cssi/SciSciGPT-SciSciNet huggingface dataset:
Cystic fibrosis testing 8 years on: Lessons learned from carrier screening and sequencing analysis

Purpose: This study reviews data from our cystic fibrosis testing program to evaluate the performance of population-based carrier screening and compare observed detection rates with predicted results of the American College of Medical Genetics/American College of Obstetricians and Gynecologists recommended panel of 23 mutations. Methods: We queried our proprietary databases containing approximately 3 million cystic fibrosis screening tests, 1300 prenatal diagnostic tests, and 2400 cystic fibrosis sequencing analyses. Results: We observed an overall cystic fibrosis carrier frequency of 1:37.6 individuals in the pan-ethnic tested population. This represents a detection rate of 77%, given an estimated US pan-ethnic carrier frequency of 1:29. For patients self-identified as white or Ashkenazi Jewish, a carrier frequency of 1:29 and 1:27 were observed, respectively. A combined frequency of 1:28, representing close to 90% of carriers, was identified in these two highest risk populations. In total, 119 affected fetuses were identified by prenatal diagnoses, a ratio of 1 affected fetus per 25,000 carrier screens. Of 62 newborns with positive immunoreactive trypsinogen and positive sweat tests, almost all of whom had been tested using the American College of Medical Genetics/American College of Obstetricians and Gynecologists panel, only two individuals would have been identified using an expanded mutation panel. Conclusion: The American College of Medical Genetics/American College of Obstetricians and Gynecologists panel of 23 mutations is performing as predicted in detecting cystic fibrosis carriers in the United States among all ethnic groups. No recurrent mutations have been detected in sufficient numbers to justify including any additional mutations to the existing panel. An expanded American College of Medical Genetics/American College of Obstetricians and Gynecologists panel would have a minimal impact on the prevention of births of children affected with cystic fibrosis.
Relative Importance of Food Composition in Free Lysine and Methionine Losses During Elevated Temperature Processing

Free lysine and methionine loss were monitored as a function of food composition (independent variables) utilizing fortified model food systems. The food systems were composed of varying quantities of protein, sugar, oil, salt, cellulose, and water, and were isothermally processed for varying time intervals at 65 or 115°C. The arnino acid losses were best modeled by first order reaction kinetics. Protein, sugar, and water activity (aw) had the predominant influence on the loss rate. The rate coefficient increased when protein or sugar levels were increased, but decreased when water activity was increased. Salt and oil had only a minor influence on the rate coefficient when compared with other variables. Interactions among food components also influenced the loss rate coefficient.
Volume-preserving energy–momentum schemes for isochoric multiplicative plasticity

Abstract This paper presents a new energy-dissipative momentum-conserving algorithm for multiplicative finite strain plasticity (F = FeFp) that also preserves exactly the plastic volume for isochoric plastic models. The new algorithm exhibits exactly the conservation laws of linear and angular momentum of the underlying physical problem as well as its energy evolution. A strictly positive energy dissipation, in fact the exact energy dissipation, is obtained by design during plastic steps while enforcing the plastic consistency (i.e. the yield condition) on the final stress appearing in the equations of motion. Exact energy conservation is attained, in particular, during elastic steps. The aforementioned preservation of the plastic volume is obtained by a new treatment of the geometric structure behind the considered multiplicative models of finite strain plasticity. Namely, we present a new approximation of the reference and elastic metrics whose contractions with the incremental total and elastic strains lead exactly to the increment of the total and elastic natural volumetric strains, respectively. The elastic metric is defined in the intermediate configuration, defined itself by the proper discrete approximation in time of the plastic deformation gradient Fp. The new algorithm extends to the plastic range existing energy–momentum-conserving schemes for nonlinear elastic problems, but incorporating a new modified elastic stress formula consistent with this new geometric setting. The inherited conservation laws of momenta and, especially, the non-negative character of the energy dissipation leads to an improved performance over existing, more classical schemes showing numerical instabilities in the considered highly nonlinear geometric setting of large deformations and strains. Several numerical simulations are presented illustrating these properties.
Transplacental clearances of inert hydrophilic tracers in rabbits of 18 days gestation.

Abstract Transplacental clearances were measured for radiolabelled Cl−, S042−, mannitol, sucrose, raffinose, PEG-900 and inulin. Maternal placental blood flows were measured with radiolabelled microspheres. At 18 days of gestation (term 31 days), the fetuses and extra fetal fluids were growing at 55 and 32 per cent per day, accounting for a net transplacental filtration rate of 14.2 nl/sec per gram placental weight. Pore theory and a least squares fit of the Patlak equation yielded an equivalent pore radius of 1.75 nm. It was demonstrated that the clearance of the largest tracer, inulin, was 30 times higher than it would have been in the absence of net filtration. Comparison with literature data showed that there was a small increase in placental permeability per gram placenta between 14 and 18 days of gestation but that the increase between 18 and 28 days ofgestation was about 14 fold for Cl− and 300 fold for inulin. There was no evidence for a decreasing equivalent pore radius in the course of gestation from 14–18 days.
Reminiscences about Josh Goldberg and general relativity

This article is a personal recollection about Josh Goldberg’s life and contributions to general relativity.
Central and peripheral norepinephrine concentrations in rat strains selectively bred for differences in response to stress: Confirmation and extension

Inbred rats from the Maudsley Reactive (MR) strain had lower concentrations of norepinephrine in hypothalamus, heart, and spleen, and lower total catecholamines in adrenal than inbred Maudsley Non-Reactive rats (MNRA line). In contrast, they had a higher concentration of telencephalic NE than MNRA rats. These results confirmed previous findings obtained on rats maintained by non-systematic breeding within the two lines. Comparisons were also made between MR and a second Maudsley Non-Reactive strain (MNR). Rats of the two Non-Reactive lines (MNRA, MNR) have been bred from the same foundation population and selected for the same behavioral characteristics, but have been genetically isolated from each other for many generations. It was found that MR rats showed differences from MNR rats in hypothalamic and peripheral (but not telencephalic) NE concentrations similar to those seen in MR/MNRA comparisons. Since rats of the two Non-Reactive lines differ appreciably from MR rats in open-field defecation (the criterion on which they were selected), their differences from MR rats in a neurochemical system involved in sympathetic function suggests that this system may be functionally related to well established behavioral and physiological differences between the lines.
Effects of Al/Si ordering on feldspar dissolution: Part I. Crystallographic control on the stoichiometry of dissolution reaction

Abstract The incongruent dissolution of feldspar is associated with the formation and evolution of Si-rich amorphous interfacial structures during its chemical weathering. The stoichiometry of dissolution is compositionally dependent, and this dependence reflects the nature of dissolution reaction as a combination of surface renewal and heterogeneous chemical reaction. We hypothesize that during continuous surface renewal, reactive sites on a feldspar’s surface will inherit characteristics from the bulk structure of the primary mineral. Hence, the dissolution rate of feldspar depends not only on water chemistry but also on its crystallographic properties. We propose a new formalism to quantify the dependence of the dissolution rates of feldspars on their crystallographic properties. A correlation between the degree of Al/Si ordering and the stoichiometry of feldspar dissolution is predicted based on this formalism. This correlation is verified by a combination of water chemistry analysis, synchrotron X-ray diffraction with structure refinement (HR-XRD), and Fourier transform infrared spectroscopy (FTIR). We find that the rates of dissolution and the degree to which dissolution is incongruent depend on the frequency of SiOSi and SiOAl linkages (chemistry) and the crystallographic characteristics of these linkages (bond lengths, bond angles, and ordering) in the dissolving mineral. The knowledge of Al/Si ordering provides a means to quantify the relative abundances of Si atoms with different reactivities. Using a C 1 ¯ -based structure model, we show that the distribution of Al within the Al-rich (T1) type of tetrahedral sites has only a minor effect on dissolution stoichiometry, whereas the distribution of Al between the T1-type and the Si-rich (T2)-type of sites affects dissolution incongruence predominantly. A greater extent of disorder results in higher dissolution incongruence. As an implication, our results suggest that the formation of interfacial structures during silicate dissolution should at least be partially affected by reactivity differences among the framework atoms of a silicate.
Experience with electrophysiologically guided therapy of ventricular tachycardia with flecainide: summary of long-term follow-up.

Abstract In a heterogeneous group of 15 patients with clinical syncope or documented sustained ventricular tachycardia (VT), with induced sustained or nonsustained VT at programmed electrical stimulation, flecainide prevented tachycardia induction in 9 of 15 patients (60%) and improved responses in 2, for a 73% initial favorable response rate. Cycle length of induced rhythms increased an average of 141 ms after the drug. Antiarrhythmic response rate was higher in the absence of coronary artery disease. Ten of these patients were selected for a long-term drug trial. After a median follow-up of 13.5 months, 8 patients (53%) continue to receive flecainide, 6 (40%) successfully treated with flecainide alone and 1 each treated with concomitant therapy with amiodarone and a programmable antitachycardia pacemaker. Minor dosage adjustments were made during early outpatient therapy in 5 patients. Those continuing on therapy show a remarkable absence of side effects and stable drug concentrations. Therapy failed in 2 patients at 0.5 and 4 months, in 1 in association with progression of cardiomyopathy and in another with recurrence of sustained (slow) VT. Although our results have been favorable, preliminary reports from other laboratories have been mixed. Therefore, further experience is needed. In summary, flecainide appears promising in selected patients with VT using a carefully monitored approach including electrophysiologic induction studies.
Safety evaluation of DT388IL3, a diphtheria toxin/interleukin 3 fusion protein, in the cynomolgus monkey.

We developed a fusion toxin, DT388IL3, consisting of the catalytic and translocation domains of diphtheria toxin (DT388) linked to interleukin 3 (IL3) for the treatment of patients with acute myeloid leukemia (AML). Our goal in this study was to estimate a range for the maximum tolerated dose (MTD) and to evaluate the dose-limiting toxicity (DLT) of DT388IL3 in cynomolgus monkeys (Macaca fasicularis), which possess cross-reactive IL3 receptors. In our previous study, we administered up to six infusions of DT388IL3 at 40, 60, or 100 μg/kg every other day to three pairs (one male monkey and one female monkey) of young adult monkeys. In five of six monkeys, results showed a dose-dependent increase in malaise and anorexia but no consistent abnormalities in serum chemistries or blood counts. There was no evidence of organ damage by blood tests or histopathology. However, the female treated at 100 μg/kg, died of moderate to severe vasculitis of multiple tissues. Based on these findings, this study repeated the 100 μg/kg group and added a group that received 150 μg/kg in an effort to confirm a dose response. Two female monkeys were treated with up to six infusions of DT388IL3 at 100 μg/kg or 150 μg/kg every other day. One additional female monkey was treated as a negative control. Monkeys in the 100 μg/kg group showed moderate malaise and anorexia, but no consistent abnormalities in blood counts or serum chemistries. Moderate elevations of liver enzymes were noted in the 150 μg/kg group in addition to severe malaise and anorexia. No significant findings were revealed at gross necropsy. The histopathological findings revealed regenerative myeloid hyperplasia and hepatic degeneration and regeneration in the 150 μg/kg group. Similar lesions of less severity were detected in the 100 μg/kg group. DT388IL3 plasma half-life was approximately 20 min with a peak concentration of approximately 2 μg/ml (30,000 pM). The IC50 for AML blasts in vitro was 6 pM. Collectively, our results suggest that DT388IL3 can be tolerated at doses up to 100 μg/kg in a nonhuman primate, which is higher than previously reported for other AML directed diphtheria toxin fusion proteins, and should in principle allow for dose escalation with reduced toxic side effects. Based on these findings a phase I clinical trial has recently been initiated with DT388IL3 for the treatment of AML.
Diaphragmatic paralysis and eventration: Newer approaches to diagnosis and operative correction

Positive contrast peritoneography allows the preoperative demonstration of the exact diaphragmatic contour in suspected eventration or paralysis. Anatomical appearances of bilateral elevation or infracardiac involvement will indicate the need for abdominal rather than transthoracic approach for repair. The use of peritoneography should permit rapid evaluation of newborns with respiratory distress and allow repair before long-standing respirator support has produced pulmonary parenchymal damage.
Risk Exposure Assessment of Dairy Parlor Workers

Modern dairy operations have evolved into a highly specialized and precise industrialized process timed critically for maximum milk production. Milking cows is a series of carefully sequenced work tasks that can be characterized as rapid, repetitive, forceful and include awkward postures of the hands, wrists, forearms, arms and shoulders. Exposure assessment using Strain Index (SI) and HAL (Hand Activity Level) was conducted in six dairy parlors at five locations throughout the Colorado region for this pilot study to evaluate the utility of these ergonomic assessment methods in dairy parlors and to estimate risk for upper extremity (UE) musculoskeletal disorders (MSDs) among dairy parlor workers. Results from our pilot study suggest that dairy parlor work is stressful to the UE with increased risk for developing MSDs.
Properties of the Eighth Nerve Action Potential

The eighth nerve action potential in the cat was recorded from the round window and from the eighth nerve. The conduction velocity, measured directly and computed from the fiber diameter, was found to be approximately 25 m/sec. Comparison of the onset of the action potential at the round window and its appearance in the eighth nerve showed a delay of 0.3 msec, based upon the theoretical time of transmission according to the conduction velocity. As the stimulus intensity was increased, a decrease in the latency of the action potential of the eighth nerve was noted.
A utility control panel for demand response planning

Demand response (DR) is the largest underutilized reliability resource in North America. This is partly due to the non-existence of a reasonably accurate model for DR in the energy industry to allow utilities to properly apply and manage their current programs. Such models could help utilities in evaluating the impact of DR programs on their system performance and determine which programs are more favorable in view of certain conditions. In this paper a new DR model is developed that is more consistent with demand dynamics compared to previous models. Using this model, various types of common DR programs are modeled and compered on different buses of the IEEE RBTS test system with various load profiles. Results of such studies would allow for a proper planning of the available DR resources based on the system adequacy and reliability needs.
Incidence of psoriasis in children: a population-based study.

Background Although psoriasis is considered to have a dual peak in age of onset, currently no studies exist regarding the incidence of psoriasis in children. Objective The objective of this study was to determine the incidence of psoriasis in childhood. Methods A population-based incidence cohort of patients aged younger than 18 years first given the diagnosis of psoriasis between January 1, 1970, and December 31, 1999, was assembled. The complete medical record of each child was reviewed and psoriasis diagnosis was validated by a confirmatory diagnosis in the medical record by a dermatologist or medical record review by a dermatologist. Age- and sex-specific incidence rates were calculated and were age and sex adjusted to 2000 US white population. Results The overall age- and sex-adjusted annual incidence of pediatric psoriasis was 40.8 per 100,000 (95% confidence interval: 36.6-45.1). When psoriasis diagnosis was restricted to dermatologist-confirmed subjects in the medical record, the incidence was 33.2 per 100,000 (95% confidence interval: 29.3-37.0). Incidence of psoriasis in children increased significantly over time from 29.6 per 100,000 in 1970 through 1974 to 62.7 per 100,000 in 1995 through 1999 ( P Limitations The population studied was a mostly white population in the upper Midwest. Conclusion The incidence of pediatric psoriasis increases with increasing age. There is no apparent dual peak in incidence. The incidence of pediatric psoriasis increased in recent years in both boys and girls.
Language endangerment and the violent ethnic conflict link in Middle Belt Nigeria

Abstract This paper highlights the fact that language endangerment in some multilingual developing societies is causal to the violent ethnic conflicts in those societies. Endangered language identity groups shift to the dominant language groups. But, over time, a concatenation of factors and nuanced realisation of perceived marginalisation (showing overtly at the political, economic, social and religious realms) leads to attrition in the wake of the endangered groups’ clamour for fair treatment. The cases of Benue, Plateau and Taraba States in Middle Belt Nigeria (involving the Tiv, Jukun, Etulo, Kuteb, Berom, Afizere, Anaguta, Taroh, and Hausa ethnic groups) reveal this fact. Highly significant calculated t-test values at an alpha level of <0.05 are found, for example, to show the disintegration of bilingual behaviour between Tiv/Jukun and Tiv/Etulo during the period of the violent ethnic clashes among them. Language endangerment/shift reversal is complex. It can create conflicts but at the same time hel...
HEMOLYTIC TRANSFUSION REACTION ASSOCIATED WITH POORLY DETECTABLE ANTI-JKA.

A hemolytic transfusion reaction, probably attributable to anti-Jka, occurred in a patient whose serum, before transfusion, reacted only very weakly with Jk(a+) cells.
Seasonal variation of bottom turbidity layer in Etauchi Bay

The beam attenuation coefficient, organic carbon (POC) and organic nitrogen (PON) contents of suspended materials in Etauchi Bay, which has little inflow of river water as well as very weak tidal current (maximum speed: 6.5cm·sec−1), were measured as a function of depth for all seasons to understand a seasonal variation of bottom turbidity layer. In spring and summer, the beam attenuation coefficient in bottom layer and POC and PON contents of suspended materials in the surface water layer increased with time, which brought the occurrence of the bottom turbidity layer. From autumn to winter, however, their concentrations became low and constant over the whole depth almost independent of time. As a result, the bottom turbidity layer disappeared in winter and beam attenuation coefficient became constant over the whole depth. From these results, it may be considered that the bottom turbidity layer was produced by phytodetritus brought from surface water layer, rather than by resuspension of bottom sediment in Etauchi Bay.
METHODS FOR TESTING THE DYNAMIC MECHANICAL RESPONSE OF SOLID FOODS

Techniques for measuring mechanical resonance, vibration transmissibility, pulse propagation velocity, and the resilience or rebound characteristics of solid food commodities are reviewed. Emphasis is placed upon measurements of the dynamic elastic properties of foods and changes in these properties as food products lose their stiffness, rigidity, or firmness. Correlations of certain elastic properties with product quality, especially texture, are presented, and a number of nondestructive dynamic methods for sorting food commodities are described.
Chemistry and Immunochemistry of the Pneumococcal Polysaccharide Vaccine with Special Reference to Cross-Reactions and Immunologic Factors

This review summarizes data on the cross-reactions observed among the subtypes of Streptococcus pneumoniae. Types 6A and 6B; 19F, 19A, 19B, and 19C; 18F, 18A, 18B, and 18C; and 23F, 23A, and 23B were examined with use of radioimmunoassay for measurement of inhibition of binding; the cross-reactions are discussed in terms of the known chemical structures of the antigens involved. Cross-reactions observed with use of rabbit antisera proved to be an unreliable guide to the responses observed thus far in humans. Cross-reactions of pneumococcal capsular polysaccharide antigens with other bacterial antigens are mentioned. These cross-reactions are analyzed with the idea of maximizing the effectiveness of the pneumococcal vaccine. Immunologic factors that may determine the quality and/or quantity of the immune response to immunization are discussed. These factors include antigenic competition and influence of preimmunization levels of antibody. Antigenic competition, although not a major concern with the present vaccine, may determine the upper limit of the number of capsular types that can be present in a single vaccine. The preimmunization level of antibody may determine the specificity of the antibody produced after vaccination.
Polarographic, potentiometric and calorimetric studies of complexes in aqueous dioxane media

Abstract Polarographic, potentiometric and calorimetric methods were used to study certain metal complexes in 50 wt.% dioxane. The acid dissociation constants of picolinic acid, pyridylacetic acid and 6-methyl-2-picolylmethylamine were determined at 15, 25 and 35°C. Stability constants were calculated for 6-methyl-2-picolymethylamine with Cu(II) Ni(II), Co(II), Zn(II) and Cd(II) by the Calvin-Bjerrum potentiometric titration technique. The over-all stability constants of Cu(II) and Cd(II) with 2-aminomethylpyridine, 6-methyl-2-aminomethylpyridine, 2-picolylmethylamine, 6-methyl-2-picolylmethylamine and picolinic acid were determined by a polarographic method. A direct calorimetric method was used to determine the heats of formation of some of these complexes.
Evaluating the diagnosis and prognosis of hypertension by automated blood pressure monitoring: Outline of a symposium

The technique of automated whole-day blood pressure monitoring by noninvasive, lightweight portable devices has recently become available for clinical use. This article, together with the six that follow it, comprise the proceedings of a symposium on the diagnostic and prognostic use of this new approach. There is a growing belief that standard clinical methods may overdiagnose hypertension (the phenomenon of "white coat" or "office" hypertension), subjecting some patients to unnecessary long-term treatment. The automated blood pressure monitoring procedure may be especially helpful in evaluating patients whose office-diagnosed hypertension is not associated with confirmatory clinical findings or history. Data derived from whole-day blood pressure measurements appear to be more reproducible than conventional blood pressure values and correlate more closely with evidence for cardiovascular changes. This symposium has addressed some of the issues associated with the monitoring techniques, including the accuracy of values obtained with noninvasive equipment, interpretation of the data, and costs of the procedure. The evidence and arguments presented by these papers suggest that automated blood pressure monitoring is becoming a justified and desirable procedure in selected patients with a preliminary clinical diagnosis of mild to moderate hypertension.
What's wrong with IVR self‐service

Purpose – Reports in the popular press suggest much consumer frustration with interactive voice response (IVR) self‐service. The present study aims to conceptualize why frustration might occur and measures attitudes toward IVR.Design/methodology/approach – Questionnaire responses were obtained from a quota sample approximately equally divided among men and women and three age groups (18‐28, 29‐48, 49 and older).Findings – Compared to a human operator, consumers perceive that transactions conducted through IVR take longer and are less customizable. Respondents strongly prefer a human operator, believe that IVR was implemented to benefit the company more than customers, and are bothered by not having an initial choice of a human operator versus IVR. Despite these negative views, satisfaction with IVR was primarily driven by transaction speed rather than concerns with these other issues. Compared to younger consumers, older respondents held a more cynical view of IVR and the companies that employ the technol...
Minimum Wages and Poverty: Will a $9.50 Federal Minimum Wage Really Help the Working Poor?

Using data drawn from the March Current Population Survey, we find that state and federal minimum wage increases between 2003 and 2007 had no effect on state poverty rates. When we then simulate the effects of a proposed federal minimum wage increase from $7.25 to $9.50 per hour, we find that such an increase will be even more poorly targeted to the working poor than was the last federal increase from $5.15 to $7.25 per hour. Assuming no negative employment effects, only 11.3% of workers who will gain live in poor households, compared to 15.8% from the last increase. When we allow for negative employment effects, we find that the working poor face a disproportionate share of the job losses. Our results suggest that raising the federal minimum wage continues to be an inadequate way to help the working poor.
Metabolism of 3,4-dihydroxyphenylacetic acid (DOPAC) in the human☆

Abstract Five subjects were infused i.v. with 75 μC of 3,4-dihydroxyphenylacetic acid-2 14 C(DOPAC) and urine collected at various intervals for 24 hr. The radioactive metabolic products in the urine were separated and identified. The results indicate that DOPAC is rapidly O -methylated to 3-methoxy-4-hydroxyphenylacetic acid (HVA). Within 24 hr after an i.v. infusion of DOPAC-2- 14 C 40 per cent of the radioactivity was recovered in the urine as HVA. Whereas HVA was the principal metabolic product, approximately 5 per cent of the DOPAC was metabolized to the conjugate of HVA. 3,4-Dihydroxybenzoic acid (DOBA) and trace amounts of vanillic acid were found, plus several unidentified metabolites.
Clinical pearls in cardiology.

At the 2001 annual conference of the American College of Physicians, a new teaching format to aid physician learning, Clinical Pearls, was introduced. Clinical Pearls is designed with the 3 qualities of physician-learners in mind. First, we physicians enjoy learning from cases. Second, we like concise, practical points that we can use in our practice. Finally, we take pleasure in problem solving. In the Clinical Pearls format, speakers present a number of short cases in their specialty to a general internal medicine audience. Each case is followed by a multiple-choice question answered live by attendees using an audience response system. The answer distribution is shown to attendees. The correct answer is then displayed and the speaker discusses teaching points, clarifying why one answer is most appropriate. Each case presentation ends with a Clinical Pearl, defined as a practical teaching point that is supported by the literature but generally not well known to most internists. Clinical Pearls is currently one of the most popular sessions at the American College of Physicians meeting. As a service to its readers, Mayo Clinic Proceedings has invited a selected number of these Clinical Pearl presentations to be published in our Concise Reviews for Clinicians section. “Clinical Pearls in Cardiology” is one of them.
Efficient HPC Data Motion via Scratchpad Memory

The energy required to move data accounts for a significant portion of the energy consumption of a modern supercomputer. To make systems of today more energy efficient and to bring exascale computing closer to the realm of possibilities, data motion must be made more energy efficient. Because the motion of each bit throughout the memory hierarchy has a large energy and performance cost, energy efficiency will improve if we can ensure that only the bits absolutely necessary for the computation are moved through the hierarchy. Toward reaching that end, in this work we explore the possible benefits of using a software-managed scratchpad memory for HPC applications. Our goal is to observe how data movement (and the associated energy costs) changes when we utilize software-managed scratchpad memory (SPM) instead of the traditional hardware-managed caches. Using an approximate but plausible model for the behavior of SPM, we show via memory simulation tools that HPC applications can benefit from hardware containing both scratchpad and traditional cache memory in order to move an average of 39% fewer bits to and from main memory, with a maximum improvement of 69%.
Identification of a mineralocorticoid receptor binding substance in the urine of patients with congenital adrenal hyperplasia

Abstract Increased amounts of circulating mineralocorticoid receptor binding substances presumed to be natural antagonists were previously demonstrated in congenital adrenal hyperplasia. In this study the feasibility of using urinary extracts for the identification of such binding substances was investigated. Urinary extracts from patients with the 21-hydroxylase defect did contain greater than normal amounts of mineralocorticoid receptor binding material. When subjected to Chromatographic separation using a radioreceptor assay to follow the course of fractionation, a major aldosterone binding competitor was identified. On the basis of its Chromatographic mobility in comparison with the labeled steroid, radioimmunoassay, ultraviolet absorption and radio-receptor assay of the native and acetylated derivative, the component was identified as 11-deoxycorticosterone and its structure confirmed by mass spectrometry. Although the major mineralocorticoid receptor binding component proved not to be an antagonist but an agonist, the results are in keeping with other evidence for overproduction of 11-deoxycorticosterone in the simple virilizing form of the disorder. Our finding did not disprove the existence of a circulating mineralocorticoid antagonist in congenital adrenal hyperplasia, but demonstrate that the major receptor binding substance in urinary extracts in that disorder is the mineralocorticoid agonist, 11-deoxycorticosterone.
Mechanistic Analysis of Local Ori Melting and Helicase Assembly by the Papillomavirus E1 Protein

Preparation of DNA templates for replication requires opening of the duplex to expose single-stranded (ss) DNA. The locally melted DNA is required for replicative DNA helicases to initiate unwinding. How local melting is generated in eukaryotic replicons is unknown, but initiator proteins from a handful of eukaryotic viruses can perform this function. Here we dissect the local melting process carried out by the papillomavirus E1 protein. We characterize the melting process kinetically and identify mutations in the E1 helicase and in the ori that arrest the local melting process. We show that a subset of these mutants have specific defects for melting of the center of the ori containing the binding sites for E1 and demonstrate that these mutants fail to untwist the ori DNA. This understanding of how E1 generates local melting suggests possible mechanisms for local melting in other replicons.
An appointment with god: AIDS, place, and spirituality.

This article describes how an African American gay man living with AIDS used his spiritual, religious, and cultural strengths to resist internalized dislocation because of heterosexism and homophobia. He was able to experience a relocation of God from places that rejected him to places that were conducive to his healing. By using these strengths, he was able to reject his physician's prediction of death and to call on God in response to an end‐stage AIDS crisis. The development of spiritual agency is addressed.
An enhancing factor in normal chicken serum augmenting saline agglutination of a Mycoplasma antigen-antibody system.

Discussion and summaryEnhancement of agglutination with antibody of chickens against MG with a heat-stable component of normal fowl serum is in accord with the studies of Orlans and Rose(7). In the research of Orlans and Rose(7) and Makinodan et al(5) bovine serum albumin was the antigen, and precipitation increased with normal fowl serum. In the present paper, limited studies with two bacterial antibodies and anti-red blood cell serum failed to exhibit increased agglutination in the presence of EF in normal serum. These same normal sera enhanced the agglutination reaction with two unrelated Mycoplasma, M. gallisepticum and Tu. This observation would possibly suggest some relation between Mycoplasma antibody and the normal enhancing factor in serum.
Sorbitol crystallization can lead to protein aggregation in frozen protein formulations.

This work examines the cause of aggregation of an Fc-fusion protein formulated in sorbitol upon frozen storage for extended periods of time at −30°C. We designed sub-ambient differential scanning calorimetry (DSC) experiments to capture the effects of long-term frozen storage. The physical stability of formulation samples was monitored by size exclusion high performance liquid chromatography (SE-HPLC). DSC analysis of non-frozen samples shows the expected glass transitions (Tg′) at −45°C for samples in sorbitol and at −32°C in sucrose. In time course studies where sorbitol formulations were stored at −30°C and analyzed by DSC without thawing, two endothermic transitions were observed: a melting endotherm at −20°C dissipated over time, and a second endotherm at −8°C was seen after approximately 2 weeks and persisted in all later time points. Protein aggregation was only seen in the samples formulated in sorbitol and stored at −30°C, correlating aggregation with the aforementioned melts. The observed melts are characteristic of crystalline substances and suggest that the sorbitol crystallizes over time. During freezing, the excipient must remain in the same phase as the protein to ensure protein stability. By crystallizing, the sorbitol is phase-separated from the protein, which leads to protein aggregation.
A simulation procedure for groundwater quality assessments of pesticides

Abstract A procedure is described for making regional assessments of pesticide residue loadings and movement in groundwater underneath and downgradient from treated fields. A Monte-Carlo numerical simulation technique is used to generate model parameters for both the unsaturated and saturated zones. Simulations are performed using the Pesticide Root Zone Model linked to a simple groundwater solute transport model. The procedure is useful for evaluating the potential for producing pesticide residues in drinking water wells before actual field applications are made. Appropriate land management options, including restrictions on pesticide application, also can be developed using this procedure. The procedure was used to assess aldicarb levels in northeastern North Carolina groundwater resulting from application of the pesticide to peanuts. Probability density functions for selected soil characteristics were developed using a direct-access soils information data base. Probability density functions for selected groundwater characteristics were developed from available data for the study area. Simulation results indicated that mass fluxes to groundwater exceeded 0.01 and 0.1 kg ha−1 approximately 6.9 and 1.0 percent of the time, respectively. No fluxes exceeded 0.1 kg ha−1 at a distance of 60 m downgradient in any of the cases evaluated.
Clinical evaluation of the mandibular staple bone plate

Some of the problems in the use of the mandibular staple bone plate are improper placement of the implant labiolingually, gingival reaction around the pins, and compression loading of the implant. The use of the patient's denture to determine proper angulation and the preparation of the transosteal posts can eliminate improper placement. Mucogingival grafting can be used to treat the inflammatory gingival reaction around the posts, and compression loading can be controlled by proper recognition during processing, placement, and patient education.
Intelligent robot trends and predictions for the new millennium

An intelligent robot is a remarkably useful combination of a manipulator, sensors and controls. The current use of these machines in outer space, medicine, hazardous materials, defense applications and industry is being pursued with vigor but little funding. In factory automation such robotics machines can improve productivity, increase product quality and improve competitiveness. The computer and the robot have both been developed during recent times. The intelligent robot combines both technologies and requires a thorough understanding and knowledge of mechatronics. In honor of the new millennium, this paper will present a discussion of futuristic trends and predictions. However, in keeping with technical tradition, a new technique for 'Follow the Leader' will also be presented in the hope of it becoming a new, useful and non-obvious technique.
Selective elimination of low‐molecular‐weight ions in MALDI‐TOF mass spectrometry using a bipolar pulsed electrostatic particle guide

This study addresses a problem inherent in the use of microchannel plates as detectors for matrix-assisted laser desorption/ionization. We have developed a unique new method of ion transport using fast bipolar pulsing of an electrostatic particle guide to provide ion deflection and enhanced ion transmission. This mode of operation effectively eliminates the intense low-mass component of the spectrum which normally saturates microchannel -plate detectors, while at the same time transporting the higher-mass component with high efficiency. Enhancement of the resulting signal-to-noise ratio has been achieved.
Rapid stimulation of rhodamine 123 efflux from multidrug-resistant KB cells by progesterone

Rhodamine 123 is a mitochondrial dye that is retained for prolonged periods by carcinoma cells. While investigating causes of retention of this dye, we found that 10 microM progesterone caused a rapid stimulation of efflux of rhodamine 123 within 15 min from KB V20C cells, which overexpress the multidrug resistance pump. Progesterone did not stimulate efflux from KB cells that do not overexpress the pump, and verapamil blocked rhodamine 123 efflux in the presence or absence of progesterone, indicating that rhodamine 123 is removed from KB V20C cells by the multidrug resistance pump. Progesterone, however, is unlikely to stimulate rhodamine 123 efflux by simply increasing pump activity for two reasons: (1) progesterone inhibited the efflux of daunomycin from KB V20C cells, so it did not stimulate efflux of all drugs, and (2) progesterone inhibited efflux of rhodamine 123 from L1210/VMDRC cells and had little effect on Adr MCF7 cells; both overexpress the multidrug resistance pump. In the experiments with KB V20C cells, progesterone was the most active steroid tested. At 10 microM, progesterone caused a 70-fold stimulation, desoxycorticosterone, testosterone, promegestone and estradiol about 20-fold, and others had little or no effect. Progesterone may act by a non-genomic mechanism to decrease intracellular binding of rhodamine 123, making the dye accessible to the multidrug resistance pump.
Growth, cytology and flow cytometry of embryogenic cell suspension cultures of Panicum maximum Jacq. and Pennisetum purpureum Schum.

Summary Embryogenic cell suspensions of Panicum maximum (4 year old) and Pennisetum purpureum (3 year old) continue rapid growth upon subculture without a marked lag phase. They have cell doubling times of 27 h and 32 h, respectively, during the exponential phase of growth. Maximum cell numbers of 2 × 10′ cells · ml -1 are reached on about the eighth day of subculture in both species. Thereafter, cell lysis and death occur progressively. By day 16, 90 % of P. purpureum cells appear non-viable. Flow cytometry of the cell suspensions showed that at any given time during the 8–9 day culture period, a majority of the cells are in G 1 phase of the cell cycle, with substantial numbers cycling through the S and G 2 phases. No marked change in this distribution pattern was seen in the first 8–9 days of growth during which the cultures did not reach stationary phase. Flow cytometry, microspectrophotometry and chromosome counts showed the cultures comprised predominantly of normal diploid cells.
Formation of Cylindrical Sliding-Wear Debris on Silicon in Humid Conditions and Elevated Temperatures

The present study investigates the mechanics of roll formation between sliding bodies at elevated temperatures and humid conditions. Silicon is used as the model material for reciprocating linear sliding tests. The evolution of tribological rolls initially involves the rapid oxidation of silicon wear debris by water, the deformation of SiO2 particles into platelets, and then the compaction of these particles into a film deposited on the wear surface. The formation of compacted silica film requires minimum adsorption of water which enhances the adhesion between silica platelets. The stress cycle imposed on the film leads to the delamination of platelets near the sliding surface. The delaminated debris cluster into multiple aggregates that are subsequently rolled into dense cylindrical particles so as to relieve the interfacial shear stress. When the film and rolls are formed, the friction and wear rate is maintained at low steady state values.
Transcriptional Repression of p53 by Human T-cell Leukemia Virus Type I Tax Protein

The human T-cell leukemia virus type I oncoprotein Tax transcriptionally deregulates a wide variety of viral and cellular genes. Tax deregulation of gene expression is mediated through interaction with a variety of structurally unrelated cellular transcription factors, as Tax does not bind DNA in a sequence-specific manner. Although most of these cellular transcription factors have been shown to mediate activation by Tax, we have recently demonstrated that members of the basic helix-loop-helix (bHLH) family of transcription factors, which play a critical role in progression through the cell cycle, mediate repression by Tax. In this report, we examined whether Tax might repress transcription of the tumor suppressor p53, as the p53 gene has recently been demonstrated to be regulated by the bHLH protein c-Myc. Furthermore, loss or inactivation of the p53 gene has been shown to be causally associated with oncogenic transformation. We show that Tax represses transcription of the p53 gene and that this repression is dependent upon the bHLH recognition element in the p53 promoter. Together, these results suggest that Tax may promote malignant transformation through repression of p53 transcription.
On the discrepancy between whole-cell and membrane patch mechanosensitivity in Xenopus oocytes.

Mechanical stimulation of voltage-clamped Xenopus oocytes by inflation, aspiration, or local indentation failed to activate an increase in membrane conductance up to the point of causing visible oocyte damage. The absence of mechanosensitivity is not due to the vitelline membrane, rapid MG channel adaptation or tension-sensitive recruitment of new membrane. Membrane capacitance measurements indicate that the oocyte surface area is at least 5 times larger than that predicted assuming a smooth sphere. We propose that this excess membrane area provides an immediate reserve that can ‘buffer’ membrane tension changes and thus prevent MG channel activation. High-resolution images of tightly sealed patches and patch capacitance measurements indicate a smooth membrane that is pulled flat and perpendicular across the inside of the pipette. Brief steps of pressure or suction cause rapid and reversible membrane flexing and MG channel activation. We propose that changes in membrane geometry induced during cell growth and differentiation or as a consequence of specific physiological and pathological conditions may alter mechanosensitivity of a cell independently of the intrinsic properties of channel proteins.
Cancer Mortality Among Woodworkers

The mortality experience of 10,322 men employed in woodworking industries was compared with that of 406,798 nonwoodworkers. All subjects were enrolled in an American Cancer Society study and followed prospectively from 1959 through 1972. Age-adjusted rates of death from all causes and from all cancers were not higher in the woodworker group, but excess rates were observed for cancers of the lung, stomach, and bladder, as well as nonmelanoma skin cancer and possibly leukemia. Woodworkers experienced significantly decreased rates of colon-rectum cancer and coronary heart disease. The elevated cancer rates could not be explained by cigarette smoking habits. If anything, there is evidence to suggest a possible interaction between employment in woodworking trades and heavy cigarette smoking, in increasing the risk of lung and bladder cancer.
Assembly of Carbon–SnO2 Core–Sheath Composite Nanofibers for Superior Lithium Storage

Protective coating: Carbon-SnO(2) core-sheath composite nanofibers are synthesized through the creative combination of electrospinning and electrodeposition processes (see figure). They display excellent electrochemical performance when directly used as binder-free anodes for rechargeable lithium ion batteries.
Alternative Tobacco Product Use and Smoking Cessation: A National Study

Objectives. We investigated the frequency of alternative tobacco product use (loose leaf, moist snuff, snus, dissolvables, electronic cigarettes [e-cigarettes]) among smokers and the association with quit attempts and intentions.Methods. A nationally representative probability-based cross-sectional survey of 1836 current or recently former adult smokers was completed in November 2011. Multivariate logistic regressions evaluated associations between alternative tobacco product use and smoking cessation behaviors.Results. Of the smokers, 38% had tried an alternative tobacco product, most frequently e-cigarettes. Alternative tobacco product use was associated with having made a quit attempt, and those intending to quit were significantly more likely to have tried and to currently use the products than were smokers with no intentions to quit. Use was not associated with successful quit attempts. Interest in future use of alternative tobacco products was low, except for e-cigarettes.Conclusions. Alternative to...