cssi/SciSciGPT-SciSciNet huggingface dataset:
Functional Consequences of Genome Evolution in Listeria monocytogenes: the lmo0423 and lmo0422 Genes Encode σC and LstR, a Lineage II-Specific Heat Shock System

Listeria monocytogenes strains belonging to phylogenetic lineage II (serotypes 1/2a, 1/2c, and 3a) carry a lineage-specific genome segment encoding a putative sigma subunit of RNA polymerase (lmo0423, herein referred to as sigC), a gene of unknown function (lmo0422) similar to the padR family of regulators, and a gene that is similar to the rodA-ftsW family of cell wall morphology genes (lmo0421). To understand the function of this set of genes, their expression patterns and the effects of null mutations in the lineage II L. monocytogenes strain 10403S were examined. The data are consistent with the three genes comprising an operon (the sigC operon) that is highly induced by temperature upshift. The operon is transcribed from three different promoters, the proximal of which (P1) depends upon sigC itself. Null mutations in sigC or lmo0422 increase the death rate at lethal temperatures and cause loss of thermal adaptive response, whereas the lmo0421 mutation causes only a loss of the adaptive response component. Only the sigC mutation affects transcription from the P1 promoter, whereas ectopic expression of lmo0422 from the PSPAC promoter complements the individual lmo0422 and sigC null mutations, showing that lmo0422 is the actual thermal resistance regulator or effector while sigC provides a mechanism for temperature-dependent transcription of lmo0422 from P1. Our genetic and phylogenetic analyses are consistent with lmo0422—renamed lstR (for lineage-specific thermal regulator)—and sigC comprising a system of thermal resistance that was ancestral to the genus Listeria and was subsequently lost during divergence of the lineage I L. monocytogenes population. Although only a relatively small number of cases of human listeriosis occur each year in the United States (estimated at 2,500 per year), the associated rates of morbidity and mortality are substantial, with nearly 30% mortality in some outbreaks (40, 58). Because the causative agent of the disease, Listeria monocytogenes, is ubiquitous in nature and possesses durable physiological characteristics, the organism is one of the most significant food safety problems in the food production industry.
Transmit beamforming for MIMO radar systems using signal cross-correlation

Proposed next-generation radar systems will have multiple transmit apertures with complete flexibility in the choice of the signals transmitted at each aperture. Here we propose the use of multiple signals with arbitrary cross-correlation matrix R, and show that R can be chosen to achieve or approximate a desired spatial transmit beampattern. Two specific problems are addressed. The first is the constrained optimization problem of finding the value of R which causes the true transmit beampattern to be close in some sense to a desired beampattern. This is approached using convex optimization techniques. The second is the problem of designing multiple constant-modulus waveforms with given cross-correlation R. The use of coded binary phase shift keyed (BPSK) waveforms is considered. A method for finding the code sequences based on random signaling with a structured correlation matrix is proposed. It is also shown that by restricting the class of admissible waveforms one reduces the set of possible signal correlation matrices.
Psychopathy versus sociopathy: Why the distinction has become crucial

The terms psychopath and sociopath are often used interchangeably, but there appears to be some hesitance by researchers in the many disciplines comprising criminology to continue this trend. The problem seems to be that as research has advanced in studies of psychopathy, which is the more common of the two terms, psychopathy now commands a much more specific definition, and this is what alienates it from its estranged cousin, sociopathy. As language can serve to hinder or confound research, it is crucial that these terms take their proper place in brain science. Here, I present how the two terms are currently used in neuroscience and psychology, and suggest how research in sociopathy should progress.
Tendon-driven control of biomechanical and robotic systems: A path integral reinforcement learning approach

We apply path integral reinforcement learning to a biomechanically accurate dynamics model of the index finger and then to the Anatomically Correct Testbed (ACT) robotic hand.We illustrate the applicability of Policy Improvement with Path Integrals (PI2) to parameterized and non-parameterized control policies. This method is based on sampling variations in control, executing them in the real world, and minimizing a cost function on the resulting performance. Iteratively improving the control policy based on real-world performance requires no direct modeling of tendon network nonlinearities and contact transitions, allowing improved task performance.
Stories and Relationships

How do the supposedly true stories we tell about the past influence our relationships in the present? What, in other words, is the rhetorical value of historical texts, written and oral? In this essay, I argue that more attention should be paid to how people socially create stories about `what really happened back then', to suit their own political interests; and how, in the process of doing so, they partition the world into cognitive territories known as `selves' and `others'.
Improving the power of chronic disease surveillance by incorporating residential history

We present a global test for disease clustering with power to identify disturbances from the null population distribution which accounts for the lag time between the date of exposure and the date of diagnosis. Location at diagnosis is often used as a surrogate for the location of exposure; however, the causative exposure could have occurred at a previous address in a case's residential history. We incorporate models for the incubation distribution of a disease to weight each address into the residential history by the corresponding probability of the exposure occurring at that address. We then introduce a test statistic which uses these incubation-weighted addresses to test for a difference between the spatial distribution of the cases and the spatial distribution of the controls, or the background population. We follow the construction of the M statistic to evaluate the significance of these new distance distributions. Our results show that gains in detection power when residential history is accounted for are of such a degree that it might make the qualitative difference between the presence of spatial clustering being detected or not, thus making a strong argument for the inclusion of residential history in the analysis of such data.
A statistical framework of data fusion for spatial prediction of categorical variables

With rapid advances of geospatial technologies, the amount of spatial data has been increasing exponentially over the past few decades. Usually collected by diverse source providers, the available spatial data tend to be fragmented by a large variety of data heterogeneities, which highlights the need of sound methods capable of efficiently fusing the diverse and incompatible spatial information. Within the context of spatial prediction of categorical variables, this paper describes a statistical framework for integrating and drawing inferences from a collection of spatially correlated variables while accounting for data heterogeneities and complex spatial dependencies. In this framework, we discuss the spatial prediction of categorical variables in the paradigm of latent random fields, and represent each spatial variable via spatial covariance functions, which define two-point similarities or dependencies of spatially correlated variables. The representation of spatial covariance functions derived from different spatial variables is independent of heterogeneous characteristics and can be combined in a straightforward fashion. Therefore it provides a unified and flexible representation of heterogeneous spatial variables in spatial analysis while accounting for complex spatial dependencies. We show that in the spatial prediction of categorical variables, the sought-after class occurrence probability at a target location can be formulated as a multinomial logistic function of spatial covariances of spatial variables between the target and sampled locations. Group least absolute shrinkage and selection operator is adopted for parameter estimation, which prevents the model from over-fitting, and simultaneously selects an optimal subset of important information (variables). Synthetic and real case studies are provided to illustrate the introduced concepts, and showcase the advantages of the proposed statistical framework.
Packaging of DNA in bacteriophage Heads: Some considerations on energetics

We have made quantitative estimates of some of the energetic factors to be considered in packaging of double-stranded DNA in virus particles. Numerical calculations were made using parameters appropriate for T4 bacteriophage. The unfavorable factors, and the Gibbs free energies per mole virus at 20°C associated with them, are bending, 1.5 × 103 kcal/mol; conformational restriction upon condensation, 5.1 × 102 kcal/mol; polyelectrolyte repulsion, 2.1 × 105kcal/mol; and melting or kinking, 6.9 × 103 kcal/mol. These must be counterbalanced in the assembled phage by noncovalent bonding interactions between protein subunits in the phage-head shell; by interactions between the DNA and polyvalent cations, especially putrescine and spermidine; nad perhaps by repulsive excluded volume and electrostatic interaction between the DNA and acidic polypeptides. Indeed, a rough estimate of the standard free energey of interaction between T4 DNA and the putrescine and spermidine contained in the head is --2.1 × 105 kcal/mol. In the absence of the other two sources of stabilization, each head protein subunit must contribute about 210 kcal/mol of binding energy.
Array-Based Transcript Profiling and Limiting-Dilution Reverse Transcription-PCR Analysis Identify Additional Latent Genes in Kaposi's Sarcoma-Associated Herpesvirus

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a B-lymphotropic herpesvirus strongly linked to both lymphoproliferative diseases and Kaposi’s sarcoma. The viral latency program of KSHV is central to persistent infection and plays important roles in the pathogenesis of KSHV-related tumors. Up to six polypeptides and 18 microRNAs are known to be expressed in latency, but it is unclear if all major latency genes have been identified. Here, we have employed array-based transcript profiling and limiting-dilution reverse transcription-PCR (RTPCR) methodologies to explore this issue in several KSHV-infected cell lines. Our results show that RNAs encoding the K1 protein are found at low levels in most latently infected cell lines. The gene encoding v-IL-6 is also expressed as a latent transcript in some contexts. Both genes encode powerful signaling molecules with particular relevance to B cell biology: K1 mimics signaling through the B cell receptor, and v-IL-6 promotes B cell survival. These data resolve earlier controversies about K1 and v-IL-6 expression and indicate that, in addition to core latency genes, some transcripts can be expressed in KSHV latency in a context-dependent manner. Kaposi’s sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8, is a B-lymphotropic herpesvirus that is strongly linked to several human tumors (see reference 25 for a review). These include Kaposi’s sarcoma (KS), which is an endothelial neoplasm (9), and tumors associated with two B-lymphoproliferative diseases, primary effusion lymphoma (PEL) (7) and multicentric Castleman’s disease (MCD) (57). Like all herpesviruses, KSHV has two distinct genetic programs, latency and lytic replication. In latency, viral gene expression is heavily restricted, with only a few KSHV genes being transcribed; the viral genome is maintained as a nuclear plasmid, no viral progeny are produced, and the host cell survives. In contrast, in lytic infection all the viral genes are expressed, in a temporally regulated cascade. Viral DNA is extensively replicated, and progeny virions are assembled and released, with concomitant death of the host cell. Because they retain the full complement of viral genes, cells that are latently infected can “switch” to the lytic program upon receipt of appropriate stimuli.
Age‐Related Changes in Hypothalamic Gonadotropin‐Releasing Hormone and N‐Methyl‐d‐Aspartate Receptor Gene Expression, and their Regulation by Oestrogen, in the Female Rat

During reproductive ageing, the oestrous cycles of female rats become irregular and eventually cease. The mechanisms for reproductive senescence in rodents are believed to involve changes in hypothalamic neurones, including gonadotropin-releasing hormone (GnRH) cells and their afferent inputs. In addition, effects of oestrogen on hypothalamic function may vary in animals of different ages. These issues were addressed using young (aged 4-5 months), middle-aged (12-14 months) and old (24-26 months) female Sprague-Dawley rats. Animals were ovariectomized and given oestrogen or vehicle replacement. They were killed and the preoptic area-anterior hypothalamus (POA-AH) and the medial basal hypothalamus-median eminence (MBH-ME) were dissected out, RNA extracted, and RNase protection assay used to quantify gene expression of several hypothalamic molecules. In the first experiment, GnRH RNA levels were measured in the POA-AH. No effects of ageing or oestrogen were observed on GnRH gene expression. This finding suggests that ageing and oestrogen may affect GnRH release from neuroterminals independently of de novo biosynthesis, and that this may involve other neurones that affect GnRH neurosecretory function. In the second experiment, we investigated changes in N-methyl-D-aspartate (NMDA) receptor subunit mRNA levels. These receptors play an important regulatory role in mediating effects of glutamate on GnRH function, and are themselves regulated by oestrogen and ageing. NMDA receptor subunit (NR) 1, 2a and 2b mRNA levels were quantified in the POA-AH and MBH-ME, the sites of GnRH perikarya and neuroterminals, respectively. In general, oestrogen had inhibitory effects on NR1 and NR2a, and differential effects on NR2b subunit mRNA levels. NMDA receptor subunit mRNA levels also changed during ageing: age-related decreases in NR1 mRNA occurred in the MBH-ME, and an age-related increase in NR2b mRNA occurred in the POA-AH. Taken together, these results demonstrate subunit- and region-specific changes in hypothalamic NMDA receptor subunit gene expression with oestrogen and ageing. These alterations could have implications for the physiological effects of glutamate on its NMDA receptor, and impact the regulation of reproductive and other neuroendocrine and autonomic functions by hypothalamic glutamatergic inputs.
Determination of siloxanes in silicone products and potential migration to milk, formula and liquid simulants

A pressurised solvent extraction procedure coupled with a gas chromatography–mass spectrometry–selective ion monitoring (GC–MS–SIM) method was developed to determine three cyclic siloxanes, octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6) and three linear siloxanes, octamethyltrisiloxane (L3), decamethyltetrasiloxane (L4), dodecamethylpentasiloxane (L5), in silicone products. Additionally, two different extraction methods were developed to measure these siloxanes migrating into milk, infant formula and liquid simulants (50 and 95% ethanol in water). The limits of quantification (LOQs) of the six siloxanes ranged from 6 ng/g (L3) to 15 ng/g (D6). Silicone nipples and silicone bakewares were extracted using pressurised solvent extraction (PSE) and analysed using the GC–MS–SIM method. No linear siloxanes were detected in the silicone nipple samples analysed. The three cyclic siloxanes (D4, D5 and D6) were detected in all silicone nipple samples with con...
Issues in software development for concurrent computers

Three approaches to programming concurrent computers are described, with attention focused on MIMD machines. These approaches involve the user preparing: the whole program; large-grain objects; and fine-grain objects. Four architectures (two homogeneous and two hierarchical) are considered. >
Surface morphology and crystallinity control in the atomic layer deposition (ALD) of hafnium and zirconium oxide thin films

Abstract Hafnium and zirconium oxide films were prepared by atomic layer deposition (ALD) from dialkylamido precursors. Water was used as the oxygen source. Nanolaminates of hafnium, zirconium and aluminum oxide were also prepared. Atomic force microscopy was used to characterize the surface morphology of 10–100 nm thick films grown from 50°C to 300°C. X-ray diffraction was used to characterize the film crystallinity. Transmission electron microscopy was used to relate the surface morphology to the film crystallinity. A model for the nucleation and growth of crystallites during an ALD deposition leading to surface roughness is developed based on these findings. Analysis of the film properties in the context of this model suggested nanolaminate strategies that can control the surface roughness and crystallite sizes of ALD films.
Unwrapping and visualizing cuneiform tablets

Cuneiform inscriptions, which scholars consider the first written language, were made in moist, clay tablets. We've developed a semiautomatic method for concisely displaying the tablets' inscribed writing, thereby providing a clear visualization that can be printed on paper. We first scan the tablets with 3D range scanners and use the scan data to construct a high-resolution 3D model (at a resolution of 50 microns). Next, we unwrap and warp the tablet surface to form a set of flat rectangles, one per side or edge of the tablet. This process permits all the writing to be seen at once, although necessarily slightly distorted. Finally, we apply curvature coloring and accessibility coloring to the unwrapped text, thereby replacing raking illumination with a nonphotorealistic rendering technique.
The Informed Patient: An Analysis of Information Seeking Behavior and Surgical Outcomes Among Men With Benign Prostatic Hyperplasia.

The Internet has placed considerable information at the disposal of patients, but the sources for credible and accurate information may be difficult for a layperson to discern. Benign prostatic hyperplasia (BPH) in elderly men can be treated with different surgical interventions. The purpose of this research was to determine information seeking behaviors (ISB) of BPH patients before and after each type of surgery. All patients who underwent surgical intervention for BPH at a tertiary training center between January 2007 and January 2013 were included in this study. A comprehensive questionnaire regarding their ISB was sent through a third-party survey center. The following areas were examined: (1) the patient’s opinion regarding information sources of BPH and its treatment, (2) the extent of ISB for each patient and its relation to the type of surgical intervention he eventually underwent, and (3) the relationship between the extent of ISB and the patient’s final satisfaction. The results indicated that t...
Economic Haul Radius as Affected by Diesel Fuel Cost

The cost of diesel fuel has remained consistently high and volatile, and the equipment-intensive construction industry has experienced increasing uncertainty in transportation costs. Therefore, this study evaluates the impact of diesel cost volatility on the economic distance for hauling aggregates. The paper proposes the calculation of an economic haul radius to quantify hauling costs over a probabilistic range of diesel prices and thereby quantify the impact of these prices. The literature defines the “economic haul distance” as the point at which the cost of hauling the material equals the supplier cost of the material at the source. The Peurifoy method was used to determine operational costs for a typical aggregate haul truck, and, from that output, the economic haul radius was determined. The results showed that the economic distance that aggregate could be hauled was a direct function of the price of the diesel fuel used in the contractor’s bid. The resulting stochastic algorithm can be used to esti...
Reflective analysis as a tool for task redesign: The case of prospective elementary teachers solving and posing fraction comparison problems

Mathematical task design has been a central focus of the mathematics education research community over the last few years. In this study, six university teacher educators from six different US institutions formed a community of practice to explore key aspects of task design (planning, implementing, reflecting, and modifying) in the context of comparing fractions using reasoning and sense-making. By presenting results of their implementation of two tasks with 63 prospective elementary teachers across three institutions and their reflective analysis of the implementation, the authors highlight the importance of collecting and analyzing data and reflecting on this analysis to inform the redesign of tasks. The authors also found that considering different types of tasks (problem solving vs. problem posing) helps illuminate different aspects of prospective elementary teachers' understanding, which can inform task redesign. Finally the authors contribute to the knowledge base on reasoning strategies for comparing fractions and prospective elementary teachers’ knowledge of these strategies.
A Self-Acquiring Knowledge Process for MCTS

MCTS (Monte Carlo Tree Search) is a well-known and efficient process to cover and evaluate a large range of states for combinatorial problems. We choose to study MCTS for the Computer Go problem, which is one of the most challenging problem in the field of Artificial Intelligence. For this game, a single combinatorial approach does not always lead to a reliable evaluation of the game states. In order to enhance MCTS ability to tackle such problems, one can benefit from game specific knowledge in order to increase the accuracy of the game state evaluation. Such a knowledge is not easy to acquire. It is the result of a constructivist learning mechanism based on the experience of the player. That is why we explore the idea to endow the MCTS with a process inspired by constructivist learning, to self-acquire knowledge from playing experience. In this paper, we propose a complementary process for MCTS called BHRF (Background History Reply Forest), which allows to memorize efficient patterns in order to promote their use through the MCTS process. Our experimental results lead to promising results and underline how self-acquired data can be useful for MCTS based algorithms.
Improved Cocure of EPDM-Polydiene Blends by Conversion of EPDM into Macromolecular Cure Retarder

Abstract The 1,2-addition of certain N-chlorothioamides to the olefinic sites of EPDM produces modified polymers which exhibit improved covulcanization in blends with polydiene rubbers. A mechanism is postulated in which the modified EPDM retards the cure of the polydiene phase and at the same time is itself activated toward crosslinking. Model compound data are presented to support these views.
Experimental pneumonia produced by Streptococcus hemolyticus

Pulmonary lesions were produced by the insufflation of a strain of Streptococcus hemolyticus isolated in Texas and kindly given us by Dr. Avery. The cultures proved to be highly virulent for white mice. A quantity of the culture was insufflated intra-bronchially into twenty-four dogs. The dose varied from 1 to 3 c.c. per kilo. Of these animals nine died in less than twenty-four hours, one died on the third day, and the rest were killed three to fifteen days after the inoculation. Dogs which survived more than two days went on to recovery, although they were ill for several days. Streptococcemia was found in all the animals which died early. It was also found in one of two dogs which was killed on the third day and in one of two killed on the fourth day after injection. Later than the fourth day no streptococci were found in the blood. Blood stained pus was present in the pleural cavity in three dogs, all having streptococci in the heart's blood. One of these animals died on the third day, one was killed o...
Exile and return: from phenomenology to naturalism (and back again)

AbstractNaturalism in twentieth century philosophy is founded on the rejection of ‘first philosophy’, as can be seen in Quine’s rejection of what he calls ‘cosmic exile’. Husserl’s transcendental phenomenology falls within the scope of what naturalism rejects, but I argue that the opposition between phenomenology and naturalism is less straightforward than it appears. This is so not because transcendental phenomenology does not involve a problematic form of exile, but because naturalism, in its recoil from transcendental philosophy, creates a new form of exile, what I call in the paper ‘exile from within’. These different forms of exile are the result of shared epistemological aspirations, which, if set aside, leave open the possibility of phenomenology without exile. In the conclusion of the paper, I appeal to Merleau-Ponty as an example of what phenomenology without epistemology might look like.
Computers: Everyone’s a Writer

This chapter deals with computers, the device that really started the digital revolution. The famous 1984 Macintosh commercial is discussed, showing how it reflected ambivalent view we have about computers and their role in society and our lives. Computers play a major role in the development of our digital culture. The ability of computers to edit texts and images and films is dealt with. Next I offer statistics showing that the sale of desktop computers has peaked, though they still sell in huge numbers. This if followed by a discussion of the ability of computers to recognize faces and the existence of programs that can scan faces and obtain reliable information about our emotions as well as medical and psychological problems.
A Micromachined Silicon Low-Voltage Parallel-Plate Electrokinetic Pump

Interest is increasing in the development of electrokinetic pumps capable of generating high flow rates (> 1 ml/min). These pumps are suitable for applications such as microcooler systems. Electrokinetic pumps offer the considerable advantages of simple architecture, no moving parts, low power consumption, and robust operation. Large electric potentials are typically involved in the operation of electrokinetic devices, limiting the use of silicon in such devices. We have devised a pump design that addresses this problem. The performance of test devices of this new design suggests that electrokinetic pumping is a viable option for fluid transport and fluidic actuation in silicon micromachined devices.
Extracorporeal Membrane Oxygenation in the Neonate with Respiratory Failure

In 1944, Kolff and Berk observed that blood became oxygenated as it passed through cellophane chambers of an artificial kidney membrane [1]. This historic observation led to the recognition that blood could be oxygenated through a semipermeable membrane lung [2]. In 1956, the development of the first membrane lung, which used an ethylcellulose membrane [3], opened the door for the study of prolonged cardiopulmonary bypass and the potential application of extracorporeal membrane oxygenation (ECMO) as an artificial lung. The concept of an artificial placenta capable of continuing ex utero the gas-exchange functions of the placenta developed in parallel with that of an artificial lung. In 1961, Callaghan and colleagues began using animal models of respiratory distress syndrome (RDS) of the newborn to test the efficacy of an extracorporeal oxygenation circuit as an artificial placenta [3], which was later expanded to premature infants [4]–[6]. This was an extremely important period for the development and refinement of the mechanical and surgical techniques that laid the foundation for the subsequent success of ECMO. The full potential of ECMO for infants in severe respiratory failure was not realized until it was used on term infants. In 1976, Bartlett et al., reported the first neonatal ECMO survivor, a term infant with severe meconium aspiration syndrome (MAS) [7]. During the subsequent 10 years, neonatal ECMO was used to treat 99 term infants with respiratory failure in three centres in the United States with an overall survival rate of 65%.
Dietary supplement interactions with antiretrovirals: a systematic review

Many patients who take antiretroviral drugs also take alternative therapies including dietary supplements. Some drug-supplement combinations may result in clinically meaningful interactions. We aimed to investigate the evidence for dietary supplement interactions with antiretrovirals. A systematic review was conducted using multiple resources including PubMed, Natural Medicine Comprehensive Database, The Review of Natural Products, and Google Scholar. All human studies or case reports evaluating an interaction between a dietary supplement and an antiretroviral were selected for inclusion. Twenty-eight pharmacokinetic studies and case-series/case reports were selected for inclusion. Calcium carbonate, ferrous fumarate, some forms of ginkgo, some forms of garlic, some forms of milk thistle, St. John's wort, vitamin C, zinc sulfate, and multivitamins were all found to significantly decrease the levels of selected antiretrovirals and should be avoided in patients taking these antiretrovirals. Cat's claw and evening primrose oil were found to significantly increase the levels of antiretrovirals and patients should be monitored for adverse effects while taking these dietary supplements with antiretrovirals. This systematic review shows the importance of screening all human immunodeficiency virus patients for dietary supplement use to prevent treatment failure or adverse effects related to an interaction.
CD40L is transferred to antigen‐presenting B cells during delivery of T‐cell help

The delivery of T-cell help to B cells is antigen-specific, MHC-restricted, and CD40L (CD154) dependent. It has been thought that when a T cell recognizes an antigen-presenting B cell, CD40L expressed on the T-cell surface engages with CD40 on the surface of B cells as long as the cells remain conjugated. By adding fluorescently labeled anti-CD40L antibody during overnight incubation of antigen-presenting B cells with antigen-specific T cells, we discovered that CD40L does not remain on the surface of the T cell, but it is transferred to and endocytosed by B cells receiving T-cell help. In the presence of anti-CD40L antibody, transferred CD40L is nearly absent on bystander B cells that are not presenting antigen, and the bystander cells do not become activated. Because transfer of CD40L to B cells correlates with B-cell activation, we speculate that persistence of helper T-cell-derived CD40L on or in B cells could permit sustained CD40 signaling enabling survival and proliferation of antigen-presenting B cells following brief interactions with helper T cells in vivo in germinal centers.
Contract’s Constitutive Core: Solving Problems by Making Deals

This article offers a positive, interpretive analysis of American contract law as an ongoing problem-solving enterprise. The article observes that solving problems is central to all life on this planet; that problem solving, both private and public, is the primary focus of American law generally and contract law in particular; and that many different decision-makers, including single individuals, small groups of collaborators, deal-making adversaries, large organizations, and governmental institutions, rely on a variety of deliberative processes in reaching and implementing solutions. The article uses this problem-solving perspective to explain American contract doctrine, including aspects that traditional bargain theory explains only with difficulty, if at all. In developing its central thesis, the analysis distinguishes between contract’s constitutive core and its regulative penumbra. The core empowers private actors to interact more effectively in reaching and implementing solutions to private problems. The penumbra consists of normative regulations that courts apply both to deal-making and to deals. When parties bring contracts claims to court, the plaintiff must show that the promises she relies on were part of an effort by the parties to use contract’s core to solve problems. Once assured of that premise, courts use the regulative penumbra to lend assistance, often enthusiastically, in interpreting, implementing, and sometimes salvaging deals struck by the parties. The article does not judge the rightness or wrongness of these judicial responses or the system of which they are part. Rather, the article contents itself with explaining what is really going on, and why.
Abstract 2199: Evaluation of critical residues in the C-terminal binding protein (CtBP) dehydrogenase domain contributing to substrate binding, catalysis, and oncogenic activity

C-terminal binding proteins (CtBP) 1 and 2 are transcriptional coregulators that are upregulated in several cancers, including a majority of studied breast, colorectal, and ovarian tumor samples. CtBPs drive many cellular oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes, such as E-cadherin, PTEN, BRCA1, and p16. CtBPs encode an intrinsic dehydrogenase activity regulated by both intracellular NADH concentration and the putative substrate 4-methylthio-2-oxobutyric acid (MTOB). NADH binding induces CtBP dimerization, which regulates the recruitment of transcriptional regulatory complexes. High levels of MTOB appear to inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. However, the function of the substrate-binding domain has yet to be examined with regard to CtBP9s oncogenic activity. To this end, we have created several point mutations in the substrate-binding pocket of CtBP and have determined key residues for CtBP9s enzymatic activity using an in vitro dehydrogenase assay. We have found that a conserved tryptophan in the catalytic domain, and specifically its aromatic moiety, is imperative for enzyme activity. This tryptophan is unique to CtBP family proteins and distinguishes the CtBP substrate-binding domain from that of all other families of dehydrogenases. Additionally, we found arginine and histidine residues lining the substrate pocket that are necessary for CtBP dehydrogenase function. Knowledge of these residues allows the directed synthesis of drugs with increased potency and higher CtBP specificity. Moreover, to investigate the importance of the catalytic domain on CtBP9s oncogenic potential, we have transfected human cancer cell lines with several CtBP substrate-binding domain mutants and observed the effects on cellular processes, including growth, survival, migration, and recruitment of key components of the transcriptional repressor complex. From this work we have investigated the utility of CtBP, and specifically the CtBP substrate-binding domain, as a target for cancer therapeutics. We also provide preliminary insights into the function of this domain in cellular models of cancer. Citation Format: Benjamin L. Morris, Priyadarshan Damle, Zaid Nawaz, Steven R. Grossman. Evaluation of critical residues in the C-terminal binding protein (CtBP) dehydrogenase domain contributing to substrate binding, catalysis, and oncogenic activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2199. doi:10.1158/1538-7445.AM2015-2199
Vowel length and vowel transition: cues to [± voice] in post-vocalic stops

Abstract Raphael (1972) demonstrates that for his synthetic tokens, listeners utilize vowel length as a cue to [± voice] in a following stop, in a continuous manner. That is, there is a range of vowel durations above which listeners will predict a following [+ voice] stop and below which they will predict a following [− voice] stop. However, within this range listeners’ predictions will vary depending on the spectral configuration of the vowel: a falling F1 cues a [+ voice] stop; a level F1 cues a [− voice] stop. The present study corroborates the findings of Raphael (1972) using real speech tokens, although the critical durations are shifted downward 70–80 ms. It is concluded that since the vowel transition serves as the operative cue during the intermediate range of vowel durations, then the only possible function of vowel length as a cue is either to reinforce or to override the transition cue at extremely long and short vowel durations. In other words, vowel length is (at best) a redundant cue or (at worst) a misleading one.
Locations Where Space Weather Energy Impacts the Atmosphere

In this review we consider aspects of space weather that can have a severe impact on the terrestrial atmosphere. We begin by identifying the pre-conditioning role of the Sun on the temperature and density of the upper atmosphere. This effect we define as “space climatology”. Space weather effects are then defined as severe departures from this state of the atmospheric energy and density. Three specific forms of space weather are reviewed and we show that each generates severe space weather impacts. The three forms of space weather being considered are the solar photon flux (flares), particle precipitation (aurora), and electromagnetic Joule heating (magnetosphere–ionospheric (M-I) coupling). We provide an overview of the physical processes associated with each of these space weather forms. In each case a very specific altitude range exists over which the processes can most effectively impact the atmosphere. Our argument is that a severe change in the local atmosphere’s state leads to atmospheric heating and other dynamic changes at locations beyond the input heat source region. All three space weather forms have their greatest atmospheric impact between 100 and 130 km. This altitude region comprises the transition between the atmosphere’s mesosphere and thermosphere and is the ionosphere’s E-region. This region is commonly referred to as the Space Atmosphere Interaction Region (SAIR). The SAIR also acts to insulate the lower atmosphere from the space weather impact of energy deposition. A similar space weather zone would be present in atmospheres of other planets and exoplanets.
Behavioral Interactions Between the Hyperparasitoid Mesochorus discitergus (Hymenoptera: Ichneumonidae) and Four Species of Noctuid Caterpillars: Evasive Tactics and Capture Efficiency

The hyperparasitoid, Mesochorus discitergus (Say), oviposits into larvae of primary parasitoids while the latter are developing inside various lepidopteran hosts. To accomplish hyperparasitism, M. ...
Phase I trial of temsirolimus (TEM) and perifosine (PER) for recurrent or progressive malignant glioma (MG).

2095 Background: PI3K/AKT/mTOR signaling is important in MG biology, and therefore a potential therapeutic target. The mTOR inhibitor TEM and the AKT inhibitor PER are well tolerated as single agen...
Killing of Candida albicans by histatin 5: cellular uptake and energy requirement.

Histatins, a group of histidine-rich proteins in human saliva, exhibit antimicrobial activity and are therefore considered to be important in the prevention of infections in the oral cavity. Although killing of C. albicans by histatins has been extensively studied, little is known about the processes responsible for this antifungal activity. Recent studies show the requirement of metabolic activity and ATP production for histatin 5 killing activity. Therefore, the goal of this study was to investigate the kinetics of histatin 5 interaction at different temperatures with C. albicanswild type cells and with respiratory deficient mutants of C. albicans. Synthetic histatin 5 was labeled with fluorescein-5-isothiocyanate (FITC) and its association with C. albicans cells was followed by epi-fluorescence microscopy and fluorescence confocal microscopy. At 37 °C, histatin 5 accumulates intracellularly, and both killing activity and uptake of unlabeled and FITC-labeled histatin 5 are time- and concentration-dependent. At 4 °C, no killing is observed and FITC-histatin 5 is only associated with the cytoplasmic membrane. Internalization and killing activity only occurs after cells are transferred to 37 °C. In addition, cellular accumulation of histatin 5 is concomitant with a moderate alteration of membrane integrity leading to the release of UV-absorbing cell components into the medium. The uptake of histatin 5, the release of UV-absorbing materials and killing of C. albicans are markedly decreased by the respiratory inhibitor sodium azide. Concomitantly, respiratory deficient mutants of C. albicans are also less susceptible to histatin 5. These results indicated that histatin 5 killing activity could be directly correlated to histatin 5 internalization. Both of these processes are prevented by modulators of cellular metabolic activity.
Fundamental Factors Impacting the Stability of Phosphonate-Derivatized Ruthenium Polypyridyl Sensitizers Adsorbed on Metal Oxide Surfaces.

A series of 18 ruthenium(II) polypyridyl complexes were synthesized and evaluated under electrochemically oxidative conditions, which generates the Ru(III) oxidation state and mimics the harsh conditions experienced during the kinetically limited regime that can occur in dye-sensitized solar cells (DSSCs) and dye-sensitized photo-electrosynthesis cells, to further develop fundamental insights into the factors governing molecular sensitizer surface stability in aqueous 0.1 M HClO4. Both desorption and oxidatively induced ligand substitution were observed on planar fluorine-doped tin oxide (FTO) electrodes, with a dependence on the E1/2 Ru(III/II) redox potential dictating the comparative ratios of the processes. Complexes such as RuP4OMe (E1/2 = 0.91 vs Ag/AgCl) displayed virtually only desorption, while complexes such as RuPbpz (E1/2 > 1.62 V vs Ag/AgCl) displayed only chemical decomposition. Comparing isomers of 4,4′- and 5,5′-disubstituted-2,2′-bipyridine ancillary ligands, a dramatic increase in the ra...
Java, Eiffel and C++: The Language Comparison

This tutorial is based on my upcoming book comparing Eiffel, Java and C++. While the object models of these languages are very similar, they are very different in the ease with which software can be built.We will examine the differences between the languages, their strengths and weaknesses in a hard-headed look. The superficial syntactic differences will be looked at, but more importantly, the semantic differences and philosophical basis of each language.We will see how these differences apply in actually developing software, as it is not just a question of theoretical niceness, but practical application, and what this means in terms of ensuring quality in software.
A detergent-insoluble membrane compartment contains Aβ in vivo

Ordered assembly of the amyloid-beta protein (A beta) into amyloid fibrils is a critical step in Alzheimer's disease (AD). To release the amyloidogenic peptide A beta from the Alzheimer amyloid precursor protein (APP), two secretases act sequentially: first, beta-secretase cleaves close to the membrane within the ectodomain and then gamma-secretase cuts within the transmembrane domain. The sites of gamma-secretase cleavage are after residues 40 or 42 of A beta. Except in those rare cases of AD caused by a mutation, levels of secreted A beta are not elevated; thus, the secretory pathway may be unaffected, and factors other than the extracellular concentration of A beta may contribute to the aggregation properties of the peptide. A beta is also present in intracellular compartments. The two gamma-secretase cleavage products, A beta42 and A beta40, were found in different compartments: A beta42 in the endoplasmic reticulum (ER)/intermediate compartment, and A beta40 in the trans-Golgi network (TGN). The cellular compartments that harbor A beta are target sites for therapeutic intervention. Here we report that in the brain, the principal compartment in which A beta resides is a detergent-insoluble glycolipid-enriched membrane domain (DIG). Also present in the DIG fractions are the endoproteolytic fragments of presenilin-1 (PS1) and APP. The presence of these proteins, which all contribute to the generation of A beta, indicates that the DIG fraction is probably where the intramembranous cleavage of APP occurs.
The Local Environmental Kuznets Curve: Civil Society Linkages between Economic Growth and Environmental Protection

An intriguing puzzle concerning urban environments is whether or not cities are characterized by a Kuznets Curve. Based on theorizing about the economic development of countries, our conjecture is this: can we assume that after cities reach a level of economic prosperity that they place greater emphasis on quality of life issues and, conversely, less emphasis on economic development? If so, wealthier cities should prioritize sustainability efforts — those programs and policies designed to mitigate environmental degradation. We examine this proposition here but move beyond a simple relationship between city income and effort toward environmental protection. Rather, we hypothesize that any such relationship is conditioned by a city’s level of environmental advocacy. The data utilized in this analysis are derived from two large-scale databases. One is a comprehensive inventory of sustainability programs and policies in fifty large American cities. The other is a set of surveys in those same 50 cities. Our multivariate model supports our hypothesis. Controlling for income growth, a city’s commitment to sustainability is strongly linked to environmentalists’ presence in the policymaking process.
Recent Advances in the Observation and Analysis of Stellar Magnetic Fields

There has been considerable progress recently in the study of magnetic fields on late-type stars. Advances in the theory include investigation of systematic effects, new and improved methods of analysis for unpolarized and circularly polarized lines, new models of stellar dynamos and of broadband linear polarization, and the first studies of the thermodynamic nature of stellar magnetic regions and their vertical structure. Observationally, there have been new measurements, particularly of young and active stars (including the first detection of a field on a pre-main sequence object, a new monitoring campaign, the first indications of the relative temperatures in stellar plages, and the first measurements of fields in a single stellar active region. I discuss the results in the framework of stellar activity and surface structure.
The impact of biology on the treatment of secondary AML.

Secondary, or therapy-related, acute myeloid leukemia (AML) developing after exposure to genotoxic agents accounts for approximately 10–20% of all AML cases. The prototype “induced AML” was described almost half a century ago in the setting of environmental exposures to DNA-damaging toxins including benzene, organic solvents, arsenicals and ionizing radiation ([Golomb et al., 1982]; [Mitelman et al., 1978]). The emergence of AML after cytotoxic therapy was initially recognized in patients with Hodgkin’s disease, one of the first malignancies cured with cytotoxic therapy. In the case of Hodgkin’s disease, the leukemia arises from the background of multi-agent cytotoxic therapy that includes alkylating agents, often in combination with radiation ([Levine & Bloomfield, 1992]; [Pedersen-Bjergaard & Larsen, 1982]). Recent reports of therapy-related myelodysplastic syndromes (MDS) and AML encountered in patients with Hodgkin’s and non-Hodgkin’s lymphoma following high-dose chemotherapy and autologous bone marrow transplantation (ASCT) have confirmed a positive relationship between the cumulative dose of alkylating agents and the risk of developing secondary AML ([Andre et al., 1998]; [Darrington et al., 1994]; [Harrison et al., 1999]; [Milligan et al., 1999]; [Pedersen-Bjergaard et al., 2000]; [Traweek et al., 1994]). In several studies, the cumulative risk of secondary MDS/AML has varied widely from 1.1% at 20 months to 24.3% 43 months after ASCT ([Pedersen-Bjergaard et al., 1997]; [Taylor et al., 1997]).