cssi/SciSciGPT-SciSciNet huggingface dataset:
Carbonic anhydrase heterozygosity and FST distributions in Kenyan baboon troops.

An analysis of the distribution of carbonic anhydrase alleles in troops of olive baboons, Papio cynocephalus, is reported. In an earlier study (Olivier, T. J., J. Buettner-Janusch and V. Buettner-Janusch, 1974, Am. J. Phys. Anthrop., 41: 175–190) the authors found a significant excess of heterozygotes with a large amount of intertroop differentiation at the CA II locus. If balancing selection is acting on the CA II locus and maintaining an excess of heterozygotes, then the degree of local differentiation observed at this locus is unexpected. In this study the analyses of the CA I and CA II data are extended and some idiosyncratic features of baboon population structure are considered. Non-idealized forms of behavior, such as adult male migration and other age-specific and sex-specific behaviors, may affect observed patterns of gene frequency distributions. The analysis reveals that the excess of heterozygotes at the CA II locus is localized in the females only and that the males are highly differentiated among the troops. These findings suggest that a female-limited heterozygous advantage exists at the CA II locus in this baboon population. A computer simulation model, RAMBLE, further suggests that recurrent male migration between troops may explain the intertroop microdifferentiation found in primate populations.
Osler at Old Blockley

AJR:195, December 2010 designation. While Osler served at the University of Pennsylvania, he would regularly come to Old Blockley to perform autopsies and use the results of these examinations as a clinical–pathologic aid to the patient consultations that he would carry out with students. Osler at Old Blockley is one of the six paintings in the “Pioneers of American Medicine” series that were commissioned by Wyeth Laboratories and completed between 1939 and 1945 by the renowned American illustrator Dean Cornwell [2, 3].
Vitamin D - Beyond Bones: Its Relationship to Obesity, Metabolic Syndrome, and Diabetes

While vitamin D has long been known as an essential nutrient for the prevention of bone disorders, vitamin D deficiency has recently been linked to a number of chronic disease states. This review analyzes the epidemiological, clinical, and mechanistic data concerning the relationship between vitamin D status and obesity, metabolic syndrome (MetS), and diabetes. The increased understanding of the role of vitamin D has promoted researchers to study vitamin D as a potential target for the prevention and treatment of multiple chronic diseases.
Nanocrystals: Almost always bright.

Colloidal nanocrystals randomly turn their photoluminescence off and on under continuous light illumination. Growing thick shells around the crystals can reduce the blinking effect dramatically, with great potential advantage for applications.
Periconceptional consumption of vitamins containing folic acid and risk for multiple congenital anomalies.

Although it has been well established that periconceptional use of multivitamins containing folic acid (FA) reduces the risk for neural tube defects, two recent U.S. studies have shown an increased risk for multiple congenital anomalies (MCAs) associated with periconceptional use of vitamins containing FA. This study assessed the association between the periconceptional use of vitamins containing FA and MCAs in a third U.S. population. Mothers of infants with MCAs and a random sample of live births (control infants) born in Iowa during 1993–1995 were eligible to participate in the Birth Defects Risk Factor Surveillance case-control study. During a telephone interview, participants reported on exposure to FA through vitamins, cereal, and food supplements. There was no association between taking vitamins containing FA during the periconceptional period (3 months before conception through the first trimester) and MCAs in the crude estimates or after adjusting for maternal race or ethnicity, education, gravidity, smoking, or alcohol use in the first trimester, or body mass index prior to pregnancy [adjusted odds ratio (aOR) = 1.12, 95% confidence interval (CI) 0.75–1.69]. There was also no association between vitamin exposure beginning in the first trimester and MCAs outcome (aOR = 1.05, 95% CI 0.59–1.87). In contrast to the two recently published reports, there was no association between periconceptional vitamin exposure and MCAs in the Iowa population. Published 2007 Wiley-Liss, Inc.
Peritubular transport of urate in rat kidneys.

Measurement in the rat of renal artery-to-vein transit times permitted evaluation of movement of14C-labelled urate and of other solutes out of the peritubular inulin spaces in the renal cortex. No interaction between urate and PAH could be demonstrated at this level. Provided the peritubular disappearance may be equated to cellular uptake a mean unidirectional urate flux across peritubular membranes equal to about 1/3 of total renal load may be calculated. This value greatly exceeds the net secretory flux of urate. Such a fact can be explained by the likelihood of significant post-proximal reabsorption of secreted urate, and/or by the conclusion that peritubular urate permeability exceeds that of the luminal side. Assignment of the limiting step in urate secretion to the luminal cell membranes, in contrast to a determining role played by peritubular membranes in PAH transport, can account for the lack of interaction between PAH and urate at the peritubular membrane in rats.
Peripheral proliferative retinopathies: An update on angiogenesis, etiologies and management

Abstract Many clinical entities may be associated with the development of peripheral retinal neovascularization. In this paper, we review the mechanisms of normal and abnormal angiogenesis in the retina. Specific disease entities associated with peripheral proliferative retinopathies are discussed. These include vascular disease with ischemia, inflammatory diseases with possible ischemia and a variety of miscellaneous causes, including hereditary diseases and tumors. Basic principles for the clinical evaluation of patients with retinal neovascularization are described. Finally, the treatments for retinal neovascularization, including cryopexy and local and panretinal photocoagulation are reviewed, and techniques and possible mechanisms of the beneficial results of treatment are described
Aedes aegypti (Diptera: Culicidae) movement influenced by availability of oviposition sites

Marked Aedes aegypti (L.) (5-6 d old) were released inside 2 groups of 5 houses (100 females per house) in a residential community in Florida, PR, to compare behavior of gravid females at sites where oviposition containers were absent to sites where containers were abundant (i.e., 2 tires and 10 ovipots were added to each yard). Two sequential releases were made so that both groups of houses were evaluated with oviposition containers removed and added. Mosquitoes resting inside the 10 release houses plus 20 additional neighboring houses were collected with backpack aspirators for 4 consecutive days, beginning 2 d after release. Because 172 of the 185 recaptured females (93%) were collected in the same houses in which they had been released, dispersal patterns were not directly comparable. However, the recapture rate in houses with containers added (13%) was significantly higher (P < 0.0001) than in houses with containers removed (6%). No difference was observed in the mean number of potential oviposition containers among the nonrelease houses at the 2 sites (3.9 versus 3.8 aquatic containers per house in the prerelease survey). Our results are consistent with the hypothesis that availability of oviposition sites is inversely correlated with the potential for female Ae. aegypti to disperse. These results have important implications because campaigns to reduce Ae. aegypti larval sites during dengue epidemics could have the undesirable effect of inducing the dispersal of infected adult female mosquitoes.
New compounds: N-substituted tetrahydroisoquinolines

The Mannich, sodium borohydride reduction, and esterification reactions were utilized for the preparation of several N-substituted tetrahydroisoquinolines. Aminolysis of ethyl cyanoacetate with tetrahydroisoquinoline provided the corresponding cyanoacetamide.
“Auer Colitis” in Rabbits Induced by Intrarectal Antigen.

ConclusionThe intrarectal instillation of specific antigen (crystalline egg albumin) in sensitized rabbits may induce a “colitis” in the distal colon, previously exposed to a mild formalin solution, to increase capillary permeability locally. The “Auer colitis” develops presumably on the basis of an antigen-antibody reaction.
GLOBAL THREE-NEUTRINO VACUUM OSCILLATION FITS TO THE SOLAR AND ATMOSPHERIC ANOMALIES

We determine the three-neutrino mixing and mass parameters that are allowed by the solar and atmospheric neutrino data when vacuum oscillations are responsible for both phenomena. The global fit does not appreciably change the allowed regions for the parameters obtained from effective two-neutrino fits. We discuss how measurements of the solar electron energy spectrum below 6.5 GeV in Super-Kamiokande and seasonal variations in the Super-Kamiokande, {sup 71}Ga, and BOREXINO experiments can distinguish the different solar vacuum solutions. {copyright} {ital 1999} {ital The American Physical Society}
Transient ultrasonic waves in a viscoelastic plate: Theory

The nearfield response of a thick viscoelastic plate at epicenter, off‐epicenter, and on the same side of the plate to a point step load acting normal to the surface is discussed. The integral expressions resulting from Fourier and Hankel transforms of the governing equations are evaluated by two procedures. An asymptotic evaluation of the frequency‐domain response is presented for high frequencies corresponding to ray arrivals. A numerical double inverse transform procedure is developed for obtaining exact time‐domain waveforms.
In vitro proliferation of saffron (Crocus sativus L.) stigma

Excised young intact stigmas plus ovaries of Crocus sativus L. were cultured on Linsmaier-Skoog media supplemented with either a cytokinin or an auxin alone or in combinations. Benzyladenine and kinetin at concentrations of 0.1, 1, and 5 mgl-1 supported growth, and crocin was biosynthesized in the stigmas in vitro. Auxins had little effect. Young excised single stigmas or half ovaries were also cultured so as to form stigma-like structures in order to explore a possible new approach to industrial production of the spice, “saffron”. On Linsmaier-Skoog and Nitsch media supplemented with kinetin at concentration of 1 or 5 mgl-1 and alpha-naphthalene acetic acid or indole-butyric acid at concentration of 0.1 or 10 mgl-1 in combinations, stigma-like structures appeared directly and indirectly (through meristematic tissue), grew and matured. The maximum number of structures were 75 per half ovary. Three kinds of yellow pigments including crocin were tentatively identified by TLC in the stigma-like structures as was the case for the in vivo grown natural stigma, although the contents were lower.
Consumers' use of alternative information sources in inference generation: A replication study

Abstract This research replicates the Ford and Smith study (1987, JCR, 14, 363–371) which reported that the same-brand information source had greater influence than the other-brand information source for inference generation when subjects were instructed to make an inference about the missing attribute. The results of the replication did not support their findings. Our study, however, found that in most cases, both the other brand and the same brand are equally influential sources of information for the subject to draw an inference about the missing attribute. An interaction effect of interattribute correlations and information source on inference generation was also identified.
Applications of SQL for informetric frequency distribution processing

Many informetric data types lend themselves to ready adaptation to relational DBMS environments for storage and processing. SQL, the standard language used for constructing and querying relational databases, provides useful tools for processing informetric data. The author demonstrates the applications and some limitations of SQL for efficient organization and tabulation of raw informetric data.
Separated-Flow Transition: Part 2 — Experimental Results

The present paper focuses on presenting the results of the experimental investigation of the transition process in separated boundary layers on a flat plate at zero incidence, with imposed adverse pressure gradients. The combined effects of Reynolds number and adverse pressure gradient strength on the transition mechanism, bubble geometry, and bubble bursting process are studied. The flow structures and the unsteady aspects associated with separated-flow transition are analyzed for three representative experimental cases. Surface pressure results and detailed boundary layer measurements using hot-wire anemometry are presented as mean and rms velocity profiles, and Reynolds shear stress distribution. Turbulent intermittency and spectral analysis results are briefly introduced.Copyright © 1998 by ASME
Hot-crush technique for separation of cast- and wrought-aluminum alloy scrap

Abstract A novel technique for the separation of cast and wrought aluminum alloy scrap is described. This technique, developed by the Bureau of Mines, exploits differences in hot ductility between cast and wrought aluminum. Tests are in progress to demonstrate its use for upgrading mixed aluminum scrap into recyclable grades of wrought and cast alloys. This paper describes (1) process development studies using conventional heating, fragmentizing and screening equipment and (2) process improvements to enhance commercial development.
Effects of ultraviolet irradiation on production of aflatoxins by Aspergillus flavus link ex. fries

A toxigenic Aspergillus flavus isolate was selected to study the effects of u.v. irradiation on aflatoxin production. The loss of conidial pigmentation and aflatoxin production resulting from an earlier u.v. irradiation treatment was reversed by prolonging the post-u.v. incubation period. Reduction in aflatoxin from cultures was 10·6 per cent in response to 13·39 × 103 erg/mm2 of near-u.v. and 42·9 per cent in response to 21·87 × 103 erg/mm2 of far-u.v. treatment. When aflatoxin extracts were irradiated directly with u.v., the concentration of aflatoxin decreased proportionally with increase of far-u.v. dosage, but increased proportionally with increase of near-u.v. dosage. However, after u.v. irradiation, neither degradation nor changes in the characteristics of aflatoxin could be detected by thin-layer chromatography or u.v. spectrophotometry.
Cell-Phone Popularity, Addiction, and Funding for Biological Effect Research [Health Effects]

The popularity of cell phones remains very high. Worldwide, there are more people who own and use cell phones than any other electronic gadgets, regardless whether it is in a rich or poor, developed, or developing country. They provide instant connectivity, whenever one wants to talk or conduct business transactions regardless of where.
Characterization of the phenolic fraction obtained from fossil-fuel materials by microcolumn liquid chromatography and its ancillary techniques

Abstract The phenolic fraction of two coal-derived liquids has been isolated prior to high-resolution liquid chromatography and spectral characterization. Over 70 high-molecular-weight compounds were separated, in each case, with a slurry-packed capillary column. Off-line mass spectrometry and on-line miniaturized fluorescence spectroscopy were used for peak characterization. Two- to five-ring structures, with a high degree of alkylation or heteroatomic features, are suggested.
MSH2/MSH6 complex promotes error-free repair of AID-induced dU:G mispairs as well as error-prone hypermutation of A:T sites.

Mismatch repair of AID-generated dU:G mispairs is critical for class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The generation of a previously unavailable Msh2−/−Msh6−/− mouse has for the first time allowed us to examine the impact of the complete loss of MutSα on lymphomagenesis, CSR and SHM. The onset of T cell lymphomas and the survival of Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice are indistinguishable from Msh2−/− mice, suggesting that MSH2 plays the critical role in protecting T cells from malignant transformation, presumably because it is essential for the formation of stable MutSα heterodimers that maintain genomic stability. The similar defects on switching in Msh2−/−, Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice confirm that MutSα but not MutSβ plays an important role in CSR. Analysis of SHM in Msh2−/−Msh6−/− mice not only confirmed the error-prone role of MutSα in the generation of strand biased mutations at A:T bases, but also revealed an error-free role of MutSα when repairing some of the dU:G mispairs generated by AID on both DNA strands. We propose a model for the role of MutSα at the immunoglobulin locus where the local balance of error-free and error-prone repair has an impact in the spectrum of mutations introduced during Phase 2 of SHM.
Acute supraglottitis--true pediatric emergency.

The most important factors in achieving a successful outcome for a child with acute supraglottitis are accurate and early diagnosis, careful monitoring, and subsequent management by an experienced, well equipped team in a proper facility. When an artificial airway becomes necessary, the technique used should not result in adverse sequelae.
Graphical approach to the spin-orbit interaction

We derive a new form for the matrix element of the two-particle mutual spin-orbit interaction in the Breit-Pauli approximation. The complexity of standard tensor-operator expansion techniques is obviated by suitably decomposing the mutual spin-orbit interaction into products of spin and orbital angular-momentum operators, whose matrix elements in the lm/sub l/sm/sub s/ scheme are obtained in a straightforward manner. Graphical representations are given for both the one- and two-particle spin-orbit interactions, thereby permitting the analytical evaluation by graphical techniques of the spin-orbit interaction between arbitrary configurations in any coupling scheme. The graphical procedure for evaluating these matrix elements is demonstrated for LS-coupled configurations having two nonequivalent electrons outside closed shells. Various properties of the two-particle mutual spin-orbit operator are easily illustrated using its graphical representation.
Characterization of Impact Damage in Ultra-High Performance Concrete Using Spatially Correlated Nanoindentation/SEM/EDX

Little work has been done to study the fundamental material behaviors and failure mechanisms of cement-based materials including ordinary Portland cement concrete and ultra-high performance concretes (UHPCs) under high strain impact and penetration loads at lower length scales. These high strain rate loadings have many possible effects on UHPCs at the microscale and nanoscale, including alterations in the hydration state and bonding present in phases such as calcium silicate hydrate, in addition to fracture and debonding. In this work, the possible chemical and physical changes in UHPCs subjected to high strain rate impact and penetration loads were investigated using a novel technique wherein nanoindentation measurements were spatially correlated with images using scanning electron microscopy and chemical composition using energy dispersive x-ray microanalysis. Results indicate that impact degrades both the elastic modulus and indentation hardness of UHPCs, and in particular hydrated phases, with damage likely occurring due to microfracturing and debonding.
Regulation of Insulin Gene Transcription by a Ca2+-Responsive Pathway Involving Calcineurin and Nuclear Factor of Activated T Cells

Immunosuppressants such as FK506 (tacrolimus), the primary cellular target of which is calcineurin, decrease β-cell insulin content and preproinsulin mRNA expression. This study offers an explanation for this effect by establishing that calcineurin is an important regulator of insulin gene expression through the activation of a transcription factor, nuclear factor of activated T cells. Three putative nuclear factor of activated T cells binding sites were located within the proximal region of the rat insulin I gene promoter (−410 to +1 bp). Expression of nuclear factor of activated T cells in both clonal (INS-1) and primary (islet) β-cells was confirmed by immunoblot and immunocytochemical analyses. Moreover, nuclear factor of activated T cells DNA-binding activity was detected in INS-1 and islet nuclear extracts by EMSAs. Activation of the insulin gene promoter by glucose or elevated extracellular K+ (to depolarize the β-cell) was totally prevented by FK506 (5–10 μm). K+-induced promoter activation was su...
Modeling steep slope devices: from circuits to architectures

Steep Slope devices, with Heterojunction Tunnel FETs (TFETs) in particular, have been proposed as a viable solution to overcome the subthreshold slope limitation in existing CMOS technology and achieve ultra-low voltage operation with acceptable performance. However, state-of-the-art FinFET technologies continue to demonstrate superior performance than steep slope devices in application domains demanding peak single threaded performance. In this context, we examine different computing paradigms where TFET technologies can be used, not just as a `drop in' replacement, but as an additional parameter to augment the architectural design space. This greatly widens the scope of optimizations for performance and power. We investigate the tradeoffs between device and architectures in general purpose processors when performance, power and temperature are individually constrained. We also synthesize examples of domain-specific accelerators used in computer vision using in-house TFET standard cell libraries to demonstrate the energy benefits of designing TFET-based accelerators. We demonstrate that synthesizing these accelerators using TFETs reduces energy by over 6X in comparison to an equivalent iso-voltage CMOS-based design and by over 30% in comparison to an iso-performance CMOS design.
Optimal Designs For Two Non-Interactive Treatment

Consider two treatments and a combination of them. Given n available experimental units, the problem is to determine the number of units n, to be assigned to the first treatment, n 2 to the second, and n, to the combination, n = Σ i , n i , n i ≥ 0, i = 1, 2, 3, subject to suitable optimality criteria. This study was motivated by an example of a weighing design with n = 18. n 1 = 2. n 2 = 9, n s = 7 given by Box and Tiao [2, Section 2.7.3]. The allocation seemed far from optimal leading to the present investigation. Four models are developed for two non-interactive treatments and the combination of them. They may be described as 1. A weighing model, 2. A sum of independent random variables model, 3. A mixtures model, and 4. A factorial model. Three optimality criteria are considered: 1. D-optimality, 2. A-optimality and 3. minimization of the variance of the difference of estimators of the two treatment means. It is shown for all criteria for Models 2, 3, 4 and for Criterion 3 for Model I that n s = 0, n ...
Decoding of movement direction using optical imaging of motor cortex

Article accompanying a poster presentation for the 2013 Computational Neuroscience Annual Meeting. This article discusses the decoding of movement direction using optical imaging of motor cortex.
Professional and Personal Development in Contemporary Gerontology Doctoral Education.

This article reports on the Gerontology Doctoral Student Assessment Model (GDSAM), a comprehensive web-based system premised on developing an evaluation mechanism attuned to the special requirements of advanced graduate education at the doctoral level. The system focuses on longitudinal tracking of selected dimensions of intellectual, professional, and personal progress. This involves interlocking elements of online personal dossier development, student self-rating assessment, faculty assessment of student progress, and a means of communicating interactive and iterative feedback among students and faculty. Preliminary findings from initial data collection using the assessment system indicate that students who have completed and passed their qualifying examinations are more confident in their ability to articulate diverse ideas in professional settings, work in direct contact with research participants, present research findings to scientific audiences, and adjust to the rigors of doctoral education. Addit...
The range of validity of the Rayleigh limit for computing Mie scattering and extinction efficiencies

Abstract For the small particle limit for scattering by either absorbing or dielectric spheres, values of the size parameter are determined below which various approximate expressions for the scattering and extinction efficiencies are accurate to within 1%. Simple, analytical criteria for ensuring 1% accuracy are given in terms of the size parameter and the complex refractive index. A much broader range of refractive indices is considered than has been studied previously.
An Isocratic HPLC-ECD Assay of Urinary Normetanephrine and Metanephrine

Abstract This report describes a procedure to quantify simultaneously urinary normetanephrine (NMTN) and metanephrine (MTN) using an isocratic HPLC-ECD methodology. An aliquot of urine (5ml) was adjusted to pH of 1.0, spiked with a known concentration of internal standard, (3-methoxy-4-hydroxy benzylamine, MHBA) and the two metabolites were hydrolyzed in a boiling water bath. The metabolites were adsorbed on a Biorex-70 column and eluted with ammonium hydroxide. Final extraction was carried out in a mixture of ethyl acetate and acetone (2:1, v/v). After drying the extract under nitrogen, it was dissolved in mobile phase, filtered through 0.2μ filters, and injected into a 4 μ Nova-Pak, C18 column of the HPLC system. Mobil phase for elution contained citric acid, sodium acetate, EDTA-Na2, sod. octyl sulfate, dibutylamine, methanol 2% and isopropanol 2%. Peaks were detected by the electrochemical detector at a potential of + 0.55V and characterized using the retention times obtained from HPLC profiles of the...
The Society for Vascular Surgery Vascular Quality Initiative

The Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) is designed to improve the quality, safety, effectiveness, and cost of vascular health care. It uses the structure of a Patient Safety Organization to permit collection of patient-identified information but protect benchmarked comparisons from legal discovery. The SVS VQI is uniquely organized as a distributed network of regional quality groups to facilitate local translation of registry data into practice change while maintaining the power of a national registry. Detailed data specific to each commonly performed open and endovascular procedure are collected, both in-hospital and at ≥1 year of follow-up. Quality measures are reported to physicians and hospitals, which allow anonymous risk-adjusted benchmarking within regions or nationally. All specialties that perform vascular procedures are included, and international participation is encouraged. This review describes the current status of the SVS VQI.
Lessons learned from conducting research with participants receiving dialysis for end-stage renal disease.

The precariousness of the situation was not apparent until we received the call from the dietitian with whom we were working to collect data. One day before we were to call a patient to schedule an...
Structure and biosynthesis of the BT peptide antibiotic from Brevibacillus texasporus.

We isolated a novel gram-positive bacterium, Brevibacillus texasporus, that produces an antibiotic, BT. BT is a group of related peptides that are produced by B. texasporus cells in response to nutrient limitation. We report here purification and determination of the structure of the most abundant BT isomer, BT1583. Amino acid composition and tandem mass spectrometry experiments yielded a partial BT1583 structure. The presence of ornithine and d-form residues in the partial BT1583 structure indicated that the peptide is synthesized by a nonribosomal peptide synthetase (NRPS). The BT NRPS operon was rapidly and accurately identified by using a novel in silico NRPS operon hunting strategy that involved direct shotgun genomic sequencing rather than the unreliable cosmid library hybridization scheme. Sequence analysis of the BT NRPS operon indicated that it encodes a colinear modular NRPS with a strict correlation between the NRPS modules and the amino acid residues in the peptide. The colinear nature of the BT NRPS enabled us to utilize the genomic information to refine the BT1583 peptide sequence to Me2-4-methyl-4-[(E)-2-butenyl]-4,N-methyl-threonine-L-dO-I-V-V-dK-V-dL-K-dY-L-V-CH2OH. In addition, we report the discovery of novel NRPS codons (sets of the substrate specificity-conferring residues in NRPS modules) for valine, lysine, ornithine, and tyrosine.
Empirical likelihood ratio test for a mean change point model with a linear trend followed by an abrupt change

In this paper, a change point model with the mean being constant up to some unknown point, and increasing linearly to another unknown point, then dropping back to the original level is studied. A nonparametric method based on the empirical likelihood test is proposed to detect and estimate the locations of change points. Under some mild conditions, the asymptotic null distribution of an empirical likelihood ratio test statistic is shown to have the extreme distribution. The consistency of the test is also proved. Simulations of the powers of the test indicate that it performs well under different assumptions of the data distribution. The test is applied to the aircraft arrival time data set and the Stanford heart transplant data set.
Multiplexed Quantitative Analysis of CD3, CD8, and CD20 Predicts Response to Neoadjuvant Chemotherapy in Breast Cancer

Purpose: Although tumor infiltrating lymphocytes have been associated with response to neoadjuvant therapy, measurement is typically subjective, semi-quantitative and does not differentiate between subpopulations. Here we describe a quantitative objective method for analyzing lymphocyte subpopulations and assess their predictive value. Methods: We develop a quantitative immunofluorescence (QIF) assay to measure stromal expression of CD3, CD8, and CD20 on one slide. We validate this assay by comparison to flow cytometry on tonsil and assess predictive value in breast cancer on a neoadjuvant cohort (n = 95). Then each marker is tested for prediction of pathologic complete response (pCR) compared to pathologist estimation of percentage lymphocyte infiltrate. Results: Lymphocyte percentage and CD3, CD8, and CD20 proportions were similar between flow cytometry and QIF on tonsil. Pathologist TIL count predicted pCR (p = 0.043, OR: 4.77[1.05-21.6]) despite fair interobserver reproducibility (kappa= 0.393). Stromal AQUA scores for CD3 (p = 0.023, OR: 2.51[1.13-5.57]), CD8 (p = 0.029, OR: 2.00[1.08-3.72]), and CD20 (p = 0.005, OR: 1.80[1.19-2.72]) predicted pCR in univariate analysis. CD20 AQUA score predicted pCR (p = 0.019, OR: 5.37[1.32-21.8]) independently of age, size, nuclear grade, nodal status, ER, PR, HER2, and Ki-67, whereas CD3, CD8, and pathologist estimation did not. Conclusions: We have developed and validated an objective, quantitative assay measuring tumor infiltrating lymphocytes in breast cancer. While this work provides analytic validity, future larger studies will be required to prove clinical utility.
Functional Microdomains in G-protein-coupled Receptors THE CONSERVED ARGININE-CAGE MOTIF IN THE GONADOTROPIN-RELEASING HORMONE RECEPTOR

Abstract An Arg present in the third transmembrane domain of all rhodopsin-like G-protein-coupled receptors is required for efficient signal transduction. Mutation of this Arg in the gonadotropin-releasing hormone receptor to Gln, His, or Lys abolished or severely impaired agonist-stimulated inositol phosphate generation, consistent with Arg having a role in receptor activation. To investigate the contribution of the surrounding structural domain in the actions of the conserved Arg, an integrated microdomain modeling and mutagenesis approach has been utilized. Two conserved residues that constrain the Arg side chain to a limited number of conformations have been identified. In the inactive wild-type receptor, the Arg side chain is proposed to form an ionic interaction with Asp3.49(138). Experimental results for the Asp3.49(138) → Asn mutant receptor show a modestly enhanced receptor efficiency, consistent with the hypothesis that weakening the Asp3.49(138)-Arg3.50(139)interaction by protonation of the Asp or by the mutation to Asn favors activation. With activation, the Asp3.49(138)-Arg3.50(139) ionic bond would break, and the unrestrained Arg would be prevented from orienting itself toward the water phase by a steric clash with Ile3.54(143). The mutation Ile3.54(143) → Ala, which eliminates this clash in simulations, causes a marked reduction in measured receptor signaling efficiency, implying that solvation of Arg3.50(139) prevents it from functioning in the activation of the receptor. These data are consistent with residues Asp3.49(138) and Ile3.54(143) forming a structural motif, which helps position Arg in its appropriate inactive and active receptor conformations.
Dynamics of early and late phases of the phrenic neurogram during maturation

We investigate the dynamics of early and late phases of the phrenic neurogram during maturation. We have used using the matching pursuit (MP) method to examine the effects of maturation on breathing patterns in both time and frequency domains. The phrenic neurogram in piglets was recorded from 9 piglets during eupnea (normal breathing) at three postnatal age groups; 3-6 days (n=3), 15-21 days (n=3) and the 25-31 days (n=3). During the first 6 days of postnatal age, the long horizontal structured components representing the continuous respiratory activity, and circular structured components, representing the burst type breathing activities, were at both the early and late phases of the phrenic neurogram. The early phase of phrenic activities is largely composed of continuous neural activity. However as maturation proceeds, but both the continuous and burst type neural activities were present during the late phase of the phrenic neurogram.
Dynamical evolution of the inner heliosphere approaching solar activity maximum: interpreting Ulysses observations using a global MHD model

In this study we describe a series of MHD simulations covering the time period from 12 January 1999 to 19 September 2001 (Carrington Rotation 1945 to 1980). This interval coincided with: (1) the Sun s approach toward solar maximum; and (2) Ulysses second descent to the southern polar regions, rapid latitude scan, and arrival into the northern polar regions. We focus on the evolution of several key parameters during this time, including the photospheric magnetic field, the computed coronal hole boundaries, the computed velocity profile near the Sun, and the plasma and magnetic field parameters at the location of Ulysses. The model results provide a global context for interpreting the often complex in situ measurements. We also present a heuristic explanation of stream dynamics to describe the morphology of interaction regions at solar maximum and contrast it with the picture that resulted from Ulysses first orbit, which occurred during more quiescent solar conditions. The simulation results described here are available at: http://sun.saic.com.
Claudin-1 overexpression in intestinal epithelial cells enhances susceptibility to adenamatous polyposis coli-mediated colon tumorigenesis

The tight junction protein Claudin-1, a claudin family member, has been implicated in several gastro-intestinal pathologies including inflammatory bowel disease (IBD) and colorectal cancer (CRC). In this regard, we have demonstrated that claudin-1 expression in colon cancer cells potentiates their tumorigenic ability while in vivo expression of claudin-1 in the intestinal epithelial cells (IECs) promotes Notch-activation, inhibits goblet cell differentiation and renders susceptibility to mucosal inflammation. Notably, a key role of inflammation in colon cancer progression is being appreciated. Therefore, we examined whether inflammation plays an important role in claudin-1-dependent upregulation of colon carcinogenesis. APCmin mice were crossed with Villin-claudin-1 transgenic mice to generate APC-Cldn1 mice. H&E stained colon tissues were assessed for tumor number, size and histological grade. Additionally, microarray and qPCR analyses of colonic tumors were performed to assess molecular changes due to claudin-1 expression. APC-Cldn1 and APCmin controls were assessed for colonic permeability via rectal administration of FITC-dextran, and bacterial translocation via qPCR analysis of 16S rDNA. Claudin-1 overexpression in APCmin mice significantly increased (~4-fold) colonic tumor growth and size, and decreased survival. Furthermore, transcriptome analysis supported upregulated proliferation, and increased Wnt and Notch-signaling in APC-Cldn1 mice. APC-Cldn1 mice also demonstrated inhibition of mucosal defense genes while expression of pro-inflammatory genes was sharply upregulated, especially the IL-23/IL-17 signaling. We predict that increased Notch/Wnt-signaling underlie the early onset of adenoma formation in APC-Cldn1 mice. An increase in mucosal permeability due to the adenomas and the inherent barrier defect in these mice further facilitate bacterial translocation into the mucosa to induce inflammation, which in turn promote the tumorigenesis. Taken together, these results confirm the role of claudin-1 as a promoter of colon tumorigenesis and further identify the role of the dysregulated antigen-tumor interaction and inflammation in claudin-1-dependent upregulation of colon tumorigenesis.
The biological limitations of transcriptomics in elucidating stress and stress responses

Global analysis of mRNA abundance via genomic arrays (i.e. transcriptomics or transcriptional profiling) is one approach to finding the genes that matter to organisms undergoing environmental stress. In evolutionary analyses of stress, mRNA abundance is often invoked as a proxy for the protein activity that may underlie variation in fitness. To provoke discussion of the utility and sensible application of this valuable approach, this manuscript examines the adequacy of mRNA abundance as a proxy for protein activity, fitness and stress. Published work to date suggests that mRNA abundance typically provides little information on protein activity and fitness and cannot substitute for detailed functional and ecological analyses of candidate genes. While the transcriptional profile can be an exquisitely sensitive indicator of stress, simpler indicators will often suffice. In view of this outcome, transcriptomics should undergo careful cost-benefit analysis before investigators deploy it in studies of stress responses and their evolution.
Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia

Oscillatory electroencephalogram (EEG) abnormalities may reflect neural circuit dysfunction in neuropsychiatric disorders. Previously we have found positive correlations between the phase synchronization of beta and gamma oscillations and hallucination symptoms in schizophrenia patients. These findings suggest that the propensity for hallucinations is associated with an increased tendency for neural circuits in sensory cortex to enter states of oscillatory synchrony. Here we tested this hypothesis by examining whether the 40 Hz auditory steady-state response (ASSR) generated in the left primary auditory cortex is positively correlated with auditory hallucination symptoms in schizophrenia. We also examined whether the 40 Hz ASSR deficit in schizophrenia was associated with cross-frequency interactions. Sixteen healthy control subjects (HC) and 18 chronic schizophrenia patients (SZ) listened to 40 Hz binaural click trains. The EEG was recorded from 60 electrodes and average-referenced offline. A 5-dipole model was fit from the HC grand average ASSR, with 2 pairs of superior temporal dipoles and a deep midline dipole. Time-frequency decomposition was performed on the scalp EEG and source data. Phase locking factor (PLF) and evoked power were reduced in SZ at fronto-central electrodes, replicating prior findings. PLF was reduced in SZ for non-homologous right and left hemisphere sources. Left hemisphere source PLF in SZ was positively correlated with auditory hallucination symptoms, and was modulated by delta phase. Furthermore, the correlations between source evoked power and PLF found in HC was reduced in SZ for the LH sources. These findings suggest that differential neural circuit abnormalities may be present in the left and right auditory cortices in schizophrenia. In addition, they provide further support for the hypothesis that hallucinations are related to cortical hyperexcitability, which is manifested by an increased propensity for high-frequency synchronization in modality-specific cortical areas.
9.4.1 Determining Reliability Requirements and Testing Costs in the Early Stages of Single Use Medical Product Design

The production of single use medical devices, particularly for home use by patients, continues to grow, and the reliability of these devices is a primary concern for manufacturers and end-users. The systems engineer tasked with the device development needs methods and tools to establish reliability requirements and provide cost estimates for the testing necessary to show compliance with those requirements. This paper examines methods for determining reliability requirements, the cost of reliability testing for single use medical devices in the design input phase of product development, and how the costs of testing and potential errors can be used to perform trade-off analysis between reliability tolerance and confidence level.
A theory of defeasible reasoning

Reasoning can lead not only to the adoption of beliefs, but also to the retraction of beliefs. In philosophy, this is described by saying that reasoning is defeasible. My ultimate objective is the construction of a general theory of reasoning and its implementation in an automated reasoner capable of both deductive and defeasible reasoning. The resulting system is named “OSCAR.” This article addresses some of the theoretical underpinnings of OSCAR. This article extends my earlier theory in two directions. First, it addresses the question of what the criteria of adequacy should be for a defeasible reasoner. Second, it extends the theory to accommodate reasons of varying strengths. Reasoning can lead not only to the adoption of beliefs, but also to the retraction of beliefs. In philosophy, this is described by saying that reasoning is defeasible. In AI, it is described by saying that reasoning is nonmonotonic. My ultimate objective is the construction of a general theory of reasoning and its implementation in an automated reasoner capable of both deductive and defeasible reasoning. The resulting system is named “OSCAR.” This article addresses some of the theoretical underpinnings of OSCAR.* I presented the basic ideas behind this theory of defeasible reasoning in Ref. 2. This article extends that theory in two directions. First, it addresses the question of what the criteria of adequacy should be for a defeasible reasoner. Second, it extends the theory to accommodate reasons of varying strengths.
Automatic visual to tactile translation. I. Human factors, access methods and image manipulation

This is the first part of a two-part paper that motivates and evaluates a method for the automatic conversion of images from visual to tactile form. In this part, a broad-ranging background is provided in the areas of human factors, including the human sensory system, tactual perception and blindness, access technology for tactile graphics production, and image processing techniques and their appropriateness to tactile image creation. In Part II, this background is applied in the development of the TACTile Image Creation System (TACTICS), a prototype for an automatic visual-to-tactile translator. The results of an experimental evaluation are then presented and discussed, and possible future work in this area is outlined.
Beta-Endorphins and Mood States during Resistance Exercise

Research examining the relationship between beta-endorphin immunoreactivity and affect has resulted in equivocal findings. To examine this relationship further, 10 male and 10 female college-age students participated in a controlled free-weight exercise session. Blood plasma samples were procured both prior to and following the exercise bout and beta-endorphin levels were determined by immunoassay. Analysis indicated that plasma beta-endorphin levels following exercise were significantly decreased from pre-exercise levels. Pearson correlations showed no significant relationship between pre- or postexercise plasma beta-endorphins and either total mood disturbance or Profile of Mood States subscores. The data support previous failure of resistance exercise to produce an increase in beta-endorphin immunoreactivity as well as the lack of a significant relationship between affect and the beta-endorphin response to exercise.
Lanthanide Compounds with Fluorinated OC6F5 Ligands: Homo- and Heterovalent Complexes of Eu(II) and Eu(III)

The fluorinated phenoxide OC6F5 forms the stable Eu(II) and Eu(III) derivatives (DME)2Eu(μ-OC6F5)3Eu(μ-OC6F5)3Eu(DME)2 and (DME)2Eu(OC6F5)3, as well as the heterovalent product (DME)2Eu(μ-OC6F5)3Eu(DME)(OC6F5)2, in redox reactions of Eu with HOC6F5 or in proton-transfer reactions of HOC6F5 with Eu(SPh)2. The divalent complex crystallizes as a trimer with three bridging phenoxides bridging each pair of metals, with the terminal metals coordinating DME and the central metal ion encapsulated totally by O(C6F5) and dative fluoride interactions. The trivalent compound is monomeric with terminal phenoxide ligands and no Eu−F interactions. The heterovalent compound has clearly localized metal valence states and coordination features that mimic the homovalent species with the terminal OC6F5 bound to the Eu(III) ion, three bridging OR ligands spanning the Eu(II) and Eu(III) ions, and dative Eu(II)−F bonds. At elevated temperatures, these compounds decompose to give a mixture of solid-state fluoride phases.
The effect of superoxide dismutase alleles on aging in Drosophila

The effects of superoxide dismutase on aging were tested using two differt experimental approaches. In the first, replicated populations with postponed aging were compared with their controls for frequencies of electrophoretic alleles at the SOD locus. Populations with postponed aging had consistently greater frequencies of the allele coding for more active SOD protein. This allele was not part of a segregating inversion polymorphism. The second experimental approach was the extraction of SOD alleles from different natural populations followed by the construction of different SOD genotypes on hybrid genetic backgrounds. This procedure did not uncover any statistical effect of SOD genotype on longevity or fecundity. There were large effects on longevity and fecundity due to the family from which a particular SOD genotype was derived. To detect the effects of SOD genotypes on longevity with high probability would require a ten-fold increase in the number of families used.