cssi/SciSciGPT-SciSciNet huggingface dataset:
T-Cell Adhesion in Healthy and Inflamed Skin

The diverse populations of tissue-resident and transitory T cells present in the skin share a common functional need to enter, traverse, and interact with their environment. These processes are largely dependent on the regulated expression of adhesion molecules, such as selectins and integrins, which mediate bidirectional interactions between immune cells and skin stroma. Dysregulation and engagement of adhesion pathways contribute to ectopic T-cell activity in tissues, leading to the initiation and/or exacerbation of chronic inflammation. In this paper, we review how the molecular interactions supported by adhesion pathways contribute to T-cell dynamics and function in the skin. A comprehensive understanding of the molecular mechanisms underpinning T-cell adhesion in inflammatory skin disorders will facilitate the development of novel tissue-specific therapeutic strategies.
Orton-Gillingham and the IDEA: analysis of the frequency and outcomes of case law.

The Individuals with Disabilities Education Act grants dissatisfied parents of students with disabilities the right to pursue legal remedies. In 2007, Rose and Zirkel found that parents of students with reading disabilities seeking Orton-Gillingham (OG) instruction under the IDEA’s central obligation for a free appropriate public education (FAPE) were largely unsuccessful in their complaints. Since that review, various factors had the potential to influence the frequency and outcomes of OG-related case law—namely, the peer-reviewed research requirement of the IDEA and growing awareness of the need for specialized reading instruction. Our updated analysis of OG-related case law revealed an increase in the number of cases but similar district-favored outcomes identified by Rose and Zirkel. In particular, the relaxed substantive FAPE standard and deference to local and state authorities diminished the likelihood of parents prevailing in their requests. Implications for parents, school district personnel, special education professionals, and education researchers are presented.
Finding Shelter in the Storm: Undoing Racism in a Predominantly White School of Social Work

This paper presents the case study of a 100+ year old school of social work recently shaken by acts of racial aggression targeted toward our Black/African American community. Following campus incidents that received national attention, minority social work students urged faculty to organize action to voice values of equity and justice, and to provide an intentional safe space within our school. In response, a volunteer faculty committee dedicated themselves to the group’s formation and implementation of the Undoing Racism Principles from the People’s Institute for Survival and Beyond (PISAB, n.d.), beginning internally and expanding outward. Representing multiple identities and positionalities of power, committee members use these principles to process our privilege. We reflect on our journeys with racism as social work educators and as individuals who are, and have been, influenced by internalized historical and contemporary racism. Guided by Pedagogy of the Oppressed (Freire 1970/ 2002) and Critical Race Theory (Sule, 2020), the praxis of reflecting in-and-on our work has evolved (Schon, 1983, 1987). Authors share their personal experiences, professional impacts, and efforts to implement anti-racist pedagogy. Contextual implications for schools of social work that aim to become anti-racist within their implicit and explicit curricula are provided by this case study.
Music and the (Real) World: Thirty Years of MTV

The case is useful for teaching students the structure of creative industries and the issues to consider when attempting disruptive innovation and entrepreneurship in these industries.Learning Objective:The case enables a discussion that introduces students to the unique structure and features of creative industries, the importance of intermediaries and taste-makers in creative industries, and allows the students to discuss and understand entrepreneurial opportunities in creative industries in the age of the Internet.
RACE, POWER, MULTIPOSITIONALITY

To understand the relationship between social position and social change, this essay examines the multipositionality of the black schoolteacher, and through it the relationship between race and power. The autobiographical writings of black teachers who worked in the American South between 1890 and 1950 uniquely reveal the complex relationship between power and culture in this phase of American history, and illustrate the ways in which subordinated people used varied tools in order to shift the vectors of power, and thus the limits of their social status as subaltern citizens. The result is a more textured view of black teachers, which rejects simple constructions of teachers as uni-dimensional individuals capable of a ‘single’ consciousness.
Hydrated α-Fe2O3(11¯02) surface structure: Role of surface preparation

Abstract The surface structure of α- Fe 2 O 3 ( 1 1 ¯ 0 2 ) was studied under two different surface preparation conditions using crystal truncation rod (CTR) diffraction. Wet chemical and mechanical polishing (CMP) at 298 K results in a crystalline surface termination in which the top layer of iron atoms is absent compared to the stoichiometric bulk termination. Annealing in air at 773 K resulted in a transformation of the surface to a structure consistent with hydroxylation of the stoichiometric termination. These results agree with theoretical predictions of Lo et al. [C.S. Lo, K.S. Tanwar, A.M. Chaka, T.P. Trainor, Phys. Rev. B 75 (2007) 075425] and clearly show an ambient pressure surface preparation path leading to a stoichiometric hydroxylated surface, which is apparently a meta-stable configuration at room temperature.
cMRI-BED: A novel informatics framework for cardiac MRI biomarker extraction and discovery applied to pediatric cardiomyopathy classification

Pediatric cardiomyopathies are a rare, yet heterogeneous group of pathologies of the myocardium that are routinely examined clinically using Cardiovascular Magnetic Resonance Imaging (cMRI). This gold standard powerful non-invasive tool yields high resolution temporal images that characterize myocardial tissue. The complexities associated with the annotation of images and extraction of markers, necessitate the development of efficient workflows to acquire, manage and transform this data into actionable knowledge for patient care to reduce mortality and morbidity. We develop and test a novel informatics framework called cMRI-BED for biomarker extraction and discovery from such complex pediatric cMRI data that includes the use of a suite of tools for image processing, marker extraction and predictive modeling. We applied our workflow to obtain and analyze a dataset of 83 de-identified cases and controls containing cMRI-derived biomarkers for classifying positive versus negative findings of cardiomyopathy in children. Bayesian rule learning (BRL) methods were applied to derive understandable models in the form of propositional rules with posterior probabilities pertaining to their validity. Popular machine learning methods in the WEKA data mining toolkit were applied using default parameters to assess cross-validation performance of this dataset using accuracy and percentage area under ROC curve (AUC) measures. The best 10-fold cross validation predictive performance obtained on this cMRI-derived biomarker dataset was 80.72% accuracy and 79.6% AUC by a BRL decision tree model, which is promising from this type of rare data. Moreover, we were able to verify that mycocardial delayed enhancement (MDE) status, which is known to be an important qualitative factor in the classification of cardiomyopathies, is picked up by our rule models as an important variable for prediction. Preliminary results show the feasibility of our framework for processing such data while also yielding actionable predictive classification rules that can augment knowledge conveyed in cardiac radiology outcome reports. Interactions between MDE status and other cMRI parameters that are depicted in our rules warrant further investigation and validation. Predictive rules learned from cMRI data to classify positive and negative findings of cardiomyopathy can enhance scientific understanding of the underlying interactions among imaging-derived parameters.
Early Events in the Steroidal Regulation of α2u Globulin in Rat Liver

1. A double-antibody radioimmunoassay for alpha2mu globulin has been developed. With the help of this highly sensitive radoimmunoassay the early effects of both androgen and estrogen treatments on the hepatic synthesis of alpha2mu globulin in the rat have been investigated. 2. Results show that the earlier observation of the long lag period in the androgenic induction of alpha2mu globulin is more apparent than real. 3. Single injections of either 5alpha-dihydrotestosterone(5alpha-dihydro-17beta-hydroxy-4-androsten-3-one) or its physiological antagonist estradiol-17beta (1,3,5(10)-estratriene-3,17beta-idol) to castrated female rats resulted in the induction of alphamu globulin reaching maximum hepatic level of the protein between 6--9 h after the hormone administration. Administration of cycloheximide 15 prior to hormone treatment blocked both androgenic andestrogenic induction of alpha2mu globulin. 4. Daily pretreatments with 5alphamu-dihydrotestosterone increased the sensitivity of subsequent androgenic response to alpha2muglobulin synthesis. On the other hand, daily pretreatments with estradiol 17beta decreased and ultimately abolished the estrogenic induction of alpha2mu globulin. 5. The possible mechanism of both androgenic and estrogenic induction of alpha2mu globulin in rat liver mediated through a sex-hormone-binding protein with dual affinity for both dihydrotestosterone and estradiol has been suggested.
The impact of amino-terminal pro-brain natriuretic peptide testing on hospital length of stay and morbidity in patients with acute decompensated heart failure.

Abstract Context.—In clinical trials, N-terminal pro-brain natriuretic peptide (NT-proBNP) testing has been shown to be valuable for diagnosis and triage of patients with acute decompensated heart ...
ISO OSI Layered Protocol Model

The sections in this article are 1 Interoperability 2 OSI Reference Model 3 OSI Application Standards 4 OSI Concepts 5 OSI Layers 6 Conclusions
Anthropological research perspectives on health problems in developing countries

Abstract Anthropological research on health problems in developing countries during the past 30 years, and present/future research on the same topic, are considered in the light of (a) the changing health picture in developing countries and (b) the major health enterprises of developing countries and participating multilateral and bilateral agencies. The author suggests that modern medicine in recent years has become the first choice of most traditional peoples most of the time. It is because the supply of modern health care cannot keep up with the demand that the Primary Health Care (PHC) movement has arisen. With respect to the use of traditional curers in PHC it is pointed out that (a) they are not replacing themselves, (b) many have become ‘neotraditional curers’ making extensive use of modern drugs and (c) spiritualist curing is replacing much traditional medicine. The question is, then, when we advocate the use of ‘traditional curers’ in PHC programs, what exactly are we proposing? All of the above? Some of the above? Traditional healers only, strictly defined? The author also suggests that some early anthropological stereotypes of health behavior need revision, particularly those having to do with effective doctor-patient interaction. Finally, if anthropologists are effectively to explore the sociocultural aspects of health and illness, they must study health care delivery systems as intensively as community/patient behavior.
Carpal impaction with the ulnar styloid process: treatment with partial styloid resection.

Carpal impaction with the ulnar styloid process (stylocarpal impaction) occurs less frequently than with the ulnar head (ulnocarpal impaction), and more commonly develops in wrists with negative ulnar variance. Physical examination, radiographic evaluation, and wrist arthroscopy are all helpful in excluding alternative causes of ulnar wrist pain. When an ulnocarpal stress test elicits pain, and radiographs suggest that this is due to carpal impaction with the ulnar styloid, partial resection of the styloid process provides successful treatment, so long as the insertion of the triangular fibrocartilage at the base of the styloid is not disrupted.
An Arsenic Forecast for China

About 140 million people worldwide drink groundwater containing unsafe levels of arsenic ( 1 ). Chronic exposure to this tasteless, odorless poison leads to health effects such as skin lesions and cancer. In China, pollution is pervasive and anthropogenic groundwater contamination has attracted attention ( 2 ). Naturally-occurring arsenic is perhaps less widespread, yet equally dangerous to those exposed. Though the problem has been known for decades ( 3 ) and mitigation is ongoing ( 4 ), estimates of the exposed population differ widely ( 5 , 6 ). On page 866 of this issue, Rodriguez-Lado et al. ( 7 ) assess the probability of the occurrence of unsafe arsenic levels in China's groundwater and identify at-risk areas where data are sparse. They suggest that more than 19 million Chinese may be drinking water above the World Health Organization guideline of 10 µg/liter. Such predictive models could guide action toward minimizing the impact of this widespread threat to human health.
1,2‐Diacylglycerol Content and Its Arachidonyl‐Containing Molecular Species Are Reduced in Sciatic Nerve from Streptozotocin‐induced Diabetic Rats

The content of 1,2-diacylglycerol (DAG) was determined in sciatic nerves from normal and streptozotocin-induced diabetic rats. In nerves frozen in situ, DAG content was reduced 22% in the proximal region and 77% in the distal region of diabetic nerve, principally because of the loss of associated fat. DAG levels in freshly dissected and desheathed diabetic nerve were decreased from 23 to 30% as compared with normal nerve. Determination of DAG molecular species distribution in desheathed normal nerve indicated that 18:0/20:4 accounted for 34%, 16:0/18:1 for 17%, and several other polyunsaturated fatty acid-containing species for 17% of the total. In diabetic nerve, the quantity of the 18:0/20:4 DAG, species was reduced by 37%, and this drop was 62% of the reduction in all molecular species. The content of the minor species, 16:0/20:4 DAG, was decreased by 48%. Our results suggest that nerve DAG arises in large part from phosphoinositide degradation. Moreover, these results provide support for the hypothesis that reduced Na+,K(+)-ATPase activity in diabetic nerve is a consequence of decreased phosphoinositide turnover, which thereby generates insufficient DAG to maintain a protein kinase C-mediated step necessary for activation of Na+,K(+)-ATPase.
Gender differences in cardiovascular risks of obese adolescents in the Bronx.

Objective: The associations between the degree of obesity and cardiovascular disease (CVD) risks and the impact of gender differences with regard to these risk factors are not well understood. The aim of our study was to examine the gender−specific differences in CVD risk factors in inner−city minority youths. Methods: A total of 269 adolescents (109 males and 160 females) were included in this retrospective study. Data on multiple metabolic variables were collected. Evaluation of abnormalities in these parameters was based on standard criteria. Pearson correlations were calculated to examine the relationship between body mass index (BMI) z−score and obesity−related parameters. Chi−square and Fisher’s tests were used to compare the frequencies of single or multiple cardiovascular risks in the two gender groups. Results: In the male group, BMI z−scores showed significant positive correlations with insulin resistance and diastolic blood pressure. In the female group, BMI z−scores showed significant positive correlations with insulin resistance and systolic blood pressure. In both genders, the prevalence of CVD risks was high, but a similar risk pattern was established in both sexes, with dyslipidemia being the highest, hypertension the second, and impaired glucose tolerance (IGT) being the least outstanding. The most important finding in this study was that the male group had a significantly higher prevalence of systolic hypertension. Conclusion: Male inner−city minority adolescents show a high prevalence of CVD risks associated with obesity. Appropriate risk stratification is critical to developing and implementing both therapeutic and preventive interventions. Conflict of interest:None declared.
Decreased consumption of rewarding sucrose solutions after injection of melanocortins into the ventral tegmental area of rats

The mesolimbic dopamine system is an important component of the neural circuitry controlling reward-related behavior. We have recently shown that the melanocortin peptides decrease normal homeostatic feeding through actions in the ventral tegmental area. It is unknown, however, whether melanocortin peptides can also act on dopamine pathways to regulate hedonic, reward-related aspects of feeding. In these studies, we tested whether injection of melanocortin receptor agonists directly into the ventral tegmental area (VTA) affected the intake of appetizing and rewarding sugar solutions in two-bottle choice tests. Varying doses of the melanocortin receptor agonist, MTII, were injected into the VTA, and the intake of different sugar solutions was measured in two-bottle choice tests to distinguish between potential effects on homeostatic versus hedonic aspects of feeding. In addition, 24-h food intake was measured throughout the experiments. Injection of MTII into the VTA dose dependently decreased the intake of 1 and 2 % sucrose solutions and 0.2 % saccharin solutions and decreased 24-h food intake in each study. Although MTII also decreased the intake of a 10 % sucrose solution, MTII appeared to be less potent in rats exposed to 10 % sucrose, as only the highest dose of MTII tested was effective at reducing 10 % sucrose intake and food intake in these rats. These studies demonstrate that melanocortins can act directly in the VTA to control reward-related feeding. Thus, these studies add to the growing body of evidence showing that melanocortins can interact with the mesolimbic dopamine system to regulate multiple reward-related behaviors.
The Development of a Computer-Based Teaching Tool for Internal Combustion Engine Courses

In this paper, the authors introduce the development of a computer-based internal combustion engine teaching tool for the undergraduate and professional training courses. The teaching tool simulates a SI (Spark Ignition) engine running in a testing facility. The physical and mathematical models, as well as the control strategies that govern the engine’s operation are embedded within the tool. It works as a virtual engine, and at the same time it displays and explains the physics behind each working process of the engine using graphical and animation features. The teaching tool serves as an assistant for the instructor of the internal combustion engine course. It provides the students with a visual and interactive environment to learn the physical processes of the internal combustion engines faster and easier.Copyright © 2004 by ASME
Naturally occurring tubulin-containing paracrystals in Allogromia: immunocytochemical identification and functional significance

Bundles of microtubules (MTs) are readily visualized in vivo by videomicroscopy in highly flattened reticulopodia of the foraminiferan protozoan Allogromia sp. strain NF. In this report we use videomicroscopy, immunocytochemistry, and high-voltage electron microscopy to characterize the dynamic changes that occur in this extensive MT cytoskeleton, and in the associated cytoplasmic transport, during induced withdrawal and subsequent reextension of reticulopodia. Within seconds after application of the withdrawal stimulus (seawater substitute made hypertonic with MgCl2) intracellular bidirectional transport along linear MT-containing fibrils ceases and is replaced by an inward, constant-velocity flow of cytoplasm along the fibrils. As withdrawal continues, most fibrils become wavy and coalesce to form phase-dense pools. These wavy fibrils and phase-dense pools contain a paracrystalline material and few if any MTs. Same-section correlative immunofluorescence and high-voltage electron microscopy reveal that the paracrystalline material contains tubulin. During recovery linear fibrils (MTs) rapidly extend from the phase-dense pools (paracrystals), which concurrently shrink in size, thus reestablishing normal network morphology and motility. We conclude that the MT cytoskeleton in Allogromia reticulopodia is transformed during withdrawal into a tubulin-containing paracrystal, which serves as a temporary reservoir of MT protein and an initiation site for MT regrowth.
Calculating a family’s asset mix

Abstract Two conclusions are reached about how a family should calculate its asset mix. First, if the assets will be used to finance retirement needs, the asset mix should be based on after-tax values, because goods and services are purchased with after-tax dollars. This novel conclusion rejects current practice. The second conclusion concerns which assets and liabilities should be included in the portfolio. If the purpose of the calculation is to consider a family’s retirement needs, the asset mix should include the promises of defined-benefit pension plans and Social Security, and the family’s mortgage should be treated as a short bond position. Also, if the family is willing to downsize or borrow against the residence, part of its value should be included in the portfolio.
Identifying Authors by Phonoprints in Their Characters’ Names: An Exploratory Study

AbstractIf authors put words together in ways that can be recognized as wordprints (; ; ), do they put sounds together in identifiable ways when they invent names? Could they have unique sound prints (phonoprints) as well? This exploratory study compared phonemic patterns of fictional names in the poorly written Manuscript Story by Spalding and the extremely well-written Lord of the Rings and related works by J. R. R. Tolkein with names from an authentic public record, the nineteenth-century US Census. Phonotactic probabilities were determined using a calculator (Vitevitch and Luce, 2004) available on the Internet. When multivariate patterns of mean phonotactic probabilities at each ordinal phoneme position were considered, phonoprints emerged that merit further examination.
Effects of regular pumping on photon statistics in masers and lasers.

In laser systems, regular pumping always reduces the photon noise. In micromaser systems, however, regular pumping may lead to photon noise reduction as well as photon noise increase depending on the operation conditions. The effect of higher-order terms in the expansion of ln(1+pu) with respect to the pumping regularity parameter p is discussed. These terms have a significant effect on the photon statistics in micromaser systems. Their effect in laser systems is quite small compared with the second order and can be neglected.
Regioselective anion generation and alkylation at carbon α to nitrogen in (CO)5WC[N(CH3)2]C6H4-p-CH3

Abstract Treatment of (CO)5WC[N(CH3)2]C6H4-p-CH3 (1) with lithium diisopropylamide (LDA) in THF at −78°C followed by quenching with D2O leads to incorporation of deuterium into the (E)-N-methyl group only. Reaction of the anion of 1 with benzyl bromide at −78°C followed by quenching with water gave the E-isomer of (CO)5WC[N(CH3)CH2CH2C6H5]C6H4-p-CH3 (2E, 26%) and recovered 1. When a mixture of the anion of 1 and benzyl bromide was warmed from −78°C to ambient temperature, a mixture of the E-isomer of the dibenzylated product (CO)5WC[N(CH3)CH(CH2C6H5)2]C6H4-p-CH was obtained. Reaction of the anion of 1 with allyl bromide gave (CO)5WC[N(CH3)CH2CH2CHCH2]C6H4-p-CH3 (5, 38%) and with methyl iodide gave a mixture of (CO)5WC[N(CH3)CH2CH3]C6H4-p-CH3 (6, 7%) and (CO)5W C[N(CH3)CH(CH3)2]C6H4-p-CH3 (7, 16%).
Calcium‐Magnesium Exchange in Aluminum Hydroxide‐Coated Montmorillonite

Aluminum hydroxide-coated montmorillonites have been shown to exhibit exchange properties which differ from those of pure montmorillonites. The direction of change was found to depend on the coating method used and the pH at which the coating is applied. The aluminum hydroxide-coated montmorillonites were prepared by two different methods at two pH's: (1) reacting aluminum chloride and sodium hydroxide in the presence of the clays (pH 7), and (2) titrating aluminum-saturated clays with calcium hydroxide to an alkaline pH (∼10). The resulting clay systems were equilibrated with calcium-magnesium solutions. The first system showed preferential adsorption of calcium over magnesium because the clays contained exchangeable sodium due to the precipitation of aluminum hydroxide in the presence of the clay. The second system showed no preference either for calcium or for magnesium. A distribution coefficient of unity resulted from compensation of exchangeable calcium by magnesium released from the aluminum hydroxide.
Ammonite evidence for long-term sea-level fluctuations between the 2nd and 3rd order in the lowest Cretaceous

Abstract The Berriasian to Barremian pelagic succession along the Rio Argos (SE Spain) has been subdivided into sequences which are precisely dated by ammonite biozones. Comparative analyses of ranges of Mediterranean ammonite species and elaborate studies of ammonite diversity revealed seven important changes in ammonite composition between (or even within) certain biozones. These changes are much greater than between most other biozones and represent important faunal turnovers. Similar changes occur at the same levels in other parts of the Mediterranean Region; they are therefore of supraregional significance. Each faunal turnover coincides with a prominent minimum in ammonite diversity and is immediately preceded by a marked maximum in diversity. The turnovers virtually coincide with particular sequence boundaries and are ascribed to severe eustatic sea-level falls with a far higher amplitude than those at most other sequence boundaries. The high diversities preceding the turnovers are ascribed to extra high eustatic sea-level stands, which correspond not only to bundles of extensively transgressive sequences in the Mediterranean Region, but also to major incursions of Tethyan organisms into the boreal seas of northern Germany and Russia. A causal relationship is assumed. The repeated high amplitude sea-level falls were ascribed to a long-term sea-level variation cycle, not apparent from the eustatic curve published by Haq et al . (1988).
Dye laser radiation in the 370-760-nm region pumped by a XeF excimer laser.

Energy conversion efficiency curves are presented for an oscillator/amplifier dye laser system for seventeen dyes covering the 370--760-nm range using a XeF excimer laser as the dye laser pumping source.
Effective use of teledermatology: defining expectations and limitations as we move forward.

To the Editor: The American Academy of Dermatology’s recent support of teledermatology is an important step toward incorporation of a novel technology that possesses the potential to improve patient care and lead to early detection of skin cancers and other cutaneous disease. This evolution in innovation will undoubtedly spread at a rapid pace and become an integrative component of the dermatology consultation process. Before we jump on the ‘‘teledermatology bandwagon,’’ it is important to proceed with caution. Our recent study found that a very large percentage of skin cancers within our health care system were diagnosed at sites remote from the lesion of concern prompting referral. Of the 149 skin cancers found by dermatologists, 61 (41%) were found at other areas that presumably might not have been included in a teledermatology consult. Although in our study we did not review teledermatology per se, we believe that these findings are provocative and warrant further study. Clearly, in areas of the world that are either remote or underserved, we agree that teledermatology may play an important role in allowing patients increased access to dermatologists. However, as physicians integrate teledermatology into their health care systems globally, both expectations and limitations must be defined to maximize effective use. If teledermatology is going to play an important role in our armamentarium to detect skin cancer, nondermatologists should have a lower threshold to include images of all lesions that represent potential concern after a total body skin examination. Assessment solely of one specific lesion of concern as may occur with teledermatology may be associated with underdiagnosis of clinically significant lesions that are not appreciated by the referring physician, and therefore must not be used as a substitute for a total body skin examination when skin cancer is suspected.
Effects of prednisolone on phospholipid metabolism in tissue culture.

Abstract The effect of prednisolone on the incorporation of 32P-phosphoric acid into asynchronously and synchronously growing Henle cells was determined. A 24 h exposure of cell cultures to prednisolone was necessary to produce a significant inhibition of total 32P incorporation into the cells. However, less than 1 h exposure to the hormone was sufficient to show an inhibition of 32P incorporation into the lipid fraction. After the separation of the phospholipid components by thin-layer chromatography, it was found that prednisolone caused no significant alteration in the distribution of the 32P label among the phosphatides. The incorporation of 32P into the phospholipid fraction of synchronously growing cells was suppressed by prednisolone during the entire division cycle.
DISULFIDE BONDS OF GLYCOPROTEIN HORMONES: Their Selective Reduction in the β Subunits of Bovine Lutropin and Thyrotropin

Treatment of the β subunit of either bovine lutropin (LH) or thyrotropin (TSH) at pH 8.2 by 5 mM dithioerythritol produces a set of partially reduced intermediates which, after alkylation with [14C] iodoacetate, can be separated by anion-exchange chromatography. Fractions from LH-β are obtained which represent molecules with 1, 2, 3 and 4 or 5 of the six disulfide bonds reduced. After full reduction, complete alkylation with non-radioactive iodoacetate and subsequent isolation of tryptic peptides, the radioactivity of each carboxymethyl cysteine residue was determined. With LH-β, the data show that disulfide bonds between half-cystines 93–100 and 26–110 open sequentially and that a third bond is between half-cystine 72 and either half-cystine 23 or 88; a specific disulfide interchange appears to have occurred between the two last positions. As reduction proceeds, extensive interchange occurs which prevents further assignment of disulfides; the half-cystines involved in disulfides 93–100 and 26–110, however, are not involved in the interchange. It is of interest that the assignments of bonds at 93–100 and 26–110 are in agreement with results of partial hydrolysis experiments from other laboratories, while the positions most involved in interchange are those where assignments from other laboratories differ. Under the same conditions of reduction, TSH-β yielded fractions containing one bond open (positions 88–95, analogous to 93–100 in LH-β) and small amounts of material in which reduction had occurred at positions 19–105 and 31–85 (analogous to 26–110 and 23–72 in LH-β). The data indicate that during the initial steps of reduction, the β subunits of LH and TSH open in a similar fashion, though disulfide interchange may begin sooner in the case of TSH. The results strongly support the assignments of two of the six disulfides in β subunits and show that unequivocal assignment of the four remaining bonds remains to be achieved.
Class numbers of imaginary quadratic fields

The classical class number problem of Gauss asks for a classification of all imaginary quadratic fields with a given class number N. The first complete results were for N = 1 by Heegner, Baker, and Stark. After the work of Goldfeld and Gross-Zagier, the task was a finite decision problem for any N. Indeed, after Oesterle handled N = 3, in 1985 Serre wrote, No doubt the same method will work for other small class numbers, up to 100, say. However, more than ten years later, after doing N = 5, 6, 7, Wagner remarked that the N = 8 case seemed impregnable. We complete the classification for all N < 100, an improvement of four powers of 2 (arguably the most difficult case) over the previous best results. The main theoretical technique is a modification of the Goldfeld-Oesterle work, which used an elliptic curve L-function with an order 3 zero at the central critical point, to instead consider Dirichlet L-functions with low-height zeros near the real line (though the former is still required in our proof). This is numerically much superior to the previous method, which relied on work of Montgomery-Weinberger. Our method is still quite computer-intensive, but we are able to keep the time needed for the computation down to about seven months. In all cases, we find that there is no abnormally large exceptional modulus of small class number, which agrees with the prediction of the Generalised Riemann Hypothesis.
The effects of ACTH4-10 on rats’ intakes of a sweetened alcoholic beverage

Standard laboratory rats were maintained on a daily regimen involving 22 h of deprivation of fluids followed by a 2-h opportunity to take water and a sweetened alcoholic beverage. The rats initially took very little of the alcoholic beverage, but after about 3 or 4 weeks they were taking about 2.0–2.5 g/kg of ethanol daily. This level of intake remained stable across subsequent daily opportunities. On the 37th day of the regimen, all subjects received a placebo prior to the opportunity to take fluids. On the next 2 days, the rats received 0, 1, 3, 10, or 30 mg of ACTH4-10 prior to the drinking session. No dose of ACTH4-10 reliably modified the rats’ intakes of the alcoholic beverage or water. This is in contrast with the report of Krishnan, Nash, and Maikel (1991) that 30 μ of ACTH4-10, given daily, reliably reduced 24-h intake of alcohol across an 8-day period.
Unintended effects of training on clinicians' interest, confidence, and commitment in using motivational interviewing

Abstract Background Improving clinicians’ interest, confidence, and commitment in using evidence-based treatment (EBT) is often an aim of training clinicians in EBT. However, the degree to which these areas actually improve through training and what their relationship is to treatment integrity is unknown. Method Using data from a multi-site study ( Martino et al., 2010 ) comparing three methods of clinician training in motivational interviewing (MI), changes in interest, confidence, and commitment over time and their relationship to MI adherence and competence were assessed using mixed-effects regression models. Individual patterns of change were examined through cluster analysis. Results Interest, confidence, and commitment declined over time across training conditions with two distinct patterns: 76% clinicians largely maintained strong interest in MI over time with only slight decreases in confidence and commitment (the “maintainers”), while 24% began with lower initial interest, confidence, and commitment, which subsequently declined over time (the “decliners”). Interest and commitment were not associated with MI adherence and competence; confidence was associated with increased competence in the use of advanced MI strategies. However, decliners demonstrated greater use of MI-inconsistent techniques than maintainers overall (d = 0.28). Conclusions Training in MI may have an unintended consequence of diminishing clinicians’ interest, confidence, or commitment in using MI in practice. While attitudinal variables in this study show mixed relationships to MI integrity, they may have some utility in identifying less enthusiastic participants, better preparing them for training, or tailoring training approaches to meet individual training needs.
Marxist and Other Thought in the Light of the Gorbachev Revolution

Examines the sources and implications of Mikhail Gorbachev′s policies insofar as they have been policies of liberalization. It is principally argued that Marxism has been a Western phenomenon and thereby a vehicle for the export of Western Enlightenment values to Third World countries but also to the Soviet Union itself. The nature and role of Marx′s analyses are considered in that light. So also are the status of nationalism in the USSR, the historical meaning and promise of socialism, the role of the legal‐economic nexus in the social reconstruction of reality in the USSR and in Central and Eastern Europe, the relevance to those developments of the emerging new European and world systems, and the relevance of all these for social economics.
Effect of a membrane-targeted sphingosine kinase 1 on cell proliferation and survival.

Numerous extracellular stimuli activate SK1 (sphingosine kinase type 1) to catalyse the production of sphingosine 1-phosphate, a bioactive lipid that functions as both an extracellular ligand for a family of G-protein-linked receptors and as a putative intracellular messenger. Phorbol esters, calcium or immunoglobulin receptors stimulate SK1 by promoting its translocation to the plasma membrane, which brings it into proximity both to its substrate (i.e. sphingosine) and to activating acidic phospholipids (e.g. phosphatidylserine). To evaluate the consequence of SK translocation, we generated an SK1-derivative tagged with a myristoylation sequence (Myr-SK1) on its N-terminus and overexpressed the construct in 3T3-L1 fibroblasts using recombinant retrovirus. Myr-SK1 overexpression increased SK activity by more than 50-fold in crude membranes, while only stimulating cytoplasmic SK activity by 4-fold. In contrast, the overexpression of WT-SK1 (wild-type SK1), as well as that of a construct containing a false myristoylation sequence (A2-Myr-SK1), markedly increased SK activity in both membrane and cytoplasmic compartments. Immunofluorescence confirmed that Myr-SK1 preferentially localized at the plasma membrane, whereas WT-SK1 and A2-Myr-SK1 partitioned in cytoplasmic/perinuclear cellular regions. Surprisingly, Myr-SK1 overexpression significantly decreased the rates of cell proliferation by delaying exit from G0/G1 phase. Moreover, expression of Myr-SK1 but not WT-SK1 or A2-Myr-SK1 protected cells from apoptosis induced by serum withdrawal. Collectively, these findings reveal that altering the subcellular location of SK1 has marked effects on cell function, with plasma membrane-associated SK having a potent inhibitory effect on the G1–S phase transition.
Effect of dietary factors on incidence of spontaneous and induced convulsions in C3H male mice.

Summary1. The incidence of “spontaneous” convulsions and of convulsive deaths in C3H male mice is greatly reduced by caloric restriction or by supplement of vit. B12 in the diet fed ad libitum. Substitution of hydrogenated vegetable fat for lard decreased the age of onset of convulsions and increased the incidence of convulsive deaths. 2. Studies with auditory and electric stimulation appear to confirm the existence of a difference between the effect of HVF and of lard.
Production and Characterization of Bifunctional Enzymes. Domain Swapping To Produce New Bifunctional Enzymes in the Aspartate Pathway

The bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli catalyzes non-consecutive reactions in the aspartate pathway of amino acid biosynthesis. Both catalytic activities are subject to allosteric regulation by the end product amino acid L-threonine. To examine the kinetics and regulation of the enzymes in this pathway, each of these catalytic domains were separately expressed and purified. The separated catalytic domains remain active, with each of their catalytic activities enhanced in comparison to the native enzyme. The allosteric regulation of the kinase activity is lost, and regulation of the dehydrogenase activity is dramatically decreased in these separate domains. To create a new bifunctional enzyme that can catalyze consecutive metabolic reactions, the aspartokinase I domain was fused to the enzyme that catalyzes the intervening reaction in the pathway, aspartate semialdehyde dehydrogenase. A hybrid bifunctional enzyme was also created between the native monofunctional aspartokinase III, an allosteric enzyme regulated by lysine, and the catalytic domain of homoserine dehydrogenase I with its regulatory interface domain still attached. In this hybrid the kinase activity remains sensitive to lysine, while the dehydrogenase activity is now regulated by both threonine and lysine. The dehydrogenase domain is less thermally stable than the kinase domain and becomes further destabilized upon removal of the regulatory domain. The more stable aspartokinase III is further stabilized against thermal denaturation in the hybrid bifunctional enzyme and was found to retain some catalytic activity even at temperatures approaching 100 degrees C.
Cross-flow membrane plasmapheresis technique for continuous ex vivo plasma sampling.

Abstract A technique is described for plasma sampling by continuous membrane plasmapheresis performed on blood flowing through an extracorporeal arteriovenous shunt. The plasmapheresis sampler in the shunt employs replaceable commercial planar membranes 2.5 cm in diameter. Validation tests were conducted for 0.6-μm pore diameter microporous membranes with several low-molecular-weight, nonmetabolized solutes that either rapidly equilibrate between plasma and formed elements or remain extracellular. Ex vivo tests were performed for bolus intravenous administration to rabbits. The technique yielded values for time-averaged plasma concentrations comparable to those obtained with serial blood and continuous blood withdrawal methods. The new technique should be particularly advantageous when the distribution of the solute of interest between plasma and formed elements of the blood undergoes significant changes during the sampling interval as a result of binding, exchange, or metabolism in the formed element phase.
Striving for creativity.

My joy in seeing the title of Eliot Marshall's article “NIH panel urges overhaul of the rating system for grants” (News & Comment, [31 May, p. 1257][1]) turned to dismay when I read that members of the National Institutes of Health (NIH) panel evaluating the peer-review system “left innovation out,” according to Hugh Stamper (extramural research director at the National Institute of Mental Health), “because it seemed a bad idea to suggest that every grant should strive for creativity.” The current very low proportion of funded grants coupled with a rating system subject to a ceiling effect effectively results in a blackball system: Even one disgruntled evaluator can knock a proposal out of the competition. Many scientists have deplored an evaluative system that they have seen as implicitly rewarding grant proposals that are not objectionable to anyone passing judgment, rather than proposals that are highly creative and therefore likely to offend at least some vested interest ([1][2]). The recommendation of the panel makes explicit what before had been implicit—the institutionalized view that scientific creativity is not a necessary condition for a grant's being reviewed favorably. Yet, the research that has mattered in science has always been that which is creative and thus often defies existing conventions. There is a problem with the rating system at NIH, but fixing the rating system won't fix the larger problem of priorities that fly in the face of the history and philosophy of science. 1. 1.[↵][3]1. R. J. Sternberg, 2. T. I. Lubart , Defying the Crowd: Cultivating Creativity in a Culture of Conformity (Free Press, New York, 1995). [1]: /lookup/doi/10.1126/science.272.5266.1257 [2]: #ref-1 [3]: #xref-ref-1-1 "View reference 1. in text"
Structural influences on the amperometric detection of opiates in high-performance liquid chromatography.

Abstract The oxidation reactions of a series of opiates occuring at a glassy-carbon electrode in amperometric high-performance liquid chromatographic detection has been investigated. A structure-reactivity correlation has been drawn for morphone, morphinan and benzomorphan derivatives. Polarography and hydrodynamic voltammography were used to show the importance of phenolic groups to this reaction. Acyl substitution on the phenol did not prevent amperometric detection.
Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guerin and subsequent challenge with lipopolysaccharide

Mice with a targeted disruption of the interferon gamma receptor gene (IFN-gamma R0/0 mice) and control wild-type mice were inoculated with the Bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis. BCG infection was not lethal for wild-type mice whereas all IFN-gamma R0/0 mice died approximately 7-9 wk after inoculation. Histological examination at 2 and 6 wk after BCG inoculation showed that livers of IFN-gamma R0/0 mice had higher numbers of acid-fast bacteria than wild-type mice, especially at 6 wk. In parallel, the livers of IFN-gamma R0/0 mice showed a reduction in the formation of characteristic granulomas at 2 wk after inoculation. Injection of lipopolysaccharide (LPS) 2 wk after BCG inoculation was significantly less lethal for IFN-gamma R0/0 mice than for wild-type mice. Reduced lethality of LPS correlated with a drastically reduced production of tumor necrosis factor alpha (TNF-alpha) in the IFN-gamma R0/0 mice. Interleukin 1 alpha (IL-1 alpha) and IL-6 levels in the serum were also significantly reduced in the IFN-gamma R0/0 mice after BCG infection and LPS challenge. The greatly reduced capacity of BCG-infected IFN-gamma R0/0 mice to produce TNF-alpha may be an important factor in their inability to resist BCG infection. These results show that the presence of a functional IFN-gamma receptor is essential for the recovery of mice from BCG infection, and that IFN-gamma is a key element in the complex process whereby BCG infection leads to the sensitization to endotoxin.
Gas-phase self-assembly of endohedral metallofullerenes

METALLOFULLERENES1,2consist of metal atoms trapped inside closed fullerene cages. Virtually nothing is known about the mechanism of metallofullerene synthesis, although the possibility of a condensed-phase mechanism has been suggested in recent studies3,4. Here we show that laser vaporization of a La2O3/graphite rod produces a number of LaC60+ isomers, including the endohedral metallofullerene and a variety of different isomers in which lanthanum seems to be bound to polycyclic polyyne rings. When heated, nearly all of the different ring isomers convert spontaneously into metallofullerenes, trapping the metal atom inside the fullerene cage with remarkably high efficiency (>98%). We suggest that in the first step of this annealing process the lanthanum atom acts as a nucleation centre and the carbon rings arrange themselves around the lanthanum atom before converting into a fullerene cage.