cssi/SciSciGPT-SciSciNet huggingface dataset:
Singled out: Profiling metabolic and proteomic heterogeneity

Tumor cell populations vary widely in their aberrant activation of metabolic, signaling, and transcriptional networks. This cell-to-cell variability is associated with the emergence of drug resistance and tumor relapse, confounding therapies targeted against specific pathways. However, classical biochemical assays based on population averages obscure heterogeneity at the single-cell level. Moreover, it has been challenging to compare molecular information across analytical techniques with incompatible formats. In a new study, Xue et al. developed a microfluidic assay to simultaneously measure four metabolites and seven related proteins from single cells. Approximately 100 glioblastoma cells (GBM39 cell line) were individually partitioned into microchambers with an adjacent “barcode” array encoding a panel of antibodies. Following lysis, four metabolites (glucose, glutathione, c-AMP, and c-GMP) were quantified using enzymatic amplification or Forster resonance energy transfer (FRET). Simultaneously, another seven metabolism-related proteins were quantified using a sandwich immunofluorescence assay. Altogether, the statistical distributions of these analytes classified two subpopulations of glioblastoma cells with distinct metabolic phenotypes: 80% of cells displayed high glucose uptake, low cAMP, and cGMP; the other 20% displayed low glucose uptake, high cAMP, and cGMP. Remarkably, after treatment with the epidermal growth factor receptor (EGFR) inhibitor erlotinib, the population was still comprised of these two metabolic phenotypes at a similar ratio. This exquisite single-cell sensitivity with multiple metabolites and proteins provides new insights that are not possible at the population level. This single-cell technology could also interrogate interconnected metabolic and proteomic signaling networks in the context of aging, diabetes, obesity, regenerative medicine, or toxicity. An exciting translational application of this technology would be for analyzing clinical samples to predict patient response to therapy and survival and to guide therapy design, particularly when limited numbers of cells are available. Nevertheless, further work will be needed to integrate this device with upstream sample processing as well as to ensure that the capture chemistry and device operation are sufficiently robust for a clinical environment. M. Xue et al ., Chemical methods for the simultaneous quantitation of metabolites and proteins from single cells. J. Am. Chem. Soc. 137 , 4066–4069 (2015). [[Abstract]][1] [1]: http://pubs.acs.org/doi/abs/10.1021/jacs.5b00944
Isolation and characterization of anti-neoplastic sturgeon factors.

Abstract Sephadex G-200 column chromatography was utilized to isolate three anti-neoplastic compounds (A, B and C) from sturgeon sera which were cytotoxic for human tumor cells but would not kill normal cells in vitro. Furthermore, it was found that most of the sturgeons studied produced one or more of these same compounds. Immunoadsorbent techniques were utilized to further purify and isolate the three factors in larger quantities. When these immunoadsorbent purified factors were studied by SDS-polyacrylamide gel electrophoresis, factors A and C consisted of only 2 protein bands with molecular weights slightly greater than 68,000 and factor B consisted of 8–10 protein bands with molecular weights ranging from 30,000 to approximately 70,000. Factor A was not destroyed by heating at 56° C for 30 min and appears to kill tumor cells by binding to the target cells. Factor B also was not destroyed by heating at 56° C for 30 min. However, this factor differs from factor A in that it did not kill by binding to the tumor cell. Instead, it appears that a soluble factor is responsible for the cytotoxic effects observed with factor B. Factor C is destroyed by heating at 56° C for 30 min and this factor kills the tumor cells by binding to the target cells. These factors were also examined for their ability to enhance macrophage mediated cytotoxicity. Sturgeon factors A and B enhance macrophage mediated cytotoxicity whereas factor C has no effect on the ability of normal human macrophages to kill human tumor cells.
The functional neuroanatomy of voluntary swallowing

Swallowing is a complex physiological process involving voluntary and reflexive motor activity, sensorimotor integration, salivation, and visceral regulation. Despite the numerous processes required for normal deglutition, traditional models of the central control of swallowing only emphasize the involvement of the brainstem and the inferior precentral gyrus (IPCG). However a number of neurological disorders involving other brain regions also cause dysphagia. To determine the brain regions participating in voluntary swallowing, we assayed regional cerebral blood flow (rCBF) with positron emission tomography (PET) while healthy human subjects swallowed, performed lateral tongue movements, or rested with their eyes closed. Voluntary swallowing produced strong rCBF increases within the IPCG bilaterally, the right anterior insula/claustrum, and the left cerebellum. The maxima in these regions differed from those induced by lateral tongue movements. Swallowing also produced rCBF increases in the putamen, thalamus, and several additional cortical areas, but these foci were not as clearly distinguishable from activity arising during tongue movements. These findings indicate that swallowing involves the recruitment of a large-scale distributed neural network that includes the anterior insula and cerebellum. The distributed nature of this network helps to explain why so many neurological conditions produce dysphagia.
An assessment of field measures of milking rate

Abstract Several measures of milking rate were taken twice per lactation during 1457 Holstein lactations in five herds. These were taken to determine which variable would be most practical as a field measure of milking rate. Milking rates were estimated by peak flow which has been taken as the standard measure for milking rate, average flow, percent of milk produced in the first 2min of machine milking, and the amount of milk produced through the 1st min, first 1.5min, and first 2min of milking. Variables constructed from possible differences among these last three variables were also assessed. A measurement solely used to indicate rate should be obtainable before the 3rd min of milking. If rate were measured after that time, an increasingly larger number of cows would have completed their milking, and their records would not be considered in determining rate of flow. The percent of milk yielded in the first 2min of machine milking had high phenotypic (.90) and genetic (1.0) correlations with peak flow. Percent 2min milk was as repeatable within lactations and as heritable as peak flow. These four properties plus the ease with which percent 2min milk was obtained indicated that percent 2min milk was an adequate field measure of milking rate.
Relationship of atrial fibrillation and stroke after coronary artery bypass graft surgery: when is anticoagulation indicated?

Background Atrial fibrillation (AF) is considered as a risk factor for stroke after coronary artery bypass grafting operations. Methods A retrospective search in our hospital's medical record database was done to identify patients with postoperative strokes who underwent coronary artery bypass grafting operations from January 1, 1993, until December 31, 2004. All cases were individually reviewed, and the temporal relationship between neurologic event and postoperative episodes of AF was determined. During the study period it was our consistent policy to use only Coumadin anticoagulation limited to patients who had persistent AF or were to be discharged in AF. Results Of the 2,964 coronary artery bypass grafting operations, 576 patients (19.4%) had AF and 32 patients (1.1%) suffered stroke. Seventeen stroke patients maintained normal sinus rhythm during their hospital stay. Of the remaining 15 patients, 9 presented with neurologic deficit before the first episode of AF, with 5 having intraoperative and 4 having postoperative stroke. Of the 6 patients with AF before neurologic event, three strokes occurred within 1 week after spontaneous conversion to normal sinus rhythm. One patient with preoperative and also with intraoperative AF who underwent emergency coronary artery bypass grafting woke up with stroke. In the remaining two cases, the AF or atrial flutter episodes lasted less than 6 hours each before the neurologic event. More aggressive anticoagulation as suggested in the published guidelines could not have prevented strokes in any of these 6 patients. Conclusions This retrospective analysis does not support the use of aggressive anticoagulation, particularly full intravenous heparinization as a bridging therapy to decrease the already low incidence of postoperative strokes after routine coronary artery bypass grafting surgery.
Financial incentives for physicians in HMOs. Is there a conflict of interest

Do financial incentives used by health maintenance organizations (HMOs) to restrain the use of health care resources represent a conflict of interest between physicians' concern about their income and their concern about patients? To explore the contractual obligations of primary care physicians in HMOs, I mailed a survey to all 595 HMOs known to be in operation as of June 1986. In all, 302 of 595 HMOs (51 percent) responded. Sixty-seven percent of plans with capitation-based arrangements and 82 percent of plans with fee-for-service arrangements withhold a percentage of their physicians' income against potential deficits, but only 21 percent of plans with salaried physicians do so. Thirty percent of HMOs have other penalties in addition to this withholding. Eighteen percent of HMOs base the return of the withheld amount on the experience of individual physicians rather than on the collective experience of a group of physicians. For-profit HMOs are less likely to use salary-based payment, more likely to withhold a percentage of income, and more likely to base the return of this withheld amount on the experience of individual physicians. Most HMOs have mechanisms for sharing surpluses with participating physicians. I conclude that contractual arrangements in HMOs vary widely. Certain financial incentives, especially when used in combination, suggest conflicts of interest that may influence physicians' behavior and adversely affect the quality of care.
Moral hazard and limited liability: The real effects of contract bargaining

Abstract I examine the standard assumption in the moral hazard agency literature that the principal has all the bargaining power at the contract offer stage. When the agent has limited liability, as is often the case in practice, the contract changes according to the distribution of bargaining power, and consequently so does the agents effort. Implications of this result are examined.
Prediction of Consistency of Pituitary Adenomas by Magnetic Resonance Imaging

Objective Pituitary adenomas are typically soft. The prevalence of fibrous adenomas is ∼ 5 to 13%. Firm tumors are difficult to remove by curettage or suction. Predicting fibrous adenomas by magnetic resonance (MR) imaging is typically difficult and unreliable. We propose a new prediction method based on MR T2-sequence intensity. Methods The MRIs of 36 consecutive patients with nonsecreting macroadenomas were evaluated preoperatively by a blinded radiologist. Using an MR T2-weighted sequence, regions of interest were sampled from the adenoma and cerebellar peduncle, and the ratio was calculated. Intraoperatively, tumors were graded prospectively for their consistency by the operating surgeon. Results There were 28 soft and 6 fibrous tumors. Unpaired t test for these ratios was found to be statistically significant (p 1.5 (sensitivity 100%; specificity 66.7%); firm tumors were associated with ratios < 1.8 (sensitivity 100%; specificity 42.9%). Conclusion Fibrous adenomas are typically diagnosed intraoperatively. However, their resection can be technically challenging. Using T2 intensity ratios on routine preoperative MRI allows identification of these challenging cases. The surgeon can then be better prepared for the surgical resection.
What Do University-Educated Women Want from Their Pleasure Travel Experiences?

This study focused on the benefits sought by university-educated women who travel for pleasure. Twenty-seven benefit statements were derived through a literature review and chosen a priori to represent nine separate benefit dimensions. A principal components analysis was used to reduce the data into benefit dimensions. Based on an outcome of nine benefit dimensions, not all of which met the a priori assumptions, cluster analysis was employed to identify similar “types” of respondents. The findings showed that there are three possible types of female travelers: rest and relaxation seekers, family/social seekers, and action seekers. When differences between the types of travelers were addressed, only employment status proved to be significant. Family/social seekers were more inclined than the other groups to be composed of working women.
Comparison of cocaine and procaine discriminative stimuli

The discriminative stimulus, abuse potential, and locomotor-activating properties of cocaine have all been attributed to dopaminergic activity. Unexplained are findings that the local anesthetic, procaine, with little or no documented dopamine agonist activity, has stimulus properties similar to cocaine and is also self-administered. The purpose of the work described here was to compare the discriminative stimulus properties of cocaine and procaine and the ability of procaine and other local anesthetics to induce rotational (circling) behavior in unilaterally 6-hydroxydopamine-lesioned rats. Rats were trained in a two-lever, food-reinforced, operant task to discriminate either cocaine (10 mg/kg, i.p.) or procaine (54.6 mg/kg, i.p.) from saline. Results show that cocaine and procaine have similar stimulus properties, administration of either resulting in partial generalization to the other. Cocainetrained animals generalized perfectly to the psychomotor stimulants amphetamine and methylphenidate. Haloperidol more effectively blocked cocaine than procaine. The alphaadrenergic blocker phentolamine was ineffective against either training drug. Apomorphine, caffeine, and nisoxetine yielded partial generalization to both of the training drugs. Upon acute administration, the local anesthetics other than cocaine showed no significant ability to induce rotation in lesioned rats.
Microcavity enhanced directional transmission through a subwavelength plasmonic slit

We show numerically that a compact structure, consisting of multiple optical microcavities at both the entrance and exit sides of a subwavelength plasmonic slit, can lead to greatly enhanced directional transmission through the slit. The microcavities can increase the reflectivity at both sides of the slit, and therefore the resonant transmission enhancement. In addition, the microcavities can greatly improve the impedance matching, and therefore the coupling between free-space waves and the slit mode. An optimized structure with two microcavities on both the entrance and exit sides of the slit leads to ~16 times larger transmission cross section per unit angle in the normal direction compared to the optimized reference slit without microcavities. We also show numerically that the operation frequency range for high emission in the normal direction is broad.
Latitudinal and seasonal models of stratospheric photochemistry on Saturn: Comparison with infrared data from IRTF/TEXES

[1] The variation of hydrocarbon abundances with altitude, latitude, and season in Saturn's stratosphere is investigated using a one-dimensional, time-variable, photochemical model. The results indicate that hydrocarbon abundances at pressures less than ∼0.01 mbar are extremely sensitive to solar flux variations due to changes in season, latitude, orbital radius, solar cycle, and ring shadowing. Long vertical diffusion times in the 0.01–1 mbar region introduce phase lags in the response to insolation changes. At pressures greater than 1 mbar, vertical diffusion timescales are longer than a Saturnian year. Therefore, relatively long-lived hydrocarbons like C2H2, C2H6, and C3H8 exhibit little seasonal variation in the lower stratosphere, and the yearly averaged solar insolation combined with vertical diffusion control species abundances in this region. Species with short photochemical lifetimes (e.g., CH3, C2H4) continue to experience seasonal variations, even at low altitudes. The model results are compared with infrared observations from the TEXES spectrometer at NASA's Infrared Telescope Facility. We find that the observed C2H2 mixing-ratio variation with latitude is reasonably well predicted, whereas the C2H6 distribution is poorly predicted by the models. Meridional transport is likely affecting the distribution of C2H6, which has a long photochemical lifetime, whereas the distribution of shorter-lived C2H2 is controlled by photochemistry and vertical diffusion. Given the different observed behavior of C2H2 and C2H6, we constrain meridional transport timescales at 2 mbar on Saturn to be in the range ∼100–700 years, corresponding to meridional wind or diffusion speeds of ∼0.4–2 cm s−1.
Towards a compact robotically steerable thermal ablation probe

The focus of this paper is on the design and evaluation of a robust drive mechanism intended to robotically steer a thermal ablation electrode or similar percutaneous instrument. We present the design of an improved screw-spline drive mechanism based on a profiled threaded shaft and nut that reduces the part count and simplifies manufacturing and assembly. To determine the optimal parameters for the profile shape, an analytical expression was derived that relates the tolerance between the nut and shaft to the angular backlash, which was validated using SolidWorks. We outline the forward kinematics of a steering mechanism that is based on the concept of substantially straightening a pre-curved Nitinol stylet by retracting it into a concentric outer cannula, and re-deploying it at a different position. This model was compared to data collected during targeting experiments performed in ex-vivo tissue samples where the distal tip of the stylet was repositioned in ex-vivo bovine tissue and the location of its distal tip was recorded with CT imaging. Results demonstrated that the drive mechanism operated robustly and targeting errors of less than 2mm were achieved.
Drugs as solubilizing agents. Solubilization of acids by water-soluble amine salts

The solubilization of several aliphatic and aromatic acids in aqueous solutions of cyclopentamine hydrochloride, ephedrine sulfate, and propoxyphene hydrochloride has been investigated. At low concentrations of the amine salts, a limited solubilizing effect was observed, but as the concentration was increased, the pattern changed sharply so that the ratio of the acid in solution to the salt became many times greater than at lower concentrations. The degree of solubilization and the temperature range in which it occurs are dependent upon the structure of both the amine and the acid. The ratios of the moles of acid per mole of the amine salt follow the Arrhenius relationship to a maximum value which does not change with further elevation of the temperature.
An Unusual Presentation of Mastocytosis: Unilateral Swelling of the Vulva

Mastocytosis is a primary, abnormal accumulation of mast cells associated with a broad range of local and systemic symptoms. We report two female adolescents with episodic, unilateral, swelling of the labia majora that was discovered to be an unusual presentation of mastocytosis. Mastocytosis is frequently misdiagnosed because of its rarity and variable clinical presentation, which often mimics other conditions. In the appropriate setting, mastocytosis should be included in the differential diagnosis of labium majus swelling.
An evaluation of electron micrographs of bacteriochlorophyll a-protein crystals in terms of the structure determined by x-ray crystallography.

Previous electron microscopic studies of different crystalline aggregates of the water-soluble bacteriochlorophyll a-protein (Bchl-protein) from the green photosynthetic bacterium Chlorobium limicola are reevaluated in terms of the structure of the protein determined by X-ray crystallography. The overall molecular packing arrangement proposed by J. M. Olson, D. F. Koenig and M. C. Ledbetter [Arch. Biochem. Biophys. 129, 42 (1969)] and L. W. Labaw and R. A. Olson [J. Ultrastruct. Res. 31, 456 (1970)] for the hexagonal crystals of the Bchl-protein is confirmed by the X-ray analysis, although the molecules are shown to be trimers rather than tetramers as assumed previously. Consideration of the molecular contacts exhibited in the hexagonal and trigonal crystal forms of the protein leads to a revised model for the tubular paracrystalline aggregates. Implications of the molecular symmetry and the observed crystal packing for the arrangement of the Bchl-protein in vivo are discussed.
Advanced age and adjuvant tamoxifen prescription in early-stage breast carcinoma patients.

BACKGROUND Adjuvant tamoxifen is recommended for all women with estrogen receptor-positive breast carcinoma without regard for age. We investigated age-dependent variations in adjuvant tamoxifen prescription patterns in a cohort of women 80 years of age and older. METHODS We studied 92 women diagnosed at four U.S. sites with primary, early-stage breast carcinoma. Each woman consented to a medical record review and participated in two telephone interviews. We compared the proportion of tamoxifen prescriptions received by women 85–92 years of age with those received by women 80–84 years of age. Relative risks (RR) and 95% confidence intervals (95% CI) were generated using generalized estimating equations. Confounding by demographic, disease, and treatment characteristics was assessed. RESULTS Before adjustment, patients 85–92 years of age were 28% less likely to receive a tamoxifen prescription compared with patients 80–84 years of age (RR = 0.72, 95% CI 0.57–0.91). In this sample, patients not prescribed tamoxifen had substantially more comorbidity. After adjusting the crude finding for comorbidity, the RR was 0.74 (95% CI 0.58–0.93). In addition, the oldest patients and those not prescribed tamoxifen were significantly less likely to be married or have living children. After adjusting the crude finding for these two factors, the RR was 0.75 (95% CI 0.59–0.95). There was no confounding by the other demographic, disease, or treatment covariates assessed. CONCLUSION Given the increasing longevity of the oldest old, undertreatment with adjuvant tamoxifen may put older breast carcinoma patients at an increased risk of disease recurrence and breast carcinoma mortality. Cancer 2002;95:2465–72. © 2002 American Cancer Society. DOI 10.1002/cncr.10985
Nonparametric EM Algorithms for estimating prior distributions

Consider a sequence of repetitive experiments E"1, E"2,..., E"N. Each E"i is represented by a pair of random vectors (Y"i, @q"i) such that Y"i is observed, @q"i is not observed, and the conditional density of Y"i given @q"i is known. The @q"i's are independent and identically distributed with common but unknown distribution function F^*(@q). The problem is to estimate F^* given the data Y"1, Y"2,..., Y"N. Two nonparametric maximum likelihood methods based on the EM algorithm are presented. Motivation for this problem comes from the analysis of the distribution of parameters in pharmacokinetic models based on population data.
Control of acetylcholine synthesis--the inhibition of choline acetyltransferase by acetylcholine.

— The inhibition of choline acetyltransferase by acetylcholine in vitro occurs at a concentration of 10 mm and increases progressively to 45 per cent at a concentration of 100 mm. The inhibition is competitive for choline and noncompetitive for acetyl-CoA. It is suggested that the synthesis of acetylcholine may be controlled by its accumulation in synaptic vesicles.
Language and government coordination: An experimental study of communication in the announcement game

One of the key roles of government is to coordinate the activities of citizens. One reason why governments are efficient facilitators of coordinated action, in addition to their ability to force compliance or tax, is that they are typically endowed with more information than the individuals they govern. This advantage creates a dilemma for them, however, since it forces them to decide on how they should distribute the information in their possession to the population. This paper investigates this question. We investigate the “Announcement Game” defined by the government and those it governs and focus on communication strategy that government uses to communicate private information to the citizens. This communication strategy involves (1) partitioning the state space in an attempt to mask the true state of the world and (2) choosing what type of language to use in order to communicate elements of this partition. We present evidence that the language used to execute a communication strategy does affect the efficiency of the equilibrium convergence process and also demonstrate that subjects playing the role of the government exhibit a great deal of sophistication in the communication strategies they employ and the language they use to execute them.
Stoichiometry and coal-type effects on homogeneous vs. Heterogeneous combustion in pulverized-coal flames☆

Results of experiments to determine the extent of heterogeneous combustion in the rapid-devolatilization regime of fuel-rich bituminous and subbituminous coal-dust flames are reported. Major gas concentrations, gas and particle temperatures, and solids proximate and elemental compositions were measured as functions of residence time in pulverized-coal/O2/Ar flames stabilized on a flat-flame burner. Proximate fixed carbon and volatile matter measurements are corrected to account for devolatilization exceeding that predicted by ASTM proximate analysis. The corrected proximate data are used to determine the fraction of volatile matter consumed heterogeneously in situ and the fraction released to the gas phase by pyrolysis. Seven to thirty-five percent of the initial corrected volatile matter is removed heterogeneously. A mass transfer analysis is applied to predict a time dependent critical particle size such that the volatiles flux emerging from larger particles is sufficient to prevent surface oxidation. Critical particle radii as large as 39 μm are calculated. Results of the volatile matter partitioning and critical radius calculations indicate that heterogeneous combustion is more important in the leaner flames and for the subbituminous coal.
Sex Differences in Revascularization Interventions after Acute Ischemic Stroke

Background Studies suggest that women are less likely than men to receive intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke (AIS). Relatively little is known about whether this sex disparity in AIS management extends beyond IV tPA use, reflects national practice patterns, or is changing. Methods Data from the Nationwide Inpatient Sample from 1997 to 2006 were used to identify adults (≥18 years of age) who were discharged with a primary diagnosis of AIS (n = 4,453,207) in the United States. Of 605,960 individuals admitted to 1056 hospitals that performed reperfusion/revascularization procedures, sex-specific rates of cerebrovascular reperfusion (e.g., IV tPA, intra-arterial therapy, angioplasty, stent, or carotid endarterectomy [CEA]), and cardiac reperfusion (e.g., catheterization, angioplasty, stent, or bypass graft) were determined before and after adjustment for sociodemographic, clinical, and hospital factors. Results Men were more likely than women to receive IV tPA (prevalence ratio [PR] 1.37, 95% confidence interval [CI] 1.32-1.42), catheter angiography (PR 1.36, 95% CI 1.33-1.38), intracranial or extracranial angioplasty/stent (PR 1.73, 95% CI 1.49-2.01), CEA (PR 1.79, 95% CI 1.72-1.86), or any cardiac reperfusion therapy (PR 1.62, 95% CI 1.53-1.71). Multivariable adjustment slightly attenuated the sex disparity. Use of all procedures except CEA rose from 1997 to 2006 in both sexes, but IV tPA use increased at a higher rate for women (compared to men); by 2006, there was no sex difference. Conclusions Over the last decade, women hospitalized for AIS in the United States were less likely than men to receive cerebrovascular and cardiac reperfusion therapies. However, the IV tPA treatment sex disparity may have been eliminated.
A Comparison of Some Shallow Wind-Driven Currents

Abstract Four sets of current measurements made in water depths ranging between 28 and 38 m over periods ranging from three to five weeks are examined and compared. The response of the water column to wind forcing is examined by computing regression coefficients between the surface wind stress and two different parameterizations of bottom stress in terms of measured currents. Coefficients computed for the different data sets vary by as much as a factor of 4. While such variations might be due to instrumental differences, it seems more likely that the assumed dynamical balance between surface and bottom stress is incomplete, i.e., other forces such as the alongshore pressure gradient are quantitatively important even when the water depth is comparable to the turbulent Ekman layer thickness.
Stimulation of alternariol biosynthesis by zinc and manganese ions

Abstract Production of the polyketides alternariol and alternariol methyl ether by mycelia ofAlternaria alternata is absolutely dependent on an adequate concentration of Zn2+ in the culture medium. Minimal alternariol synthesis occurs with 1.0 μM Zn2+, and concentrations between 10 and 100 μM stimulate alternariol synthesis maximally. Mn2+ acts synergistically with Zn2+ to provide a further threefold stimulation of alternariol synthesis. The relationship between Zn2+ stimulation and light inhibition of alternariol synthesis is discussed.
A stage-specific inhibitor of adenylate cyclase in Dictyostelium discoideum

Abstract A sudden increase in adenylate cyclase activity occurs during the chemotaxis and aggregation of Dictyostelium discoideum . Preincubation of extracts from the pre-aggregation stage, in which adenylate cyclase activity was low, with post-aggregation stages, in which the increase in activity occurred, resulted in the demonstration of a heat-stable inhibitor of adenylate cyclase (ACI) that was present only during the early stages of development. Cellular fractionation studies showed that ACI was present in both the 100 000 g pellet and supernatant fractions. The inhibitor was not inactivated by proteases or protease inhibitors. A heat-treated preparation of the inhibitor was dialysable. The effect of ACI was dependent upon a pre-incubation treatment, with notable inhibition occurring only after a 20 min pre-incubation period. The apparent inhibition was not artifactual, due to the degradation of the substrate, ATP, or to the loss of the reaction product, cAMP. Additionally, the inhibitor was specific for adenylate cyclase, as it had no effect on the activity of several other enzymes, including cAMP phosphodiesterase.
Neonatal haemostasis and the management of neonatal thrombosis

Two detailed reviews of the management of neonatal thrombosis were published in 2012; one was an up-dated version of guidance first issued in 2004 and the other was a comprehensive review. Both of these publications gave very similar advice regarding the practical aspects of the indications, dosage and management of antithrombotic therapy. The authors stated that the evidence supporting most of their recommendations for anti-thrombotic therapy in neonates remained weak and so the therapy for a neonate with a thrombosis has to be based on an individualized assessment of estimated risk versus potential benefit. The aim of this present review is to give the treating physician an outline of the unique physiology of neonatal coagulation and how this affects the monitoring, dosing and even the choice of therapeutic strategy for the management of thrombosis in the neonate.
Glycoproteomic Analysis of Human Lung Adenocarcinomas Using Glycoarrays and Tandem Mass Spectrometry: Differential Expression and Glycosylation Patterns of Vimentin and Fetuin A Isoforms

Human lung cancer is a major cause of cancer mortality worldwide. Advances in pathophysiologic understanding and novel biomarkers for diagnosis and treatment are significant tasks. We have undertaken a comprehensive glycoproteomic analysis of human lung adenocarcinoma tissues. Glycoproteins from paired lung adenocarcinoma and normal tissues were enriched by the lectins Con A, WGA, and AIL. 2-D PAGE revealed 30 differentially expressed protein spots, and 15 proteins were identified by MS/MS, including 8 up- (A1AT, ALDOA, ANXA1, CALR, ENOA, PDIA1, PSB1 and SODM) and 7 down-regulated (ANXA3, CAH2, FETUA, HBB, PRDX2, RAGE and VIME) proteins in lung cancer. By reverse-transcription PCR, nine proteins showed positive correlation between mRNA and glycoprotein expression. Vimentin and fetuin A (alpha(2)-HS-glycoprotein) were selected for further investigation. While for vimentin there was little correlation between total protein and mRNA abundance, expression of WGA-captured glycosylated vimentin protein was frequently decreased in cancer. Glycoarray analysis suggested that vimentins from normal and cancerous lung tissue differ in their contents of sialic acid and terminal GlcNAc. For fetuin A, both total protein and mRNA abundance showed concordant decrease in cancer. WGA- and AIL-binding glycosylated fetuin A was also consistently decreased in cancer. Glycoarray analysis suggested that high mannose glycan structures on fetuin A were only detectable in cancer but not normal tissue. The intriguing expression patterns of different isoforms of glycosylated vimentin and fetuin A in lung cancer illustrate the complexities and benefits of in-depth glycoproteomic analysis. In particular, the discovery of differentially glycosylated protein isoforms in lung adenocarcinoma may represent avenues towards new functional biomarkers for diagnosis, treatment guidance, and response monitoring.
Acoustic Analysis of Correct and Misarticulated Semivowels

Four children who produced correct /w,r,l,j/, four children with developmental w/r and w/l substitutions, and four articulation impaired children with w/r and w/l substitutions were subjects. They ...
Performance testing of advanced lead—acid batteries for electric vehicles

Abstract New applications for lead—acid batteries, such as electric vehicle propulsion, demand high specific energy and power and good cycle life. A research
Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface

Members of the epidermal growth factor receptor family (EGFR/ERBB1, ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are key targets for inhibition in cancer therapy. Critical for activation is the formation of an asymmetric dimer by the intracellular kinase domains, in which the carboxy-terminal lobe (C lobe) of one kinase domain induces an active conformation in the other. The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2 (refs 3-5). Crystal structures of complexes between the EGFR kinase domain and a fragment of MIG6 show that a approximately 25-residue epitope (segment 1) from MIG6 binds to the distal surface of the C lobe of the kinase domain. Biochemical and cell-based analyses confirm that this interaction contributes to EGFR inhibition by blocking the formation of the activating dimer interface. A longer MIG6 peptide that is extended C terminal to segment 1 has increased potency as an inhibitor of the activated EGFR kinase domain, while retaining a critical dependence on segment 1. We show that signalling by EGFR molecules that contain constitutively active kinase domains still requires formation of the asymmetric dimer, underscoring the importance of dimer interface blockage in MIG6-mediated inhibition.
Hydrophobic salts markedly diminish viscosity of concentrated protein solutions.

Reducing viscosities of concentrated solutions of therapeutic proteins is important for their subcutaneous and intravenous delivery. Although inorganic salts and optimizing the pH were previously reported to dramatically lower the viscosity of a monoclonal antibody solution, herein we have determined these effects not to be general. Separately, we have found that hydrophobic ionic excipients, both anionic and cationic, substantially decrease the viscosity of concentrated (300–400 mg/mL) aqueous solutions of bovine serum albumin and γ-globulin. The more hydrophobic the excipient, the greater its viscosity-lowering effect is. With cationic ones, the concomitant contribution of the counter-ion broadly follows the chaotropic order. The most potent excipients lower the viscosity over fourfold to levels far below the 50 cP threshold for subcutaneous injections. The observed viscosity reductions are rationalized in terms of three-dimensional transient protein networks formed in concentrated solutions due to hydrophobic and, to a lesser extent, ionic interactions. These reversible protein aggregates are responsible for strong resistance to flow in concentrated protein solutions and hence their high viscosity; hydrophobic ions apparently effectively compete for these interprotein interactions, thereby giving rise to less viscous solutions. Biotechnol. Bioeng. 2011; 108:632–636. © 2010 Wiley Periodicals, Inc.
Experimental Investigation of Coefficient of Friction During the Friction Stir Processing of Aluminum

There is a lack in understanding of the frictional contact condition during friction stir processes. High temperature, force and work material adhesion to and from the tool make the coefficient of friction difficult to measure. In this study, an experiment was set up to simultaneously measure the temperature and normal and frictional forces between a rotating tool and a stationary workpiece at steady state conditions. The coefficient of friction was measured for increasing temperature. A simple model was created to convert the thermocouple temperature measurement to the temperature at the point of contact between the tool and workpiece. It was found that the coefficient of friction had a decreasing trend as temperature approached the solidus temperature of the work material. The results and analysis of the experiments are presented.Copyright © 2010 by ASME
The effect of hysterectomy on hormone-induced lordosis behavior in hamsters.

Abstract Ovariectomized-hysterectomized (OH) and ovariectomized-sham hysterectomized (OSH) hamsters were tested for lordosis behavior following treatments including either 1, 5, or 10 μg estradiol benzoate (EB) in combination with 0.1, 0.25, and 0.5 mg progesterone. Few animals responded at the 1 μg dose of EB and there were no differences in latency to the first display of lordosis or in the total lordosis duration among responding animals in the 5 and 10 μg EB groups. However, there was significantly more positive tests in the OSH group injected with 5 μg EB than in the OH group and this difference approached statistical significance in the 10 μg EB groups. The results are compared to similar studies in rats and possible mechanisms for the effects of hysterectomy are discussed.
Parallel Picoliter RT-PCR Assays Using Microfluidics

The development of microfluidic tools for high-throughput nucleic acid analysis has become a burgeoning area of research in the post-genome era. Here, we have developed a microfluidic chip to perform 72 parallel 450-pL RT-PCRs. We took advantage of Taqman hydrolysis probe chemistry to detect RNA templates as low as 34 copies. The device and method presented here may enable highly parallel single cell gene expression analysis.
Plasticity of annual cycle in Vespula pensylvanica shown by a third year polygynous nest and overwintering of queens inside nests

Excavations of 4 nests of the western yellowjacket, Vespula pensylvanica (Saussure) (Hymenoptera: Vespidae) in southern California revealed situations that deviated from the typical annual, single-queen life history of yellowjacket colonies. Three nests that were collected well after colony decline (in December through February) consisted of more queens than workers. An additional nest excavated in April (a time when nests are typically being initiated by single foundress queens) revealed a large polygynous nest that was rearing workers, males, and queens, was very active, and was entering its 3rd year. These life history traits show a plasticity of behavior expressed in the warmer regions of the range of V. pensylvanica and may be more common than previously recorded.
Qué derechos para las minorías culturales

Michel Walzer points to the kind of conflicts that arouse between parochial groups and the body of citizens (the liberal democratic state) when facing the problem of group rights. According to him this kind of conflicts are manegeable depending on the features of groups. Thus, inward pluralized groups are able to reconise the plural identities and loyalties of its memebers and, as it follows, its accomodation causes no problem in democratic societies. The problem lies, still, in totalized and closed groups. Here there is sheer incompability, and thus settlement is much more complex. In fact, political theory has no principled answer for this problem. Walzer suggest a guide for pragmatic solutions: as far as these groups are not a threat for the democratic order that allows tolerance, they should be tolerated, and even supported in their reproduction. On the contrary, when these groups become a threat to the democratic arrangement they should by fighted against.
The relationship of estrogen to placental steroidogenesis in the baboon

In previous studies in pregnant baboons, estrogen deprivation produced by the administration of the estrogen antagonist MER-25 resulted in a decline in plasma progesterone. In the present study, pregnant baboons in whom the corpus luteum-bearing ovary was removed early in pregnancy were used to distinguish between a luteal or placental effect of this estrogen deprivation. MER-25, administered from days 35 through 48 of pregnancy, resulted in a significant decline in plasma progesterone, indicating a direct placental action of estrogen deprivationon progesterone production. In a second experiment using intact pregnant baboons, concomitant administration of the nonsteroidal estrogen diethylstilbestrol (DES) prevented the inhibitory effect of MER-25 on placental progesterone, indicating that the effect was due to antiestrogenic action of MER-25 and not to some other pharmacological effect of the antagonist. Since DES administration alone had no effect on plasma progesterone levels, the role of estrogen may b...
Organization and recall of pictures and words in children

Recall and category clustering of pictures and words were investigated among Ss from the third, fourth, and sixth grades. Both recall and organization were greater among older Ss and for pictorial stimuli. Recall was correlated with scores on a standardized achievement test designed to measure paragraph comprehension (PC). The Z-score measure of clustering was found to yield more reliable and consistent results than the adjusted ratio of clustering. Some of the change in recall as a function of age was associated with both category clustering and PC scores. This finding was interpreted as supporting the view that memory does not develop as an isolated skill, but reflects the child’s developing ability to transform surface structures into abstractly organized deep structures. It was suggested that pictures are easier to recall because the transformation of surface structure representations into organized deep structures is less influenced by the context of encoding than it is in the case of words.
Behavioral measures of spectral sensitivity of the goldfish at different temperatures

Abstract Spectral sensitivity was determined behaviorally in the goldfish at two different temperatures, 25° and 15°. A rather broad function, decreasing in sensitivity at both spectral extremes, was observed at 25°. When the temperature was decreased to 15°, leaving other experimental conditions constant, a midspectral depression in sensitivity was noted. Histological examination of the retinae of goldfish under both conditions revealed the eye to be in a light-adapted state, as judged by photomechanical criteria. A three-component additive model gave a satisfactory fit to the 25° data, and by retaining the same constants but omitting the midspectral contribution, a two-component additive model provided a satisfactory fit for the 15° data. Possible mechanisms for this midspectral deficit were discussed.
Training-Related Changes in the Brain: Evidence from Human Auditory-Evoked Potentials

Auditory-evoked potentials are being used to examine training-related changes in the human central auditory system, and there is converging evidence that focused listening training, using various training methods and different types of stimuli alters evoked neural activity. Such training-related changes are often described in terms of PHYSIOLOGICAL PLASTICITY, a process whereby the neural representation of the acoustic cue is modified with training. In this review, the concept of plasticity is discussed from a broader perspective. Specifically addressed is how electrophysiological methods are being used to study physiological modifications that occur with training, and how this information might contribute to the rehabilitation of people who wear hearing aids and cochlear implants.
Antioxidant activity and quality of asparagus affected by microwave-circulated water combination and conventional sterilization

Abstract Green asparagus ( Asparagus officinalis L.), as a healthy and perishable vegetable, is processed after harvest to minimize the deterioration of its physical and chemical quality. In our research, fresh asparagus was sterilized using several methods, including a pilot-scale 915 MHz microwave-circulated water combination (MCWC) heating system, pressured hot-water heating and steam-heating in a retort. Rutin content of asparagus processed by these methods did not show significant difference. But antioxidant activity of asparagus after MCWC treatment was significantly greater than that processed by other methods. Although the shear stress of asparagus spears was significantly decreased by eight times after sterilization, no significant difference existed among the textures of asparagus processed by these methods. Asparagus processed by MCWC showed greener colour with negative a * value and greater hue value ( H 0 ) than did hot water- and retort-treated asparagus. Therefore, asparagus sterilized by MCWC showed greater antioxidant activity and greener colour than did asparagus processed by the conventional methods.
Experimental investigation of fatigue damage accumulation

IN 1945, M. A. Miner presented his approach for cumulative damage in metal fatigue to the American Society of Mechanical Engineers. In this approach, the expended life of a specimen is defined to be equal to the summation of the number of cycles that are applied at each different stress level when expressed as a percentage of the number of cycles that would cause failure. The Miner approach is mathematically expressed as shown in equation (1).
Defective translation in RC - cells.

Mutation in the RC gene results in the formation of a species of β galactosidase with reduced specific activity and increased thermolability.
Use of the GDC crescent for embolization of tumors fed by cavernous and petrous branches of the internal carotid artery. Technical note.

✓ This report presents two cases of hypervascular tumor in which the cavernous and petrous internal carotid artery feeding vessels were successfully occluded using a new endovascular device, the crescent-shaped platinum Guglielmi detachable coil (GDC). With this new embolic agent the risk of unwanted embolization of normal intracranial arteries was significantly reduced. The GDC “crescent” seems particularly useful when distal, superselective, and controllable occlusion of small arterial feeding vessels is the goal of the treatment.