expression of Matrix Metalloproteinases in Mouse Blood Flow Cessation Model

Background —The matrix-degrading activity of matrix metalloproteinases (MMPs), required for cell migration and general tissue reshaping, is thought essential for pathological arterial remodeling in atherosclerosis and restenosis. Methods and Results —We triggered remodeling of the carotid artery in C57BL/6 mice by blood flow cessation to study the relationship with gelatinases MMP-9 and MMP-2. Ligated and contralateral carotid arteries from ligated and sham-operated mice were harvested fresh, for biochemical analyses, or were perfusion-fixed, for histological studies, at 0, 1, 3, 7, 14, and 28 days after ligation. An early statistically significant ( P Conclusions —MMP-9 induction is associated with the formation of intimal hyperplasia and does not require frank mechanical injury. Our data also show that a significant increase in MMP-9 expression preceded the positive geometrical remodeling of arteries, suggesting a potentially beneficial role for this matrix-degrading enzyme.
Should we leverage natural-language knowledge? An analysis of user errors in a natural-language-style programming language

Should programming languages use natural-language-like syntax? Under what circumstances? What sorts of errors do novice programmers make? Does using a natural- language-like programming language lead to user errors? In this study, we read the entire online interactions of sixteen children who issued a total of 35,047 commands on MOOSE Crossing, an educational MUD for children, We counted and categorized the errors made. A total d 2,970 errors were observed. We define natural-language errors as those errors in which the user failed to distinguish between English and code, issuing an incorrect command that was more English-like than the correct one. A total of 314 natural-language errors were observed. In most of those errors, the child was able to correct the problem either easily (41.1% of the time) or with some effort (20.7%). Natural-language errors were divided into five categories. In order from most to least frequent, they are: syntax errors, guessing a command name by supplying an arbitrary English word, literal interpretation of metaphor, assuming the system is keeping more state information than is actually the case, and errors of operator precedence and combination. We believe that these error rates are within acceptable limits, and conclude that leveraging users natural-language knowledge is for many applications an effective strategy for designing end-user-programming languages.
Child and caregiver psychosocial functioning in pediatric immunodeficiency disorders.

Background Children with chronic illness have been found to be at an increased risk of behavioral and emotional difficulties. To date, children with pediatric immunodeficiency disorders (PIDDs) and their families have not been the focus of extensive published psychosocial research. Objective To determine if children with PIDDs and their caregivers have altered psychosocial function and whether the severity of the PIDD was associated with such difficulties. Methods Twenty children with PIDDs and 20 children with asthma were recruited for this study. Children and their caregivers completed various psychosocial questionnaire forms. Responses were compared with normative data for the appropriate measure and with other variables. Results Higher frequencies of children with PIDDs were found to have a number of elevated psychosocial concerns when contrasted with normative data, particularly from parent report. These concerns included depression, anxiety, somatization, social withdrawal, and social skills. The severity of the PIDDs was significantly associated with a number of behavioral adjustment issues, including receiving psychiatric diagnoses and special education services. Although children with PIDDs had significantly more psychiatric diagnoses than did asthmatic children, these groups did not differ significantly on questionnaire scores regarding child or caregiver psychosocial adjustment. Conclusions Children with PIDDs have significant behavioral problems. Children receiving intravenous immunoglobulin or immunomodulatory treatments were reported to have more problems than children not receiving them. This study highlights the need for further research in psychosocial functioning of children with PIDDs in an effort to develop interventions to promote their overall adjustment.
Dynamic and Quasi-Static Propagation of Compaction Waves in a Low-Density Epoxy Foam

We conducted dynamic and quasi-static compression experiments with low-density (ρ = 120 kg/m3) epoxy foam specimens. The specimens had a 10.0-mm-square cross-section and a length of 19.3 mm. Dynamic experiments were conducted with a modified split Hopkinson pressure bar (SHPB), and the quasi-static experiments were conducted with a hydraulic load frame device (MTS-810). In both cases, the specimens were loaded from one end at a constant velocity. Equally spaced grid lines were marked on the specimens to monitor the deformation history. Digital images taken at equally spaced time intervals gave the positions of each grid line. These images showed that a constant end-face velocity V produced a compaction wave front that traveled at a constant velocity C in both dynamic and quasi-static experiments. We described these results with a shockwave analysis that used a locking solid material model.
American Indians in feature films: beyond the big Screen

Purpose – The purpose of this paper is to examine whether library collections accurately represent the breadth of portrayals of American Indians in feature film. It also provides collection development resources for developing and strengthening feature film collections by and about American Indians. Design/methodology/approach – This study compares WorldCat holdings of a sample of theatrically released films about American Indians with independent American Indian-made films. Findings – WorldCat holdings as a whole do not represent the breadth of portrayals of American Indians in feature film. Originality/value – There are no studies that examine library holdings of feature films by and about American Indians. This paper presents an opportunity to examine our collecting habits and recommends resources for building feature film collections that better represent the manifold Native American experience.
Planting Method Affects Yield of Summer Squash

ABSTRACT Effects of planting methods and row cover on the production of yellow crookneck squash, Cucurbita pepo L. var. melopepo Alef., were evaluated over a two-year period at the E.V. Smith Research Center, Shorter, Alabama. Summer squash was direct-seeded or transplanted in the field with or without black plastic mulch and grown with or without row cover. Yield of transplanted squash was significantly higher than that of direct-seeded squash. Except for plant height, neither plastic mulch nor row cover had an effect on summer squash production.
Likelihood Models for Multivariate Traits in Human Genetics1

The formulation of likelihood functions for multivariate genetic traits in humans is discussed, and exact computing formulas presented for families and simple pedigrees. The model described incorporates all the features of the original ELSTON and STEWART (1971) formulation and that of LANGE et al. (1976, 1983); the integration of the two models is achieved through the introduction of quantities we call “relatedness coefficients.” These are subsequently used to define “status indices,” which turn out to be the key to the computational problem, for the polygenic and mixed models of genetic transmission. The highest order of matrices that enter into the calculation is pXp for a p-variate trait, instead of npXnp, where n is the size of the pedigree. The expressions that are presented can be extended to complex pedigree structures.
Chemical synthesis of N-acetylhexosamine 6-sulfates

The 6-sulfates of N-acetylglucosamine and N-acetylgalactosamine were synthesized using triethylamine-N-sulfonic acids as the sulfating agent. The products of the reaction were purified by fractionation on an anion-exchange column, desalted by means of an ion-retardation resin and converted to the barium salts by passage through the barium form of a cation-exchange resin. Evidence for the homogeneity of the 6-sulfates was provided by chemical analysis, paper chromatography. electrophoresis, colorimetric assay and infrared spectra. Proof for the position of the sulfate group on the primary hydroxyl of the N-acetylhexosamines was provided by periodate consumption studies, the detection of glycolaldehyde sulfate as an end product of periodate oxidation and comparison with a sample of N-acetylglucosamine 6-sulfate synthesized by an unambiguous route. The latter product was prepared via the 6-trityl intermediate as described in the text.
Pharmacology of barbiturate tolerance/dependence: GABAa receptors and molecular aspects

Barbiturates are central nervous system depressants that are used as sedatives, hypnotics, anesthetics and anticonvulsants. However, prolonged use of the drugs produces physical dependence, and the drugs have a high abuse liability. The gamma-aminobutyric acidA (GABAA) receptor is one of barbiturates' main sites of action, and therefore it is thought to play a pivotal role in the development of tolerance to and dependence on barbiturates. Recent advances in the study of the GABAA receptor/chloride channel complex allow us to examine possible mechanisms that underlie barbiturate tolerance/dependence in a new light. In this minireview, we mainly focus on molecular and cellular aspects of the action of barbiturates and the possible mechanisms that contribute to development of tolerance to and dependence on barbiturates.
The varieties of grief experience.

The bereavement literature has yet to show consensus on a clear definition of normal and abnormal or complicated grief reactions. According to DSM-IV, bereavement is a stressor event that warrants a clinical diagnosis only in extreme cases when other DSM categories of psychopathology (e.g., Major Depression) are evident. In contrast, bereavement theorists have proposed a number of different types of abnormal grief reactions, including those in which grief is masked or delayed. In this article, we review empirical evidence on the longitudinal course, phenomenological features, and possible diagnostic relevance of grief reactions. This evidence was generally consistent with the DSM-IV's view of bereavement and provided little support for more complicated taxonomies. Most bereaved individuals showed moderate disruptions in functioning during the first year after a loss, while more chronic symptoms were evidenced by a relatively small minority. Further, those individuals showing chronic grief reactions can be relatively easily accommodated by existing diagnostic categories. Finally, we found no evidence to support the proposed delayed grief category. We close by suggesting directions for subsequent research.
An exploration of point, annual, and lifetime prevalence in characterizing recurrent aphthous stomatitis in USA children and youths.

Background: This report presents and contrasts the prevalence of recurrent aphthous stomatitis (RAS) in 51 471 children and adolescents from two major studies: the Third National Health and Nutrition Examination Survey, 1988–1994 (NHANES III) and the National Survey of Oral Health in USA Schoolchildren, 1986–1987 (OHSC), large USA studies based on multistage probability sampling. Methods: Prevalence proportions, 95% confidence limits and multivariate logistic regression models were constructed for point, 12-month, and lifetime RAS prevalence using SAS-callable SUDAAN 8.0.2. Results: Examinations were performed on 51 471 children and adolescents. Point prevalence was 1.51% (NHANES III) and 1.21% (OHSC); annual prevalence was 19.84% (NHANES III); and lifetime prevalence was 40.18% (OHSC). Multivariate logistic models showed that being white, having a history of herpes labialis, (NHANES III), and being white and an adolescent (OHSC) were predictors of RAS. Conclusions: Caution should be used in interpreting 12-month and lifetime RAS prevalence based a subject's recall.
THE WITCH AND THE PRINCESS: THE FEMININE FANTASTIC IN THE FICTION OF ANNE HÉBERT

(1985). THE WITCH AND THE PRINCESS: THE FEMININE FANTASTIC IN THE FICTION OF ANNE HEBERT. American Review of Canadian Studies: Vol. 15, No. 2, pp. 137-146.
The effects of BMY-14802 against L-DOPA- and dopamine agonist-induced dyskinesia in the hemiparkinsonian rat.

l-DOPA continues to be the primary treatment for patients with Parkinson’s disease; however, the benefits of long-term treatment are often accompanied by debilitating side effects known as dyskinesias. In recent years, several 5-HT1A receptor agonists have been found to reduce dyskinesia in clinical and experimental models of PD. The purported sigma-1 antagonist, BMY-14802 has been previously demonstrated to reduce l-DOPA induced dyskinesia in a 5-HT1A receptor dependent manner. In the present study, we extend these findings by examining the anti-dyskinetic potential of BMY-14802 against l-DOPA, the D1 receptor agonist SKF81297 and the D2 receptor agonist, quinpirole, in the hemi-parkinsonian rat model. In addition, the receptor specificity of BMY-14802’s effects was evaluated using WAY-100635, a 5-HT1A receptor antagonist. Results confirmed the dose-dependent (20 > 10 > 5 mg/kg) anti-dyskinetic effects of BMY-14802 against l-DOPA with preservation of anti-parkinsonian efficacy at 10 mg/kg. BMY-14802 at 10 and 20 mg/kg also reduced dyskinesia induced by both D1 and D2 receptor agonists. Additionally, BMY-14802’s anti-dyskinetic effects against l-DOPA, but not SKF81297 or quinpirole, were reversed by WAY-100635 (0.5 mg/kg). Collectively, these findings demonstrate that BMY-14802 provides anti-dyskinetic relief against l-DOPA and direct DA agonist in a preclinical model of PD, acting via multiple receptor systems and supports the utility of such compounds for the improved treatment of PD.
A method for biomechanical analysis of bicycle pedalling

This paper reports a new method, which enables a detailed biomechanical analysis of the lower limb during bicycling. The method consists of simultaneously measuring both the normal and tangential pedal forces, the EMGs of eight leg muscles, and the crank arm and pedal angles. Data were recorded for three male subjects of similar anthropometric characteristics. Subjects rode under different pedalling conditions to explore how both pedal forces and pedalling rates affect the biomechanics of the pedalling process. By modelling the leg-bicycle as a five bar linkage and driving the linkage with the measured force and kinematic data, the joint moment histories due to pedal forces only (i.e. no motion) and motion only (i.e. no pedal forces) were generated. Total moments were produced by superimposing the two moment histories. The separate moment histories, together with the pedal forces and EMG results, enable a detailed biomechanical analysis of bicycle pedalling. Inasmuch as the results are similar for all three subjects, the analysis for one subject is discussed fully. One unique insight gained via this new method is the functional role that individual leg muscles play in the pedalling process.
The Paf oncogene is essential for hematopoietic stem cell function and development

Hematopoietic stem cells (HSCs) self-renew to maintain the lifelong production of all blood populations. Here, we show that the proliferating cell nuclear antigen-associated factor (Paf) is highly expressed in cycling bone marrow HSCs and plays a critical role in hematopoiesis. Mice lacking Paf exhibited reduced bone marrow cellularity; reduced numbers of HSCs and committed progenitors; and leukopenia. These phenotypes are caused by a cell-intrinsic blockage in the development of long-term (LT)-HSCs into multipotent progenitors and preferential loss of lymphoid progenitors caused by markedly increased p53-mediated apoptosis. In addition, LT-HSCs from Paf(-/-) mice had increased levels of reactive oxygen species (ROS), failed to maintain quiescence, and were unable to support LT hematopoiesis. The loss of lymphoid progenitors was likely due the increased levels of ROS in LT-HSCs caused by treatment of Paf(-/-) mice with the anti-oxidant N-acetylcysteine restored lymphoid progenitor numbers to that of Paf(+/+) mice. Collectively, our studies identify Paf as a novel and essential regulator of early hematopoiesis.
Extended lung preservation with UW solution does not adversely affect graft outcome.

INTRODUCTION: In orthotopic lung transplantation (OLT) in humans, 6 hours is generally regarded as the extent of total ischemic time. At UW, our practice has been to use organs that have sustained greater than 6 hours of cold ischemic time for transplantation. Standard preservation techniques include 1mg of PGE prior to cross clamp, infusion of 4L UW solution (4C), and retrograde pulmonary vein flushing of 1000cc UW solution per lung. METHODS: From October 1988 to March 1999, 122 consecutive OLT’s were retrospectively analyzed for preservation time (PT, cross clamp to pulmonary re-perfusion) and outcome (time to poor function). Poor function was defined as time to BOS1 (.20% decrease in FEV1 from post-op baseline) or graft loss. Recipients were divided into two groups; Group 1 PT,8hrs (n580), Group 2 PT.8hrs (n542). Groups were further sub divided by donor age; a ,22yrs, b 23-37yrs, c .38yrs. Bilateral OLT recipients PT were time to second lung re-perfusion. Inter group significance (p,0.05) was determined using chi-square and life table analysis. RESULTS: There were no significant differences between the two groups in terms of recipient age, recipient sex, donor age, and donor sex. Group 1 had significantly more COPD patients (p50.011), whereas Group 2 had significantly more bilateral transplant recipients (p50.0018). There were no significant differences between the two groups in terms of outcome (p50.139). When sub groups were examined for outcome vs. donor age, no significant difference was noticed: Group 1a vs 2a (p50.2953), Group 1b vs 2b (p50.6426) and Group 1c vs 2c (p50.3922). CONCLUSIONS: Preservation times in human orthotopic lung transplantation can be extended beyond 8 hours using UW solution without significantly compromising recipient outcomes.
Construction of protein backbone pieces using segment-based FBCCD and Cryo-EM skeleton

Cryo-Electron Microscopy is a biophysical technique that generates volumetric images of macromolecules. Although it is hard to distinguish the backbone from the density map at medium resolutions such as 5-10A, the location of major secondary structure traces and the skeleton can be detected from such density maps. We introduce an effective method to construct pieces of backbone conformations for α-helices, β-strands and loops using α-traces, β-traces and skeleton trace that can be detected from a density map. A test of nineteen cases shows that our fragment-based FBCCD method can quickly build a model that aligns well with a spline trace with a small RMSD from the native.
Fine structure mapping and phenotypic analysis of five temperature-sensitive mutations in the second largest subunit of vaccinia virus DNA-dependent RNA polymerase

We have used plasmid clones spanning the region encoding the 132-kDa subunit of the cowpox virus RNA polymerase (CPV rpo 132) to marker rescue each of five vaccinia virus (VV) temperature sensitive (ts) mutants, ts 27, ts 29, ts 32, ts 47, and ts 62, which together constitute a single complementation group. The experiments fine-map the vaccinia mutations to a 1.3-kb region containing the 3' end of the CPV rpo 132 gene. Phenotypic characterization shows that all five mutants are affected to varying extents in their ability to synthesize late viral proteins at the nonpermissive temperature, similar to other ts mutants with lesions in the 22- and the 147-kDa subunits of the VV RNA polymerase. Two mutants, ts 27 and ts 32, exhibit a delay in the synthesis of late viral proteins at both the permissive and the nonpermissive temperatures. We conclude that the five VV mutants affect the 132-kDa subunit of the VV RNA polymerase. Additional genetic experiments demonstrate intragenic complementation between ts 62 and three other members of this complementation group, ts 27, ts 29, and ts 32.
Optical frequency measurements of 6 s S 1 ∕ 2 2 – 6 p P 3 ∕ 2 2 transition in a Cs 133 atomic beam using a femtosecond laser frequency comb

Optical frequencies of the hyperfine components of the ${D}_{2}$ line in $^{133}\mathrm{Cs}$ are determined using high-resolution spectroscopy and a femtosecond laser frequency comb. A narrow-linewidth probe laser excites the $6s\phantom{\rule{0.2em}{0ex}}^{2}S_{1∕2}(F=3,4)\ensuremath{\rightarrow}6p\phantom{\rule{0.2em}{0ex}}^{2}P_{3∕2}(F=2,3,4,5)$ transition in a highly collimated atomic beam. Fluorescence spectra are taken by scanning the laser frequency over the excited-state hyperfine structure. The laser optical frequency is referenced to a Cs fountain clock via a reference laser and a femtosecond laser frequency comb. A retroreflected laser beam is used to estimate and minimize the Doppler shift due to misalignment between the probe laser and the atomic beam. We achieve an angular resolution on the order of $5\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}6}\phantom{\rule{0.3em}{0ex}}\mathrm{rad}$. The final uncertainties $(\ensuremath{\sim}\ifmmode\pm\else\textpm\fi{}5\phantom{\rule{0.3em}{0ex}}\mathrm{kHz})$ in the frequencies of the optical transitions are a factor of 20 better than previous results [T. Udem et al., Phys. Rev. A 62, 031801 (2000).]. We find the centroid of the $6s\phantom{\rule{0.2em}{0ex}}^{2}S_{1∕2}\ensuremath{\rightarrow}6p\phantom{\rule{0.2em}{0ex}}^{2}P_{3∕2}$ transition to be ${f}_{D2}=351\phantom{\rule{0.2em}{0ex}}725\phantom{\rule{0.2em}{0ex}}718.4744(51)\phantom{\rule{0.3em}{0ex}}\mathrm{MHz}$.
A note on interpreting damn expressives: Transferring the blame

Expressives like damn convey a negative attitude toward an entity or toward a situation. What is particularly interesting about such expressions is the looseness of the relation between their syntax, which is the syntax of normal attribute adjectives, and their interpretation (Potts 2005, 2007). An experiment on various negative expressives manipulated the placement of the expressive as a prior utterance, or inside the subject or inside an object of the verb or preposition. Experimental participants were asked what the speaker was most likely to have a negative attitude towards − the subject, the object, or the entire situation. The test items were of two types, ‘non-causal’ and ‘causal’, exemplified by The holiday is on the damn weekend and The dog is on the damn couch. In the non-causal items, the subject (holiday) cannot plausibly be taken as being responsible for the state of affairs described. However, in the causal items, the subject might be responsible for the state of affairs described. The same range of interpretations was observed for all placements of damn. The prior utterance condition (Damn. The dog is on the couch.) yielded more entire situation interpretations than the sentence-internal damn items. Overall, subject damn items yielded more subject interpretations than object damn items. However, as predicted by the hypothesis that blame would devolve on a potentially responsible agent (the culprit hypothesis), there were more subject interpretations in the causal items than in the non-causal items. The results suggest that considerable pragmatic inferencing is involved in the interpretation of expressives, consistent with a proposal that an expressive constitutes a separate speech act.
Alfalfa cyclitols in the honeydew of an aphid

Abstract The free cyclitols pinitol, ononitol and myo-inositol occur in the honeydew (excreta) of pea aphids (Acyrthosiphon pisum) which feed on pea aphid-susceptible alfalfa (Medicago sativa cv Caliverde). These cyclitols also occur in the leaves and stems of alfalfa. Aphids were incapable of de novo synthesis of these cyclitols. Honeydew production by the pea aphid results from ingesting phloem-sap, so the occurrence of cyclitols in honeydew results from their translocation in the phloem. The relatively high content of myo-inositol in honeydew indicates that it is selectively translocated. The most abundant alfalfa cyclitol, pinitol, had no effect on aphid feeding behavior at concentrations up to 1% (w/v; artificial diet).
A counting renaissance

Motivation: Statistical methods for comparing relative rates of synonymous and non-synonymous substitutions maintain a central role in detecting positive selection. To identify selection, researchers often estimate the ratio of these relative rates () at individual alignment sites. Fitting a codon substitution model that captures heterogeneity in across sites provides a reliable way to perform such estimation, but it remains computationally prohibitive for massive datasets. By using crude estimates of the numbers of synonymous and non-synonymous substitutions at each site, counting approaches scale well to large datasets, but they fail to account for ancestral state reconstruction uncertainty and to provide site-specific estimates. Results: We propose a hybrid solution that borrows the computational strength of counting methods, but augments these methods with empirical Bayes modeling to produce a relatively fast and reliable method capable of estimating site-specific values in large datasets. Importantly, our hybrid approach, set in a Bayesian framework, integrates over the posterior distribution of phylogenies and ancestral reconstructions to quantify uncertainty about site-specific estimates. Simulations demonstrate that this method competes well with more-principled statistical procedures and, in some cases, even outperforms them. We illustrate the utility of our method using human immunodeficiency virus, feline panleukopenia and canine parvovirus evolution examples. Availability: Renaissance counting is implemented in the development branch of BEAST, freely available at http://code.google.com/p/beast-mcmc/. The method will be made available in the next public release of the package, including support to set up analyses in BEAUti. Contact:philippe.lemey@rega.kuleuven.be or msuchard@ucla.edu Supplementary information:Supplementary data are available at Bioinformatics online.
Panel - the technological literacy of undergraduates: identifying the research issues

This panel reported the results of a workshop and symposium on the technological literacy of undergraduates convened at the National Academy of Engineering on April 18-19, 2005. This National Science Foundation sponsored workshop sought to identify and define the current research issues regarding the broad understanding of technology by all undergraduates. Participants included individuals who successfully implemented courses on technological literacy for undergraduates, representatives other disciplines such as Science Technology and Society (STS), history of technology, education, and the humanities, and representatives of the National Science Foundation and the National Academy of Engineering. The symposium included: a review of successful implementations, obstacles to courses on technology, learning objectives and student outcomes, relevant assessment tools and techniques, strategies for developing a scholarly community in the area, potential means of stimulating growth of interest in the topic, implementation in different types of institutions including community colleges, perspectives and issues concerning women and underrepresented minorities
Patient-to-Patient Variation of Susceptibility-Induced B0 Field in Bilateral Breast MRI

Purpose To evaluate inter-subject variability of susceptibility-induced static field inhomogeneity in breast and to assess effectiveness of whole-body higher order shimming applied to bilateral breast.
Distributed algorithms for sleep scheduling in wireless sensor networks

It has been found that the sensor nodes dissipate a significant proportion of their energy in redundant sensing and idle listening. The former occurs when multiple sensor nodes perform their sensing activity in the same region. The latter occurs when sensor nodes have their radios switched on awaiting incoming communication from other sensor nodes, but none is received since no sensor node is wanting to communicate with it. Researchers have proposed putting the sensors and/or the radios of sensor nodes to sleep (switch them off) so as to conserve energy. The task of scheduling when the sensors and/or radios need to be in sleep/active mode is referred to as sleep scheduling. Sensor sleeping may result in interesting events being missed by the network or may lead to a lower quality of data being sensed. Radio sleeping may lead to communication delays in the network. In this work we propose several distributed algorithms to perform sensor and radio sleep scheduling in wireless sensor networks while trying to minimize its negative impact
Dyspnea--heart or lungs?

Dyspnea is a common complaint. A wide variety of conditions can give rise to dyspnea, but by far the most common are disorders of the heart and lungs. For most patients, establishing the predominant cause of dyspnea is not difficult. A thorough history is important, with particular attention being paid to activities that reproducibly cause or are associated with dyspnea. The patient’s daily activities and the degree to which dyspnea interferes with these activities are informative because the symptom of dyspnea is not always associated with impaired exercise tolerance. A complete physical examination and laboratory evaluation, including routine blood tests, chest roentgenogram, electrocardiogram, and pulmonary function tests, should be performed. Spirometry (forced vital capacity, forced expiratory volume in 1 second, and maximal voluntary ventilation) is usually sufficient, unless there is suspicion of parenchymal lung disease. In that case, complete pulmonary function testing, including determinations of lung volumes and diffusing capacity for carbon monoxide, is indicated. If the patient has a clinical history of bronchospasm, spirometry after the administration of a bronchodilator is useful. In the patient with suspected bronchospasm, a bronchial challenge test (spirometry before and after exercise, methacholine, or cold air hyperventilation) may be diagnostic. Results of the above-mentioned tests are occasionally not consistent with the magnitude of the patient’s dyspnea, or there may be evidence for disease of both the heart and the lungs. In this setting, cardiopulmonary exercise testing has proved valuable. Two basic questions are addressed by exercise testing: (1) to what degree is the patient objectively impaired (that is, is dyspnea organically based)? and (2) which organ system is predominantly at fault? Answering the former question is not trivial, for it has been clearly shown that the clinical estimation of exercise tolerance