cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5324: Pan-cancer identification of mutated pathways and protein complexes

Large-scale cancer sequencing efforts such as The Cancer Genome Atlas (TCGA) and others have shown that tumors exhibit extensive mutational heterogeneity with relatively few genes mutated at significant frequency and many genes mutated in only a small number of individuals. This long tail phenomenon complicates the identification of driver mutations by their observed frequency. The long tail is explained in part by the fact that driver mutations target genes in signaling and regulatory pathways, and these pathways may be perturbed by different mutations in different tumors. We developed two complementary algorithms, HotNet2 and Dendrix++, to analyze combinations of mutations in known or novel pathways. HotNet2 uses prior knowledge of pathways and protein complexes represented in a genome-scale protein-protein interaction network, and identifies significantly mutated subnetworks using a heat diffusion model. HotNet2 simultaneously assesses both the significance of mutations in individual proteins and the local topology of protein interactions. Dendrix++ identifies combinations of mutations de novo, without prior knowledge of pathways or protein interactions, by finding sets of mutations that are mutually exclusive across the tumor cohort. There are numerous examples of mutually exclusive mutations between interacting proteins; e.g. BRAF and KRAS in colorectal cancer. Dendrix++ generalizes this idea to find larger groups of mutually exclusive mutations. We applied HotNet2 and Dendrix++ to whole-exome sequencing and copy number aberration data from 3299 samples of twelve tumor types from TCGA Pan-Cancer project. Both algorithms identified gene sets that overlap well-known cancer pathways (e.g. TP53, MAPK, and RAS signaling pathways), as well as genes and complexes with less characterized roles in cancer (e.g. the cohesin and condensin complexes). HotNet2 subnetworks also contained novel candidate cancer genes that were rarely mutated in this cohort and thus not reported by single-gene tests of significance, including KDM5A, SHPRH, and ARID4A, each of which interacts with well-known cancer genes. Many of these gene sets have biological functions often perturbed in cancer, such as chromatin modification (e.g. the SWI/SNF and BAP1 complexes) and DNA damage repair (e.g. SHPRH). These results demonstrate the ability of HotNet2 and Dendrix++ to identify novel combinations of mutations in thousands of tumors, prioritizing genes and mutations in the long tail for further experimental studies. Citation Format: Mark D. Leiserson, Fabio Vandin, Hsin-Ta Wu, Jason R. Dobson, Benjamin R. Raphael. Pan-cancer identification of mutated pathways and protein complexes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5324. doi:10.1158/1538-7445.AM2014-5324
Assessment of Social Behavior in Children with Autism: The Development of the Behavioral Assessment of Social Interactions in Young Children.

Abstract There are a limited number of assessments available to examine social skills deficits in young children with Autism Spectrum Disorders (ASDs). The Behavioral Assessment of Social Interactions in Young Children (BASYC) was developed as a direct assessment of social deficits in young children with ASD relative to children without ASD. The BASYC is a semi-structured assessment designed to be administered by clinicians and teachers working with children with a possible ASD. The purpose of this study was to determine whether the BASYC discriminates social behaviors between children with and without ASD. There were 77 participants ( n = 48 children with ASD; n = 29 children without ASD) in this study. Scores on the BASYC significantly predict group membership. Sensitivity and specificity of the BASYC was .977 and .871, respectively. Item discrimination indices revealed that the majority of items on the Social Responsivity scale discriminated well between groups; however, this was not the case for the Social Initiation scale. Although additional research is required, the BASYC is currently an instrument that is easy to administer, discriminates well between children with and without ASD based on social behaviors and may assist in goal planning and monitoring of social skills treatment progress.
PIP2 Modulates T-Tubule Remodeling During Heart Failure by Working as a Binding Substrate for BIN1

The membrane curvature-forming protein BIN1 is known to be involved in T-tubule formation. Phosphatidylinositol-4,5-bisphosphate (PIP2) has been shown to anchor BIN1 and maintain its localization to the sarcolemma. Since heart failure (HF) is characterized by T-tubule remodeling and dyssynchronous Ca2+ release, we hypothesized that PIP2-mediated targeting of BIN1 to sarcolemma is compromised during the development of HF and is responsible for T-tubule remodeling. We developed an in-vitro model using HL1 cells that developed tubule-like extensions during BIN1 overexpression. These exogenous BIN1-induced tubules were continuous with the sarcolemma (RH-237 staining) similar to T-tubules in ventricular myocytes. To further understand if the BIN1/PIP2 complex is disrupted in HF, we depleted PIP2 in HL1 cells by inhibition of PI4K or activation of PLCβ1. We treated transfected HL1 cells with wortmannin, endothelin-1 (Et-1), m-3M3FBS and a combination of Et-1 + m-3M3FBS. Treated cells showed significantly more tubule degeneration compared to non-treated cells and membrane PIP2 levels decreased as measured by transfecting HL1 cells with a fluorescent PIP2 reporter (PLCδ1-PH-GFP construct). To further determine whether depletion of PIP2-mediated T-tubules loss is correlated with defects in Ca2+ cycling, we isolated adult rat ventricular myocytes, treated them with the same PIP2 depletion agents, then stained them with di-4-ANEPPS in order to assess T-tubule organization. All treated cells showed significantly reduced T-tubule organization than control cells. We also measured Ca2+ cycling in these cells during basal (2000ms) and rapid (1000ms) pacing using flou-2AM. Ca2+ release was delayed in certain cellular regions in treated myocytes and rise time, time to peak and decay time were significantly increased at both pacing rates. These results show that depletion of PIP2 can lead to T-tubule disruption and suggests that PIP2 is required for T-tubule maintenance and function.
Molecular MRI assessment of vascular endothelial growth factor receptor-2 in rat C6 gliomas.

Angiogenesis is essential to tumour progression and a precise evaluation of angiogenesis is important for tumour early diagnosis and treatment. The quantitative and dynamic in vivo assessment of tumour angiogenesis can be achieved by molecular magnetic resonance imaging (mMRI). Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the main regulatory systems in angiogenesis and have been used as hot targets for radionuclide-based molecular imaging. However, little research has been accomplished in targeting VEGF/VEGFRs by mMRI. In our study, we aimed to assess the expression of VEGFR2 in C6 gliomas by using a specific molecular probe with mMRI. The differential uptake of the probe conjugated to anti-VEGFR2 monoclonal antibody, shown by varied increases in T1 signal intensity during a 2 hr period, demonstrated the heterogeneous expression of VEGFR2 in different tumour regions. Microscopic fluorescence imaging, obtained for the biotin group in the probe with streptavidin-Cy3, along with staining for cellular VEGFR2 levels, laminin and CD45, confirmed the differential distribution of the probe which targeted VEGFR2 on endothelial cells. The angiogenesis process was also assessed using magnetic resonance angiography, which quantified tumour blood volume and provided a macroscopic view and a dynamic change of the correlation between tumour vasculature and VEGFR2 expression. Together these results suggest mMRI can be very useful in assessing and characterizing the expression of specific angiogenic markers in vivo and help evaluate angiogenesis associated with tumour progression.
A renormalized equation of transfer for Rayleigh scattering

Abstract We consider a certain asymptotic limit of the Rayleigh scattering vector equation of transfer describing the Stokes parameters of light. This limit corresponds to near thermodynamic equilibrium. By introducing appropriate scalings in the vector equation to describe this limit, a renormalized scalar equation of transfer is derived for the total specific intensity of radiation. This equation is both the leading order result as well as the next higher order result of an asymptotic analysis. Numerical testing of this renormalized equation for the exponential decay rate in diffuse reflection halfspace problems demonstrates the very good accuracy of this scalar description. This good accuracy is extant for conditions even far from the asymptotic limit under consideration, thus establishing the robustness of this treatment. In particular, this equation is more accurate than the scalar equation of transfer commonly used to describe light transport through a Rayleigh scattering medium. This asymptotic analysis also yields simple estimates of the state of polarization of the light. Carrying the analysis to still one higher order leads to a fundamentally different scalar equation for the total intensity. This equation can also be cast into the form of a renormalized equation of transfer, but only formally.
Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells

The first wave of transcription, called zygotic genome activation (ZGA), begins during the 2-cell stage in mouse preimplantation development and marks a vital transition from the maternal genetic to the embryonic genetic program. Utilizing DNA microarray data, we looked for genes that are expressed only during ZGA and found Zscan4, whose expression is restricted to late 2-cell stage embryos. Sequence analysis of genomic DNA and cDNA clones revealed nine paralogous genes tightly clustered in 0.85 Mb on mouse chromosome 7. Three genes are not transcribed and are thus considered pseudogenes. Among the six expressed genes named Zscan4a-Zscan4f, three - Zscan4c, Zscan4d, and Zscan4f - encode full-length ORFs with 506 amino acids. Zscan4d is a predominant transcript at the late 2-cell stage, whereas Zscan4c is a predominant transcript in embryonic stem (ES) cells. No transcripts of any Zscan4 genes are detected in any other cell types. Reduction of Zscan4 transcript levels by siRNAs delays the progression from the 2-cell to the 4-cell stage and produces blastocysts that fail to implant or proliferate in blastocyst outgrowth culture. Zscan4 thus seems to be essential for preimplantation development.
Dehydroepiandrosterone metabolism in the female rhesus monkey: Oral versus intravenous administration

Abstract Because of the biologic effects on a variety of end points reported for dehydroepiandrosterone (DHA) and its sulfate (DHAS) after oral administration, we studied the metabolism of DHA in six female rhesus monkeys after oral and after intravenous administration. We administered [4- 14 C]DHA p.o. and [7- 3 H]DHA i.v. simultaneously, drawing blood samples at increasingly longer intervals for 24 h. The mean ± SE metabolic clearance rate of the intravenous DHA was 404 ± 49 L/day. The mean metabolic clearance rate was 2,601 ± 261 L/day after oral administration, and the calculated absorption was 16.3 ± 2.5%. There was rapid conversion of p.o. DHA to DHAS, as the conversion ratio of the orally administered DHA measured in the blood as [4- 14 C]DHAS was 63.3 ± 13.6, whereas the conversion ratio of intravenously administered DHA to DHAS was 9.3 ± 2.0. Small amounts of DHA were measured in the blood as testosterone and androstenedione after both forms of administration. We conclude that there is marked metabolism in splanchnic tissue of orally administered DHA to DHAS prior to its entry into the bloodstream, and the absorption of DHA itself is minimal when administered by mouth to the rhesus monkey.
Chemical sensors based on hydrophobic porous sol-gel films and ATR-FTIR spectroscopy

A new chemical sensor based on attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy has been fabricated by coating an ATR crystal with a hydrophobic mesoporous silica film. The highly porous coating can extract hydrophobic analytes, such as benzene, from aqueous solutions and concentrate them inside the film. The enrichment of the analytes inside the film provides the sensor with enhanced sensitivity. The hydrophobic porous film can efficiently exclude water from the region probed by the evanescent wave, thus eliminating the spectral interference due to water absorption bands. Measurement of nitrogen adsorption and desorption isotherms of the films using surface acoustic wave techniques has been used to characterize the pore structure of the films. Relationships between the structure of the porous film and sensor performance are discussed.
Gamete transport in the superovulated cow

Abstract Reduced efficiency of sperm transport in superovulated cows can be inferred from fertilization rates, which generally average about 65%, or about 20% lower than those found in single-ovulating cattle. Also, most fertilized ova recovered from superovulated cattle have no accessory sperm in the zona pellucida, which suggests minimal numbers of sperm at the site of fertilization. Low fertility of either cows or bulls reduces the fertilization rate, probably through an effect on survival of sperm or efficiency of sperm transport in the cow. Other factors that affect fertilization rate, presumably also acting through sperm survival or transport, include age of the cow, season of the year, interval after calving, stage of the estrous cycle at which the superovulation treatment is begun, total dose of FSH used, number and timing of artificial inseminations, and site of deposition of the inseminate. Use of purified FSH to induce superovulation has improved the fertilization rate markedly in some instances, and insemination with high numbers of sperm in fresh undiluted semen has raised the fertilization rate above 90%. The apparent inhibition of sperm transport in superovulated cows may be mediated through changed patterns of steroid hormone secretion. Ova seem to pass through the oviducts faster in superovulated cows than in single-ovulating cows. The rate of passage may be shortened by a day or more in some cases, but the proportion of superovulated cows with hastened ovum transport is not known, and the consequences of rapid transport on survival of embryos has not been ascertained.
Alexandrium peruvianum (Balech and Mendiola) Balech and Tangen a new toxic species for coastal North Carolina

Abstract Routine sampling of the water quality stations in the New River Estuary (Jacksonville, North Carolina, USA) during November 2004 revealed the presence of a previously unidentified dinoflagellate. Preliminary observations of its morphology suggested it to be consistent with that of Alexandrium peruvianum (Balech et Mendiola) Balech et Tangen. Observations using brightfield, epifluorescence and scanning electron microscopy confirmed the diagnostic thecal plates to be those of A. peruvanium . Clonal cultures established from cells isolated from the New River Estuary samples were also used for further studies of morphology and for the presence of toxins. Thecal morphology was consistent with that described by Balech clearly separating it from the sister species Alexandrium ostenfeldii . Three classes of toxins were detected from these cultures. An erythrocyte lysis assay (ELA) was used to confirm the presence of hemolytic toxins in A. peruvianum cultures. A cellular EC 50 for lysis was 1.418 × 10 4 cells, well within the range the maximal cells densities found in the New River and more potent when compared on a cellular basis with Prymnesium parvum . Another toxin class detected in A. peruvianum cultures was the fast acting 13-desmethy C and D spirolides also produced by the sister species A. ostenfeldii . The last toxin type detected in the A. peruvianum cultures was the paralytic shellfish toxins, GTX 2, 3, B1, STX and C1,2. These findings expand the geographic range of occurrence for A. peruvianum in the U.S. to be much greater than previously considered. The morphological characters agreed with previously reported molecular data in separating A. peruvianum from A. ostenfeldii . It is also the first confirmed report that this species produces PSP toxins, spirolides and naturally occurring hemolytic substances. In light of these findings additional attention is needed for the detection of Alexandrium species in all coastal waters of the U.S. This added effort will enhance the evaluation of the relative impacts of the species to shellfish safety and bloom surveillance.
THE ABSOLUTE YIELD OF BACTERIOCHLOROPHYLL FLUORESCENCE IN VIVO

Abstract— –The method of Weber and Teale for determining absolute fluorescence quantum yield of dyes in solution was modified for determination of the yield of bacteriochlorophyll fluorescence from chromatophores and whole cells of photosynthetic bacteria. Measured yields ranged from about 1–6 per cent. The yield depended on intensity and wavelength of the exciting light. The higher yield at higher light intensity was interpreted as due to saturation of photosynthesis. The lower yield in some strains when excited at 810 nm was attributed to preferential excitation of the reaction center pigment P800. From this study and the lifetime measurements of others, the relation τ=Q.τ0 was substantiated for the fluorescence of bacteriochlorophyll in vivo, τ being the actual lifetime, τ0 the intrinsic lifetime as estimated from the absorption band area, and Q the quantum yield of fluorescence.
Septic Shock Induced From An Implantable Cardioverter-Defibrillator Lead-Associated Candida albicans Vegetation

In recent years, the use of implantable cardioverter-defibrillators has made a significant impact in the treatment of cardiac disease. With the advent of this therapy, infection has become a growing concern, with a reported incidence of 1-11%. Although device-related infections are most frequently caused by bacterial pathogens, fungal etiologies are uncommon and carry an exceedingly high mortality rate. To date, there is only one published report of an implantable cardioverter-defibrillator lead-associated infection secondary to Candida albicans. This case report presents the second such case. A review of the literature regarding fungal endocarditis as well as diagnosis and therapy of this rare and dangerous disease is discussed.
Mutagenesis directed by phosphotriester analogues of oligonucleotides: a way to site-specific mutagenesis in vivo.

Abstract A new approach to induce directed mutations in genes of study through simple cotransfection of E. coli cells by the mixture of primer and template was developed. This method is based on the use of synthetic phosphotriester analogues of oligonucleotides as site-specific mutagenic primers. The achieved yield of mutant clones was 2–3%.
A quantum-field theory approach to the calculation of energy levels in helium-like Rydberg atoms

We discuss the fine structure splitting of the energy levels in Rydberg states of helium or helium-like ions on the basis of quantum electrodynamics, using time-independent perturbation theory and the radiation gauge. For the zero-order description of the states we use products of Dirac-type wavefunctios with shielding for the outer electron. The perturbing interaction includes the residual electrostatic potential, the interaction coming from the exchange of virtual photons, and the creation of virtual electron-positron pairs. It is shown that the level shifts for low-Z ions are given to high accuracy by a procedure followed previously. This consists of adding the expectation value of a retardation-correction potential V/sup corr//sub 2//sub ..gamma../(r/sub 2/), arising from two-photon exchange, to the result obtained from relativistic multiple-Coulomb exchange. For principal quantum number of the Rydberg electron of the order of ten, we describe the range of values of Z for which this procedure gives the splitting to one-percent accuracy. Copyright 1987 Academic Nress, Inc.
Psychosis and epilepsy: Seizure‐type comparisons and high‐risk variables

Compared 153 patients with temporal lobe epilepsy (TLE) and 79 patients with generalized epilepsy on the Goldberg Index, an MMPI-derived measure of psychosis. Analysis of covariance indicated that seizure type was not related to psychosis. Multiple regression analyses indicated that, in TLE, being female was correlated positively with Goldberg Index scores. In the group with generalized epilepsy, none of the variables was associated significantly with psychosis scores.
Submaximal effort tolerance as a predictor of all‐cause mortality in patients undergoing cardiac rehabilitation

Background Submaximal effort tolerance is routinely available during cardiac rehabilitation, but its prognostic value in relation to underlying referral diagnosis is not known. Hypothesis Treadmill effort capacity during submaximal exercise training predicts all-cause mortality after cardiac rehabilitation. Methods We followed 600 consecutive patients (450 men and 150 women, mean age 65 years) who were referred to a 12-week outpatient program of cardiac rehabilitation; 37% had a prior myocardial infarction (MI), 44% had a recent percutaneous intervention (PCI), and 39% had history of coronary artery bypass surgery (CABG). Results There were 48 deaths during a mean follow-up period of 1603 ± 822 days. By multivariate Cox analysis, exit MET activity was the most significant predictor of all-cause mortality. In this model, each 1 MET increase in exit submaximal effort tolerance was associated with a 34% decrease in mortality (hazard ratio [HR] 0.66, 95% confidence interval 0.56–0.77) alone and 28% decrease after adjustment for age (HR = 0.72, confidence interval 0.60–0.85). Enty MET level also had predictive value. Subgroup analysis revealed that the predictive value of exit METs was limited to patients after recent CABG and with MI. None of the variables predicted death after PCI, in whom mortality was significantly lower than in the other groups. Conclusions Submaximal effort tolerance at completion of cardiac rehabilitation, and also at entry, is a strong and age-independent predictor of mortality in patients who have had either recent CABG or MI without intervention, but not in patients after recent PCI. Copyright © 2007 Wiley Periodicals, Inc.
Determination and in-depth chromatographic analyses of alkaloids in South American and greenhouse-cultivated coca leaves

Methodology is described for the detection and/or determination of cocaine and minor alkaloids in South American coca as well as in greenhouse- and tropical-cultivated field coca of known taxonomy. Coca leaf from Bolivia, Peru, Ecuador and Colombia were subjected to the determination of cocaine, cis- and trans-cinnamoylcocaine, tropacocaine, hygrine, cuscohygrine and the isomeric truxillines. The greenhouse samples were cocaine-bearing leaves of the genus Erythroxylum and included E. coca var. coca, E. novogranatense var. novogranatense and E. novogranatense var. truxillense, and the alkaloids determined were cocaine, ecgonine methyl ester, cuscohygrine, tropacocaine and the cinnamoylcocaines. The tropical-cultivated coca were E. novogranatense var. novogranatense and E. coca var. coca. Cocaine and minor alkaloids were isolated from basified powdered leaf samples using a toluene extractant, followed by acid-Celite column chromatography. The isolated alkaloids were determined by capillary gas chromatography with flame ionization or electron-capture detection. Methodology is also presented for the isolation and mass spectral analysis of numerous trace-level coca alkaloids of unknown structure.
Theory of the temperature-dependent plastic flow in L12, alloys with unstable APBs on {111} planes

Abstract A model is developed for the thermally activated motion of 1/2〈110〉 superpartial dislocations on {010} planes and 1/3〈112〉 superpartials on {111} planes, when antiphase boundaries on {111} planes are unstable. These two superpartials are sessile because they have non-planar cores. The model is based on Duesbery′s model for the thermally activated formation of double kinks on sessile dislocations and on the results presented in the accompanying paper. The model successfully replicates the behaviour observed in single-crystal Pt3Al: the temperature dependence of the yield stress, (111) slip occurring for compression axes located on the [001] side of the unit triangle, and (001) slip occurring on the other side. The model also predicts that the location of the boundary between these two areas in the unit triangle should be temperature-dependent, and furthermore that in this boundary region (11l)[[lbar]l0] slip may also occur.
Percutaneous Balloon Valvuloplasty for Critical Aortic Stenosis: A Bridge to Safer Noncardiac Surgical Procedures

In this issue of the Proceedings (pages 753 to 757), Hayes and associates describe their experience with use of percutaneous aortic balloon valvuloplasty to decrease the risk of noncardiac surgical and invasive diagnostic procedures in 15 elderly patients (mean age, 79 years) who had critical aortic stenosis. All 15 patients had dyspnea on exertion, 8 had symptoms of angina, and 3 had syncope. The noncardiac condi­ tions for which surgical treatment was needed were hip fractures, known cancers, undiagnosed lung masses, and active gastrointestinal or urinary tract bleeding. Of the 15 patients, 7 were thought not to be candidates for aortic valve replacement because of active bleeding or other medical contraindications. The other eight patients were not candidates because of known or suspected metastatic cancer. Balloon valvuloplasty, performed with use of ei­ ther single or double balloons and standard val­ vuloplasty techniques, resulted in hemodynamic im­ provement. The results were comparable to those previously reported for aortic valvuloplasty. The mean aortic gradient decreased from 58 to 32 mm Hg, and the aortic valve area increased from 0.49 to 0.85 cm 2 . The cardiac index was unchanged. Of the 15 patients, 5 had major complications related to the aortic valvuloplasty. One patient died after left ventricular perforation. In two other pa­ tients, left ventricular perforation was successfully treated by pericardiocentesis. One patient required surgical repair of bilateral femoral pseudoaneurysms, and one patient had left bundle-branch block and transient congestive heart failure. The noncardiac surgical and invasive diagnostic procedures that were performed included total hip
Bridgman-Stockbarger Growth of Binary Alloyed Semiconductor Crystals with Steady Magnetic Fields

Single crystals of alloyed compound semiconductor crystals such as gallium‐aluminum‐antimonide are needed for optoelectronic devices. These crystals are solidified from a solution of molten gallium‐antimonide and aluminum‐antimonide in a Bridgman‐Stockbarger furnace. During the growth of alloyed semiconductor crystals, the solute’s concentration is not small so that the density differences in the melt are very large. These compositional variations drive compositionally driven buoyant convection, or solutal convection, in addition to thermally driven buoyant convection. These buoyant convections drive convective species transport, which produce nonuniformities in the concentration in both the melt and the crystal. A numerical model is presented for the unsteady transport for the growth of alloyed semiconductor crystals during the vertical Bridgman‐Stockbarger process with a steady axial magnetic field. Predictions of alloy concentration in the crystal and in the melt at several different stages during crystal growth are presented.
Glycoscience: integrating a key macromolecule more fully into the curriculum.

The recent report from the National Research Council, Transforming Glycoscience: A Roadmap for the Future, explores an important area of the life sciences. Glycoscience examples are suitable additions to many areas of the curriculum, and their inclusion will help ensure that students have an understanding of the diverse functions played by this key class of macromolecules.
Binary Mixing Approximations and Relations between Specific Conductance, Molar Conductance, Equivalent Conductance, and Ionar Conductance for Mixtures†

Simple linear approximations to the specific conductance of a mixture can be written in terms of various solute fractions (molar, equivalent, or ionic strength) and the specific conductances of its constituent binary systems. These binary conductances are evaluated at some type of “constant” concentration which characterizes the mixture (constant total molarity, constant total equivalents, or constant total ionic strength). These expressions can be made exact for fitting experimental data by including a correction term. General forms have been derived for transforming these binary approximations for the specific conductance and their corresponding correction terms to the analogous binary approximations for “concentration conductances” such as molar, equivalent, or ionar (ionic strength) conductance. Conversely, simple binary approximations for any concentration conductance in terms of arbitrary fractions for an arbitrary binary evaluation strategy lead to binary approximations for the specific conductance...
χ″ peak measurements in HTSC single crystals

Abstract The use of AC inductance techniques to measure AC absorption (χ″) in high-temperature superconducting materials is discussed. A single sharp peak in χ″ versus temperature is typically seen for good crystals of YBa 2 Cu 3 O 7− x , However, some crystals of this material show multiple χ″ peaks which have different magnetic field and frequency dependences. Crystals of Bi 2 Sr 2 Ca 1 Cu 2 O 8+ y and Tl 2 Ba 2 Ca 1 Cu 2 O 8+ y show only single χ″ peaks. Magnetic field, temperature, and measurement frequency dependences of χ″ of these materials are presented. A critical state model is used to interpret these results. Multiple peak behavior is explained as the presence of different superconducting domains in the crystals. Attempts to alter these domains by modifying the oxygen content and distribution in crystals of YBa 2 Cu 3 O 7− x by oxygen annealing were unsuccessful. Etching experiments did not show any surface contribution to the magnetic properties of these samples.
The Morphology and Function of the Hyoid Region in the Tree Sloths, Bradypus and Choloepus

The sloth hyoid region has unique structural features, associated with inverted feeding and dependence upon the tongue and lips for food manipulation and ingestion. The hyoid apparatus functions as a unit and is large and robust. The basihyal is strongly bound to the skull posterior in comparison to other mammals. The anterior digastric is enlarged and fused medially, covering the mylohyoid in Choloepus but exposing its anterior aspect in Bradypus . Posteriorly, the muscle fuses with the sternohyoid to form a wide sternomandibularis with a loose tendinous connection to the basihyal. The proposed model of hyoid function predicts that this arrangement aids an inverted sloth in opening the mouth fully against gravity while permitting the hyoid to move anteriorly during tongue extension independent of the sternomandibularis. In upright feeding, contraction of the posterior digastric-sternomandibularis complex allows a similar function. In all postures, increasing gape improves the ability of the hyoglossus and styloglossus muscles to act jointly in moving the tongue laterally. Hyoid retraction, in all postures, occurs with contraction of the modified sternothyroid, which arises from the mid-dorsum of the manubrium sternum and inserts on the ossified thyroid cartilage. The sloth palate also facilitates inverted feeding. The mucosa shows tubercles and grooves which channel food particles toward a central groove. Food is then returned to the toothrows by the tongue for further mastication or passed along a posteriorly deepening groove for bolus formation prior to swallowing.
Venous leg ulcers: an analysis of underlying venous disease

Patients with venous leg ulcers have a readily recognized clinical syndrome of shallow ulcers, oedema, leg pain, venous ankle blush, lipodermatosclerosis, varicose veins, hyperpigmentation, and atrophie blanche, and they are assumed to have venous abnormalities. We examined 43 patients with venous leg ulcers, and compared those with obvious venous abnormalities (defined as historical or clinical evidence of deep venous thrombosis or varicose veins) with those with presumed venous abnormalities (defined as lacking any such evidence), to see if they presented with different clinical features. We found that both groups had similar clinical features, with the exception that lipodermatosclerosis was present more frequently in those patients with obvious venous abnormalities (94 vs. 36%, P < 0.001). Most patients with presumed venous abnormalities had musculoskeletal conditions which might cause calf pump dysfunction (91%). Using air plethysmography, we were unable to confirm that all patients with presumed venous abnormalities did have intrinsic venous abnormalities. We propose that ulcers occurring in this clinical syndrome be designated as calf pump dysfunction ulcers (CPD ulcers), rather than venous ulcers.
Protein phosphorylation and the nuclear organization of pre-mRNA splicing

Controlled execution of transcription and pre-mRNA splicing is crucial for proper gene expression. The organization of these essential events within the cell nucleus is only beginning to be understood. Here, we describe a model for the cellular arrangement of transcription and pre-mRNA splicing based on recent biochemical and morphological data: transcription and pre-mRNA splicing are spatially and temporally coordinated, and protein phosphorylation regulates both the activity and the subnuclear localization of pre-mRNA splicing factors in nuclear subcompartments.
Expression of Bcl-2 Increases Intracellular Glutathione by Inhibiting Methionine-Dependent GSH Efflux☆☆☆

Overexpression of Bcl-2 and related anti-apoptotic gene products has been shown to increase the intracellular concentration of the antioxidant tripeptide glutathione in neuronal and hematopoietic cells. A similar examination of HeLa cells that stably overexpress Bcl-2 (Bcl-2/HeLa) demonstrated that the reduced form of glutathione (GSH) was increased by 60% compared to control cells (80 nmol GSH/mg protein compared to 50 nmol GSH/mg). Expression of gamma-glutamylcysteine synthetase, the rate limiting enzyme for glutathione synthesis was found to be independent of Bcl-2 overexpression, as determined by Northern blot analysis and immunoprecipitation of [35-S]-labeled enzyme. Bcl-2 overexpression did not alter the rate of GSH biosynthesis, measured under steady state conditions. Thus, the increase in GSH concentration was not the result of increased synthesis. Two activities have been described which govern efflux of reduced glutathione (GSH), RsGshT known as the sinusoidal transporter and RcGshT, known as the canalicular transporter. Both are low affinity, bidirectional, ATP and Na-independent. Consistent with expression of sinusoidal activity, DTT was found to stimulate GSH efflux while the amino acid methionine inhibited efflux in both HeLa and Bcl-2/HeLa cells. However, methionine-dependent inhibition of efflux was found to be significantly increased by expression of Bcl-2. To test the prediction that the increase in GSH observed in Bcl-2/HeLa cells was mediated by methionine; Bcl-2/HeLa cells were cultured for 24 hrs in methionine-free growth medium. Under these conditions, the GSH concentration of the Bcl-2/HeLa cells dropped to the level observed in HeLa cells (50 nmol GSH/mg protein). These studies suggest that overexpression of Bcl-2 increases GSH levels by altering methionine-dependent GSH efflux, an activity associated in HeLa cells with expression of the RsGshT transporter.
The relationship between smoking history and current functioning in disabled community-living older adults

Purpose: This study was conducted to determine characteristics associated with continued cigarette use in frail older adults and to examine how smoking history relates to current psychiatric, cognitive, and occupational functioning.Methods: Archival records were gathered for 1,064 patients (69% women) who entered On Lok SeniorHealth Services between January 1996 and December 2000. Participants were interviewed on program entry and assessed for smoking history, depressive symptoms, affective disorders, cognitive functioning, alcohol use, and physical functioning (activities of daily living [ADLs] and instrumental ADLs). Cross-sectional analyses were conducted to examine functioning at enrollment relative to smoking history.Results: Smoking history was related to age at program entry, with current smokers entering On Lok at an earlier age than former or never smokers. Current smokers were more likely to be male, to be of Caucasian or African American descent, to consume alcohol on a regular basis, and to be more independent on ADLs. Specifically, they were more independent on tasks related to their capacity to procure cigarettes or continue smoking, including shopping, using transportation, managing money, dressing themselves, and walking. Smoking history was related to depression, with symptoms lower for current and former smokers.Conclusions: Current smokers present for services at an earlier age and have higher levels of independence on ADLs instrumental to nicotine use. Data indicate characteristics associated with continued smoking and provide a foundation for targeting older individuals for cessation efforts.
Abstract 5657: Ursolic acid prevents activation of oncogenic factors in UV-treated HaCaT cells

The aim of this study was to determine the anti-cancer potential of the phytonutrient ursolic acid (UA) in a UV-treated HaCaT human keratinocyte cell line. Earlier studies have shown UA strongly inhibits DMBA/TPA-mediated carcinogenesis in SENCAR mice, but effects of UA on UV-induced skin cancer are unknown. Our hypothesis was that treating cells with UA, found in plant sources including rosemary and apple, may inhibit UV-induced cell death, ROS production, and transcription and activation of oncogenes and oncoproteins. These in vitro studies would suggest UA may inhibit UV-mediated skin carcinogenesis. HaCaT cells were seeded at 2,000 cells/well for MTT and DHR assays, and at 1.6 × 104 cells/cm2 for RT-PCR and Western blotting. 24 hours after seeding, cells were treated with concentrations of UA up to 25 μM. Cells were UV-treated with various doses using a transilluminator emitting 36% of its energy in the UVA range and 64% in the UVB range with a peak of 312 nm. For cell death assays, cells were incubated for 4 hours in media with MTT, UV treated, then dissolved in DMSO after various timepoints prior to measuring the absorbance at 570 nm. For quantification of intracellular H2O2, cells were incubated in media containing 5 µM DHR 123 for 1 hour prior to UV-treatment, followed by reading fluorescence at 530 nm with an excitation of 485 nm. RT-PCR was performed for bcl-2 and c-jun using SYBR green probe. Western blotting for phospho-p38 MAPK was done with whole cell lysates, isolated using RIPA buffer. Phospho-p65 and phospho-c-jun were quantified by blotting nuclear and cytosolic fractions, which were isolated using a hypotonic/hypertonic nuclear extraction procedure. We find that treating cells for 24 hours before UV and 12 hours post-UV with non-toxic doses of UA does not protect cells from UV-death. Also, pretreating this cell line with these doses of UA does not inhibit a UV-induced rise in intracellular H2O2 within an hour post-UV. However, RT-PCR results show UA treatment exacerbates a UV-induced rise in bcl-2 RNA levels and inhibits a UV-mediated increase in c-jun RNA 1 hour post-UV. Also, Western blotting reveals that 25 μM UA inhibits a 500 mJ/cm2-induced increase in phospho-p38 MAPK by 85%, and that treatment with 10 μM UA reduces 100 mJ/cm2-initiated nuclear accumulation of oncogenic phospho-c-jun by 47.6%, 1 hour after UV. Finally, treatment with 10 and 25 μM UA dose-dependently contributes to a decrease in nuclear phospho-p65 seen 1 hour post-UV treatment. These in vitro results show UA may prevent UV-mediated skin cancer by modulating the activities of the oncogenic transcription factors AP-1 and NFκB. Supported by NIH grants CA 102747 and P30 CA 54174-16S1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5657.
Medical student perspective: Working toward specific and actionable clinical clerkship feedback

Background: Feedback on the wards is an important component of medical student education. Medical schools have incorporated formalized feedback mechanisms such as clinical encounter cards and standardized patient encounters into clinical curricula. However, the system could be further improved as medical students frequently feel uncomfortable requesting feedback, and are often dissatisfied with the quality of the feedback they receive.Aims: This article explores the shortcomings of the existing medical student feedback system and examines the relevant literature in an effort to shed light on areas in which the system can be enhanced. The discussion focuses on resident-provided feedback but is broadly applicable to delivering feedback in general.Methods: A review of the organizational psychology and business administration literature on fostering effective feedback was performed. These insights were then applied to the setting of medical education.Results: Providing effective feedback requires training and...
The debonding and fracture of Si particles during the fatigue of a cast Al-Si alloy

Constant-amplitude high-cycle fatigue tests (σmax=133 MPa, σmax/σy=0.55, and R=0.1) were conducted on cylindrical samples machined from a cast A356-T6 aluminum plate: The fracture surface of the sample with the smallest fatigue-crack nucleating defect was examined using a scanning electron microscope (SEM). For low crack-tip driving forces (fatigue-crack growth rates of da/dN 1 × 10−6 m/cycle), silicon particles ahead of the crack tip were fractured, and the crack subsequently propagated through the weakest distribution of prefractured particles in the Al-Si eutectic. Only small rounded silicon particles were observed to debond while the fatigue crack grew at high rates. Using fracture-surface markings and fracture mechanics, a macroscopic measure of the maximum critical driving force between particle debonding vs fracture during fatigue-crack growth was calculated to be approximately K max tr ≈6.0 MPa √m for the present cast A356 alloy.
On the Characteristics and Mechanism of Rolling Instability and Chatter

A nonlinear model describing the dynamical interaction between work rolls and metal sheets and the initiation of fifth octave rolling chatter is presented. The model, which comprises a work roll sub-model and a metal sheet roll-bite sub-model, enables the instability of strip rolling to be qualitatively and quantitatively studied as a function of rollstack stiffness, rolling speed, inter-stand tension, roll-bite entry and exit thickness, and the sheet force resulted from the interactive action of the work roll with the plastic deformation of the rolled strip. It is concluded that, even though the governing dynamics is highly nonlinear, rolling chatter instability is none other than mode excitation or beating, and thus linear. Analyzed results correspond well with what have been observed in physical rolling mills. Specifically, the natural frequency predicted for a 4-H rolling stand fits the fifth octave chatter at 550∼650 Hz and there is a critical rolling speed (2.54 m/sec for the material and sheet configurations considered in the paper) beyond which rolling instability will occur This research establishes the fundamental knowledge base required for the understanding of chatter characteristics and mechanism, and thus provides the essential bases for effective control of rolling instability and chatter-free roll mill design.
Abstract B70: Conexic: A Bayesian framework to detect drivers and their function uncovers an endosomal signature in melanoma

Genomics is revolutionizing our understanding of cancer biology. Tumor samples assayed for comprehensive chromosomal and gene expression data are accumulating at a staggering rate. A major challenge involves the development of analysis methods to uncover biological insights from these data, including the identification of the key mutations that drive cancer and how these events alter cellular regulation. We have developed Conexic, a novel computational framework to integrate chromosomal copy number and gene expression data to detect genetic alterations in tumors that drive proliferation, and to model how these alterations perturb normal cell growth/survival. The underlying assumption to our approach is that significantly recurring copy number change, coinciding with its ability to predict the expression patterns varying across tumors, strengthens the evidence of a gene9s causative role in cancer. This method not only pinpoints specific regulators within an a large region of copy number variation, but can shed light on the way in which gene regulation is altered We applyed our Conexic framework to a melanoma dataset (Lin et al, Cancer Research, 2007) comprising 65 paired measurements of gene expression and copy number, with interesting results. Our analysis correctly identified many known ‘driver’ events, while also connecting these to many of their known targets (e.g. MITF). Our global integrative analysis reveals insight into how the drivers alter transcriptional programs. An interesting recurring characteristic is that there are a number of different ways by which drivers can be altered; e.g., the expression of a driver may be altered through copy number variation or other mechanisms, but its influence downstream remains the same. In addition to confirming the role of known drivers in melanoma, our analysis suggests a number of novel drivers. Most strikingly, these point to a major role in regulation of protein trafficking and endosome biology in this malignancy. These results have linked endosomal processing and sorting to adhesion and survival. Preliminary experimental validation supports three novel drivers including TBC1D16, RAB7A and RAB27A. Together, these results affirm the potential of Conexic to elaborate novel driver modules with biological and possibly therapeutic importance in melanoma and other cancers. Citation Information: Cancer Res 2009;69(23 Suppl):B70.
Separation of Human and Animal Cells by Steric Field-Flow Fractionation

In this work, the feasibility of separating and characterizing cell populations by steric field-flow fractionation (steric FFF) is demonstrated by application to fixed human and avian red cells, fresh blood from several species, and viable HeLa cells. The basis for this work is established by means of a discussion of the role of steric FFF in the broad family of field-flow fractionation techniques. The behavior of steric FFF is then characterized by application to standard polystyrene latex beads and to fixed red blood cells. Studies of these standards and of the other cells noted under various conditions of field strength and flow velocity are used to improve the separation conditions and approach optimization. It is shown that the fixed human and avian red cells can be separated in a time of less than 15 min. In addition, it is shown that HeLa cells maintain their viability after passage through the separation channel.