cssi/SciSciGPT-SciSciNet huggingface dataset:
Rates of benthic mixing in deep-sea sediment as determined by radioactive tracers

A series of closely spaced radiocarbon measurements on a carbonate-rich box core from the western equatorial Pacific show a mixed layer at least 7 cm thick, with 14C ages between 4000 and 5000 years, and an orderly progression of ages below this layer, indicating an average sedimentation rate of about 2 cm/103 yr. The profile can be simulated using a numerical extension of the mixing model of Guinasso and Schink (1975) and a numerical exponential mixing model. The best-fit iteration indicates an apparent mixing coefficient of K = 120 cm2/103 yr which also fits well the excess 210Pb distribution. The best-fit also indicates that a small amount of sediment was lost on the top, and that there was a reduction in sedimentation rate within the early Holocene.
Effect of Uncertainty on Deterministic Runway Scheduling

Active runway scheduling involves scheduling departures for takeoffs and arrivals for runway crossing subject to numerous constraints. This paper evaluates the effect of uncertainty on a deterministic runway scheduler. The evaluation is done against a firstcome-first-serve scheme. In particular, the sequence from a deterministic scheduler is frozen and the times adjusted to satisfy all separation criteria; this approach is tested against FCFS. The comparison is done for both system performance (throughput and system delay) and predictability, and varying levels of congestion are considered. The modeling of uncertainty is done in two ways: as equal uncertainty in availability at the runway as for all aircraft, and as increasing uncertainty for later aircraft. Results indicate that the deterministic approach consistently performs better than first-come-first-serve in both system performance and predictability.
The collision rate of small drops undergoing thermocapillary migration

Abstract The pairwise collision rate of small spherical drops undergoing thermocapillary migration in a dilute dispersion is predicted using a trajectory analysis. The emphasis of our analysis is the effects of drop interactions on collision rate, as described by the collision efficiency. It is found that increases in the viscosity and/or thermal conductivity of the drop fluid decrease the collision efficiency due to the effects of hydrodynamic and thermocapillary interactions. It is of particular interest that the relative velocity of two unequal drops changes sign as they become very close together, if the thermal conductivity of the drop fluid is sufficiently large relative to that of the surrounding fluid. Under these conditions, drop collision does not occur unless in the presence of other driving forces such as an attractive van der Waals force.
Discrete trials teaching.

The advantages of emphasizing discrete trials teaching over discrete trials training are presented first, followed by a discussion of discrete trials as a method of teaching that emerged historically—and as a matter of necessity for difficult learners such as those with autism—from discrete trials as a method for laboratory research. The elements of discrete trials teaching are presented next, and after that a set of guidelines for discrete trials teaching is given and elaborated upon. A final note on deciding what to teach and how best to teach it concludes the article. © 2007 Wiley Periodicals, Inc. Psychol Schs 44: 667–679, 2007.
Evidence for Non-Cosmological Redshifts - QSOs Near Bright Galaxies and Other Phenomena

All of the speakers at this meeting except me have assumed, or will assume, without question that redshifts are measures of distance. This reflects a point of view which is not borne out by all of the evidence. I shall attempt to give you some of the flavor of the evidence which so many wish to ignore. It comes from individuals who perhaps not surprisingly, have not been invited to speak.
An online phase margin monitor for digitally controlled switched-mode power supplies

This paper presents a practical injection-based method for continuous monitoring of the crossover frequency and phase margin in digitally controlled switched-mode power supplies (SMPS). The proposed approach is based on Middlebrook's loop-gain measurement technique, adapted to digital controller implementation. A digital square-wave signal is injected in the loop, and the injection signal frequency is adjusted while monitoring loop signals to obtain the system crossover frequency and phase margin online, i.e., during normal SMPS operation. The approach does not require open loop or steady-state SMPS operation and is capable of convergence in the presence of load transients or other disturbances. Experimental results are presented for various power stage configurations demonstrating close matches between monitored and expected crossover frequencies and phase margins.
Predicting indirect branches via data compression

Branch prediction is a key mechanism used to achieve high performance on multiple issue, deeply pipelined processors. By predicting the branch outcome at the instruction fetch stage of the pipeline, superscalar processors become able to exploit Instruction Level Parallelism (ILP) by providing a larger window of instructions. However, when a branch is mispredicted, instructions from the mispredicted path must be discarded. Therefore, branch prediction accuracy is critical to achieve high performance. Existing branch prediction schemes can accurately predict the direction of conditional branches, but have difficulties predicting the correct targets of indirect branches. Indirect branches occur frequently in Object-Oriented Languages (OOL), as well as in Dynamically-Linked Libraries (DLLs), two programming environments rapidly increasing in popularity. In addition, certain language constructs such as multi-way control transfers (e.g., switches), and architectural features such as 64-bit address spaces, utilize indirect branching. In this paper, we describe a new algorithm for predicting unconditional indirect branches called Prediction by Partial Matching (PPM). We base our approach on techniques proven to work optimally in the field of data compression. We combine a viable implementation of the PPM algorithm with dynamic per-branch selection of path-based correlation and compare its prediction accuracy against a variety of predictors. Our results show that, for approximately the same hardware budget, the combined predictor can achieve a misprediction ratio of 9.47%, as compared to 11.48% for the previously published most accurate indirect branch predictor.
Thermal ignition theory applied to diesel engine autoignition

AbstractThe diesel community has used one-equation models for ignition delay in engines for decades. The inverse Arrhenius forms characterizing many of these expressions thus lump together liquid fuel evaporation, mixing of the vapour with the charge and the chemical delay. As a result, correlations apply only to the injector, engine and operating conditions tested. Additionally, they typically exhibit energies or temperatures of activation that can be as much as ten times lower than those obtained in well-mixed, controlled systems that isolate and study the chemical delay. Here the latter system is modelled first, using classical analysis techniques. The result is then extended to the relatively straightforward fluid mechanic environment of a laminar counterflow burner to clarify how both chemistry and mixing can be included in a more general one-equation model. This new model is validated with ignition limit data for ethane or ethene with O2/N2 either premixed or unmixed in the counterflow arrangement a...
Department Store Apparel Buyers: Relationships Among Environmental Characteristics, Environmental Uncertainty, Boundary Spanning Activities, Managerial Discretion and Power:

The purpose of the study was to explore the relationships among environmental characteristics, uncertainty, boundary spanning activities, managerial discretion, and power of the department store apparel buyer who assumes combination or independent buyer responsibilities. Almubarek's Model of Organizational Boundary Spanning and Duncan's (1972) Model of Environmental Uncertainty were used as conceptual frameworks. A questionnaire was mailed to buyers who purchased merchandise in the moderate-to-better sportswear areas in the top 10 department store groups in the United States.The results generated support for the nature of relationships found among the variables in Almubarek's Model: a complex, dynamic environment leads to environmental uncertainty and perceptions of uncertainty trigger the use of boundary spanning activities which enhances the power of the buyer. In addition, the placement of apparel retailers within Duncan's (1972) Model should be revised to reflect a highly uncertain environment.
Optimum and sub-optimum detection of physics-based ultra-wideband signals in presence of inter-symbol interference

The paper represents a major step toward receiver structures under the framework of the per-path pulse distortion using more realistic channel models. We extend our previous framework to include the important phenomenon of inter-symbol interference (ISI). ISI ultimately limits the maximum achievable data rate. We find that the per-path pulse distortion has impact on this maximum achievable data rate in the presence of ISI. As examples of this discovery, we investigate the optimum receiver structure and two sub-optimum receivers with zero-forcing and minimum mean square error (MMSE) equalizers. We use the high-rise building channel model as the underlying pulse propagation model. This model captures many properties that are not available in the IEEE 802.15.4a model.
When sex work isn't `work' Hospitality, gay life, and the production of desiring labor

This interview-based research explores the lived experiences of gay hosts who `work' in a gentrifying urban tourist district in the City of Manila, the Philippines. My analysis complicates research...
Taxane-platinum combinations in advanced non-small cell lung cancer: a review.

Platinum-based chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC). As a result of their single-agent activities and synergistic effects, taxane-platinum combinations are often used as first-line therapy for this disease. Four large, multicenter, randomized phase III clinical trials (the TAX 326 trial, the Southwest Oncology Group 9509 trial, the Italian Lung Cancer Project, and the Eastern Cooperative Oncology Group 1594 trial) have compared taxane-platinum combinations (docetaxel and paclitaxel) with other platinum combinations (vinorelbine and gemcitabine) in chemotherapy-naive patients with good performance status scores and advanced disease. The end points for these large randomized clinical trials were survival, response rate, adverse events, and quality of life (QOL). Of the taxane-platinum combinations tested, docetaxel-cisplatin was the only platinum combination to yield survival and response rates superior to another platinum combination. In adverse event terms, the taxane-platinum combination of paclitaxel-carboplatin demonstrated less grade 3 or 4 neutropenia and lower rates of febrile neutropenia than other taxane-platinum combinations but higher rates of irreversible grade 3 or 4 peripheral neuropathy than any of the other taxane-platinum combinations. Additional differences emerged when QOL data were evaluated. The docetaxel-platinum combination demonstrated broad QOL benefits for patients receiving this combination, and this benefit was not observed with the other platinum or taxane-platinum combinations. As our use of these taxane-platinum combinations expands, these differences in survival, response rate, adverse events, and QOL will permit us to better balance our treatment goals for all patients with all stages of NSCLC.
Evolutionary Balancing Is Critical for Correctly Forecasting Disease-Associated Amino Acid Variants

Computational predictions have become indispensable for evaluating the disease-related impact of nonsynonymous single-nucleotide variants discovered in exome sequencing. Many such methods have their roots in molecular evolution, as they use information derived from multiple sequence alignments. We show that the performance of current methods (e.g., PolyPhen-2 and SIFT) is improved significantly by optimizing their statistical models on evolutionarily balanced training data, where equal numbers of positive and negative controls within each evolutionary conservation class are used. Evolutionary balancing significantly reduces the false-positive rates for variants observed at highly conserved sites and false-negative rates for variants observed at fast evolving sites. Use of these improved methods enables more accurate forecasting when concordant diagnosis from multiple methods is regarded as a more reliable indicator of the prediction. Applied to a large exome variation data set, we find that the current methods produce concordant predictions for less than half of the population variants. These advances are implemented in a web resource for use in practical applications (www.mypeg.info, last accessed March 13, 2013).
Alternative repair support methods

Material support for new electronic systems has traditionally been a mixture of Original Equipment Manufacturer (OEM) and organic (Navy industrial/depot) repair support. The Seawolf program office decided to rely primarily on OEM support for Contractor Furnished Equipment (CFE) for the life of the system, and not develop organic capabilities unless tangible cost or mission benefits resulted. This is very similar to the type of support that might be used for a Commercial Off-the-Shelf (COTS) system. Iterative review and management of repair sources and repairability issues, including material obsolescence, is required to ensure continuing, viable, and cost effective material readiness. An Integrated Process Team (IPT) structure was identified to recommend, prioritize, and implement material support strategies. Support decisions will be monitored and continuously re-evaluated to enable response to changes in the environment. This paper describes the goals that were used in CFE electronics maintenance planning, the approach used to develop maintenance recommendations, and the repair decision process. It concludes with a discussion of support options that may be applied in the future to accommodate changes that can be expected as the support environment evolves.
iDEAL: Inter-router Dual-Function Energy and Area-Efficient Links for Network-on-Chip (NoC) Architectures

Network-on-Chip (NoC) architectures have been adopted by a growing number of multi-core designs as a flexible and scalable solution to the increasing wire delay constraints in the deep sub-micron regime. However, the shrinking feature size limits the performance of NoCs due to power and area constraints. Research into the optimization of NoCs has shown that a reduction in the number of buffers in the NoC routers reduces the power and area overhead but degrades the network performance. In this paper, we propose iDEAL, a low-power area-efficient NoC architecture by reducing the number of buffers within the router. To overcome the performance degradation caused by the reduced buffer size, we propose to use adaptive dual-function links capable of data transmission as well as data storage when required. Simulation results for the proposed architecture show that reducing the router buffer size in half and using the adaptive dual-function links achieves nearly 40% savings in buffer power, 30% savings in overall network power and about 41% savings in the router area, with only a marginal 1-3% drop in performance. Moreover, the performance in iDEAL can be further improved by aggressive and speculative flow control techniques.
On-line approximation-based tracking of uncertain systems

This paper considers the design and analysis of online approximation based controllers for a general class of uncertain nonlinear dynamical systems. An adaptive bounding design is used to show that the overall online approximation based control system guarantees semi-global uniform ultimate boundedness within a neighborhood of zero tracking error. The theoretical results are illustrated through a simulation example.
Linear fractional relations in Banach spaces: interior points in the domain and analogues of the Liouville theorem

In this paper we study linear fractional relations defined in the following way. Let Bi, B 0 i , i = 1,2, be Banach spaces. We denote the space of bounded linear operators by L. Let T 2 L(B1 B 2,B 0 B
MixtureTree: a program for constructing phylogeny

MixtureTree v1.0 is a Linux based program (written in C++) which implements an algorithm based on mixture models for reconstructing phylogeny from binary sequence data, such as single-nucleotide polymorphisms (SNPs). In addition to the mixture algorithm with three different optimization options, the program also implements a bootstrap procedure with majority-rule consensus. The MixtureTree program written in C++ is a Linux based package. The User's Guide and source codes will be available at http://math.asu.edu/~scchen/MixtureTree.html The efficiency of the mixture algorithm is relatively higher than some classical methods, such as Neighbor-Joining method, Maximum Parsimony method and Maximum Likelihood method. The shortcoming of the mixture tree algorithms, for example timing consuming, can be improved by implementing other revised Expectation-Maximization(EM) algorithms instead of the traditional EM algorithm.
Sire by Region Interaction for Production Traits in Dairy Cattle

Abstract During the past decade considerable attention has been given to sire by herd interactions, but data have not been available to consider the broader regional aspects of this problem. Sire by region interactions for milk production, fat production, and fat test were examined, utilizing the first available DHIA record of 10,548 artificially sired daughters of 46 Holstein sires used in the northern and southern regions of the United States. Daughter records were expressed as deviations from adjusted herd-mate averages. Correlations between the average breeding values of the sires in the two regions for the three traits approached 1.00, indicating that the ranking of sires was essentially the same in both regions. Estimates of the sire by region interaction variances for the three traits also were essentially zero. Although additional confirmation is needed, these results suggest that influences associated with a particular region should not unduly confuse the ranking of sires in the different regions when herd-mate comparisons from artificially sired daughters are used.
The role of molecular diffusion in the adhesion of elastomers

Butyl rubber (polyisobutylene-co-isoprene) mixed with polyisobutylene was crosslinked to yield elastomeric macromolecular networks containing dissolved linear macromolecules. Adhesion of these materials to themselves (self-adhesion) and to an inert substrate was investigated over a wide range of peel rates and test temperatures. Greatly enhanced self-adhesion was found when linear polyisobutylene molecules of high molecular weight were present, but the strength of adhesion to a rigid inert substrate was hardly affected. The enhancement of self-adhesion is attributed to interdiffusion of polyisobutylene molecules. It was greatest at intermediate peel rates and temperatures, becoming insignificant at extremely low rates, probably because the diffusing species can then migrate readily, and at high effective rates of peel when the polymer approaches the glassy state and the strength of adhesion is high in all cases. A transition to somewhat lower levels of adhesion at relatively high rates of peel is tentatively ascribed to the onset of molecular fracture in place of pullout. The presence of large amounts of low-molecular-weight polyisobutylene (Mv = 50,000 g/mol) increased the level of self-adhesion and of adhesion to an inert substrate to a similar degree, over a broad range of peel rates. This effect is attributed primarily to enhanced viscous losses in the elastomeric layer during separation. Application of these results to crack and weld-line healing in glassy plastics is discussed.
Design and evaluation of algorithms to compute the transitive closure of a database relation

Recursive query evaluation is a capability of deductively-augmented database systems that conventional database systems do not support well, if at all. Many recursive queries involve computation of the transitive closure of a relation. Previously published algorithms for transitive closure are iterative in nature, performing repeated joins, unions, and differences until convergence is obtained. In this paper, we present an adaptation of Warren's algorithm for computing the transitive closure of a relation. Warren's algorithm was originally designed for a bit matrix representation of a binary relation; we have adapted it for use with a binary relation represented as a set of tuples, as in a relational database management system. This adapted algorithm computes the transitive closure in two passes over the relation. We analyze the performance of this algorithm, and compare it to the performance of two algorithms based on relational algebra: an iterative algorithm, and an improved version of the iterative algorithm that eliminates unnecessary I/O at the expense of more computation. We evaluate the performance of the algorithms for different source relation sizes, available memory sizes, join selectivities, and maximum path length. Our results show that no algorithm has uniformly superior performance; the adaptation of Warren's algorithm is superior when the source and result relations are not too much larger than main memory. We conclude that in future systems with large main memory, Warren's algorithm generally performs best, and thus should be implemented with the option of switching to an iterative algorithm when the source or result sizes are very large.
Horizontal energy propagation in a barotropic atmosphere with meridional and zonal structure

Abstract To investigate how the propagation of energy away from steady sources may be influenced by the horizontal structure of the time-averaged flow in the troposphere, solutions to a barotropic model are displayed and interpreted. The model is steady and linearized about a basic state which varies in latitude and longitude. Emphasis is placed on cases where the longitudinal variations are gradual. Many of the results can be analyzed by locally applying tools developed for zonally symmetric basic states, e.g., ray tracing and refractive indices. Simple background flows are constructed which have longitudinally confined critical lines, reflective surfaces, wave guides, and regions conducive to propagation. An example is given in which longitudinal derivatives of the basic state are significant. The theory of ray tracing in a two-dimensional wind must be employed as an interpretive tool in this case. It is concluded that zonal variations tend to enhance poleward (equatorward) propagation in large-scale tr...
Host Genetic Control of the Microbiota Mediates the Drosophila Nutritional Phenotype

A wealth of studies has demonstrated that resident microorganisms (microbiota) influence the pattern of nutrient allocation to animal protein and energy stores, but it is unclear how the effects of the microbiota interact with other determinants of animal nutrition, including animal genetic factors and diet. Here, we demonstrate that members of the gut microbiota in Drosophila melanogaster mediate the effect of certain animal genetic determinants on an important nutritional trait, triglyceride (lipid) content. Parallel analysis of the taxonomic composition of the associated bacterial community and host nutritional indices (glucose, glycogen, triglyceride, and protein contents) in multiple Drosophila genotypes revealed significant associations between the abundance of certain microbial taxa, especially Acetobacteraceae and Xanthamonadaceae, and host nutritional phenotype. By a genome-wide association study of Drosophila lines colonized with a defined microbiota, multiple host genes were statistically associated with the abundance of one bacterium, Acetobacter tropicalis. Experiments using mutant Drosophila validated the genetic association evidence and reveal that host genetic control of microbiota abundance affects the nutritional status of the flies. These data indicate that the abundance of the resident microbiota is influenced by host genotype, with consequent effects on nutrient allocation patterns, demonstrating that host genetic control of the microbiome contributes to the genotype-phenotype relationship of the animal host.
Investigation of the dynamic stress–strain response of compressible polymeric foam using a non-parametric analysis

Abstract Dynamic stress–strain response of rigid closed-cell polymeric foams is investigated in this work by subjecting high toughness polyurethane foam specimens to direct impact with different projectile velocities and quantifying their deformation response with high speed stereo-photography together with 3D digital image correlation. The measured transient displacement field developed in the specimens during high stain rate loading is used to calculate the transient axial acceleration field throughout the specimen. A simple mathematical formulation based on conservation of mass is also proposed to determine the local change of density in the specimen during deformation. By obtaining the full-field acceleration and density distributions, the inertia stresses at each point in the specimen are determined through a non-parametric analysis and superimposed on the stress magnitudes measured at specimen ends to obtain the full-field stress distribution. The process outlined above overcomes a major challenge in high strain rate experiments with low impedance polymeric foam specimens, i.e. the delayed equilibrium conditions can be quantified.
Gender-based legislation and female labor productivity in argentine factories, 1895-1935

espanolEste documento de trabajo examina el genero basado en la legislacion destinada a proteger a las trabajadoras y limitar sus actividades laborales en la fabricacion de las fabricas en la Argentina entre 1895 a 1935. El objetivo es discutir las contradicciones entre la legislacion basada en el genero y la productividad de la mano de obra femenina. Mi investigacion, hasta ahora, muestra que el trabajo femenino era productivo entre los anos 1895 y 1935, pese a las leyes restrictivas que limitaron lo que las mujeres podian hacer en la fabrica. Dos consecuencias son que la legislacion laboral fue minimamente o no se aplicaba en las fabricas. En segundo lugar las trabajadoras, en particular las que trabajaban en las fabricas textiles, se centraron en la pieza de trabajo de mano de obra que se completo en su casa y mas alla de la legislacion protectora. EnglishThis working paper examines gender-based legislation intended to protect working women and limit their work activities in manufacturing factories in Argentina from 1895-1935. The goal is to discuss the contradictions between gender-based legislation and female labor productivity. My research, thus far, shows that female labor was productive between 1895 and 1935 despite restrictive legislation limiting what women could do in the factory. Two implications include that labor legislation was either minimally or not enforced in factories. Second, female laborers, in particular those working in textile factories, focused on labor-intensive piece work that they completed at home and beyond the limits of protective legislation.
Abstract A75: Bioactive tanshinones in Salvia miltiorrhiza for prostate cancer chemoprevention

Prostate cancer is the second‐leading cause of cancer death in American men. Current therapeutic approaches have made significant progression in the control of prostate cancer progression. On the other hand, conventional therapeutics have variable efficacies and are usually associated with metastatic recurrence and/or high cytotoxicity. Therefore the search for effective chemopreventive agents with minimal side effects has remained one of the top priorities in prostate cancer research. Some Chinese herbal medicines have been used for centuries, thus certain Chinese medicines with active anti‐cancer ingredients may be effective candidates for the prevention and/or treatment of prostate cancer. Danshen (Salvia miltiorrhiza) has been widely adopted in the traditional Chinese medicinal preparations for treatment of cerebrovascular disorders with minimal side effects. We thus evaluated the effects of several major Danshen components, tanshinones IIA (T2A), tanshinone I (T1) and cryptotanshinone (CT) on the growth of prostate cancer cells and identified the potential molecular targets that were responsive to and might be responsible for the treatments. CT, T2A and T1 significantly inhibited the growth of prostate cancer cells with the IC50s at a few Ms associated with cell cycle arrests and apoptosis induction in vitro, whereas their growth inhibition effects on normal prostate epithelial cells were dramatically reduced by 5–10 folds. T1 showed the most potent activity among the three compounds, but the combination of CT and T2A showed synergistic effects against prostate cancer cell growth. The pilot animal study verified that T1 inhibited the growth of DU145 tumors in a dose‐dependent manner. By using the real time PCR arrays for epigenetic markers, we identified Aurora A kinase gene as a potential molecular target of tanshinones. Aurora A gene and protein were up‐regulated in prostate cancer cell lines when compared with that in the normal cells, and the tanshinone treatments significantly down‐regulated its expression. These results demonstrated potent anti‐prostate cancer activities of tanshinones and identified Aurora A as a potential molecular target of tanshinones actions. Further in vivo studies of the chemopreventive effects of tanshinones and the CT and T2A combination on prostate cancer development and/or progression are warranted. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A75.
Nomenclatural Changes for Some North American Uredinales

(1956). Nomenclatural Changes for Some North American Uredinales. Mycologia: Vol. 48, No. 4, pp. 601-608.
Recent studies of the herpesviruses.

The viruses of the herpes group are relatively large and possess an ether-sensitive envelope which surrounds a nucleocapsid composed of 162 capsomeres. The viral genome consists of a doubly-stranded molecule of DNA with a molecular weight of approximately 100 × 106 daltons. Following adsorption and penetration into their host cells, the herpesviruses inhibit the synthesis of cell-specific products and, instead, the infected cells begin to form virus-specific components. Viral DNA is synthesized in the nucleus and viral proteins in the cytoplasm, whence they migrate to the nucleus, the site of assembly of the nucleocapsids. The nucleocapsids acquire their envelopes by budding from the nuclear membrane. The cellular membranes are altered drastically by infection. Structural viral glycoproteins become part of the nuclear membranes. A viral nonstructural glycoprotein that becomes part of the cytoplasmic membranes is also synthesized by the infected cells. When the virus is inactivated by ultraviolet irradiation, some of the virions lose their ability to kill the infected cells, but these inactivated virions can still transfer some of their functions to these cells. The oncogenic potential of the virus can be detected under these conditions. The possible correlation of the virus-induced alterations of the cellular membranes and the oncogenic potential of the virus are discussed.
Toward Elimination of Hepatitis B Virus Using Novel Drugs, Approaches, and Combined Modalities

Hepatitis B virus (HBV) causes significant morbidity and mortality worldwide. The majority of chronically infected individuals do not achieve a functional and complete cure. Treated persons who achieve a long-term sustained virologic response (undetectable HBV DNA), are still at high risk of developing morbidity and mortality from liver complications. This review focuses on novel, mechanistically diverse anti-HBV therapeutic strategies currently in development or in clinical evaluation, and highlights new combination strategies that may contribute to full elimination of HBV DNA and covalently closed circular DNA from the infected liver, leading to a complete cure of chronic hepatitis B.
Impaired Transmission from Photoreceptors to Bipolar Cells: Mouse Models

In response to light, photoreceptors normally decrease the rate of glutamate release at their terminal. This change is detected by two classes of bipolar cells, which are distinguished by whether they depolarize (DBCs) or hyperpolarize (HBCs) in response to light. The electroretinogram (ERG) can be used to monitor this process as the ERG a-wave reflects photoreceptor activity while the b-wave is generated by bipolar cell responses. As a consequence, a selective reduction in the ERG b-wave is usually indicative of a defect in transmission between photoreceptors and bipolar cells. This situation is encountered in naturally occurring and genetically engineered mice, the study of which shed light on the development and maintenance of the photoreceptor-to-bipolar cell synaptic process. For example, null mutations in the genes encoding mGluR6 or Gα0 eliminate the b-wave and confirm the role of these proteins in DBC signal transduction. A similar ERG pattern is seen in the nob (no b-wave) mouse, which is caused by a defect in nyx, encoding nyctalopin. Although the precise function of nyctalopin is unknown, the localization of nyctalopin transcripts to the outer nuclear layer indicates that this protein may play a critical role in the DBC response. Despite the lack of DBC function, ribbon synapses form normally in nob mice. Presynaptically, glutamate release is controlled by L-type calcium channels located on the photoreceptor terminal. The b-wave is selectively reduced in CNSβ2-null mice, lacking the β2 subunit of the L-type calcium channel in the central nervous system. In addition, the normal distribution of the pore-forming α1F subunit is markedly disturbed, indicating that the β2 subunit is required to guide the formation of a functional channel. Such channels are likely to be required for ribbon synapse formation, as ribbon structures are rarely encountered in CNSβ2-null mice. As the nob and CNSβ2-null mice involve genes that underlie two forms of congenital stationary night blindness, study of these animal models will expand our understanding of these rare human disorders.
Radiosensitization of Human Cancers by Smac Agonists.

Resistance to current treatment regimens such as radiation therapy remains a major concern in oncology and may be caused by defects in apoptosis programs. Since “Inhibitor of apoptosis proteins” (IAPs), which are expressed at high levels in many tumors, block apoptosis at the core of the apoptotic machinery by inhibiting caspases, therapeutic modulation of IAPs could target a key control point in resistance. Here, we report for the first time that full length or mature Smac, an inhibitor of IAPs, significantly enhanced γ-irradiation-induced apoptosis and reduced clonogenic survival in neuroblastoma, glioblastoma or pancreatic carcinoma cells. Notably, Smac had no impact on DNA damage/DNA repair, activation of NF-κB, upregulation of p53 and p21 proteins or cell cycle arrest following γ-irradiation indicating that Smac did not alter the initial damage and/or cellular stress response. Smac enhanced activation of caspase-2, -3, -8 and -9, loss of mitochondrial membrane potential and cytochrome c release upon γ-irradiation. Inhibition of caspases also blocked γ-irradiation-induced mitochondrial perturbations, indicating that Smac facilitated caspase activation, which in turn triggered a mitochondrial amplification loop. Interestingly, mitochondrial perturbations were completely blocked by the broad range caspase inhibitor zVAD.fmk or the relatively selective caspase-2 inhibitor zVDVAD.fmk, whereas caspase-8 or caspase-3 inhibitors only inhibited the increased drop of mitochondrial membrane potential provided by Smac, suggesting that caspase-2 was acting upstream of mitochondria upon γ-irradiation. In conclusion, our findings provide evidence that targeting IAPs, e.g. by Smac agonists, is a promising strategy to enhance radiosensitivity in human cancers.
Selective Loss of a Putative Precursor Population of B-Chronic Lymphocytic Leukemia Cells Following Immunization with hCD40L/IL-2 Expressing Autologous Tumor Cells

Side-population (SP) cells, defined on the basis of their ability to rapidly expel Hoechst dye, may be precursor cells for normal and malignant tissues and are more resistant to chemotherapy. We have now characterized a malignant SP subset in the peripheral blood of B-CLL patients and show how vaccination with CD40L/IL-2 expressing autologous tumor cells can induce a T cell immune response that reduces or eliminates this tumor subpopulation. Hoechst 33342 staining combined with CD5/CD19 antibody labeling of peripheral blood mononuclear cells showed a distinct CD5+CD19+ SP phenotype (median=0.22%, range; 0.2–2.17%) in 85% (18/21) of B-CLL patients (Stage I–III). We sorted SP and non-SP (NSP) cells and extracted RNA and performed a comprehensive gene expression analysis by microarray (n=9 donor SP and NSP pairs), finding 85 genes overexpressed (>2-fold log ratio) in SP compared to NSP, and 228 genes higher in NSP versus SP. The analysis showed that compared to NSP cells from the same patient, the SP subset consistently and significantly overexpressed genes associated with cellular activation, proliferation and survival including eIF4A1 (p<.05), Wnt10a (p<.05), Bcl2L12 (p<.05) and Rel A (p=.07), a difference confirmed by qPCR. Conversely, NSP significantly overexpressed GSK3β (p<.05) compared to SP. CD40 mediated activation of B-CLL tumor cells further enhanced relative expression of these genes in the SP fraction, and induced overexpression of the proliferation-associated genes Ki-67 and PCNA in SP compared to NSP cells by 8-fold and 132-fold, respectively. We found SP cells were more resistant to exposure to chemotherapeutic agents including 50 mM fludarabine than NSP. Analysis of results in patients who had received an autologous B-CLL cell tumor vaccine expressing CD40L and IL-2, however, showed that B-CLL SP cells were vulnerable to a T cell mediated immune response. Hence, 3–8 subcutaneous injections CD40L/IL-2 B-CLL cells had no immediate effect on total B-CLL cell numbers in the peripheral blood, but Hoechst analysis showed a disappearance of SP cells in 7/8 immunized patients, associated with a rise in B-CLL-reactive T cells. CD8+ T cell clones isolated and expanded with CD40-activated autologous B-CLL tumor cells specifically responded to autologous SP cells, suggesting that SP depletion is mediated vaccine induced B-CLL-specific T cells. In 6/7 patients SP cells returned within a few weeks of completing the course of vaccination, coincident with a decline in T cell immunity. In one patient, however, immunity was longer lived and in this patient control of SP B-CLL cells persisted for more that 12 months. In this individual there was a delayed (by 6 months), but progressive disappearance of the bulk (non-SP) tumor cells. These results are consistent with the existence of an SP tumor precursor population of B-CLL, that can be targeted by immune T cells in vivo, and removal of which leads to later disappearance of their non-SP progeny.
BIOSYNTHESIS OF FATTY ACIDS AND POSSIBLE CHAIN TERMINATION MECHANISMS IN PLANT TISSUES

ABSTRACT Most plant lipids have only C 16 and C 18 fatty acids as acyl components of their complex lipids. A small number of plants, however, have markedly altered patterns, i.e. either C 10–14 fatty acids or C 20–22 fatty acids in the complex lipids of their seeds. We shall examine these three different groups of plant systems and suggest possible mechanisms responsible for these remarkable patterns.
Framework for Sustaining Innovation at Baker Library, Harvard Business School.

ABSTRACTBaker Library at Harvard Business School is increasingly asked by the school's faculty to create custom digital information products to enhance course assignments and to find novel ways of electronically disseminating faculty research. In order to prioritize these requests, as well as facilitate, manage, and track the resulting projects, the library staff developed the Research Innovation Framework. Informed by design thinking techniques and recent research on building innovation strategies and innovative cultures, the Research Innovation Framework has been particularly impactful to Baker's intra-organizational communication, allowing for more robust collaboration across the entire library. Tools and resources contained within the Framework have allowed Baker to adapt to the diverse and evolving needs of its customers.
An improved high-moment method for reliability analysis

For reliability analysis, there may be several potential distributions for a random variable due to limited samples available. For the same reason, a distribution may not be available. Simply assuming a normal distribution may result in a large error for the reliability prediction. Moment-based methods use only moments of random variables for reliability analysis and can effectively address the problem of multiple distributions or lack of distributions. The existing moment-based methods, however, may produce large errors or may result in instability in the analysis process. This study extends the high-moment method for higher accuracy of the reliability prediction by including the parameters ignored by the existing high-moment method. The proposed method derives the reliability index from the first four moments of random input variables based on the statistical properties of the standard normal random variable. Compared with the existing method, the proposed method is more accurate and stable for problems for which the distributions of input random variables are unknown. Numerical examples show the improved accuracy from the proposed method.
Social trust and the liquidity of cross-listed securities

Abstract This paper examines various measures of market liquidity in American Depositary Receipts (ADRs) while conditioning on the level of trust in the ADR's home country. Multivariate tests show that as home-country levels of trust increase, ADR liquidity is dramatically improved. To draw stronger causal inferences, we use a difference-in-difference approach to examine liquidity surrounding an (arguably) exogenous reduction in trust and find that liquidity worsens in response to the event. These results support our hypothesis that trust is an important determinant in the liquidity of financial markets.
Wind Tunnel Modeling of Building Internal Pressure

An inspectional analysis is made on the differential equations governing the fluctuations of the building internal pressure generated by wind for both single and multi-room buildings. The result is used to find the similarity parameters required for wind tunnel modeling of the internal pressure. How the results are to be used in practice is analyzed.
Defects, Process Parameters and Signatures for Online Monitoring and Control in Powder-Based Additive Manufacturing

Additive Manufacturing (AM) is a process that is based on manufacturing parts layer by layer in order to avoid any geometric limitation in terms of creating the desired design. In the early stages of AM development, the goal was just creating some prototypes to decrease the time of manufacturing assessment. But with metal-based AM, it is now possible to produce end-use parts. In powder-based AM, a designed part can be produced directly from the STL file (Standard Tessellation Language/ stereolithography) layer by layer by exerting a laser beam on a layer of powder with thickness between 20 μm and 100 μm to create a section of the part. The Achilles’ heel of this process is generation of some defects, which weaken the mechanical properties and in some cases, these defects may even lead to part failure under manufacturing. This prevents metal-based AM technology from spreading widely while limiting the repeatability and precision of the process. Online monitoring (OM) and intelligent control, which has been investigated prevalently in contemporary research, presents a feasible solution to the aformentioned issues, insofar as it monitors the generated defects during the process and eliminates them in real-time. In this regard, this paper reveals the most frequent and traceable defects which significantly affect quality matrices of the produced part in powder-based AM, predominately focusing on the Selective Laser Sintering (SLS) process. These defects are classified into “Geometry and Dimensions,” “Surface Quality (Finishing),” “Microstructure” and the defects leading to “Weak Mechanical Properties.” In addition, we introduce and classify the most important parameters, which can be monitored and controlled to avoid those defects. Furthermore, these parameters may be employed in some error handling strategies to remove the generated defects. We also introduce some signatures that can be monitored for adjusting the parameters into their optimum value instead of monitoring the defects directly.
Large Deviations for Martingales

Let X1,X2… be variables satisfying (i) (i) |X n | ≤ 1 and (ii) X(X n |X 1,…,X n-1)=0, and put n =X 1+…X n .
Theories, Models, and Practices for Understanding Gender, Race, and Ethnicity in Clinical Assessment

For most psychologists, assessment is an important and commonly practiced clinical activity. Addressing our professional curiosity and understanding about the human experience are a complex process that involves the understanding of factors with varied etiologies, varied course of progress, and varied multidimensional qualities and characteristics. Formal assessment can begin to help us organize these complex factors. Analogous to manipulating and transforming a “ball of wax” handed to us by our clients, assessment is likely to be impacted by who is doing the perceiving and handling of the “wax.” That is, the practitioner’s level of training, experience, and competency in assessment. The assessment process is also shaped by the referral question. Moreover, results from an assessment have a plethora of outcomes and consequences for the recipient of the evaluation. In this chapter, we discuss assessment as practiced by various psychologists, including clinical, projective, and objective assessment procedures, and explore ways to consider race, ethnicity, gender, and their intersectionality within these various assessment domains. We also provide recommendations for considering race, ethnicity, and gender in the assessment process and conclude with a case study that illustrates how to consider these variables in the scoring, interpretation, and formulation process.
Institutional Pressures on Primary Science and the New Ecosystem of Knowledge

This chapter considers the relatively long-standing effect of the broader institutional environment on what is taught and learned in primary science in a variety of East Asian systems. A stable institutional environment yields similarities across systems including emphasis on scientific literacy, constructivism, and inquiry/process skills. The chapter also addresses what the rapidly changing technical environment might mean for the primary science curriculum, arguing that developments in information and communication technology radically alter the “ecosystem of knowledge” in ways that curriculum makers must take into account explicitly if schooling is to empower pupils fully. Some educational systems are better positioned than others, in their guiding principles and particular practices, to prepare pupils to leverage their access to information technology for powerful science learning.
A methodology with a distributed algorithm for large-scale trajectory distribution prediction

In this paper, we propose a method for predicting the distributions of people’s trajectories on the road network throughout a city. Specifically, we predict the number of people who will move from ...