cssi/SciSciGPT-SciSciNet huggingface dataset:
Mutational signatures of complex genomic rearrangements in human cancer

Complex genomic rearrangements (CGRs) are common in cancer and are known to form via two aberrant cellular structures--micronuclei and chromatin bridge. However, which mechanism is more relevant to CGR formation in cancer cells and whether there are other undiscovered mechanisms remain open questions. Here, we analyze 2,014 CGRs from 2,428 whole-genome sequenced tumors and deconvolute six CGR signatures based on the topology of CGRs. Through rigorous benchmarking, we show that our CGR signatures are highly accurate and biologically meaningful. Three signatures can be attributed to known biological processes--micronuclei- and chromatin-bridge-induced chromothripsis and extrachromosomal DNA. More than half of the CGRs belong to the remaining three newly discovered signatures. A unique signature (we named "hourglass chromothripsis") with highly localized breakpoints and small amount of DNA loss is abundant in prostate cancer. Through genetic association analysis, we find SPOP as a candidate gene causing hourglass chromothripsis and playing important role in maintaining genome integrity. Our study offers valuable insights into the formation of CGRs.
Circulating Fibroblast Growth Factor-2 precipitates HIV-nephropathy in mice

Over 80% of all children living with HIV reside in Africa and are at risk of developing HIV-associated nephropathy (HIVAN). Once HIVAN is established in children, it is difficult to revert its progression to chronic kidney failure even using antiretroviral drugs. Therefore, new therapeutic strategies are needed. Previous studies showed that the risk of developing HIVAN increases in children with high circulating levels of FGF-2, but it is unclear whether FGF-2 per se precipitates HIVAN. To unravel the role of circulating FGF-2 in childhood HIVAN, we used the HIV-Tg26 mouse model of HIVAN. Briefly, we demonstrated that circulating FGF-2 was preferentially recruited in the kidney of HIV-Tg26 mice with renal disease, and precipitated HIVAN in young mice without pre-existing kidney disease by activating the pERK pathway in renal epithelial cells without previously inducing the expression of HIV-1 genes. Wild type mice injected with recombinant adenoviral FGF-2 vectors (rAd-FGF-2) carrying a secreted form of human FGF-2 developed transient and reversible HIVAN-like lesions, including proteinuria and glomerular enlargement. HIV-Tg26 mice injected with rAd-FGF-2 developed more significant proliferative and pro-fibrotic inflammatory lesions, similar to those seen in childhood HIVAN. These lesions were partially reversed in mice treated with the FGF/VEGF receptor tyrosine kinase inhibitor PD173074. In conclusion, we developed a new FGF-2-inducible model of childhood HIVAN, and showed that high circulating levels of FGF-2 precipitated HIVAN without inducing the renal expression of HIV-genes. These findings suggest that high plasma FGF-2 levels may be an independent risk factor for precipitating HIVAN in young children.
Relationships between daily mood states and real-time cognitive performance in individuals with bipolar disorder and healthy comparators: A remote ambulatory assessment study.

OBJECTIVE Neuropsychological impairments are observed in individuals with Bipolar Disorder (BD), yet knowledge of how cognitive deficits unfold in real-time remains limited. Given intraindividual variability in mood observed in people with BD, and the potential for mood and cognition to be mutually influential, we employed ambulatory assessment technologies to examine potential contemporaneous (same survey) and lagged (next survey) relationships of congition and mood. METHODS Outpatients with BD (n = 46) or no psychiatric disorders (heathy volunteers [HV]; n = 20) completed in-laboratory neurobehavioral assessments and 14 days of smartphone-administered mobile cognitive tests and ratings of affective variables. Linear mixed-effects models were used to analyze real-time relationships between mobile cognitive test performance and mood. RESULTS On in-laboratory tests, participants with BD showed worse cognitive performance than HVs as well as mild depression severity; mood and cognitive performance were unrelated. On mobile cognitive tests and surveys, participants with BD showed somewhat worse cognitive performance and ratings of lower energy and greater sadness relative to HV participants. Among those with BD, mania and sadness earlier in the day related to worse processing speed and better working memory performance, respectively, on the next survey. In contrast, same survey ratings of greater stress related to better working memory, and greater happiness related to better processing speed. CONCLUSIONS Real-time assessments of mood and cognition provide incremental information beyond what can be gleaned from laboratory assessments. Understanding how these affect-related changes in processing speed emerge and play out in daily life may provide clinically useful information for treatment planning.
Genetics in applied microbiology

Publisher Summary This chapter discusses the genetics in applied microbiology. Mutation and selection have gained universal acceptance as the principal tools for strain development. More effort needs to be made to increase the discrimination of the selective systems because rational screening is an integral part of any program to improve an existing fermentation, or to discover a new product. Proposed projects employing genetic recombination as an approach to strain improvement have been received reluctantly. This pessimism is largely based upon a misunderstanding of the probable results of a breeding program. Recombination is a means of introducing new genetic information in an organism and increasing its variability. The new information and more precise techniques will have to be considered in the design of strain improvement programs and in the search for new products. The success of an applied microbiologist depends on his ability to assimilate new ideas and to adapt existing methods in order to accommodate a particular microbe or product.
Assay of lactosylceramide synthase and comments on its potential role in signal transduction.

Publisher Summary Increases in GAIT-2 activity have been associated with cell fusion in small Fu-1 cells, atherosclerotic tissue, and polycystic kidney diseased cells, as well as in renal cancer. This is accompanied by the accumulation of large amounts of LacCer in these tissues. Interestingly, atherosclerotic tissue is also enriched with oxidized low-density lipoproteins (Ox-LDL) and proinflammatory cytokines, such as tumor necrosis factor-a (TNF-a). A possible role of GalT-2 in cell proliferation was suggested by the finding that Ox-LDL could activate GalT-2 at an early step in the signaling pathway. In turn, LacCer served as a lipid second messenger that orchestrated an oxidant-sensitive signal transduction pathway, ultimately leading to cell proliferation in human aortic smooth muscle cells, as well as the proliferation of human kidney proximal tubular cells. In human aortic smooth muscle cells, the LacCer-mediated generation of superoxide stimulates the GTP loading of p21 ras . Subsequently, the kinase cascade (Raf-1, Mek-2, and p 44 MAPK) is activated. The phosphorylated form of p 44 MAPK translocates from the cytoplasm to the nucleus and engages c-fos expression, proliferating cell neutral antigen (PCNA) (cyclin) activation and cell proliferation. This chapter presents a method to measure the activity of GAIT-2 and focuses on the biological role of GalT-2 regarding signal transduction pathways leading to cell proliferation and cell adhesion.
Fellow-Feeling and the Moral Life: C. D. Broad's defense of moral sense theories in ethics

“SOME REFLECTIONS” To my knowledge, “Some Reflections on Moral Sense Theories in Ethics” is the only work in twentieth-century analytical moral philosophy that states and defends a version of moral sense theory. It is a provocative and ironic essay that is very underappreciated nowadays. I propose to revisit it in some detail, for several reasons. Most importantly I find its argument to be of extraordinary value as a coherent statement of what a modern moral sense theory might be like, and how it might be defended against (mainly rationalistic) critics who would attack or merely dismiss it. Broad shows fairness, ingenuity, humor and plain good sense in exploring what we are doing when we make ethical judgments; and despite the technicality of some of his language, his own illustrations to support moral sense theory – for example his discussion of “how we learn ethical words as children” – always seem to me to be true to what is “real, not invented or imagined.” Finally, although he mentions Hutcheson's name only once in the paper, and though his stated purpose is “to treat independently and in modern terminology some of the questions with which [Richard] Price was mainly concerned” in his A Review of the Principal Questions of Morals , I cannot help believing that he has taken many important cues from Hutcheson himself in shaping his own case.
Block of Sodium Channels in Planar Lipid Bilayers by Guanidinium Toxins and Calcium

The block of single, batrachotoxin-activated sodium channels by saxitoxin (STX), tetrodotoxin (TTX), and Ca2+ has been investigated in planar bilayers. All three substances block in a voltage-dependent manner with hyperpolarizing potentials favoring block. Extracellular Ca2+ competitively inhibits binding of STX and relieves STX block. Trimethyloxonium, a carboxyl-methylating agent, eliminates block by STX and TTX and dramatically reduces block by Ca2+. These results suggest that STX, TTX, and Ca2+ compete for a negative site on the outside of the channel. The voltage dependence of block by STX (divalent cation) and TTX (monovalent) was similar (40 mV/e-fold), suggesting that voltage dependence is due to a conformational change in the channel rather than to the toxins entering the membrane electric field to block. A physical model, with an external binding site for toxins and Ca2+ and another site deeper within the electric field (associated with the "selectivity filter") that is accessible to Ca2+ but not toxins, predicts voltage-dependence Ca2+ block without invoking the conformational change needed to explain the voltage dependence of block by TTX and STX.
External Cooling of Reactor Vessels during Severe Accident

Chapter 16 is devoted to the so called external cooling of reactor vessels during severe accident. It is a technology allowing arresting the melt inside the vessel of some initial conditions are fulfilled. First the state of the art is presented. Then a brief description of the phenomenology leading to melt in the lower head is discussed: dry core melting scenario, melt relocation, wall attack, focusing effect. Brief mathematical model description is given appropriate for a set of model assumptions. The model describes: the melt pool behavior, the two-dimensional heat conduction through the vessel wall, the total heat flow from the pools into the vessel wall, the vessel wall ablation, the heat fluxes, the crust formation and the buoyancy driven convection. Solution algorithm is provided for a set of boundary conditions adequate for real situations. A summary of the state of the art regarding the critical heat flux for externally flowed lower head geometry is provided. On a several practical applications different effects are demonstrated: the effect of vessel diameter, the effect of the lower head radius, the effect of the relocation time, the effect of the mass of the internal structures. Varying some important parameters characterizing the process the difference between high powered pressurized- and boiling water reactor vessel behavior is demonstrated.
Medical Examiners, Coroners, and Public Health: A Review and Update

Abstract Context.—Traditionally, the emphasis of work done by medical examiners, coroners, and the death investigation community has been viewed as serving the criminal justice system. During the last several decades, however, an important role for these 3 groups has emerged within public health. Objective.—To provide important background information on death investigation systems, the evolution and framework of public health entities that rely on information gathered by medical examiners and coroners, and the role of medical examiners and coroners in epidemiologic research, surveillance, and existing public health programs and activities. Data Sources.—Previous articles on epidemiologic aspects of forensic pathology and the role of medical examiners and coroners in epidemiologic research and surveillance; a review of the Web sites of public health and safety agencies, organizations, and programs that rely on medical examiner and coroner data collected during medicolegal investigations; and a review of re...
Learning that comes from the negative interpretation of life experience

Life experience is the basis for much of the learning that takes place in adulthood. While the learning may at times be difficult, even painful, the adult learning and development literature overwhelmingly conveys the image of learning from life experienceas fundamentally positive, leading to growth‐enhancing outcomes. But what of learning that is largely negative, that results in growth‐inhibiting outcomes such as anger, distrust, intolerance, or a constricted worldview? What happens in the process of learning from life experience when the result is debilitating, rather than enriching? Might such a process be reversed? The purpose of this study was to understand how learning from a negatively interpreted life experience can result in debilitating, growth‐inhibiting outcomes. Eighteen adults who self‐identified a negative outcome from life experience learning were interviewed in depth. Analysis of interview data revealed that if a life experience challenges some central defining aspect of the self, and th...
Metallographic Characterization of Additive-Layer Manufactured Products by Electron Beam Melting of Ti-6Al-4V Powder

Abstract Optical metallography and electron metallography (SEM and TEM) techniques are applied to the characterization of additive-layer manufactured products and prototypes by electron beam melting (EBM) of Ti-6Al-4V atomized precursor powder. In addition, microstructure-property comparisons are made by hardness and tensile test measurements which demonstrate prospects for controlled property-performance variations by varying process parameters including temperature profiles and cooling rates in manufactured prototypes.
Inhibited apoptosis and drug resistance in acute myeloid leukaemia

Despite extensive investigation into mechanisms of drug resistance in acute myeloid leukaemia (AML), the aetiology of therapeutic resistance is unclear. We found that five leukaemia cell lines (K562, HL-60, CEM. CEM induced to overexpress bcl-2, and REH) displayed parallel sensitivity to four antileukaemia drugs with different mechanisms of action, with K562 generally being the least sensitive and REH being the most sensitive. The amount of spontaneous apoptosis in the cell lines after serum-free culture paralleled their drug sensitivity: K562 cells displayed the least apoptosis at 24h (2.50 +/- 0.24%) and REH the most (24.47 +/- 8.22%). The extent of spontaneous apoptosis of leukaemic blasts from 39 patients with newly diagnosed de novo AML also correlated with the success of the intensive, infusional cytarabine-based induction therapy. There was a median of 19.5% (range 3.6-64%) apoptotic AML cells after 24 h of serum-free culture in patients who entered a complete remission compared with 4.2% (1.8-7.0%) apoptotic AML cells in patients who did not achieve a complete remission (P = 0.0007). Thus, inhibited apoptosis was associated with both in vitro and in vivo pan-resistance to antileukaemic chemotherapy. The cause of inhibited apoptosis in AML is probably a function of interactions among multiple signals that influence apoptosis. Assessment of spontaneous apoptosis may serve as an important prognostic factor for AML.
Policy and reality of Environmentally Sensitive Areas in Whitman County, Washington, USA

The Washington State Environmental Policy Act (SEPA) promotes the conservation of natural resources through procedural review of proposed actions which may impact natural systems. There are, however, many actions specifically exempt from the SEPA review process. Since many exempt actions could have significant adverse effects on natural resources at one location and not another, the SEPA statute contains a provision that enables local governments to designate Environmentally Sensitive Areas (ESAs). Within the ESAs, these potentially adverse activities are subject to SEPA review. Local governments have complete control over the exact definition of the ESA criteria and the types of local projects exempt from SEPA. Whitman County, the most productive wheat-producing county in Washington, has recognized the need for conservation of its natural resources in its comprehensive plan but has not implemented the ESA provision. A representative watershed within Whitman County was used as a case study to identify areas which would qualify for ESA status. In these areas, specific soil, water, and biological characteristics or resources were identified as sensitive to certain common land uses. Significant differences were found between state and county policies regarding ESAs and actual conditions within the watershed. It may be more effective for the state to manage ESAs on a consistent and regional basis.
WITHDRAWN: Defining the Role of Adjuvant Therapy: Cholangiocarcinoma and Gallbladder Cancer

Biliary tract cancers are a rare subgroup of malignancies that include gallbladder carcinoma and cholangiocarcinoma. They generally carry a poor prognosis based on the advanced nature of disease at presentation and overall treatment refractoriness. Surgical resection remains the optimal treatment for long-term survival, with consideration of neo-adjuvant or adjuvant therapies. In this review, we summarize the role of adjuvant treatments including radiation therapy, chemotherapy, and concurrent chemoradiation with the existing clinical evidence for each treatment decision. Given the rarity of these tumors, the evidence provided is based largely on retrospective studies, SEER database inquiries, single- or multi-institutional prospective studies, and a meta-analysis of adjuvant therapy studies. Currently, there is no adjuvant therapy that has been agreed upon as standard of care. Results from prospective, multi-institutional phase II and III trials are awaited, along with advances in molecularly-targeted therapies and radiation techniques, which will better define treatment standards and improve outcomes in this group of diseases.
Detection of Salmonella in feces by using Felix-01 bacteriophage and high-performance liquid chromatography

Abstract Utilizing the Felix-01 bacteriophage and high-performance liquid chromatographic technique, a method was devised making possible the detection of approximately 106Salmonella typhimurium/g of human feces within 8–9 h of sample collection. Using overnight enrichment, as few as 103S.typhimurium/g of feces were detectable.
Lipopolysaccharide-induced alterations in oxygen consumption and radical generation in endothelial cells.

Oxygen consumption rate (OCR) and generation of superoxide and nitric oxide (NO) in mouse aortic endothelial cells (MAECs) treated with lipopolysaccharide (LPS) were studied. The OCR was determined in cell suspensions at 37 °C by electron paramagnetic resonance (EPR) spectroscopy. LPS significantly altered the OCR in a dose and time-dependent fashion. The OCR was significantly elevated immediately following the treatment of MAECs with LPS (5 and 10 μg/ml) and NADPH (100 μM) whereas the same was depressed 1 h after exposure to similar conditions of incubation. Under similar experimental conditions, superoxide generation was also determined by EPR spectroscopy and cytochrome c reduction assays. A marginal increase in the superoxide production was observed when the cells were treated with LPS and NADPH alone whereas the same was further enhanced significantly when the cells were treated with LPS and NADPH together. The increase in oxygen consumption and superoxide production caused by LPS was inhibited by diphenyleneiodonium (DPI), suggesting the involvement of NAD(P)H oxidase. A significant increase in the NO production by MAECs was noticed 1 h after treatment with LPS and was inhibited by L-NAME, further suggesting the involvement of nitric oxide synthase (NOS). Thus, on a temporal scale, LPS-induced alterations in oxygen consumption by MAECs may be under the control of dual regulation by NAD(P)H oxidase and NOS. (Mol Cell Biochem 278: 119–127, 2005)
Prograde evolution of the Scottish Caledonides and tectonic implications

Abstract Recent thermometric analyses of samples collected in thrust-parallel structural transects across the Scandian (435–415 Ma) orogenic wedge in northwest Scotland provide a comprehensive characterization of the synorogenic retro-wedge thermal architecture. However, the paucity of petrologically-important metamorphic mineral phases (e.g., staurolite, Al-silicates) has limited investigation of pressure–temperature ( P – T ) histories, which hinders our ability to examine the nature of orogen-scale kinematic and thermal coupling. New data collected along a foreland-to-hinterland transect from the Moine to the Naver thrust sheets provides additional constraints for characterizing the prograde metamorphic evolution. In addition, we characterized Ti diffusion profiles in quartz inclusions in garnet to constrain duration of metamorphic heating. These results are used to develop coupled kinematic-thermal models of Scandian orogenic evolution. Early garnet core growth conditions are constrained by isopleth intersections, with peak P – T estimates determined by conventional exchange and net transfer thermobarometry and thermodynamic calculations. Most samples follow normal prograde heating and burial profiles, with peak conditions of 450 °C and 5.0 kbar in the immediate hanging wall to the Moine thrust, increasing in temperature and pressure to 733 °C and 9.5 kbar in the immediate hanging wall to the Naver thrust. These normal prograde pressure trajectories are interpreted to reflect burial of incipient thrust sheets beneath the overriding wedge at the leading edge of the orogen. Prograde heating coeval with burial is interpreted to result from surface-directed isotherm perturbation due to thrust-related advection in the overriding wedge. One exception to this is a sample from the top of the Moine thrust sheet, where prograde heating occurs during decompression (540 °C and 8.1 kbar to 590 °C and 7.0 kbar). In this case, the short lag times between motion on the Moine and Ben Hope thrusts may have limited advectionary heating until after exhumation associated with motion on the underlying Moine thrust was underway. Ti diffusion profiles in quartz inclusions in garnet suggest the near-peak thermal evolution of these rocks occurred over very short time scales ( 9 kbar are probably of detrital origin.
Pattern-specific sustained activation of tyrosine hydroxylase by intermittent hypoxia: role of reactive oxygen species-dependent downregulation of protein phosphatase 2A and upregulation of protein kinases.

Abstract We investigated the role of protein phosphatases (PP) and protein kinases in tyrosine hydroxylase (TH) activation by two patterns of intermittent hypoxia (IH) in rat brainstem. Rats exposed to either IH15s (15 s, 5% O2; 5 min, 21%O2) or IH90s (90 s each of 10% O2 & 21%O2) for 10 days were used. IH15s but not IH90s caused a robust increase in TH activity, dopamine (DA) level, and TH phosphorylation at Ser-31 and Ser-40 in the medulla but not in the pons. Likewise, IH15s but not IH90s decreased activity and expression of protein phosphatase 2A (PP2A) and increased activity of multiple protein kinases. In vitro dephosphorylation with PP2A nearly abolished IH15s-induced increase in TH activity. IH15s increased generation of reactive oxygen species (ROS) in brainstem medullary regions which was nearly threefold higher than that evoked by IH90s. Antioxidants prevented IH15s-induced downregulation of PP2A and increases in multiple protein kinase activity with subsequent reversal of serine phosphorylatio...
A comparative study of PtCo, PtCr, and PtCoCr catalysts for oxygen electro-reduction reaction

Abstract A comparative study of carbon supported Pt30Co70, Pt30Cr70, and Pt30Co30Cr40 catalysts for oxygen electro-reduction reaction (ORR) activity was performed. In alloy catalysts synthesized via NaBH4 reduction, more than a 3-fold improvement was observed in ORR specific activity compared with that of Pt/C catalyst, while mass activities did not show significant improvement. After annealing at 900 °C under reducing conditions, the ORR specific activities of the alloy catalysts increased to give a relative ORR catalytic activity ordering of PtCo/C-900 (2800 μA c m Pt − 2 ) > PtCoCr/C-900 (1770 μA c m Pt − 2 ) > PtCr/C-900 (871 μA c m Pt − 2 ) > Pt/C-900 (393 μA c m Pt − 2 ) > Pt/C (334 μA c m Pt − 2 ). On the other hand, the ORR mass activity followed an order of PtCr/C-900 (140 mA m g Pt − 1 ) > PtCoCr/C-900 (111 mA m g Pt − 1 ) > PtCo/C-900 (84.1 mA m g Pt − 1 ). Cyclic voltammetry results suggest that incorporation of Cr resulted in a large electrochemically active surface area producing higher mass activity in the PtCr/C-900 catalyst although it showed the lowest specific activity among the alloy catalysts. The intermediate EAS and ORR activity values of the PtCoCr/C-900 catalyst suggest that the characteristics of the PtCo/C-900 (low mass and high specific activities) and PtCr/C-900 (high mass and low specific activities) are combined by alloying of Pt with both Co and Cr.
Neural Network Imputation: An Experience with the National Resources Inventory Survey

Imputation is needed in almost all major surveys. Imputation tools are often adopted according to the convenience and the contexts of the surveys. Traditional hot-deck imputation needs extensive knowledge of the survey variables. Explicit model-based imputation needs a valid model for every survey variable. In large-scale national surveys, different groups of people with different backgrounds work on different stages of surveys and often the statistical estimation group has little or insufficient communication with the other groups. In such situations, it is difficult to use hot-deck imputation. On the other hand, because of the complex nature of the survey, finding a suitable model for every survey variable may not be easy and thus a nonparametric method— such as neural network imputation—may be attractive. One such large-scale national survey is the U.S. Department of Agriculture’s National Resources Inventory Survey (NRI). By design, the survey has missing values. The missing values are imputed using a donor-based method. This article develops a neural network imputation model and compares its performance with that of the existing imputation method. The end result looks promising.
Perceptions of Competencies Needed by Older Adults for Independent Living.

This study was conducted to determine the competencies needed to meet the individual needs of older adults when they choose independent living. The ob jectives were to determine the perceptions of 150 older adults, age 60 or over, and 251 home economists with regard to the levels of competencies needed by older adults for independent living in: (a) housing, (b) clothing, (c) personal and family relations, (d) foods and nutrition, and (e) home management and con sumer economics. The competencies were listed on two Likert-type question naires. Findings revealed that there were significant differences, at 0.05 and 0.01 levels of significance, as to the perceptions of older adults and home economists as to the importance of each competency needed. Since significant differences were perceived in all five competency areas, home economists should include older adults on advisory boards when designing programs and curricula for them.
Effects of Surface Features on Adsorption of SO2 on Graphite Oxide/Zr(OH)4 Composites

Zirconium hydroxide/graphene composites were synthesized from zirconium chloride and graphite oxide with the content of the graphene component between 5 and 50%. They were used as adsorbents of sulfur dioxide at ambient conditions. The initial and exhausted materials were characterized using adsorption of nitrogen, infrared spectroscopy, potentiometric titration, scanning electron microscopy and thermal analysis. The results indicated enhanced adsorption of SO2 on the composites, which is linked to the formation of new basic sites and porosity as a result of interactions between zirconium hydroxide units and the oxygen groups attached to the graphene layers. Both physical adsorption and reactive adsorption of SO2 via formation of sulfites play a role in the retention process. The graphene component catalyzes oxidation of SO2 and leads to the formation of sulfates.
Production of radionuclides for medicine

Naturally occurring, nuclear reactor-produced, cyclotron-produced, and generator-produced radionuclides are reviewed with special reference to nuclear medical and biological use. General methods of labeling, and 99mTc, 131I, 125I, 123I, 11C, 13N, 15O, 3H, and 14C labeling methods are described.
Attenuation of nicotine’s discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists

Reports have indicated that administration of nicotine inhibits, while withdrawal of chronically administered nicotine augments effects of serotonergic 5HT2A/2C agonists. It was our objective to determine whether 5HT2A/2C agonists can modulate the discriminative stimulus effects of nicotine in rats or its locomotor activity effects in mice. Adult male Sprague–Dawley rats were trained to discriminate 0.3 mg/kg nicotine base from saline in a two-lever, fixed-ratio (FR10), food-reinforced, operant-conditioning task during daily (Monday–Friday) 15-min experimental sessions. After characterizing a dose–response curve for nicotine, we tested the ability of the 5HT2A/2C agonists (+/−)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCL (DOI; 0.18–1.0 mg/kg) and 1-(4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB; 0.1–1.0 mg/kg), the 5HT2C agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212; 0.1 mg/kg–1.0 mg/kg), and the 5HT1A agonist (±)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.01 mg/kg–1.0 mg/kg) to modulate nicotine’s discriminative stimulus effects. After finding that DOI was able to attenuate the percentage nicotine lever responding (%NLR), we tested for it to also reverse nicotine’s effects on locomotor activity in mice. The 5HT2A/2C agonists—in particular DOI—dose dependently attenuated %NLR. The effects of DOI were reversed by the 5HT2A/2C antagonist ketanserin. MK 212 and 8-OH-DPAT had irregular effects among rats and only reduced %NLR to below 50% levels at doses markedly suppressing responding. DOI also dose dependently blocked nicotine’s acute rate-lowering locomotor activity effects. These results indicate that activation of serotonin 5HT2A/2C receptors can blunt the discriminative stimulus and locomotor activity effects of nicotine and presents the possibility that activation of these receptors might also be able to attenuate other effects of nicotine.
Varied representation of the Atlantic Meridional Overturning across multidecadal ocean reanalyses

Abstract The Atlantic Meridional Overturning Circulation (AMOC) is an integral part of the circulation in the Atlantic Ocean. The AMOC is typically characterized by the meridional streamfunction, which is also an indicator of the thermohaline circulation. This paper explores the mean state and long-term variability of the Atlantic meridional streamfunction and Atlantic meridional heat transport from six multidecadal ocean reanalysis. Statistics based on the meridional overturning streamfunction and the meridional heat transport are computed in the same manner across the products, and analyzed. The maximum streamfunction values in the Atlantic are located between 35°N and 50°N for the various ocean reanalyses. The Atlantic heat transport is greater between the Greater Antilles (at about 20°N) and 25°N, similar to the observations. The streamfunction and heat transport have stronger seasonality in the deep tropics. In the North Atlantic the annual harmonic of the streamfunction has greater amplitude in July between 40°N and 50°N. Even though there are differences in the mean strength of the streamfunction and the heat transport, there are robust similarities in their seasonal cycle across ocean reanalyses. Furthermore, although the year-to-year variability of the meridional heat transport is not consistent across products, there are other aspects that are consistent. The relationship between streamfunction and meridional heat transport at 30°N (i.e., in the northern hemisphere) shows greater consistency than that between streamfunction and meridional heat transport at 30°S (i.e., in the southern hemisphere). Also, even though the North Atlantic sea surface temperature (SST) anomalies are greatly consistent, their relationship with the meridional streamfunction is disparate. However, the relationship between North Atlantic SST anomalies and meridional heat transport shows some consistency with respect to the meridional profile. The greater numbers of temperature data assimilated may help in constraining the meridional heat transport more than the streamfunction, thereby indicating the meridional heat transport to be an important field to analyze with respect to observed changes in the AMOC.
Nerem receives 2006 geodesy section award

R. Steven Nerem received the Geodesy Section Award at the 2006 AGU Fall Meeting in San Francisco, Calif. The award is given in recognition of major advances in geodesy. Steve Nerem has been at the forefront of geodetic and oceanographic research since receiving his Ph.D. from the University of Texas at Austin, in 1989. He is currently professor of aerospace engineering sciences at the University of Colorado, Boulder, and is a Fellow of the Colorado Institute for Research in Environmental Sciences. He also serves as associate director of the Colorado Center for Astrodynamics Research.
Increasing Vitamin C Content in Plant Foods to Improve Their Nutritional Value—Successes and Challenges

Vitamin C serves as a cofactor in the synthesis of collagen needed to support cardiovascular function, maintenance of cartilage, bones, and teeth, as well as being required in wound healing. Although vitamin C is essential, humans are one of the few mammalian species unable to synthesize the vitamin and must obtain it through dietary sources. Only low levels of the vitamin are required to prevent scurvy but subclinical vitamin C deficiency can cause less obvious symptoms such as cardiovascular impairment. Up to a third of the adult population in the U.S. obtains less than the recommended amount of vitamin C from dietary sources of which plant-based foods constitute the major source. Consequently, strategies to increase vitamin C content in plants have been developed over the last decade and include increasing its synthesis as well as its recycling, i.e., the reduction of the oxidized form of ascorbic acid that is produced in reactions back into its reduced form. Increasing vitamin C levels in plants, however, is not without consequences. This review provides an overview of the approaches used to increase vitamin C content in plants and the successes achieved. Also discussed are some of the potential limitations of increasing vitamin C and how these may be overcome.
Genetic relations between iron and stony meteorites

The main group pallasites and the mesosiderites fall within the oxygen isotope group previously determined for the calcium-rich achondrites (eucrites, howardites and diogenites), consistent with derivation from a common source material, and perhaps a common parent body. The group IIE iron meteorites were derived from the same source material as H-group ordinary chondrites. The chondrite-like silicate inclusions in group IAB iron meteorites are not related to the ordinary chondrites, but may be related to the enstatite chondrites. Several meteorites previously considered “anomalous” fall into these groups: Pontlyfni and Winona with the IAB irons, and Netschaevo possibly with the H chondrites and IIE irons. The unusual pallasites Eagle Station and Itzawisis have remarkable oxygen isotopic compositions, and have more of the 16O-rich component than any other meteorite. Bencubbin and Weatherford are also unusual in their isotopic compositions, and may bear some relationship to the C2 carbonaceous chondrites. Lodran and Enon are isotopically similar to one another and are close to the achondrite-mesosiderite-pallasite group.
Reeling in the Catch: Advancing Cleavable Linkers for Proteomics

In global proteomic applications that focus on the characterization of proteins that have been derivatized using bioorthogonal chemistry, a challenge persists in the release of labeled proteins from supports used for purification. In this issue, Yang and coworkers (2010) present a detailed study of the diazobenzene-cleavable linker system as an effective solution for proteomic studies.
A new large species of Sivapithecus from the Siwaliks of Pakistan

Abstract A new species of Sivapithecus, S. parvada, is described on the basis of a large sample of dental-gnathic and postcranial remains from a single locality (Sethi Nagri, ca. 8·8 My old) in the Siwalik sequence of the Potwar Plateau, Pakistan. Its most striking feature is its very large size compared to other Siwalik Sivapithecus species. It also differs in mandibular dental proportions, having very large premolars and M3 relative to M1 and M2. The temporal position of S. parvada is analyzed in the context of other Siwalik hominoid samples and Siwalik mammal faunas generally. A brief review of Siwalik hominoid taxonomy and a new diagnosis of the genus Sivapithecus are also presented. The holotype of Gigantopithecus giganteus, whether an M2 or an M3, accords better with the mandible of G. “bilaspurensis” than with any Sivapithecus species, and the synonymy of these two taxa is upheld.
Developing the surveillance algorithm for detection of failure to recognize and treat severe sepsis.

Abstract Objective To develop and test an automated surveillance algorithm (sepsis "sniffer") for the detection of severe sepsis and monitoring failure to recognize and treat severe sepsis in a timely manner. Patients and Methods We conducted an observational diagnostic performance study using independent derivation and validation cohorts from an electronic medical record database of the medical intensive care unit (ICU) of a tertiary referral center. All patients aged 18 years and older who were admitted to the medical ICU from January 1 through March 31, 2013 (N=587), were included. The criterion standard for severe sepsis/septic shock was manual review by 2 trained reviewers with a third superreviewer for cases of interobserver disagreement. Critical appraisal of false-positive and false-negative alerts, along with recursive data partitioning, was performed for algorithm optimization. Results An algorithm based on criteria for suspicion of infection, systemic inflammatory response syndrome, organ hypoperfusion and dysfunction, and shock had a sensitivity of 80% and a specificity of 96% when applied to the validation cohort. In order, low systolic blood pressure, systemic inflammatory response syndrome positivity, and suspicion of infection were determined through recursive data partitioning to be of greatest predictive value. Lastly, 117 alert-positive patients (68% of the 171 patients with severe sepsis) had a delay in recognition and treatment, defined as no lactate and central venous pressure measurement within 2 hours of the alert. Conclusion The optimized sniffer accurately identified patients with severe sepsis that bedside clinicians failed to recognize and treat in a timely manner.
Decentralization and educational performance: evidence from the PROHECO Community School Program in rural Honduras

We analyze the effectiveness of the Programa Hondureno de Educacion Comunitaria (PROHECO) community school program in rural Honduras. The data include standardized tests and extensive information on school, teacher, classroom and community features for 120 rural schools drawn from 15 states. Using academic achievement decompositions we find that PROHECO schools do a better job of maximizing teacher effort and involving parents in the school, both of which translate into higher levels of achievement. But these efficiency advantages are offset (to some degree) by lower levels of teacher experience, training, parental education, as well as a reliance on smaller class sizes. The results help extend the community school and school based management (SBM) literatures by identifying plausible mechanisms in the chain linking increased community involvement with better student outcomes, while also highlighting the importance of local capacity.
Syntheses and structural characterizations of iron(II) complexes containing cyclic diphosphine ligands with positioned pendant nitrogen bases

A series of new iron(II) complexes that contain cyclic diphosphine ligands with pendant amine bases, P2RN2R‘, have been synthesized and characterized (where P2RN2R‘ are substituted 1,5-diaza-3,7-diphosphacyclooctanes). These compounds include [Fe(P2PhN2Ph)(CH3CN)4](BF4)2 (5), cis-[Fe(P2PhN2Ph)2(CH3CN)2](BF4)2 (6a), cis-[Fe(P2PhN2Bz)2(CH3CN)2](BF4)2 (6b), cis-[Fe(P2CyN2Bz)2(CH3CN)2](BF4)2 (6c), trans-[HFe(P2PhN2Ph)2(CH3CN)](BF4) (7), and cis-Fe(P2PhN2Ph)2(Cl)2 (8). The molecular structures of 5, 6b, and 7 have been confirmed by X-ray diffraction studies. For all complexes the cyclic diphosphine ligands contain one six-membered ring in a chair conformation and one six-membered ring in a boat conformation. For complex 7, the two rings that are in boat conformations result in N−H distances between the pendant amine nitrogens and the hydride ligand of 2.6 to 2.7 A. Protonation of the pendant bases in complex 7 has been found to form several products. A structural assignment for a dominant protonated isomer has...
Secondary Taste Neurons that Convey Sweet Taste and Starvation in the Drosophila Brain

The gustatory system provides vital sensory information to determine feeding and appetitive learning behaviors. Very little is known, however, about higher-order gustatory circuits in the highly tractable model for neurobiology, Drosophila melanogaster. Here we report second-order sweet gustatory projection neurons (sGPNs) in the Drosophila brain using a powerful behavioral screen. Silencing neuronal activity reduces appetitive behaviors, whereas inducible activation results in food acceptance via proboscis extensions. sGPNs show functional connectivity with Gr5a(+) sweet taste neurons and are activated upon sucrose application to the labellum. By tracing sGPN axons, we identify the antennal mechanosensory and motor center (AMMC) as an immediate higher-order processing center for sweet taste. Interestingly, starvation increases sucrose sensitivity of the sGPNs in the AMMC, suggesting that hunger modulates the responsiveness of the secondary sweet taste relay. Together, our results provide a foundation for studying gustatory processing and its modulation by the internal nutrient state.
Evaluation of Thematic Mapper data for mapping forest, agricultural and soil resources

Color composite TM film products which include TM5, TM4, and a visible band (TM1, TM2, or TM3) are superior to composites which exclude TM4 for discriminating most forest and agricultural cover types and estimating area proportions for inventory and sampling purposes. Clustering a subset of TM data results in a spectral class map which groups diverse forest cover types into spectrally and ecologically similar areas suitable for use as a stratification base in traditional forest inventory practices. Analysis of simulated Thematic Mapper data indicate that the location and number of TM spectral bands are suitable for detecting differences in major soil properties and characterizing soil spectral curve form and magnitude.
SIGACT News complexity theory column 32

We describe some recent or not-so-recent results in the model of learning known as exact learning from queries. Some results are chosen because they led to a result in complexity theory, and others are chosen because they seem to indicate an interesting line of research at the common ground of learning and complexity. More precisely, we survey: (1) an improvement of the Karp-Lipton collapse that stemmed from a learning algorithm for Boolean circuits, (2) recent advances in distinguishing information-theoretic from complexity-theoretic difficulty of learning, and (3) recent results on learning small-depth circuits with modular gates that call for a systematic study of the expressive power of so-called Multiplicity Automata.
BIOGEOGRAPHY OF BATRACHOSPERMUM HELMENTOSUM (BATRACHOSPERMALES, RHODOPHYTA) IN NORTH AMERICA USING MOLECULAR AND MORPHOLOGICAL DATA

Twelve collections of the freshwater red alga Batrachospermum helmentosum were investigated using molecular sequence and morphological data. Collections were from streams throughout the range of this species in North America, from Louisiana and Tennessee in the south to Michigan and Massachusetts in the north. Eleven morphometric characters were measured for each of the specimens sequenced. Both the rubisco large subunit gene (rbcL) and the ribosomal DNA internal transcribed spacers (ITS1 & 2) were sequenced. Morphometic results showed individuals from the various locations to be morphologically uniform with little variation in pertinent characters. In the analysis of the rbcL data, samples from Connecticut, Ohio, Louisiana, North Carolina and Indiana were identical in sequence and the Rhode Island and Massachusetts samples were most derived. The Michigan and Tennessee samples were closely related to each other but not the other samples. For the ITS data, the tree topology was similar to that obtained with the rbcL data. In comparison with rbcL, sequence variation in the ITS region among samples was greater and showed more resolution among the stream sites. In terms of biogeography, three geographically close samples (Connecticut, Rhode Island, Massachusetts) were most closely related. However, genetic relationships did not necessarily reflect geographic distance. For example, two distant populations, Louisiana and Indiana, were most closely related. Variation in ITS sequence data among individuals from a single stream site will be discussed.