cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 896: Enhancing mTOR targeted therapy in bladder cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Bladder cancer is the 4th most commonly diagnosed cancer in the United States. Because superficial bladder cancer (SBC) recurs in about 60% of cases, standard treatment involves tumor resection followed by intravesical therapies to prevent recurrence, as well as lifelong periodic cystoscopy. There is an urgent need for better intravesical therapies to prevent both the recurrence and progression of SBC. The Mammalian Target Of Rapamycin (mTOR) complex is upregulated in many bladder cancer tumors. We have targeted both the mTORc1 and mTORc2 complexes with drugs that inhibit both complexes. We used PP242 and a second inhibitor, OSI-027, which is currently in a phase I clinical trial for solid tumors ([NCT00698243][1]). Our in vitro model targets cell proliferation in three bladder cancer cell line (HT1376, T24 and UM-UC-3). Both drugs are effective in inhibiting the growth of bladder cancer cell lines with IC50 values between 0.6 and 18µM. In comparison with rapamycin, both drugs demonstrate effects on downstream targets of both the mTORc1 and mTORc2 pathways including 4EBP1 and pAkt. Receptor tyrosine kinases are another therapeutic target for bladder cancer. Lapatinib which targets EGFR and Her3, in combination with OSI-027 forms a highly synergistic treatment that inhibits bladder cancer cell line growth. Downstream molecular targets of the combination therapy, including the apoptosis markers PARP and caspase 3, were evaluated by Western blots. Our in vitro data suggests that a combination of dual mTOR inhibitors with RTK inhibitors may provide a novel effective therapeutic treatment for bladder cancer. Future studies of the in vivo efficacy of these drug combinations in a mouse model are planned. 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 896. doi:1538-7445.AM2012-896 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00698243&atom=%2Fcanres%2F72%2F8_Supplement%2F896.atom
Immune-mediated loss of transgene expression in skin: implications for cutaneous gene therapy.

Abstract A clearer understanding of the immune-mediated loss of transgene from cutaneous epithelium is necessary for development of effective clinical gene therapy protocols for patients who carry null mutations in the target gene. We have used retrovirus-mediated transfer of lacZ to mouse skin as a model to investigate the mechanism of immune-mediated transgene loss in skin. Transduction of C57Bl/6 mouse skin resulted in elicitation of both humoral and cellular immune responses. Antibody responses did not play a major role in the loss of transgene. Infiltration of the transduced skin with CD4 + and CD8 + cells and induction of transgene-specific cytotoxic T lymphocytes implied a role for T-cell-mediated responses. Transduction of mice deficient in either major histocompatibility complex (MHC) class I or class II molecules resulted in transient transgene expression. Only in MHC −/− mice lacking expression of both class I and class II MHC molecules was persistent transgene expression seen. These data indicate a primary role for T-cell-mediated responses in the immune-mediated loss of transgene expression. Furthermore, CD4 and CD8 T cells have overlapping roles and either population can effectively eliminate transduced cells. Therefore, long-term cutaneous gene therapy may require development of strategies to interfere with activation or function of both T cell populations.
What is Life? Defining Life in the Context of Emergent Complexity

Erwin Schrodinger defined life not only as a “self-reproducing” aperiodic crystal of DNA coding for proteins but within the context of living entities increasing their order by dissipating matter/energy gradients to maintain themselves away from equilibirium. Since then most definitions of life have focused on the former. But living cells do more than replicate their DNA. Cells also have membrane barriers across which metabolites must move, via which energy transduction as well as information processing occurs, and within which metabolic transformation occurs. An approach of complex systems dynamics, including nonequilibrium thermodynamics, may provide a more robust approach for defining life than a “naked replicator” at the origin of life. The crucial issue becomes the process of emergence of life from pre-biotic chemistry, concomitant with the emergence of function, information, and semiosis. Living entities can be viewed as bounded, informed autocatalytic cycles feeding off matter/energy gradients, exhibiting agency, capable of growth, reproduction, and evolution. Understanding how life might have emerged should sharpen our definition of what life is.
Applying the realized probability of dying to cancer survival

Age comparisons of survival in cancer cohorts generally utilize relative survival rates, which are based on indicators of the probability of survival for a given number of years after diagnosis. Cancer relative survival rates for the same number of years tend to decline as age at diagnosis increases. However, the same number of years of survival reflects higher relative longevity at older ages than at younger ages. The realized probability of dying (RPD) is a survival measure that expresses individual survival time after diagnosis relative to the survival distribution of an age-, race-, and sex-specific reference population, in effect weighing individual survival time more heavily as age at diagnosis increases. The purpose of this study was to apply the RPD as a survival measure in cancer epidemiology. Two cohorts of cancer patients, white males with prostate cancer and white females with breast cancer, aged 55 years and over at diagnosis, were followed for 15 years. Although older subjects survived less time after diagnosis than younger subjects, they achieved more favorable RPD values. We present survival analysis methods for analyzing the RPD in this population, an approach not previously used with this measure. The implications for use of the RPD in cancer epidemiology are discussed.
Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype

Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to its cognate transfer RNA and therefore plays an essential role in protein biosynthesis. We used exome sequencing, aminoacylation assays, homology modeling, and immuno-isolation of transfected MARS to identify and characterize mutations in the methionyl-tRNA synthetase gene (MARS) in an infant with an unexplained multi-organ phenotype. We identified compound heterozygous mutations (F370L and I523T) in highly conserved regions of MARS. The parents were each heterozygous for one of the mutations. Aminoacylation assays documented that the F370L and I523T MARS mutants had 18 ± 6% and 16 ± 6%, respectively, of wild-type activity. Homology modeling of the human MARS sequence with the structure of E. coli MARS showed that the F370L and I523T mutations are in close proximity to each other, with residue I523 located in the methionine binding pocket. We found that the F370L and I523T mutations did not affect the association of MARS with the multisynthetase complex. This infant expands the catalogue of inherited human diseases caused by mutations in aminoacyl-tRNA synthetase genes.
Weak convergence results for sequential regression in memoryless systems

Weak convergence results are obtained for a sequential regression algorithm that arises in the identification of nonlinear, memoryless systems and the adaptive design of moving average filters. The algorithm is shown to be weakly consistent if the system input is a wide-sense stationary sequence of order four that satisfies certain covariance and fourth-cumulant conditions. The conditions are essentially asymptotic independence requirements that permit one to relax the (usually required) strict independence requirements on the input data.
Baroclinic Waves in a Container with Sloping End Walls

The effects of sloping upper and lower boundaries on baroclinic waves in a differentially heated rotating fluid annulus have been studied experimentally. Measurements have been made of the internal temperature structure, the transition from axisymmetric to non-axisymmetric flow, the wave numbers and flow types, the drift rates and the heat transfer. The sloping boundaries influence the baroclinic waves in two distinct ways: if they are parallel the energy releasing mechanism is directly affected, while if they are not parallel effects similar to the latitudinal variation of coriolis parameter in a planetary atmosphere (the (3-effect) are introduced. In order to identify essentially non-linear effects the results on the transition from axisymmetric to non-axisymmetric flow, the wave numbers and the drift rates have been compared with an appropriately extended version (by Hide) of Eady’s linear perturbation theory of baroclinic instability. In the case of the transition from axisymmetric to non-axisymmetric flow, when account was taken of concomitant changes in the internal temperature structure, surprisingly good agreement with linear theory was obtained. Within the regular wave regime, the azimuthal wave numbers agreed quite well when the theoretically predicted value was 1, 2 or 3 but for higher predicted wave numbers the observed wave numbers were smaller. In the case of oppositely sloping boundaries the observed drift rates relative to the mean flow were generally 30 % less than that of the unstable waves of the linear theory. Another departure from the linear theory also occurred when the boundaries sloped in opposite senses, namely the occurrence at sufficiently rapid rotation rates of two separate wave trains of limited radial extent and differing wave numbers and drift speeds; one dominated the flow near the inner cylinder and the other dominated the flow near the outer cylinder. This result suggests that the variation of coriolis parameter with latitude can determine the radial extent of the baroclinic waves. Apart from its intrinsic interest as a fluid-mechanical study this work bears on the role played by the (3-effect and large-scale topography in natural systems such as the atmosphere and oceans. It also shows that at the higher rotation rates used the sloping eeopotentials inevitably present in previous laboratory experiments on baroclinic waves have important effects, and in particular explains the failure of previous theories to account for the position of part of the transition from axisymmetric to non-axisymmetric flow.
TU‐G‐103‐02: Clinical Evaluation of VirtualDose — a Software for Tracking and Reporting CTDI, DLP, Organ and Effective Dose for Adult and Pediatric Patient

Purpose: To update the development and clinical testing of a new Software as a Service (SaaS) ‐ VirtualDose for tracking and reporting CT doses. Methods: Incorporating SaaS technology and the comprehensive original dose data derived from Monte Carlo simulations on a family of adult and pediatric computational phantoms, covering 50th‐percentile adults and children at different ages, pregnant females at three gestational stages, and a set of overweight and obese phantoms, VirtualDose is being designed as a Web based CT dose reporting platform. For the client‐and server‐side scripting, JavaScript, Hypertext Markup Language, Cascading Style Sheets, and C# were used. A JSON (JavaScript Object Notation) is used as a request‐response interaction pattern to connect both the client‐and server‐side. Organ doses and effective doses are computed using ICRP Publication 60 and 103. Patient‐specific dosimetry capabilities are included by integrating a DICOM reader function module which could automatically extract dose, patient, and CT scanner (e.g., CTDI, DLP, kVp, mAs, weight, age, gender, etc.) information. Results: VirtualDose has been developed as a CT dose reporting SaaS by offering a web‐based dynamic user‐friendly interface. Based on the user‐specified scanning parameters, VirtualDose rapidly report the organ dose data from the remote server‐side database and interactively tabulate and plot the results of interest within a web browser. Clinical testing found the dose up to 24% different as compared to those derived from the stylized MIRD‐type phantoms. The morbidly obese phantom received up to 60% smaller CT dose than that of the normal weight phantomConclusion: VirtualDose is now available in the following website: http://www.virtualphantoms.com and being tested at more than 20 medical centers nationwide. Using a large library of adult and pediatric phantoms, it provides more accurate dose data and is expected to improve both the accuracy and usability in CT dose reporting in the future.
A Genetic Selection Method for the Transfer of HSV-1 Glycoprotein B Mutations from Plasmid to the Viral Genome: Preliminary Characterization of Transdominance and Entry Kinetics of Mutant Viruses

Abstract A genetic selection procedure has been devised to transfer mutations from a plasmid to the viral genome. Reagents were constructed so that the recombination events that occur during cotransfection rescue a mutation in a recipient viral genome and, simultaneously, transfer a mutation in an adjacent (target) gene to the viral genome. In the example presented here the two adjacent genes are essential for viral replication, so that a transformed cell line that expresses both genes and another cell line that expresses only the target gene are required. Ideally the recipient viral genome should be deleted for the entire target gene, and the deletion should extend a short distance into the adjacent gene. In the present study UL27 (glycoprotein gB) of herpes simplex virus type 1 (KOS) is the target gene for mutation transfer and the upstream gene UL28, which specifies the ICP185 polypeptide, is the marker-rescue gene. A recipient virus that was deleted for DNA sequences encoding the C-terminal 74 residues of ICP18.5 and the N-terminal 711 residues of gB was constructed. All of the gR mutant plasmids used overlap the ICP18.5 deletion, and therefore, recombination events that rescue the ICP185 deletion must transfer a gB mutation present in codons 1-711 of the rescuing plasmid. Recombinant viruses that contain the gR mutation, unlike the parental gB/18.5 - virus, will grow on cells that express only gB (D6). This procedure has been used to transfer insertion, deletion, and chain termination mutations into the gB gene of the KOS genome Southern blot analysis confirmed the transfer of the mutations to the viral genome. Analysis of radioactively labeled, infected cell lysates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), before and after immune precipitation with gB-specific antibodies, confirmed the presence of the mutant polypeptides in the lysates. The incorporation of the mutant polypeptides into the envelopes of purified released viruses was measured. The yield of plaque forming units per cell was determined from single step growth curves after infection of permissive D6 cells. Virus yield, a measure of transdominance, varied for the different mutants. The maximum reduction in virus yield observed was sixfold relative to the wild-type virus. Transdominance was a result of both the lack of glycoprotein processing and the presence of gB-oligomerization sites. A reduced yield was also observed for a previously isolated gB-null mutant virus, K082. The amount of gB produced in D6 cells, infected with K082, was less than that produced in KOS infected cells, which may account for the reduced yield. A delay in the entry of mutant viruses into D6 cells was observed for all of the mutants which may be due both to reduced amounts of gB in the transformed D6 cells and to the presence of the mutant proteins in the envelopes of intracellular virions.
Diffuse Bands and Predissociation of Iodine Monochloride

THE absorption spectrum of iodine monochloride consists of a group of bands (group Cl) with an upper convergence limit at about 17430 cm.-1 corresponding to the dissociation of ICl into a normal iodine atom and a chlorine atom in the 22P1 state. There is also another group (group I) of which only two members (17446 cm.-1 and 17570 cm.-1) were observed by Gibson and Ramsperger. Several further members of this group have since been observed (Gibson: unpublished measurements). These are visible in the region between the convergence and the absorption maximum of the continuum of group Cl.
Target station shielding issues at the spallation neutron source

Recent spallation neutron source shielding activities in support of the neutron beam shutters and the hot cell walls are presented. Existing neutron beam shutters can be replaced with concrete at low power or with concrete and steel at approximately 500 kW of beam power. Potential voids in the hot cell walls are analysed to determine the impact on dose rates as a function of void size. A change in the type of shielding work is noted as the project moved from the early design stages as a 'green field' site to the current stage as a construction project nearing completion, where issues to be addressed are approaching retrofit-type analyses.
Interstitial Silica and pH in Marine Sediments: Some Effects of Sampling Procedures

The temperature at which the interstitial water was squeezed from a marine sediment had a profound effect on the measured interstitial silica concentrations which showed an average increase of 51 percent after the sediment was exposed to a temperature 20°C higher than the in situ temperature. Similar effects were not found for interstitial phosphate or alkalinity, but the pH was slightly higher in the water squeezed at the higher temperature. These tempreature-induced changes were completed in a few hours. The use of filter paper can significantly lower the pH of expressed pore waters. Until some important questions about temperature effects are answered, all future data on the pH and silica concentration of pore waters of marine sediments should be obtained from samples extracted at in situ temperatures.
Regulation of ovarian steroidogenesis in vitro in the viviparous shark, Squalus acanthias

We investigated the steroid biosynthetic capabilities of ovarian granulosa and thecal elements of the viviparous dogfish, Squalus acanthias. In this report we present evidence that granulosa cells secrete quantitatively important amounts of progesterone (P), testosterone (T) and estradiol-17β (E), while theca has a more limited capacity to synthesize T and E. Ovarian granulosa cells were obtained from animals at each stage of gestation. After collagenase dispersion, an aliquot of 250,000 cells was incubated at 18°C in basal medium, containing Eagle's salts, glutamine, penicillin, streptomycin and adjusted with 136 mM sodium chloride and 350 mM urea. After a 4 hour incubation, the content of P, T, and E in medium was determined by radioimmunoassay. P was not detectable at any time, while E was present throughout the cycle, being maximal when gestation is three quarters complete (Stage C). T gradually increased from Stage B toward late pregnancy. In Stage C granulosa cells, E production increased in the presence of graded doses of T substrate. Also, a homologous pituitary extract (1/25 equivalents) and the calcium ionophore A23187 stimulated production of all 3 steroids. Using radioisotopes, granulosa cells showed a wide range of synthetic capacities. In Stage C thecal tissue, E production also increased in the presence of graded doses of T substrate, while pituitary extract only increased T. When granulosa and theca were recombined, in the presence of pituitary extract, P levels decreased with a corresponding increase in T, when compared to granulosa alone. These data suggest a possible interaction between granulosa and theca for steroid biosynthesis. They further indicate that granulosa cells alone have the capacity to synthesize P, T, and E, without any input from theca.
Sample size requirements for matched case‐control studies of gene–environment interaction

Consideration of gene-environment (GxE) interaction is becoming increasingly important in the design of new epidemiologic studies. We present a method for computing required sample size or power to detect GxE interaction in the context of three specific designs: the standard matched case-control; the case-sibling, and the case-parent designs. The method is based on computation of the expected value of the likelihood ratio test statistic, assuming that the data will be analysed using conditional logistic regression. Comparisons of required sample sizes indicate that the family-based designs (case-sibling and case-parent) generally require fewer matched sets than the case-control design to achieve the same power for detecting a GxE interaction. The case-sibling design is most efficient when studying a dominant gene, while the case-parent design is preferred for a recessive gene. Methods are also presented for computing sample size when matched sets are obtained from a stratified population, for example, when the population consists of multiple ethnic groups. A software program that implements the method is freely available, and may be downloaded from the website http://hydra.usc.edu/gxe.
Low energy particle signature of substorm dipolarization

The low energy particle signature of substorm dipolarization is exhibited through a case study of RIMS data on DE-1 at approximately 2100 MLT, ILAT = 59 deg approximately 65 deg, L = 3.8 approximately 5.4 R(sub E), and geocentric distances 2.6 approximately 2.9 R(sub E). A strong cross-field-line, poleward outflow that lasts for a few minutes with a velocity that reaches at least 50 km/s is correlated with substorm activity evidenced in the AE index and the MAG-1 data. All the major species (H+, He+, O+) are observed to have the same bulk velocity. The parallel velocities are strongly correlated with the perpendicular velocities. The parallel acceleration is shown to result from the centrifugal force of the ExB drift induced by the dipolarizing perturbation of the magnetic field.
Charles Francis Hockett (1916–2000)

MIT, in Australia, and from the U.S. Southwest. Now we await the publication of Hale and Keyser, Prolegomenon to a Theory of Lexical Argument Structure (2002). His obituary in the Economist (November 3, 2001), and the feature "Kenneth Hale ... an Extraordinary American," in Alistair Cooke's "Letter from America" (December 3, 2001) is a testament to his accomplishments and breadth of influence outside that of academia.
Salmonella enterica serovar typhimurium invasion is repressed in the presence of bile.

As enteric pathogens, the salmonellae have developed systems by which they can sense and adapt appropriately to deleterious intestinal components that include bile. Previously, growth in the presence of bile was shown to repress the transcription of prgH, a locus encoding components of the Salmonella pathogenicity island I (SPI-1) type III secretion system (TTSS) necessary for eukaryotic cell invasion. This result suggested an existing interaction between salmonellae, bile, and eukaryotic cell invasion. Transcription assays demonstrated that invasion gene regulators (e.g., sirC and invF) are repressed by bile. However, bile does not interact with any of the invasion regulators directly but exerts its effect at or upstream of the two-component system at the apex of the invasion cascade, SirA-BarA. As suggested by the repression of invasion gene transcription in the presence of bile, Western blot analysis demonstrated that proteins secreted by the SPI-1 TTSS were markedly reduced in the presence of bile. Furthermore, Salmonella enterica serovar Typhimurium grown in the presence of bile was able to invade epithelial cells at only 4% of the level of serovar Typhimurium grown without bile. From these data, we propose a model whereby serovar Typhimurium uses bile as an environmental signal to repress its invasive capacity in the lumen of the intestine, but upon mucous layer penetration and association with intestinal epithelial cells, where the apparent bile concentration would be reduced, the system would become derepressed and invasion would be initiated.
Cannibalism, cell survival, and endocrine resistance in breast cancer

Breast cancer cells often respond to an endocrine therapy by altering expression of specific estrogen-responsive genes and inducing autophagy, a cannibalistic lysosomal pathway. Autophagy eliminates damaged or other organelles, allowing the recovery of the energy stored in their macromolecules to attempt restoration of metabolic homeostasis. Induction of autophagy can result from activation of the unfolded protein response following metabolic stress, the final cell fate often being determined by the extent and duration of autophagy. A study by Gonzalez-Malerva and colleagues builds upon this extensive knowledge, adding HSPB8 to the list of altered genes associated with endocrine resistance in breast cancer and describing the ability of HSPB8 to regulate autophagy and confer tamoxifen resistance.
Demographic characteristics of U.S. Chinese older adults in the Greater Chicago area: assessing the representativeness of the PINE study.

Objective: We aimed to assess the representativeness of the demographic characteristics of the PINE study to the Chinese aging population in the Greater Chicago area. Method: The PINE study is a population-based study of Chinese older adults aged 60 and over in the Greater Chicago area. In preparation of the PINE study, we conducted a random block census study in Chicago. Demographic characteristics of the PINE study were compared with the data drawn from U.S. Census 2010 and random block census study using chi-square tests. Results: The PINE study is representative of the Chinese aging population in the Greater Chicago area. No significant difference was found in key attributes including age, sex, income, education, number of children, and country of origin. Discussion: Our report is critical in understanding the vast socio-demographic diversity of U.S. Chinese older adults. Rigorous studies are needed to explore the heterogeneity among the diverse aging populations.
Inhibition of Contraction-Stimulated AMP-Activated Protein Kinase Inhibits Contraction-Stimulated Increases in PAS-TBC1D1 and Glucose Transport Without Altering PAS-AS160 in Rat Skeletal Muscle

OBJECTIVE Phosphorylation of two members of the TBC1 domain family of proteins, Akt substrate of 160 kDa (AS160, also known as TBC1D4) and TBC1D1, has been implicated in the regulation of glucose transport in skeletal muscle. Insulin-stimulated phosphorylation (measured using the phospho-Akt substrate [PAS] antibody) of AS160 and TBC1D1 appears to occur in an Akt-dependent manner, but the kinases responsible for contraction-stimulated PAS-AS160 and PAS-TBC1D1 remain unclear. AMP-activated protein kinase (AMPK) and Akt, both activated by contraction, can each phosphorylate AS160 and TBC1D1 in cell-free assays. RESEARCH DESIGN AND METHODS To evaluate the roles of AMPK and Akt on insulin- or contraction-stimulated PAS-AS160, PAS-TBC1D1, and glucose transport, rat epitrochlearis was incubated with and without compound C (inhibitor of AMPK) or Wortmannin (inhibitor of phosphatidylinositol [PI] 3-kinase, which is upstream of Akt) before and during insulin stimulation or contraction. RESULTS Insulin-stimulated glucose transport and phosphorylation of both AS160 and TBC1D1 were completely inhibited by Wortmannin. Wortmannin eliminated contraction stimulation of phospho-Ser 21/9 glycogen synthase kinase 3α/β (pGSK3; Akt substrate) and PAS-AS160 but did not significantly alter pAMPK, phospho-Ser 79 acetyl CoA carboxylase (pACC; AMPK substrate), PAS-TBC1D1, or glucose transport in contraction-stimulated muscle. Compound C completely inhibited contraction-stimulated pACC and PAS-TBC1D1 and partially blocked glucose transport, but it did not significantly alter pAkt, pGSK3, or PAS-AS160. CONCLUSIONS These data suggest that 1 ) insulin stimulates glucose transport and phosphorylation of AS160 and TBC1D1 in a PI 3-kinase/Akt–dependent manner, 2 ) contraction stimulates PAS-AS160 (but not PAS-TBC1D1 or glucose transport) in a PI 3-kinase/Akt–dependent manner, and 3 ) contraction stimulates PAS-TBC1D1 and glucose transport (but not PAS-AS160) in an AMPK-dependent manner.
The American Concept of Schizophrenia

The American concept of schizophrenia is built primarily upon concepts advanced by Kraepelin, Bleuler, and Schneider. Because of the influence of major research studies such as the International Pilot Study of Schizophrenia and the U.S./U.K. study, emphasis has been placed on developing reliable descriptions of symptoms and a precise definition of the disorder. This research also led to a recognition that the American concept of schizophrenia was relatively broad in comparison with that used in the rest of the world. This led to a critical reappraisal of American diagnostic practices during the 1970's, culminating in the narrower definition of schizophrenia in the third edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-III). This definition requires the presence of psychotic features, established chronicity, evidence of deterioration, and the exclusion of affective and "organic" features. In comparison with this definition, the Soviet concept appears to be much broader and to include non-psychotic forms. Treatment implications of these differences are discussed.
Training of LBL-SSC model dipole magnets at 1.8 K

The 1.8 K training behavior of SSC (Superconducting Supercollider) magnets, several of which have reached a peak current of 9400 A is presented. For the SSC Project, more than 30 one-meter-long dipole magnets have been built and tested. Magnet operation, primarily reaching design field without premature training, is expected to be superior in superfluid helium at 1.8 K as compared with helium at 4.3 K. Not only is the critical current increased at the lower temperature, but the heat transfer is much improved. LBL (Lawrence Berkeley Laboratory) has had an operating helium II facility for nine years and the standard test sequence has been to check for training in helium I at 4.3 K and then cool the system down to 1.8 K and train the magnet to its new, high limit. Because the mechanical forces are much greater at the higher currents and fields achieved at the lower temperature, information on the adequacy of the mechanical design has been obtained. Even for those magnets in which training quenches occurred in the inner layer at 4.3 K, many of the quenches at 1.8 K occurred in the outer layer. >
The “Amazonian Trial of the Century”: Indigenous Identities, Transnational Networks, and Petroleum in Ecuador:

This examination of the work of three organizations in the northeastern Ecuadoran Amazon, FEINCE, OISE, and FOISE, explores how they engage and produce representations of indigeneity in relation to an on-going lawsuit against Chevron Texaco. Each of these organizations has used distinct network associations and performances based on their particular histories in relation to petroleum in order to mediate cultural, political, and economic possibilities for their constituencies. As these organizations mobilize support for local causes through specific network connections, they produce and articulate distinct meanings of indigeneity, with distinct consequences for the future of their constituencies. I argue that an analysis of how collective indigenous identity, localities, and social networks shape and are shaped by representative organizations can help productively explore the social relations through which knowledge about Ecuadoran Amazon peoples and places is produced.
The Political Economy and Stigmatization of HIV/AIDS in Patients Attending a Clinic in Lagos, Nigeria

Background: The aim of the study was to highlight the political economy of HIV/AIDS in people living with HIV/AIDS (PLWHA) through use of relevant literature and administration of self-administered questionnaires. The study was carried out in the south- western region of Nigeria, using patients attending the HIV/AIDS clinic at the Lagos University Teaching Hospital, Lagos Nigeria. Method: The questionnaires were distributed in the HIV/AIDS clinic and respondents were interviewed by the Principal Investigator and medical students. Results were collated and analysed using computer software. Chi Square analysis was used to test for association between categorical variables at a P value of 0.05. Results were presented in tables and charts. Further, the study determined changes if any in the socio- demographic pattern of the patients particularly in marital status, employment status and residential status since diagnosis. In addition, the study sought to determine areas of stigmatization as well as the fraction of monthly income spent on HIV/AIDS care. Results: Literature showed that employers were not willing to employ a person with HIV/AIDS and that vulnerable employment was the predominant form of employment in sub-Saharan Africa. This was re-affirmed by the study. Thirteen (13%) respondents lost their jobs after diagnosis and about 75 (75.0%) of respondents were in vulnerable employment. Sixty-four (64%) of the respondents were married before diagnosis and 53 (53.0%) were still married after diagnosis, five of the respondents’ spouses had died, 3 had been divorced, and 4 had been separated from their spouses (P < 0.05). Sixty-one (61.0%) of the respondents got their financial support from their family. Stigmatization increased with the number of people that knew of their diagnosis (P < 0.05). Conclusion: Loss of job occurred in respondents when the employers knew of the diagnosis. The household income spent on HIV/AIDS care ranged from one-third to half of the monthly income. It was recommended that the government provide incentives for employers to hire PLWHA. Health education should target employers. Self-sustaining financing schemes should be developed to help PLWHA.
The gift is life

“He's in serious trouble—someone better talk to the mother about it,” said the nurse, as I approached the patient's room. As the attending physician, I was the designated “someone” who had to tell a mother that she would be taking her teenage son home to die. I paused in the hallway to review the patient's chart. The boy had a neuro-metabolic degenerative disease. He had gradually lost physical strength and coordination to the point of requiring assistance with simple daily activities. He had been admitted many times in the past year for dehydration, pneumonia, and seizures. He was the youngest child of a poor, small, frail woman who had tried to care for him at home despite her recent surgery. While attempting to reposition him in bed, her surgical sutures had split open and she was forced to bring him to the hospital. The boy had a severe infection that caused multiorgan failure. His health deteriorated rapidly despite modern medical treatment. From this point on, there would be more caring than curing. It was a sunny fall day, but the room was dark and quiet. The mother had pulled the shades down, hoping her son would get a few more moments of rest. “Good morning, Ma'am,” I said softly. She looked up slowly, and a weary gaze searched my face for answers to her unspoken questions. She seemed detached as we discussed his treatment. She had previously indicated she wanted to take her son home to his family and friends, so her question was not entirely unexpected. “Dr. D, when can I take him home?” “Let me talk to the hospice …
The efficacy of superior oblique split Z-tendon lengthening for superior oblique overaction.

Abstract Purpose To evaluate the efficacy of superior oblique muscle split Z-tendon lengthening in the treatment of superior oblique muscle overaction with respect to normalization of superior oblique ductions and versions, reduction of A -pattern strabismus and correction of vertical deviations. In addition, to determine the incidence of complications of the procedure including overcorrection and the effect of the procedure on horizontal deviation. Methods A retrospective review was performed of 19 patients who underwent superior oblique muscle split Z-tendon lengthening for A -pattern strabismus or significant vertical deviation associated with superior oblique overaction between June 1980 and September 1999. Ten males and 9 females were included, ranging in age from 2 to 45 years (mean: 9 years). Patients underwent either a unilateral or bilateral superior oblique tendon lengthening based on the patient’s clinical picture. Results Ten of 11 patients (91%) who underwent unilateral tendon lengthening and 10 of 16 eyes (63%) that underwent bilateral superior oblique tendon had complete normalization of superior oblique action. Seven of 10 patients (70%) who underwent unilateral or bilateral tendon lengthening for a clinically significant A -pattern had the A -pattern completely eliminated or brought to a clinically insignificant level. All 8 patients who underwent a unilateral tendon lengthening for a clinically significant vertical deviation had reduction of the vertical deviation. There was no statistically significant effect of either the unilateral or bilateral procedure on horizontal deviation. Conclusions The superior oblique muscle split Z-tendon lengthening procedure is highly effective for normalization of superior oblique muscle function and reduction of A -pattern strabismus and vertical deviations associated with superior oblique muscle overaction.
From norms to programs: The United Nations Global Compact and global governance

Norms shape policy when they get translated into concrete programs. What if a widely shared norm gets translated into a weak program? How might this influence the program's legitimacy? We examine these issues in the context of the United Nations Global Compact, a voluntary program that embodies the widely shared norm of corporate responsibility. While both international intergovernmental organization (IGO) and international non-governmental organization (INGO) networks support this norm, they differ on the adequacy of the Compact's program design. We explore how this tension affects the diffusion of the Compact across countries, which vary in their levels of embeddedness in IGO and INGO networks. Our findings suggest that embeddedness in IGO networks encourages adoption, while embeddedness in INGO networks discourages it. Our analysis provides important lessons for sponsors of voluntary governance mechanisms. Widespread support for a norm does not automatically ensure support for a program that claims to embody it.
Tuning Rectification in Single-Molecular Diodes

We demonstrate a new method of achieving rectification in single molecule devices using the high-bias properties of gold–carbon bonds. Our design for molecular rectifiers uses a symmetric, conjugated molecular backbone with a single methylsulfide group linking one end to a gold electrode and a covalent gold–carbon bond at the other end. The gold–carbon bond results in a hybrid gold-molecule “gateway” state pinned close to the Fermi level of one electrode. Through nonequilibrium transport calculations, we show that the energy of this state shifts drastically with applied bias, resulting in rectification at surprisingly low voltages. We use this concept to design and synthesize a family of diodes and demonstrate through single-molecule current–voltage measurements that the rectification ratio can be predictably and efficiently tuned. This result constitutes the first experimental demonstration of a rationally tunable system of single-molecule rectifiers. More generally, the results demonstrate that the high...
Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia

Abstract The functional integrity of the dorsolateral prefrontal cortex (DLPFC) is altered in schizophrenia leading to profound deficits in working memory and cognition. Growing evidence indicates that dysregulation of glutamate signaling may be a significant contributor to the pathophysiology mediating these effects; however, the contribution of NMDA and AMPA receptors in the mediation of this deficit remains unclear. The equivocality of data regarding ionotropic glutamate receptor alterations of subunit expression in the DLPFC of schizophrenics is likely reflective of subtle alterations in the cellular and molecular composition of specific neuronal populations within the region. Given previous evidence of Layer II/III and V pyramidal cell alterations in schizophrenia and the significant influence of subunit composition on NMDA and AMPA receptor function, laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells in the DLPFC. Comparisons were made between individuals diagnosed with schizophrenia, bipolar disorder, major depressive disorder and controls ( n = 15/group). All subunits were expressed at detectable levels in both cell populations for all diseases as well as for the control group. Interestingly, GRIA1 mRNA was significantly increased in both cell types in the schizophrenia group compare to controls, while similar trends were observed in major depressive disorder (Layers II/III and V) and bipolar disorder (Layer V). These data suggest that increased GRIA1 subunit expression may contribute to schizophrenia pathology.
Variation in Ilmenite Element Composition within and Among Drainage Basins: Implications for Provenance

ABSTRACT The elemental composition (Ti, Fe, Mn, Mg, V, Zn, Cr, Ni, and Cu) of detrital ilmenite grains from three large drainage basins in Virginia was found to be relatively unchanged over hundreds of kilometers distance downstream from the Blue Ridge Mountains to the Coastal Plain. The igneous Blue Ridge Complex apparently contributes a sufficient quantity of ilmenite in each river system such that the input of distinctly different ilmenite compositions from tributaries does not change the overall ilmenite composition in the main river. This is not the case for nonopaque heavy minerals, which change in abundance and type downstream due to tributary input. Despite a similar primary source, each major river has a distinctly different ilmenite composition which can be discriminated at better th n a 0.95 confidence level. This enhances the ability to determine the source river for sands in the depocenter. Initial results on ilmenite from small-drainage-basin tributaries dominated by one or two source-rock types known to contain ilmenite show that compositional differences exist for granitic, mafic igneous, metamorphic, and sedimentary sources.
Engineering a distributed computational collaboratory

This paper presents the design, implementation, and deployment of the DISCOVER Web-based computational collaboratory. Its primary goal is to bring large distributed simulations to the scientists'/engineers' desktop by providing collaborative Web-based portals for monitoring, interaction and control. DISCOVER supports a 3-tier architecture composed of detachable thin-clients at the front-end, a network of interaction servers in the middle, and a control network of sensors, actuators, and interaction agents at the back-end. The interaction servers enable clients to connect and collaboratively interact with registered applications using a conventional browser. The application control network enables sensors and actuators to be encapsulated within and directly deployed with the computational objects. The application interaction gateway manages overall interaction. It uses the Java Native Interface to create Java proxies that mirror computational objects and allow them to be directly accessed at the interaction server. Security and authentication are provided using customizable access control lists and SSL-based secure servers.
ANOMALIES OF MYELIN‐ASSOCIATED GLYCOPROTEINS IN‘QUAKING MICE

— Proteins and glycoproteins in a myelin fraction isolated from Quaking mutant mice were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate and stained with Fast Green or with periodic acid-Schiff reagents. Double labelling experiments with [3H]fucose and [14C]fucose were also used to compare glycoproteins in myelin from the mutant mice with those from control mice. In the myelin fraction from the Quaking mice the basic proteins and proteolipid protein were decreased relative to the high molecular weight proteins. Some glycoproteins which are present in small amounts in myelin from normal mice were increased relative to the major glycoprotein in the myelin fraction of the Quaking mice. Furthermore, the major myelin-associated glycoprotein was shifted toward higher apparent molecular weight in comparison with controls of the same age or even with 9-day-old controls. The abnormal glycoproteins in the mutant myelin fraction could be a factor in the impairment of myelination.
Update on the pathophysiology of aortic stenosis

The objective of this review is to explain the basis for the current appreciation of the role of active atherosclerotic and bone-forming processes in the pathophysiology of calcific aortic stenosis (AS). Relevant epidemiological, histopathological, and experimental studies are reviewed. Calcific AS and atherosclerosis share similar risk factors, including elevated LDL cholesterol levels, hypertension, male gender, smoking, and diabetes mellitus. Both atherosclerosis and calcific AS often occur in individuals with familial hypercholesterolaemia, and elderly patients with AS are also at an increased risk of myocardial infarction and death from cardiovascular causes. Lipoprotein deposition is prominent in both conditions. Aortic valve mineralisation occurs as the result of mechanisms similar to those active in bone formation, including upregulation of the Lrp5 pathway and the presence of an osteoblast phenotype in calcified valves. An active atherosclerosis-type pathophysiology involving oxidative stress, inflammation, and endothelial dysfunction in aortic valves has been induced by hypercholesterolaemia, and inhibited by administering HMG-CoA reductase inhibitors (statins), in animal models. Evidence of endothelial dysfunction with neovascularisation and an increase in endothelial macrophages and metalloproteinases has been found in surgically excised human valves with calcific AS. The initiating factors and pathophysiology of calcific AS are broadly similar to those of atherosclerosis of coronary and other arteries. The sclerosis and calcification of aortic valves may therefore be addressed with pharmacological therapies that are effective in slowing or reversing atherosclerosis.
Non-Biological Signals

Although we would like to think of signals as being continuous in time and state, in reality, we observe and process signals in discrete time steps using countable (perhaps, infinitely countable) states.