cssi/SciSciGPT-SciSciNet huggingface dataset:
Red cell-derived microparticles (RMP) as haemostatic agent

Among circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 µm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.
Metabolic Activation of the Tobacco Carcinogen 4-(Methylnitrosamino)-(3-pyridyl)-1-butanone by Cytochrome P450 2A13 in Human Fetal Nasal Microsomes

Among human P450s studied to date, P450 2A13 is the most efficient catalyst of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-hydroxylation. This reaction is a key bioactivation pathway in NNK-induced carcinogenesis. P450 2A13 mRNA has been detected in human tissues, but it is unknown whether the enzyme is functional in vivo. Therefore, we studied NNK alpha-hydroxylation in human fetal nasal mucosal microsomes, which have been shown to contain high levels of P450 2A protein, presumed to be a mixture of P450 2A6 and 2A13. The microsomes efficiently catalyzed NNK alpha-hydroxylation at the methylene and methyl carbons, as well as carbonyl reduction. Antibodies against mouse P450 2A5 inhibited alpha-hydroxylation by these microsomes greater than 90%. K(m) and V(max) values for alpha-methylene hydroxylation were 6.5 +/- 1.1 muM and 3.0 +/- 0.1 pmol/min/mg; for alpha-methyl hydroxylation, they were 6.7 +/- 0.8 microM and 0.85 +/- 0.03 pmol/min/mg. The K(m) values agree closely with those for NNK metabolism by P450 2A13. Using a new technique, we separated P450 2A13 from P450 2A6 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Quantitative immunoblot analysis indicated that the level of P450 2A13 in the pooled fetal nasal microsome sample used for kinetic analysis was approximately 1.6 pmol/mg protein. In the same sample, P450 2A6 was not detected (detection limit, 67 fmol/mg protein). These kinetic, immunoinhibition, and immunoblot data confirm that P450 2A13 is a functional enzyme and the catalyst of NNK alpha-hydroxylation in human fetal nasal mucosa. The results are also the first to demonstrate high efficiency NNK alpha-hydroxylation in a human tissue.
Genetics of schizophrenia: I. Familial patterns and mode of inheritance

The purpose of this article is to review and condense the available literature on genetic modeling in schizophrenia research. The principles underlying genetic models and the various applications of these models to family data are reviewed. It is concluded that despite the advances in statistical genetics, the mode of inheritance of schizophrenia remains elusive. The conflicting results are attributed to variation in methods for data collection and analysis and to the heterogeneous nature of the disorder. The possibility is also raised that most previous genetic analyses of schizophrenia may have been compromised by methodological drawbacks. Although the use of advanced genetic models in conjunction with adequate data may shed more light on the genetic contribution to schizophrenia, the limitations of this approach in genetically heterogeneous disorders must be recognized. Alternative methods, such as studies with biological susceptibility traits and genetic markers, may be more useful in unraveling the specific genetic components that underlie the transmission of schizophrenia.
Cytidylate cyclase: the product isolated by the method of Cech and Ignarro is not cytidine 3',5'-monophosphate.

Abstract When mouse liver homogenates were incubated with [α-32P]-CTP according to the method of Cech and Ignarro (4,5), a [32P] product (100–120 pmoles/mg protein/minute) was isolated by chromatography on alumina column, in the same fraction as [3H]-cyclic CMP. 1 However this product did not behave as cyclic CMP in various chromatographic systems. Moreover the amount of this [32P] product isolated was markedly reduced by removal of protein prior to chromatography on alumina. Chromatography of the enzymatic reaction product either before or after alumina purification on Dowex 1 — formate column indicated that 5′-CMP and CDP are the major products, with no formation of cyclic CMP. These results indicate that the [32P] labeled material isolated by Cech and Ignarro is mainly if not entirely 5′-CMP and CDP.
Polysomy and p16 deletion by fluorescence in situ hybridization in the diagnosis of indeterminate biliary strictures.

Background The diagnosis of indeterminate biliary strictures is limited because of the low sensitivity of cytology. However, an accurate diagnosis of malignancy is critical in the management of patients with suspected biliary malignancy. Testing for chromosomal aneuploidy by fluorescence in situ hybridization (FISH) may increase the yield. Objective To evaluate the diagnostic accuracy of FISH in indeterminate biliary strictures and the additional value of including deletion of 9p21 (p16) in the diagnostic criteria of malignant biliary strictures. Design Retrospective review. Setting Academic medical center. Patients This study involved 76 consecutive patients who were seen for the evaluation of indeterminate strictures at our institution. These patients were screened, and 50 patients with either a final pathologic diagnosis or ≥12 months' conclusive follow-up were included in the analysis. Main Outcome Measurements Sensitivity, specificity, and area under the curve (AUC) analysis of cytology alone compared with the presence of FISH polysomy versus FISH polysomy and 9p21 deletion. Results The presence of increased copy numbers (polysomy) of chromosome 3, 7, or 17 by FISH increased the sensitivity of brush cytology from 21% to 58%, and when the presence of 9p21 deletion was included, the sensitivity increased to 89%. The specificity of FISH was 97% (vs 100% for cytology). The accuracy of cytology combined with FISH polysomy (AUC = 0.93) or p16 deletion was significantly greater than the accuracy of cytology alone (AUC 0.6; P P ≤ .05). Limitations Sample size. There is a relatively high incidence of malignant biliary strictures in the entire cohort but low incidence among primary sclerosing cholangitis patients, and the majority of cancers are cholangiocarcinomas (as opposed to pancreatic). Conclusion FISH significantly improves the diagnostic accuracy of brush cytology in indeterminate biliary strictures. In our series, the addition of 9p21 deletion to FISH polysomy and cytology further improved sensitivity. This suggests that 9p21 deletion may be added to the diagnostic criteria in indeterminate strictures.
Molecular markers to individualize adjuvant therapy for colon cancer

While many patients with early-stage colon cancer are cured with surgery alone, the standard of care remains a uniform approach to adjuvant chemotherapy based primarily on tumor stage. Recently, increasing awareness of the need for more individualized decision-making in cancer care has led to the development of several potential prognostic and predictive markers in colon cancer. While adjuvant chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin is clearly beneficial to patients with stage III disease, well-validated molecular markers might help define which patients with stage II disease are likely to benefit from adjuvant therapy as well. Here, we review the data on the clinical development of molecular markers to individualize adjuvant therapy in colon cancer.
The Influence of Learning Characteristics on Evaluation of Audience Response Technology

AUDIENCE RESPONSE TECHNOLOGY (ART) has been widely adopted on college campuses, and prior research indicates that, on average, it receives positive evaluations from students. However, research has not yet examined how characteristics of students as learners influence their responses to ART. The current study examined aptitude for learning, objective learning (i.e., class performance), subjective learning (i.e., self-perceived learning), and conceptualizations of the learning process as influences on students' evaluation of ART. Students who had used ART over the course of a semester in one of three large lecture classes (N=703) completed surveys assessing their learning characteristics, perceptions of ART influence on their attendance, motivation, and learning, liking for ART, and evaluations of the course and instructor. Controlling for course and instructor evaluations, aptitude and objective learning were weakly but negatively associated with evaluations of ART and subjective learning was positively associated with evaluations of ART. Further, different conceptualizations of learning have distinctive associations with ART evaluations. Discussion focuses on the implications of these findings for instructors' use of ART.
Does gender discrimination contribute to India’s population imbalance? A household level analysis

Son preference in India results in abortion of female foetuses, and excess female infant mortality due to childhood neglect. Whether the increased use of abortion will reduce female infant mortality is a matter of debate. Using India’s National Family Health Survey (NFHS) 2005–2006, this paper demonstrates that after controlling for socioeconomic variables, an increase in the number of abortions will reduce female infant mortality. From a policy perspective, the results call for urgent enforcement of abortion laws to prevent its increasing abuse to abort female foetuses, and the need to encourage women’s education to reduce both female mortality disadvantages.
Synthetic control of composition and crystallite size of silver ferrite composites: profound electrochemistry impacts

A paradigm for concomitant control of crystallite size and composition of bimetallic composites via co-precipitation is introduced. Direct preparation of composites of silver ferrite and amorphous maghemite via nonstoichiometric synthesis was demonstrated. Notable impact on electrochemistry was observed, with ∼200% increase in reversible capacity for the small crystallite material.
Chronic hepatitis B

Interferon alpha, lamivudine, and adefovir are the three drugs currently approved for the treatment of chronic hepatitis B virus (HBV). There are pros and cons associated with the use of each drug. Individualization of therapy, based upon factors such as patient comorbidities, response to prior therapies, and stage of disease, is recommended. Patients with abnormal liver enzymes, indices of active viral replication (HBV DNA positive hepatitis B early antigen positive) or evidence of necroinflammatory activity on liver biopsy, and compensated liver disease are potential candidates for treatment with interferon, lamivudine, or adefovir. Patients with abnormal liver enzymes, indices of active viral replication (HBV DNA positive HB(e)Ag positive), and decompensated liver disease are candidates for treatment with lamivudine or adefovir. Consideration of liver transplantation should occur concurrently. Interferon alpha treatment results in hepatitis B surface antigen loss and sustained suppression of HBV DNA replication in 30% to 40% of treated patients. Loss of HBsAg occurs in nearly 10% of patients and a higher than expected frequency of HBsAg loss occurs long-term. The main limitation of therapy is the side effects and the need for parenteral administration. Additionally, interferon therapy is not applicable to all patient groups. Lamivudine achieves HB(e)Ag seroconversion in 15% to 20% of patients treated for 12 months, but (HBsAg) loss is rare. Reduction in HBV DNA to undetectable levels (by hybridization assay) during treatment is nearly universal, and histologic improvement is seen in about 55% of patients. The main limitation of lamivudine therapy is the development of drug resistance, which occurs in 20% of patients after 12 months and increases with duration of therapy (55% at 3 years). Adefovir achieves HB(e)Ag seroconversion in 12% of patients treated for 12 months, but HBsAg loss is rare. An average 3.5 log reduction in HBV DNA levels is and histologic improvement occurs in 50% to 60% of patients. It is effective against both wild-type and lamivudine-resistant HBV. The risk of drug resistance is low and estimated to be approximately 2% to 3% after 2 years of treatment. Several new antiviral agents are currently under evaluation in clinical trials. In addition, there are two drugs (tenofovir and emtricitabine) that have been approved for HIV infection and that have anti-HBV activity. In the future, combination therapy for chronic HBV infection can be anticipated. Utilization of two or more anti-HBV drugs would be predicted to enhance efficacy and reduce the likelihood of emergence of drug resistance.
Hot Spots of Inorganic Nitrogen Availability in an Alpine-Subalpine Ecosystem, Colorado Front Range

Inorganic nitrogen (N) availability hot spots have been documented in many ecosystems, but major uncertainties remain about their prevalence, timing, and causes. Using a novel mathematical definition of hot spots, spatially explicit measurements of KCl-extractable inorganic N, 2-week soil incubations in the field, ion-exchange resins deployed for 1 year, and a set of associated biotic and abiotic variables, we investigated inorganic N availability hot spots within a 0.89 km2 alpine-subalpine ecosystem in the Colorado Front Range. Measurements of KCl-extractable NH4 + and NO3 − taken on multiple dates showed that hot spots of N availability were present in some but not all parts of the study site and that hot spot location varied over the course of the season. Ion-exchange resins showed that over a 1-year period hot spots were important contributors to resin-available N at the landscape level, with 14% of resin locations accounting for 58% of total resin-extractable inorganic N. The KCl-extractable and resin-available inorganic N measurements showed that although spatial variation in the timing of hot spots (that is, hot moments) spreads the influence of short-term hot spots across the landscape to some extent, spatial variation in inorganic N availability is still important when integrated over 1 year. Resin-available N was poorly correlated with the biotic and abiotic variables that we measured, though we did observe that hot spots of resin-available N were twice as common below tree and shrub canopies than in herbaceous areas. Beyond this relationship with canopy structure, neither KCl-extractable nor resin-available inorganic N hot spots were closely related to plant species identity. Instead, the most effective predictor of KCl-extractable NH4 + was the size of the soil organic matter (SOM) N pool, with nearly all hot spots appearing in soils that had greater than 1.4% SOM N.
Probing heterotypic cell interactions: Hepatocyte function in microfabricated co-cultures

Replacement of liver function using extracorporeal bioartificial systems has been attempted with limited success. The instability of the hepatocyte phenotype in vitro has restricted the useful lifetime of these devices. Co-cultivation of hepatocytes with mesenchymal cells is one method that has been widely utilized to stabilize the liver-specific function of isolated cells; however, co-culture has yet to be successfully incorporated in a bioreactor setting. In this study, we probed heterotypic cell interactions in co-cultures of hepatocytes and 3T3 in order to better understand the cellular microenvironment necessary to induce and stabilize liver-specific functions. Using microfabrication and conventional techniques to control the heterotypic interface, the effects of varying degrees of heterotypic interaction on tissue function (albumin and urea synthesis) were examined. Our data indicated maximal induction of liver-specific functions in cultures with maximal initial heterotypic interaction, and that ind...
General Air Pollution and Cancer in the United States

Abstract General air pollution may be defined as a body of contaminated air extending over a population area of appreciable size (a town, city, etc.). It excludes occupational, personal, or neighborhood pollution exposure to dusts or fumes. In the American Cancer Society's study of a half million men, subjects who had lived in the same neighborhood for at least 10 years were classified into various categories by place of residence, and whether or not they were occupationally exposed to dusts, fumes, or vapors. Lung cancer rates were computed standardized by age and smoking habits. Men who said they were occupationally exposed had mortality rates of lung cancer 14% greater than the nonexposed. Among those not exposed, there were little or no differences in mortality ratios by urban-rural place of residence, in Los Angeles and nearby counties; by whether they lived in cities with high, medium, or low levels of total suspended particulate matter or benzene-soluble organic matter. We conclude the general air pollution at present has very little effect, if any, on the lung cancer death rate.
Expression of a potyvirus non-structural protein in transgenic tobacco

A cDNA fragment encoding the cytoplasmic inclusion protein of tobacco vein mottling virus was inserted into the plant expression cassette of a Ti plasmid-based binary vector. The vector was transferred to Agrobacterium tumifaciens, and following a modified leaf disc procedure, transformed tobacco plants were obtained. Analysis of poly(A)+ RNA from transgenic plants revealed a novel RNA of approximately 2100 nucleotides possessing tobacco vein mottling virus sequences. Also, immunoprecipitation of protein extracts of [35S]methionine-labeled transformed callus using anti-cytoplasmic inclusion protein antiserum revealed a polypeptide of approximately 70 kDa. This size is consistent with that predicted from the inserted tobacco vein mottling virus coding sequences. Together these data demonstrate the expression of the cytoplasmic inclusion protein in the absence of viral infections.
Impaired perception of mnemonic oldness, but not mnemonic newness, after parietal lobe damage

In studies of episodic memory retrieval, recognition paradigms are known to elicit robust activations in the inferior parietal lobe. However, damage to this region does not produce severe deficits in episodic memory performance as indexed by typical accuracy measures. Rather, because problems with memory confidence are frequently reported, the observed deficits may be best described as “metamemory” or subjective memory deficits. Here, we further investigated the inferior parietal lobe’s role in recognition memory as well as metamemory. We tested the hypothesis that the inferior parietal lobe gauges the perceived oldness of items, given several neuroimaging findings suggesting that a portion of the left inferior parietal lobe is sensitive to perceived oldness. We tested two patients with bilateral parietal lobe lesions and matched controls on an old/new recognition task. From these data we constructed receiver operating characteristic (ROC) curves by fitting the data with the unequal-variance signal-detection (UVSD) model. The results revealed no memory impairment in terms of patients’ accuracy. However, patients exhibited lower hit rates and false alarms rates at high confidence levels. Further, patients and controls differed in how they set decision criteria for making recognition responses. Patients’ decision criteria for “old” responses were shifted in a conservative fashion such that they were unwilling to endorse recognized target items with high levels of confidence. These findings provide constraints on models of inferior parietal lobe contributions to episodic memory retrieval.
Observation of homonuclear double-quantum correlations in plastic crystals using cross polarization and magic-angle spinning

The homonuclear doublequantum correlation experiment INADEQUATE (I7) represents an important capability for structure determination using NMR. In this experiment, spin-spin (scalar) coupling is used to generate double-quantum coherence between pairs of magnetic nuclei. In the two-dimensional version of this experiment, the double-quantum frequencies are allowed to evolve for a time t, . Then, after an appropriate readout pulse, magnetization is detected during time tz. In the two-dimensional spectrum, coupled nuclei with chemical-shift offsets of 6, and 8* in the F2 dimension are observed in F, at a frequency of 6, + 6z, thus allowing connectivities to be established. Well used and documented in the area of liquid-state NMR, the technique has not yet been applied to problems using cross polarization/magic-angle spinning (CP/MAS) NMR because of the difficulties associated with the observation of scalar coupling in CP/MAS NMR. In usual CP/MAS NMR samples, dipolar coupling usually obscures any scalar coupling which might be present. There are, however, a number of CP/MAS samples where scalar homonuclear couplings can be observed. Plastic crystals are an example of a type of sample which cross polarizes and can still show homonuclear scalar coupling. This note illustrates scalar double-quantum observation using two different plastic crystalline samples. Dipolar double-quantum spectra have been observed using cross polarization with an isotopically enriched single crystal of glycine (8). Although the pulse experiment used in the single crystalline glycine study is very similar to the sequence described in this work, there is a major difference in the experimental details. In the dipolar case, T delays necessary to generate doublequantum coherence are relatively short due to the strong dipolar interaction strength, while in the case of scalar couplings, 7 delay times are relatively long due to the weak interaction of the scalar coupling. The results reported in this paper are more closely related to the liquid-phase INADEQUATE experiment than to the glycine study referenced above. The solids INADEQUATE pulse sequence, illustrated in Fig. 1, was based on a liquid-state experiment which uses a 45” read pulse (6) and requires 128 scans for a complete phase cycle. For the solids experiment, the initial 90” pulse was replaced by a proton decoupler 90” pulse and a Hartmann-Hahn cross-polarization pulse (CP). Spin temperature alternation was also incorporated into the phase cycling to eliminate artifacts. After 128 scans are acquired to complete the phase cycle, the phase of the
Conflict, Religious Identity, and Ethnic Intolerance in Croatia

The purpose of this article is to answer the question, Does religiosity cause ethnic intolerance? We define ethnic intolerance as the unwillingness to extend economic, political, and social rights to other ethnic groups. According to the "resurgence hypothesis," religious revivals associated with frequent church attendance and intense religious beliefs arepartly responsiblefor intolerant attitudes toward minorities. The "salience hypothesis," on the other hand, suggests that ethnic intolerance and religiosity arejointly determined by in-group/out-group polarization resultingfrom competition and conflictfor scarce resources. Under the salience hypothesis, religiosity is hypothesized to be merely a carier of group identity and is not expected to affect intolerance. We evaluate these hypotheses with survey data from Croatia collected in 1996. Results support the salience hypothesis: the effect of religiosity on ethnic intolerance is largely spurious, caused by the joint determination of religiosity and ethnic intolerance by in-group/out-group polarization. These findings call into question popular views that posit resurgent religiosity as a significant motivator of intolerance in situations of ethnic conflict.
Plant resistance mechanisms to air pollutants: rhythms in ascorbic acid production during growth under ozone stress.

Relationships between ozone (O3) tolerance and leaf ascorbic acid concentrations in 03-susceptible (O3S) ‘Hark’ and O3-resistant (O3R) 'Hood'soybean, Glycine max (L.) Merr., cultivars were examined with high-performance liquid chromatography (HPLC). Leaf samples were analyzed at 4 h intervals during a 24 h period. Soybean cultivars grown in the greenhouse with charcoal filtered (CF) and nonfiltered (NF) air showed daily oscillations in ascorbic acid production. Highest ascorbic acid levels in leaves during light coincided with highest concentrations of photochemical oxidants in the atmosphere at 2:00 p.m. The resistant genotype produced more ascorbic acid in its trifoliate leaves than did the corresponding susceptible genotype. Under CF air (an O3-reduced environment) O3-S and O3-R cultivars showed rhythms in ascorbic acid production. In NF air (an O3 stress environment) the O3-R cultivar alone showed rhythms in ascorbic acid production. Results indicated that superior O3 tolerance in the Hood soybean cul...
Staphylococcus aureus catheter-associated bacteremia. Minimal effective therapy and unusual infectious complications associated with arterial sheath catheters.

Objective: To determine factors that predict complications and examine outcomes of Staphylococcus aureus bacteremia according to the duration of antibiotic therapy. Methods: Clinical data were extracted from charts of patients with positive blood cultures for S aureus at a single institution during a 2-year period. Results: Of 102 patients with S aureus bacteremia, 55 were considered to have bacteremia attributable to an intravascular catheter, including five patients who were bacteremic after percutaneous transluminal coronary angioplasty. Among the other 50 patients with S aureus catheter-associated bacteremia, infection was community acquired in 18 and nosocomial in 32. Septic pulmonary emboli were more common in patients with community-acquired S aureus catheter-associated bacteremia, most of whom had Hickman catheters or venous access disks. Delayed removal of the infected catheter was associated with persistence of bacteremia ( P =.01). With patients with early complications excluded, patients treated for 10 to 15 days had clinical characteristics similar to those of patients treated with longer courses of antibiotics and had similarly low rates of relapse (0% vs 4.7%). In contrast, treatment with parenteral antibiotics for less than 10 days appeared to be inadequate in that relapse occurred in two of three such patients. Staphylococcus aureus catheter-associated bacteremia associated with percutaneous transluminal coronary angioplasty was complicated by a femoral artery mycotic aneurysm in two of five patients. Conclusion: Approximately one third of S aureus catheter-related bacteremias were community acquired, reflecting increased usage of intravascular devices for home parenteral support. A 10- to 15-day course of parenteral antibiotics was equivalent to longer courses of therapy in patients without early complications. (Arch Intern Med. 1995;155:1161-1166)
3D whiteboard: collaborative sketching with 3D-tracked smart phones

We present the results of our investigation of the feasibility of a new approach for collaborative drawing in 3D, based on Android smart phones. Our approach utilizes a number of fiduciary markers, placed in the working area where they can be seen by the smart phones' cameras, in order to estimate the pose of each phone in the room. Our prototype allows two users to draw 3D objects with their smart phones by moving their phones around in 3D space. For example, 3D lines are drawn by recording the path of the phone as it is moved around in 3D space, drawing line segments on the screen along the way. Each user can see the virtual drawing space on their smart phones' displays, as if the display was a window into this space. Besides lines, our prototype application also supports 3D geometry creation, geometry transformation operations, and it shows the location of the other user's phone.
Interaction of endothelial eccrine mechanisms and human adrenomedullin on vascular resistance in canine bone

Adrenomedullin is a novel peptide known to be one of the most potent vascular smooth muscle relaxing agents in vivo. The aim of this study is to investigate the effect of adrenomedullin in relation to nitric oxide, prostaglandins and endothelium-derived hyperpolarized factor (EDHF). A 0.1 -ml bolus of I nmol human adrenomedullin is a potent inhibitor of the pressor response to exogenous norepinephrine infusion in an ex vivo canine tibia perfusion model for a duration of at least 70 min (P < 0.005). This attenuation of vascular smooth muscle contraction occurs even when nitric oxide production is blocked by N G -monomethyl-L-arginine acetate (L-NMMA) infusion and EDHF is blocked by tetraethylammonium infusion, although the effect is of shorter duration (at least 10 min). Indomethacin as well does not affect the suppression of norepinephrine-induced vascular smooth muscle contraction. Based on these data, human adrenomedullin has both nitric oxide- and EDHF-dependent mechanism as well as a nitric oxide- and EDHF-independent mechanism.
Stress corrosion cracking of an aluminum alloy used in external fixation devices

Treatment for compound and/or comminuted fractures is frequently accomplished via external fixation. To achieve stability, the compositions of external fixators generally include aluminum alloy components due to their high strength-to-weight ratios. These alloys are particularly susceptible to corrosion in chloride environments. There have been several clinical cases of fixator failure in which corrosion was cited as a potential mechanism. The aim of this study was to evaluate the effects of physiological environments on the corrosion susceptibility of aluminum 7075-T6, since it is used in orthopedic external fixation devices. Electrochemical corrosion curves and alternate immersion stress corrosion cracking tests indicated aluminum 7075-T6 is susceptible to corrosive attack when placed in physiological environments. Pit initiated stress corrosion cracking was the primary form of alloy corrosion, and subsequent fracture, in this study. Anodization of the alloy provided a protective layer, but also caused a decrease in passivity ranges. These data suggest that once the anodization layer is disrupted, accelerated corrosion processes occur.
Discrimination with jointly equicorrelated multi-level multivariate data

In this article we study a linear as well as a quadratic discriminant function for multi-level multivariate repeated measurement data under the assumption of multivariate normality. We assume that the m-variate observations have jointly equicorrelated covariance structure in addition to a Kronecker product structure on the mean vector. The new discriminant functions are very effective in discriminating individuals when the number of observations is very small. The proposed classification rules are demonstrated on a real data set. The error rates of the proposed classification rules are found to be much less than the error rates of the traditional classification rules, when in fact the traditional classification rules fail most of the time owing to the small sample sizes.
Problem management in decision support systems: a knowledge-based approach

The purpose of this paper is to discuss the importance of problem management in DSS. This study proposes a knowledge-based approach to design a problem manager that acts as an in-charge for the entire problem solving process. The required functionality of the problem manager is also outlined. The model is then applied to investment portfolio optimization problems, which are chosen as a problem domain. The prototype problem manager and the required user interface is developed in PROLOCr and Visual BASIC, respectively. The issues involved in the design and development of the prototype are discussed. Finally, the paper concludes with the suggestions for the future research directions.
CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas

Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas. In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively. Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%. CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.
Post-injury substance abuse among persons with brain injury and persons with spinal cord injury.

Alcohol and drug use at the time of injury have been strongly implicated as causal factors of spinal cord injury (SCI) and traumatic brain injury (TBI). Researchers have only begun their efforts to investigate the pre-injury incidence of substance abuse in an effort to identify persons at risk for traumatic injury. No studies have compared brain and spinal cord injury populations. This investigation was based in an urban, level one trauma center federally designated as a model system of comprehensive rehabilitative services for persons with TBI and persons with SCI. Pre-injury patterns of alcohol and illicit drug use were compared among patients with SCI and patients with TBI, matched for age, gender, race, and mechanism of injury (n= 52). In accordance with previous research, participants were primarily young, unmarried, males with at least a high school education. Eighty-one percent of patients with TBI and 96% of patients with SCI reported pre-injury alcohol use. The rate of pre-injury heavy drinking for both groups was alarmingly high. Fifty-seven percent of persons with SCI and 42% of persons with TBI were heavy drinkers. Implications for risk identification, treatment, and future research are discussed.
HitWalker: variant prioritization for personalized functional cancer genomics

Summary: Determining the functional relevance of identified sequence variants in cancer is a prerequisite to ultimately matching specific therapies with individual patients. This level of mechanistic understanding requires integration of genomic information with complementary functional analyses to identify oncogenic targets and relies on the development of computational frameworks to aid in the prioritization and visualization of these diverse data types. In response to this, we have developed HitWalker, which prioritizes patient variants relative to their weighted proximity to functional assay results in a protein–protein interaction network. It is highly extensible, allowing incorporation of diverse data types to refine prioritization. In addition to a ranked list of variants, we have also devised a simple shortest path-based approach of visualizing the results in an intuitive manner to provide biological interpretation. Availability and implementation: The program, documentation and example data are available as an R package from www.biodevlab.org/ HitWalker.html.
Chaotic cardiac arrhythmias

To understand the behavior of the heart under chaotic conditions, a computer simulation was made considering it as coupled biological oscillators. Piece-wise linear and non-linear equations were used to characterize the observed phase response behavior of the myocardial cells. Models predict phase locking and chaotic regions that correspond to the AV blocks and fibrillations during cardiac arrhythmias.
On the implementation of adaptive filters with adjustable linear constraints

Linearly constrained systems are specified using a set of vector inner products with the filter weights in which each of the M inner products is constrained to equal a scalar value. The constraint vectors are presumed known and fixed while adaptation takes place on the M constraint scalars. The filter structure simultaneously adapts to minimize output power while maintaining the adjustable linear constraints. >
Tamoxifen induces the expression of maspin through estrogen receptor-α

Abstract Maspin (mammary serine protease inhibitor) is a tumor suppressor gene that plays an important role in inhibiting tumor growth, invasion and metastasis. Maspin expression is down regulated at transcription level in primary and metastatic breast tumor cells. Previous studies on hormonal regulation of maspin prompt us to test whether an estrogen antagonist tamoxifen (TAM) [1] can exert its anti-tumor function by up regulating maspin gene expression. For this purpose, we first tested whether maspin promoter could be activated in normal and several breast tumor cells. We then carried out a series of promoter analysis in which estrogen receptors and TAM were reconstituted in an in vitro cell culture system. Here we report our new finding that tumor suppresser gene maspin is one of the TAM target genes. TAM induces a maspin/luciferase reporter in cell culture and this induction requires the presence of (estrogen receptor alpha) ERα but not estrogen receptor-β (ERβ). Maspin promoter deletion and mutation analysis showed that the cis element(s) within a region between −90 and+87 bp but not the HRE site (−272 bp) was involved in TAM induction of maspin expression. TAM bound ERα may directly control maspin gene expression through the interaction with cofactor (s). Analysis using several ERα mutants showed that the N-terminal A/B motif (AF-1) was critical for maspin basal level transcription activation. An ERα mutant with point mutations at DNA binding domain abolished estrogen induction of an ERE–luciferase reporter but was still active in activating maspin promoter by TAM. LBD-AF2 domain was required for ERα-dependent TAM induction. Deletion of LBD-AF2 or a point mutation in the ERα LBD-AF2 region (LBDmtL539A) completely abolished the activation of maspin promoter, suggesting that TAM induction of maspin involves the recruitment of cofactor(s) by ERα to the maspin promoter region. This finding indicates that one of the pathways for cancer prevention and tumor inhibition by TAM is mediated through the activation of tumor suppressor gene maspin in breast cancer.
A Virus-Virus Interaction Circumvents the Virus Receptor Requirement for Infection by Pathogenic Retroviruses

During ongoing C-type retrovirus infection, the probability of leukemia caused by insertional gene activation is markedly increased by the emergence of recombinant retroviruses that repeatedly infect host cells. The murine mink cell focus-inducing (MCF) viruses with this property have acquired characteristic changes in the N-terminal domain of their envelope glycoprotein that specify binding to a different receptor than the parental ecotropic virus. In this report, we show that MCF virus infection occurs through binding to this receptor (termed Syg1) and, remarkably, by a second mechanism that does not utilize the Syg1 receptor. By the latter route, the N-terminal domain of the ecotropic virus glycoprotein expressed on the cell surface in a complex with its receptor activates the fusion mechanism of the MCF virus in trans. The rate of MCF virus spread through a population of permissive human cells was increased by establishment of trans activation, indicating that Syg1 receptor-dependent and -independent pathways function in parallel. Also, trans activation shortened the interval between initial infection and onset of cell-cell fusion associated with repeated infection of the same cell. Our findings indicate that pathogenic retrovirus infection may be initiated by virus binding to cell receptors or to the virus envelope glycoprotein of other viruses expressed on the cell surface. Also, they support a broader principle: that cooperative virus-virus interactions, as well as virus-host interactions, shape the composition and properties of the retrovirus quasispecies.
Assessing Emotion Regulation in Social Anxiety Disorder: The Emotion Regulation Interview

Social anxiety disorder (SAD) is thought to involve emotional hyper-reactivity and emotion dysregulation. However, the precise nature of the emotion dysregulation in SAD has not been well characterized. In the present study, the Emotion Regulation Interview (ERI) was developed to quantify the frequency and self-efficacy of five emotion regulation strategies specified by Gross’s (Review of General Psychology 2: 271–299, 1998) process model of emotion regulation. Forty-eight individuals with SAD and 33 healthy controls (HCs) were interviewed about responses during (a) a laboratory speech task and (b) two recent social anxiety-evoking situations. Individuals with SAD reported greater use of avoidance and expressive suppression than HCs, as well as lesser self-efficacy in implementing cognitive reappraisal and expressive suppression. These regulation deficits were not accounted for by differences in emotional reactivity. These findings highlight specific emotion regulation deficits in SAD, and support the idea that the Emotion Regulation Interview may be usefully applied to other clinical disorders.
Robust optimization for performance tuning of modern database systems

Abstract Issues regarding design and management of database systems have been studied by applying operations research (OR) techniques. The purpose of this study is to propose a new alternative towards database performance tuning for query-processing needs of modern database systems from the perspective of operations research using robust optimization. We use a query-driven approach to specify database structures (schema) so that they are robust to uncertainty and dynamics of queries in a changing environment and allow fast and timely information retrieval and exchange. Instead of applying hardware tuning or traditional database tuning techniques, we examine queries by their types and properties to derive database structures that are robust at efficiently processing future queries of any type. This query-driven approach improves the efficiency of processing queries by setting up database structures based on the queries’ information needs. This new methodology provides a new approach of tuning database performance that is robust to unexpected changes and dynamics. To further demonstrate the idea, we develop a robust optimization model using a non-linear von Neumann–Morgenstern expected utility function and present two computational examples.
IMPROVEMENT OF TRIANGLE TEST DATA BY USE OF INCENTIVES

The objectives of this study were to determine the distribution of the sensory panelists’ ability to detect differences and to improve the triangle test by minimizing unnecessary guessing. The triangle test was modified to include the use of economic incentives through which panelists voluntarily revealed their ability to detect differences. Panelists were asked to estimate their ability to detect differences and the probability of identifying the odd sample in a triangle test. They were then organized into three ability groups according to their responses. Double triangle tests, followed by triangle tests with economic incentives, were used to evaluate a cereal product and a beverage. The ability to detect differences was modeled as a probability, and the distribution of panelists was estimated. The economic incentives test was more effective when used with the beverage in which differences were less difficult to detect. We found that the economic incentive test discouraged the panelists from guessing unnecessarily, thus increasing the motivation of the panelists to detect differences, and allowing researchers to determine the distribution of discrimination ability.
Emitter Uniformity and Application Efficiency for Centre‐ Pivot Irrigation Systems

A significant portion of the intensively cultivated agricultural areas in the Southern Great Plains of the USA is located in the Texas High Plains. Agriculture in this region mainly depends on water from the vast underground Ogallala Aquifer. Due to excess withdrawal and a slow recharge process, groundwater levels are declining in many areas of the aquifer. Recently, regulations have been enacted in the Texas High Plains for restricting the amount of water pumped from the Ogallala Aquifer. In addition to pumping restrictions, conserving water by promoting irrigation systems with high application efficiency is also a priority. We investigated the emitted uniformity and application efficiency of 14 centre-pivot irrigation systems in the Texas High Plains. Application efficiencies were in the range of 60–70% for mid-elevation spray application (MESA) systems, 70–80% for low-elevation spray application (LESA) systems, and greater than 90% for low-energy precision application (LEPA) systems. Correction of the small number of defective emitters per system would not realize significant water savings. However, water savings could be realized by switching fromMESA or LESA to LEPA, assuming the choice of crop allowed it. Copyright © 2015 JohnWiley & Sons, Ltd. key words: irrigation auditing; emitter uniformity; application efficiency; mid-elevation spray application; low elevation spray application; low-energy precision application Received 29 April 2014; Revised 29 July 2014; Accepted 29 July 2014
Growth rates in a wild primate population: ecological influences and maternal effects

Growth rate is a life-history trait often linked to various fitness components, including survival, age of first reproduction, and fecundity. Here we present an analysis of growth-rate variability in a wild population of savannah baboons (Papio cynocephalus). We found that relative juvenile size was a stable individual trait during the juvenile period: individuals generally remained consistently large-for-age or small-for-age throughout development. Resource availability, which varied greatly in the study population (between completely wild-foraging and partially food-enhanced social groups), had major effects on growth. Sexual maturity was accelerated for animals in the food-enhanced foraging condition, and the extent and ontogeny of sexual dimorphism differed with resource availability. Maternal characteristics also had significant effects on growth. Under both foraging conditions, females of high dominance rank and multiparous females had relatively large-for-age juveniles. Large relative juvenile size predicted earlier age of sexual maturation for both males and females in the wild-feeding condition. This confirmed that maternal effects were pervasive and contributed to differences among individuals in fitness components.