cssi/SciSciGPT-SciSciNet huggingface dataset:
Munc18c phosphorylation by the insulin receptor links cell signaling directly to SNARE exocytosis

How the Sec1/Munc18–syntaxin complex might transition to form the SNARE core complex remains unclear. Toward this, Munc18c tyrosine phosphorylation has been correlated with its dissociation from syntaxin 4. Using 3T3-L1 adipocytes subjected to small interfering ribonucleic acid reduction of Munc18c as a model of impaired insulin-stimulated GLUT4 vesicle exocytosis, we found that coordinate expression of Munc18c–wild type or select phosphomimetic Munc18c mutants, but not phosphodefective mutants, restored GLUT4 vesicle exocytosis, suggesting a requirement for Munc18c tyrosine phosphorylation at Tyr219 and Tyr521. Surprisingly, the insulin receptor (IR) tyrosine kinase was found to target Munc18c at Tyr521 in vitro, rapidly binding and phosphorylating endogenous Munc18c within adipocytes and skeletal muscle. IR, but not phosphatidylinositol 3-kinase, activation was required. Altogether, we identify IR as the first known tyrosine kinase for Munc18c as part of a new insulin-signaling step in GLUT4 vesicle exocytosis, exemplifying a new model for the coordination of SNARE assembly and vesicle mobilization events in response to a single extracellular stimulus.
An Open Letter to Melford E. Spiro

Then one morning we had to stop. One of the tin lizzies was on the blink, and everybody got out to help. Then something happened that amazed me. I had made up my mind that these men were straight out of the Stone Age. I myself am not a mechanic; I hate machines; I am all thumbs; I don't understand machines; horses, yes; machines, no. And here I was, watching these Stone Age men unscrew and rescrew and take things apart or out of the engine and spread them on a piece of canvas on the ground ... but the amazing thing to me was their argumentation. It was perfectly logical. "... Can't be the ignition, look, I get a spark... I tell you, it's the transmission ... Now pull that lever..." Maybe I was over-simplifying because the simplest machine smells of magic to me ... But certainly they made use of logic just as any white man would. Finally the engine, or whatever was wrong, was repaired. Then I overheard one young fellow say to another: "You know why this happened? Because he has been sleeping with his woman while she was menstruating! That's against the rules."
Categorization of enzyme deactivations using a series-type mechanism

Abstract A series-type enzyme deactivation model involving an active enzyme precursor and a final enzyme state with possible non-zero activity is proposed to categorize enzyme deactivation curves. The enzyme activity is a weighted function of the active enzyme states. The deactivation curves may be broadly classified into two major categories wherein the activity is either always less than or it may be more than the initial activity for some time period. Data taken from the literature may be classified into 14 cases. Complex enzyme deactivation curves exhibiting enzyme stabilization and a flex are some of the features that are classified.
Microbial communities in the tonsils of healthy pigs

The tonsils of mammals such as humans and pigs are colonized with an extensive microbiota and are frequently the site for asymptomatic carriage of bacterial pathogens. The goal of this study was to determine the composition of the microbial community of the tonsils in healthy pigs. Tonsils were collected from eight pigs from two different healthy herds. Samples of the tonsils from each pig were used for culture dependent and culture independent identification of the microbial community. Aerobic cultivation identified Pasteurella multocida, Actinobacillus spp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus suis, Streptococcus dysgalactiae, and Escherichia coli from ≥ 50% of the pigs in both herds. For culture independent studies, microbial community members were identified by 16S rRNA sequences using the Ribosomal Database Project Pipeline programs developed at Michigan State University. Dominant genera identified by 16S rRNA analysis in pigs from both herds included Actinobacillus, Haemophilus, Pasteurella, Porphyromonas, Fusobacterium, Bacteroides, and Prevotella. These genera were detected in nearly every pig regardless of herd. In contrast, there was an asymmetric distribution of minor genera between the two herds, suggesting herd-specific differences in the microbial communities. In addition, we demonstrated primer bias between two frequently used forward primers when targeting the tonsillar community. Our results suggest that the major bacterial community members found in porcine tonsils are the same regardless of herd, while the minor species are unique to each herd. This is the first analysis using 16S rRNA sequence libraries of the composition of microbial communities in the porcine upper respiratory tract.
Analytic approximations for (s,S) inventory policy operating characteristics

The operating characteristics of (s,S) inventory systems are often difficult to compute, making systems analysis a tedious and often expensive undertaking. Approximate expressions for operating characteristics are presented with a view towards simplified analysis of systems behavior. The operating characteristics under consideration are the expected values of: total cost per period, period-end inventory, period-end stockout quantity, replenishment cost per period, and backlog frequency. The approximations are obtained by a two step procedure. First, exact expressions for the operating characteristics are approximated by simplified functions. Then the approximations are used to design regression models which are fitted to the operating characteristics of a large number of inventory items with diverse parameter settings. Accuracy to within a few percent of actual values is typical for most of the approximations.
Assessment of clinical and nonclinical characteristics associated with health-related quality of life in patients with high-grade gliomas: a feasibility study

Purpose Results from several studies suggest that there is value in evaluating the association between nonclinical characteristics of patients and quality of life (QoL), but few studies have focused on brain cancer. The primary goal of this feasibility study was to explore the relationship between clinical factors and nonclinical factors and QoL in brain cancer patients.
The clinical spectrum of hexosaminidase deficiency diseases

Hexosaminidase deficiency diseases or G m2 -gangliosidoses were originally described as infantile encephalopathies. Recently, hexosaminidase deficiencies have been found with different phenotypes, including juvenile and adult encephalopathies, cerebellar ataxias, and motor neuron diseases. Individual cases have resembled Ramsey-Hunt syndrome, olivopontocerebellar ataxia, Friedreich ataxia, amyotrophic lateral sclerosis, Kugelberg-Welander disease, Fazio-Londe disease, and Charcot-Marie-Tooth disease. Tremor, dystonia, spastic paresis, and psychosis have been seen. Since few diagnosable causes for these system atrophies are known, these patients should be tested for hexosaminidase deficiency. These recessive disorders fit a multiple loci/multiple alleles genetic scheme, and a clinical genetic classification is presented.
Rapid removal of vancomycin by continuous veno-venous hemofiltration.

We describe a 14-year-old girl with staphylococcal (coagulase-negative) ventriculo-peritoneal shunt infection, who developed oliguric acute renal failure and was found to have a serum vancomycin concentration of 250 µg/ml. Since only about 10%–50% of vancomycin is bound to protein in blood, we employed continuous veno-venous hemofiltration (CVVH) with a high ultrafiltration rate (1,800 ml/h) for increased convective clearance to remove vancomycin, which may have contributed to the acute renal failure. At the end of 38 h of CVVH, the vancomycin concentration had decreased in an exponential manner to 27 µg/ml. Over the subsequent 3–4 days, her renal function improved and the vancomycin concentration decreased further to <5 µg/ml. In conclusion, we believe that a high serum vancomycin concentration may be nephrotoxic and demonstrate that CVVH can be used effectively to remove vancomycin in children with acute renal failure.
Annealing environment effects in solid-phase epitaxial regrowth of Fe-implanted Al2O3☆

Abstract Samples of c -axis Al 2 O 3 were implanted with Fe (160 keV, 4 × 10 16 cm −2 ) at liquid nitrogen temperature and then thermally annealed at temperatures of 900, 960 and 1100°C in an oxidising environment (flowing O 2 ) or in a reducing environment (flowing 96% Ar, 4% H). Rutherford backscattering spectrometry, ion channeling, and transmission electron microscopy of the crystals revealed differences in the annealing characteristics of the implanted layers that depended on the annealing environment. These results indicate the importance of the annealing atmosphere in determining the characteristics of epitaxially regrown layers in ion-implanted and thermally annealed Al 2 O 3 .
The timing of major life events: Effects of departing from the social clock

It is widely believed that social norms govern the timing of major life events, such that events experienced off time are considerably more stressful than events experienced on time. Experiencing life events either earlier or later than one's peers presumably reduces opportunities for social support and may also invite social disapproval. Relatively few empirical studies have investigated these ideas, however, and those that have suffer from several limitations. The present study made use of a general population survey to investigate the effects of normative versus nonnormative timing of major life events on psychological functioning, interpersonal resources, and interpersonal tensions. Desirable and undesirable events were examined separately, as were the effects of departures from perceived versus statistical age norms. The results of the study offered only limited support for social clock theory. Implications for further research and for the relevance of the theory in a less age-differentiated society are discussed.
The extent of the odontoblast process in rhesus monkeys (Macaca mulatta) as observed by scanning electron microscopy

Abstract Monkeys were perfused with Karnovsky phosphate-buffered formalin-glutaraldehyde (PBF-GTA). Molars were removed and postfixed in PBF-GTA, demineralized in EDTA, freeze-fractured, and critical-point dried. Odontoblast processes were observed in tubules of the predentine, the pulpal inner third of dentine and in the peripheral dentine, but not in the middle third. Peripheral processes showed close adaptation to dentinal tubules with branches penetrating into canaliculi close to the dentine-enamel junction.
Antiretroviral therapy for prevention of HIV transmission: Potential role for people who inject drugs in Central Asia

Interest in the use of antiretroviral therapy (ART) for prevention stems from mounting evidence from research studies demonstrating that ART is associated with a decrease in sexual HIV transmission among serodiscordant couples and, perhaps, in other populations at risk. There is paucity of data on the efficacy of ART for prevention in key populations, including persons who inject drugs (PWID). In this paper, we examine the current status of HIV services for PWID in Central Asia, the use of ART by this population and explore ART for prevention for PWID in this context. We also discuss research and implementation questions with relevance to such a strategy in the region.
Dispersion hazard from spills of LNG on land and on water

Abstract Previously published data on the dispersion of vapours from LNG spills on both land and water are correlated using common dispersion relationships
Ion-selective supported liquid membranes placed under steady-state diffusion control.

Supported liquid membranes are used here to establish steady-state concentration profiles across ion-selective membranes rapidly and reproducibly. This opens up new avenues in the area of nonequilibrium potentiometry, where reproducible accumulation and depletion processes at ion-selective membranes may be used to gain valuable analytical information about the sample. Until today, drifting signals originating from a slowly developing concentration profile across the ion-selective membrane made such approaches impractical in zero current potentiometry. Here, calcium- and silver-selective membranes were placed between two identical aqueous electrolyte solutions, and the open circuit potential was monitored upon changing the composition of one solution. Steady state was reached in ∼1 min with 25-μm porous polypropylene membranes filled with bis(2-ethylhexyl) sebacate doped with ionophore and lipophilic ion exchanger. Ion transport across the membrane resulted on the basis of nonsymmetric ion-exchange process...
On the mechanism of the yolk-lysis reaction

(1) The reaction by which yolk platelets isolated from frog eggs undergo lysis in the presence of low concentrations of calcium ions is described and kinetic data are presented. (2) A crude yolk precipitate, prepared by salting-in and reprecipitating the material of intact yolk platelets, undergoes the same reaction as do the intact platelets. (3) Data are presented on the pH dependence and thermal inhibition of the reaction. (4) The yolk contains a material, perhaps a protein, which catalyzes the lysis reaction. This material is not the soluble product of the reaction, since the kinetics are not those of an autocatalytic process. (5) A possible mechanism for the reaction is discussed.
Effect of nicardipine on determinants of myocardial ischemia occurring during acute coronary occlusion produced by percutaneous transluminal coronary angioplasty

In 10 patients undergoing percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery (LAD), the clinical, electrocardiographic and hemodynamic effects of acute intravenous calcium channel antagonism with nicardipine (2 mg over 1 minute, followed by a constant infusion of 25 to 50 micrograms/min) were assessed during temporary LAD occlusion. Onset of myocardial ischemia during coronary occlusion was prevented or delayed after administration of nicardipine in 7 of the 10 patients. During infusion of nicardipine and during LAD occlusion, residual great cardiac vein blood flow increased in 9 of 10 patients compared with residual flow during occlusion before nicardipine (10%, p less than 0.05). Nicardipine also decreased mean aortic pressure, but was associated with a reflex-mediated increase in heart rate. Overall, the double product, an index of global myocardial oxygen demand, decreased 7% (p less than 0.05). Thus, nicardipine usually diminished ischemia induced by acute transient coronary occlusion by increasing collateral flow while oxygen demand decreased.
Specific heat of YBa2Cu3O7−σ: paramagnetic centers; evidence for line nodes in the energy gap

Specific-heat data on YBa 2 Cu 3 O 7-δ , 0 < δ <0.2, have been analyzed to show the presence of spin-2, as well as spin-1/2, paramagnetic centers. Evidence of line nodes in the energy gap, including conformity to a predicted scaling relation, is reported.
Aerobic Capacity in Patients Entering Cardiac Rehabilitation

Background Symptom-limited treadmill testing is commonly performed on entry to cardiac rehabilitation (CR) for its prognostic value and to design a safe and effective exercise program. Normative values for this evaluation are not available. The primary goals of this study were to establish normative values for peak aerobic capacity (peak V(O2)) for patients entering CR and to create nomograms for conversion of peak V(O2) to a percentage of predicted exercise capacity,stratified by age, gender, and diagnosis. Methods and results Peak V(O2) was measured in 2896 patients entering CR from 1996 to 2004. Peak V(O2) was higher in men than in women: 19.3 +/- 6.1 mL.kg(-1).min(-1) (range, 5.2 to 49.7 mL.kg(-1).min(-1)) versus 14.5 +/- 3.9 mL.kg(-1).min(-1) (range, 3.8 to 29.8 mL.kg(-1).min(-1)) (P Conclusions Values of peak V(O2) on entry to CR are extremely low, particularly in women, approaching values seen with severe chronic heart failure. This underscores the importance of CR after a major cardiac event to improve physical function and long-term prognosis.
Sacred pictures, sacred rocks: Ideological and social space in the North Norwegian stone age

Space is not a passive arena for adaptation but a social and ideological product actively manipulated in social strategies. Late Stone Age rock carvings at Alta, Finnmark, are viewed as a discourse legitimating social relations. Geographical fixing of this discourse produces spatial inequalities in access to information. These inequalities are part of the matrix of social relations for which the rock art serves as a legitimation discourse. Lithic materials are linked to this discourse in a common ‘spatial ideology’. Since lithics are portable, they operate as mobile signifiers for the ideological system encoded in the rock carvings, offsetting spatial inequalities.
The identification of phosphorylated neo-inositol as an anionic component of the Amoeba cell surface☆☆☆

Abstract A nonreducing polyol, previously called pre-mannose [Allen et al. (1974) J. Cell Biol. 60 , 26–38], present in the isolated cell surface of Amoeba has been identified as neo inositol. The polyol was present on the cell surface as a highly phosphorylated but nonpolymerized phosphate ester. Cold acid extraction of Amoeba homogenates and alkaline precipitation of the acid-soluble fraction gave a preparation containing the polyol as the major neutral sugar residue. The polyol was identified by gas-liquid chromatography and mass spectrometry of its trimethylsilyl ether and acetate ester derivatives. The acid-labile phosphate ester present in isolated surface fractions was found to be separable from the acid-stable phosphate ester. Current data indicated that the labile phosphate was polyphosphate.
SU-GG-J-81: Geometric Accuracy of Imaging Systems on Trilogy MX Using an Automated Geometric Test Tool

Purpose: To characterize the geometric accuracy of the imaging systems of a newly designed accelerator (Trilogy MX, Varian Medical Systems, Palo Alto, CA) using a fully automated, geometric calibration tool. Methods: A geometric calibration tool ‐ consisting of a phantom containing 16 tungstencarbide ball‐bearings and a MV collimator insert with a central pin ‐ has been used to characterize the geometric coincidence of MV and kV imaging equipment with the radiation isocenter of Trilogy MX. Three sets of data are acquired: MV images at multiple MV collimator rotations, and both MV and kV images at multiple gantry angles. The MV collimatorimages are used to identify the central axis of the MV beam, and the MV images at different gantry angles are then used to identify the MV radiation isocenter. Calculations then determine the corrections needed to move both the MV and kV imagers so that their central pixels exactly align with the projection of the radiation isocenter. The Trilogy MX employs a new control system so corrections can be downloaded to the control system and used to physically correct the imager positions while the gantry is being rotated. The positions of the imagers have been verified using the geometric calibration tool and a Winston‐Lutz test. Results: Coincidence between the MV isocenter ‐ measured using the geometric tool ‐ and the central imager pixels of both imagers was less than ±0.1mm. The coincidence between the central pixels of both imagers and the projection of the Winston‐Lutz BB was better than ±0.3mm. Conclusions: An automated tool for calibrating the geometry of MV and kV imaging equipment has been developed and tested. The tool gives similar results to conventional Winston‐Lutz measurements. The geometric accuracy of the imaging systems of Trilogy MX is better than ±0.3mm.
Racial disparity in fetal aneuploidy risk in an ultrasound screening population: A result of selection bias?

POPULATION: A RESULT OF SELECTION BIAS? DAVID STAMILIO, ANTHONY ODIBO, HARISH SEHDEV, LINDA DUNN, GEORGE MACONES, University of Pennsylvania, Obstetrics and Gynecology, Philadelphia, Pennsylvania, Pennsylvania Hospital, Maternal Fetal Medicine, Philadelphia, Pennsylvania, Chestnut Hill Hospital, Obstetrics and Gynecology, Philadelphia, Pennsylvania OBJECTIVE: There is evidence for racial differences in the incidence of fetal aneuploidy, utilization of prenatal genetic tests, and predictive value of screening markers. Our aim is to compare the risk of fetal aneuploidy across maternal race & to explore potential causes of disparity. STUDY DESIGN: Between 2002 & 2005 we performed a multicenter prospective cohort study of 2900 pregnant patients of variable risk level referred for a fetal ultrasound that included standard aneuploidy markers. A standardized ultrasound was performed between 15 & 22 gestational weeks. Using bivariate and multivariable statistical methods we compared fetal aneuploidy rates across maternal race. We used logistic regression to explore for confounding and sources of racial differences in aneuploidy rates. RESULTS: Patients of African origin were younger, 47% less likely to have an aneuploidy risk factor, underwent a screening ultrasound later in gestation and more commonly received care at the community versus university hospitals than other races. After controlling for multiple confounders, patients of African origin had a fetal aneuploidy rate 80% less than other races.
Support vector machines for predicting distribution of Sudden Oak Death in California

In the central California coastal forests, a newly discovered virulent pathogen ( Phytophthora ramorum ) has killed hundreds of thousands of native oak trees. Predicting the potential distribution of the disease in California remains an urgent demand of regulators and scientists. Most methods used to map potential ranges of species (e.g. multivariate or logistic regression) require both presence and absence data, the latter of which are not always feasibly collected, and thus the methods often require the generation of ‘pseudo’ absence data. Other methods (e.g. BIOCLIM and DOMAIN) seek to model the presence-only data directly. In this study, we present alternative methods to conventional approaches to modeling by developing support vector machines (SVMs), which are the new generation of machine learning algorithms used to find optimal separability between classes within datasets, to predict the potential distribution of Sudden Oak Death in California. We compared the performances of two types of SVMs models: two-class SVMs with ‘pseudo’ absence data and one-class SVMs. Both models performed well. The one-class SVMs have a slightly better true-positive rate (0.9272 ± 0.0460 S.D.) than the two-class SVMs (0.9105 ± 0.0712 S.D.). However, the area predicted to be at risk for the disease using the one-class SVMs (18,441 km 2 ) is much larger than that of the two-class SVMs (13,828 km 2 ). Both models show that the majority of disease risk will occur in coastal areas. Compared with the results of two-class SVMs, the one-class SVMs predict a potential risk in the foothills of the Sierra Nevada mountain ranges; much greater risks are also found in Los Angles and Humboldt Counties. We believe the support vector machines when coupled with geographic information system (GIS) will be a useful method to deal with presence-only data in ecological analysis over a range of scales. © 2004 Elsevier B.V. All rights reserved.
Sustainability Practices in Food Supply Chains: How is Wine Different?

Environmental stewardship has received much attention in the wine industry, but firms must also address social sustainability to be considered a ‘sustainable’ company. In this research, we compare qualitative and quantitative evidence of sustainability practice adoption of wine and other food producers. To this end, we first performed interviews with 14 winery and 18 food processing operations managers or owners in the northwestern United States. We then used the interviews to develop a questionnaire and surveyed all wine and food producers in the same region, receiving responses from 56 wineries and 61 food processors. The results indicate differences in sustainability practices and performance impacts across the two sectors. Specifically, we find that winery managers place more emphasis on certain environmental practices, which in turn improve product quality. Additionally, wineries with higher adoption rates of social sustainability practices find that these efforts pay off in better wine quality and b...
Modern electron accelerators for radiography

Over the past dozen years or so, there have been significant advances in electron accelerators designed specifically for radiography of hydrodynamic experiments. Accelerator technology has evolved to accommodate the radiographers' continuing quest for multiple images in time and space. Improvements in electron beam quality have resulted in smaller radiographic spot sizes for better resolution, while a higher radiation dose now provides improved penetration of large, dense objects. Inductive isolation and acceleration techniques have played a key role in these advances.
Multifocal neoplasia involving the colon and appendix in ulcerative colitis: Pathological and molecular features☆☆☆

A patient with ulcerative colitis, extensive dysplasia, multifocal colon cancer, and an appendiceal cystadenoma is described. A 48-year-old man with a 26-year history of ulcerative colitis (UC) had extensive dysplasia involving nearly the entire colon and four dysplasia-associated mass lesions (DALMs). Four invasive adenocarcinomas were present. This case is the first documentation of a DALM (mucinous cystadenoma) arising in the appendix in the setting of UC. The genetic alterations present in the various lesions were analyzed. The molecular profiles of the neoplastic lesions differed. Mutations were found in p53 and ras genes, and one site showed microsatellite instability in a single genetic locus. These molecular abnormalities develop before invasive cancer develops, and may undergo clonal expansion to create large mucosal patches containing certain cells with genetic alterations. The diversity of the early changes suggests that the recurrent inflammation characteristic of long-standing UC randomly damages genes known to participate in colon carcinogenesis and that it affects multiple target genes. The findings also support a multiclonal origin of synchronous tumors because the molecular phenotypes of the preinvasive lesions differed at various sites.
Assessment of Free Energy Predictors for Ligand Binding to a Methyllysine Histone Code Reader

Methyllysine histone code readers constitute a new promising group of potential drug targets. For instance, L3MBTL1, a malignant brain tumor (MBT) protein, selectively binds mono- and di-methyllysine epigenetic marks (KMe, KMe(2) ) that eventually results in the negative regulation of multiple genes through the E2F/Rb oncogenic pathway. There is a pressing need in potent and selective small-molecule probes that would enable further target validation and might become therapeutic leads. Such an endeavor would require efficient tools to assess the free energy of protein-ligand binding. However, due to an unparalleled function of the MBT binding pocket (i.e., selective binding to KMe/KMe(2) ) and because of its distinctive structure representing a small aromatic "cage," an accurate assessment of its binding affinity to a ligand appears to be a challenging task. Here, we report a comparative analysis of computationally affordable affinity predictors applied to a set of seven small-molecule ligands interacting with L3MBTL1. The analysis deals with novel ligands and targets, but applies widespread computational approaches and intuitive comparison metrics that makes this study compatible with and incremental to earlier large scale accounts on the efficiency of affinity predictors. Ultimately, this study has revealed three top performers, far ahead of the other techniques, including two scoring functions, PMF04 and PLP, along with a simulation-based method MM-PB/SA. We discuss why some methods may perform better than others on this target class, the limits of their application, as well as how the efficiency of the most CPU-demanding techniques could be optimized.
Light Chain Separated from the Rest of the Type A Botulinum Neurotoxin Molecule Is the Most Catalytically Active Form

Botulinum neurotoxins (BoNT) are the most potent of all toxins. The 50 kDa N-terminal endopeptidase catalytic light chain (LC) of BoNT is located next to its central, putative translocation domain. After binding to the peripheral neurons, the central domain of BoNT helps the LC translocate into cytosol where its proteolytic action on SNARE (soluble NSF attachment protein receptor) proteins blocks exocytosis of acetyl choline leading to muscle paralysis and eventual death. The translocation domain also contains 105 A -long stretch of ∼100 residues, known as “belt,” that crosses over and wraps around the LC to shield the active site from solvent. It is not known if the LC gets dissociated from the rest of the molecule in the cytosol before catalysis. To investigate the structural identity of the protease, we prepared four variants of type A BoNT (BoNT/A) LC, and compared their catalytic parameters with those of BoNT/A whole toxin. The four variants were LC + translocation domain, a trypsin-nicked LC + translocation domain, LC + belt, and a free LC. Our results showed that Km for a 17-residue SNAP-25 (synaptosomal associated protein of 25 kDa) peptide for these constructs was not very different, but the turnover number (kcat) for the free LC was 6-100-fold higher than those of its four variants. Moreover, none of the four variants of the LC was prone to autocatalysis. Our results clearly demonstrated that in vitro, the LC minus the rest of the molecule is the most catalytically active form. The results may have implication as to the identity of the active, toxic moiety of BoNT/A in vivo.
Comparison of the mortality profiles of Archaic, Middle Woodland, and Middle Mississippian skeletal populations

Mortality profiles were constructed for four American Indian skeletal populations for the purpose of comparing the frequencies of deaths at given ages between and within the populations. An interpretation of the differential mortality frequencies is then possible. Selected for study were the Archaic population from Indian Knoll, Kentucky, an Illinois Archaic series and a Middle Woodland Hopewellian population, both from the Klunk Mounds in southwestern Illinois, and a Middle Mississippian population from Dickson Mounds, Illinois. It was found that in the Archaic populations there were significantly higher percentages of deaths throughout the first three decades than among either the Hopewell or Middle Mississippian populations. Although the mortality profiles of the latter two groups more closely approximated each other, the average age at death was greater for the Hopewellian population. Suggested are different behavioral adjustments to stress. However, with a few notable exceptions, the fluctuations in the frequencies of death follow similar profiles in the mortality curves, indicating that common to all four populations were certain ages at which time death was more likely to occur. Various interpretations are offered to explain these periods of greater mortality.
The School Counselor's Role in School Dropout Prevention

The role of the school counselor has undergone numerous revisions over the past few decades. The current emphasis on accountability and academic performance of students has forced counselors to scrutinize their role in promoting students' academic success and school completion. In this article, the authors review the problem of school dropout from the school counselor's perspective and offer guidelines for how school counselors can deliver empirically supported strategies to address this problem as part of their comprehensive guidance programs.
A corticotropin-releasing factor receptor antagonist improves urodynamic dysfunction produced by social stress or partial bladder outlet obstruction in male rats

Barrington's nucleus, in the pons, regulates micturition through spinal projections to preganglionic parasympathetic neurons. The stress neuropeptide CRF is prominent in these projections and has an inhibitory influence. Social stress in rats causes urinary retention and abnormal urodynamics resembling those produced by partial bladder outlet obstruction (pBOO), and this is associated with CRF upregulation in Barrington's nucleus. Here, we examined the role of CRF in social stress- and pBOO-induced urodynamic dysfunction by assessing the ability of a CRF1 receptor antagonist to alter these effects. Male rats exposed to repeated resident-intruder stress were administered vehicle or a CRF1 antagonist (NBI-30775) daily prior to the stress. Urodynamic function was recorded in the unanesthetized state 72 h after the final stress. NBI-30775 prevented the increased intermicturition interval, micturition volume, and bladder capacity produced by social stress, but not the increase in CRF expression in Barrington's nucleus neurons. The urinary dysfunction was also partly prevented by shRNA targeting of CRF in Barrington's nucleus, suggesting that stress-induced urinary dysfunction results, in part, from CRF upregulation in Barrington's nucleus and enhanced postsynaptic effects in the spinal cord. Finally, NBI-30775 improved urodynamic function of rats that had pBOO of 2-wk duration when administered daily during the second week but did not block the increase in CRF expression in Barrington's nucleus neurons. These findings implicate a role for Barrington's nucleus CRF in stress- and pBOO-induced urodynamic changes and suggest that CRF1 antagonists may be useful therapeutic agents for the treatment of urinary dysfunction.
Gene transcriptional networks integrate microenvironmental signals in human breast cancer.

A significant amount of evidence shows that microenvironmental signals generated from extracellular matrix (ECM) molecules, soluble factors, and cell–cell adhesion complexes cooperate at the extra- and intracellular level. This synergetic action of microenvironmental cues is crucial for normal mammary gland development and breast malignancy. To explore how the microenvironmental genes coordinate in human breast cancer at the genome level, we have performed gene co-expression network analysis in three independent microarray datasets and identified two microenvironment networks in human breast cancer tissues. Network I represents crosstalk and cooperation of ECM microenvironment and soluble factors during breast malignancy. The correlated expression of cytokines, chemokines, and cell adhesion proteins in Network II implicates the coordinated action of these molecules in modulating the immune response in breast cancer tissues. These results suggest that microenvironmental cues are integrated with gene transcriptional networks to promote breast cancer development.
Genome Rearrangements in Maize Induced by Alternative Transposition of Reversed Ac/Ds Termini

Alternative transposition can induce genome rearrangements, including deletions, inverted duplications, inversions, and translocations. To investigate the types and frequency of the rearrangements elicited by a pair of reversed Ac/Ds termini, we isolated and analyzed 100 new mutant alleles derived from two parental alleles that both contain an intact Ac and a fractured Ac (fAc) structure at the maize p1 locus. Mutants were characterized by PCR and sequencing; the results show that nearly 90% (89/100) of the mutant alleles represent structural rearrangements including deletions, inversions, translocations, or rearrangement of the intertransposon sequence (ITS). Among 37 deletions obtained, 20 extend into the external flanking sequences, while 17 delete portions of the intertransposon sequence. Interestingly, one deletion allele that contains only a single nucleotide between the retained Ac and fAc termini is not competent for further alternative transposition events. We propose a new model for the formation of intertransposon deletions through insertion of reversed transposon termini into sister-chromatid sequences. These results document the types and frequencies of genome rearrangements induced by alternative transposition of reversed Ac/Ds termini in maize.
Automated Drop-on-Demand System with Real-Time Gravimetric Control for Precise Dosage Formulation

Many of the therapies for personalized medicine have few dosage options, and the successful translation of these therapies to the clinic is significantly dependent on the drug/formulation delivery platform. We have developed a lab-scale integrated system for microdosing of drug formulations with high accuracy and precision that is capable of feedback control. The designed modular drug dispensing system includes a microdispensing valve unit and is fully automated with a LabVIEW-controlled computer interface. The designed system is capable of dispensing drug droplets with volumes ranging from nanoliters to microliters with high accuracy (relative standard deviation <1%). We have determined that the system is capable of accurate dosing and in-line real-time gravimetric control.
Esthetic smile preferences and the orientation of the maxillary occlusal plane

Statement of problem The anteroposterior orientation of the maxillary occlusal plane has an important role in the creation, assessment, and perception of an esthetic smile. However, the effect of the angle at which this plane is visualized (the viewing angle) in a broad smile has not been quantified. Purpose The purpose of this study was to assess the esthetic preferences of dental professionals and nondentists by using 3 viewing angles of the anteroposterior orientation of the maxillary occlusal plane. Material and methods After Institutional Review Board approval, standardized digital photographic images of the smiles of 100 participants were recorded by simultaneously triggering 3 cameras set at different viewing angles. The top camera was positioned 10 degrees above the occlusal plane (camera #1, Top view); the center camera was positioned at the level of the occlusal plane (camera #2, Center view); and the bottom camera was located 10 degrees below the occlusal plane (camera #3, Bottom view). Forty-two dental professionals and 31 nondentists (persons from the general population) independently evaluated digital images of each participant's smile captured from the Top view, Center view, and Bottom view. The 73 evaluators were asked individually through a questionnaire to rank the 3 photographic images of each patient as ‘most pleasing,' ‘somewhat pleasing,' or ‘least pleasing,' with most pleasing being the most esthetic view and the preferred orientation of the occlusal plane. The resulting esthetic preferences were statistically analyzed by using the Friedman test. In addition, the participants were asked to rank their own images from the 3 viewing angles as ‘most pleasing,' ‘somewhat pleasing,' and ‘least pleasing.' Results The 73 evaluators found statistically significant differences in the esthetic preferences between the Top and Bottom views and between the Center and Bottom views ( P P Conclusions The esthetic preference for the maxillary occlusal plane was influenced by the viewing angle with the higher (Top) and center views preferred by both dental and nondental evaluators. The participants themselves preferred the higher view of their smile significantly more often than the center or lower angle views ( P
Weak population regulation in ecological time series

How strongly natural populations are regulated has a long history of debate in ecology. Here, we discuss concepts of population regulation appropriate for stochastic population dynamics. We then analyse two large collections of data sets with autoregressive-moving average (ARMA) models, using model selection techniques to find best-fitting models. We estimated two metrics of population regulation: the characteristic return rate of populations to stationarity and the variability of the stationary distribution (the long-term distribution of population abundance). Empirically, longer time series were more likely to show weakly regulated population dynamics. For data sets of length > or = 20, more than 35% had characteristic return times > 6 years, and more than 29% had stationary distributions whose coefficients of variation were more than two times greater than would be the case if they were maximally regulated. These results suggest that many natural populations are weakly regulated.
Recombinant Herpes Simplex Virus Type 1 (HSV-1) Codelivering Interleukin-12p35 as a Molecular Adjuvant Enhances the Protective Immune Response against Ocular HSV-1 Challenge

An important aspect of ocular herpes simplex virus type 1 (HSV-1) vaccine development is identification of an appropriate adjuvant capable of significantly reducing both virus replication in the eye and explant reactivation in trigeminal ganglia. We showed recently that a recombinant HSV-1 vaccine expressing interleukin-4 (IL-4) is more efficacious against ocular HSV-1 challenge than recombinant viruses expressing IL-2 or gamma interferon (IFN-γ) (Y. Osorio and H. Ghiasi, J. Virol. 77:5774-5783, 2003). We have now constructed and compared recombinant HSV-1 viruses expressing IL-12p35 or IL-12p40 molecule with IL-4-expressing HSV-1 recombinant virus. BALB/c mice were immunized intraperitoneally with IL-12p35-, IL-12p40-, IL-12p35+IL-12p40-, or IL-4-expressing recombinant HSV-1 viruses. Controls included mice immunized with parental virus and mice immunized with the avirulent strain KOS. The efficacy of each vaccine in protecting against ocular challenge with HSV-1 was assessed in terms of survival, eye disease, virus replication in the eye, and explant reactivation. Neutralizing antibody titers, T-cell responses, and expression of 32 cytokines and chemokines were also evaluated. Mice immunized with recombinant HSV-1 expressing IL-12p35 exhibited the lowest virus replication in the eye, the most rapid virus clearance, and the lowest level of explant reactivation. The higher efficacy against ocular virus replication and explant reactivation correlated with higher neutralizing antibody titers, cytotoxic-T-lymphocyte activities, and IFN-γ expression in recombinant HSV-1 expressing IL-12p35 compared to other vaccines. Mice immunized with both IL-12p35 and IL-12p40 had lower neutralizing antibody responses than mice immunized with IL-12p35 alone. Our results confirm that recombinant virus vaccines expressing cytokine genes can enhance the overall protection against infection, with the IL-12p35 vaccine being the most efficacious of those tested. Collectively, the results support the potential use of IL-12p35 as a vaccine adjuvant, without the toxicity-associated concerns of IL-12.
A study of the application of the spouted bed technique to wheat drying

A description has been given of a method which can be used to agitate solids that are of too coarse and uniform a particle size to be fluidized satisfactorily. This method has been applied to the drying of wheat. The following variables have been studied on a small pilot-plant scale: feed moisture content, feed rate, bed depth and inlet air temperature. A description has been given of the temperature and humidity profiles within a wheat bed agitated by this technique.
Carro de las donas: Translating Francesc Eiximenis for Queenly Edification

Francesc Eiximenis’ Llibre de les dones (1396) was widely disseminated and read by a diverse array of readers between the fourteenth and the sixteenth centuries, including Queen Isabel the Catholic and her descendants. The Catalan text was not only translated into Castilian in the fifteenth century (Libro de las donas) but was also adapted and refashioned in 1542 by an anonymous author who changed its title to Carro de las donas. My study seeks to investigate how the concept of female sovereignty becomes transformed from Eiximenis’ Catalan original to the 1542 Castilian rendition. A comparison between these two texts and their impact on their recipients equally enable us to validate some hypotheses about the dynamics of reading in the medieval and early modern period, namely, that the popularity of a text neither implies a tacit acceptance of everything contained therein nor inescapably demonstrates that all readers interpreted what they read equally.
Disability: how successful are we in determining disability?

Individuals who have severe back pain have trouble bending, may not be able to put on their shoes, have difficulty in ambulation, and may not be able to clean their own houses. What distinguishes these individuals with low back pain from those afflicted with other conditions (i.e., congestive heart failure, metastatic cancer, symptomatic acquired immune deficiency syndrome) is prognosis. Back pain essentially never shortens life. Acute back pain has a very benign prognosis, with more than 90% of the individuals returning to functional status equivalent to their baseline status within 3 months of the onset of pain. Patients who have chronic back pain have a significantly worse prognosis, but most cohort studies show that substantial numbers of chronic back pain patients improve over time with supportive therapy.
Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans

A major challenge in neuroscience is to reliably activate individual neurons, particularly those in deeper brain regions. Current optogenetic approaches require invasive surgical procedures to deliver light of specific wavelengths to target cells to activate or silence them. Here, we demonstrate the use of low-pressure ultrasound as a non-invasive trigger to activate specific ultrasonically sensitized neurons in the nematode, Caenorhabditis elegans. We first show that wild-type animals are insensitive to low-pressure ultrasound and require gas-filled microbubbles to transduce the ultrasound wave. We find that neuron-specific misexpression of TRP-4, the pore-forming subunit of a mechanotransduction channel, sensitizes neurons to ultrasound stimulus, resulting in behavioural outputs. Furthermore, we use this approach to manipulate the function of sensory neurons and interneurons and identify a role for PVD sensory neurons in modifying locomotory behaviours. We suggest that this method can be broadly applied to manipulate cellular functions in vivo.
Case 34: An Aggressive Surgeon

This is your third day in a new hospital. You are assigned to do a general anesthetic for an 89-year-old woman (65 kg and 5 ft 8 in.) with an ingrown toenail on her left big toe. You meet the patient in the preoperative area. She arrives in a wheelchair, being pushed by her daughter. The daughter, who is a nurse, tells you that her mother is a “cardiac cripple,” continuously in and out of congestive cardiac failure. The mother takes a large amount of cardiac medications including furosemide 80 mg twice a day. She has had several cardiac stents but unfortunately still gets angina at rest. Her exercise tolerance is poor as she becomes excessively breathless with angina even with dressing herself. When you meet her, she wants to talk only about her ingrown toenail. She has systemic hypertension and moderate pulmonary hypertension. She has stopped her Coumadin and her coagulation studies are normal.