cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacogenetics: a possible pragmatic perspective in neoplasm predictability.

I N THE OTHER ARTICLES in this issue, little attention has been focused on the role of environmental factors in the etiology of cancer. Perhaps this is not surprising, given the nature of this issue and given that, in the geneticist’s traditional dichotomy, the environment is the antithesis of heredity. However, since it has been estimated that environmental agents may be responsible for 80% of human neoplasms,’ examination of the potential interface between the environment and inherited characteristics is in order. Although such mechanisms operant in man still await definitive characterization, it will become evident in this article that the metabolic potentiation of chemical carcinogens represents one of the best-understood phenomena operating at the gene-environment interface in mammals. Whereas the term “pharmacogenetics” usually brings to mind well-established disorders having as their basis recognized protein polymorphisms or discrete mutations, we have come to learn in recent years, largely through the efforts of Vesell,’ Evans,3s4 Motulsky,5 and others, that a great deal of the interindividual variation in drug metabolism in man is under genetic control. Population studies suggest that these differences in drug metabolism are often multifactorial, and thus in all likelihood polygenic. One of the major drug-metabolizing enzyme systems, the microsomal cytochrome P-4.50-dependent monooxygenases, is responsible for the metabolism of a great variety of hydrophobic substances,6-10 including many environmental carcinogens. We shall begin this article by examining the role of this system in the metabolism of certain chemical carcinogens and other xenobiotics; evidence is presented that such biotransformations, while facilitating excretion, may simultaneously potentiate carcinogenicity and toxicity. We shall then consider the genetic regulation of cytochrome P-450 induction by carcinogens and related compounds. Lastly, evidence will be presented that heritable
Capsule Commentary on Warner et al., Faculty Promotion and Attrition: the Importance of Coauthor Network Reach at an Academic Medical Center

U nderrepresented Minorities in Medicine (URMM) (consisting of Blacks, Latinos and Native Americans) continue to be poorly represented in medical faculties across the USA. While the cause of this is multifactorial, Dr. Warner and colleagues examine one aspect of faculty promotion and attrition at Harvard Medical School, coauthor network reach. For 4 years they studied coauthor network reach and then compared URMM faculty to White faculty to determine differences. Men and Whites were found to have significantly larger coauthor networks when compared to women and URMM faculty members. They also found a positive correlation between network reach and promotion, as well as retention. These findings at HMS reflect what URMM faculty have experienced for decades—a lack of mentoring and isolation. Research on URMM faculty suggests that many disparities including racism, isolation, lack of mentorship, clinical disparities, diversity efforts disparities and promotion disparities negatively affect URMM faculty and are significant barriers to increasing URMM faculty presence. Among the solutions suggested to improve URMM representation is improving URMMnetworking opportunities. Dr.Warner and colleagues are to be commended for quantifying this phenomenon. Providing solid evidence and statistics, her team has made it clear that improving network reach is one solution to the problem of URMM attrition from medical faculties. The study also begs the question of why do women and minorities have smaller networks? Is there a reason that URMM faculty have less network reach or is it an artifact of their low representation? And when URMM faculty have similar network reach as their non-URMM colleagues, will we see any alleviation in the promotion disparity? Dr. Warner and colleagues' work gives us at least one answer to this problem. Collaboration with URMM faculty is to be increased if we are to sustain the current representation of URMM faculty at medical schools in the US. Without it, there is not hope for population parity or even progress toward that goal.
Undamped longitudinal plasma waves

Abstract We have derived necessary and sufficient conditions for the existence of undamped nonlinear plasma waves in one dimension. The analysis establishes the existence of exact nonlinear plasma waves which are predicted to Landau damp according to the standard linear theory, but which in fact do not damp.
Patriarchal designs: The genetic engineering of human embryos

Abstract This paper describes medical research pertaining to the future potential for genetic engineering of human embryos, and considers some of the consequences that this technology may have for women's lives. It points to both the religious right and the medical profession as groups that could potentially benefit from human genetic engineering and emphasizes the need for feminists to monitor and respond to emerging reproductive technologies.
Remote Exosites of the Catalytic Domain of Matrix Metalloproteinase-12 Enhance Elastin Degradation

How does matrix metalloproteinase-12 (MMP-12 or metalloelastase) degrade elastin with high specific activity? Nuclear magnetic resonance suggested soluble elastin covers surfaces of MMP-12 far from its active site. Two of these surfaces have been found, by mutagenesis guided by the BINDSIght approach, to affect degradation and affinity for elastin substrates but not a small peptide substrate. Main exosite 1 has been extended to Asp124 that binds calcium. Novel exosite 2 comprises residues from the II-III loop and β-strand I near the back of the catalytic domain. The high degree of exposure of these distal exosites may make them accessible to elastin made more flexible by partial hydrolysis. Importantly, the combination of one lesion each at exosites 1 and 2 and the active site decreased the catalytic competence toward soluble elastin by 13-18-fold to the level of MMP-3, homologue and poor elastase. Double-mutant cycle analysis of conservative mutations of Met156 (exosite 2) and either Asp124 (exosite 1) or Ile180 (active site) showed they had additive effects. Compared to polar substitutions observed in other MMPs, Met156 enhanced affinity and Ile180 the k(cat) for soluble elastin. Both residues detracted from the higher folding stability with polar mutations. This resembles the trend in enzymes of an inverse relationship between folding stability and activity. Restoring Asp124 from combination mutants enhanced the k(cat) for soluble elastin. In elastin degradation, exosites 1 and 2 contributed in a manner independent of each other and Ile180 at the active site, but with partial coupling to Ala182 near the active site. The concept of weak, separated interactions coalescing somewhat independently can be extended to this proteolytic digestion of a protein from fibrils.
Kinetics of the C3H7O2 + NO Reaction: Temperature Dependence of the Overall Rate Constant and the i-C3H7ONO2 Branching Channel

The temperature dependence of the overall rate constant for the C3H7O2 + NO reaction and the rate constant for the minor branching channel resulting in the production of i-C3H7ONO2 have been measur...
Chemical classification of iron meteorites—X. Multielement studies of 43 irons, resolution of group IIIE from IIIAB, and evaluation of Cu as a taxonomic parameter

Abstract We report structural and compositional data leading to the classification of 41 iron meteorites, increasing the number of classified independent iron meteorites to 576. We also obtained data on a new metal-rich mesosiderite and on two new iron masses that are paired with previously studied irons. For the first time in this series we also report concentrations of Cr, Co, Cu, As, Sb, W, Re and Au in each of these 44 meteorites. We determined 7 of these elements (all except Sb) in 30 previously studied ungrouped or unusual irons, and obtained Cu data on 104 irons, 21 pallasites, and 3 meteorite phases previously studied by E. Scott. We show that Cu possesses characteristics well suited to a taxonomic element: a siderophile nature, a large range among all irons, and a low range within magmatic groups. For the first time we report the partial resolution of the C-rich group IIIE from its populous twin group IIIAB on element-Ni diagrams other than Ir-Ni. Cachiyuyal previously classified ungrouped and Armanty (Xinjiang) previously classified IIIAB are reclassified IIIE. Despite the addition of 3 new irons and the reanalysis of 3 previously studied irons the members of the set of 15 ungrouped irons having very low Ga ( 100 ≤ Ni ≤ 180 mg/g and compositional similarities to IIICD, but A80104 increases the Garden Head trio to a quartet. Algoma is reclassified from ungrouped to IIICD-an and Hassi-Jekna and Magnesia from IIICD to IIICD-an. The metal of Horse Creek and Mount Egerton is compositionally closely related to metal from EH chondrites. We suggest that the P-rich Bellsbank trio irons formed in the IIAB core in topographic lows filled with an immiscible, P-rich second liquid.
Parental Protest, Public Opinion, and War Termination: Israel's ‘Four Mothers’ Movement

Peace movements that challenge national security policies typically remain politically marginal. However, the unusual cases that evince causal linkages among grass-roots activism, public opinion shifts, and a government's decision to change policy suggest hypotheses about the sorts of organizational characteristics and political conditions that can increase movements' prospects for influence. This article considers the case of Israel's Four Mothers – Leaving Lebanon in Peace that in the late 1990s successfully sought to end Israel's war in southern Lebanon. The article adopts a political-mediation model of peace movement outcomes that draws on Giugni's (2004) model of movements' policy impact. It finds support for the idea that when grass-roots activists and their elite supporters among politicians and the media act jointly, they can exert influence on policy outcomes. Anti-war movements led by soldiers' family members may have particularly abilities to shift public opinion against the war so as to create...
Evaluation of lumbar sympathectomy

Abstract Lumbar sympathectomy is a valuable palliative procedure in the treatment of selected cases of peripheral vascular disease. Clinical evaluation, plus objective and subjective response to lumbar sympathetic block, is helpful in selecting patients who will probably be helped by lumbar sympathectomy. Patients may have improvement of symptoms following lumbar sympathectomy but recurrence may occur later as the arteriosclerotic disease progresses. The results in a series of 138 sympathectomies in 100 patients are reported.
ARNT-deficient mice and placental differentiation.

We used homologous recombination in embryonic stem cells to generate mice heterozygous for an aryl hydrocarbon nuclear translocator (ARNT) null mutation. These mice were intercrossed, but no live homozygousArnt−/− knockout mice were produced among 64 newborns. Homozygotes diein uterobetween 9.5 and 10.5 days of gestation. Abnormalities included neural tube closure defects, forebrain hypoplasia, delayed rotation of the embryo, placental hemorrhaging, and visceral arch abnormalities. However, the primary cause of lethality appears to be failure of the embryonic component of the placenta to vascularize and form the labyrinthine spongiotrophoblast. This may be related to ARNT's known role in hypoxic induction of angiogenesis. We found no defects in yolk sac circulation.
The replacement principle and tree structured preferences

Abstract In this note I answer a question posed by William Thomson in a recent survey paper. That paper considers the application of a principle, called welfare domination under replacement , to the problem of choosing the level of a public good from an interval when agents preferences are single peaked over that interval. In this paper I consider the generalization to the case when agents preferences are defined over the points of a tree as is the level of the public good.
The strange and critical intersection of hepatitis C and lipoprotein metabolism: "C-zing" the oil.

Since its discovery in 1989, a substantial amount of research has emerged regarding the close association of hepatitis C virus (HCV) replication and hepatic lipoprotein metabolism. Even before the identification of the HCV virus, a link to fat metabolism was suspected based on clinical observations regarding steatosis as a common feature of what used to be known as “non-A, non-B hepatitis.”1 This relationship was later extended in studies that revealed that HCV-infected patients with steatosis often lack common risk factors for fatty liver, such as obesity.2 These early observations, along with subsequent studies that identified circulating viral particles in low-density, more-buoyant plasma fractions (partitioned with plasma centrifugation in sucrose or iodixanol gradients), fueled a now extensive and growing body of literature on this key aspect of HCV replication.3 Investigations performed over the past 23 years have defined replicative pathways of HCV involving mechanisms and biochemical pathways right out of the “play book” of fatty liver disease (FLD).
Selective isolation and culture of a proliferating epithelial cell population from the hamster trachea.

A reliable cell isolation technique was developed to allow the cultivation of cells from the hamster respiratory tract. Repeated thermolysin treatments and gradient centrifugation yielded a cell culture completely free from contamination by fibroblasts. Viable cells could be isolated from as little tissue as a single hamster trachea, but in vitro proliferation occurred only if the hamster was less than 4 months of age. The cultured cells could be repeatedly passaged and subcultured for weeks by employing normal tissue culture techniques. Morphologically, the monolayers appeared to be a homogeneous population of epithelial cells, and successful cloning of freshly isolated single cells resulted in apparently identical cultures. The epithelial origin of these cells was also suggested by continued growth in minimum essential medium withd-valine substituted forl-valine. The relative ease with which this cell type can be isolated, cultured, and manipulated in vitro should encourage its application as a model of the respiratory epithelium.
Within-Year Retention among Ph.D. Students: The Effect of Debt, Assistantships, and Fellowships.

This study employs the 2007–2008 National Postsecondary Student Aid Study and the National Research Center’s survey data, “A Data-Based Assessment of Research-Doctorate Programs in the United States,” to investigate the (1) the effects of debt in relation to tuition and fees paid and (2) the effects of teaching assistantships, research assistantships, and fellowships on within year retention among Ph.D. students. We created an innovative conceptual model for this study by merging a socioeconomic model for graduate students and a graduate student socialization model. We used propensity score weights for estimating average treatment effects and average treatment effect on the treated as well as a series of control and balancing variables. This study provides timely insights into which of these financial strategies are likely to improve the already low doctoral retention rates nationwide. To the best of our knowledge, this is the first study that includes proxies of socialization variables in examining the role of various funding mechanisms in doctoral retention using a national representative dataset.
Effects of Solutes on Optical Properties of Biological Materials: Models, Cells, and Tissues

Abstract Perturbations of scattering background for absorbance measurements by photon diffusion techniques complicate algorithms used for determining the concentration of blood and the saturation of hemoglobin in tissues. In order to better define these perturbations, we have undertaken a study of the effect of solutes, some of physiological importance, upon the scattering of three types of model systems: a lipid vessel suspension (Intralipid), a cell suspension (Baker′s yeast), and a tissue (perfused liver). A simple formula relates absorbancy change to proportional changes of the input/output separation ρ and the square root of μa and μ′s in relation to a relevant model system. Thus, absorbance changes at 850 nm and slopes and intercepts are measured as a function of ρ; the absorption and reduced scattering coefficient, μa and μ′s, are calculated. We studied each of these cases as a function of the perturbation induced by low-molecular-weight polyhydroxy solutes, generally sugars (mannitol, fructose, sucrose, and glucose), alcohols (propanediol and methanol), and electrolytes (sodium and potassium chloride). Dilatometric studies indicate volume changes of the solvent system and afford correction factors. The slopes are ∼−1 ± 0.5 × 10−4 OD/mM solute per centimeter separation of input/output per percent scatter (yeast or Intralipid) and indicate possible physiological detection of solutes in tissues in the millimolar range. The large optical effects of temperature upon the solute effect on model systems and of osmotic and perfusion pressures on the perfused liver further complicate the possibility of quantitative in vivo studies of these solutes.
The effect of the narcotic antagonists naloxone, naltrexone and nalorphine on spinal cord c-fiber reflexes evoked by electrical stimulation or radiant heat☆

C-fiber reflexes were recorded from an S1 ventral root in the acute decrebrate low spinal cat following stimulation of the ipsilateral superficial peroneal nerve or application of radiant heat to the metacarpel footpad. Naloxone when administered i.v. increased the electrically evoked C-fiber reflex to 158% (±23.8% S.E.M.) of control 10 min after administration; whereas, naltrexone, 0.0025 mg/kg, increased the C-fiber reflex to 206 ± 26.1% (S.E.M.) of control. Naloxone in a dose of 0.050 mg/kg increased the radiant heat evoked ventral root reflex to 161 ± 19.5% of control. Nalorphine, 1 mg/kg, facilitated the electrically evoked C-fiber reflex to f282 ± 75% of control. These finding that naloxone and naltrexone facilitated these reflexes in doses too small to have non-specific excitatory effects and that nalorphine facilitated the C-fiber reflex at a dose level that is depressant to the flexor reflex in the chronic spinal dog are consistent with a hypothesis that these are due to antagonism of a naturally occuring opiate-like inhibitory substance.
Temporal and spatial variations of marine aerosols over the Atlantic Ocean

Abstract Aerosol samples, collected daily were analyzed with electron microscopy for particle concentration and size distribution. The chemical compositions of individual particles were determined with X-ray energy spectrometry and specific morphological tests. The results demonstrated clear and significant dependencies of aerosol properties on air trajectories computed from a backtrack model. Air parcels, such as American air pollution and Sahara dust, were identified. Their physical mixing and chemical reactions with marine aerosols as well as aerosol wet deposition are discussed.
Relationship of study approach and exam performance

Abstract This study considers the relationship between study approach and examination performance. The data show a significant relationship between performance on complex examination questions and the use of a deep study approach, ceteris paribus. No significant relationships occur between the use of a deep study approach and performance on questions that are less complex or between the use of a surface study approach and any examination results. The findings also show that prior academic achievement, as indicated by cumulative GPA, and motivation for taking the course, as indicated by students’ plans to seek an accounting job, are the best predictors of examination performance. These findings imply that accounting educators should encourage students to develop and use a deep study approach to become more proficient with complex material. Examples of how this may be done are provided.
Fever of unknown origin (FUO) attributable to indolent lymphoproliferative disorder due to a plasmacytoma expressing immunoglobulin A.

Abstract Background The most common categories causing fevers of unknown origin (FUOs) include infective rheumatic/inflammatory disorders and malignancies. Among neoplastic causes of FUOs, lymphomas, hepatomas, renal hypo-nephromas, and hepatomas are the most common. Other malignancies rarely present with FUOs (eg, multiple myeloma). Case Report We describe a 58-year-old man who presented with an FUO accompanied by night sweats, weight loss, and a groin mass. A biopsy of the groin mass (ie, his lymph node) was negative for infectious diseases, rheumatic or inflammatory diseases, and malignancies. Histochemical and immunological studies of the lymph node showed it to contain a plasmacytoma expressing immunoglobulin A (IgA). An immunohistochemical study of the plasma-cell infiltrate demonstrated strong CD138 staining. A bone marrow biopsy was negative for multiple myeloma. Conclusion We believe this is the first reported rare case of an indolent, lymphoproliferative disorder attributable to an IgA-secreting plasmacytoma presenting as an FUO.
Histochemical demonstration of acid mucopolysaccharides in human gingival epithelial intercellular spaces.

Abstract Specimens of human gingival tissue were obtained at biopsy, fixed, embedded and sectioned by both conventional means and freeze-dry techniques. Tissue sections were stained with Hale's iron absorption, toluidine blue at pH 6.0 and 2.5 and periodic acid-Schiff (PAS) techniques. Control sections were incubated with testicular and bacterial hyaluronidase, chondroitinase and α-amylase. Results indicate that gingival epithelium contains intercellular acid mucopolysaccharides. The moiety of the intercellular cementing substances not removable by known polysaccharases could be chondroitin sulphate B and/or unknown tissue component(s) giving characteristic mucopolysaccharide staining reactions. In vivo, in periodontitis, there is disaggregation of the intercellular mucopolysaccharides, presumably due to the action of as yet unidentified bacterial enzymes. Depolymerization of the intercellular substance of the epithelium is a possibility as the first step in the pathogenesis of periodontal disease.
The Cepheids of Population II and Related Stars

The Type II Cepheids include most intrinsic variables with periods between 1 and about 50 days, except for the classical Cepheids and the shortest semiregular variables of type M. The Type II Cepheids may be divided in groups by period, such that the stars with periods beween 1 and 5 days (BL Her class), 10-20 days (W Vir class), and greater than 20 days (RV Tau class) have differing evolutionary histories. The chemical composition of Type II Cepheids reflects the material they were made from as modified by their internal nuclear evolution and mixing. Finally, RV Tau stars are affected by mass loss by dust and species attached to the dust. The populations to which the various classes of Type II Cepheids are assigned constitute important clues to the origin and evolution of the halo of our Galaxy and the dwarf spheroidal systems from which at least part of the halo seems to have been accreted.
The patterning of retinal horizontal cells: normalizing the regularity index enhances the detection of genomic linkage.

Retinal neurons are often arranged as non-random distributions called “mosaics”, as their somata minimize proximity to neighboring cells of the same type. The horizontal cells serve as an example of such a mosaic, but little is known about the developmental mechanisms that underlie their patterning. To identify genes involved in this process, we have used three different spatial statistics to assess the patterning of the horizontal cell mosaic across a panel of genetically distinct recombinant inbred strains. To avoid the confounding effect cell density, which varies two-fold across these different strains, we computed the “real/random regularity ratio”, expressing the regularity of a mosaic relative to a randomly distributed simulation of similarly sized cells. To test whether this latter statistic better reflects the variation in biological processes that contribute to horizontal cell spacing, we subsequently compared the genetic linkage for each of these two traits, the regularity index and the real/random regularity ratio, each computed from the distribution of nearest neighbor (NN) distances and from the Voronoi domain (VD) areas. Finally, we compared each of these analyses with another index of patterning, the packing factor. Variation in the regularity indexes, as well as their real/random regularity ratios, and the packing factor, mapped quantitative trait loci (QTL) to the distal ends of Chromosomes 1 and 14. For the NN and VD analyses, we found that the degree of linkage was greater when using the real/random regularity ratio rather than the respective regularity index. Using informatic resources, we narrow the list of prospective genes positioned at these two intervals to a small collection of six genes that warrant further investigation to determine their potential role in shaping the patterning of the horizontal cell mosaic.
Puberty questions asked by early adolescents: What do they want to know?

Objective: We undertook the following study to document questions asked by early adolescents regarding pubertal development. Methods: As part of a health education program, 159 sixth-grade students (mean = 12.1 years) were surveyed to obtain their questions about puberty and their self-assessed pubertal stage. Questions were coded for content and gender specificity. Results: Of 159 initial subjects, 111 generated a total of 200 questions. A majority of the questions reflected biological topics (88%), such as genital physiology (26%) and sexuality and reproduction (26%). Only 6% addressed psychosocial questions. Both females and Asians (compared with other ethnic or racial groups) expressed greater interest in the differences between male and female development ( P P P Conclusions: We found that biological questions concerning puberty predominated over psychosocial topics, and that the gender, race or ethnicity, and stage of development determined the kinds of questions that early adolescents have about pubertal development. Health educators and clinicians may need to focus on physiologic areas to provide more meaningful information about development to early adolescents.
Variables Influencing Extraction of Nucleic Acids from Microbial Plankton (Viruses, Bacteria, and Protists) Collected on Nanoporous Aluminum Oxide Filters

Anodic aluminum oxide (AAO) filters have high porosity and can be manufactured with a pore size that is small enough to quantitatively capture viruses. These properties make the filters potentially useful for harvesting total microbial communities from water samples for molecular analyses, but their performance for nucleic acid extraction has not been systematically or quantitatively evaluated. In this study, we characterized the flux of water through commercially produced nanoporous (0.02 μm) AAO filters (Anotop; Whatman) and used isolates (a virus, a bacterium, and a protist) and natural seawater samples to test variables that we expected would influence the efficiency with which nucleic acids are recovered from the filters. Extraction chemistry had a significant effect on DNA yield, and back flushing the filters during extraction was found to improve yields of high-molecular-weight DNA. Using the back-flush protocol, the mass of DNA recovered from microorganisms collected on AAO filters was ≥100% of that extracted from pellets of cells and viruses and 94% ± 9% of that obtained by direct extraction of a liquid bacterial culture. The latter is a minimum estimate of the relative recovery of microbial DNA, since liquid cultures include dissolved nucleic acids that are retained inefficiently by the filter. In conclusion, we demonstrate that nucleic acids can be extracted from microorganisms on AAO filters with an efficiency similar to that achievable by direct extraction of microbes in suspension or in pellets. These filters are therefore a convenient means by which to harvest total microbial communities from multiple aqueous samples in parallel for subsequent molecular analyses.
Three‐photon excitation fluorescence imaging of biological specimens using an all‐solid‐state laser

We demonstrate that three-photon excitation images of both fixed and living biological specimens can be readily obtained using an all-solid-state Nd:YLF laser excitation source. Optically sectioned images of fixed Caenorhabditis elegans embryos stained with DAPI and embryos triple-labeled with DAPI, fluorescein and Texas Red are presented. Time series images of a living LLC-PK cell stained with Hoechst 33342 during the progression from metaphase to telophase are also presented. The mode of excitation was inferred from the power-law of anthracene and Hoechst 33342 fluorescence versus incident laser power and an axial resolution comparison of anthracene fluorescence with two-photon excited Calcium Crimson fluorescence. Multiphoton excitation imaging is an attractive method for optically sectioning live specimens because of the lower levels of phototoxicity produced compared to other optical sectioning techniques. The combination of two- and three-photon excitation extends the capabilities of a multiple- photon imaging system since a single wavelength can provide localized excitation of a wide variety of fluorophores whose collective emission spectra can span the entire visible spectrum.
LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA: EXTENSION OF INDICATIONS BASED ON MOLECULAR MARKERS

Background/Aims Liver transplantation usually cures hepatocellular carcinoma when the Milan selection criteria are applied, whereas there is substantial risk of posttransplant recurrence with tumors beyond these criteria. This study uses molecular data to identify a subgroup of patients who, despite having hepatocellular carcinoma beyond Milan criteria, have favorable outcomes. Methods Allelic imbalance of 18 microsatellites was analyzed in 70 consecutive patients (35 within Milan, 35 beyond Milan criteria) transplanted for hepatocellular carcinoma of whom 24 had recurrence and 46 survived at least 5 years recurrence-free. Fractional allelic imbalance (the fraction of significant microsatellites that demonstrated allelic imbalance) and relevant clinical/pathological variables were tested for correlation with time to recurrence. Results Allelic imbalance in 9/18 microsatellites correlated with recurrence. Fractional allelic imbalance >0.27 and macrovascular invasion were independent predictors of recurrence in patients with tumors beyond Milan criteria; the probability of recurrence at 5 years was 85% with fractional allelic imbalance ⩾0.27 vs. 10% when p =0.0002). An algorithm including Milan criteria and fractional allelic imbalance status is 89% accurate in predicting tumor recurrence after transplantation. Conclusion Analysis of allelic imbalance of 9 microsatellites identifies a subgroup of patients who, despite having hepatocellular carcinoma beyond Milan criteria, have a low risk of posttransplant recurrence.
Abstract 2055: p21CIP1 mediates reciprocal switching between invasion and proliferation during metastasis

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Cell proliferation and invasion are critical for malignant progression, yet how these processes relate to each other and whether they regulate one another during metastasis is unknown. We show that invasiveness of breast cancer cells is associated with growth arrest due to p21CIP1 upregulation. Knockdown of p21CIP1 increases proliferation and suppresses invasion. Since p21CIP1 acts to inhibit Cyclin E during cell cycle progression, we demonstrated that a constitutively active form of Cyclin E had similar effects to p21CIP1 inhibition resulting in increased proliferation and suppressed invasion. We tested these findings in vivo in the Polyoma middle T mammary tumor model in which p21CIP1 was deleted. p21CIP1 knockout mice exhibited dramatic suppression of metastasis, independent of tumor growth. Metastasis suppression was associated with striking cytoskeletal reorganization leading to a shift from stress fibers to cortical actin, tightening of cell junctions, and cytokeratin upregulation. Thus, P21CIP1 regulates metastasis by mediating dynamic switching between invasion and proliferation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2055. doi:1538-7445.AM2012-2055
Neutralizing antibody to Herpes simplex virus type 1 in patients with oral cancer

Neutralizing antibody to Herpes simplex virus type 1 (HSV-1), type 2, and measles virus was measured in the serum of patients with oral cancer, patients with oral leukoplakia, and in control subjects who were smokers and nonsmokers. Significantly higher titers to HSV-1 were found in controls who smoked than in controls who did not smoke. Patients with untreated oral cancer had HSV-1 neutralizing titers similar to those of the controls who smoked, but those with later stage tumors had higher titers than those with earlier stage tumors. In patients who were tumor free after treatment for oral cancer, higher antibody titers to HSV-1 were associated with longer survival times. No association was found between clinical status and antibody to measles virus. The data are consistent with a role for both HSV-1 and smoking in the pathogenesis of oral cancer.
Assessing temperature‐based PET equations under a changing climate in temperate, deciduous forests

Despite the availability of numerous approaches to estimate potential evapotranspiration (PET), temperature-based PET equations such as the Hamon equation and Thornthwaite equation are still used to predict changes in hydrology in a changing climate as temperature is one of the primary reported outputs from general circulation models. To isolate the actual dependence of PET on temperature, we analysed meteorological and energy balance measurements from five AmeriFlux deciduous forest sites in the eastern United States during periods with minimal soil moisture control on transpiration. For all five sites, when PET measurements with similar net radiation are grouped, temperature does not correlate to PET within each group. Conversely when PET measurements with similar temperature are grouped, net radiation strongly correlates to PET within each group. In terms of assessing standard PET models, when dormant and growing season PET are separated, we found that the Priestley–Taylor equation (a model primarily dependent on net radiation) consistently explained more of the variation in PET than temperature-based methods such as the Hamon equation (median R2 of 0·88 vs 0·66). We illustrate that the moderate ability of temperature-based equations to predict PET arises from the correlation between temperature and net radiation when the meteorological observations are averaged over at least several days. However, we suggest that because temperature is not the fundamental driver of PET and because the relationship between temperature and net radiation underlying temperature-based equations will shift with climate change, temperature-based equations in their current state will likely exaggerate PET in a changing climate. Copyright © 2010 John Wiley & Sons, Ltd.
A method for assessing alternative effects functions that uses simulation with EMDEX data.

A method for evaluating a variety of alternative biologically plausible effects functions through the use of simulation studies conducted on personal-monitor exposure data is described. Using magnetic field time series collected with EMDEX instruments, we demonstrate how the method can be used to explore (1) how the outputs from various effects functions simulations compare to the results obtained by assuming that effects are proportional to time average field strength; (2) how the results of epidemiological studies might be used to assess the relative likelihood that each of the alternative effects functions describes biological reality; and (3) how the results might be used to assess possible health risks. Although the available data are sufficient to demonstrate the general method, they are not yet sufficient to support actual discrimination among possible alternatives. The arguments on the use of the method are for illustrative purposes only. © 1995 Wiley-Liss, Inc.
Atom-economical reduction of carbon monoxide to methanol catalyzed by soluble transition metal complexes at low temperatures

Hydrocarbons and methanol are considered the preferred products of catalytic reduction of carbon monoxide derived from clean natural gas. In this paper, we focus on atom-economical synthesis of methanol catalyzed by soluble transition metal complexes as single-site catalyst precursors under mild reaction conditions. Of the metal systems reported in the literature, Ni complexes activated by alkoxide bases affected homogeneous CO reduction to methanol at low temperatures (80°–130 °C) and low pressures (2000–5000 kPa) to achieve CO conversion and methanol selectivity of >90 and >95, respectively. The involvement of mono- and multi- nuclear Ni species that readily interconvert under methanol producing conditions is invoked. A process based on such an active catalyst system would position methanol to be considered an inexpensive feedstock for the synthesis of other derivatives.
Thalamic Relay of Spontaneous Retinal Activity Prior to Vision

Before vision, retinal ganglion cells produce spontaneous waves of action potentials. A crucial question is whether this spontaneous activity is transmitted to lateral geniculate nucleus (LGN) neurons. Using a novel in vitro preparation, we report that LGN neurons receive periodic barrages of postsynaptic currents from the retina that drive them to fire bursts of action potentials. Groups of LGN neurons are highly correlated in their firing. Experiments in wild-type and NMDAR1 knockout mice show that NMDA receptor activation is not necessary for firing. The transmission of the highly correlated retinal activity to the LGN supports the hypothesis that retinal waves drive retinogeniculate synaptic remodeling. Because LGN neurons are driven to fire action potentials, this spontaneous activity could also act more centrally to influence synaptic modification within the developing visual cortex.
Effect of calcium channel blockers on proteoglycan synthesis by vascular smooth muscle cells and low density lipoprotein--proteoglycan interaction.

Abstract Calcium channel blockers are known to retard atherosclerosis. In this study, we tested the hypothesis that one mechanism by which calcium channel blockers retard atherosclerosis is through the modulation of proteoglycan metabolism by vascular smooth muscle cells. We investigated the effect of amlodipine and nifedipine on proteoglycan synthesis by human aortic smooth muscle cells and the ability of the newly synthesized proteoglycans to bind low density lipoprotein (LDL). Confluent smooth muscle cells were incubated with [ 35 S]sulfate alone or [ 35 S]sulfate and [ 3 H]leucine in the presence and absence of different concentrations of amlodipine and nifedipine (0.1–20 μg/ml) for 24 h, and newly synthesized proteoglycans were analyzed. Both amlodipine and nifedipine inhibited proteoglycan synthesis by smooth muscle cells in a dose-dependent manner; however, amlodipine was significantly more potent than nifedipine in this regard. In the presence of 20 μg/ml amlodipine, media and cellular proteoglycans decreased by 56%. This was due to inhibition of de novo proteoglycan synthesis by amlodipine. Compared with the proteoglycans synthesized by control smooth muscle cells, those synthesized by cells exposed to amlodipine were smaller and less sulfated, and contained fewer glycosaminoglycan chains. In addition, proteoglycans synthesized by cells treated with amlodipine bound LDL with low affinity. These results suggest that amlodipine may protect against atherosclerosis through a proteoglycan-mediated mechanism.
Sperm exposure and development of preeclampsia.

Abstract Objective: Length of sperm exposure has been proposed to influence the risk of preeclampsia. The main objective was to determine the relationship between extent of exposure to sperm, both before and during pregnancy, and the risk of preeclampsia. Study Design: A case-control design was used where women with preeclampsia (cases) were matched with two women without preeclampsia (controls) by age and parity. Data were analyzed by Student t test, χ 2 test, and logistic regression analysis. Results: A total of 113 cases were compared with 226 controls. Women with a short period of cohabitation ( P =.004). Conclusion: Fewer than 4 months of cohabitation among users of barrier methods for contraception is associated with a significantly increased risk for preeclampsia. (Am J Obstet Gynecol 2003;188:1241-3.)
Attenuation of the effects of ethanol on social behavior by alpha2-adrenoceptor antagonists

In a social behavior test in mice ethanol (2 g/kg) significantly reduces the time spent in social interaction and increases locomotor activity. The relatively selective alpha2-adrenoceptor antagonists atipamezole and idazoxan alone have no significant effect on either social interaction or locomotor activity in this test. However, when coadministered with 2 g/kg ethanol, atipamezole (0.3–3.0 mg/kg) significantly attenuated the ethanol-induced reduction in the time spent in social interaction without any effect on ethanol's locomotor stimulant action. Idazoxan (0.3–1.0 mg/kg) also showed a trend towards reversing the reduction in the time spent in social interaction although this was accompanied by a significant attenuation of the locomotor stimulant effect of ethanol. The results indicate that alpha2-adrenoceptors may modulate ethanol's effects on social interaction in mice.
Magnetic and electrical properties of rhodium(III)oxide(III)

Abstract Rh2O3(III) crystallizes with an orthorhombic corundum-related structure and is Pauli paramagnetic. Its electrical behavior is characterized by a small activation energy, and the Seebeck coefficient indicates p-type conduction. This oxide may be considered as a semimetal, and its properties are discussed in terms of face and edge sharing of RhO6 octahedra.
An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle

This paper describes an ultra-compliant parylene-platinum neural probe embedded in a biodissolvable delivery vehicle. High probe compliance is achieved using thin wires (width of 10.0 μm and thickness of 2.7 μm) and by meandering the probe. The insertion of the ultra-compliant probe is achieved by encasing it in a dissolvable delivery vehicle made from molded carboxy-methylcellulose. In vivo implantations of delivery vehicles with 1.5 mm long shanks, widths of 100 μm and 300 μm and a targeted thickness of 135 μm have been done through the dura in the cortex of Sprague-Dawley rats at a speed of 80 mm-s−1. The delivery vehicle becomes a gel over a period of less than three minutes, after which the handling portions of the delivery vehicle are removed leaving the shanks embedded in the brain.
Science, Progress and Pluralism in the Study of International Relations

The article looks at one of the central arguments of Patrick Jackson’s book The Conduct of Enquiry in International Relations: the attempt to advance methodological pluralism and dialogue among contending metatheoretical schools of International Relations. The article supports the goal of pluralism but argues that there is a significant gap in Jackson’s support of it and that his version of pluralism inhibits metatheoretical engagement of different schools of thought. The latter in turn limits the possibility of progress in the field. The article outlines the missing steps in Jackson’s argument, the way in which he unduly limits the contribution that the philosophy of science can make to scientific progress and an alternative argument for pluralism that leaves a role for genuine philosophical engagement and the possibility of progress in IR.
(±)‐(cis‐8a‐Hydr­oxy‐2‐oxoperhydro­naphthalen‐4a‐yl)propane­nitrile: hydrogen bonding in a Robinson‐annulation inter­mediate

The title racemate, C13H19NO2, is a pre-dehydration inter­mediate isolated from the base-catalysed Robinson annulation of (+/−)-2-(2-cyano­ethyl)cyclo­hexa­none. Centrosymmetric dimers are formed by reciprocal hydroxyl-to-ketone hydrogen bonding [O⋯O = 2.7902 (13) A and O—H⋯O = 176°]. One inter­molecular C—H⋯O close contact is found to the hydroxyl group.
An improved distal extension removable partial denture base

Abstract A technique for combining the advantages of an impression of the teeth made in an elastic impression material with those of a functional wax impression of the soft tissues has been described.
Column chromatographic analysis of tryptophan with the basic amino acids.

Abstract A simple and direct column chromatographic system has been described for the determination of tryptophan, the basic amino acids, and tyrosine and phenylalanine. The new system employs only one buffer (pH 5.30) and temperature (55°C). Application to the analysis of plasma deproteinized with trichloroacetic acid was tested, and the results obtained were similar to those of previous methods that require a separate assay for tryptophan.
Comparing child health, access to care, and utilization of health services between Ohio Appalachia's River and non-river bordering counties.

Appalachia’s River and non-River Bordering Counties. Children living in Ohio’s Appalachian counties that border the Ohio River are disproportionally exposed to adverse environmental conditions prevalent along the river that may contribute to disparities in health, access to care and care utilization. This study examined if there were differences in health, access to care and care utilization between Ohio’s Appalachian children living in counties that border the Ohio River and those living in counties that do not border the river. A secondary analysis of the 28 Appalachian counties from Ohio’s 88 counties included in the 2008 Ohio Family Health Survey was conducted using a Bayesian Hierarchical Modeling strategy. Descriptive analyses comparing geographic groups across demographic, health, access, utilization, and health insurance also were conducted. Childhood asthma was more prevalent in the river-bordering counties (16.4%) compared to the non-river counties (9.4%). Children with asthma had more sere symptoms in the river bordering counties (8.2%) compared to the non-river bordering counties (4.4%). Children residing in river bordering counties had higher rates of obesity (24.4%) and overweight (17%). After controlling for child health and insurance status, children living in the river bordering counties had less access to care (est. −7.14, CI = −17.3,0.74) and more difficulty accessing specialty care. Children residing in the non-river counties had more sickness care utilization (est. 0.25, CI = 0.01, 0.49). Regardless of region, children with a regular health care provider and place for care were healthier. Differences in child health, access to care and utilization of services exist within Ohio’s Appalachian region.
From connective particle to sentence-final particle: a usage-based analysis of shi ‘and’ in Japanese

Abstract Based on written and spoken corpora, this paper examines the on-going functional shift of the Japanese connective shi ‘and, and so’ into a sentence-final particle. The paper will first identify and clarify the functions of this newly emerging usage. As a sentence-final particle, shi indicates the speaker’s emotional stance (that is often negative) toward the proposition, context, or the addressee. We then propose that the reanalysis of shi from a coordinate conjunction to a sentence-final particle is an instance of ‘subjectification’ and ‘intersubjectification’ ( Traugott, 2003 ). We also argue that the change is motivated by the frequency of the specific structural and communicative context of its use.