cssi/SciSciGPT-SciSciNet huggingface dataset:
Rotavirus diversity and evolution in the post-vaccine world.

Rotaviruses (RVs) are a large genetically diverse population of segmented double-stranded (ds) RNA viruses that are important causes of gastroenteritis in many animal species. The human RVs are responsible for the deaths of nearly 450,000 infants and young children each year, most occurring in developing countries. Recent large-scale sequencing efforts have revealed that the genomes of human RVs typically consist of phylogenetically linked constellations of eleven dsRNA segments. The presence of such preferred constellations indicate that the human RV genes have co-evolved to produce protein sets that work optimally together to support virus replication. Two of the viral genes encode virion outer capsid proteins (VP7 and VP4) whose antigenic properties define the G/P type of the virus. From year-to-year and place-to-place, the G/P type of human RVs associated with disease can fluctuate dramatically, phenomena that can be associated with the presence and behavior of genetically distinct RV clades. The recent introduction of two live attenuated RV vaccines (RotaReq™ and Rotarix™) into the childhood vaccination programs of various countries has been highly effective in reducing the incidence of RV diarrheal disease. Whether the widespread use of these vaccines will introduce selective pressures on human RVs, triggering genetic and antigenic changes that undermine the effectiveness of vaccinations programs, is uncertain and will require continued surveillance of human RVs.
The region in myosin S-1 that may be involved in energy transduction

Newly-reported structural information about certain proximities between points on bound nucleotide and points on the heavy chain of myosin S-1 are incorporated into a previously-reported [Botts, J. Thomason, J.F. & Morales, M.F. Proc. Nat. Acad. Sci. USA,86, 2204-2208 (1989)] structure of S-l. The resulting, enhanced structure is then used to identify some functionalities (e.g., the ATP-perturbable tryptophans), and to explain certain observations (e.g., some concerning the role of bound Mg2+ in the spectral response of TNBS-labelled Lys-83, and some concerning the response of the S-1 CD signal to nucleotide binding and to temperature change). These considerations lead to the suggestion that a strand of the 50 kDa “domain” (residues 510 to 540), and a strand of the 20 kDa ‘domain” (residues 697–719) are involved in transmitting the effects of nucleotide binding and hydrolysis to the loop (constituted from the same “domains”) that reaches a major (S-l)-actin interface.
Application of Immunohistochemistry in Diagnosis of Renal Cell Neoplasms

Renal neoplasms comprise a heterogeneous group of tumors with divergent clinicopathological and molecular characteristics as well as therapeutic options. Therefore, accurate diagnosis and classification of the different subtypes of renal cell carcinoma (RCC), and to verify the renal primary in the setting of metastatic disease are critical for patient management and determining prognosis. In the last three decades, more and more subtypes of RCC have been described and many of them have overlapping clinicomorphologic features. Incorporating diagnostic immunohistochemistry and molecular tests in diagnosis of renal tumors is a critical component of our daily surgical pathology practice. In this chapter, we will discuss the immunohistochemical markers that are commonly used in clinical laboratories. In addition, common diagnostic problems that deserve special attention in the differential diagnosis of major RCC subtypes will also be addressed.
Sunday Drivers, or Too Fast and Too Furious?

The recent influx of electric scooters (e-scooters) has left cities scrambling to answer how to best to regulate them. To help inform policymaking, we studied e-scooter riding behavior through observations of speed and rider distractions. Observations show e-scooter riders travel faster on streets and slower on sidewalks and slightly slower than cyclists on streets. Additionally, few e-scooter riders wear helmets, and some may be distracted by headphones but not by handling cellphones.
Foucault on Correspondence as a Technique of the Self

This paper begins with a discussion of Foucault's examination of Seneca's epistles in his late essay, "Self Writing." I argue that Foucault offers an accurate and interesting account of the practices Seneca employs in his epistles pursuant to his art of living. This paper then considers Foucault's interpretation of Seneca's art of living as an aesthetics of existence. I argue that this interpretation is unsatisfactory, instead suggesting that Seneca's art of living is a plausible response to the problem of suffering. I close by arguing that such a conception of Seneca's art of living makes it relevant for present-day human beings, who, like Seneca, are subject to the problem of suffering.
Toward Integrated Processual Theories of Crime: Assessing the Developmental Effects of Executive Function, Self-Control, and Decision-Making on Offending:

Research on executive function indicates that self-control stems partially from normative brain development. Extant research has also provided evidence of an association between self-control and of...
Approaches to Eviction Prevention

This Article provides a general overview of eviction prevention approaches and strategies that are currently being employed, or could be adapted, to prevent eviction and homelessness during the COVID-19 pandemic. This document provides an overview of strategies that could prevent or mitigate eviction for nonpayment of rent, including 1) eviction and foreclosure moratoria, 2) housing stabilization, 3) landlord relief programs, 4) equitable approaches to the eviction process, and 5) post-eviction mitigation measures. Many of these policies and interventions predate the COVID-19 pandemic, and were employed during the Great Recession of 2008, and could be adapted to the pandemic environment.
Severe Acute Respiratory Syndrome Coronavirus 2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

BACKGROUND: Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children. METHODS: We conducted a prospective cohort study of children and adolescents (<21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay. RESULTS: Of 382 children, 293 (77%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have asthma (p=0.005), and more likely to have an infected sibling contact (p=0.001) than uninfected children. Children ages 6-13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs. 48%; p=0.01) or adolescents (29% vs. 60%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p<0.0001), gastrointestinal (27% vs. 9%; p=0.002), and sensory symptoms (42% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.01]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONS: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.
Silicon Photonic Modulator Neuron

Neural networks based on optoelectronics could be more than a million times as fast as electronic implementations, opening uncharted regimes of information processing. Despite advances in laser-based neurons and programmable Si photonic interconnects, a photonic neuron compatible with a photonic network is missing. These challenges could be addressed by photonic-modulator-based neurons that were integrable on the same platform as Si interconnects. The authors fabricate a Si photonic-modulator neuron and observe all essential networking properties of fan-in, cascadability, and high-gain nonlinearity, plus programmable, multi-input, time-resolved, and self-feedback processing behaviors.
A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Nonessential Modes of Oncogenic Transformation.

Mutations in ARID1A rank among the most common molecular aberrations in human cancer. However, oncogenic consequences of ARID1A mutation in human cells remain poorly defined due to lack of forward genetic models. Here, CRISPR/Cas9-mediated ARID1A knockout (KO) in primary TP53-/- human gastric organoids induced morphologic dysplasia, tumorigenicity, and mucinous differentiation. Genetic WNT/β-catenin activation rescued mucinous differentiation, but not hyperproliferation, suggesting alternative pathways of ARID1A KO-mediated transformation. ARID1A mutation induced transcriptional regulatory modules characteristic of microsatellite instability and Epstein-Barr virus-associated subtype human gastric cancer, including FOXM1-associated mitotic genes and BIRC5/survivin. Convergently, high-throughput compound screening indicated selective vulnerability of ARID1A-deficient organoids to inhibition of BIRC5/survivin, functionally implicating this pathway as an essential mediator of ARID1A KO-dependent early-stage gastric tumorigenesis. Overall, we define distinct pathways downstream of oncogenic ARID1A mutation, with nonessential WNT-inhibited mucinous differentiation in parallel with essential transcriptional FOXM1/BIRC5-stimulated proliferation, illustrating the general utility of organoid-based forward genetic cancer analysis in human cells. SIGNIFICANCE: We establish the first human forward genetic modeling of a commonly mutated tumor suppressor gene, ARID1A. Our study integrates diverse modalities including CRISPR/Cas9 genome editing, organoid culture, systems biology, and small-molecule screening to derive novel insights into early transformation mechanisms of ARID1A-deficient gastric cancers.See related commentary by Zafra and Dow, p. 1327.This article is highlighted in the In This Issue feature, p. 1307.
Counteracting COVID-19 Healthcare Inequity: Supporting Antiracist Practices at Bedside.

In “Racism and Bioethics: the myth of color blindness” Braddock (2021) convincingly argues that a “color blind” approach to triage and resource allocation in the setting of the COVID-19 pandemic pe...
Edge Load Solutions for Conical Shells

Solutions of the governing equations for truncated conical shells are developed for stress couples and transverse shear resultants at each end of the shell. Because of the rapid dissipation of the ...
A Multi-Task-Learning-Based Transfer Deep Reinforcement Learning Design for Autonomic Optical Networks

Deep reinforcement learning (DRL) enables autonomic optical networking by allowing the network control and management systems to self-learn successful networking policies from operational experiences. This paper proposes a transfer learning approach for effective and scalable DRL in optical networks. We first present a modular DRL agent design to facilitate retrieving and transferring relevant knowledge between tasks requiring different dimensions of network state data. In particular, we partition network state data into common states, which contain generic information critical to multiple tasks (e.g., the spectrum utilization on fiber links), and task-specific states that are only used by a specific task (e.g., the utilization of virtual network functions). Separate neural network blocks are employed to process different state data. Based on the modular agent design, a multi-task learning (MTL) aided knowledge transferring scheme is proposed. The proposed scheme trains an MTL agent that can master multiple tasks simultaneously and thus enables to learn and transfer better-generalized knowledge across tasks. We perform case studies on the proposed transfer DRL approach considering two scenarios, namely, knowledge transferring between routing, modulation and spectrum assignment (RMSA) tasks for different networks and knowledge transferring from RMSA tasks to anycast service provisioning tasks. The DRL designs for RMSA and anycast service provisioning, including the state, action, and reward formulations and the training mechanisms, are also elaborated. Performance evaluations under both scenarios show that the proposed approach can effectively expedite the training processes of the target tasks and improve the ultimate service throughput.
Liposomal Bupivacaine Versus Immediate-Release Bupivacaine for Postoperative Pain Control.

BackgroundLiposomal bupivacaine (LB) is increasingly being used for postoperative pain control, but there are conflicting efficacy data when compared with immediate-release bupivacaine (IRB).Object...
A bacteria-based assay to study SARS-CoV-2 protein-protein interactions

Methods for detecting and dissecting the interactions of virally encoded proteins are essential for probing basic viral biology and providing a foundation for therapeutic advances. The dearth of targeted therapeutics for the treatment of COVID-19, an ongoing global health crisis, underscores the importance of gaining a deeper understanding of the interactions of SARS-CoV-2-encoded proteins. Here we describe the use of a convenient bacteria-based two-hybrid (B2H) system to analyze the SARS-CoV-2 proteome. We identify sixteen distinct intraviral protein-protein interactions (PPIs), involving sixteen proteins. We find that many of the identified proteins interact with more than one partner. We further show how our system facilitates the genetic dissection of these interactions, enabling the identification of selectively disruptive mutations. We also describe a modified B2H system that permits the detection of disulfide bond-dependent PPIs in the normally reducing Escherichia coli cytoplasm and we use this system to detect the interaction of the SARS-CoV-2 spike protein receptor-binding domain (RBD) with its cognate cell surface receptor ACE2. We then examine how the RBD-ACE2 interaction is perturbed by several RBD amino acid substitutions found in currently circulating SARS-CoV-2 variants. Our findings illustrate the utility of a genetically tractable bacterial system for probing the interactions of viral proteins and investigating the effects of emerging mutations. In principle, the system could also facilitate the identification of potential therapeutics that disrupt specific interactions of virally encoded proteins. More generally, our findings establish the feasibility of using a B2H system to detect and dissect disulfide bond-dependent interactions of eukaryotic proteins. ImportanceUnderstanding how virally encoded proteins interact with one another is essential in elucidating basic viral biology, providing a foundation for therapeutic discovery. Here we describe the use of a versatile bacteria-based system to investigate the interactions of the protein set encoded by SARS-CoV-2, the virus responsible for the current pandemic. We identify sixteen distinct intraviral protein-protein interactions, involving sixteen proteins, many of which interact with more than one partner. Our system facilitates the genetic dissection of these interactions, enabling the identification of selectively disruptive mutations. We also describe a modified version of our bacteria-based system that permits detection of the interaction between the SARS-CoV-2 spike protein (specifically its receptor binding domain) and its cognate human cell surface receptor ACE2 and we investigate the effects of spike mutations found in currently circulating SARS-CoV-2 variants. Our findings illustrate the general utility of our system for probing the interactions of virally encoded proteins.
Hypocrisy and the Politics of Politeness: Manners and Morals from Locke to Austen

In Hypocrisy and the Politics of Politeness, Jenny Davidson considers the arguments that define hypocrisy as a moral and political virtue in its own right. She shows that these were arguments that thrived in the medium of eighteenth-century Britain's culture of politeness. In the debate about the balance between truthfulness and politeness, Davidson argues that eighteenth-century writers from Locke to Austen come down firmly on the side of politeness. This is the case even when it is associated with dissimulation or hypocrisy. These writers argue that the open profession of vice is far more dangerous for society than even the most glaring discrepancies between what people say in public and what they do in private. This book explores what happens when controversial arguments in favour of hypocrisy enter the mainstream, making it increasingly hard to tell the difference between hypocrisy and more obviously attractive qualities like modesty, self-control and tact.
Why Co-Utilization?

The land application of by-products from agricultural, industrial or municipal sources is certainly not a new phenomena. Wood ashes, manures, crop residues and even some of the first food processing wastes, such as oyster shells, were applied to the land and, dependant upon site specifics, probably showed a beneficial response by the next crop. These positive responses led to agricultural practices which were continued over time. Today, with renewed interest in concepts such as sustainability, biodynamic farming, and natural resource conservation, the practice of applying by-products to land continues.
Conflicting Preferences: Avoidance Proceedings in Bankruptcy Liquidation and Reorganization

The law of preferential transfers permits the trustee of a bankruptcy estate to avoid transfers made by the debtor to a creditor on account of a prior debt in the 90 days leading up to the bankruptcy proceeding. The standard for avoiding these preferential transfers is one of strict liability, on the rationale that preference actions exist to ensure that all general creditors of the bankruptcy estate recover the same proportional amount, regardless of the debtor’s intent to favor any one creditor or the creditor’s intent to be so favored. However, preference law also permits certain exceptions to strict preference liability and gives the estate trustee discretion in pursuing preference actions. These exceptions and the use of discretion permit the continuation of preferences to certain creditors. Such practices undermine the policy of equal distribution by permitting some creditors to fare better than others in the bankruptcy distribution. However, these practices are arguably necessary to promote conflicting bankruptcy policies that seek to maximize the estate for the benefit of creditors and encourage the survival of struggling businesses. As a result, the law of preferences is internally inconsistent and controversial, attempting unsuccessfully to serve multiple policy masters at the same time. Much of the analysis on preferences up to now has proposed amending preference law generally in an attempt to satisfy these often conflicting demands. This article recommends consideration of a more dramatic approach; returning preference law to a mechanism of equal distribution in liquidation proceedings by eliminating true exceptions to the rule, and doing away with preference law altogether in the context of bankruptcy reorganization.
Matrix Activism: Media, Neoliberalism, and Social Action in Italy

Using the case of the Rome-based media group ZaLab, this article examines the articulations that shape and define the multiple dynamics of connected activism in contemporary societies. The first section engages the existing literature on convergence, commodity activism, and connectivity as theoretical frameworks of my analysis of ZaLab. The second section provides some context on the Italian mainstream and activist mediascapes, both of which shape ZaLab’s media practices. The last section examines a few specific examples of ZaLab’s productions and the activist campaign created to promote them. I conclude with some reflections on the nature of contemporary media practices as part of what I call “matrix activism.”
The use of sodium perchlorate in deproteinization during the preparation of nucleic acids

Sodium perchlorate in high concentrations will remove from solution the detergent sodium dodecyl sulphate and protein complexed with it. This and the failure of proteins to be precipitated by ethanol from solutions containing a high concentration of sodium perchlorate can be utilized as efficient, rapid and simple deproteinization procedures during the preparation of nucleic acids.
An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality

An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality
ARIES/KVL: A Key-Value Locking Method for Concurrency Control of Multiaction Transactions Operating on B-Tree Indexes

This paper presents a method, called ARIES/ KVL (Algorithm for Recovery and Isolation Exploiting Semantics using Key-Value Locking), for concurrency control in B-tree indexes. A transaction may perform any number of nonindex and index operations, including range scans. ARIES/KVL guarantees serializability and it supports very high concurrency during tree traversals, structure modifications, and other operations. Unlike in System R, when one transaction is waiting for a lock on a key value in a page, reads and modifications of that page by other transactions are allowed. Further, transactions that are rolling back will never get into deadlocks. ARIESIKVL, by also using for key value locking the IX and SIX lock modes that were intended originally for table level locking, is able to better exploit the semantics of the operations to improve concurrency, compared to the System R index protocols. These techniques are also applicable to the concurrency control of the classical links-based storage and access structures which are beginning to appear in modern systems also.
Inhibition of intracellular proteolysis in muscle cultures by multiplication-stimulating activity

The effects of the insulin-like growth factor, multiplication-stimulating activity (MSA), on chick myotube cultures are studied. The results indicate that MSA is an effective anabolic agent regulating protein metabolism and amino acid uptake, but not sugar transport. Similar size effects on protein metabolism and amino acid uptake in serum-free media were observed in parallel studies with insulin, although insulin levels well in excess of the normal physiological range are required to produce significant effects. It is suggested that there is a generally low insulin sensitivity in cultured chick myotubes relative to adult tissues.
Ex vivo killing of primary melanocytes by syngeneic mononuclear cells from active, autoimmune vitiligo lesions in Smyth chickens (BA7P.152)

In humans autoimmune vitiligo is characterized by the loss of pigment-producing melanocytes in the skin. The vitiligo-prone Smyth line (SL) chicken together with the MHC-matched parental Brown line (BL) and vitiligo-resistant Light Brown Leghorn line of chickens constitute a spontaneous, non-transgenic animal model for this disorder. Cell-mediated immunity (CMI) is known to contribute to the etiopathology of vitiligo. Furthermore, CMI was demonstrated in vivo in vitiliginous SL chickens based on the delayed wattle response (DWR) to melanocyte lysates. Immunohistochemical analysis of DWR-positive tissue revealed extensive T cell infiltration indicative of a CMI response. In order to examine CMI in SL vitiligo (SLV) ex vivo we developed a co-culture assay using primary effector and target cells from growing feathers (the target tissue). Mononuclear cells (MNCs) were harvested from feathers of chickens with active SLV and BL controls. Target cells (melanocytes) were isolated from pigmented feathers prior to development of SLV. To detect melanocyte-specific death a modified flow cytometric method of Lee-MacAry et al (2001) was used. Regardless of whether melanocytes were isolated from chickens that did or did not eventually develop SLV, co-culture with MNCs from SLV chickens resulted in greater melanocyte death compared to controls. Use of this ex vivo system with sorted MNCs from active, autoimmune SLV lesions will help identify roles of individual subsets in melanocyte death.
Determination of [3h]- and [14c]hematoporphyrin derivative distribution in malignant and normal tissue.

The synthesis and tissue-localizing ability of [14C]- and [3H]hematoporphyrin derivative (HPD) in mice have been described. Tissue levels and distributions were the same for both radioactive compounds, indicating that in vivo tritium exchange did not occur with [3H]HPD. The amount of [14C]HPD or [3H]HPD which localized in the transplanted tumor tissue of mice at various times following i.p. injection (10 mg/kg) was higher than in skin or muscle tissue but was less than in liver, kidney, or spleen tissue. These results tend to disprove the generalization that HPD accumulates in malignant tissue to a higher degree than in all normal tissue. It is also reported that gross visualization of porphyrin fluorescence cannot be correlated with actual tissue concentrations of the dye.
Robotic-assisted FAMM flap for soft palate reconstruction.

Objectives/Hypothoses: TORS (Trans Oral Robotic Surgery) has been demonstrated to be an acceptable alternative to chemoradiation for the treatment of early stage malignant lesions of the oropharynx, with equivalent tumor control and enhanced functional outcomes. Surgical ablation of tumors of the oropharynx under conditions of limited access, however, creates the need to adapt the robotic platform to surgical reconstruction and to assess reconstructive outcomes. We present our experience with the Facial Artery Musculomucosal (FAMM) flap with robotic assistance for the reconstruction of defects of the soft palate. Methods: We reviewed the records of five patients who underwent combined robot-assisted resection of malignant lesions of the oropharynx with immediate reconstruction. The reconstructions included four ispilateral and one bilateral FAMM flaps. Patients were assessed for complications and functional results. Results: Successful closure of the defect was achieved in all five patients. There were no major complications; however, three patients developed minor wound dehiscence and two were revised at the time of planned subsequent lymphadenectomy. All five patients achieved a good functional outcome. Conclusions: The FAMM flap is reliable and easy to raise and transfer, with the surgical robot making it a good candidate for reconstruction of moderate-sized defects created by TORS applied to malignancies of the soft palate. Minor wound dehiscence is not infrequent, but reconstructive outcomes are nevertheless good. A unilateral FAMM flap will reach to the contralateral border of the uvula and is best limited to defects with a width of 2 cm or less.
Monte Carlo simulations of low-energy cosmogenic neutron fluxes near the bottom of cliff faces

Cosmogenic radionuclide analysis for determining exposure ages and erosion rates is becoming more extensively utilized. Due to the complexity of the neutron absorption production avenue, the interpretation of 36Cl data is a complex problem, particularly for non-trivial landform geometries. This work provides a numerical, Monte Carlo simulation analysis of variations in in situ cosmogenic 36Cl production rate near the bottom of vertical cliffs. It is found that in comparison with production at height (more than a thermal neutron mean free path length in air) the production rate in the cliff face increases with decreasing height, but within a thermal neutron mean free path length in rock near the bottom of the cliff, the production rate exhibits a sharp decrease.
Parallel labeling experiments with [U-13C]glucose validate E. coli metabolic network model for 13C metabolic flux analysis.

Abstract 13 C-metabolic flux analysis (MFA) is a widely used method for measuring intracellular metabolic fluxes in living cells. 13 C MFA relies on several key assumptions: (1) the assumed metabolic network model is complete, in that it accounts for all significant enzymatic and transport reactions; (2) 13 C-labeling measurements are accurate and precise; and (3) enzymes and transporters do not discriminate between 12 C- and 13 C-labeled metabolites. In this study, we tested these inherent assumptions of 13 C MFA for wild-type E. coli by parallel labeling experiments with [U- 13 C]glucose as tracer. Cells were grown in six parallel cultures in custom-constructed mini-bioreactors, starting from the same inoculum, on medium containing different mixtures of natural glucose and fully labeled [U- 13 C]glucose, ranging from 0% to 100% [U- 13 C]glucose. Macroscopic growth characteristics of E. coli showed no observable kinetic isotope effect. The cells grew equally well on natural glucose, 100% [U- 13 C]glucose, and mixtures thereof. 13 C MFA was then used to determine intracellular metabolic fluxes for several metabolic network models: an initial network model from literature; and extended network models that accounted for potential dilution effects of isotopic labeling. The initial network model did not give statistically acceptable fits and produced inconsistent flux results for the parallel labeling experiments. In contrast, an extended network model that accounted for dilution of intracellular CO 2 by exchange with extracellular CO 2 produced statistically acceptable fits, and the estimated metabolic fluxes were consistent for the parallel cultures. This study illustrates the importance of model validation for 13 C MFA. We show that an incomplete network model can produce statistically unacceptable fits, as determined by a chi-square test for goodness-of-fit, and return biased metabolic fluxes. The validated metabolic network model for E. coli from this study can be used in future investigations for unbiased metabolic flux measurements.
Markov limit of line of decent types in a multitype supercritical branching process

Abstract In a multitype ( d types) supercritical positively regular Galton–Watson branching process, let { X n , X n − 1 , … , X 0 } denote the types of a randomly chosen (i.e., uniform distribution) individual from the n th generation and this individual’s n ancestors. It is shown here that this sequence converges in distribution to a Markov chain { Y 0 , Y 1 , … } with transition probability matrix ( p i j ) 1 ≤ i , j ≤ d and having the stationary distribution. We also consider the critical case conditioned on non-extinction.
A qualitative probabilistic model of microbial outbursts in foods

Sequences of counts of potentially harmful organisms in foods usually exhibit an irregular fluctuating pattern. The counts are determined by the interplay of numerous random factors that tend to promote or inhibit the organisms' growth. The counts can be recorded as zero, indicating that either the organism is not present or is below a minimum detectable level, or they can fluctuate randomly within characteristic bounds. An outburst is said to occur when the population surpasses a specified threshold determined by safety or quality considerations. The growth pattern in this 'explosive' mode is also governed by a combination of random mechanisms that determine the growth rate and eventual decline of the population. This paper presents a probabilistic model for such scenarios. The model parameters represent the underlying distribution of the fluctuations, the detection and explosion thresholds and the probability of continued growth after an outburst has begun. A simplified version of the model was used to simulate examples of microbial histories that resemble those of sensitive foods. It is also used to elucidate how the frequency, intensity and duration of outbursts are affected by the parameters of the model. In addition, we demonstrate how to estimate the model's parameters from actual records and illustrate the efficacy of the estimation method with simulated data. The utility of such models for risk assessment will depend on the availability of long records of microbial counts that include outbursts in order to test their predictive ability. Because the presence of a harmful agent is not always sufficient to cause food poisoning, models of this kind can only estimate the expected frequency of outbursts but not the frequency of actual food-poisoning outbreaks. Un modele de probabilite de developpement explosif de bacteries dans un aliment est presente. Le modele tient compte des fluctuations, des seuils de detection, et des probabilites de progression de la multiplication des microorganismes apres cet evenement. L'utilite de ce modele dans l'evaluation des risques depend des comptages disponibles dans des evenements connus.
SU-FF-T-572: Dose Tolerance Limits and DVH Evaluation for SBRT

Purpose: To determine stereotactic body radiation therapy(SBRT)dose tolerance limits and to develop a way to conveniently ensure the limits are being met for each patient. Methods and Materials: An extensive literature review was conducted to determine emerging dose tolerance limits to critical structures for SBRTtreatments of various cranial and extracranial targets. We developed a program called the DVH Evaluator to overlay the appropriate tolerance limits onto dose volume histogram (DVH) results, and to highlight any instances where the tolerance limit goals are not met. This can be used interactively to improve the treatment plan by periodically exporting the dose distribution to the DVH Evaluator to quickly and quantitatively see which parts of the plan need improvement. If dose tolerance limits are not met the chance of adverse events to the patient may increase. Results: The literature review uncovered 375 dose tolerance limits for critical anatomical structures throughout the body, for one to five fractions of SBRT. Conclusion: This work represents significant progress towards cumulating a comprehensive collection of dose tolerance limits for SBRT, but 375 limits is too many to be practical for daily clinical use. The DVHevalutor provides a convenient and effective tool to help manage the variety of dose tolerance limits and help assess individual plans. Still, we recommend formation of AAPM and ASTRO task groups to thoroughly address this issue from both physics and physician perspectives.
Synthesis and Structure−Activity Relationship Studies for Hydantoins and Analogues as Voltage-Gated Sodium Channel Ligands

We previously developed a preliminary 3-D QSAR model for the binding of 14 hydantoins to the neuronal voltage-gated sodium channel; this model was successful in designing an effective non-hydantoin ligand. To further understand structural features that result in optimum binding, here we synthesized a variety of compound classes and evaluated their binding affinities to the neuronal voltage-gated sodium channel using the [3H]-batrachotoxinin A 20-alpha-benzoate ([3H]BTX-B) binding assay. In order to understand the importance of the hydantoin ring for good sodium channel binding, related non-hydantoins such as hydroxy amides, oxazolidinediones, hydroxy acids, and amino acids were included. Two major conclusions were drawn: (1) The hydantoin ring is not critical for compounds with long alkyl side chains, but it is important for compounds with shorter side chains. (2) Relative to Khodorov's pharmacophore, which contains two hydrophobic regions, a third hydrophobic region may enhance binding to provide nanomolar inhibitors.
Influence of Pharmacokinetic Diurnal Variation on Bioavailability Estimates

The effects of diurnal variation on bioavailability assessments were examined using computer-simulated data based on the changes observed in theophylline kinetics. During one 12-hour dosage interval (noon to midnight), clearance was assumed to be larger than during the other dosage interval (midnight to noon). Oral data was simulated until steady-state occurred. Intravenous bolus data, which represented a stable-isotope pulse dose, was also simulated for both the high and low clearance dosage intervals. When the respective areas under the serum concentration-time curves were compared, the systemic availability (F = AUCpo/AUCiv) during the dosage interval with the larger clearance was greater than 1.0, but during the dosage interval with the smaller clearance it was less than 1.0. When computing the bioavailability of a drug, diurnal variations should be assessed as a potential cause of variation.
The wear mechanisms occurring in abradable seals of gas turbines

Abstract Metallographic investigations of worn abradable coatings have been carried out to identify and characterize the main wear mechanisms occuring in turbomachine seals. The following mechanisms have been found: cutting, smearing, adhesive transfer, crushing, melting and tribo-oxidation. Three other mechanisms occur without blade-seal interaction: erosion, corrosion and high-temperature oxidation. Using the data from these investigations as a reference, rub tests have been conducted on a specially designed high-speed—high-temperature rig. The many correlations obtained between test values and wear mechanisms allow the generation of ‘wear mechanism maps’ for coatings of the AlSi-plastic family. Mechanism orientated model tests are needed to understand the correlations between structural parameters and coating behaviour during blade-coating interactions. Wear mechanism maps will help modelling coating systems to be able to withstand severe service conditions. Avoiding the onset of adhesive or melting wear and simultaneously favouring cutting wear produces better abradable seals which will help improve both the operational safety and the economy of modern turbomachines.
Growth hormone receptor regulates β cell hyperplasia and glucose-stimulated insulin secretion in obese mice

Insulin, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) play key roles in the regulation of β cell growth and function. Although β cells express the GH receptor, the direct effects of GH on β cells remain largely unknown. Here we have employed a rat insulin II promoter-driven (RIP-driven) Cre recombinase to disrupt the GH receptor in β cells (βGHRKO). βGHRKO mice fed a standard chow diet exhibited impaired glucose-stimulated insulin secretion but had no changes in β cell mass. When challenged with a high-fat diet, βGHRKO mice showed evidence of a β cell secretory defect, with further deterioration of glucose homeostasis indicated by their altered glucose tolerance and blunted glucose-stimulated insulin secretion. Interestingly, βGHRKO mice were impaired in β cell hyperplasia in response to a high-fat diet, with decreased β cell proliferation and overall reduced β cell mass. Therefore, GH receptor plays critical roles in glucose-stimulated insulin secretion and β cell compensation in response to a high-fat diet.
A difference equation approach to parameter estimation for differential-delay equations

A finite difference scheme for estimating parameters in linear differential-delay equations is investigated. Convergence results and rates of convergence are obtained for a simple explicit (Euler's) method. Numerical examples are given to illustrate the convergence for the Euler method. Numerical results for a ''higher order'' scheme are also discussed.
21-inch common large-area display set for multiple military command and control workstation applications

Battelle is under contract with Warner Robins Air Logistics Center to design a common large area display set (CLADS) for use in multiple airborne C4I applications that currently use unique 19 inch CRTs. Engineers at Battelle have determined that by taking advantage of the latest flat panel display technology and the commonality between C4I applications, one display head (21 inch diagonal, 1280 by 1024) can be used in multiple applications. In addition, common modules are being designed by Battelle to reduce the number of installation- specific circuit card assemblies required for a particular application. Initial USAF applications include replacements for the E-3 AWACS color monitor assembly, E-8 Joint STARS graphics display unit, and ABCCC airborne color display. Initial U. S. Navy applications include the E-2C ACIS display. For these applications reliability and maintainability are key objectives. The common design reduces the number of unique subassemblies in the USAF inventory by 56 to 66%. In addition to total module reductions, CLADs module/subassembly re-use across nine potential applications is estimated to be 73%. As more platforms implement CLADS, the percentage of module re-use increases. The new design is also expected to have a MTBF of at least 3350 hours, an order of magnitude better than one of the current systems. In the Joint STARS installation, more than 1400 pounds can be eliminated from the aircraft. In the E-3 installation, the CLADs is estimated to provide a power reduction of approximately 1750 watts per aircraft. This paper discuses the common large area display set design and it use in a variety of C4I applications that require a large area, high resolution, full color display.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Symmetry-adapted filter diagonalization: Calculation of the vibrational spectrum of planar acetylene from correlation functions

A symmetry-adapted filter-diagonalization method is used to calculate the vibrational spectrum of planar acetylene. In this method, vibrational eigenvalues in a given symmetry are obtained by solving a generalized eigenproblem in which the Hamiltonian and overlap matrices are assembled from symmetry-adapted correlation functions. Since no filtered state is explicitly needed, the calculation requires a relatively small memory. The numerical efficiency is further improved as the correlation functions belonging to various symmetry species are generated from a single wave packet. Comparison with existing data for the acetylene system confirms its accuracy and efficiency.
Larger numbers of CD4bright dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation

Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34 + cells influence relapse and event-free survival (EFS) after BMT. The study population consisted of 113 consecutive patients with hematologic malignancies who underwent non–T-cell–depleted BMT from HLA-matched siblings. Sixty-four patients had low-risk diagnoses (ALL/AML CR1, MDS RA/RARS, and CML CP1); 49 patients had high-risk diagnoses (all others). CD34 + cells, T cells, B cells, natural killer cells, monocytes, and a rare population of CD3 − , CD4 bright cells in the allografts were measured by flow cytometry. The CD3 − , CD4 bright cells in bone marrow had the same frequency and phenotype as CD123 bright type 2 dendritic cell (DC) progenitors, and they differentiated into typical DCs after short-term culture. Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3 + T cells, CD34 + hematopoietic cells, and CD4 bright cells as covariates for EFS, relapse, and nonrelapse mortality. Recipients of larger numbers of CD4 bright cells had significantly lower EFS, a lower incidence of chronic graft-versus-host disease (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of CD34 + cells had improved EFS; recipients of fewer CD34 + cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, the content of donor CD4 bright cells was associated with decreased cGVHD and graft-versus-leukemia effects in recipients of allogeneic bone marrow transplantation, consistent with a role for donor DCs in determining immune responses after allogeneic BMT.
Nonholonomic double-bracket equations and the Gauss thermostat

In this Rapid Communication we consider certain equations that arise from imposing a constant kinetic-energy constraint on a one-dimensional set of oscillators. This is a nonlinear nonholonomic constraint on these oscillators and the dynamics are consistent with Gauss's law of least constraint. Dynamics of this sort are of interest in nonequilibrium molecular dynamics. We show that under certain choices of external potential these equations give rise to a generalization of the so-called double-bracket equations which are of interest in studying gradient flows and integrable systems such as the Toda lattice. In the case of harmonic potentials the flow is described by a symmetric bracket and periodic solutions are obtained.
Murine gammaherpesvirus-68 infects microglia and induces high levels of pro-inflammatory cytokine production

Murine gammaherpesvirus-68 (MHV-68) has been established as a tractable model for the study of human herpesvirus infections. Recent associations between herpesvirus infections and inflammatory central nervous system (CNS) disorders, including multiple sclerosis (MS), have prompted us to investigate the susceptibility of cultured microglia and astrocytes to MHV-68 infection. In the present study, we demonstrate that MHV-68 can infect both cell types. Importantly, we show that MHV-68-infected microglia and astrocytes can produce pro-inflammatory cytokines. Such cytokine production may either contribute to protective host responses to viral challenges or could exacerbate damaging CNS inflammation.
THE MECHANISM OF ACTION OF THYROID HORMONES

The possibility that the thyroid hor? mones exert their biological effects by specifically inhibiting or stimulating key en? zymes has been most actively investigated. It was early shown (Rohrer, 1924) that the oxygen consumption of certain tissues excised from thyrotoxic animals is greater than normal. Because of the pronounced calorigenic effect of the hormones in vivo, most investigators have concentrated their efforts on those enzymes upon which the respiratory activity of the cell depends. Of these, the two enzymatic processes most extensively studied are those concerned with coupled oxidative phosphorylation and with succinate oxidation.
Development of an atrophic nonunion model and comparison to a closed healing fracture in rat femur

Although most fractures heal, some fail to heal and become nonunions. Many animal models have been developed to study problems of fracture healing. The majority of nonunion models have involved segmental bone defects, but this may not adequately represent the biologic condition in which nonunions clinically develop. The objective of the present study is to develop a nonunion model that better simulates the clinical situation in which there is soft tissue damage including periosteal disruption and to compare this model to a standard closed fracture model utilizing identical fracture stabilization, providing a similar mechanical environment. A total of 96 three month old Long Evans rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three-point bending device. To create a nonunion, 48 of the rats received additional surgery to the fractured femur. The fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. Fracture healing was evaluated with serial radiographs every two weeks. Animals were maintained for intervals of two, four, six or eight weeks after surgery. Specimens from each time interval were subjected to biomechanical and histological evaluation. None of the cauterized fractures healed throughout the eight weeks experimental duration. The radiographical appearance of nonunion models was atrophic. This investigation showed pronounced differences between the experimental nonunions and standard closed fractures both histologically and biomechanically. In conclusion, we have developed a reproducible atrophic nonunion model in the rat femur that simulates the clinical condition in which there is periosteal disruption but no bone defect.