cssi/SciSciGPT-SciSciNet huggingface dataset:
Persistence of Cerebral Palsy Diagnosis Assessment of a Low-Birth-Weight Cohort at Ages 2, 6, and 9 Years

We examined the stability of nondisabling and disabling cerebral palsy at age 2 in a longitudinally followed tri-county low-birth-weight (<2000 g) birth cohort. A total of 1105 newborns were enrolled, 901 (81.5%) survived to age 2, and 86% (n = 777) were followed up. Of the 113 cerebral palsy diagnoses at age 2, 61 (9% of the cohort, n = 61/777) had disabling cerebral palsy and 52 (7%, n = 52/777) had nondisabling cerebral palsy. Of 48 followed children diagnosed with disabling cerebral palsy at age 2, 98% were again classified as having cerebral palsy at school age, and 1 had an uncertain cerebral palsy status. By contrast, 41% (n = 17) of the 43 children diagnosed with nondisabling cerebral palsy at age 2 were classified as not having cerebral palsy. Of the 517 followed children who were not diagnosed with cerebral palsy at age 2, 7% (n = 35) were classified as having late emerging nondisabling cerebral palsy at school age.
Low-loss high power microwave switching using novel nitride based MOS heterostructure field-effect transistors

A microwave switch based on a novel nitride based metal-oxide-semiconductor heterostructure field effect transistor (MOSHFET) is proposed and demonstrated. Due to record high saturation current and breakdown voltage, negligible gate leakage current and low gate capacitance, the proposed switch allows for less than 0.3 dB insertion loss and more than 35 dB isolation. The unique feature of the MOSHFET based switch is the maximum switching power, in excess of 80 W for a 1 mm wide active element.
Enhancement of superconductivity in La 1 -x Sm x O 0.5 F 0.5 BiS 2

The superconducting and normal-state properties of ${\mathrm{La}}_{1\ensuremath{-}x}{\mathrm{Sm}}_{x}{\mathrm{O}}_{0.5}{\mathrm{F}}_{0.5}{\mathrm{BiS}}_{2} (0.1\ensuremath{\le}x\ensuremath{\le}0.9)$ have been studied via electrical resistivity, magnetic susceptibility, and specific heat measurements. By using suitable synthesis conditions, Sm exhibits considerable solubility into the ${\mathrm{CeOBiS}}_{2}$-type ${\mathrm{LaO}}_{0.5}{\mathrm{F}}_{0.5}{\mathrm{BiS}}_{2}$ lattice. In addition to a considerable enhancement of the superconducting volume fraction, it is found that the superconducting transition temperature ${T}_{c}$ is dramatically enhanced with increasing Sm concentration to 5.4 K at $x=0.8$. These results suggest that ${T}_{c}$ for ${\mathrm{SmO}}_{0.5}{\mathrm{F}}_{0.5}{\mathrm{BiS}}_{2}$ could be as high as $\ensuremath{\sim}6.2$ K, and comparably high ${T}_{c}$ values might also be obtained in the compounds $Ln{\mathrm{O}}_{0.5}{\mathrm{F}}_{0.5}{\mathrm{BiS}}_{2} (Ln=\text{Eu}\ensuremath{-}\text{Tm})$ if they can be synthesized.
Comparison of levalbuterol and racemic albuterol based on cardiac adverse effects in children.

OBJECTIVE To compare the cardiac effects of levalbuterol with those of racemic albuterol based on changes in heart rate (HR) in pediatric patients. METHODS The medical records of hospitalized children ages 1 month to 12 years, who received either levalbuterol or racemic albuterol via nebulizer for 3 consecutive doses between January 2006 and December 2008 were reviewed. The documented HR was collected prior to and after each administered dose of bronchodilator. The primary outcome was the largest percentage of change in HR between groups. Secondary outcomes of comparisons of the number of patients who had more than a 10% change in HR and incidence of tachycardia were included. RESULTS A total of 50 patients, 25 in each group, was included in the study. All patients in the racemic albuterol group received 2.5 mg per dose, while most of the patients in the levalbuterol group received 0.63 mg per dose (19 patients, 76%). Only 6 levalbuterol patients received a dose of 1.25 mg. Nineteen of 25 patients (76%...
Improving reading comprehension and social studies knowledge in middle school

This study aimed to determine the efficacy of a content acquisition and reading comprehension treatment implemented by eighth-grade social studies teachers. Using a within-teacher design, the eighth-grade teachers’ social studies classes were randomly assigned to treatment or comparison conditions. Teachers (n = 5) taught the same instructional content to both treatment and comparison classes, but the treatment classes used instructional practices focused on teaching essential words, text as a source for reading and discussion, and team-based learning approaches. Students in the treatment conditions (n = 261) scored statistically higher than students in the comparison conditions (n = 158) on all three outcomes: content acquisition (ES = 0.17), content reading comprehension (ES = 0.29), and standardized reading comprehension (ES = 0.20). Findings are interpreted as demonstrating support for the treatment in improving both knowledge acquisition and reading comprehension within content area instruction.
PSYCHOLOGICAL CONDITIONS OF FREEDOM

Strmmasy.-This paper documents ways in which psychology can contribute to policy discussions of freedom. Some of the more important psychological variables that are relevant to the degree ro which persons are free include ability to handle unwanted experiences (fear, anxiety, etc.) and control personality processes that might undermine choice, intensity of conflicting motives and needs, degree of flexibility, and dependency. Further research is encouraged by indicating where existing disagreements between theories and present lack of research limit our knowledge about personal freedom. With a few notable excepcions (such as Bay, 1958), discussions of freedom in political science, economics, policy studies, and sccial philosophy are carried on with few references to any but the most superficial psychological variables. It is the thesis of this paper that psychology has much to contribute to discussions of actual (and not merely perceived) freedom, that many of its theories and research studies are relevant to and important for assessing the level of personal freedom. The content of these theories (Freud, Murray, Maslow, Kelly, etc.) is well-known to psychologists and needs no documenting here. The purpose of this paper is to show in what ways these theories are relevant to freedom. Some scientists and practitioners are understandably skeptical of any discussions of topics such as freedom, feeling that these are topics which ate at best normative and at worst metaphysical. To allay such concerns, it woi~ld be possible to claim as Oppenheim (1961) does that some definitions of freedom are purely descriptive. But even if we are more cautious and allow that linking any set of descriptive statements with the word "freedom" makes the definition normative, the definiens remains descriptive and we can ask in what ways the theories and empirical results chat form the subject matter of psychology are relevant to the conditions described. One of the reasons for the neglect of psychology in these discussions is the restricted concepts of freedom that have been used. We shall use a more comprehensive concept (Draughon, 1978b) and one that also happens to accord reasonably well with the ordinary perceived meaning of the word (Draughon, 1978a, 1978~; Steiner, 1970). It is not the purpose here to argue in favor of this conception, since such arguments are available elsewhere (Draughon, 1978b). The reason for choosing this definition over ochers is The author gratefully acknowledges suggestions made by Dr. Margaret Stefan Draughon during the development of this paper.
Forebrain lesions disrupt development but not maintenance of song in passerine birds

The magnocellular nucleus of the anterior neostriatum is a forebrain nucleus of passerine birds that accumulates testosterone and makes monosynaptic connections with other telencephalic nuclei that control song production in adult birds. Lesions in the magnocellular nucleus disrupted song development in juvenile male zebra finches but did not affect maintenance of stable song patterns by adult birds. These results represent an instance in which lesions of a discrete brain region during only a restricted phase in the development of a learned behavior cause permanent impairment. Because cells of the magnocellular nucleus accumulate androgens these findings raise the possibility that this learning is mediated by hormones.
Activity of Liver Fructose Diphosphatase from Chick Embryos Treated with Aminoguanidine Sulfate

Abstract Injection of chick embryos with aminoguanidine sulfate (AGS) on the fourth day of incubation resulted in a decreased specific activity of liver fructose diphosphatase (FDPase) prior to hatch time. This decreased FDPase specific activity was found to be the consequence of increased levels of an enzyme inhibitor (adenosine 5′-monophosphate) rather than a specific repression of enzyme synthesis.
Building and Understanding Adaptive Systems: A Statistical/Numerical Approach to Factory Automation and Brain Research

Successes with expert systems and other specialized systems have revived hopes for factory automation and productivity growth. A full realization of these potentials will require conscious effort to overcome obsolete rigidities, to develop unified and adaptive methods for integrating complex systems, and to increase our understanding of these systems (understanding which is vital to human productivity in developing software). How adaptive systems may be built and understood by extending control theory and statistics is discussed. Adaptive systems, like human infants, are less agile than young monkeys but have something important to contribute as they mature. It argues that the old dream of understanding intelligence in generalized terms, permitting a unified understanding of adaptive systems and of the human mind, was not incorrect; rather, the early attempts in that direction failed because they did not make full use of research possibilities in statistics, control theory, and numerical analysis (many of which are still unexploited) and were limited by hardware costs which are now coming down. A basic adaptive system derived from this approach fits the fundamental, qualitative empirical facts of human brain physiology in some detail (unlike the usual "general neuron models," which rarely even discriminate between basic components of the brain), and offers opportunities for further research; it can even translate certain fundamental ideas of Freud into something more mathematical and scientific. The mathematics of the basic system, and the fit to the brain, are described in detail.
Tryptophan metabolites in hypoglycemia associated with neoplasia

Studies on tryptophan metabolites in the blood and urine of 5 additional patients having symptoms of hypoglycemia associated with neoplasia are reported. Three patients having islet cell tumors and hypoglycemia had normal levels of tryptophan metabolites in the blood and urine during hypoglycemia. A patient with metastatic carcinoma of the breast and a patient with metastatic adrenal carcinoma also had normal values for tryptophan metabolites in the blood and urine during hypoglycemia. These patients are compared with 2 previously reported patients who had extrapancreatic neoplasms, hypoglycemia and high levels of tryptophan metabolites in the blood and urine. The findings suggest that, when a patient has high levels of tryptophan metabolites in the blood and urine during hypoglycemia, a diligent search for extrapancreatic neoplasm should be undertaken. When tryptophan metabolites in the blood and urine are normal during hypoglycemia, a careful search for an islet cell neoplasm is indicated.
Trade Agreement vs. Open Shop: Employers' Choices before WWI

Neither cultural individualism nor hostility to craft control adequately explains American employers' rejection of collective bargaining before World War I. Evidence from selected cases in the U.S. and Britain suggests both that open-shop policies and trade agreements helped employers manage workplace conflict amid major changes in production practices, and that the relative timing and pace of changes in technology, market structure, and union growth shaped employers' choices.
Independence Problems for Certain Tests Based on the Shine-Bower Error Term

It is shown for the Shine-Bower single-subject ANOVA that the numerator and denominator of all F tests based on the Shine-Bower error term are independent of each other. It is also shown that the same property holds for all such tests in the Shine Combined ANOVA except for the test for the trial by subject interaction.
A Unified Theory of Optimization of Structures with Displacement and Compliance Constraints

ABSTRACT ABSTRACT A recently developed theory of design sensitivity analysis is applied to obtain rigorous and computable expressions for the derivative of structural displacement with respect to design. This derivative is used to obtain op-timality criteria for a variety of problems, including optimization of beam and plate structures with constraints on deflection at known points, maximum displacement, and compliance. Most results in the literature are shown to follow from the optimally criteria derived here. Finally, applications of the design differentiation theory are suggested to resolve difficulties with numerical methods that have been used in the past.
HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B-cell lymphomas.

Human immunodeficiency virus (HIV)-I infection is associated with the development of aggressive extranodal B-cell non-Hodgkin's lymphomas. Using microvascular endothelial cell (MVEC)-enriched bone marrow stromal cultures, HIV infection of stromal MVECs from lymphoma patients induced the outgrowth of malignant B cells. MVECs were the only HIV-infected cells in the stroma, and purified brain MVECs also induced a phenotype supportive of neoplastic B-cell attachment and proliferation. HIV infection of MVECs stimulated surface expression of CD40 and allowed preferential induction of the vascular cell adhesion molecule VCAM-1 after CD40 triggering. B-lymphoma cells expressed the CD40 ligand (CD40L), and blocking of CD40–CD40L interactions between HIV-infected MVECs and B-lymphoma cells inhibited B-cell attachment and proliferation. These observations suggest that HIV promotes B-lymphoma cell growth through facilitating attachment of lymphoma cells to HIV-infected MVECs and represent a novel mechanism through which viruses may induce malignancies.
Effects of cimaterol on muscle protein metabolism and its actions in hypothyroid and hyperthyroid rats

Objectives were to examine mechanisms underlying anabolic actions of cimaterol in skeletal muscle and to evaluate cimaterol's actions in hypothyroid and hyperthyroid rats. In the first study growing rats were fed either a control diet or a diet containing cimaterol for 10 days. In a second study sham-thyroidectomized and thyroidectomized (Tx) rats were assigned to one of 5 treatments: control (sham-Tx), Tx, Tx supplemented with cimaterol, Tx injected with triiodothyronine (T3), and Tx rats injected with T3 and supplemented with cimaterol. Effects of treatments on growth, muscle weights and urinary NT-methylhistidine (NMH) excretion were evaluated in both trials. Muscle was also collected for determinations of DNA, RNA, protein and activities of several proteolytic enzymes. Cimaterol caused muscle hypertrophy and increased urinary NMH excretion. Hence, anabolic actions of cimaterol may result from an increase in myofibrillar protein synthesis which exceeds changes in myofibrillar protein degradation. Urinary NMH excretion was reduced by thyroidectomy and increased in hyperthyroid rats and both hypothyroidism and hyperthyroidism were characterized by myopathy. Cimaterol increased muscle weights in hypothyroid but not in hyperthyroid rats. Therefore, cimaterol's anabolic properties are thyroid hormone-independent and antagonized by excess thyroid hormone. Anabolic actions of cimaterol in hypothyroid rat muscle were attributed to an action on protein synthesis because urinary NMH excretion was not affected by cimaterol but muscle RNA concentration was increased. Activities of cathepsins B, D and L and neutral proteinase were dose-related to thyroid status, however, were unrelated to cimaterol-dependent perturbations in NMH excretion. Control of muscle protein balance by thyroid hormones may involve regulation of these enzymes; however, control of muscle protein degradation by cimaterol is likely directed towards other proteolytic mechanisms or to mechanisms which alter susceptibility of myofibrillar proteins to degradation.
Circumflex Coronary Artery Aneurysm Visualized by Real-Time Cross-Sectional Echocardiography: A Possible Sequelae of Previously Unrecognized Coronary Arteritis in the Adult

Real-time cross-sectional echocardiography disclosed an aneurysm of the circumflex branch of the left coronary artery in an asymptomatic 30-year-old man. Plain chest roentgenogram showed an abnormal silhouette along his left heart border. He also was found to have an abnormal contraction pattern of the posterolateral wall of the left ventricle and a reduced left ventricular ejection fraction. Left ventricular and coronary angiography showed a similar impairment in left ventricular function and occlusion of the circumflex branch of the left coronary artery. Surgery and pathologic examination confirmed the presence of the aneurysm. The echocardiographic characteristics of this lesion and the left ventricular contraction abnormalities suggest the possibility that it resulted from a remote episode of coronary arteritis. Real-time cross-sectional echocardiography, by virtue of its ability to provide visualization of structures along the posterior border of the heart as well as information about regional wall motion, may be of considerable value in localizing and defining lesions occurring in this area.
Insolation forcing of Holocene climate change in Southern California: a sediment study from Lake Elsinore

Lake Elsinore is the largest natural lake in Southern California. As such, the lake provides a unique opportunity to investigate terrestrial climate on timescales otherwise underrepresented in the region’s terrestrial environment. In November 2003, three ∼10 m drill cores were extracted from the depocenter region of Lake Elsinore. These drill cores, spanning the past 9,500–11,200 calendar years, represent the first complete Holocene record of terrestrial climate from Southern California. In this paper, we focus on two adjacent, depocenter cores (LEGC03-2 and LEGC03-3), which have been correlated to develop a single composite core. Twenty-two AMS 14C dates on bulk organic matter and one cross-correlated exotic pollen age constitute the composite core’s age control. Several methods of analysis, including mass magnetic susceptibility, % total organic matter, % total carbonate, % HCl-extractable Al, and total inorganic P are used to infer climate for the past 9,500 calendar years in Southern California. Together, these data indicate a wet early Holocene followed by a long-term drying trend. Recent lake-level reconstructions from Owens Lake and Tulare Lake support our contention for a wetter-than-today early Holocene. Lacustrine sediments from the Mojave Desert also support our conclusions. We suggest that over the duration of the Holocene changing summer/winter insolation alters the region’s long-term hydrologic balance through its modulation of atmospheric circulation and its associated storm tracks. Minimum early Holocene winter insolation and maximum summer insolation act together to increase the region’s total annual precipitation by increasing the frequency of winter storms as well as enhancing the magnitude and spatial extent of the North American monsoon, the frequency of land-falling tropical cyclones in Southern California, and regional convective storms, respectively. Gradual decreases in summer insolation and increases in winter insolation produce the opposite effect with maximum drying in the late Holocene.
Genetic control of mRNA decay in T4 phage-infected Escherichia coli.

Abstract Several T4 phage mutations were isolated that resulted in the hyperproduction of certain phage-induced proteins in infected Escherichia coli hosts. These mutations map in T4 gene reg A and affect a diffusable substance that plays a role in the control of structural and functional decay of a small number of mRNA species that are synthesized during early times after phage infection. The reg A gene product may either by a specific ribonuclease or may indirectly affect mRNA decay by influencing the selectivity of translation.
Determinants of PHC productivity and resource utilization: a comparison of public and private physicians in Macedonia

The dominant reform paradigm for developing countries introduces market forces into health care provision to improve quality and efficiency. Yet, there is very little empirical evidence as to how individual physicians respond to such incentives. Using a survey of primary health care providers in the Republic of Macedonia, the effect of privatization on physician workload and resource utilization is examined. The survey of physicians in public and private clinics provides extensive data on physician demographics, practice patterns and capital inputs, with an innovation being a measure of physician skill based on responses to several clinical vignettes. Physician production of patient visits is modeled as a jointly determined process of workload and input utilization. Such a formulation acknowledges the endogeneity of input and output and, more importantly, allows the straightforward estimation of the demand equations for labor and capital inputs. Controlling for physician and practice characteristics, private physicians do exhibit higher productivity and greater capital resource use per patient. Major factors influencing workload and resource use are skill and referral rates, both of which have important implications for designing comprehensive and effective physician incentive systems.
Nanoclusters self-assembled from conformation-stabilized influenza M2e as broadly cross-protective influenza vaccines

Abstract Influenza vaccines with broad cross-protection are urgently needed. The highly conserved ectodomain of the influenza matrix protein 2 (M2e) can be a promising candidate if its low immunogenicity was overcome. In this study, we generated protein nanoclusters self-assembled from conformation-stabilized M2e tetramers (tM2e) to improve its immunogenicity. The resulting nanoclusters showed an average hydrodynamic diameter of 227nm. Vaccination with the nanoclusters by an intranasal route elicited high levels of serum antigen-specific IgG in mice (approximately 100-fold higher than that obtained with soluble tM2e), as well as antigen-specific T cell and mucosal antibody responses. The immunity conferred complete protection against lethal challenge with homo- as well as heterosubtypic viruses. These results demonstrate that nanoclusters assembled from conformation-stabilized M2e are promising as a potential universal influenza A vaccine. Self-assembly into nanoclusters represents a novel approach for increasing the immunogenicity of vaccine antigens. From the Clinical Editor In order to develop more effective influenza vaccination, the highly conserved ectodomain of M2e could be a promising candidate. Unfortunately, it is a weak antigen for vaccination purposes. In this study, self-assembled protein nanoclusters of tM2e were generated and tested. The nanoclusters demonstrated superior vaccination properties, with complete protection against lethal challenge in the studied rodent model, raising hope for the introduction of similar vaccines to challenge human influenza outbreaks.
Biological oxidation and the mobilization of mitochondrial calcium during the differentiation of Physarum polycephalum.

We have previously reported that calcium is required for the starvation-induced differentiation of the slime mold, Physarum polycephalum. With the exception of calcium, each component of the complex starvation medium may be withheld and the organism will still differentiate into spherules. The results of the present study reveal that spherulation will proceed normally when the microplasmoidal cells are transferred from nutrient medium to a citrate buffer containing only 8 mM Ca CI2. Electron microscopy and X-ray microprobe analysis reveal that there is an initial increase in the population of calcium-containing mitochondrial granules when the microplasmodia are induced to differentiate. However, as differentiation proceeds, these granules decrease in number and are virtually absent from the mitochondria of mature spherules. The accumulation and depletion of calcium-containing granules is not observed in a nondifferentiating strain of Physarum cultured under standard conditions, but is observed when this strain is first treated with a calcium-enriched nutrient medium that conditions it for spherulation. Changes in the cellular concentrations of NADH and lipid peroxides, and in the activity of superoxide dismutase, correspond temporally to the pattern of increase and depletion of the calcium-containing inclusions. The oxidative stress associated with starvation-induced spherulation may be a consequence of the active accumulation of calcium; the mobilization of this calcium may then be the event that initiates differentiation.
The phase-field method: simulation of alloy dendritic solidification during recalescence

An overview of the phase-field method for modeling solidification is given and results for nonisothermal alloy dendritic growth are presented. By defining a “phase-field” variable and a corresponding governing equation to describe the state (solid or liquid) in a material as a function of position and time, the diffusion equations for heat and solute can be solved without tracking the liquid-solid interface. The interfacial regions between liquid and solid involve smooth, but highly localized variations of the phase-field variable and the composition. Simple finite-difference techniques on a uniform mesh can be used to treat the evolution of complex growth patterns. However, large-scale computations are required. The method has been applied to a variety of problems, including thermally driven dendritic growth in pure materials, solute-driven isothermal dendritic growth in alloys, eutectic growth (all at high supercoolings or supersaturations), solute trapping at high velocity, and coarsening of liquid-solid mixtures. To include thermal effects in solute-driven dendritic growth in alloys, a simplified approach is presented here that neglects the spatial variation of temperature in the computational domain but provides for changes with time and thus includes recalescence. Growth morphologies and solute patterns in the liquid and solid obtained for several values of an imposed heat flux are compared to results for isothermal growth.
The tyranny of experts: economists, dictators, and the forgotten rights of the poor, by William Easterly

Bill Easterly’s new book is a meandering melange of anecdotes, parts of Why Nations Fail (Acemoglu and Robinson 2012), and miscellaneous pages from human rights reports, sprinkled with history of e...
Genome-wide comparison of paired fresh frozen and formalin-fixed paraffin-embedded gliomas by custom BAC and oligonucleotide array comparative genomic hybridization: facilitating analysis of archival gliomas

Array comparative genomic hybridization (aCGH) is a powerful tool for detecting DNA copy number alterations (CNA). Because diffuse malignant gliomas are often sampled by small biopsies, formalin-fixed paraffin-embedded (FFPE) blocks are often the only tissue available for genetic analysis; FFPE tissues are also needed to study the intratumoral heterogeneity that characterizes these neoplasms. In this paper, we present a combination of evaluations and technical advances that provide strong support for the ready use of oligonucleotide aCGH on FFPE diffuse gliomas. We first compared aCGH using bacterial artificial chromosome (BAC) arrays in 45 paired frozen and FFPE gliomas, and demonstrate a high concordance rate between FFPE and frozen DNA in an individual clone-level analysis of sensitivity and specificity, assuring that under certain array conditions, frozen and FFPE DNA can perform nearly identically. However, because oligonucleotide arrays offer advantages to BAC arrays in genomic coverage and practical availability, we next developed a method of labeling DNA from FFPE tissue that allows efficient hybridization to oligonucleotide arrays. To demonstrate utility in FFPE tissues, we applied this approach to biphasic anaplastic oligoastrocytomas and demonstrate CNA differences between DNA obtained from the two components. Therefore, BAC and oligonucleotide aCGH can be sensitive and specific tools for detecting CNAs in FFPE DNA, and novel labeling techniques enable the routine use of oligonucleotide arrays for FFPE DNA. In combination, these advances should facilitate genome-wide analysis of rare, small and/or histologically heterogeneous gliomas from FFPE tissues.
Clinical evaluation of acetyl-digitoxin

Dtherapy of heart failure and the arrhythmias has been greatly extended and made more precise with the advent of the cardiac glycosides. Differences ‘exist in clinical effect from one glycoside to another and may be due to variations in degree of absorption, serum binding power, toxic cumulation and dissipation. Also, it is well-known that the individual response to digitalis is quite variable, suggesting that experimentation is highly desirable to find the right glycoside which will be most beneficial to any given patient. However, most physicians prefer to limit the number of drugs in any one category and are ever on the lookout for a single drug which will serve the greatest number of patients. In a search for a glycoside having a broad range of application, Stoll and Kreis’ isolated Acylanid@ from digitalis lanata by subjecting lanatoside A to enzyme hydrolysis. Acylanid is acetyldigitoxin, differing from digitoxin through the presence of an acetyl radical attached to the third digitoxose in the molecule. Pharmacologic study by Rothlin, Bircher, and Schalch2 has demonstrated acetyl-digitoxin to be strongly bradycardic, well-absorbed, and less toxic than
Activated ion electron capture dissociation for mass spectral sequencing of larger (42 kDa) proteins.

In previous studies, electron capture dissociation (ECD) has been successful only with ionized smaller proteins, cleaving between 33 of the 153 amino acid pairs of a 17 kDa protein. This has been increased to 99 cleavages by colliding the ions with a background gas while subjecting them to electron capture. Presumably this ion activation breaks intramolecular noncovalent bonds of the ion's secondary and tertiary structure that otherwise prevent separation of the products from the nonergodic ECD cleavage of a backbone covalent bond. In comparison to collisionally activated dissociation, this “activated ion” (AI) ECD provides more extensive, and complementary, sequence information. AI ECD effected cleavage of 116, 60, and 47, respectively, backbone bonds in 29, 30, and 42 kDa proteins to provide extensive contiguous sequence information on both termini; AI conditions are being sought to denature the center portion of these large ions. This accurate “sequence tag” information could potentially identify indiv...
Rising surface ocean dissolved inorganic carbon at the Hawaii Ocean Time-series site

Abstract Surface ocean dissolved inorganic carbon (DIC) and titration alkalinity have been measured for 7 years as a part of the Hawaii Ocean Time-series (HOT) program. The time-series data set displays an interannual increase in the inventory of surface ocean DIC which we interpret as a response to increasing atmospheric carbon dioxide concentrations. The rate of increase in surface ocean DIC at the open ocean HOT site is approximately 1 μ mol kg −1 yr −1 with a 95% confidence interval of 0.72 to 1.37 μ mol kg −1 yr −1 . This accumulation rate is consistent with the rate of increase predicted from the rise in boundary layer p CO 2 .
Storage and retrieval of life history data

Recently many social scientists have begun collection and analysis of life history data. The analysis of these data is made possible largely because of appropriate computer storage and retrieval techniques. These techniques differ in several aspects from the conventional procedures employed in most social science research. The paper discusses some alternate methods for storage of these data and suggests some general capabilities for a retrieval system for life-history data.
Further investigations on balanced arrays

Abstract In this paper we obtain some results on the number of constraints for some balanced arrays (B-arrays) with two symbols.
Outcomes with External Beam Partial Breast Irradiation and Concurrent Chemotherapy (PBICC) Compared to Whole Breast Irradiation and Sequential Chemotherapy (WBISC) in Triple Negative Breast Cancer (TNBC) Patients

chemotherapy, or radiotherapy) for breast cancer. The study was approved by the Cancer Foundation of China Institutional Review Board. Results:Amongthe4,211patientsenrolled,3760patientswhoreceivedmastectomyandaxillarydissectionwereanalyzedinthis study. Of them, 675 patients (18.0%) received PMRT. Of the 3760 patients, 3083 had available staging information and were divided into three groups based on the risk of recurrence. There were 1090 patients (35.4%) in high-risk group (T3-4Nany and TanyN2-3), 721 (23.4%) in intermediate-risk group (T1-2N1) and 1272 (41.3%) in low-risk group (T1-2N0). 38.8% of patients in high-risk group, 12.8% in intermediate-risk group and 4.8% in low-risk group received PMRT. There was a trend for increasing use of radiotherapy in high-risk patients from year 1999 to 2008 (27.7%, 32.6%, 28.7%, 32.5%, 42.9%, 42.7%, 47.7%, 46.7%, 45.1%, 37.9%, respectively). Among 665 patients who received PMRTand had available radiation data, chest wall was irradiated in 88.9%, supraclavicular node in 91.6%, axilla in 29.9% and internal mammary chain in 44.8% of the patients. There was a decrease trend in irradiating internal mammary chain from year 1999 to 2008 (81.8%, 61.2%,53.1%, 54.5%, 54.1%,56.6%, 35.3%, 32.6%, 25.5%, 25.3%, respectively). Conclusions: The overall compliance to postmastectomy radiotherapy guideline is reasonable except that there is a significant underuse of PMRT in high-risk group patients. Further study is warranted to investigate the reasons for this non-compliance. AuthorDisclosure:S.Wang:None.Y. Li:None.B. Zhang:None.Z.Tang:None.X. Xie:None.H. Yang:None.J. He:None.J. Li:
pH-responsive copolymer assemblies for controlled release of doxorubicin

pH-Responsive drug carriers have the potential to provide selective drug release at therapeutic targets including tumors and in acidic intracellular vesicles such as endosomes and lysosomes. We have developed a new approach to the design of acid-sensitive micelles by incorporating hydrophobic acetal groups on the core block of a micelle-forming block copolymer. Hydrolysis of the acetals at mildly acidic pH is designed to reveal polar groups on the core-forming block, thus changing its solubility and disrupting the micelle, triggering drug release. The anticancer drug doxorubicin (DOX) was encapsulated in these pH-sensitive micelles, and the acetal hydrolysis rates and DOX release rates were determined in the pH range of 4.0 to 7.4 and were compared to those of control systems. The micelle disruption was investigated by dynamic light scattering. The in vitro toxicities of the empty and DOX-loaded micelles were determined, and the intracellular fate of the encapsulated DOX was compared to free DOX using fluorescence confocal microscopy.
Measurement of protein surface shape by solid angles

Abstract A method for measuring the gross shape of local regions of protein surface is presented and applied to an examination of three proteins. Any point on the protein surface can be assigned a number that measures the degree of convexity or concavity of the surface in the vicinity of the point. This number is computed by centring a sphere at that point and measuring how much of the sphere lies inside the protein. The sphere radius is a parameter chosen according to the scale of the features that are being analysed. The amount of sphere intersecting the protein is interpreted as a solid angle, denoted omega. Three proteins are analysed by this method: lysozyme, Superoxide dismutase and chymotrypsin. The resulting omega values are used to colour code the protein surfaces displayed on a colour raster graphics terminal. The method can be seen to reliably identify protrusions and depressions. The difficulty of developing a generally useful method for measuring protein surface shape is discussed. Possible applications of the solid-angle method include the analysis of shape complementarity at protein interfaces, the development of computer algorithms for predicting complexes between proteins, or between proteins and ligands, the identification of homologous epitopes on different proteins that might be immunologically crossreactive, and the determination of correlations between surface geometry and chemical properties.
Genetic Linkage of Autosomal Dominant Juvenile Glaucoma to 1q21-q31 in Three Affected Pedigrees

Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of this disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. We describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12 cM.
Theory of electron-spin-resonance linewidth and line-shift effects in spin-glasses with anisotropy and zero remanent magnetization

The dramatic increase in the width of the electron-spin-resonance line in Ruderman-Kittel-Kasuya-Yosida spin-glasses at temperatures above the transition temperature ${T}_{f}$, recently regarded as evidence in favor of a phase transition, is explained as an effect of the small measuring frequency. The present theory also gives an explanation for the line-shift behavior as a function of the measuring frequency and the temperature.
Comparative Quantitative Analysis of the Electrocardiogram and the Vectorcardiogram Correlations with the Coronary Arteriogram

Simultaneously recorded standard electrocardiograms (ECG) and Frank vectorcardiograms (VCG) were correlated with the coronary arteriograms and the left ventriculograms of 210 patients. Quantitative criteria were applied to ECG measurements made by manual technics and to VCG measurements obtained by computer technics. As the extent of significant arteriographic disease increased, the frequency of ECG and VCG evidence of "definite" myocardial infarction (MI) increased. The VCG was diagnostic of MI in a greater number of patients than the ECG (50 versus 39, P < 0.01) and excelled in the detection of multiple areas of infarction in a greater number of patients (13 versus six, P < 0.05). This increased sensitivity was gained in anterior, inferior, and true posterior infarcts. Excluding patients with myocardiopathy, all MIs diagnosed from the VCG and all but one from the ECG were associated with significant arteriographic disease in the distribution of the predicted nutrient artery. Quantitative VCG analysis ap...
Indexing the aperture 3 hexagonal discrete global grid

Over the past decade there has been interest in the computer representation of global data based on multi-resolution subdivisions of regular polyhedra. A simple and efficient indexing of the cells of such a subdivision, called A3-coordinates, is introduced. These can be used to encode the 4.3^n+2 cells at the nth level of resolution of the octahedral aperture 3 hexagonal discrete global grid using n+3 digits, each digit from the set {-1,0,1}.
Gauge-Invariant Scaling Model of Current Interactions with Regge Behavior and Finite Fixed-Pole Sum Rules

A general nonperturbative model for the entire Compton amplitude which incorporates Bjorken scaling, gauge invariance, and Regge behavior is presented. We show that a covariantly regularized model based on the infinite-momentum-frame techniques of Drell, Levy, and Yan is equivalent to the manifestly covariant nonperturbative parton model of Landshoff, Polkinghorne, and Short. We also demonstrate that a general consequence of composite theories of hadrons with field-theoretic constituents which incorporates the above properties is the existence of a constant energy-independent and ${q}^{2}$-independent term in ${T}_{1}(\ensuremath{\nu}, {q}^{2})$ (a "Kronecker delta" ${\ensuremath{\delta}}_{J0}$ term) and a $J=0$ fixed pole in ${T}_{2}(\ensuremath{\nu}, {q}^{2})$. Sum rules for general Compton amplitudes are derived and a discussion of mass renormalization for electromagnetic self-energy corrections of hadrons is presented. We demonstrate that such sum rules are always finite, even in the presence of Regge behavior, when subtraction terms in the underlying parton-proton $u$-channel dispersion relation are taken into account. Analytic continuation in $\ensuremath{\alpha}$ is thus justified.
Serum concentrations of branched chained amino acids (BCAA) in neonates with classic maple syrup urine disease (MSUD) in the first 4 days of life

Although serum levels of BCAA are elevated in MSUD at the time of diagnosis, data on serum levels of amino acids prior to development of symptoms are very limited. We have measured serum levels of BCAA during the first 4 days of life in 7 neonates from 3 families with affected offsprings. Three infants had MSUD and 4 were normal. All infants received 5% glucose in water for the first 12-24 hours and then were started on a formula devoid of BCAA. Valine and isoleucine were mildly elevated in cord sera of all 3 affected infants but leucine levels overlapped with those of normal siblings. Serumlevels of all BCAA increased as early as 4 hours after birth while these levels decreased in normal infants during the same period. Isoleucine levels decreased below normal in affected infants at 2nd and 4th days of life while other BCAA continued to rise. These data indicate that diagnosis of MSUD can be made within a few hours of life even before feeding. (Supported by GCRC grant n. RR-75).
Interleukin 1 receptor signaling regulates DUBA expression and facilitates Toll-like receptor 9-driven antiinflammatory cytokine production.

The interleukin 1 receptor (IL-1R) and the Toll-like receptors (TLRs) are highly homologous innate immune receptors that provide the first line of defense against infection. We show that IL-1R type I (IL-1RI) is essential for TLR9-dependent activation of tumor necrosis factor receptor-associated factor 3 (TRAF3) and for production of the antiinflammatory cytokines IL-10 and type I interferon (IFN). Noncanonical K63-linked ubiquitination of TRAF3, which is essential for type I IFN and IL-10 production, was impaired in Il1r1−/− CD11c+ dendritic cells. In contrast, degradative ubiquitination of TRAF3 was not affected in the absence of IL-1R1 signaling. Deubiquitinating enzyme A (DUBA), which selectively cleaves K63-linked ubiquitin chains from TRAF3, was up-regulated in the absence of IL-1R1 signaling. DUBA short interference RNA augmented the TLR9-dependent type I IFN response. Mice deficient in IL-1RI signaling showed reduced expression of IL-10 and type I IFN and increased susceptibility to dextran sulphate sodium–induced colitis and failed to mount a protective type I IFN response after TLR9 ligand (CpG) administration. Our data identifies a new molecular pathway by which IL-1 signaling attenuates TLR9-mediated proinflammatory responses.
Observation of spatial quantum beating with separated photodetectors.

When signal and idler photons produced in the process of parametric down-conversion are mixed together, and directed to two photodetectors that respond to nonoverlapping optical frequencies centered at ${\ensuremath{\omega}}_{1}$ and ${\ensuremath{\omega}}_{2}$, it is found that the joint probability of two-photon detection exhibits a modulation of the form $cos({\ensuremath{\omega}}_{1}\ensuremath{-}{\ensuremath{\omega}}_{2})\ensuremath{\tau}$, where $c\ensuremath{\tau}$ is the path difference. The experimental results are well described by a simple quantum-mechanical analysis.
Combinatorial cysteine mutagenesis reveals a critical intramonomer role for cysteines in prestin voltage sensing.

Prestin is a member of the SLC26 family of anion transporters and is responsible for electromotility in outer hair cells, the basis of cochlear amplification in mammals. It is an anion transporting transmembrane protein, possessing nine cysteine residues, which generates voltage-dependent charge movement. We determine the role these cysteine residues play in the voltage sensing capabilities of prestin. Mutations of any single cysteine residue had little or no effect on charge movement. However, using combinatorial substitution mutants, we identified a cysteine residue pair (C415 and either C192 or C196) whose mutation reduced or eliminated charge movement. Furthermore, we show biochemically that surface expression of mutants with markedly reduced functionality can be near normal; however, we identify two monomers of the protein on the surface of the cell, the larger of which correlates with surface charge movement. Because we showed previously by Forster resonance energy transfer that monomer interactions are required for charge movement, we tested whether disulfide interactions were required for dimerization. Using Western blots to detect oligomerization of the protein in which variable numbers of cysteines up to and including all nine cysteine residues were mutated, we show that disulfide bond formation is not essential for dimer formation. Taken together, we believe these data indicate that intramembranous cysteines are constrained, possibly via disulfide bond formation, to ensure structural features of prestin required for normal voltage sensing and mechanical activity.
Small Interfering Double-Stranded RNAs as Therapeutic Molecules to Restore Chemosensitivity to Thymidylate Synthase Inhibitor Compounds

RNA interference is a post-transcriptional mechanism by which double-stranded RNA specifically silence expression of a corresponding gene. Small interfering double-stranded RNA (siRNA) of 21-23 nucleotides can induce the process of RNA interference. Studies from our laboratory have shown that translation of thymidylate synthase (TS) mRNA is controlled by its own protein end-product TS in a negative autoregulatory manner. Disruption of this process gives rise to increased synthesis of TS and leads to the development of cellular drug resistance to TS-targeted compounds. As a strategy to inhibit TS expression at the mRNA level, siRNAs were designed to target nucleotides 1058-1077 on human TS mRNA. Transfection of TS1058 siRNA into human colon cancer RKO cells resulted in a dose-dependent inhibition of TS expression with an IC(50) value of 10 pM but had no effect on the expression of alpha-tubulin or topoisomerase I. Inhibition of TS expression by TS1058 was maximal at 48 h and remained suppressed for up to 5 days. Pretreatment of RKO cells with TS1058 siRNA suppressed TS protein induction following exposure to raltitrexed. In addition, TS1058 restored chemosensitivity of the resistant RKO-HTStet cell line to various TS inhibitor compounds. On treatment with TS1058, IC(50) values for raltitrexed, 1843U89, and 5-fluoro-2'-deoxyuridine decreased by approximately 15-16-fold. These studies suggest that TS-targeted siRNAs are effective inhibitors of TS expression and may have therapeutic potential by themselves or as chemosensitizers in combination with TS inhibitor compounds.