cssi/SciSciGPT-SciSciNet huggingface dataset:
"Without Handicap": Issues of Medical Schools and Physically Disabled Students.

The Americans with Disabilities Act of 1990 requires that access to education not be denied simply on the basis of disability. The law requires definition of "basic qualifications" required of all applicants, "essential elements" of the curriculum, and whether accommodation would alter the "fundamental nature" of the learning experience or impose "undue burden." Medical schools have a very low proportion of physically disabled students, which the author argues is largely a result of schools' conception of the "undifferentiated graduate" as being capable of performing the history, physical examination, and any medical procedure without an intermediary. But the author maintains that medical students need not be unblemished physically; medical educators' obligation is to educate those students who are qualified to become physicians by virtue of intelligence, professional attitude, and ability to effectively interact and communicate. With respect to clinical training, it is important to consider whether personal, hands-on experience is required for adequate learning to occur. Because most physicians limit the scopes of their practices and do not perform all procedures, because those physicians who develop physical disabilities are not precluded from continuing in some forms of medical practice, and because technologic advances allow for the substitution of imaging and diagnostic testing for the more conventional approach to the physical examination, the requirement for hands-on capability becomes less compelling. Yet not every physically disabled applicant should be admitted to medical school, and those admitted require coaching, guidance, and career advice in order to succeed with their physical limitations. The author suggests that one of the seminal concepts of medical education, "without handicap," should be seen not as referring to the pre-existing physical status of students but instead as the obligation of educators to provide all their students with the broadest possible learning experiences so that they will be without the handicap of inadequate education when they proceed to their chosen fields.
Calibrating photon-counting detectors to high accuracy: background and deadtime issues

When photon-counting detectors are calibrated in the presence of a background signal, deadtime effects can be significant and must be carefully accounted for to achieve high accuracy. We present a method for separating the correlated signal from the background signal that appropriately handles deadtime effects. This method includes consideration of pulse timing and afterpulsing issues that arise in typical avalanche photodiode (APD) detectors. We illustrate how these effects should be accounted for in the calibration process. We also discuss detector timing issues that should be considered in detector calibration.
A stable isotope assay for pseudoracemic warfarin from human plasma samples

A pseudoracemic technique utilizing a seable isotope in one enantiomer was employed for the simultaneous determination of (R) and (S)-warfarin from plasma of human subjects. The assay includes high performance liquid chromatographic clean-up prior to mass spectral analysis to eliminate ion interferences from either co-administered drugs or contamination of the source. The assay is reliable, accurate and precise to within 5% at the submicrogram level.
After school work in Mexico: Competing for children's time success

In recent decades, Mexico and other developing countries have enacted labor, education, and child welfare policies to shift working children out of the labor force and into the school system. Such policies take three principle forms: prohibiting certain work by children; increasing the minimum working age; and, extending compulsory schooling. Yet, child labor persists in many countries despite all these policies (International Labour Organization, 1999), and in Mexico it invariably appears within public debates about the impact of economic crisis and structural adjustment (La Jornada, 1999). By this and other accounts, as many as five million Mexican children under age 15 work for pay. As an indicator of the seriousness with which Mexico views child labor, the government recently initiated a massive scholarship program, PROGRESA, targeted at the least developed regions of the country. It provides direct payments—as a substitute for lost wages—to the families of children attending secondary school. In this paper we discuss one important outcome overlooked in the ensuing debate over policy effectiveness: consequences for children’s learning and
Differential proliferative responses of cultured Schwann cells to axolemma and myelin-enriched fractions. II. Morphological studies.

Axolemma-enriched and myelin-enriched fractions were prepared from bovine CNS white matter and conjugated to fluorescein isothiocyanate (FITC). Both unlabelled and FITC-labelled axolemma and myelin were mitogenic for cultured rat Schwann cells. Treatment of Schwann cells with the FITC-labelled mitogens for up to 24 h resulted in two distinct morphological appearances. FITC-myelin-treated cells were filled with numerous round, fluorescent-labelled intracellular vesicles, while FITC-axolemma-treated cells appeared to be coated with a patchy, ill-defined fluorescence, primarily concentrated around the cell body but extending onto the cell processes. These observations were corroborated under phase microscopy. Electron microscopy revealed multiple, membrane-bound, membrane-containing phagosomes within myelin-treated cells and to a far lesser extent in axolemma-treated cells. The effect on the expression of the myelin-mediated and axolemma-mediated mitogenic signal when Schwann cells were treated with the lysosomal inhibitors, ammonium chloride and chloroquine, was evaluated. The mitogenicity of myelin was reduced 70–80% by these agents whereas the mitogenicity of axolemma was not significantly altered under these conditions. These results suggest that axolemma and myelin stimulate the proliferation of cultured Schwann cells by different mechanisms. Myelin requires endocytosis and lysosomal processing for expression of its mitogenic signal; in contrast, the mitogenicity of axolemma may be transduced at the Schwann cell surface.
The Role of Physical Activity Participation in Weight Loss Outcomes Following Weight Loss Surgery

Weight loss surgery (WLS) is an effective intervention for the reduction of body mass and the resolution of obesity-related comorbidities. Excess weight loss following WLS has been reported in the range of 40% to 78% depending on the surgery type and the follow-up time period. Initial weight loss outcomes and weight loss maintenance have been shown to depend on several factors, including the type of surgical procedure, preexisting comorbidities, and compliance with postoperative medical, nutritional, and behavioral recommendations. One factor that has received limited attention in the scientific literature is the role of physical activity in initial weight loss and maintenance following WLS. Physical activity participation of sufficient frequency, intensity, and duration during both the pre- and postoperative time periods has the potential to reduce surgical complications, enhance weight loss outcomes, and improve physical fitness and overall health following WLS. In addition, physical activity has the po...
Maximising the effect of combination HIV prevention in Kenya.

1426 www.thelancet.com Vol 384 October 18, 2014 Authors’ reply We agree with Sally Blower and Brian Coburn that the aim of HIV prevention programmes is to reduce HIV incidence among men and women and that focusing resources on those locations with the greatest intensity of transmission can increase the eff ect of these programmes. When limited resources are allocated in a way that maximises their eff ect, three factors determine where the investments are made. First, is the epidemiological context, which was captured in our model through fitting to multiple indicators, including the sex ratio of HIV prevalence. The second determinant is what interventions are available, their efficacy, and their cost. Whereas men can directly benefit from low cost and highly eff ective circumcision interventions, there is unfortunately no such analogous intervention for women. A number of additional strategies that were not modelled, such as cash transfer to girls and interventions that can prevent intimate partner violence, are promising interventions for women, and could also be considered for inclusion in programmes. The fi nal factor is the budget. With the budget available, the greatest overall effect was not achieved by, for example, provision of all low risk women with pre-exposure prohylaxis (PrEP), but by focusing its use to sex workers in the highest Maximising the eff ect of combination HIV prevention in Kenya
Biological interactions of extremely-low-frequency electric and magnetic fields

Abstract A description is given of the fundamental physical properties of extremely-low-frequency (ELF) electromagnetic fields, and the mechanisms through which these fields interact with the human body at a macroscopic level. Evidence is presented that cell membranes play an important role in transducing ELF signals. Both experimental evidence and theoretical models are described that relate pericellular currents and electrochemical events at the outer membrane surface to transmembrane signaling pathways and cytoplasmic responses. Biological responses to ELF fields at the tissue, cellular and molecular levels are summarized, including new evidence that ELF field exposure produces alterations in messenger RNA synthesis, gene expression and the cytoplasmic concentrations of specific proteins.
Dissolution study of metatorbernite: thermodynamic properties and the effect of pH and phosphate.

The uranyl copper-phosphate, metatorbernite, has been identified in the shallow vadose zone of the 300 A area at the Hanford site, WA, USA. Consequently, modeling the evolution of U concentrations ...
Computation of exact confidence intervals for the odds ratio.

Abstract A time-sharing program written in BASIC language has been developed to compute exact confidence limits for the odds ratio parameter in a 2 × 2 table. The program offers the user a choice between the classical exact limits and limits based upon a recent redefinition of the exact p -value aimed at avoidance of conservatism in the classical procedure. The user selects the degree of confidence desired during a run of the program, which then computes the exact limits and p -value.
Mining whining in support forums with frictionary

Millions of people request help with software in support forums, creating a massive repository of user experiences ripe for mining. We present Frictionary, a tool for automatically extracting, aggregating, and organizing problem described in support forums, enabling timely problem frequency and prevalence metrics. We applied it to 89,760 Firefox support requests from 4 sources gathered over 10 months. Interviews with the Firefox principal designer and support lead suggest that Frictionary could be a useful tool for prioritizing engineering efforts, but that the extraction would need to be more precise to be useful.
The effect of 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide on tissue cholinesterase and carboxylesterase activities of the rat

Abstract The dose-response (0.1 to 1000 mg/kg sc) effects of 2-( o -cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP; a metabolite of the organophosphorus compound tri- o -cresylphosphate) on total cholinesterase (ChE) and carboxylesterase (CaE) activities in tissues from the rat were examined. Doses of CBDP greater than 1.0 mg/kg inhibited CaE activity maximally (>99%) in plasma and lung, two important sites for detoxification of organophosphorus toxicants. A biphasic dose-dependent inhibition of ChE activity was seen in all tissues; the ED50 values showed a difference of two orders of magnitude between the first and the second phases of the dose-response curves. CBDP inhibited the blood esterases in the order plasma CaE ⋙ plasma ChE ⪢ red blood cell (RBC) ChE. The biphasic dose-response curve and preferential inhibition of the blood esterases may reflect the inhibition of butyrylcholinesterase in preference to acetylcholinesterase in these tissues. At doses of CBDP below 1.0 mg/kg, plasma, RBC, and brain regional ChE activities were inhibited by less than 10%, whereas at doses above 2.0 mg/kg, ChE activities were inhibited substantially (up to 80% in plasma, up to 60% in RBC, and greater than 90% in brain regions). On the basis of these results, a dose of CBDP between 1.0 and 2.0 mg/kg should prove useful as a pretreatment for studies of OP toxicity in the rat.
Nonbank Financial Intermediaries, Credit Expansion, and Monetary Policy

N ONBANK FINANCIAL INTERMEDIARIES (henceforth in this paper referred to as NFI) have grown and continue to grow in importance in many countries of the world. Their development has led to serious consideration of the question whether the efficient conduct of monetary policy requires closer regulation of these institutions. At present, in most countries they are regulated in much the same manner as commercial corporations. This paper is an attempt to clarify their role in the expansion of credit and to examine the manner in which they differ from commercial banks; the results of this investigation are then used to assess some of the implications of the growth of NFI for monetary policy.'
Christian Holy Women and the Exercise of Religious Authority in the Medieval West

The essay reviews scholarship on female mystics and other holy women in late Medieval Europe (1100–1400), as a collective case study in how religious authority has been negotiated in the history of Christianity. Recent scholars view the firm exclusion of women from institutional leadership by male clerics in this period as an essential condition of the rise of such women to importance as persons with charismatic authority, i.e., in Max Weber’s terminology, an authority rooted in personal gifts and attributes. Some scholars have viewed charismatic women as essentially subversive of, or resistant to, the powers of clerics. Others see them in more positive terms as staking out their own complementary authority. Scholars have also considered the attitude of clerics toward such women, which was often characterized by acute awareness of the ways in which the women’s charismatic powers compensated for the inadequacies of clerical authority. Very recent scholars have further nuanced these insights by asking how the dynamics of the interplay of institutional and charismatic authority may or may not be evident in local situations.
Cortical slow negative waves following non-paired stimuli: effects of modality, intensity and rate of stimulation.

Abstract Using a simple stimulus counting task, negative after-waves following single (unpaired) stimuli were investigated under a variety of stimulus conditions. Responses were obtained to tones at 3 intensities, to light flashes at 3 intensities, and to tones at 3 rates of presentation. The acoustic stimuli led to a negative after-wave that peaked at frontal sites around 500 or 600 msec, and then trailed off to a more central scalp representation. This negative after-wave was increased in amplitude by slowing the rate of stimulus presentation. In comparison, no appreciable or sustained after-wave was elicited by visual stimuli. No significant effects in the negative after-wave were associated with intensity, either for visual or for acoustic stimuli. When analyzed by Principal Components Analysis, the negative after-waves were shown to comprise in all cases two underlying factors, although the factors contributed less to the total wave form for visual stimuli than for acoustic stimuli. Two interpretations for the negative after-wave were contrasted, one considering it to be an integral feature of the auditory evoked potential. A second interpretation, more compatible with the data obtained here, links the negative after-wave with non-specific activation processes.
The clinical significance of nitrate tolerance in patients with chronic heart failure.

Tolerance develops during the prolonged use of organic nitrates in patients with chronic heart failure in a fashion similar to its development in patients with angina pectoris, the magnitude of tolerance development being directly proportional to the frequency of dosing. When nitroglycerin is given continuously or when isosorbide dinitrate is administered frequently throughout the day (e.g., every 4 h), haemodynamic tolerance develops completely in most patients within 24–48 h. Such tolerance can be avoided, however, when these drugs are given intermittently (e.g., every 8 or 12 h). Unfortunately, most clinical trials with isosorbide dinitrate have attempted to produce continuous haemodynamic effects by administering the drug at frequent intervals; this may explain why these trials have produced equivocal results. Two mechanisms have been proposed to explain the development of tolerance in patients with chronic heart failure. According to the first hypothesis, tolerance develops as a result of the depletion of intracellular sulfhydryl groups that are essential to the ability of nitroglycerin to activate guanylate cyclase—the key enzyme in the action of nitrates on blood vessels. According to the second hypothesis, tolerance develops as a result of the activation of endogenous neurohormonal systems; the resulting vasoconstriction limits the direct effects of the nitrovasodilators. A better understanding of both mechanisms may lead to interventions that will circumvent the development of tolerance and enhance the efficacy of long-term nitrate therapy.
Instability of diborane gas in silicon epitaxial film growth

Abstract The instability of diborane gas and its influence on silicon epitaxial film growth are evaluated, for the first time, from the viewpoint of the chemical behavior of boranes in a silicon epitaxial reactor which is mainly made of silicon oxide (quartz) and stainless steel. On the surface of silicon oxide, deposition of a film mainly composed of boron can occur above 500 K. The fluctuation of the diborane gas concentration in the order of ppm in the stainless-steel tube at room temperature intensely influences the reproducibility of the boron incorporation into the silicon epitaxial film grown in a diborane–trichlorosilane–hydrogen system. The mechanism causing the instability of diborane gas is discussed from the viewpoint of thermolysis, adsorption and desorption of boranes.
Photoacoustic Microscopy in Tissue Engineering.

Photoacoustic tomography (PAT) is an attractive modality for noninvasive, volumetric imaging of scattering media such as biological tissues. By choosing the ultrasonic detection frequency, PAT enables scalable spatial resolution with an imaging depth of up to ∼7 cm while maintaining a high depth-to-resolution ratio of ∼200 and consistent optical absorption contrasts. Photoacoustic microscopy (PAM), the microscopic embodiment of PAT, aims to image at millimeter depth and micrometer-scale resolution. PAM is well-suited for characterizing three-dimensional scaffold-based samples, including scaffolds themselves, cells, and blood vessels, both qualitatively and quantitatively. Here we review our previous work on applications of PAM in tissue engineering and then discuss its future developments.
The power of rights and the rights of power: what future for human rights?

This article explores the tensions between geopolitics and human rights under present conditions of world politics. It takes notes of the rise of human rights as a discourse in international law, and draws attention to the use of this discourse by powerful states, especially the United States, to validate non-defensive uses of force. It also notes the role of the media in facilitating the geopolitical agenda associated with exerting pressure on some conditions (Darfur, China, Cuba) but exempting other situations as serious or more so (Gaza, Saudi Arabia). This article also discusses the reliance on the human rights discourse by oppressed groups and by countries in the South, and the emergence of a counter-hegemonic tradition in human rights that challenges geopolitical projects in a variety of settings. The main conclusion is that neither an uncritical endorsement nor a cynical dismissal of human rights is appropriate at this time. Keywords: human rights; geopolitics; hegemony; counter-hegemony; international law Citation: Ethics & Global Politics 2008. DOI: 10.3402/egp.v1i1.1815
Oxygen free radical effects in sciatic nerve in experimental diabetes

We previously reported the presence of endoneurial hypoxia, ischemia, impairment of the blood-nerve barrier, and reduction of norepinephrine and 6-ketoprostaglandin F 1α in chronic streptozocin-induced diabetic neuropathy (SDN) and interpreted these findings as suggesting the involvement of oxygen free radicals (OFRs) but did not directly measure indices of OFR activity. In this study, we report on sciatic nerve conjugated dienes, hydroperoxides, norepinephrine, and malondialdehyde in SDN at 1, 4, and 12 mo in male Sprague-Dawley rats. Severe hyperglycemia was present throughout in diabetic rats. Conjugated dienes were consistently increased at all time points, hydroperoxides were consistently reduced, and malondialdehyde was not significantly different in diabetes compared with controls. These findings are consistent with increased OFR activity in experimental diabetes. It is necessary to monitor several indices of OFR activity in a metabolically active tissue such as the peripheral nerve.
Localization transition in the Mermin model

We study the dynamical properties of the Mermin model, a simple quantum dissipative model with a monochromatic environment, using analytical and numerical methods. Our numerical results show that the model exhibits a second order phase transition to a localized state before which the system is effectively decoupled from the environment. In contrast to the spin-boson model, the Mermin model exhibits an ``orthogonality catastrophe,'' defining the critical point, before dissipation has destroyed all coherent behavior. An analytic approach based on the Liouvillian technique, although successful in describing the phase diagram of spin-boson and related models, fails to capture this essential feature of the Mermin model.
Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC-MS/MS

Abstract All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV), abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination. In order simultaneously to measure intracellular levels of the triphosphates (-TP) of ZDV, ABC (carbovir, CBV) and 3TC, either together or individually, we have developed a cartridge-LC–MS/MS method. The quantitation range was 2.5–250 pg/μl for 3TC-TP, 0.1–10.0 pg/μl for ZDV-TP and 0.05–5.00 pg/μl for CBV-TP. This corresponds to 0.1–11.0 pmol 3TC-TP per million cells, 4–375 fmol ZDV-TP per million cells and 2–200 fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4 h post-dose times.
Slc7a5 helps T cells get with the program.

T cell activation requires an influx of amino acids. Slc7a5, an amino-acid transporter induced by the T cell antigen receptor, facilitates the influx of large neutral amino acids and in doing so promotes metabolic reprogramming necessary for T cell differentiation.
FLT3 kinase inhibitor TTT-3002 overcomes both activating and drug resistance mutations in FLT3 in acute myeloid leukemia

There have been a number of clinical trials testing the efficacy of FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) in patients with acute myeloid leukemia (AML) harboring a constitutively activating mutation in FLT3. However, there has been limited efficacy, most often because of inadequate achievement of FLT3 inhibition through a variety of mechanisms. In a previous study, TTT-3002 was identified as a novel FLT3 inhibitor with the most potent activity to date against FLT3 internal tandem duplication (FLT3/ITD) mutations. Here, the activity of TTT-3002 is demonstrated against a broad spectrum of FLT3-activating point mutations, including the most frequently occurring D835 mutations. The compound is also active against a number of point mutations selected for in FLT3/ITD alleles that confer resistance to other TKIs, including the F691L gatekeeper mutation. TTT-3002 maintains activity against patients with relapsed AML samples that are resistant to sorafenib and AC220. Studies utilizing human plasma samples from healthy donors and patients with AML indicate that TTT-3002 is only moderately protein bound compared with several other TKIs currently in clinical trials. Tumor burden of mice in a FLT3 TKI-resistant transplant model is significantly improved by oral dosing of TTT-3002. Therefore, TTT-3002 has demonstrated preclinical potential as a promising new FLT3 TKI that may overcome some of the limitations of other TKIs in the treatment of FLT3-mutant AML. Cancer Res; 74(18); 5206-17. ©2014 AACR.
Intraoperative myocardial protection in the context of coronary revascularization

I T IS NOT BY CHANCE that advances in the diagnosis and treatment of ischemic heart disease have paralleled the development of efficacious modalities for intraoperative myocardial protection. The manifestations of coronary artery disease are the consequences of an uncontrolled ischemic event. Knowledge gleaned from this disease process could be applied to a surgically planned period of ischemia to devise strategies about the pathophysiologic consequences attendant to deprivation of coronary blood flow. It is the purpose of this review to track the rationale and development of current myoprotective regimens, to summarize the experimental and clinical results, and to amplify current issues that are unique to the surgical treatment of occlusive coronary artery disease.
Context sensitive labeling of spinal structure in MR images

We present a new method for automatic detection of the lumbar vertebrae and disk structure from MR images. In clinical settings, radiologists utilize several images of the lumbar structure for diagnosis of lumbar disorders. These images are co-registered by technicians and represent orthogonal features of the lumbar region. We combine information from T1W sagittal, T2W sagittal and T2W axial MR images to automatically label disks and vertebral columns. The method couples geometric and tissue property information available from the three types of images with image analysis approaches to achieve 98.8% accuracy for the disk labeling task on a test set of 67 images containing 335 disks.
The impact of extinct taxa on understanding the early evolution of Angiosperm clades: an example incorporating fossil reproductive structures of Saxifragales

A cladistic analysis was performed including five Cretaceous and 31 extant taxa within Saxifragales using a combination of molecular sequence and morphological data in order to elucidate the utility of extinct taxa in illuminating saxifragalean evolution. The results suggest that Saxifragales as well as most major infraordinal clades lack unambiguous morphological synapomorphies among the characters examined; that the major lineages of Saxifragales were distinct by ca. 90–70 Ma; and that the ca. 90 Ma taxa lack characteristic derived features present in modern taxa. General conclusions concerning the advantages of joint extinct-extant taxon phylogenetic analyses explored herein include: 1) Prediction of the morphological characters present in early members of a clade; 2) Determination of minimum ages for lineage divergences; 3) Resolution of the order in which synapomorphies may have evolved; and 4) Circumscription of the time interval during which synapomorphies may have evolved.
Emotion complexity and emotion regulation across adulthood

This research used data from a study on daily emotional experience in adulthood to examine the associations between age, emotion complexity, and emotion regulation. Data were drawn from a study of daily stress that included 239 participants ranging in age from 18 to 89 from North Central Florida. Two indicators of emotion complexity were considered: emotion differentiation and the co-occurrence of positive and negative affect. Emotion regulation was assessed in terms of individuals’ likelihood of maintaining adaptive emotion states. There were no age differences in adults’ co-occurrence of positive and negative emotions. In contrast to theories suggesting age would be associated with greater emotion complexity, the findings revealed that older adults had lower differentiation scores than younger adults. Age was also associated with more adaptive patterns of emotion regulation. Specifically, older adults persisted in low negative states and moved out of high negative states more readily than younger adults. Finally, neuroticism, self-concept incoherence, mean daily stress, and emotion complexity were associated with emotion regulation. Notably, adults who reported a greater mix of positive and negative affect moved out of high negative affect states more rapidly than adults with lower co-occurrence scores. This finding is in keeping with a growing body of work suggesting that positive affect promotes recovery from negative affect. Overall, the findings suggest that although emotion complexity is associated with emotion regulation, it does not appear to be a key factor underlying age differences in emotion regulation.
Model-based characterization of charged-defect transport and apparent gas-phase permeation in mixed-conducting perovskite membranes

Abstract A computational approach is implemented to characterize multicomponent charged-defect transport and apparent gas-phase permeation associated with proton-conducting perovskite membranes across a very wide range of gas-phase environments. The Nernst–Planck–Poisson (NPP) model predicts charged-defect and electrostatic-potential profiles within the membrane as well as apparent gas-phase fluxes entering and leaving the membrane surfaces. Results are represented as two-dimensional contour maps, enabling the large amounts of information to be presented in a compact graphical format. The results provide qualitative and quantitative insights about membrane permeation phenomena as functions of gas-phase environments across the membrane. Although the study considers the properties of a particular yttria-doped barium zirconate (BZY20), the modeling approach and qualitative insights are more widely applicable to classes of similar materials.
MYH Y165C and G382D mutations in hepatocellular carcinoma and cholangiocarcinoma patients.

Purpose: Production of reactive oxygen species (ROS) during chronic inflammation has been implicated in the progression of liver diseases and carcinogenesis. Subjects with inflammatory liver disease and one non-functional allele of the base excision repair gene, MYH, may be more susceptible to progression to cancer due to MYH haploinsufficiency in repairing oxidative damage caused by ROS. Here, we investigated the association of two common germline MYH mutations in patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma. Methods: DNA from patients with HCC (n=48) or cholangiocarcinoma (n=84) compared to non-cancerous controls (n=308) were genotyped for the Y165C and G382D mutations in MYH. Results: There was no significant difference in MYH mutation carrier status between patients with HCC (1/48), cholangiocarcinoma (3/84), and non-cancerous controls (4/308). Conclusions: Patients with HCC or cholangiocarcinoma do not have an increased incidence of monoallelic MYH mutations pre-disposing them to disease.
DIFFUSION-CONTROLLED SYNKINEMATIC GROWTH OF GARNET FROM A HETEROGENEOUS PRECURSOR AT PASSO DEL SOLE, SWITZERLAND

Nous decrivons des porphyroblastes syncinematiques de grenat provenant de Passo del Sole, en Suisse, qui font preuve de caracteristiques texturales et chimiques typiques de mecanismes de cristallisation regis par une diffusion intergranulaire et influences par une heterogeneite compositionnelle. Une analyse texturale quantitative mene a une indication de correlations entre dimension et degre d'isolation, qui temoignent de la suppression de la diffusion au cours de la croissance, due a la competition pour les elements nutritifs requis parmi les cristaux voisins. Une zonation en composition, en particulier une zonation oscillatoire exceptionelle en Ca, revele une relation non documentee auparavant: il y a une proportionalite directe entre le rayon des cristaux et leur taux de croissance radiale. Cette relation decoule d'une croissance regie par la diffusion a partir d'un precurseur heterogene; une diffusion intergranulaire lente conserve les heterogeneites locales dans la distribution des elements nutritifs requis pour la croissance, ce qui a cause une croissance des cristaux a un taux dependant de la disponibilite locale de ces elements; les cristaux qui ont cru plus rapidement sont plus gros a tous les stades du processus. Ces resultats ne concordent donc pas avec l'hypothese voulant que la deformation au cours du metamorphisme puisse eliminer les influences de la diffusion sur la croissance des porphyroblastes par tranfert accelere des elements nutritifs. Des taux variables de re-equilibrage chimique au cours de la croissance menent a des degres variables d'uniformite en zonation chimique parmi les cristaux de grenat. Tout comme dans la documentation precedente, le Fe et le Mg semblent avoir pu s'equilibrer a l'echelle de la roche tout au long de l'intervalle de cristallisation, tandis que le manganese, en faibles quantites dans le coeur des cristaux aptes a subir des restrictions en disponibilite de cet element, indique un desequilibre aux stades precoces de la croissance, a faible temperature. En revanche, et contrairement a ce que l'on pourrait s'attendre suite aux etudes precedentes, des traces complexes mais identiques en zonation oscillatoire en Ca font penser que l'equilibrage etait atteint a l'echelle de la roche pour le Ca pour la plupart, sinon toute, la duree de la cristallisation du grenat.
Determination of 241 Am in Urine Using Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICP-MS).

Quantification of 241Am in urine at low levels is important for assessment of individuals’ or populations’ accidental, environmental, or terrorism-related internal contamination, but no convenient, precise method has been established to rapidly determine these low levels. Here we report a new analytical method to measure 241Am as developed and validated at the Centers for Disease Control and Prevention (CDC) by means of the selective retention of Am from urine directly on DGA resin, followed by SF-ICP-MS detection. The method provides rapid results with a limit of detection (LOD) of 0.22 pg/L (0.028 Bq/L), which is lower than 1/3 of the C/P CDG for 241Am at 5 days post-exposure. The results obtained by this method closely agree with CDC values as measured by liquid scintillation counting, and with National Institute of Standards Technology (NIST) Certified Reference Materials (CRM) target values.
Vanishing of Some Cohomology Groups and Bounds for the Shafarevich-Tate Groups of Elliptic Curves

Abstract Let E be an elliptic curve over Q and l be an odd prime. Also, let K be a number field and assume that E has a semi-stable reduction at l . Under certain assumptions, we prove the vanishing of the Galois cohomology group H 1 ( Gal ( K ( E [ l i ] ) / K ) , E [ l i ] ) for all i ⩾ 1 . When K is an imaginary quadratic field with the usual Heegner assumption, this vanishing theorem enables us to extend a result of Kolyvagin, which finds a bound for the order of the l -primary part of Shafarevich–Tate groups of E over K. This bound is consistent with the prediction of Birch and Swinnerton–Dyer conjecture.
A Physiologically Based Model for Gastrointestinal Absorption and Excretion of Chemicals Carried by Lipids

Pharmacokinetic models which incorporate independently measured anatomical characteristics and physiological flows have been widely used to predict the pharmacokinetic behavior of drugs, anesthetics, and other chemicals. Models appearing in the literature have included as many as 18,(1) or as few as 5 tissue compartments.(2) With the exception of the multiple-compartment delay trains used by Bischoff(3) to model the delays inherent to the appearance of drug metabolites in bile and segments of the intestinal lumen, very little effort has been made to incorporate the available information on gastrointestinal anatomy and physiology into more accurate gastrointestinal absorption/enterohepatic recirculation submodels. Since several authors have shown that the lymphatic system is the most significant route of absorption for highly lipophilic chemicals, we have constructed a model of gastrointestinal absorption that emphasizes chylomicron production and transport as the most significant route of absorption for nonvolatile, lipophilic chemicals. The absorption and distribution of hexachlorobenzene after intravenous vs. oral dosing are used to demonstrate features of this model.
Surface analytic techniques in corrosion science

Abstract The corrosion scientist now has a selection of several surface sensitive techniques in which commercial instruments and equipment are available to examine and analyze corrosion problems. These techniques include ellipsometry, Auger electron spectroscopy (AES), electron spectroscopy for chemical analysis (ESCA), ion scattering spectrometry (ISS), secondary ion mass spectrometry (SIMS), and electron stimulated desorption (ESD). With these surface techniques, the outer surface (monolayers) of corrosion products can be examined. Also by utilizing sputter etching, depth profiles of films can be obtained and interfaces analyzed. Passivation layers and effects of thermal and chemical treatments on the surface films can be studied. The basic principles and types of information obtained on various materials using these surface analytical tools are discussed.
Effects of refractive turbulence on coherent laser radar.

The leading-order effects of refractive turbulence are calculated for a general coherent laser radar with beam-angle and beam-offset misalignment. The effects of refractive turbulence are important for 10-μm operation in the atmospheric surface layer for typical daytime conditions and paths longer than 3 km. The effects for near-infrared and visible wavelengths are more pronounced. The behavior of different parameter regimes are related to the scintillation scales of the transmitted beam. In certain cases, the small-scale scintillation structure produces a measure of beam misalignment that is more sensitive than the free-space case. The phase approximation of the extended Huygens–Fresnel principle is shown to be correct in the limit of large path-integrated refractive turbulence.
Coding and Visualizing Eye Tracking Data in Simulated Anesthesia Care

Eye tracking can be a valuable tool for collecting data about perception and attention in task performance, but its use in human factors research has been limited. This may be due to the fact that the coding and visualization of eye tracking data can be difficult and time-consuming. In this paper we introduce a video-coding application for coding and analyzing eye tracking data. We discuss various methods for visualizing these data for the purposes of identifying patterns or trends that can then be more formally analyzed. We also present several visualization examples from the simulated anesthesia care environment.
PRODUCTION OF ALTERNARIOL AND ALTERNARIOL METHYL ETHER BY ALTERNARIA SPP.

Five isolates of Alternaria alternata, five isolates of A. tenuis, one isolate of A. hemicota and three isolates of unidentified Alternaria spp. were examined for their production of alternariol methyl ether (AME) and alternariol (AOH) in complex liquid media. The data were compared with the production of these two toxins on solid substrate rice cultures. A new high-performance liquid chromatography method with minimum detection levels for AME and AOH of 20 ng and 40 ng, respectively, was used to quantitate the toxins. All isolates produced AME and AOH, but the amount varied considerably with the isolates and media tested. Of the three different liquid media tested, the highest quantity of AME and AOH was produced in a modified Czapek-Dox broth. The highest yield of toxins was obtained in the solid rice cultures. As much as 125 mg of AME and 16 mg of AOH were produced by one A. tenuis isolate on 300 g of rice after 14 days of incubation at 25°C in darkness.
Fault reactivation and fluid flow along a previously dormant normal fault in the northern North Sea

Detailed seismic imaging and in situ stress and pore-pressure measurements are used to analyze reverse-fault reactivation of a long-dormant normal fault in the northern North Sea. Fault reactivation is caused by three factors: (1) a recent increase in the compressional stress in the area associated with postglacial rebound, (2) locally elevated pore pressure due to the presence of natural gas in a hydrocarbon reservoir on the footwall side of the fault, and (3) a fault orientation that is nearly optimally oriented for frictional slip in the present-day stress field. We demonstrate that the combination of these three factors induces fault slippage and gas leakage along sections of the previously sealing reservoir-bounding fault. We argue that similar pore-pressure triggering of fault slip in the crust may occur because of the accumulation of gas columns of, e.g., CO2 and He in the vicinity of tectonic faults.
Invasion of the Emperor's Grackle

Summary. The great-tailed grackle Quiscalus mexicanus was introduced by Aztec Emperor Auitzotl beyond its native range in 16th century Mexico. Haemig (2011) provides valuable details on the transport, introduction, establishment, and spread of this species. However, here I argue that while this is an interesting account of a historical bird translocation, this is not the reason why this species has undergone one of the greatest range expansions of any native North American species during the 20th century. Fossil records indicate that the species was already present in areas further north before this historical translocation. Moreover, it is a very plastic species and human commensal. Therefore, the northward expansion of this tropical species has been aided by anthropogenic habitat changes rather than a consequence of the active translocation by the Aztec Emperor Auitzotl.
The prescription of addiction medications after implementation of chronic care management for substance dependence in primary care.

Abstract People with addictive disorders commonly do not receive efficacious medications. Chronic care management (CCM) is designed to facilitate delivery of effective therapies. Using data from the CCM group in a trial testing its effectiveness for addiction ( N =282), we examined factors associated with the prescription of addiction medications. Among participants with alcohol dependence, 17% (95% CI 12.0–22.1%) were prescribed alcohol dependence medications. Among those with drug dependence, 9% (95% CI 5.5–12.6%) were prescribed drug dependence medications. Among those with opioids as a substance of choice, 15% (95% CI 9.3–20.9%) were prescribed opioid agonist therapy. In contrast, psychiatric medications were prescribed to 64% (95% CI 58.2–69.4%). Absence of co-morbid drug dependence was associated with prescription of alcohol dependence medications. Lower alcohol addiction severity and recent opioid use were associated with prescription of drug dependence medications. Better understanding of infrequent prescription of addiction medications, despite a supportive clinical setting, might inform optimal approaches to delivering addiction medications.
Rationale and design of the OPTIME CHF trial: outcomes of a prospective trial of intravenous milrinone for exacerbations of chronic heart failure.

Abstract Background The optimal management of an acute exacerbation of chronic heart failure (CHF) is uncertain. There is little randomized evidence available to support the various treatment strategies for patients hospitalized with an exacerbation of CHF. Inotropic agents may produce beneficial hemodynamic effects, and although they are currently used in these patients, their effect on clinical response and impact on clinical outcome is unclear. We present a unique and simple study designed to determine whether a treatment strategy for CHF exacerbations that includes an intravenous agent with inotropic properties can reduce hospital length of stay and lead to improved patient outcome. Methods The OPTIME CHF (Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure) trial is an ongoing multicenter, randomized, placebo-controlled trial of a treatment strategy for patients with acute exacerbations of CHF. The design of this study provides a novel approach to the evaluation of treatment strategies in the care of this population. The OPTIME CHF design uses early initiation of intravenous milrinone as both an adjunct to the best the medical therapy and to facilitate optimal dosing of standard oral therapy for heart failure. Patients with known systolic heart failure requiring hospital admission for a CHF exacerbation are randomly assigned within 48 hours of admission to receive a 48-hour infusion of either intravenous milrinone or placebo. The primary end point of this design is a reduction in the total hospital days for cardiovascular events within 60 days after therapy. Enrollment of 1000 patients began July 7, 1997, at 80 US centers and is projected to conclude in late 1999. (Am Heart J 2000;139:15-22.)
Exceptional Amyloid β Peptide Hydrolyzing Activity of Nonphysiological Immunoglobulin Variable Domain Scaffolds

Nucleophilic sites in the paired variable domains of the light and heavy chains (VL and VH domains) of Ig can catalyze peptide bond hydrolysis. Amyloid β (Aβ)-binding Igs are under consideration for immunotherapy of Alzheimer disease. We searched for Aβ-hydrolyzing human IgV domains (IgVs) in a library containing a majority of single chain Fv clones mimicking physiological VL-VH-combining sites and minority IgV populations with nonphysiological structures generated by cloning errors. Random screening and covalent selection of phage-displayed IgVs with an electrophilic Aβ analog identified rare IgVs that hydrolyzed Aβ mainly at His14-Gln15. Inhibition of IgV catalysis and irreversible binding by an electrophilic hapten suggested a nucleophilic catalytic mechanism. Structural analysis indicated that the catalytic IgVs are nonphysiological structures, a two domain heterodimeric VL (IgVL2-t) and single domain VL clones with aberrant polypeptide tags (IgVL-t′). The IgVs hydrolyzed Aβ at rates superior to naturally occurring Igs by 3-4 orders of magnitude. Forced pairing of the single domain VL with VH or VL domains resulted in reduced Aβ hydrolysis, suggesting catalysis by the unpaired VL domain.Angstrom level amino acid displacements evident in molecular models of the two domain and unpaired VL domain clones explain alterations of catalytic activity. In view of their superior catalytic activity, the VL domain IgVs may help attain clearance of medically important antigens more efficiently than natural Igs.
Vortex Breakdown over Unsteady Delta Wings and Its Control

One objective of this work is to provide information about the variation of swirl angle. The second objective is the control of leading-edge vortices. For this purpose, leading-edge vortices and vortex breakdown over a delta wing with variable sweep was investigated by flow vizualisation and laser Doppler velocimetry (LDV) measurements. Periodic variations of the sweep angle are used to control breakdown location for a pitching delta wing.