cssi/SciSciGPT-SciSciNet huggingface dataset:
Atomistic Kinetic Model for Population Shift and Allostery in Biomolecules

Allosteric signaling in biomolecules is a key mechanism for a myriad of cellular processes. We present a general yet compact model for protein allostery at atomic detail to quantitatively explain and predict structural-dynamics properties of allosteric signal propagation. The master equation-based approach for allostery by population shift (MAPS) is introduced that derives the time scales, amplitudes, and pathways of signal transmission in peptides and proteins from dihedral angle dynamics observed in extended molecular dynamics simulations. The MAPS approach is first applied to the alanine-pentapeptide, and the results are tested against an explicit simulation in the presence of local conformational constraints, confirming the validity and accuracy of the model. We then apply the approach to a larger Markovian system based on a millisecond all-atom protein molecular dynamics trajectory of BPTI (Shaw et al. Science2010, 330, 341–346). We use MAPS to illustrate in silico the propagation of a local perturba...
Axis formation in zebrafish

Recent advances in our understanding of axis formation and patterning in zebrafish relate the developmental mode of this aspiring genetic model organism to higher vertebrates. The effect of UV irradiation and lithium treatment, as well as detailed early lineage analyses, have shed some light on dorsoventral axis formation. However, the molecular mechanism of axis formation, as well as the identity of a fish Nieuwkoop center, are still open issues. A Vg1 homolog is expressed in zebrafish, and activin as well as the mouse nodal gene product have been demonstrated to induce mesoderm and ectopic axes, respectively, in zebrafish. The zebrafish organizer is defined by the expression domains of goosecoid, axial, and lim1. The cyclops gene is involved in maintaining goosecoid expression in axial mesoderm of the head. Large mutagenesis screens provide the basis for a genetic analysis of axis formation.
Satisfaction and Morale Among Parish Clergy: What American Catholic and Orthodox Priests Can Learn from Each Other

The Roman Catholic and Eastern Orthodox churches share a similar theology and a hierarchical church administration. Local parish communities are organized in similar ways. However, the Roman Catholic and Orthodox Christian churches occupy different places in the context of American culture, and they have developed distinct notions of priesthood. Findings explore similarities and differences in the attitudes and experience of Catholic and Orthodox clergy. Most striking, the younger clergy (less than 45 years of age) report more conservative attitudes about the priesthood, “democracy” in church government, and empowering lay persons in the ministry.
NUMERICAL OPTIMIZATION OF EVAPORATIVE MISTING SYSTEMS

ABSTRACT, A new method for implementing evaporative misting of broiler houses was developed and investigated. The method consisted of a nonlinear optimization of an objective function for bird comfort, subject to a set of constraints defining a thermal balance on the building. The method predicted the interior state point of the air, the ventilation rate and evaporative efficiency. The misting evaporation rate was specified at different values. The objective function utilized was a temperature-humidity index (THI). Minimizing THI with specified evaporation rates resulted in surprisingly low ventilation rates over an extremely wide range for outside conditions. Comparison of these results with conventional misting operations showed substantial reductions in THI (2° C for a typical case). Application of the proposed new method is discussed.
Lessons from Unsuccessful Attempts to Establish Spodoptera pectinicornis (Lepidoptera: Noctuidae), a Biological Control Agent of Waterlettuce

We released nearly 332 000 Spodoptera pectinicornis individuals for biological control of the floating aquatic weed Pistia stratiotes (waterlettuce) at 22 sites in Florida during December 1990-December 1997. Predation (by boat-tailed grackles, fire ants, and spiders) and Allee effects (resulting from rapid dispersal of adults) prevented populations from persisting during early attempts. These efforts consisted of small releases at multiple sites, with no nurturing of the introduced populations. Modification of our initial approach resulted in a series of release strategies that consisted of multiple releases at fewer sites and employed progressively more intensive nurturing of the introduced populations. The most successful strategy incorporated: (i) cages to restrict adult dispersal and exclude flying predators; (ii) plant-free zones around the cages to exclude crawling predators; (iii) enhancement of the nutritional quality of waterlettuce in the cages; and (iv) frequent inoculation of the cages with la...
Oxidation of Ultra-High Molecular Weight Polyethylene and Its Influence on Contact Fatigue and Pitting of Knee Bearings

Tibial hearings of total knee replacements are generally made from ultra-high molecular weight polyethylene (UHMWPE). Failure of those hearings has been found to result in many cases from subsurface crack initiation and propagation. Two types of subsurface-originated failure modes are investigated in this study: macroscopic contact fatigue and microscopic pitting. The cracks responsible for both modes of failure initiate in polyethylene material that has been embrittled by oxidation; this oxidation is an undesirable outcome of the gamma irradiation (in air) used to sterilize the tibial bearings. Accelerated aging was used in this work to achieve oxidation levels similar to those found in retrieved bearings. Tribotesting of the aged bearing materials was carried out under simulated service conditions using a rolling/sliding tester. Macroscopic fatigue cracks and microscopic surface pitting developed in UHMWPE specimens tested on the rolling/sliding tester, and the damage was similar to that found in retrie...
TGF-β2 treatment enhances cytoprotective factors released from embryonic stem cells and inhibits apoptosis in infarcted myocardium.

We investigated whether factors released from mouse embryonic stem (ES) cells primed with and without transforming growth factor (TGF)-β2 inhibit iodoacetic acid (IAA)- and H2O2-induced apoptosis i...
Mapped Vector Basis Functions for Electromagnetic Integral Equations

The method-of-moments solution of the electric field and magnetic field integral equations (EFIE and MFIE) is extended to conducting objects modeled with curved cells. These techniques are important for electromagnetic scattering, antenna, radar signature, and wireless communication applications. Vector basis functions of the divergence-conforming and curl-conforming types are explained, and specific interpolatory and hierarchical basis functions are reviewed. Procedures for mapping these basis functions from a reference domain to a curved cell, while preserving the desired continuity properties on curved cells, are discussed in detail. For illustration, results are presented for examples that employ divergence-conforming basis functions with the EFIE and curl-conforming basis functions with the MFIE. The intended audience includes electromagnetic engineers with some previous familiarity with numerical techniques.
Near-threshold deuteron photodisintegration: An indirect determination of the Gerasimov-Drell-Hearn sum rule and forward spin polarizability ( γ 0 ) for the deuteron at low energies

It is shown that a measurement of the analyzing power obtained with linearly polarized \ensuremath{\gamma}-rays and an unpolarized target can provide an indirect determination of two physical quantities. These are the Gerasimov-Drell-Hearn (GDH) sum rule integrand for the deuteron and the sum rule integrand for the forward spin polarizability (${\ensuremath{\gamma}}_{0}$) near photodisintegration threshold. An analysis of data for the $d(\stackrel{\ensuremath{\rightarrow}}{\ensuremath{\gamma}},n)p$ reaction and other experiments is presented. A fit to the world data analyzed in this manner gives a GDH integral value of $\ensuremath{-}603\ifmmode\pm\else\textpm\fi{}43\ensuremath{\mu}$b between the photodisintegration threshold and 6 MeV. This result is the first confirmation of the large contribution of the ${}^{1}{S}_{0}(M1)$ transition predicted for the deuteron near photodisintegration threshold. In addition, a sum rule value of 3.75\ifmmode\pm\else\textpm\fi{}0.18 fm${}^{4}$ for ${\ensuremath{\gamma}}_{0}$ is obtained between photodisintegration threshold and 6 MeV. This is a first indirect confirmation of the leading-order effective field theory prediction for the forward spin-polarizability of the deuteron.
Pancreatitis and fatal ARDS following high-dose cytarabine induction for acute myelogenous leukemia:

Objective. To describe a case of fatal acute respira tory distress syndrome (ARDS) and pancreatitis aris ing from high-dose cytarabine induction therapy.Case Summary. A 50-year-old male without a h...
A Parallel Algorithm for Contact in a Finite Element Hydrocode

A parallel algorithm is developed for contact/impact of multiple three dimensional bodies undergoing large deformation. As time progresses the relative positions of contact between the multiple bodies changes as collision and sliding occurs. The parallel algorithm is capable of tracking these changes and enforcing an impenetrability constraint and momentum transfer across the surfaces in contact. Portions of the various surfaces of the bodies are assigned to the processors of a distributed-memory parallel machine in an arbitrary fashion, known as the primary decomposition. A secondary, dynamic decomposition is utilized to bring opposing sections of the contacting surfaces together on the same processors, so that opposing forces may be balanced and the resultant deformation of the bodies calculated. The secondary decomposition is accomplished and updated using only local communication with a limited subset of neighbor processors. Each processor represents both a domain of the primary decomposition and a domain of the secondary, or contact, decomposition. Thus each processor has four sets of neighbor processors: (a) those processors which represent regions adjacent to it in the primary decomposition, (b) those processors which represent regions adjacent to it in the contact decomposition, (c) those processors which send it the data from which it constructsmore » its contact domain, and (d) those processors to which it sends its primary domain data, from which they construct their contact domains. The latter three of these neighbor sets change dynamically as the simulation progresses. By constraining all communication to these sets of neighbors, all global communication, with its attendant nonscalable performance, is avoided. A set of tests are provided to measure the degree of scalability achieved by this algorithm on up to 1024 processors. Issues related to the operating system of the test platform which lead to some degradation of the results are analyzed. This algorithm has been implemented as the contact capability of the ALE3D multiphysics code, and is currently in production use.« less
Efficient solution-phase synthesis of 4,5,7-trisubstituted pyrrolo[3,2-d]pyrimidines.

We have developed an efficient and robust route to synthesize 4,5,7-trisubstituted pyrrolo[3,2-d]pyrimidines as potent kinase inhibitors. This solution-phase synthesis features a SNAr substitution reaction, cross-coupling reaction, one-pot reduction/reductive amination and N-alkylation reaction. These reactions occur rapidly with high yields and have broad substrate scopes. A variety of groups can be selectively introduced into the N5 and C7 positions of 4,5,7-trisubstituted pyrrolopyrimidines at a late stage of the synthesis, thereby providing a highly efficient approach to explore the structure–activity relationships of pyrrolopyrimidine derivatives. Four synthetic analogs have been profiled against a panel of 48 kinases and a new and selective FLT3 inhibitor 9 is identified.
Building A Health Care Workforce For The Future: More Physicians, Professional Reforms, And Technological Advances

Traditionally, projections of US health care demand have been based upon a combination of existing trends in usage and idealized or expected delivery system changes. For example, 1990s health care demand projections were based upon an expectation that delivery models would move toward closed, tightly managed care networks and would greatly decrease the demand for subspecialty care. Today, however, a different equation is needed on which to base such projections. Realistic workforce planning must take into account the fact that expanded access to health care, a growing and aging population, increased comorbidity, and longer life expectancy will all increase the use of health care services per capita over the next few decades—at a time when the number of physicians per capita will begin to drop. New technologies and more aggressive screening may also change the equation. Strategies to address these increasing demands on the health system must include expanded physician training.
Convergence of Web 2.0 and Semantic Web: A Semantic Tagging and Searching System for Creating and Searching Blogs

During the last several years, the volume of user- generated content on the web has skyrocketed. Today, the major Internet players such as MySpace, Wordpress, and YouTube all provide a variety of Web 2.0 based applications that allow users to post photos, share video, and manage blogs with multimedia content. Keyword-based tags are used to classify the submitted content and to conduct searches for retrieval. Use of simple keyword-based tags provide less than optimal classification leading to poor search results. This work examines several proposed solutions to this problem and proposes a solution based on semantic tagging of online contents. These proposed semantic tags are intended to be "understandable" to both machines and humans; additionally we allow the user to specify a context for each tag. The combination of these measures permits searches based on inferences and synonyms in addition to simple keyword matches. Initial tests demonstrate that use of the proposed scheme leads to more accurate content classification and search results with a greater number of hits and higher relevancy. We describe the design and, implementation of a prototype system as proof of concept of our proposed solution. The prototype has been implemented with extensive use of open source software such as Jena, jBoss, the Spring framework, PostgreSQL database, and other freely available resources such as Wordnet.
Solomon, Exorcism, and the Son of David

A comprehensive view of the Son of David in the New Testament requires facing the following problem: on the one hand, Davidic quotations, metaphors, and the descent theme are derived from the Old Testament royal tradition as it is channeled through Jewish texts; on the other, the title Son of David is found only in the synoptic gospels and is associated primarily with a figure who is so addressed by people in need of exorcism or healing. The usual solution to this problem in works on Christology is to say that a) miracle working is not associated with the Jewish royal Messiah in general or the Son of David in particular in contemporaneous Jewish literature, and b) it is early Christian tradition and/or redaction which has transformed the traditional royal conception and linked it with miracle working.
Effects of cholinomimetics on glucose utilization in rat brain optic systems

Physostigmine and oxotremorine effects on local cerebral glucose utilization (LCGU) in rat brain optic systems were examined by the [14C]2-deoxy-D-glucose procedure. Both drugs significantly stimulated LCGU in the superior colliculus (superficial layer) and nucleus of the optic tract, but not in the visual cortex. Physostigmine, but not oxotremorine, stimulated LCGU in components of the accessory optic system. The effects in the accessory optic system apparently result from nicotinic actions of physostigmine.
Heliothis Cytoplasmic Polyhedrosis Virus and Its Effect upon Microbial Contaminant-Free Heliothis virescens

Abstract Cytoplasmic polyhedrosis virus (CPV) of Heliothis is infectious to all larval instars except prepupal. Three, 4-, 5-, and 6-day-old larvae were more susceptible to CPV infection than older larvae. Among neonate, 1-, 2-, 3-, and 4-day-old larvae, the period to pupation was significantly longer in CPV-infected larvae than in controls. Pupation time of larvae infected at an older age was not different from controls. Neonate, 1-, 2-, and 3-day-old larvae treated with CPV required more time to reach the adult stage than controls. In general, the use of contaminant-free insects provides a lower mortality rate when exposed to Heliothis CPV. Both CPV-infected males and females transmit virus to the F1 generation.
Genesis II - Standards Based Grid Computing

In the past years, hype over Web services and their uses in emerging software applications has prompted the creation of many standards and proto-standards. The OGF has seen a number of standards making their way through design and edit pipelines. While this standards process progresses, it is important that implementations of these standards develop in parallel in order to validate the efforts of the standards authors while also providing feedback for further specification refinement. No specification exists in isolation but rather composes with others to form higher order products. These specifications will form the grid infrastructure of the future and an evaluation of this emerging work becomes increasingly relevant. Genesis II is a grid system implemented using these standards that serves both to provide the feedback described above as well as to function as a production level grid system for research at the University of Virginia.
“The Spirit of the Sierra Maestra”: Five Observations on Writing about Cuban Foreign Policy

For a variety of reasons, explanations of Cuban foreign policy lack in persuasiveness. Some authors adopt a kitchen-sink approach in which any number of factors are adduced to explain Cuban behavior, but they do not pay adequate attention to how these various pieces fit together into a coherent whole. Other writers concentrate on a single factor to explain Cuba's globalism, but in the process load more explanatory power than it can bear onto a sole variable. Still others have a penchant for prescribing proper foreign policy for the United States, with the result that the study of Cuban policy in its own terms is often shortchanged. Only by studying the character, world view, and charismatic influence of Fidel Castro can a center of gravity be found for the study of Cuban foreign policy.
Rabbit lung indolethylamine N-methyltransferase. cDNA and gene cloning and characterization.

Abstract Indolethylamine N-methyltransferase (INMT) catalyzes the N-methylation of tryptamine and structurally related compounds. This reaction has been studied because of its possible role in the in vivo synthesis of psychoactive compounds or neurotoxins and has been characterized biochemically in preparations of rabbit lung. Therefore, we set out to purify rabbit lung INMT, to clone and express its cDNA, and to clone and structurally characterize its gene as steps toward understanding the function and regulation of this enzyme. Rabbit lung INMT was purified and partial amino acid sequence was obtained. A polymerase chain reaction-based approach was then used to clone a rabbit lung INMT cDNA with a 792-base pair open reading frame that encoded a 263-amino acid protein with a predicted molecular mass of 29 kDa. When the cDNA was expressed in COS-1 cells, the encoded protein catalyzed the methylation of tryptamine and structurally related compounds, and was inhibited by two products of the reaction,S-adenosyl-l-homocysteine (AdoHcy) andN,N-dimethyltryptamine, as well as antimigraine drugs that are structurally related to N,N-dimethyltryptamine. Northern blot analysis demonstrated the presence of 2.0-kilobase mRNA species in rabbit lung, liver and, at lower levels, in brain. The cDNA was then used to clone the rabbit INMT gene. That gene had three exons and was structurally similar to the genes for nicotinamideN-methyltransferase and phenylethanolamineN-methyltransferase in several species. Cloning and expression of a rabbit lung INMT cDNA and cloning of the rabbit INMT gene represent important steps toward determination of the function and regulation of this mammalian methyltransferase enzyme.
Gesture as a Window and a Tool

Gestures can give us a window in to the thought processes of the gesturer, and gesture production can impact the thought processes of the gesturer. Working from the gestures-as-simulated-action framework (Hostetter and Alibali, 2008), possible explanations for mechanisms by which this might occur are explored. These include that gestures can add action to the gesturer’s conceptual knowledge structure, that there is effort involved in inhibiting gesture, and that gesture can serve as a supplemental resource with which to interact with information. An important applied consideration of this work is whether these mechanisms operate to different extents in spontaneous gestures and induced gestures. Evidence for these perspectives and previous research on how gestures relate to the thoughts of those producing them is summarized, and a new experiment is proposed to extend this understanding. Applications of our knowledge about gestures are discussed in the context of psychological research methods, and user int...
Microlinguistic deficits in the narrative discourse of adults with traumatic brain injury.

Background: Recent studies of microlinguistic impairments in the narrative discourse of adults with traumatic brain injury (TBI) have applied syntactic analyses, with some noting no deficits and others specific problems with sentence formulation. An alternative approach to examining the microlinguistic dysfunction in the discourse of individuals with TBI is through the use of propositional analysis. The advantage of propositional analysis is that it enables one to assess semantic complexity of utterances apart from sentence structure and grammaticality.Aims: The present study applied propositional analysis to the story narratives of participants with TBI and participants with no brain injury (NBI). Specifically, the mean number of propositions within a sentence was tallied, in other words the participants' ability to insert multiple ideas into single surface sentences. It was hypothesized that the participants with TBI would produce fewer propositions per sentence because of organizational problems than t...
Protocols for an optical star interconnect for high speed mesh networks

Optical networks can provide higher throughputs while high speed electronic networks possess the intelligence for network control and management. We present a two level high speed network architecture that combines the throughput advantage of optical networks and the intelligence of electronic processing. One level is a high speed mesh LAN which uses wormhole routing, source routing and hop-by-hop flow control mechanisms with mesh routers (asynchronous pipelined crossbar switches) to provide a high speed electronic network. The second level is an optical star network interconnecting high speed mesh networks distributed across metropolitan area distances. We obtain analytical expressions for the average message (worm) delays for the GTDM (group time division multiplexing) multi-access protocol (which includes as special cases TDM and DAS) for single-hop packet switching in the optical network of such an architecture. We use a two state discrete time Markov chain to model the arrival of messages to the optical network. Results for both uniform traffic and non-uniform traffic are presented. Finally, a modified dynamic allocation scheme is presented for single-hop packet switching which handles the message as a unit rather than sending a message as several fixed sized packets.
Variability of Body Temperature in the Normal Chick

Abstract IN CONNECTION with other studies involving variations in the temperatures of chicks during the first two weeks of life, it was necessary to determine first the normal variations and environmental conditions affecting them during that period. So far as could be ascertained the only data on this subject obtained with adequate numbers of chicks under normal conditions of brooding and diet are the unpublished figures of Fronda (1922) which indicate that at one and two weeks of age the temperature is about 3°F. higher than at hatching. Card’s (1921) unwatered chicks, kept to five days, showed considerable diurnal variation in temperature. The present writers sought to find (1) possible sources of error in determination of temperature, (2) an adequate technic for temperature determination in baby chicks, (3) normal temperature variations in relation to age, weight, sex, and breed of the chick from hatching until it approaches the normal temperature of . . .
Heterogeneity and plasticity of T helper cells

CD4 T helper (Th) cells play critical roles in adaptive immune responses. They recruit and activate other immune cells including B cells, CD8 T cells, macrophages, mast cells, neutrophils, eosinophils and basophils. Based on their functions, their pattern of cytokine secretion and their expression of specific transcription factors, Th cells, differentiated from naive CD4 T cells, are classified into four major lineages, Th1, Th2, Th17 and T regulatory (Treg) cells, although other Th lineages may exist. Subsets of the same lineage may express different effector cytokines, reside at different locations or give rise to cells with different fates, whereas cells from different lineages may secrete common cytokines, such as IL-2, IL-9 and IL-10, resulting in massive heterogeneity of the Th cell population. In addition, the pattern of cytokine secretion may switch from that of one lineage toward another under certain circumstances, suggesting that Th cells are plastic. Tregs are also more heterogeneous and plastic than were originally thought. In this review, we summarize recent reports on heterogeneity and plasticity of Th cells, and discuss potential mechanisms and implications of such features that Th cells display.
Gastrointestinal surgery for severe obesity

The 1991 Consensus Development Panel was instrumental both in establishing criteria for selection of patients for surgical treatment and in recognition of operations that have been shown to be safe and reasonably effective in the long term. The Panel may have been premature in endorsement of any form of banded gastroplasty because the long-term weight loss results of these procedures are frequently disappointing. It seems likely that a consensus panel on the same subject would be worthwhile in the next decade to carefully evaluate such procedures as biliopancreatic bypass and the various laparoscopic techniques for gastric banding. In 1996 surgery remains the only effective treatment for patients with medically severe (morbid) obesity.
Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application

Research into human biotransformation and elimination systems continues to evolve. Various clinical and in vivo studies have been undertaken to evaluate the effects of foods and food-derived components on the activity of detoxification pathways, including phase I cytochrome P450 enzymes, phase II conjugation enzymes, Nrf2 signaling, and metallothionein. This review summarizes the research in this area to date, highlighting the potential for foods and nutrients to support and/or modulate detoxification functions. Clinical applications to alter detoxification pathway activity and improve patient outcomes are considered, drawing on the growing understanding of the relationship between detoxification functions and different disease states, genetic polymorphisms, and drug-nutrient interactions. Some caution is recommended, however, due to the limitations of current research as well as indications that many nutrients exert biphasic, dose-dependent effects and that genetic polymorphisms may alter outcomes. A whole-foods approach may, therefore, be prudent.
Organics in meteorites - Solar or interstellar?

GL, Carnegie Institution of Washington,5251 Broad Branch Road, Washington DC 20015, USAemail: g.cody@gl.ciw.edu, m.fogel@gl.ciw.edu, hyabuta@gl.ciw.eduAbstract.The insoluble organic material (IOM) in primitive meteorites is related to the organicmaterial in interplanetary dust particles and comets, and is probably related to the refractoryorganic material in the diﬀuse interstellar medium. If the IOM is representative of refractoryISM organics, models for how and from what it formed will have to be revised.Keywords.Comets, asteroids, ISM: dust
A large-grain data flow architecture utilizing multiple levels of parallelism

A data flow architecture is presented that utilizes several levels of parallelism by a three-level hierarchical hardware structure. Task level parallelism was exploited by the architectural structure of a distributed memory multiprocessor and a load distribution strategy that supports parallel execution of procedure activations. Block and instruction level parallelism was utilized by token-passing, similar to large-grain data flow. Subinstruction level parallelism was exploited by single instruction, multiple data (SIMD) evaluation of complex machine instructions. >
Effects of Growth Mode and Pyruvate Carboxylase on Succinic Acid Production by Metabolically Engineered Strains of Escherichia coli

Escherichia coli NZN111, which lacks activities for pyruvate-formate lyase and lactate dehydrogenase, and AFP111, a derivative which contains an additional mutation in ptsG (a gene encoding an enzyme of the glucose phophotransferase system), accumulate significant levels of succinic acid (succinate) under anaerobic conditions. Plasmid pTrc99A-pyc, which expresses the Rhizobium etli pyruvate carboxylase enzyme, was introduced into both strains. We compared growth, substrate consumption, product formation, and activities of seven key enzymes (acetate kinase, fumarate reductase, glucokinase, isocitrate dehydrogenase, isocitrate lyase, phosphoenolpyruvate carboxylase, and pyruvate carboxylase) from glucose for NZN111, NZN111/pTrc99A-pyc, AFP111, and AFP111/pTrc99A-pyc under both exclusively anaerobic and dual-phase conditions (an aerobic growth phase followed by an anaerobic production phase). The highest succinate mass yield was attained with AFP111/pTrc99A-pyc under dual-phase conditions with low pyruvate carboxylase activity. Dual-phase conditions led to significant isocitrate lyase activity in both NZN111 and AFP111, while under exclusively anaerobic conditions, an absence of isocitrate lyase activity resulted in significant pyruvate accumulation. Enzyme assays indicated that under dual-phase conditions, carbon flows not only through the reductive arm of the tricarboxylic acid cycle for succinate generation but also through the glyoxylate shunt and thus provides the cells with metabolic flexibility in the formation of succinate. Significant glucokinase activity in AFP111 compared to NZN111 similarly permits increased metabolic flexibility of AFP111. The differences between the strains and the benefit of pyruvate carboxylase under both exclusively anaerobic and dual-phase conditions are discussed in light of the cellular constraint for a redox balance.
Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region

Chromosome 22q11.2 heterozygous deletions cause the most common deletion syndrome, including the DiGeorge syndrome phenotype. Using a mouse model of this deletion (named Df1) we show that the aortic arch patterning defects that occur in heterozygously deleted mice (Df1/+) are associated with a differentiation impairment of vascular smooth muscle in the 4th pharyngeal arch arteries (PAAs) during early embryogenesis. Using molecular markers for neural crest, endothelial cells and vascular smooth muscle, we show that cardiac neural crest migration into the 4th arch and initial formation of the 4th PAAs are apparently normal in Df1/+ embryos, but affected vessels are growth-impaired and do not acquire vascular smooth muscle. As in humans, not all deleted mice present with cardiovascular defects at birth. However, we found, unexpectedly, that all Df1/+ embryos have abnormally small 4th PAAs during early embryogenesis. Many embryos later overcome this early defect, coincident with the appearance of vascular smooth muscle differentiation, and develop normally. Embryos born with aortic arch patterning defects probably represent a more severely affected group that fails to attain sufficient 4th PAA growth for normal remodelling of the PAA system. Our data indicate that Df1/+ embryos are able to overcome a localized arterial growth impairment and thereby reduce the penetrance of birth defects.
New Concepts in Collision Avoidance Logic

Airborne collision avoidance logic is being developed to take advantage of the accurate bearing measurements provided by the Enhanced TCAS II system. This system issues horizontal and vertical resolution advisories, and should give fewer unnecessary alarms than earlier systems. Design tradeoffs and new techniques are described for threat detection, modeling of potential escape maneuvers, and the selection of resolution advisories. Plans for further development and evaluation are described.
Electrical impedance measurements predict cellular transformation

Cellular transformation is the first step in cancer development. Two features of cellular transformation are proliferation in reduced serum and loss of contact inhibition. Electronic Cell-Substrate Impedance Sensing (ECIS) measurements have been used to measure cellular proliferation, cytotoxicity, apoptosis, and attachment. We have used impedance measurements to distinguish normal cells from cells transformed with a constitutively active chemokine receptor, CXCR2. CXCR2, a member of the G-protein coupled receptor (GPCR) family, is normally involved in cellular activation and migration, but a single amino acid substitution leads to constitutive activity. NIH3T3 cells were transformed with a constitutively active CXCR2 (D143V_CXCR2) and growth in reduced serum and foci formation were measured using established biological assays and compared to data from ECIS. The results of this study show that impedance measurements provide a quick and reliable way of measuring cellular transformation and provide real time assessment of transformed cellular parameters. Use of the ECIS system could allow a rapid screening of anti-cancer drugs that alter cellular transformation.
A new short memory turbo code with good BER performance and low decoding complexity

A new rate 1/2 turbo code with short memory 2 is developed in this paper. The proposed turbo code consists of two 4-state parallel concatenated non-punctured systematic rate-2/3 convolutional codes. Using a modified maximum a posteriori (MAP) decoding algorithm working on dual codes, its bit error rate (BER) performance is comparable to that of the classic 16-state turbo code at short block lengths, such as k=1024, while its decoding complexity is less than 1/8 that of the classic 16-state turbo codes; for information block length k=504, its BER performance is better than that of the (1008, 3, 6) LDPC codes with comparable decoding complexity. The dual code decoding algorithm is intrinsically partial parallel and a considerably higher throughput of the turbo decoder can be obtained compared with classic turbo codes consisting of punctured codes. The simulation results show that the proposed turbo code can be a competitive technique for short block length applications.
Human Genetics, Paleoenvironments, and Malaria: Relationships and Implications for the Settlement of Oceania

Lapita is a distinctive ceramic style that first appeared in the Bismarck Archipelago about 3600 B.P. and over the next few centuries spread throughout island Melanesia. For many prehistorians the distribution of Lapita sherds identifies the expansion of Austronesian-speaking populations through Oceania. This article addresses the Lapita language question by exploring the implications of the relationship among gamma globulin (Gm) genetics, paleoenvironments, malaria, natural selection, and prehistoric settlement patterns. Archeological sites with Lapita ceramics are consistently located in coastal lowlands, which in some parts of Oceania would have been malarious areas. Drawing on recent evidence that Austronesian-speaking populations in Near Oceania possess a genetic advantage over Non-Austronesian speakers with regard to malaria, we contend that Austronesian speakers have been able to occupy—on a permanent basis—malarious coastal lowlands that were detrimental to Non-Austronesian speakers. It follows, therefore, that the inhabitants of those Lapita sites spoke one or more of the Austronesian languages.
Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults.

Context In addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability. Objective To increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene × environment interactions of child abuse, level of non–child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5. Design, Setting, and Participants A cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non–child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007. Main Outcome Measures Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non–child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus. Results Level of child abuse and non–child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs ≥2 types of abuse, 20.93 [14.32]; and for no non–child abuse trauma, 3.58 [6.27] vs ≥4 types, 16.74 [12.90]; P Conclusions Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non–child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.
Engineering database hardware and software together

Since its inception, Oracle's database software primarily ran on customer configured off-the-shelf hardware. A decade ago, the architecture of conventional systems started to become a bottleneck and Oracle developed the Oracle Exadata Database Machine to optimize the full hardware and software stack for database workloads. Exadata is based on a scale-out architecture of database servers and storage servers that optimizes both OLTP and Analytic workloads while hosting hundreds of databases simultaneously on the same system. By using database specific protocols for storage and networking we bypass limitations imposed by conventional network and storage layers. Exadata is now deployed at thousands of Enterprises including 4 of the 5 largest banks, telecoms, and retailers for varied workloads such as interbank funds transfers, e-commerce, ERP, Cloud SaaS applications, and petabyte data warehouses.Five years ago, Oracle initiated a project to extend our database stack beyond software and systems and into the architecture of the microprocessor itself. The goal of this effort is to dramatically improve the performance, reliability and cost effectiveness of a new generation of database machines. The new SPARC M7 processor is the first step. The M7 is an extraordinarily fast conventional processor with 32-cores per socket and an extremely high bandwidth memory system. Added to its conventional processing capabilities are 32 custom on-chip database co-processors that run database searches at full memory bandwidth rates, and decompress data in real-time to increase memory bandwidth and capacity. Further, the M7 implements innovative fine-grained memory protection to secure sensitive business data.In the presentation we will describe how Oracle's engineering teams integrate software and hardware at all levels to achieve breakthrough performance, reliability, and security for the database and rest of the modern data processing stack.
Constrained inference of protein interaction networks for invadopodium formation in cancer.

Integrating prior molecular network knowledge into interpretation of new experimental data is routine practice in biology research. However, a dilemma for deciphering interactome using Bayes’ rule is the demotion of novel interactions with low prior probabilities. Here the authors present constrained generalised logical network (CGLN) inference to predict novel interactions in dynamic networks, respecting previously known interactions and observed temporal coherence. It encodes prior interactions as probabilistic logic rules called local constraints, and forms global constraints using observed dynamic patterns. CGLN finds constraint-satisfying trajectories by solving a k-stops problem in the state space of dynamic networks and then reconstructs candidate networks. They benchmarked CGLN on randomly generated networks, and CGLN outperformed its alternatives when 50% or more interactions in a network are given as local constraints. CGLN is then applied to infer dynamic protein interaction networks regulating invadopodium formation in motile cancer cells. CGLN predicted 134 novel protein interactions for their involvement in invadopodium formation. The most frequently predicted interactions centre around focal adhesion kinase and tyrosine kinase substrate TKS4, and 14 interactions are supported by the literature in molecular contexts related to invadopodium formation. As an alternative to the Bayesian paradigm, the CGLN method offers constrained network inference without requiring prior probabilities and thus can promote novel interactions, consistent with the discovery process of scientific facts that are not yet in common beliefs.
Considering Decision-Making and Sexuality in Menstrual Suppression of Teens and Young Adults with Intellectual Disabilities.

A guardian’s request to sterilize a woman with intellectual disabilities is not ethically justifiable unless the woman assents and it is to her benefit.
Methodologies for Identifying Food System Research Priorities: Dispatch from Alaska

Alaska faces unique challenges to sustainable food systems and food security, including extreme climate conditions and geographical remoteness, and yet the state is similar to the "Lower 48" states with respect to many indicators that can be used to characterize the health of our food systems. Due to common concerns over such indicators as obesity rates, food insecurity rates, and recruitment of new farmers, food system stakeholders in Alaska are promoting a resurgence of food systems research and advocacy that is exemplified in the work of the Alaska Food Policy Council (AFPC). Identifying and prioritizing the specific food systems research needs of a state as large and diverse as Alaska is a challenge, but one that is being met with methodical, straightforward approaches. This commentary outlines two examples of recent formal, yet relatively simple, methods for identifying food system research and action priorities, and concludes by sharing some of the latest identified Alaska food system priority research projects, ideas, and needs.
INFLAMMATORY EFFECTS OF PYROGENIC STEROIDS IN ANIMALS.

SummaryThree steroid pyrogens known to produce fever and inflammation in man were examined for inflammatory activity in rabbits, guinea pigs, hamsters, rats and dogs. Etiocholanolone, 11-ketopregnanolone and lithocholic acid are all capable of eliciting intense inflammatory reactions in experimental animals, although considerable variation in individual and species sensitivity was observed. Lithocholic acid, like the neutral steroids, failed to produce fever in rabbits, rats, dogs, cats and monkeys, thus confirming the highly specific nature of this activity in humans.
EPN and S,S,S,-Tributyl Phosphorotrithioate as Synergisms of Methyl Parathion in Resistant Tobacco Budworm Larvae (Lepidoptera: Noctuidae)

EPN [O-ethyl O-( p -nitrophenyl)phenylphosphonothioate] and TBPT ( S,S,S, -tributyl phosphorotrithioate) were synergists for methyl parathion in the laboratory against a resistant strain of the tobacco bud worm, Heliothis virescens (F.). When compared directly with larvae of a susceptible strain at the LD90,315-fold resistance to methyl parathion was reduced to ll-fold and 9-fold resistance to methyl parathion/EPN and methyl parathion/ TBPT mixtures, respectively. Piperonyl but oxide and triphenyl phosphate were not effective as synergists. Results are discussed in relation to toxokinetic interactions, including inhibition of hydrolases and other detoxificative enzymes of synergists.
Biochemical Characterization of the Human Mitochondrial Replicative Twinkle Helicase: SUBSTRATE SPECIFICITY, DNA BRANCH MIGRATION, AND ABILITY TO OVERCOME BLOCKADES TO DNA UNWINDING.

Mutations in the c10orf2 gene encoding the human mitochondrial DNA replicative helicase Twinkle are linked to several rare genetic diseases characterized by mitochondrial defects. In this study, we have examined the catalytic activity of Twinkle helicase on model replication fork and DNA repair structures. Although Twinkle behaves as a traditional 5′ to 3′ helicase on conventional forked duplex substrates, the enzyme efficiently dissociates D-loop DNA substrates irrespective of whether it possesses a 5′ or 3′ single-stranded tailed invading strand. In contrast, we report for the first time that Twinkle branch-migrates an open-ended mobile three-stranded DNA structure with a strong 5′ to 3′ directionality preference. To determine how well Twinkle handles potential roadblocks to mtDNA replication, we tested the ability of the helicase to unwind substrates with site-specific oxidative DNA lesions or bound by the mitochondrial transcription factor A. Twinkle helicase is inhibited by DNA damage in a unique manner that is dependent on the type of oxidative lesion and the strand in which it resides. Novel single molecule FRET binding and unwinding assays show an interaction of the excluded strand with Twinkle as well as events corresponding to stepwise unwinding and annealing. TFAM inhibits Twinkle unwinding, suggesting other replisome proteins may be required for efficient removal. These studies shed new insight on the catalytic functions of Twinkle on the key DNA structures it would encounter during replication or possibly repair of the mitochondrial genome and how well it tolerates potential roadblocks to DNA unwinding.