cssi/SciSciGPT-SciSciNet huggingface dataset:
Computational fluid dynamics of DNA origami folding in microfluidics

DNA origami science is a promising field to arrange materials with high precision on a nanometer scale. The field has attracted much attention due to the robust self-assembly, with applications emerging in pharmaceuticals, nano-engineering, and single molecule recognition. In this research, a computational fluid dynamics (CFD) study was performed on various microfluidic reactor designs, including single-phase laminar flow, gas–liquid segmented flow, and single-phase Dean flow reactors. A new DNA origami folding kinetic model was developed, which enables the prediction of the transition of DNA origami crystal structures as well as their distribution throughout each reactor. Folding of the DNA origami is thermodynamically controlled at a higher temperature of 329 K while the kinetics control the folding at a lower temperature of 325 K, with 327 K corresponding to the optimal temperature for rapid constant temperature folding. The influence of the staple strand concentration was also considered for the first time. The liquid slug length (0.5 mm) and the Dean number (De = 100) were optimized to better understand the appropriate microfluidics. Batch PCR vials and microfluidic gas–liquid multiphase flow provide >90% yields of DNA origami faster than other designs and with less polydispersity, which makes the latter attractive for manufacturing scenarios. However, the microfluidic single-phase laminar flow forms DNA origami faster at the cost of polydispersity, which makes it attractive for high-throughput screening of the kinetics and/or in situ characterization studies. Microfluidics has tremendous potential to impact the field of DNA origami science.
Exploiting Acoustic and Lexical Properties of Phonemes to Recognize Valence from Speech

Emotions modulate speech acoustics as well as language. The latter influences the sequences of phonemes that are produced, which in turn further modulate the acoustics. Therefore, phonemes impact emotion recognition in two ways: (1) they introduce an additional source of variability in speech signals and (2) they provide information about the emotion expressed in speech content. Previous work in speech emotion recognition has considered (1) or (2), individually. In this paper, we investigate how we can jointly consider both factors to improve the prediction of emotional valence (positive vs. negative), and the relationship between improved prediction and the emotion elicitation process (e.g., fixed script, improvisation, natural interaction). We present a network that exploits both the acoustic and the lexical properties of phonetic information using multi-stage fusion. Our results on the IEMOCAP and MSP-Improv datasets show that our approach outperforms systems that either do not consider the influence of phonetic information or that only consider a single aspect of this influence.
Laboratory Evaluation of Continuous Cuff Pressure Control Methods

Background: Automatic cuff pressure (Pcuff) control devices (ACPCD) for artificial airways are available, yet there are no standards and few data to support their necessary. We hypothesized that (A) airway pressure change during mechanical ventilation (MV) is transmitted to Pcuff and (B) 3 different ACPCD and 1 manual method will result in zero drift in mean Pcuff during 12 h of simulated MV.. Methods: Experiments lasted 12 h, at 2 inspiratory target pressures (PIT), with 3 endotracheal tubes (ETT), 3 different ACPCD (Intellicuff Standalone, Pressure Eyes and Tracoe) and 1 manual method, for a total of 24 twelve-hour experimental runs. A Laerdal mannequin was intubated with an 8mm ID ETT and ventilated with: mode = PC-CMV, f (breaths/min) = 20, TI (s) = 1.0, PEEP (cm H2O) = 10, PIT (cm H2O above PEEP) = 10 and 40. For ACPCDs, the ETT pilot balloon was connected to the 1st port of a 3-way stopcock. The 2nd port was connected to a pressure transducer and data acquisition system. The 3rd port was connected to the ACPCD. For manual method, the data acquisition system was not used. The ETT was initially inflated to Pcuff = 25 cm H2O. The final pressure at 12 hours (disconnected from ventilator) was measured with an AG CUFFILL device, corrected for pressure drop due to measurement (-1.1 cm H2O). The drift in mean Pcuff was calculated as Pdrift = initial mean Pcuff — final mean Pcuff. Results: Airway pressure fluctuations from MV were reflected in changing Pcuff amplitudes ranging from 2 to 23 cm H2O. A large Pdrift occurred with the manual method (-11.1 cm H2O), but was only ± 0.4 cm H2O for automatic devices. Conclusions:ACPCDs do regulate mean Pcuff and keep Pdrift well below a clinically important threshold. However, the large Pdrift seen with the manual method warrants periodic monitoring. Further studies are needed to determine the source of leak for this method, and the physiologic effects of Pcuff amplitude changes during MV.
Saturated Space, Signs of Devotion in South Indian Temples

In this article, I investigate the significance of contemporary Tamil temple signs that have been laid, hung, and sometimes painted over earlier stone inscriptions. I am particularly interested in ...
Same Concept Different Outcomes: Sugars Determine Circadian Clock Protein Fate in Animals and Plants.

SUMMARY The circadian clocks of plants and animals are recruiting similar cellular systems to regulate PTMs of circadian clock proteins, but distinctions remain. Circadian clocks in both autotrophic and heterotrophic organisms can be refined by PTM cascades, but the same PTMs can have different functional outcomes. The role of protein glycosylation is a clear example of this dichotomy, where circadian clock transcription factors in plants and animals are modified by sugars but this results in opposite effects on protein stability.
Markets, Self-Regulation, and Government Enforcement in the Protection of Personal Information, in Privacy and Self-Regulation in the Information Age by the U.S. Department of Commerce.

A good deal of recent attention has focused on the potential for "self-regulation" on the Internet and more generally. This article proposes a general framework for deciding among markets, self-regulation and government enforcement in the protection of personal information. Self-regulation is tempting because of failures in a pure market or pure government approach. The article defines self-regulation, noting that it has the same separation of powers components (legislation, enforcement, adjudication) as traditional law. The case for self-regulation is based on: industry expertise; the creation and enforcement of industry norms of behavior; increase in reputational capital of the industry; improvement of technical standards; and the possibility that the risk of government action will lead to desirable self-regulation. Each of these potential benefits, however, may prove unpersuasive in a particular setting. Self-regulation may also promote cartel behavior or disfavor consumers or other groups not included in the "self." The paper concludes with a set of empirical questions to explore in any given choice among market, self-regulatory, and government approaches.
GSK2593074A blocks progression of existing abdominal aortic dilation

Objective Receptor interacting proteins kinase 1 and 3 (RIPK1 and RIPK3) have been shown to play essential roles in the pathogenesis of abdominal aortic aneurysms (AAAs) by mediating necroptosis and inflammation. We previously discovered a small molecular inhibitor GSK2593074A (GSK'074) that binds to both RIPK1 and RIPK3 with high affinity and prevents AAA formation in mice. In this study, we evaluated whether GSK'074 can attenuate progression of existing AAA in the calcium phosphate model. Methods C57BL6/J mice were subjected to the calcium phosphate model of aortic aneurysm generation. Mice were treated with either GSK'074 (4.65 mg/kg/day) or dimethylsulfoxide (DMSO) controls starting 7 days after aneurysm induction. Aneurysm growth was monitored via ultrasound imaging every 7 days until harvest on day 28. Harvested aortas were examined via immunohistochemistry. The impact of GSK'074 on vascular smooth muscle cells and macrophages were evaluated via flow cytometry and transwell migration assay. Results At the onset of treatment, mice in both the control (DMSO) and GSK'074 groups showed similar degree of aneurysmal expansion. The weekly ultrasound imaging showed a steady aneurysm growth in DMSO-treated mice. The aneurysm growth was attenuated by GSK'074 treatment. At humane killing, GSK'074-treated mice had significantly reduced progression in aortic diameter from baseline as compared with the DMSO-treated mice (83.2% ± 13.1% [standard error of the mean] vs 157.2% ± 32.0% [standard error of the mean]; P < .01). In addition, the GSK'074-treated group demonstrated reduced macrophages (F4/80, CD206, MHCII), less gelatinase activity, a higher level of smooth muscle cell-specific myosin heavy chain, and better organized elastin fibers within the aortic walls compared with DMSO controls. In vitro, GSK'074 inhibited necroptosis in mouse aortic smooth muscle cells; whereas, it was able to prevent macrophage migration without affecting Il1b and Tnf expression. Conclusions GSK'074 is able to attenuate aneurysm progression in the calcium phosphate model. The ability to inhibit both vascular smooth muscle cell necroptosis and macrophage migration makes GSK'074 an attractive drug candidate for pharmaceutical treatment of aortic aneurysms. Clinical Relevance Previous clinical trials evaluating pharmaceutical treatments in blocking aneurysm progression have failed. However, most agents used in those trials focused on inhibiting only one mechanism that contributes to aneurysm pathogenesis. In this study, we found GSK'074 is able to attenuate aneurysm progression in the calcium phosphate model by inhibiting both vascular smooth muscle cell necroptosis and macrophage migration, which are both key processes in the pathogenesis of aneurysm progression. The ability of GSK'0474 to inhibit multiple key pathologic mechanisms makes it an attractive therapeutic candidate for aneurysm progression.
Stochastic Acceleration and Non-Thermal Radiation in Clusters of Galaxies

We calculate the distribution of electrons in clusters of galaxies, resulting from thermalization processes in the presence of stochastic acceleration due to plasma waves. We show that the electron distribution can deviate from a Maxwell-Boltzmann distribution, due to the effect of the stochastic energy gain, provided waves can be sustained against damping. The non-thermal tail of electrons can generate as bremsstrahlung emission a flux of hard X-rays compatible with the ones recently detected in some clusters of galaxies.
The Role of Mastectomy in De Novo Stage IV Inflammatory Breast Cancer.

The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population. Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007–2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local–regional recurrence patterns were described and survival analyses were conducted. All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2−]: 31.1% vs. 44.2%; HR-negative [HR−]/HER2+: 24.4% vs. 15.4%; and HR−/HER2−: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p < 0.001). Of the 47 patients who completed trimodality therapy, 6 (12.8%) had a local–regional recurrence. Median overall survival (OS) was 19 months in the non-MRM group and 58 months in the MRM group (p < 0.001). On multivariable analysis, clinical N3 disease (hazard ratio 2.16, 95% confidence interval [CI] 1.07–4.37; p = 0.03) as well as tumor subtypes HR+/HER2− (hazard ratio 4.98, 95% CI 1.15–21.47; p = 0.03) and HR−/HER2− (hazard ratio 7.18, 95% CI 1.66–31.07; p = 0.008) were associated with decreased OS. Partial/complete response of distant disease to chemotherapy (hazard ratio 0.43, 95% CI 0.24–0.77; p = 0.005) and receipt of MRM (hazard ratio 0.52, 95% CI 0.29–0.93; p = 0.03) were independently associated with improved OS. In our retrospective study, MRM in de novo stage IV IBC patients is an independent factor associated with improved OS. Our findings strongly support the need for prospective randomized trials evaluating possible survival benefits of MRM in de novo stage IV IBC patients.
Nonlinearity in the Return to Education

This study estimates marginal rates of return to investment in schooling in 12 countries. Significant systematic nonlinearity in the marginal rate of return is found. In particular, the marginal rate of return is increasing significantly at low levels of education, and decreasing significantly at high levels of education. This may help explain why estimates of the return to schooling are often considerably higher when instrumenting for education.
A Strategy for Automatic Verification of Stabilization of Distributed Algorithms

Automatic verification of convergence and stabilization properties of distributed algorithms has received less attention than verification of invariance properties. We present a semi-automatic strategy for verification of stabilization properties of arbitrarily large networks under structural and fairness constraints. We introduce a sufficient condition that guarantees that every fair execution of any (arbitrarily large) instance of the system stabilizes to the target set of states. In addition to specifying the protocol executed by each agent in the network and the stabilizing set, the user also has to provide a measure function or a ranking function. With this, we show that for a restricted but useful class of distributed algorithms, the sufficient condition can be automatically checked for arbitrarily large networks, by exploiting the small model properties of these conditions. We illustrate the method by automatically verifying several well-known distributed algorithms including linkreversal, shortest path computation, distributed coloring, leader election and spanning-tree construction.
US IRBs confronting research in the developing world

Increasingly, US-sponsored research is carried out in developing countries, but how US Institutional Review Boards (IRBs) approach the challenges they then face is unclear. METHODS I conducted in-depth interviews of 2 hours each, with 46 IRB chairs, directors, administrators and members. I contacted the leadership of 60 IRBs in the United States (US) (every fourth one in the list of the top 240 institutions by National Institutes of Health (NIH) funding), and interviewed IRB leaders from 34 (55%).
Neutron Star Structure and Superfluidity: A 1991 Perspective

Our present understanding of neutron star structure and superfluidity is briefly summarized.
Techniques for online exploration of large object-relational datasets

Reviews techniques for exploring large object-relational scientific and statistical databases in an interactive online manner. The idea is to provide continuously updated running estimates of the final query results to the user, along with an indication of the precision of the estimates. The user can then halt the query as soon as the answer is sufficiently precise-the time required to obtain an acceptable approximate answer can be faster by orders of magnitude than the time needed to completely process the query. We describe methods for online processing of aggregation queries, online visualization and online display of a set of result records. We also describe methods that use precomputed results to rapidly obtain approximate query answers.
Wage Discrimination and Occupational Crowding in a Competitive Industry: Evidence from the American Whaling Industry

We test for wage discrimination and occupational crowding in the nineteenthcentury American whaling industry. Although our results indicate little evidence of wage discrimination, we cannot reject the hypothesis that certain groupsspecifically blacks and Portuguese-experienced some occupational crowding, though it was by no means complete and the minority-dominated occupations were not low-paying ones. In addition, we find that members of the majority group-white American and Northern European seamen-did accept a negative compensating wage differential for working with members of their own group.
The North–South divide and security in the Western Hemisphere: United States–South American relations after September 11 and the Iraq war

This paper examines the economics–security nexus in US policy toward South America, and the implications for South America of the ‘securitization’ of US foreign economic policy during the Bush administration. There has always been a tight linkage between the US foreign economic and security agendas but the real issue is the degree of ‘tightness’ at a given point in time. After the Alliance for Progress lost its way the United States tended to pursue its economic and security interests in South America in separate tracks, even if preventing Soviet intrusions in the region remained in the background. Yet after the collapse of the Free Trade Area of the Americas (FTAA) negotiations in 2004 a US strategy of ‘divide and conquer’ through bilateral trade deals has been accompanied by a ‘securitization’ discourse and there are some indications that it may ‘securitize’ as a new threat the social movements and neopopulist regimes that oppose neoliberal economic policies. The paper discusses the limits of the securitization thesis. The conclusion examines the future of US–South American relations and argues that the United States needs to renew its commitment to genuine multilateralism and re-engage the region to establish an effective and lasting partnership for dealing with common economic and security challenges in the twenty-first century.
Short Time Existence and Borel Summability in the Navier–Stokes Equation in ℝ3

We consider the Navier–Stokes initial value problem, where &#x1d4ab; is the Hodge-Projection to divergence free vector fields in the assumption that ‖f‖μ, β 3, where and [fcirc] (k) = ℱ [f (·)] (k) is the Fourier transform in x. By Borel summation methods we show that there exists a classical solution in the form t ∈ ℂ, , and we estimate α in terms of ‖ [vcirc]0 ‖μ+2, β and ‖ [fcirc] ‖μ, β. We show that ‖ [vcirc] (·; t) ‖μ+2, β < ∞. Existence and t-analyticity results are analogous to Sobolev spaces ones. An important feature of the present approach is that continuation of v beyond t = α−1 becomes a growth rate question of U(·, p) as p → ∞, U being is a known function. For now, our estimate is likely suboptimal. A second result is that we show Borel summability of v for v 0 and f analytic. In particular, Borel summability implies a the Gevrey-1 asymptotics result: , where , with A 0 and B 0 are given in terms of to v 0 and f and for small t, with ,
Modeling trust dynamics in strategic interaction

Abstract We present a computational cognitive model that explains transfer of learning across two games of strategic interaction – Prisoner's Dilemma and Chicken. We summarize prior research showing that, when these games are played in sequence, the experience acquired in the first game influences the players’ behavior in the second game. The same model accounts for human data in both games. The model explains transfer effects with the aid of a trust mechanism that determines how rewards change depending on the dynamics of the interaction between players. We conclude that factors pertaining to the game or the individual are insufficient to explain the whole range of transfer effects and factors pertaining to the interaction between players should be considered as well.
Efficiently detecting clusters of mobile objects in the presence of dense noise

We address the problem of detecting and tracking clusters of moving objects in very noisy environments. Monitoring a crowded football stadium for small groups of individuals acting suspiciously is an example of one such environment. In this scenario the vast majority of individuals are not part of suspicious groups and are considered noise. Existing spatio-temporal clustering algorithms are either incapable of detecting small clusters in extreme noise, or have high computation and storage requirements that prohibit their use in real-time alerting systems. We propose a technique called Dynamic Density Based Clustering (DDBC) that utilizes the relational history of the moving objects to increase the accuracy of the clustering algorithm. The incorporation of this information into the clustering algorithm is done efficiently and implicitly by using a relationship graph. The relationship graph incrementally estimates the strength of the relationships between moving objects. A modified DBSCAN algorithm is then used to find clusters of highly related objects from the relationship graph. We evaluate the DDBC technique experimentally on a number of data sets of mobile objects. The experiments show that DDBC outperforms both Trajectory Mining and Moving Cluster Mining techniques in terms of accuracy, memory usage, and computation time as the density of noise increases.
Induction of citrate synthase by aldosterone in the rat kidney.

The possible induction of renal citrate synthase (E.C. 4.1.3.7) by aldosterone was evaluated in the adrenalectomized rat. Three hours after administration of aldosterone (0.8 microgram/100 g body wt), renal cortical and medullary citrate synthase activity was significantly increased as reported previously by Kinne and Kirsten (Kinne, R., Kirsten, R. 1968. Pfleugers Arch. 300:244). In contrast, no change in this activity was detected in the renal papilla or the liver, under the same conditions. Kinetic analysis revealed that injection of aldosterone had no effect on the KmS for acetyl-CoA and oxalacetate but augmented Vmax of renal medullary citrate synthase activity by 40%. The aldosterone-dependent increase in medullary citrate synthase activity was proportionate to the associated increase in the quantity of antiserum (specific for citrate synthase) required for half-maximal immuno-precipitation. The possibility that aldosterone induced the synthesis of citrate synthase was evaluated in two sets of experiments. In the first set, adrenalectomized rats were injected intraperitoneally with either aldosterone (0.8 microgram/100 g body wt) or the diluent, and simultaneously with 3H or 35S methionine (500 muCi/rat). The isotopes were reversed in about half of the experiments. Three hours after the injection, renal citrate synthase was isolated by ATP-sepharose column chromatography and immuno-precipitation with the specific antiserum. Aldosterone augmented methionine incorporation into renal citrate synthase by 55% but had no effect on incorporation into the hepatic enzyme. In the second set, adrenalectomized rats were injected with either aldosterone (0.8 microcram/100 g body wt) or the diluent, the kidneys were removed 1 hr later and medullary slices were incubated in either 3H- or 35S-methionine at 20 degrees for 2 hr. Mitochondrial citrate synthase was isolated either by ATP-sepharose column chromatography and immuno-precipitation, or by polyacrylamide gel electrophoresis. Aldosterone increased methionine incorporation into the immuno-precipitates by 30% and into the enzyme peak resolved by polyacrylamide gel electrophoresis by 43%. The latter increase was eliminated by prior administration of either actinomycin D (70--80 microgram/100 g body wt) or spirolactone (SC-26304) (80 microgram/100 g body wt). An equimolar dose of dexamethasone (0.8 microgram/100 g body wt) had no effect on the isotope ratio associated with citrate synthase activity in the polyacrylamide gels.
Down-regulation of argininosuccinate synthetase is associated with cisplatin resistance in hepatocellular carcinoma cell lines: implications for PEGylated arginine deiminase combination therapy.

Background Many advanced human tumors, including hepatocellular carcinomas (HCC) are auxotrophic for arginine due to down-regulation of argininosuccinate synthetase (ASS1), the rate-limiting enzyme in arginine synthesis. The arginine-lowering agent PEGylated arginine deiminase (ADI-PEG 20) has shown efficacy as a monotherapy in clinical trials for treating arginine-auxotrophic tumors and is currently being evaluated in combination with cisplatin in other cancer types. Epigenetic silencing via methylation of the ASS1 promoter has been previously demonstrated in other cancer types, and a reciprocal relationship between ASS1 expression and cisplatin resistance has also been observed in ovarian cancer. However, the mechanism of ASS1 down-regulation, as well as the correlation with cisplatin resistance has not been explored in HCC. The present study investigates ADI-PEG 20 and cisplatin sensitivities in relation to ASS1 expression in HCC. In addition, we show how this biomarker is regulated by cisplatin alone and in combination with ADI-PEG 20.
“Homeopathic” dynamical systems

Homeopathy contends that higher dilutions of the active ingredient in a remedy (fewer molecules in each dose) produce stronger medical effects [1]. This idea is inconsistent with observed doseresponse relationships of conventional drugs, where the effects increase with the concentration of the active ingredient in the body [2]. The conventional dose-response relationship has been found in numerous scientific studies on organisms as diverse as nematodes [3], rats [4], and humans [5]. Further it is consistent with the behavior of simple physical and chemical systems, -e.g. the larger the force on a spring, the larger the displacement (Hooke’s law), or the larger the voltage on a resistor, the larger the current (Ohm’s law), and the larger the concentration difference within a solution, the larger the particle flux (Fick’s law), the larger the temperature difference on a solid the larger the heat flow, and so on.
Evaluation of radiorespirometry for the determination of monoamine oxidase activity in vivo utilizing [11c]octylamine as a substrate

Abstract The inhibition of MAO in vivo by pargyline in mice has been studied to evaluate the usefulness of n-octylamine · HC1[1-11C], a substrate of MAO that is rapidly metabolized to 11CO2, as a probe of MAO activity in vivo. In pargyline-pretreated mice, the rate of decline in tissue levels of [11C]n-octylamine after intravenous administration was decreased to an extent that varied with the particular tissue and the time after pargyline pretreatment. Likewise, pargyline-treated mice showed a reduced excretion of 11CO2 after [11C]n-octylainine administration but not after octanoie acid[1-11C] or octanol[1-11C] injection. The duration of inhibition of 11CO2 excretion after pargyline treatment paralleled reasonably well the inhibition of MAO measured directly in intestine and liver, but the inhibition of MAO in the lung, kidney and brain persisted longer. Direct measurement of mitochondrial MAO activity using [14C]octylamine showed the following: intestine > liver > lung > brain 》 kidney. At 94 hr after pargyline administration, 11CO2 excretion was close to the control value yet the MAO activity of brain, lung and kidney was less than half of the control value. Thus, the rate-determining step in the overall rate of 11CO2 excretion appears not to be the MAO-catalyzed step but the reactions occurring after deamination.
Evaluating Parenting Coordination Programs: Encouraging Results From Pilot Testing a Research Methodology

A subset of families who separate and divorce become embroiled in conflict and demand a disproportionate amount of court resources both during and after their legal divorce process. The court system has responded by establishing parenting coordination (PC) programs to assist parents in resolving conflict without utilizing court resources to do so. In spite of widespread implementation, empirical research into the effects of PC programs is “practically nonexistent” (Henry, Fieldstone, & Bohac, 2009). The present study is a pilot study of a PC program in one jurisdiction to investigate the use of a methodology not previously used within the parenting coordination literature to test the effectiveness of PC programs. Variables relating to the amount of judicial, court personnel, outside agency, and parental time that was spent on each case were coded from legal divorce files. Results indicate that the PC program reduced the number of: motions filed by parents, documents processed by court personnel, judicial ...
Ichthyophthirius multifiliis: a model of cutaneous infection and immunity in fishes

The parasitic ciliate Ichthyophthirius multifiliis offers a useful system for the study of cutaneous immunity against an infectious microorganism. Naive fish usually die following infection, but animals surviving sublethal parasite exposure become resistant to subsequent challenge. This resistance correlates with the presence of humoral antibodies in the sera and cutaneous mucus of immune fish. A mechanism of immunity has recently been elucidated that involves antibody binding to surface proteins (referred to as immobilization antigens or i-antigens) located on the parasite cell and ciliary membranes. Antibody-mediated cross-linking of i-antigens triggers a response by the parasite resulting in its exit from the host. These effects can be observed directly on the surface of live fish. In addition to allowing the observation of effector responses in vivo, Ichthyophthirius also provides a means to study the ontogeny of the mucosal immune response. The sites of antigen capture and presentation, and the sites of antibody production, are unknown with regard to cutaneous immunity. Because the external epithelial surfaces of fish are often the points of pathogen entry, a basic understanding of the inductive immune mechanisms and immune cell interactions in the skin and gills is extremely important with regard to vaccine development. The development of Ichthyophthirius as an experimental system and how it might be used to address these issues are discussed in this review.
Qualitative evaluation of thermal desorption-programmable temperature vaporization-comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry for the analysis of selected halogenated contaminants

Abstract The separation of 38 toxic and predominant polychlorinated biphenyl (PCB) congeners, 11 persistent halogenated pesticides, 1 brominated biphenyl (BB), and 8 polybrominated diphenyl ethers (PBDEs) has been optimized using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC–TOFMS). A thermal desorption-programmable temperature vaporization (TD-PTV) step was used for the injection. Different column sets were investigated, and a 100% dimethylpolysiloxane ( 15 m ×0.25 mm i.d.×0.25 μm film thickness) narrowbore capillary column coupled to a high temperature (8% phenyl)-polycarborane-siloxane ( 2 m ×0.10 mm i.d.×0.10 μm film thickness) microbore column set was selected. Of the 58 compounds investigated, only one pair of PCBs was not resolved. All other analytes were either baseline separated into the chromatographic plane or were virtually separated using the deconvolution capability of the TOFMS.
Alterations in matrix metalloproteinase-9 levels and tissue inhibitor of matrix metalloproteinases-1 expression in a transforming growth factor-β transgenic model of hydrocephalus

The development of spontaneous hydrocephalus in mouse models resulting from the overexpression of transforming growth factor-beta (TGFbeta-1) has been previously described, although the mechanism by which this occurs remains obscure. It has been previously demonstrated that increased expression of TGFbeta has consequences for the levels of matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitors of MMPs, or TIMPs). These remodeling proteins play an important role in extracellular matrix (ECM) maintenance through degradation and deposition of ECM components. The present study investigated the relationship between elevated levels of TGFbeta-1, the ECM modulators TIMP-1 and MMP-9, and development of hydrocephalus in the neonatal mouse. In newborn pups, TIMP-1 mRNA levels were equal between animals expressing the TGFbeta-1 transgene and littermates without the transgene. However, immunohistochemistry of littermate pups shows that the distribution of TIMP-1 was changed from homogeneous with large punctate concentrations of signal to uniform, dense staining in hydrocephalic animals carrying the TGFbeta-1 transgene. The mRNA levels of MMP-9 were decreased in the transgenic animals, as were the activity levels MMP-9. These results suggest that the remodeling protein MMP-9 and its specific inhibitor, TIMP-1, may contribute to the spontaneous development of hydrocephalus in this transgenic model by altering the ECM environment.
Thatcher receives 2004 Charles A. Whitten medal

Wayne Thatcher received the Whitten Medal at the 2004 Fall Meeting Honors Ceremony on 15 December, in San Francisco, California. The medal is given for outstanding achievement in research on the form and dynamics of the Earth and planets.
Preferential interaction of a 25 kDa protein with an A6 pre-mRNA substrate for RNA editing in Trypanosoma brucei

Mitochondrial gene expression in kinetoplastids is controlled after transcription, potentially at the levels of RNA maturation, stability and translation. Among these processes, RNA editing by U-insertion/deletion catalysed by multi-subunit editing complexes is best characterised at the molecular level. Nevertheless, mitochondrial RNA metabolism overall remains poorly understood, including the potential regulatory factors that may interact with the relevant catalytic molecular machines and/or RNA substrates. Here we report on a approximately 25kDa polypeptide in mitochondrial extracts that exhibits a preferential "zero-distance" photo-crosslinking interaction with an A6 pre-mRNA model substrate for RNA editing containing a single [(32)P] at the first editing site. The approximately 25kDa polypeptide purified away from editosomes upon ion-exchange chromatography and glycerol gradient sedimentation. Competition assays with homologous and heterologous transcripts suggest that the preferential recognition of the A6 substrate is based on relatively low-specificity RNA-protein contacts. Our mapping and substrate truncation analyses suggest that the crosslinking activity primarily targeted a predicted stem-loop region containing the first editing sites. Consistent with the notion that pre-mRNA folding may be required, pre-annealing with guide RNA abolished crosslinking. Interestingly, this preferential protein interaction with the A6 substrate seemed to require adenosine 5'-triphosphate but not hydrolysis. As in other biological systems, fine regulation in vivo may be brought about by transient networks of relatively low-specificity interactions in which multiple auxiliary factors bind to mRNAs and/or editing complexes in unique higher-order assemblies.
Reliability estimation for the exponential distribution

This paper is concerned with classical statistical estimation of the reliability function for the exponential density with unknown mean failure time θ, and with a known and fixed mission time τ. The minimum variance unbiased (MVU) estimator and the maximum likelihood (ML) estimator are reviewed and their mean square errors compared for different sample sizes. These comparisons serve also to extend previous work, and reinforce further the nonexistence of a uniformly best estimator. A class of shrunken estimators is then defined, and it produces a shrunken quasi-estimator and a shrunken estimator. The mean square errors for both these estimators are compared to the mean square errors of the MVU and ML estimators, and the new estimators are found to perform very well. Unfortunately, these estimators are difficult to compute for practical applications. A second class of estimators, which is easy to compute is also developed. Its mean square error properties are compared to the other estimators, and it outperf...
Vaccinia virus-mediated high level expression and single step purification of recombinant Jak2 protein.

Abstract Jak2 functions as a non-receptor tyrosine kinase and has been linked to pathologies such as cancer and cardiovascular disease. Because of this, many studies have tried to better understand its function. Unfortunately, very little information is known about its catalytic or biochemical properties as purification of significant amounts of functional Jak2 protein has been exceedingly difficult. Here, Jak2 was expressed in BSC-40 cells using a vaccinia virus-mediated expression system. Significant amounts (∼10 μg) of Jak2 protein were expressed from a single 100-mm cell culture dish. The protein was first harvested using three different methods of extraction to determine the relative efficiency of each lysis method with respect to Jak2 protein yield and catalytic activity. We found that lysis methods utilizing detergents increased the efficiency of protein extraction about 3-fold when compared to a method lacking detergent. However, with respect to catalytic activity, Jak2 isolated from cells using detergent-containing lysis buffers had significantly less catalytic activity than when compared to the method that was detergent free. Expression was then scaled up and Jak2 protein was purified via a one step immunoaffinity purification scheme using both the detergent-free and a modified detergent-containing method of extraction that maintained catalytic activity. In vitro kinase assays demonstrated that the purified product was highly catalytic as measured by its ability to tyrosine phosphorylate Stat1. Collectively, the results show that (1) Jak2 can be expressed at very high levels in mammalian cells, (2) it can be purified to homogeneity via a single step purification scheme, and (3) the purified product is biologically active.
State of stress within a bending spherical shell and its implications for subducting lithosphere

SUMMARY The state of stress within a bending spherical shell has some special features that are caused by sphericity. While most lithospheres are more like spherical shells than flat plates, our ideas of the state of stress have been dominated by flat-plate models. As a consequence, we might be missing some important aspects of the state of stress within subducting lithospheres. In order to examine this problem, we analyse spherical-shell bending problems from basic equations. We present two approaches to solve sphericalshell bending problems: one by the variational approach, which is suitable for globalscale problems, and the other by the asymptotic equation, which is valid to first order in h/R, where h is the thickness of the lithosphere and R is its curvature radius (i.e. under the assumption of small curvature). The form of the equation for displacement shows that wavelengths of deformation are determined by the spherical (elastic) eVect and the gravitational buoyancy eVect, for which only the latter eVect is included in the usual flat-plate formulations. In the case of the Earth, the buoyancy force is dominant and, consequently, spherical eVects are suppressed to a large extent; this explains why flat-plate models have been successful for Earth’s lithospheric problems. On the other hand, the state of stress shows interesting spherical eVects: while bending (fibre) stress along the subduction zone is always important, bending stress along the trench-strike direction can also be important, in particular when the subduction zone arc is small. Numerical results also indicate that compressive normal stress along the trench-strike direction is important when a subduction zone arc is large. These two stresses, the bending stress and the compressive normal stress, both along the trench-strike direction, may have important implications for intraplate earthquakes at subduction zones.
Physical Model for Drag Reduction in Turbulent Pipe Flow

WHEN small amounts of certain soluble high molecular weight polymers are added in a turbulent fluid flowing in a pipe, the frictional drag can be significantly reduced. This phenomenon is generally attributed to viscoelasticity. The explanations are, however, of a qualitative nature and based on a comparison between time scales, length scales or velocity scales of the turbulence and of the viscoelastic fluid1–3.
Treatment of depression in patients with heart disease

There is a growing body of evidence that depression significantly and adversely affects cardiovascular health. Perhaps the most prominent finding is the documented increase in mortality rate in patients with depression after myocardial infarction. The critical questions of interest to both the clinician and researcher are whether there are safe and effective treatments for depression in patients with heart disease and whether treatment of depression reduces the increased risk of cardiac morbidity and mortality. Though the data are limited and are primarily from open or comparator trials, the tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and specific psychotherapies appear to be effective for treatment of depression in patients with ischemic heart disease (IHD), and response rates are comparable to those reported in depressed patients without heart disease; however, there has been only one placebo-controlled trial to date, and therefore it is premature to come to definitive conclusions regarding the efficacy of antidepressant therapies in this patient population. With respect to safety, the TCAs are associated with documented adverse cardiovascular effects, including increases in heart rate, orthostatic hypotension, and conduction delays. Use of TCAs in patients with IHD carries a proven increased risk of cardiac morbidity and perhaps of mortality as well. The SSRIs appear to be relatively safe and effective treatment for depression in patients with comorbid IHD.
Development of free convection flow of a gas in a heated vertical open tube

Abstract The system is a vertical tube open at both ends and heated at the wall. An ambient gas (Pr = 0.7) enters the bottom of the tube with uniform velocity and temperature and flows up through the tube due to natural convection. The flow is assumed to be both stable and laminar. The incompressible thermal boundary layer equations for this situation were solved by a finite difference method for conditions of constant wall temperature and constant wall heat flux. From the velocity and temperature profiles obtained for various stages of the flow development, a graphical correlation was found between dimensionless tube length and two dimensionless quantities representative of the volumetric flow rate and the rate of heat dissipation. For the case of constant wall temperature these results were compared with those of Elenbaas [3], and excellent agreement was obtained. The results for constant wall heat flux were compared with those of Kays [8] on laminar forced convection. His calculations, in which the transverse velocity component was assumed negligible, gave Nusselt numbers near the entrance that are 20–30 per cent higher than the present results.
The subjects of the world’s books: A further examination of Unesco’s book production statistics

The Unesco Statistical Yearbook includes in its annual volumes tables reporting the number of books published by countries in subject classes according to the UDC classification system. These statistics are examined to assess global trends in subjects areas such as pure, social, medical, and applied sciences, and literature. Data from Asia, Latin America, Africa, and North America are found to be highly inconclusive due to nonreporting patterns. Data from Europe and the USSR are more comprehensive. According to these data, social science titles form the largest percentages of the world's production, followed by applied sciences and literature. Overall, literature and medical science titles appear to be increasing in production faster than other subject areas.
Joining the war: Masculinity, nationalism and war participation in the Balkans war of secession, 1991–1995*

Why do people go to war? My own interest in this question emerged from the context of my dissolving country and Serbia's increased engagement in a very strident form of ethnonationalism. Although s...
Differential responses of the right ventricle to abnormal loading conditions in vivo: possible pathophysiologic mechanisms.

Objective The right ventricle (RV) demonstrates differential adaptations in response to pressure versus volume loading, a phenomenon that may be important in the management of children and adults with congenital heart disease (CHD). The purpose of this study is to elucidate possible transcriptional mechanisms of the RV response to pressure versus volume loading in vivo. Methods Fetal lambs had aortopulmonary shunting or pulmonary artery (PA) banding. Four weeks after spontaneous delivery, ovine hearts were evaluated for hemodynamic changes and changes in expression of sarcomeric gene proteins and transcriptional factors. Western blot densitometry and chromatin immunoprecipitation were applied using standard techniques. Transactivation assays were performed using transient transfections in Schneider's Drosophila line 2 cells in culture. Results After PA banding, the RV pressure increased from 36 ± 4 mm Hg (n = 4) to 96 ± 8 mm Hg (n = 4, P Drosophila line 2 cells, acetylation of Sp3 converted it from a transcriptional repressor to an activator. Conclusions Posttranslational modifications of the transcriptional repressor Sp3, by acetylation, may be an important mechanism in the differential response of the RV to abnormal loading conditions. Sp3 may serve as a biomarker for RV failure for various heart defects in children and adults with CHD. These findings may have therapeutic implications in the management of right heart failure.
A Generalized Influence Model for Networked Stochastic Automata

The joint dynamics of a collection or network of interacting discrete-time automata can often be described by a single Markov chain. In general, however, analyzing such a chain is computationally intractable for even moderately sized networks because of the explosion in the size of the state space. Asavathiratham introduced the influence model (IM) as a framework for overcoming such limitations. The IM imposes constraints on the update behavior of a network of automata, allowing efficient analysis while still permitting interesting global behavior. However, some of the constraints of the IM are unnecessarily restrictive. The generalized IM (GIM) presented here relaxes some restrictions of the IM, thereby permitting more complex behavior without losing many of the attractive properties of the IM and actually enabling simpler proofs of several results. The GIM is explained and illustrated in relation to the IM from a variety of different perspectives, including geometric. Several examples of GIMs are presented.
Adaptive designs for comparative effectiveness research trials

AbstractMedical and health policy decision-makers require improved design and analysis methods for comparative effectiveness research (CER) trials. In CER trials, there may be limited information to guide initial design choices. In general settings, adaptive designs (ADs) have effectively overcome limits on initial information. However, CER trials have fundamental differences from standard clinical trials including population heterogeneity and a vaguer concept of a “minimum clinically meaningful difference”. The objective of this article is to explore the use of a particular form of ADs for comparing treatments within the CER trial context. To achieve this, the authors review the current state of clinical CER. They also identify areas of CER as particularly strong candidates for application of novel AD and illustrate the potential usefulness of the designs and methods for two group comparisons. The authors found that ADs can stabilize power. Furthermore, the designs ensure adequate power for true effects ...