cssi/SciSciGPT-SciSciNet huggingface dataset:
Somatic cell genetics approach to dissecting mammalian DNA repair

This review article examines the application of the methods and concepts of somatic cell genetics to the study of DNA repair. The first steps of this approach involve classical procedures of mutant isolation, complementation analysis, and mapping of genes using hybrid cells. Subsequent steps utilize the techniques of DNA-mediated gene transfer and methodologies of the recombinant DNA field. Several human repair genes have been cloned, but they have not been used to overproduce proteins thus far. This article highlights the more important developments and attempts to review in detail all of the isolated mutant cell lines that may be altered in the repair processes. Faster methods of gene cloning are greatly needed because the procedures for making secondary transformants from total genomic DNA are tedious.
«This will clear your mind»: the use of metaphors for medication in psychiatric settings

Psychiatric medications are an important part of the interaction between patients and clinicians in psychiatric settings. This article examines metaphors used by patients and clinicians to talk about the effects of antipsychotic medication. Metaphors provide a way to communicate about issues of identity and change involved in giving and taking medication. Although metaphorical language can contribute to misunderstandings between patients and clinicians, metaphor is also a major way in which clinical experiences are given shared meanings.
Expression of prestalk and prespore proteins in minute, two-dimensional Dictyostelium slugs

We show that exceedingly small two-dimensional slugs of Dictyostelium differentiate normally and have an anterior prestalk zone and a posterior prespore zone. Using GFP as a marker attached to the appropriate promoter, prestalk expression is concentrated in the anterior, while prespore expression is produced in the posterior, closely resembling what is found in normal, large slugs.
Displacement Thresholds in ZnO

Two displacement thresholds have been observed in ZnO single crystals. Above the lower energy threshold of 310 keV, the carrier removal rate increases quadratically with increasing electron beam energy. Above the second threshold at 900 keV, a sharp reduction in the free carrier microwave absorption is observed. Accompanying this, the EPR resonances for several iron group impurities and for the F+ center (ionized oxygen vacancy) become activated and are observable. The color centers which have been associated with F centers are also activated. After a thermal anneal to remove these color centers, irradiation at lower energies yields the same energy dependence for the production of F+ centers as is observed with the electrical measurements as well as the same threshold at 310 keV. The lower threshold at 310 keV is associated with oxygen displacements while the upper threshold at 900 keV is associated with zinc displacements. On the basis of these assignments, a value for the maximum atomic recoil energy of 57 eV is obtained for both zinc and oxygen displacements.
Fishing pressure and its influence on Monday catches of

Until about 1955 Atlantic menhaden (Brevoortia tyrannus) purse seine catches in Chesa-peake Bay were distributed equally among week days from Monday to Friday. From 1956 to 1961 the catch landed on Mondays averaged about 22% of the weekly totals. As fishing pressure increased and the population decreased after 1961, the percentage of the catch landed on Mondays rose, averaging about 34% of the weekly total. The increase in Monday catches is attributed to greater availability of fish after reduced fishing over the weekend.
Automatic Identification of Replicated Criminal Websites Using Combined Clustering

To be successful, cyber criminals must figure out how to scale their scams. They duplicate content on new websites, often staying one step ahead of defenders that shut down past schemes. For some scams, such as phishing and counterfeit-goods shops, the duplicated content remains nearly identical. In others, such as advanced-fee fraud and online Ponzi schemes, the criminal must alter content so that it appears different in order to evade detection by victims and law enforcement. Nevertheless, similarities often remain, in terms of the website structure or content, since making truly unique copies does not scale well. In this paper, we present a novel combined clustering method that links together replicated scam websites, even when the criminal has taken steps to hide connections. We evaluate its performance against two collected datasets of scam websites: fake-escrow services and high-yield investment programs (HYIPs). We find that our method more accurately groups similar websites together than does existing general-purpose consensus clustering methods.
Natural Language, Sortal Reducibility and Generalized Quantifiers

Recent work in natural language semantics leads to some new observations on generalized quantifiers. In §1 we show that English quantifiers of type 〈1, 1〉 are booleanly generated by their generalized universal and generalized existential members. These two classes also constitute the sortally reducible members of this type.Section 2 presents our main result — the Generalized Prefix Theorem (GPT). This theorem characterizes the conditions under which formulas of the form (Q1x1…QnxnRx1…xn and q1x1…qnxnRx1…xn are logically equivalent for arbitrary generalized quantifiers Qi, qi. GPT generalizes, perhaps in an unexpectedly strong form, the Linear Prefix Theorem (appropriately modified) of Keisler & Walkoe (1973).
Mechanistic Studies of the Zirconium−Triisopropanolamine-Catalyzed Enantioselective Addition of Azide to Cyclohexene Oxide†

The mechanism of the enantioselective ring-opening of cyclohexene oxide by Me3SiN3, catalyzed by zirconium complexes of the C3-symmetric ligand (+)-(S,S,S)-triisopropanolamine, has been investigated. Measurements of molecular weights of precatalyst species show that complexes are formed with average trimeric aggregation. Kinetics measurements reveal the overall process to be approximately half order in total zirconium, epoxide, and Me3SiN3 components. The reaction also shows a strong nonlinear relationship between enantiomeric excess of product azido ether vs the incorporation of (R,S,S)-triisopropanolamine ligand in the catalyst mixture. On the basis of these and other results, a preequilibrium interconversion of dimeric and tetrameric zirconium−triisopropanolamine species is proposed to occur rapidly with respect to the rate of epoxide ring-opening, with the dimeric form being the active catalyst. The reaction is accelerated by silyl ethers or by small amounts of water or alcohol, whereas larger amounts...
Transient temperature response of an avalanche diode

Abstract The thermal impedance is calculated for an avalanche diode under pulse bias conditions. The diode is represented by a circular heat source on the surface of an infinite solid cylinder and the calculation is made for the application of a single pulse and for periodic pulses. The temperature response is characterized by a time constant tc = R2/α, where R is the radius of the diode and α is the diffusivity of the heat sink. The results can be used to derive peak and average power limits and energy per pulse limits for high-efficiency avalanche diode oscillators operating under pulsed conditions. A simple, non-destructive technique is described for measuring the temperature of a junction when pulsed into avalanche breakdown.
Detection of Point Defect Chains in Ion Irradiated Silicon by High Resolution Electron Microscopy

In a lattice imaging study of As+ ion damaged Si, we have detected =110> chain type defects which are not associated with any significant strain or configurational changes. By image matching of the experimental and calculated micrographs of vacancies and interstitials, it is established that about 100% more interstitial atoms may incorporate into a defective chain. A structure model of this defect is proposed wherein a di-interstitial, occupying the =100> split position, is incorporated into every available site along a =110> chain.
A standby system with two types of repair persons

A continuously monitored one-unit system, backed by an identical standby unit, is perfectly repaired by an in-house repair person, if achievable within a random or deterministic patience time (DPT), or else by a visiting expert, who repairs one or all failed units before leaving. We study four models in terms of the limiting availability and limiting profit per unit time, using semi-Markov processes, when all distributions are exponential. We show that a DPT is preferable to a random patience time, and we characterize conditions under which the expert should repair multiple failed units (rather than only one failed unit) during each visit. We also extend the method when life- and repair times are non-exponential. Copyright © 2009 John Wiley & Sons, Ltd.
Three-dimensional numerical simulations of susceptibility-induced magnetic field inhomogeneities in the human head

Three-dimensional numerical simulations of the static magnetic field in the human head were carried out to assess the field inhomogeneity due to magnetic susceptibility differences at tissue interfaces. We used a finite difference method and magnetic permeability distributions obtained by segmentation of computed tomography images. Computations were carried out for four models, consisting of the head and the neck; the head, neck, and shoulders; the head, neck, and thorax; and the head tilted backwards, including the neck and the shoulders. Considerable magnetic field inhomogeneities were observed in the inferior frontal lobes and inferior temporal lobes, particularly near the sphenoid sinus and the temporal bones. Air/tissue interfaces at the shoulders were found to induce substantial magnetic field inhomogeneities in the occipital lobes and the cerebellum, whereas air/tissue interfaces in the lungs appeared to have less influence on the magnetic field in the brain. Tilting the head backwards could significantly reduce the field inhomogeneities superior to the planum sphenoidale as well as in the occipital lobes and the cerebellum.
Two Forms of the γ‐Aminobutyric Acid Synthetic Enzyme Glutamate Decarboxylase Have Distinct Intraneuronal Distributions and Cofactor Interactions

Glutamate decarboxylase (GAD) catalyzes the production of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter. The mammalian brain contains two forms of GAD, with Mrs of 67,000 and 65,000 (GAD67 and GAD65). Using a new antiserum specific for GAD67 and a monoclonal antibody specific for GAD65, we show that the two forms of GAD differ in their intraneuronal distributions: GAD67 is widely distributed throughout the neuron, whereas GAD65 lies primarily in axon terminals. In brain extracts, almost all GAD67 is in an active holoenzyme form, saturated with its cofactor, pyridoxal phosphate. In contrast, only about half of GAD65 (which is found in synaptic terminals) exists as active holoenzyme. We suggest that the relative levels of apo-GAD65 and holo-GAD65 in synaptic terminals may couple GABA production to neuronal activity.
Diagnostic concordance of the interview and questionnaire versions of the eating disorder examination

Developed to measure both cognitive and behavioral symptoms of eating disorders (ED), the interview (EDE)1 and questionnaire (EDE-Q)2 versions of the Eating Disorder Examination are among the most widely used assessments of ED pathology. The psychometric properties of both the EDE and EDE-Q have been extensively studied and are detailed in a recent review3. Additionally, over a dozen studies have examined the convergence of EDE and EDE-Q scores on both the subscales and behavioral frequency items, finding good convergence for the subscale scores and the items that measure the frequency of compensatory behaviors (i.e., self-induced vomiting). However, scores on the items used to measure binge eating (BE) frequency have demonstrated weaker convergence4. These results have important implications for several reasons: a specific frequency of BE is required for a diagnosis of bulimia nervosa (BN) in DSM-IV-TR5, the proposed DSM-5 criteria6 require a specific frequency of BE for both BN and binge eating disorder (BED) diagnoses, and both instruments can be used to generate ED diagnoses. There is surprisingly little research on the concordance of ED diagnoses derived by the EDE and EDE-Q. Three studies have poor to fair agreement between the EDE and EDE-Q for the classification of individuals as “binge eaters”7-9, with kappas ranging from .26 to .47. In a sample of 60 women seeking treatment for AN10, the overall agreement between the EDE and EDE-Q was moderate for the overall diagnosis of AN (κ=.56), and good for the subtyping of those with AN (κ=.79). Lastly, in a sample of women seeking treatment for substance abuse11, the diagnostic concordance of the EDE and EDE-Q improved when full-threshold and subthreshold ED diagnoses were combined. Of the five studies described above, only one included a clinical ED sample10. Although ED symptoms were reported in the other samples, the majority of participants in those studies did not meet criteria for an ED, which could potentially inflate the diagnostic agreement between the EDE and EDE-Q12. Additionally, the one ED sample10 was composed entirely of patients who met criteria for full-threshold Anorexia Nervosa (AN), which limits the generalizability of the findings. Thus, the objective of the current study was to examine the diagnostic concordance of the EDE and EDE-Q in a sample of ED patients with varied clinical presentations. Additionally, given that there is no published research on the diagnostic concordance of the EDE and EDE-Q when using the proposed DSM-5 ED criteria, a secondary objective of the study was to compare the diagnostic concordance of the EDE and EDE-Q when using the DSM-IV-TR criteria versus the proposed DSM-5 criteria.
Differences in academic and executive function domains among children with ADHD Predominantly Inattentive and Combined Types

Differences between the subtypes of Attention Deficit Hyperactivity Disorder (ADHD) continue to have a place in the clinical and research literature. The purpose of this study was to examine differences specific to academic and executive function deficits in a sample of 40 children, aged 9-15 years. Although there was a tendency for the Predominantly Inattentive (PI) group to evidence lower performance on calculation and written expression tasks, these differences dissipated when IQ was included as a covariate. For executive function domains of set shifting, interference, inhibition, and planning, differences emerged for interference, but only when girls were excluded from the analysis and no control for IQ was made. For parent ratings of executive function, expected differences were found on the Inhibit scale with the Combined Type (CT) group evidencing greater problems in this area; this difference remained even when girls were excluded and IQ was controlled. Implications for research and practice are presented.
Rapidly progressive periodontal disease associated with HIV infection: report of case

A case of rapidly progressive periodontal disease associated with human immunodeficiency virus (HIV) infection is presented. Rapid horizontal bone loss, with only mode rate inflammation, occurred during a 13-month period. Pocket depth was significantly less than anticipated, given the degree o f bone loss. The patient had no signs or symptoms of acquired immune deficiency syndrome (AIDS). The cause, features, diagnosis, and management are discussed.
Phylogenetic relationships among spiny pocket mice (Heteromys) inferred from mitochondrial and nuclear sequence data

In recent years molecular data have been used increasingly to estimate phylogenies and aid in species delimitation. We generated and analyzed sequence data for spiny pocket mice (Heteromys) for the mitochondrial gene cytochrome b (1,140 base pairs [bp]) and 2 nuclear gene segments, MYH6 (252 bp) and EN2 (189 bp). We used maximum-parsimony, maximum-likelihood, and Bayesian optimality criteria to estimate relationships among species and provide a framework for using a species-delimitation method to investigate the possibility of multiple species within the widespread H. desmarestianus group. We recovered several well-supported clades within this complex, including H. goldmani, H. oresterus, and H. nubicolens. Incorporating karyotype, allozyme, and morphological data from earlier studies, we found sufficient supporting evidence to justify maintaining H. goldmani, H. oresterus, and H. nubicolens as species and identifying 4 additional clades as candidate species. We present a revised taxonomic arrangement within the genus. The subgenus Xylomys should be retained and be composed of H. nelsoni. The subgenus Heteromys should be divided into 3 species groups: the H. anomalus group (H. anomalus and H. australis) together with H. catopterius, H. oasicus, and H. teleus (insertae sedis); the H. gaumeri group (H. gaumeri); and H. desmarestianus group (H. desmarestianus, H. goldmani, H. oresterus, H. nubicolens, and the 4 candidate species). DOI: 10.1644/09-MAMM-A-287.1.
Population structure and genetic heterogeneity in the Upper Markham valley of New Guinea

An analysis is presented of the standardized Wahlund's variances (f) in gene frequencies of the ABO, Rh and MNS blood group systems among 19 villages of the Atsera isolate of the upper Markham Valley, Papua New Guinea. In the past, there has been some disagreement over the relative importance of population structure and natural selection in the determination of these variances. The Lewontin-Krakauer test is presented as a means of resolving this disagreement. According to this test, selectively neutral variation in gene frequencies should generate essentially homogeneous values of f for all loci, a homogeneity which can be tested by comparing the value of (formula: see text) to a theoretical (formula: see text) expected when variations in (formula: see text) are due solely to sampling error. The observed value of (formula: see text) for the Atsera isolate is 2.9 x 10(-5), which is not significantly different from the expected values that range from 1.23 x 10(-5) to 2.46 x 10(-5) depending on the constant used in calculating (formula: see text). Therefore it appears that nonselective aspects of population structure such as genetic drift and intervillage migration are responsible for the recorded genetic variation in this isolate.
An investigation of fire scars in Pseudotsuga macrocarpa by Scanning X-Ray Fluorescence Microscopy

Abstract Fire scars in dated sequences of tree-rings are regularly used for the reconstruction of histories of forest fire frequency and investigations of various exogenous factors (climate in particular) which may control such events. The potential of the tree-ring archive in this regard is such that in circumstances where no scarring occurs following a particular fire, or where sampling is limited to increment cores which may miss the zone of scarring, alternate means of detecting tree-ring evidence for fire impact must be sought. One possible alternative may be detection of changes in tree-ring chemistry associated with growth years following forest fires. If it was possible to characterize such a change in chemistry an independent proxy for forest fires in tree-ring series might be established. The behavior of various elements within the xylem is however extremely complex so for a dendrochemical approach to fire history to be established, new techniques are required to enhance existing knowledge of elemental behavior in trees affected by fire. In this study, elemental intensities were mapped across scarred and un-scarred vectors of Pseudotsuga macrocarpa (Vasey) Mayr (bigcone Douglas-fir) tree-rings from a site in the Los Padres National Forest, Southern California, using Scanning X-Ray Fluorescence Microscopy (SXFM). The aims were: to assess the potential of this technique for understanding elemental change in relation to fire scars and undamaged contemporary growth; to provide new information on specific elemental behavior in this species; and to contribute to wider research for dendrochemically establishing fire histories. The results highlight the potential of SXFM for mapping elemental changes associated with compartmentalization, callus and woundwood as well as providing some evidence for depletion of certain elements in contemporary un-scarred rings. They also provide a first step towards future work to use cores for dendrochemical construction of fire histories.
Bronchoconstriction and apnea induced by cigarette smoke: nicotine dose dependence.

Recently, evidence was presented to suggest that nicotine absorbed from cigarette smoke was the main cause of smoke-induced bronchoconstriction (Hartiala et al., J Appl Physiol (1985) 59(1): 64–71). However, due to the qualitative nature of the data, it remains unclear whether cigarette-smoke-induced bronchoconstriction is related to the nicotine content of the smoke in a dose-dependent manner. Experiments were performed on intact anesthetized dogs (n = 6). Each animal spontaneously inhaled 300 cc smoke containing low (0.37 mg), medium (1.46 mg), or high (1.80 mg) levels of nicotine. Isometric tension was measured in an isolated tracheal segment not exposed to the smoke as an index of bronchoconstriction. In all dogs there was a nicotine dose-dependent increase in tracheal tension. The time in expiration (Te) in the breath following smoke inhalation was prolonged, the magnitude of prolongation being dependent upon the nicotine content of the smoke. These results suggest that bronchoconstriction and changes in Te induced by cigarette smoke are nicotine-dependent.
Observation of thermal fluctuations in superconducting microbridges

Thermal fluctuations of the type described by Langer and Ambegaokar and by McCumber and Halperin have been observed in superconducting thin-film rings containing microbridge sections. A peak in the fluctuation rate was found near the transition temperature. The temperature dependence of the observed rates is in agreement with the McCumber-Halperin fluctuation-rate equations and the deduced parameters are consistent with the theory.
Subcutaneous infusion of human C1 inhibitor in swine

Hereditary angioedema afflicts patients with unpredictable episodes of swelling that can be life threatening. Treatments approved by the Food and Drug Administration for routine prophylaxis include danazol given orally and the nanofiltered human C1 esterase inhibitor, CINRYZE™, which is approved for intravenous administration. Approved for the treatment of acute attacks are the C1 esterase inhibitor, Berinert®, given intravenously, and the kallikrein inhibitor, KALBITOR®, given subcutaneously. C1 inhibitor has generally been non-toxic and neither pro-inflammatory nor pro-fibrotic, suggesting that it may be suitable for subcutaneous infusion. The current study used a swine model to compare blood levels of human C1 inhibitor following intravenous and subcutaneous infusion, and the effect of infusion route on heart and skin pathology. Levels of C1 inhibitor achieved with SC infusion compared favorably with levels achieved after IV infusion and were relatively more stable than those after IV infusion. Neither cardiac nor skin toxicity was observed.
Data Book Focuses attention on women's health issues

W ith the publication this month of the second edition of The Women’s Health Data Book, The Jacobs Institute of Women’s Health continues a valued service to the community of health care providers, researchers, and policymakers concerned with women’s health issues. No other resource is available that compiles current, comprehensive information about U.S. women’s health from a variety of national data sets and presents the data in so accessible a format. The first edition of the Data Book’ made women’s health visible and vividly illustrated that women’s health issues extend beyond the traditional focus on reproductive health. The Data Book clearly documented the range of women’s health problems, including both conditions shared with men and conditions unique to women, and discussed key risk factors for these conditions. It defined violence against women as a health problem. It showed how health problems are distributed within the female population by age groups and by racial and ethnic backgrounds. It documented the particular problems women have in accessing health care, including both financial and nonfinancial barriers to services. Finally, it summarized the scope and limitations of national data sets with regard to women’s health information. The new edition of the Data Book, which provides updated information on all topics covered in the first edition, appears at a critical time in the movement to improve women’s health. In the last few years, there has been growing support for an expanded women’s health research agenda, as exemplified in the Women’s Health Initiative. Although much of the emphasis has been on biomedical research, providers are becoming increasingly aware of the need to improve the delivery of health services for women. Our job today is to maintain the momentum and clarify the issues of women’s access to appropriate health services. In the recent attempt at national health care reform, women’s health care needs were not a clearly articulated component of the debate, but much was at stake for women.’ As the Data Book points out, women are less likely than men to have health insurance through their own employment and more likely than men to be dependent on public insurance including Medicaid. Due to no or inadequate insurance coverage, many women, especially low-income women, are unable to obtain the health care they neede3 In addition, average
CdSe Quantum Dot Sensitized Solar Cells. Shuttling Electrons Through Stacked Carbon Nanocups

The charge separation between excited CdSe semiconductor quantum dots and stacked-cup carbon nanotubes (SCCNTs) has been successfully tapped to generate photocurrent in a quantum dot sensitized solar cell (QDSC). By employing an electrophoretic deposition technique we have cast SCCNT−CdSe composite films on optically transparent electrodes (OTEs). The quenching of CdSe emission, as well as transient absorption measurements, confirms ultrafast electron transfer to SCCNTs. The rate constant for electron transfer increases from 9.51 × 109 s−1 to 7.04 × 1010 s−1 as we decrease the size of CdSe nanoparticles from 4.5 to 3 nm. The ability of SCCNTs to collect and transport electrons from excited CdSe has been established from photocurrent measurements. The morphological and excited state properties of SCCNT−CdSe composites demonstrate their usefulness in energy conversion devices.
A qualitative and quantitative study of rete ovarii development in the fetal rat: correlation with the onset of meiosis and follicle cell appearance.

Development of the rete ovarii and its contribution to the cells of the ovary were examined in fetal rats. Histochemical and autoradiographic techniques were used for the observations between days 15 and 21 of gestation. The data presented indicate that the rete system contributes somatic cells to the ovary before birth. The basement membrane which surrounds the cuboidal epithelium of the mesonephric tubules immediately adjacent to the ovary becomes discontinuous on day 15 of gestation. The mesonephric epithelial cells in this region form a knot or clump of pleiomorphic cells, with no apparent tubular organization, and this clump later becomes surrounded by a basement membrane. On day 17 of gestation the newly established fetal rete ovarii is comprised of three regions; (1) the extraovarian mesonephric tubules (ER), (2) intraovarian cords of flattened epithelioid cells which surround the oogonia (IR), and (3) a knot or clump of cells connecting the ER and IR regions (CR). The entire rete system is enclosed by a continuous basement membrane as defined by Periodic Acid-Schiff Reagent techniques. Autoradiographic and quantitative analyses demonstrate that the ER tubule cells proliferate and are incorporated into the other regions of the rete system. These processes begin on day 17 and continue until at least day 21 of gestation. The role these mesonephric tubule cells may play in the regulation of meiosis and their early contribution to the presumptive granulosa cell population is discussed.
Thermodynamic modeling of the U–Zr system – A revisit

Abstract A new thermodynamic description of the U–Zr system is developed using the CALPHAD (CALculation of PHAse Diagrams) method with the aid of ab initio calculations. Thermodynamic properties, such as heat capacity, activities, and enthalpy of mixing, are well predicted using the improved thermodynamic description in this work. The model-predicted enthalpies of formation for the bcc and δ phases are in good agreement with the results from DFT + U ab initio calculations. The calculations in this work show better agreements with experimental data comparing with the previous assessments. Using the integrated method of ab initio and CALPHAD modeling, an unexpected relation between the enthalpy of formation of the δ phase and energy of Zr with hexagonal structure is revealed and the model improved by fitting these energies together. The present work has demonstrated that ab initio calculations can help support a successful thermodynamic assessment of actinide systems, for which the thermodynamic properties are often difficult to measure.
Under-sensitivity and under-volatility in aggregate consumption expenditures

Abstract This paper derives and tests exact restrictions on the sensitivity of changes in consumption to univariate innovations in labor income. Under the maintained hypothesis that labor income is difference stationary, changes in consumption are shown to be far too insensitive to innovations in labor income to be consistent with the Permanent Income Hypothesis. The under-sensitivity result complements recent work on the under-volatility of consumption. Several potential explanations for under-sensitivity are examined (for example, costly adjustment, unanticipated capital gains) but none is found to be entirely satisfactory.
Abstract 1708: Induction of GDF15 by cisplatin triggers apoptotic cell death in ovarian cancer cells

Ovarian cancer is the fifth most common cause of death among women. The overall five year survival is 45.6% as a result of late diagnosis when treatment is mostly ineffective. Current treatment consists of complete resection followed by a combination of a taxane and a platinum -based chemotherapy regardless of the subtype. After standard treatment, 70% of patients will develop chemoresistance, creating a major challenge in the treatment of this type of cancer. Therefore, there is great interest in understanding the mechanisms by which tumors develop resistance. From the microarray data of a high grade serous ovarian cancer cell line (A2780) treated with varying concentrations of cisplatin and at varying time points, we identified four genes (CDKN1A, FDXR, TP53I3 and GDF15) which were significantly up-regulated by cisplatin in a time and dose dependent manner. The time and dose dependent upregulation of these genes were further validated by real-time RT-PCR and Western blot analysis in A2780 and two other ovarian cancer cell lines. We further tested whether GDF15 expression correlated with cisplatin response. RNA and protein from 6 different cell lines with different IC50 to cisplatin revealed a positive correlation between GDF15 induction and sensitivity to cisplatin. To further investigate the role GDF15 plays in the chemoresponse of ovarian cancer cell, we knocked down the expression of GDF15 by shRNA. Ovarian cancer cells with GDF15 knockdown showed a decrease in PARP cleavage, suggesting a pro-apoptotic role for GDF15. Thus, our results suggest that induction of GDF15 by cisplatin is one of the mechanisms that triggers apoptotic cell death in ovarian cancer cells. On the other hand, we were not able to detect an induction of GDF15 by cisplatin in a cisplatin resistant cell line A2780cp20. Thus, the lost of GDF15 induction could be one of the mechanisms of developing chemoresistance. Future studies to decipher the mechanism by which cisplatin induces GDF15 expression have the potential of identifying new targets that could circumvent chemoresistance to cisplatin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1708. doi:10.1158/1538-7445.AM2011-1708
Modeling and Identification of Polyurethane Foam in Uniaxial Compression: Combined Elastic and Viscoelastic Response

Polyurethane foam used in automotive seating applications is a highly nonlinear and viscoelastic material. These properties are manifested even in its quasi-static response. In this paper, two different approaches to model and identify these material properties are presented. In both the approaches the viscoelastic property is assumed linear and modeled by a convolution of the input with a relaxation kernel that is a sum of exponentials (hereditary integral approach). The elastic force contribution is however assumed nonlinear and modeled by a polynomial in one approach, and by a model derived from Ogden strain energy function in the other. Uniaxial compression data from experiments is used to identify the parameters of the models. The robustness of the identification procedures and the issues associated with them are also discussed.Copyright © 2003 by ASME
Plasmin Regulation through Allosteric, Sulfated, Small Molecules

Plasmin, a key serine protease, plays a major role in clot lysis and extracellular matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer 32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45 μM, efficacy = 100%). Michaelis-Menten kinetic studies revealed an allosteric inhibition of plasmin by these inhibitors. Studies also indicated that the most potent inhibitors are selective for plasmin over thrombin and factor Xa, two serine proteases in coagulation cascade. Interestingly, different inhibitors exhibited different levels of efficacy (40%-100%), an observation alluding to the unique advantage offered by an allosteric process. Overall, our work presents the first small, synthetic allosteric plasmin inhibitors for further rational design.
Nonquasi-static effects in saturated bipolar circuits

A nonquasi-static (NQS) model accounting for intrinsic carrier propagation delays in both B/E and B/C junctions is implemented in the ASTAP circuit simulator to evaluate the impact of non-quasi-static effects in saturated bipolar circuits. It is shown that while the extra delay introduced by the NQS effects during the turn-on transition is primarily due to the normal mode B/E NQS delay time, the more severe NQS delay in the turnoff transition is caused mainly by the removal of the saturation overdrive charges and the longer inverse mode B/C NQS delay time. >
Earthquake locations and three‐dimensional fault zone structure along the creeping section of the San Andreas fault near Parkfield, CA: Preparing for SAFOD

[1] Arrival-time data from 453 local earthquakes and 6 explosions at Parkfield, CA, are inverted for earthquake locations and three-dimensional Vp and Vp/Vs structure. The structure is dominated by the velocity contrast across the SAF, with the southwest side about 20–25% faster, consistent with previous studies. Nearly all the earthquakes occur almost directly beneath the fault trace. We find high-Vp/Vs anomalies that correlate with low-resistivity features in a magnetotelluric model that are interpreted to represent fluids. We locate a magnitude 2 earthquake that is a potential target event for the final stage of SAFOD drilling, yielding a depth of 3.1 km below surface and an epicenter 100 m southwest of the fault trace. Nonlinear analyses indicate 95%-confidence relative and absolute uncertainties on the order of 500–700 m vertically and 200–300 m horizontally for this target earthquake.
Persuasion, Compulsion and Freedom in Plato's Laws

One of the distinctions that Plato in the Laws stresses most heavily in his discussion of the proper relation between the individual citizen and the laws of the city is that between persuasion and compulsion. Law, Plato believes, should try to persuade rather than compel the citizens. Near the end of the fourth book of the Laws, the Athenian Stranger, Plato's spokesman in this dialogue, asks whether the lawgiver for their new city of Magnesia should in making laws ‘explain straightaway what must and must not be done, add the threat of a penalty, and turn to another law, without adding a single bit of encouragement or persuasion [παραμυθας δ κα πeιθος … ἓν] to his legislative edicts’ (Laws 720a 1–2). A few lines later, the Athenian Stranger himself condemns such a procedure as ‘the worse and more savage alternative’ (τo χeῖρον τοῖν δυοῖν κα γριώτeρον 720e4). The better method is for the laws themselves to try to persuade (πeθeιν) the citizens to act in the manner that they prescribe. And as a means of doing this, Plato proposes attaching preludes (προομια) to particular laws and to the legal code as a whole: such preludes will supplement the sanctions attached to the laws and will aim at persuading the citizens to act in the way that the laws direct for reasons other than fear of the penalties attached to the law. Such a practice, Plato believes, is an innovation: it is something that no lawgiver has ever thought of doing before (722b–e). And we have no reason to think that Plato is here excluding his earlier self, e.g. the Plato of the Republic and the Politicus, from this criticism.
Effect of Exogenous Somatostatin Infusion on Gastrointestinal Blood Flow and Hormones in the Conscious Dog

The purpose of this study was to investigate the effects of intravenous somatostatin infusion on gastrointestinal blood flow and hormone release in conscious dogs. Gastric, duodenal, jejunal, and pancreatic blood flows, quantitated using radioactive microspheres, were significantly decreased during somatostatin infusion (200 and 500 ng/kg · min), resulting in an overall 30% reduction in summed portal blood flow. Fasting blood levels of glucose fell an average of 10 mg/dl. Immunoreactive insulin, gastrin, glucagon, and pancreatic polypeptide were all profoundly suppressed by somatostatin infusion. Our studies provide one possible explanation for somatostatin's apparent effectiveness in the control of upper gastrointestinal hemorrhage.
Cases and Biographies: An Essay on Routinization and the Nature of Comparison

▪ Abstract Routines, protocols, and organization charts focus attention, structure cognition, and shape decision making. Participants in organizations, legal systems, and markets compare cases, deciding which protocol governs the treatment of each case in a stream. But situations vary in the extent to which thought and action are effectively governed by routines and standard operating procedures. In less structured or more chaotic situations, biography is an alternative form of analysis that shapes cognition and helps people make sense of otherwise uninterpretable events. Biography and narrative do their work by constructing the causal unity of objects over time rather than by constructing causation from a comparison across similar cases. Using examples such as critically ill infants, animals, heirlooms, the penalty phase of capital trials, juvenile justice, the lower criminal courts, religious relics, and cloth, the paper compares case and biographical analysis in organizations, legal settings, and marke...
A case-control study of clinicopathologic features, prognosis, and therapeutic responses in patients with granulomatous mycosis fungoides

Background Granulomatous mycosis fungoides (GMF) is an uncommon variant of mycosis fungoides (MF). Objective We sought to analyze the relative frequency, clinicopathologic characteristics, prognosis, and therapeutic responses of GMF. Methods We conducted a retrospective case-control study of patients with GMF and age- and stage-matched patients with classic MF between 1981 and 2012. Results A total of 27 patients with GMF were identified, representing 6.3% of all patients with MF at our center. Skin manifestations were similar to classic MF having an atypical lichenoid CD4 + CD8 − lymphocytic infiltrate with interstitial histiocytes and/or perivascular granulomas with giant cells. Fewer patients with GMF achieved a partial response or complete response with topical (57% vs 83%; P = .002) or ultraviolet light (62% vs 90%; P = .006) therapy. The 5- and 10-year progression-free survival rates were significantly lower in patients with GMF (59% and 33%) compared with patients with classic MF (84% and 56%; P = .02), but overall survival was similar between groups (86% and 72% vs 85% and 85%; P = .54). Limitations The retrospective methodology may underestimate the frequency of GMF. The median follow-up time may be too short to detect possible differences in overall survival. Conclusion More frequent disease progression and poorer response to skin-directed therapies were observed in patients with GMF. Our findings may be helpful in selecting the most appropriate treatment for these patients.
Synergistic use of higher-protein diets or nutritional supplements with resistance training to counter sarcopenia.

Resistance exercise training helps older people treat sarcopenia. The consumption of diets that include sources of high-quality protein and total protein intakes that are moderately above the recommended dietary allowance of 0.8 g ˙ kg-1˙ d-1 while regularly performing resistance exercises can help older people retain or increase whole-body fat-free mass and muscle mass. Limited research suggests that protein-enriched nutritional supplements do not influence training-induced improvements when adequate dietary protein is consumed
Constraints of Simultaneous Resistance to a Fungal Pathogen and an Insect Herbivore in Lima Bean ( Phaseolus lunatus L.)

The existence of tradeoffs among plant defenses is commonly accepted, however, actual evidence for these tradeoffs is scarce. In this study, I analyzed effects of different direct defenses of wild lima bean plants (Phaseolus lunatus) that were simultaneously exposed to a fungal pathogen (Colletotrichum lindemuthianum) and an insect herbivore, the Mexican bean beetle (Epilachna varivestis). Although plants were derived from spatially widely separated populations, I observed a common tradeoff between resistance to pathogens and herbivores. Plants with high levels of anti-herbivore defense (cyanogenesis) showed low levels of resistance to pathogens (polyphenol oxidase activity and phenolic compounds), and vice versa. Competition for resources generally is considered to be the basis for tradeoffs. However, I report direct inhibition of polyphenol oxidase by cyanide, making simultaneous expression of both defenses at high levels impossible. I argue that populations composed of individuals investing in one type of defense have an advantage in environments that periodically favor either pathogen or herbivore plant antagonists.
Rapid downward transport of the neurotoxin domoic acid in coastal waters.

The diatom Pseudo-nitzschia produces the neurotoxin domoic acid, known to cause illness and death in marine mammals and humans. Measurements of surface- and deep-water domoic acid concentrations off the coast of California suggest that this toxin is rapidly transported to depth following diatom blooms.
Laboratory methods to improve SELDI peak detection and quantitation

Background: Protein profiling with surface-enhanced laser desorption-ionisation time-of-flight mass spectrometry (SELDI-TOF MS) is a promising approach for biomarker discovery. Some candidate biomarkers have been identified using SELDI-TOF, but validation of these can be challenging because of technical parameters that effect reproducibility. Here we describe steps to improve the reproducibility of peak detection. Methods: SELDI-TOF mass spectrometry was performed using a system manufactured by Ciphergen Biosystems along with their ProteinChip System. Serum from 10 donors was pooled and used for all experiments. Serum was fractionated with Expression Difference Mapping kit-Serum Fractionation from the same company and applied to three different ProteinChips. The fractionations were run over a one month period to examine the contribution of sample batch and time to peak detection variability. Spectra were processed and peaks detected using the Ciphergen Express software and variance measured. Results: Experimental parameters specific to the serum fraction and ProteinChip, including spot protocols (laser intensity and detector sensitivity) were optimized to decrease peak detection variance. Optimal instrument settings, regular calibration along with controlled sample handling and processing nearly doubled the number of peaks detected and decreased intensity variance. Conclusion: This report assesses the variation across fractionated sera processed over a onemonth period. The optimizations reported decreased the variance and increased the number of peaks detected.
MicroglassificationTM: A Novel Technique for Protein Dehydration

ABSTRACT The dehydration of biologics is commonly employed to achieve solid-dose formulation and enhanced stability during long-term preservation. We have developed a novel process, Microglassification TM , which can rapidly and controllably dehydrate protein solutions into solid amorphous microspheres at room temperature. Single bovine serum albumin (BSA) microdroplets were suspended in pentanol or decanol using a micropipette, and the dynamic changes in droplet dissolution were observed in real-time and correlated to protein's water of hydration, medium's water activity, and microsphere protein concentration. Microglassification TM was also carried out at bulk scale, and changes in BSA secondary structure were analyzed by Fourier transform infrared spectroscopy and fluorescence spectroscopy; multimer formation was detected by native gel electrophoresis. BSA concentration in the microsphere increased with solvent exposure time and decreasing water activity. Image analysis at single particle and bulk scale showed the formation of solid BSA microspheres with a maximum protein concentration of 1147 ± 32 mg/mL. The native BSA samples were dehydrated to approximately 450 waters per BSA, which is well below monolayer coverage of 1282 waters per BSA. The secondary structure of Microglassified TM BSA reverted to native-like conformation upon rehydration with only minor irreversible aggregation (2.7%). Results of the study establish the efficacy of the Microglassification TM for the successful dehydration of biologics.