cssi/SciSciGPT-SciSciNet huggingface dataset:
Late Fathers' Later Children: Reconceiving the Limits of Survivor's Benefits in Response to Death-Defying Reproductive Technology

When Congress instructed the Social Security Administration to begin paying a social insurance benefit to “widows and orphans” in the 1930s, it simplified the process of determining an applicant’s relationship to an insured decedent in two significant ways: First, Congress ordered the agency to honor the intestate laws of each state when determining whether an applicant was actually the child of a decedent, and second, it ordered the agency to treat any child who could qualify as an intestate heir as if that child actually depended on the parent financially at the time of the parent’s death. Three-quarters of a century later, advances in reproductive technology make it possible for a child to be born decades after the death of one or both of her genetic parents. As the law begins to explore the rights and responsibilities of the parents who choose postmortem reproduction and the children whose lives come into being through those procedures, the heuristics that facilitated efficiency in the 1930s may yield unintended consequences. This Note explores some of those consequences and suggests minor alterations to the rules governing survivor’s-benefits eligibility intended to preserve the program’s social insurance function as reproductive technology transforms life after death from a hope or a fear into a choice.
Metadata-Based Analysis of Physical–Social–Civic Systems to Develop the Knowledge Base for Hurricane Shelter Planning

AbstractEmergency shelters are essential to protect evacuees from any threats posed by a hurricane and provide them with basic needs and assistance until it is safe to return to their homes. In a p...
Daratumumab-induced lymphopenia predicts adverse events and outcomes in patients with myeloma.

e20534Background: Daratumumab, a monoclonal antibody against CD38, is very effective in patients with Multiple Myeloma (MM). CD38 is expressed on MM cells but also on normal lymphocytes. Therapy-in...
Cardiac rhythm devices of today and tomorrow

Abstract After 50 years of a fundamentally unchanged pacemaker schema—a pulse generator with battery and electronics connects to insulated conductors (leads) that sense and stimulate atrial and/or ventricular myocardium—the basic paradigm of how cardiac tissue is stimulated to treat arrhythmias is dramatically changing. The aim of this chapter is to review pertinent contemporary and emerging pacing technologies and to present concepts and the available clinical evidence evaluating their safety and efficacy. These range from algorithms to extend device longevity and minimize ventricular pacing, to leadless pacemakers and His bundle pacing, which eliminate leads or leverage the heart’s own conductive tissues to effectively distribute stimulation, respectively. Basic pacemaker functions, sensing and pacing, are aptly discussed elsewhere and are the not the focus of this chapter. Rather, we will review more recent advances of the components of pacing systems as well as of the algorithms that govern their function. Implantable cardioverters defibrillators and cardiac resynchronization therapy systems are discussed at length in other chapters of this book and will therefore not be included in the scope of this chapter.
Twitter Communication During an Outbreak of Hepatitis A in San Diego, 2016–2018

Objectives. To examine how and what information is communicated via social media during an infectious disease outbreak.Methods. In the context of the 2016 through 2018 hepatitis A outbreak in San Diego County, California, we used a grounded theory-based thematic analysis that employed qualitative and quantitative approaches to uncover themes in a sample of public tweets (n = 744) from Twitter, a primary platform used by key stakeholders to communicate to the public during the outbreak.Results. Tweets contained both general and hepatitis A-specific information related to the outbreak, restatements of policy and comments critical of government responses to the outbreak, information with the potential to shape risk perceptions, and expressions of concern regarding individuals experiencing homelessness and their role in spreading hepatitis A. We also identified misinformation and common channels of content driving themes that emerged in our sample.Conclusions. Public health professionals may identify real-time public risk perceptions and concerns via social media during an outbreak and target responses that fulfill the informational needs of those who seek direction and reassurance during times of uncertainty.
Drosophila MOV10 regulates the termination of midgut regeneration

The molecular mechanisms by which stem cell proliferation is precisely controlled during the course of regeneration are poorly understood. Namely, how a damaged tissue senses when to terminate the regeneration process, inactivates stem cell mitotic activity, and organizes ECM integrity remain fundamental unanswered questions. The Drosophila midgut intestinal stem cell (ISC) offers an excellent model system to study the molecular basis for stem cell inactivation. Here, we show that a novel gene, CG6967 or dMOV10, is induced at the termination stage of midgut regeneration, and shows an inhibitory effect on ISC proliferation. dMOV10 encodes a putative component of the microRNA (miRNA) gene silencing complex (miRISC). Our data, along with previous studies on the mammalian MOV10, suggest that dMOV10 is not a core member of miRISC, but modulates miRISC activity as an additional component. Further analyses identified direct target mRNAs of dMOV10-containing miRISC, including Daughter against Dpp (Dad), a known inhibitor of BMP/TGF-β signaling. We show that RNAi knockdown of Dad significantly impaired ISC division during regeneration. We also identified six miRNAs that are induced at the termination stage and their potential target transcripts. One of these miRNAs, mir-1, is required for proper termination of ISC division at the end of regeneration. We propose that miRNA-mediated gene regulation contributes to the precise control of Drosophila midgut regeneration.
Red Blood Cell Contribution to Hemostasis

Red Blood Cells (RBCs) have been increasingly recognized to play important roles in hemostasis and the mechanisms by which they do so continue to be elucidated. First and foremost, RBC biomechanics are the principal determinant of viscosity and flow dynamics of blood, which strongly influence all features of hemostasis. Of note, morphologic pathology, such as that found in sickle cell disease, leads to increased risk of thrombotic disease. RBC surface interactions govern signaling between platelets and RBCs and also aid in the conversion of prothrombin to thrombin. Additionally, RBCs generate microparticles which have been shown to reduce clotting time. Finally, blood clot structure and maturation are dependent on the inclusion of RBCs in forming thrombi. Here, we review the above mechanisms of RBC contribution to hemostasis.
ECONOMIC ANALYSIS OF MILK PRODUCTION IN ALWAR DISTRICT OF RAJASTHAN

An attempt has been made in this study to compare the cost and returns from milk production across members and non-members of dairy cooperative societies in Alwar District of Rajasthan during the year 2005–06. The study covered 75 cooperative member milk producers and 75 non-member milk producers. The results of the study revealed that the net cost of maintaining a buffalo was relatively higher in case of member group (Rs.47.99 per day) as compared to non-member group (Rs.44.22 per day), while corresponding figures for maintaining a cow were Rs.38.42 and Rs.36.56 respectively. The net maintenance cost was found to decrease with the increase in herd size categories in both member and non-member groups. The per litre cost of buffalo milk production was worked out to be Rs.11.43 and Rs.11.76 for member and non-member groups, respectively. The corresponding figures for cow milk production were Rs.10.20 and Rs.10.50, respectively. The net income of buffalo per day was relatively higher in case of member group (Rs.7.38) compared to non-member group (Rs.2.70), while corresponding figures for maintaining a cow was Rs. 5.37 and Rs. 1.82.
Integration of Speaker Recognition into Conversational Spoken Dialogue Systems

In this paper we examine the integration of speaker identification/verification technology into two dialogue systems developed at MIT: the Mercury air travel reservation system and the Orion task delegation system. These systems both utilize information collected from registered users that is useful in personalizing the system to specific users and that must be securely protected from imposters. Two speaker recognition systems, the MIT Lincoln Laboratory textindependent GMM based system and the MIT Laboratory for Computer Science text-constrained speaker-adaptive ASRbased system, are evaluated and compared within the context of these conversational systems.
Insulin interactions with liver plasma membranes. Independence of binding of the hormone and its degradation.

Abstract Insulin interactions with purified plasma membranes of rat liver were studied with respect to insulin degradation and specific binding to receptors. 125I-insulin was rapidly degraded upon exposure to liver membranes. After only 5 min of incubation at 30° of 125I-insulin (0.3 nm) and liver membranes (1 to 2 mg of protein per ml), 40 to 60% of the labeled hormone was degraded as measured by its ability to specifically bind to a second aliquot of membranes. After 90 min of exposure, less than 10% of the 125I-insulin was intact when measured by its ability to bind specifically to membranes. Binding by anti-insulin antibody, precipitation by trichloroacetic acid, and adsorption by talc were less sensitive methods of measuring degradation. Degradation of 125I-insulin was dramatically reduced at 1°. No significant deiodination was associated with the degradation process. Gel filtration patterns suggested that 125Iinsulin degradation products are composed mainly of small peptide fragments that loosely adsorb to the gel and are eluted after the salt peak. The independence of binding to receptors and degradation is strongly suggested by the following findings. (a) 125I-desalanine-desaparagine insulin, which has an affinity for receptors that is only 2% that of insulin, is degraded to the same extent as 125I-insulin. (b) There is no relationship between the bioactivity of an insulin analogue and its ability to prevent the degradation of 125I-insulin. (c) The apparent Km for insulin degradation is 1.7 x 10-7 m, which is 40-fold more than that concentration of insulin that produces half-maximal inhibition of specific binding of 125I-insulin to receptors in the liver membrane. (d) Insulin that is recovered from membranes upon dissociation of the hormone-receptor complex is undergraded. Proinsulin is very slowly degraded by the liver membranes, but may act as a competitive inhibitor of insulin degradation. This is similar to the findings by others of the insulin-specific protease of muscle and liver. These studies provide evidence that interaction of insulin with liver plasma membranes is a complex phenomenon that involves at least two processes, degradation and binding to receptors. These two processes are largely independent and unrelated under a variety of conditions. Degradation of insulin must be accounted for in making precise quantitative measurements of the interaction of insulin with its receptors in the plasma membrane.
Evidence against insulin-stimulated phosphorylation of calmodulin in 3T3-L1 adipocytes.

Abstract To examine the possibility that insulin might stimulate calmodulin phosphorylation in intact cells, we compared autoradiographs of two-dimensional gels of [35S]methionine- and 32P-labeled proteins from 3T3-L1 adipocytes, before and after immunoprecipitation with anti-calmodulin antiserum. Insulin stimulated the phosphorylation of one or two proteins of approximately 22 kDa and pI 4.6; this increased phosphorylation was accompanied by an apparent shift in the position of the analogous [35S]methionine-labeled proteins towards the anode. In contrast, insulin had no effect on the phosphorylation state of another protein of 18-22 kDa and pI 4.6. This protein was very heavily labeled with [35S]methionine, co-migrated exactly with purified calmodulin, reacted specifically with two anti-calmodulin antibodies by Western blotting, and was specifically immunoprecipitated with the anti-calmodulin antiserum. Similar amounts of [35S]methionine-labeled calmodulin were immunoprecipitated from control and insulin-stimulated cells, arguing against the possibility that insulin-stimulated phosphorylation of calmodulin changed its affinity for the antibody. We conclude that calmodulin is phosphorylated to a negligible extent in serum-deprived 3T3-L1 adipocytes and that insulin does not stimulate its phosphorylation under conditions in which it stimulates the phosphorylation of one or more neighboring proteins.
SYNTHESIS OF PEPTIDES OF METHIONINE AND THEIR CLEAVAGE BY PROTEOLYTIC ENZYMES

In a previous communication from this laboratory (l), a method was described for the enzymatic resolution of Dr.,-methionine. The ready availability of the optically active enantiomorphs has made possible the application of the carbobenzoxy method to the synthesis of peptides of Land n-methionine. A search of the literature has indicated that the only methionine peptide described thus far is glycyl-L-methionine (2), which was obtained by the treatment of L-methionine with chloroacetyl chloride, followed by the amination of the resulting chloroacetylamino acid. The rotation of the peptide was not reported, however, and, as is noted in the experimental section of this communication, the melting point of this product is about 55’ lower than that found for glycyl-nmethionine prepared by the carbobenzoxy method. In what follows, there is described the synthesis of a series of methionine peptides and peptide derivatives, and a number of these have been examined with regard to their susceptibility to the hydrolytic action of several proteolytic enzymes. In addition, the availability of such peptides of methionine makes possible the study of other metabolic reactions involving compounds in which this amino acid is bound in peptide linkage. The results of such studies will be reported in future communications. Synth,esis of Peptides of Methionine-In the experimental section, directions are given for the synthesis of the free peptides glycyl-nand n-methionine, Land n-methionylglycine, ru-L-glutamyl-L-methionine, L-
Neurotrophins differentially stimulate the growth of cochlear neurites on collagen surfaces and in gels

The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant.
Structure, function, and evolution of transfer RNAs (with appendix giving complete sequences of 178 tRNAs).

Publisher Summary The chapter discusses the structure, function, and evolution of transfer RNAs (tRNA). A comparison of the sequences of tRNA's has provided new and supportive information concerning: (a) secondary and tertiary structures; (b) minor modified nucleotides and their possible roles; and (c) binding sites for specific and nonspecific interactions between tRNA and the aminoacyl-tRNA synthetase. The statistical data reveal that invariant or conserved nucleotides are present in each prokaryotic and eukaryotic tRNA. These invariant positions, determined for >60% and >90% of the tRNA's, suggest evolutionary or “primordial” structures that may have differentiated into the highly specific structures required for the aminoacylation process. The study of variant residues indicate that the prokaryotic and eukaryotic tRNA's, although stemming from a common “proto” tRNA, have evolved in two directions. Interestingly, tRNA structure has not changed drastically during this evolution. A statistical analysis of 129 tRNA's from eukaryotic, prokaryotic, and viral sources is carried out in an attempt to answer the following questions, which are: (a) what are the invariant (conserved) nucleoloids in tRNAs, (b) is the tertiary structure of yeast tRNA Phe representative of the tertiary bonds in other tRNAs, (c) what is the nature of the modified nucleotides in tRNAs, (d) what, if any, are the differences between prokaryotic and eukaryotic modifications, (e) how does the T-ψ-C sequence, a feature of most tRNAs, vary in certain tRNAs, (f) can the chapter predict one or more specific interaction sites between tRNA and the cognate synthetase after determining the variant and the invariant residues between the isoacceptor sequences.
Social Science in Law: A Psychological Case for Abandoning the 'Discriminatory Motive' under Title VII

The legal policy goals of Title VII are clearly stated, but disparate treatment doctrine, which is framed around a judicially created search for a “discriminatory motive,” is incoherent. Drawing on the insights from decades of social-psychological research on discrimination, we propose an alternative framework for the disparate treatment cause of action that rejects the “discriminatory motive” requirement in favor of a focus on the extent to which employers evidence a commitment to the goal of merit-based decision-making. Using several examples, we illustrate how the proposed framework could be reliably used to resolve even complex disparate treatment cases. In terms of administrability and satisfaction of the policy goals underlying Title VII, the proposed framework improves on existing doctrine. Finally, the proposed framework embodies a novel approach for using empirical social science to inform the development of legal doctrine, one with the potential to open new doors for socially beneficial collaboration between the two academic fields.
Exploring Cancer Risk Perceptions of Turf and Lawn Pesticide Professionals in New York State

A pilot study was conducted to better understand the knowledge, perceptions, and concerns of turf and lawn care pesticide professionals in New York State (NYS) regarding cancer and other health risks. Data were collected from 31 focus group participants and 104 questionnaire respondents in applicator trainings and other meetings around the state. Three distinct themes emerged from focus group discussions: cultural shift in pesticide management practices, costs and benefits of pesticide regulations, and challenges of understanding and communicating about health risks. Factor analysis yielded three subscales: control disease, reduce chemical risk, and concern. Exploratory regression analysis yielded predictive relationships between work experience, cancer risk knowledge, and attitudes in support of reducing chemical risk, which in turn predicted precautionary pesticide behavior, such as reading the label and using personal protective equipment. Results suggest the need to incorporate cancer risk education i...
Increasing paramedics' comfort and knowledge about children with special health care needs.

This study evaluated a continuing education program for paramedics about children with special health care needs (CSHCN). Pretraining, posttraining, and follow-up surveys containing two scales (comfort with CSHCN management skills and comfort with Pediatric Advanced Life Support [PALS] skills) were administered. Objective measures of knowledge were obtained from pre- and posttraining tests. Differences in average scores were assessed using t-tests. Response rates for paramedics completing the program ranged from 94% for the posttraining survey, 81% for the initial comfort survey, 56% for the knowledge pretest, and 56% for the follow-up survey. PALS comfort scores were significantly higher than CSHCN comfort scores both before and after training, both P < .01. Posttraining surveys showed an increase in CSHCN comfort, P < .01. The follow-up surveys showed a significant decline in CSHCN comfort, P = .05. Scores on the tests showed a similar pattern, with a significant increase in knowledge from pre- to posttraining (P = .02) and a significant decrease in knowledge from posttraining to follow-up (P < .01). Comfort was significantly higher for standard pediatric skills than for specialized management skills. Completion of the self-study program was associated with an increase in comfort and knowledge, but there was some decay over time.
Modeling and simulation of pulsed laser annealing and ablation of solid materials

A previously developed one-dimensional (ID) computational model for heat flow and nonequilibrium phase change phenomena induced by pulsed-laser irradiation has been extended to two-dimensions. The 2D modeling focuses attention on the heat flow from localized sources embedded in an otherwise planar matrix. For example, nucleation events occurring in undercooled liquids such as molten Si formed by pulsed-laser melting of amorphous Si (a-Si) and inhomogeneous absorption due to randomly occurring defects in targets used for pulsed-laser ablation can be treated. Concepts introduced in the ID modeling, such as the state diagram and the state array are extended to 2D and refined. As an example of the calculations that are now possible, the laser-induced formation and propagation of buried liquid layers are followed in two dimensions for the case of a-Si on a crystalline silicon substrate. It is demonstrated how solid phase growth from individual nucleation sites gives rise to a nearly planar liquid layer propagating through the a-Si. Another example briefly addresses questions related to the early stages of the laser ablation of insulators such as MgO, where it is believed that the absorption of the laser radiation occurs at localized but extended regions of high concentrations of defects. The 2-D program has been rewritten for massively parallel machines such as the Intel Paragons in ORNL`s Center for Computational Sciences by one of us (CLL), thus allowing larger and more accurate calculations for complex systems to be carried out in reasonable times.
Investigating health at Kerma: sacrificial versus nonsacrificial individuals.

This analysis examines heterogeneity in risks by assessing the health status of individuals in two distinct burial contexts from the Nubian site of Kerma: sacrificial (n = 100) and nonsacrificial (n = 190) burial areas dated to the classic Kerma period (∼1750–1500 BC). Indicators of physiological stress that were examined include cribra orbitalia, dental enamel hypoplasia, tibial osteoperiostitis, and femur length. The analysis presented here shows that the people interred in the sacrificial and nonsacrificial burial contexts at Kerma in Upper Nubia had similar health profiles that were comparable with other contemporaneous samples from the region. If sacrificial individuals did not experience the same risk of death as nonsacrificial individuals, it was not evident in the frequencies of nonspecific stress indicators. However, this differential risk of death may be blurred by our inability to examine nonadults for childhood disease. This research demonstrates the complexities involved in understanding the multiple factors that result in heterogeneity in skeletal samples. Am J Phys Anthropol, 2008. © 2008 Wiley-Liss, Inc.
Failure of pepsin-digested donor specific alloantibody to prolong renal allograft survival in dogs.

Donor specific F(ab')2 alloantibody fragments, prepared by pepsin digestion of IgG obtained from hyperimmune cytotoxic alloantisera raised in third party dogs, was administered to canine renal allograft recipients in an attempt to allow expression of immunological enhancing properties of alloantibody in a species in which hyperacute rejection occurs. Pepsin digestion did abrogate the ability of donor specific cytotoxic alloantibody to mediate hyperacute rejection, but renal allograft survival in F(ab')2 treated dogs was not prolonged over graft survival in untreated dogs. Factors which may contribute to the inability of this technique to prolong graft survival include (1) the difficulty, when using outbred animals, of assuring that the alloantibody is directed against all the antigens present in the donor and absent in the recipient, and (2) the decreased potency of F(ab')2, when compared to an equivalent amount of intact IgG, as an inhibitor of a specific immune response.
Regulation of T lymphocyte function by glycosylphosphatidylinositol (GPI)-anchored proteins

Abstract Monoclonal antibody binding to GPI-anchored proteins, e.g. Thy-1 and Ly-6, on the surface of T lymphocytes usually leads to stimulation of interleukin-2 production. This phenomenon is dependent upon expression of the ζ-chain of the T cell receptor complex and requires the GPI anchor. Recent studies suggest that this activation may proceed through a common pathway resulting in tyrosine phosphorylation of intracellular substrates and association of various GPI-anchored proteins to src-family tyrosine kinases. Several models are discussed to explain the signaling capabilities of GPI-anchored proteins. In contrast, under some experimental conditions antibody binding to selected GPI-anchored proteins, i.e. Ly-6A/E and sgp60 (CD48), leads to inhibition of T cell activation. Furthermore, induction of Ly-6A/E expression on CD4 effector T cells correlates with a decreased capacity to secrete IL-2. These latter results suggest that Ly-6A/E may also function to down-regulate an immune response.
Ten Lively Lessons Using the Daily Newspaper

(1994). Ten Lively Lessons Using the Daily Newspaper. The Clearing House: A Journal of Educational Strategies, Issues and Ideas: Vol. 67, No. 3, pp. 163-164.
LIQUID PHASE SINTERED METAL MATRIX COMPOSITE MATERIALS

ABSTRACT Iron-base and aluminum-base composite materials reinforced with various ceramic particulates have been fabricated via powder metallurgy and liquid phase sintering. The advantage of this manufacturing route is that conventional powder metallurgy processing equipment can be used to fabricate metal matrix/ceramic composites. Furthermore, this approach makes it possible to manufacture these composites to near-net-shape. A number of matrix/ceramic combinations have been examined: Fe-C-Si and Fe-Cu with ZrO2 additions and a Al-Cu-Si-Mg alloy with SiC or Al2O3 additions. The interfacial structures were characterized and found to play a significant role in controlling the properties of the composites. Reinforcement was observed in several systems. However, a glassy interfacial layer forms when Si additions and oxide reinforcements are present; the resultant particle/matrix bond strength is weak and reinforcement.
Hausdorff Dimension of Continuous POLYAKOV’S Random Surfaces

In this paper we compute exactly, using the scaling properties of the Liouville theory, the Hausdorff dimension of the continuous random surfaces of Polyakov for D≤1. We find that for D<1, the mean square size of the surface grows as a logarithm of the area of the surface as well as the area of the surface raised to a power, the power being minus the string susceptibility. For D=1 the behavior changes, as expected, because the model undergoes a phase transition. In that case we find that the mean square size of the surface behaves as a combination of terms that grow as a logarithm of the area as well as its square, in qualitative agreement with the results of numerical experiments in discrete models.
Colorimetric High-Throughput Screen for Detection of Heme Crystallization Inhibitors

Malaria infects 500 million people annually, a number that is likely to rise as drug resistance to currently used antimalarials increases. During its intraerythrocytic stage, the causative parasite, Plasmodium falciparum , metabolizes hemoglobin and releases toxic heme, which is neutralized by a parasite-specific crystallization mechanism to form hemozoin. Evidence suggests that chloroquine, the most successful antimalarial agent in history, acts by disrupting the formation of hemozoin. Here we describe the development of a 384-well microtiter plate screen to detect small molecules that can also disrupt heme crystallization. This assay, which is based on a colorimetric assay developed by Ncokazi and Egan (K. K. Ncokazi and T. J. Egan, Anal. Biochem. 338: 306-319, 2005), requires no parasites or parasite-derived reagents and no radioactive materials and is suitable for a high-throughput screening platform. The assay9s reproducibility and large dynamic range are reflected by a Z factor of 0.74. A pilot screen of 16,000 small molecules belonging to diverse structural classes was conducted. The results of the target-based assay were compared with a whole-parasite viability assay of the same small molecules to identify small molecules active in both assays.
Cardiomyopathy in a Male with Cystinosis

Cystinosis is a lysosomal storage disease classically associated with renal failure, photophobia, and hypothyroidism. Multi-organ dysfunction tends to develop over time, a factor of increasing significance as patient survival improves. Herein, we describe a male patient with cystinosis who developed a restrictive cardiomyopathy associated with myocardial cystine deposition and an ap-proximately 1000-fold elevation in myocardial cystine levels. Renal failure necessitated a kidney transplant at age 12. At age 31, the patient was diagnosed with progressive cardiac failure poorly responsive to aggressive antifailure therapy and risk factor modification. The patient died at age 33 in hypovolemic shock due to a ruptured pseudoaneurysm at an old renal transplant site.
Risk of breast cancer with progestins in combination with estrogen as hormone replacement therapy.

Two recent studies have suggested that progestins substantially increase the relative risk (RR) of breast cancer when added to estrogens as hormone replacement therapy (HRT) (1-2). If correct this information could substantially change clinical practice. Here we review biological epidemiological and clinical data regarding the effects of progestins on the breast. From this analysis we conclude that no definitive proof exists to establish a causal relationship between progestins and breast cancer risk. However a wide range of biological and clinical data provides strong supportive evidence of such an effect. Based on this we believe that it is prudent to inform patients that progestin use may add to the increased risk imparted by estrogens. Patients should understand however that this increased risk is small particularly when associated with the short-term use of HRT. (excerpt)
Statistical properties of estimates of signal-to-noise ratio and number of scatterers per resolution cell

Elementary theory underlying the relationship between the number of scatterers per resolution cell (N) and echo intensity signal-to-noise ratio (SNR) is reviewed. A relationship between the probability density functions for estimates of N and SNR2 is derived. This relationship is validated using a computer simulation. Phantom and in vitro experiments are described. In one set of experiments on phantoms, empirical distributions of estimates of N and SNR2 are measured and compared to theoretical predictions. The utility of SNR2 for discrimination of phantoms with different values for N is assessed using receiver operating characteristic (ROC) analysis. In another set of experiments, the frequency dependence of the SNR2 estimate is investigated for a two-component phantom and for excised dog kidney. It is shown that the frequency dependence of the SNR can help to identify the presence of two or more scattering components that are spatially mixed. With regard to kidney data, measurements performed both parallel and perpendicular to the predominant nephron orientation are reported. The observed anisotropy is compared to the anisotropy of backscatter coefficient encountered in previous investigations.
Lack of age effects on human brain potentials preceding voluntary movements

Abstract We examined age effects on Movement related potentials (MRPs) in 13 young (mean age = 29.3 years) and 13 old (mean age = 67.2 years) normal adults in right, left and bimanual self-paced button press conditions. Both the groups generated a slowly rising readiness potential (RP) at about 1000 ms, a negative shift (NS′) at about 450 ms and a motor potential (MP) at about 100 ms prior to movement. The RP was symmetrical, bilaterally distributed and maximal at the vertex in all conditions in both the groups. Both the groups produced contralaterally enhanced NS′ and MP components in unimanual conditions. In contrast to prior reports, topographical distribution, onset latency and mean amplitude were comparable between young and old subjects for the RP, NS′ and MP components of the MRP. The results indicate that motor programming as indexed by MRPs is unaffected by normal aging.
The lattice of integer partitions

In this paper we study the lattice L"n of partitions of an integer n ordered by dominance. We show L"n to be isomorphic to an infimum subsemilattice under the component ordering of certain concave nondecreasing (n+1)-tuples. For L"n, we give the covering relation, maximal covering number, minimal chains, infimum and supremum irreducibles, a chain condition, distinguished intervals; and show that partition conjugation is a lattice antiautomorphism. L"n is shown to have no sublattice having five elements and rank two, and we characterize intervals generated by two cocovers. The Mobius function of L"n is computed and shown to be 0,1 or -1. We then give methods for studying classes of (0,1)-matrices with prescribed row and column sums and compute a lower bound for their cardinalities.
Goal-setting behavior of asthmatic, diabetic and healthy children

Goal-setting behavior and self-expectations of asthmatic children have been studied in relation to psychosomatic theories of asthmagenesis, but fathers' influence has been generally ignored and approriate control groups have been often lacking. The present study utilized a level of aspiration task and a measure of the family climate to evaluate 16 asthmatic children compared to 16 diabetic children, 16 healthy children who had asthmatic siblings, and 16 healthy children from families with no chronic illness. Overall, the data failed to support specificity theories of bronchial asthma. The presence of chronic childhood illness, rather than asthma per se, was associated with most of the significant variation between study groups.
Assessment of Three-Year-Olds with the Stanford-Binet Fourth Edition

The Stanford-Binet, Fourth Edition was normed for children 30 months of age and older, but its usefulness with young children (e.g., 36 months) has received little attention. This study of 121 three-year-old children examined possible administration problems, provided correlations with three environmental measures, and compared scores with those of the Peabody Picture Vocabulary Test--Revised. Problems of administration did arise on some subtests, correlations with environmental measures were moderate, and scores on the Stanford-Binet IV and PPVT-R were moderately correlated. The Stanford-Binet IV is a useful test in assessment of a broad range of intellectual abilities.
TM2-TM7 interaction in coupling movement of transmembrane helices to activation of the angiotensin II type-1 receptor.

Agonist-induced rigid body motion of transmembrane (TM) helices has been established as a unifying mechanism in the activation of the G protein-coupled receptors. In attempts to measure specific conformational transitions during the activation of the type 1 receptor for angiotensin II (AT1), we found a decrease in accessibility of Cys76 in the second TM helix, suggesting that the orientation of TM2 is altered (Miura, S., and Karnik, S. S. (2002) J. Biol. Chem. 277, 24299–24305). Now we provide evidence that the TM2 helical movement plays a role in regulating the activated state of the AT1 receptor, and this role may involve an interaction between TM2 and TM7. Alanine substitution of native Cys296in TM7 leads to increased accessibility of Cys289 and diminished response to bound agonist. Both effects of the C296A mutation are suppressed when combined with F77A and N111G mutants. The TM7 conformation and the sensitivity of Cys289 altered by C296A mutation are suppressed by the F77A mutation in TM2 to salvage function. We show that the F77A mutant alters orientation of both TM2 and TM7 but does not induce constitutive activity in suppressing the C296A mutant effects. Thus, interaction of TM2 and TM7 is important for transmembrane signal transduction in the AT1 receptor.
The effect of residual stress on the fatigue crack growth behavior of Al-Si-Mg cast alloys—Mechanisms and corrective mathematical models

The fatigue crack growth (FCG) behavior of various types of alloys is significantly affected by the presence of residual stress induced by manufacturing and post-manufacturing processes. There is a qualitative understanding of the effects of residual stress on fatigue behavior, but the effects are not comprehensively quantified or accounted for. The difficulty in quantifying these effects is largely due to the complexity of residual-stress measurements (especially considering that parts produced in similar conditions can have different residual-stress levels) and the lack of mathematical models able to convert experimental data with residual stress into residual-stress-free data. This article provides experimental, testing, and mathematical techniques to account for residual-stress effects on crack growth rate data, together with two methods for eliminating residual stresses in crack growth test specimens. Fracture-mechanics concepts are used to calculate, in simple and convenient ways, stress-intensity factors caused by residual stresses. The method is advantageous, considering that stress-intensity factors are determined before the actual test is conducted. Further on, residual-stress-intensity factors are used to predict the residual-stress distribution in compact tension (CT) specimens prior to testing. Five cast Al-Si-Mg alloys with three Si levels (in unmodified (UM) as well as Sr-modified (M) conditions) were analyzed both with and without residual stress. Fatigue cracks are grown under both constant stress ratio, R=0.1, and constant maximum stress-intensity factor, K max = const., conditions. The mechanisms involved in crack growth through residual-stress fields are presented.
Local INR control had some effect on the benefits of dabigatran over warfarin for major bleeding in atrial fibrillation

Source Citation Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke preventi...
Diagnostic yield of CT-guided sampling in suspected sternoclavicular joint infection

To determine the prevalence of infection diagnosed by percutaneous computed tomography (CT)-guided sternoclavicular (SC) sampling in cases of suspected joint infection. A retrospective search was performed in reports of SC joint CT-guided biopsies in adults from July 1992 to July 2012. We reviewed medical records, radiology, microbiology, laboratory, and surgical reports. A positive result was defined as demonstration of a pathogenic organism, either by microscopy or growth in culture, confirming the diagnosis of SC joint infection. A negative result was defined as the absence of such findings. Patients in whom sampling was unsuccessful or not subjected to microbiology were excluded. In addition, CT images were reviewed by the consensus of two musculoskeletal radiologists. A total of 41 patients (mean age 57.1 years) underwent CT-guided SC joint sampling, 27 of whom underwent microbiology studies. Sampling was performed using core biopsy alone in 19 %, fine needle aspiration alone in 44 %, and aspiration combined with core biopsy in 37 %. Positive results were found in 52 % (14/27) of patients. Related diseases and predisposing conditions for infection were found in 79 % of positive patients. Negative results were found in 48 % (13/27) of patients. There were no procedure-related complications. The dominant CT findings were soft tissue swelling (negative group), and effusion and/or capsular hypertrophy/distension (positive group). CT-guided sampling is a safe procedure with positive microbiological cultures in slightly more than half of cases.
The humean obstacle to evidential arguments from suffering: On avoiding the evils of “appearance”

Many of us - believers as well as nonbelievers, car mechanics as well as philosophers - have at some times in our lives felt instances of suffering in this world to be evidence against theism, according to which the universe is the creation of a wholly good Being who loves his creatures, and who lacks nothing in wisdom and power. If it has proven hard to turn this feeling into a good argument, it has, perhaps, proven just as hard to get rid of it. Indeed, the most logically sophisticated responses to the "problem of evil" can leave one wondering whether our intuitive perplexities have not been lost in the gears of the formal machinery brought to bear on them. Maybe this is an unavoidable epiphenomenon of analysis; nevertheless, I want to try to mitigate it here. For this reason (and a second forthcoming one), my springboard will be William Rowe's recent formulation of the case from suffering against theism} Rowe exemplifies the recent turn away from "logical" (or "deductive," or "demonstrative s ) formulations, construing the case instead as "evidential" (or "inductive," or "probabilistic") in nature. The crux of his argument is that much suffering "does not appear to serve any outweighing good." This "does not appear" defence is succinct and non-technical, affording considerable insight into our ordinary intuitions, but also making itself easy prey to misconstrual. I shall thus be amplifying Rowe's argument and defending it against specious criticisms, as well as - ultimately rebutting it. This close attention to Rowe and his critics, however, is not an endin-itself. It is a means of elucidating and vindicating a perspective from which we can see why a theist should, as Hume puts it, "never retract his belief'' on account of the suffering atheologians are inclined to adduce as evidence against theism. Vindicating this perspective requires coming to close grips with the most lucid atheological evidential case one can find - and this is my second reason for taking Rowe's work as a springboard.
Modulation of fatty acid-binding capacity of heart fatty acid-binding protein by oxygen-derived free radicals.

In this study, we examined the effects of exposure of heart fatty acid-binding protein (h-FABP) to chemically generated O2− or OH · with respect to its oleate binding and to its electrophoretic properties. Purified rat h-FABP at 40 μM scavenged as much as 30% O2− and 85% OH ·. On the other hand, when 2 nmol (4 μM) FABP were exposed to free radicals, the maximum oleate binding capacity as measured by Scatchard analysis was reduced only by 14% and 27% for O2− and OH ·, respectively. The electrophoretic pattern of free radical-exposed FABP was not markedly different when examined either by the non-denaturing or by denaturing PAGE, suggesting the absence of any degradation or aggregation of FABP by O2− or OH ·. It is hypothesized that O2− or OH · in physiological concentration may not alter the function of FABP markedly in the ischemic-reperfused myocardium.
Flow cytometric analysis of lymphocyte subsets of mice maintained on an ethanol-containing liquid diet

Alcoholic patients often have impaired immune function, yet little is known about the precise mechanism(s) of this impairment. We have previously shown that ethanol consumption by mice alters copolymer-specific humoral and cellular immune responses. In this study, we asked whether alcohol consumption by mice would phenotypically alter lymphocyte populations. Female C57BL/6 mice were fed a nutritionally complete liquid diet containing 35% ethanol-derived calories for up to 8 days. As controls, mice either were fed a liquid control diet that isocalorically substitutes sucrose for ethanol or remained on a standard solid diet and water ad libitum. Although mice fed ethanol-containing liquid or pair-fed control liquid diets have decreased numbers of spleen cells compared with solid diet controls, only the ethanol-containing diet allowed normally nonresponder C57BL/6 spleen cells to make antibody responses to the poly(Glu50Tyr50) synthetic copolymer antigen. Flow cytometric analysis of splenic lymphocyte populations of mice on the ethanol-containing diet shows an increase in the relative proportion of T-lymphocytes as compared with mice on either solid or liquid control diets. No such change is seen for either B-cell or natural killer cell populations in these same mice. Both liquid control and liquid ethanol diets caused a slight decrease in the CD4:CD8 ratios of splenic T-lymphocytes. We see the relative percentage of T-cells bearing the αβ-cell receptor (TcR) increases in the spleens of liquid ethanol diet mice; a smaller increase TcRαβ usage is seen in the spleens of liquid control mice, compared with solid diet mice. Flow cytometric analysis shows that little, if any, difference exists in TcRγδ expression between the liquid ethanol and either the liquid control or solid diet groups. Preliminary analysis of TcRαβ subsets suggest that ethanol increases the percentage of T-cells expressing Vβ5 and Vβ8, and decreases the percentage of Vβ11 expressing cells. These findings suggest that, in addition to modifying the immune response, ethanol alters the phenotypic expression of lymphocyte subsets.
Mechanisms of parenchymal cell death in-vivo after microvascular hemorrhage.

Objective: In vitro studies suggest that microhemorrhages with escape of red cells into the tissue may be cytotoxic to parenchymal cells due to oxygen free radical formation. We examined in the rat mesentery the impact of microhemorrhages on parenchymal cell death, as detected by propidium iodide staining, using an intravital approach.Methods and Results: Postcapillary venules were punctured with a closed-end micropipette, permitting escape of blood cells and plasma into the mesentery interstitium. Over a period of 2 h, no significant increase in parenchymal cell death was encountered in tissues with hemorrhagic sites compared with nonhemorrhagic control sites. Interstitial microinjections of plasma derived from whole blood incubated for several hours with and without a combination of sodium azide (2mM) and hydrogen peroxide (1 mM) led to significantly increased levels of cell death compared to control experiments. Interventions against the hydroxyl radical with dimethylthiourea (DMTU, 2 mM) or 2,2'-dipyr...