cssi/SciSciGPT-SciSciNet huggingface dataset:
Circulating tumor DNA analysis in the era of precision oncology.

// Rabih Said 1 , 2 , * , Nicolas Guibert 3 , 4 , * , Geoffrey R. Oxnard 3 and Apostolia M. Tsimberidou 1 1 Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Oncology, St. George Hospital University Medical Center, University of Balamand, Beirut, Lebanon 3 Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 4 Thoracic Oncology, Toulouse University Hospital, Toulouse, France * Co-authorship Correspondence to: Apostolia M. Tsimberidou, email: atsimber@mdanderson.org Keywords: circulating tumor DNA analysis; clinical trials; targeted therapy; genomic profiling Received: August 01, 2019 Accepted: December 16, 2019 Published: January 14, 2020 ABSTRACT The spatial and temporal genomic heterogeneity of various tumor types and advances in technology have stimulated the development of circulating tumor DNA (ctDNA) genotyping. ctDNA was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is associated with significant risk, when tumor tissue is insufficient or inaccessible, and/or when repeated assessment of tumor molecular abnormalities is needed to optimize treatment. The role of ctDNA is now well established in the clinical decision in certain alterations and tumors, such as the epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer and the v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in colorectal cancer. The role of ctDNA analysis in other tumor types remains to be validated. Evolving data indicate the association of ctDNA level with tumor burden, and the usefulness of ctDNA analysis in assessing minimal residual disease, in understanding mechanisms of resistance to treatment, and in dynamically guiding therapy. ctDNA analysis is increasingly used to select therapy. Carefully designed clinical trials that use ctDNA analysis will increase the rate of patients who receive targeted therapy, will elucidate our understanding of evolution of tumor biology and will accelerate drug development and implementation of precision medicine. In this article we provide a critical overview of clinical trials and evolving data of ctDNA analysis in specific tumors and across tumor types.
Doing the work: Crafting and implementing liaison competencies

Recently at Joyner Library, the main library for West Campus at East Carolina University (ECU), three heads of service completed a project to revise the library’s liaison competencies. The head of collection development, the head of research and instructional services, and the scholarly communication librarian took the competencies from a task-oriented document and turned them into one that allows liaisons to choose what and how they want to learn. The new document is built around learning statements, is goal-oriented, and serves liaison librarians much better than the previous document. This article will cover the creation and use of the new liaison competencies document.
Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach.

Abstract Background Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for > 80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.
Why All the Fuss about Oxidative Phosphorylation (OXPHOS)

Certain subtypes of cancer cells require oxidative phosphorylation (OXPHOS) to survive. Increased OXPHOS dependency is frequently a hallmark of cancer stem cells and cells resistant to chemotherapy and targeted therapies. Suppressing the OXPHOS function might also influence the tumor microenvironment by alleviating hypoxia and improving the antitumor immune response. Thus, targeting OXPHOS is a promising strategy to treat various cancers. A growing arsenal of therapeutic agents is under development to inhibit this biological process. This Perspective provides an overview of the structure and function of OXPHOS complexes, their biological functions in cancer, relevant research tools and models, as well as the limitations of OXPHOS as drug targets. We also focus on the current development status of OXPHOS inhibitors and potential therapeutic strategies to strengthen their clinical applications.
Monitoring of the fluidized bed particle drying process by temperature and pressure drop measurements

This work aimed to monitor the temperature and the pressure drop behaviors in bed during the drying of Persian clover and arrowleaf clover seeds in a fluidized bed. The inlet air temperatures were ...
A randomized controlled trial of three-dimensional versus two-dimensional imaging system on duration of surgery and mental workload for laparoscopic gastropexies in dogs.

Objective To evaluate the effect of three-dimensional (3D) laparoscopy compared to two-dimensional (2D) laparoscopy when evaluating duration of surgery for canine intracorporeally sutured gastropexy. Study design Randomized controlled clinical trial. Animals Thirty client-owned dogs. Methods Dogs were randomized into 2D or 3D groups and underwent a three-port laparoscopic intracorporeally sutured incisional gastropexy with barbed suture. Procedures were performed by a single board-certified surgeon. Duration of surgery was recorded and workload was assessed immediately after surgery using the NASA Task Load Index (TLX). Results Median duration of surgery was 3 min shorter for 3D versus 2D (95%CI -10 to 13; p = .51). Surgical component durations, total and component TLX scores, and intraoperative complications also did not differ between groups. In a subgroup analysis excluding the first eight cases due to presumption of a learning curve with suturing technique, total TLX score (p = .004) and all component scores were lower for 3D as compared to 2D laparoscopy, although duration of surgery did not differ (p = .20). Conclusion The use of 3D laparoscopy was not associated with shorter duration of surgery when compared to 2D laparoscopy. Clinical significance 3D laparoscopy requires further investigation in veterinary medicine to determine its utility in decreasing surgical duration, surgical complications or surgeon mental or physical workload.
“We Are the Future”: Critical Inquiry and Social Action in the Classroom:

This study explored how engaging in critical inquiry through Project-Based Inquiry (PBI) Global fostered social action with high school students. Drawing on theoretical perspectives from critical i...
Micromechanical Study of Porosity Effects on Coupled Moisture-Mechanical Responses of Viscoelastic Asphalt Concrete

AbstractThe present paper offers a micromechanical modeling approach to evaluate the impact of the porosity structure on the response of asphalt concrete as a viscoelastic multiphase material under...
Mid- to late- gestational maternal nutrient restriction followed by realimentation alters development and lipid composition of liver and skeletal muscles in ovine fetuses.

Maternal nutrient restriction during gestation adversely affects offspring growth and development of liver and skeletal muscle tissues. Realimentation following nutrient restriction may alleviate these negative impacts on development but may alter metabolism and tissue composition. Forty-eight ewes, pregnant with singletons, were fed to meet 100% National Research Council (NRC) recommendations starting at the beginning of gestation. On d 50 of gestation, 7 ewes were euthanized (BASE), and fetal liver, skeletal muscles, and blood samples were collected. The remaining animals were fed either 100% of NRC recommendations (CON) or 60% NRC recommendations (RES), a subset were euthanized at d 90 of gestation (n = 7/treatment), and fetal samples were collected. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to the alternate diet (CON-RES, RES-CON; n = 7/treatment). On d 130 of gestation, the remaining ewes were euthanized, and fetal samples were collected. At d 130 of gestation, maternal nutrient restriction during late-gestation (RES-RES and CON-RES) decreased fetal liver weight (P < 0.01) and cross-sectional area in triceps brachii (P = 0.01; TB), longissimus dorsi (P = 0.02; LM), and semitendinosus (P = 0.05; STN) muscles. Maternal nutrient restriction during mid-gestation increased hepatocyte vacuole size at d 130 of gestation. Late-gestational maternal nutrient restriction increased mRNA expression of insulin-like growth factor (IGF) binding protein-1 (P < 0.01), glycogen synthase 2 (P = 0.01; GYS2), and pyruvate dehydrogenase kinase 1 (P < 0.01; PDHK1) in the liver and IGF receptor 1 (P = 0.05) in the LM. Lipid concentration in the LM was decreased by late-gestational nutrient restriction (P = 0.01) and increased by mid-gestational nutrient restriction in STN (P = 0.03) and TB (P < 0.01). Principal component analysis of lipidomics data demonstrated clustering of principal components by day of gestation and elastic net regression identified 50, 44, and 29 lipids that classified the treatments in the fetal liver, LM, and blood, respectively. In conclusion, restricting maternal nutrition impacts fetal liver and muscle morphology, gene expression, and lipid metabolism, whereas realimentation attenuated some of these effects. Therefore, realimentation may be a viable strategy to reduce the impacts of nutrient restriction, but can lead to alterations in lipid metabolism in sheep.
Sediment Transport and Diffusion: Columbia Estuary and Entrance

Review of past studies and investigations, including prototype measurements and hydraulic model tests; reveal some indications of sediment transport and diffusion in the vicinity of the Columbia Estuary and Entrance. These indications reveal a unique pattern of sediment transport and diffusion prevailing in this region. This leads to the conclusion that the estuary is acting as a trap for collection of bottom sediments and that, immediately offshore, the forces of erosion and accretion have established a regime that is also worthy of detailed further study.
Neonatal encephalopathy, sentinel events, and the placenta

Objective: To examine the frequency and types of placental pathology observed in encephalopathic newborns presenting for therapeutic hypothermia. Study Design: Between May 2006 and April 2010, 140 term newborns with neonatal encephalopathy were admitted for cooling. The presence or absence of recognized asphyxial ("sentinel") birth events was noted. Placental pathology was categorized as vascular, inflammatory, or other. Result: Placental surgical pathology reports were available for 100 newborns, of whom 51% had sentinel events. Abnormalities were reported in 51% of placentas, 29% with and 73% without sentinel events (p = 0.0001). Inflammatory pathology was more frequent in infants without sentinel events (43% vs. 14%, p = 0.0016), especially in infants with pH below 7.0 (p = 0.012). Conclusion: Placental pathology was common in infants with neonatal encephalopathy admitted for therapeutic hypothermia, especially in those with no clinically recognized sentinel birth events. Severe acidosis was often observed in infants without sentinel events who had inflammatory placental pathology.
Marked alteration of sterol metabolism and composition without compromising retinal development or function.

PURPOSE. To evaluate the consequences of altering retinal sterol metabolism and composition on the development, histologic organization, and electrophysiological function of the retina, under conditions that mimic the biochemical hallmarks of the Smith‐Lemli‐Opitz (SLO) syndrome. METHODS. Pregnant Sprague‐Dawley rats were fed cholesterol-free chow containing AY9944 (treated group), an inhibitor of 3b-hydroxysterol D 7 -reductase, from gestational day 6 through postnatal day (P)28. Control animals were fed the same chow, but without AY9944. In addition, progeny in the treated group were injected subcutaneously every other day from birth to P28 with an olive oil emulsion containing AY9944; control animals received olive oil emulsion alone. At various postnatal times, tissues from treated and control animals were harvested, and their sterol profiles were analyzed by reversed-phase high-performance liquid chromatography. Companion eyes from animals of both groups were examined histologically at P1. At P28, animals were evaluated by electroretinography; tissues were then harvested for biochemical analysis and companion eyes were subjected to histologic and ultrastructural analyses. RESULTS. Treatment of developing rats with AY9944 caused markedly abnormal accumulation of 7-dehydrosterols and severely reduced cholesterol levels in all tissues examined, relative to control animals. Despite this, treated animals exhibited normal retinal development and had no overt ocular defects or decrease in electroretinographic function, up to P28. CONCLUSIONS. These results were unexpected, given the known biophysical effects of such sterol alterations on membrane properties and the profound dysmorphic and cognitive abnormalities associated with genetic defects in 3b-hydroxysterol D 7 -reductase that have been linked to the SLO syndrome. The results suggest that 7-dehydrosterols can substitute functionally for cholesterol in the retina or perhaps can act synergistically with subthreshold levels of residual cholesterol to allow normal cellular structure and function to be achieved. (Invest Ophthalmol Vis Sci. 1999;40: 1792‐1801)
Influence of Transformability on the Formation of Superinfection Double Lysogens in Haemophilus influenzae

Superinfection of growing (nontransformable) cells of defectively lysogenic strains of Haemophilus influenzae with wild-type or with mutant phage HP1 resulted in a number of double lysogens and a small number of monolysogens with altered prophage. The double lysogens were identified by analysis of their monolysogenic segregants and by examining their deoxyribonucleic acid in certain test crosses. The results indicate that the majority had been formed by insertion of the infecting phage genome within the resident prophage. Superinfection of transformable bacteria gave rise to cells with altered prophages (presumably transformants) and to double lysogens which had gained or lost wild-type prophage loci.
The effect of coherence and noise on the decomposition of the time reversal operator

Active sonar in shallow water in shallow water is often reverberation-limited and the detectability is often limited by the presence of too many false alarms. The decomposition of the time reversal operator (DORT) is a method that potentially alleviates this problem by separating echoes from different depths in the water column. For example, DORT can separate a target in the water column from reverberation on the bottom. DORT requires a set of echoes recorded on a line array that result from a set of independent transmissions from a source array. A short derivation of DORT using the sonar equation is given. Because DORT is inherently a frequency-domain method, the time-frequency domain is derived to implement the algorithm on the data. Lastly, the similarity of DORT to adaptive beam forming is shown. In this paper, data taken on the Atlantic shelf, east of Cape May, NJ, during Geoclutter 03 and TREX-04 experiments, is processed and shown. The data was taken with a 64 element vertical line array of source-receiver elements. The target was an echo repeater using an XF4 source from 500 to 2500 Hz or an ITC 200 source from 2500 to 3500 Hz. The data cover six 500 Hz-bands from 500 Hz to 3500 Hz. The data are processed using DORT in the time-frequency domain. The analysis produces singular values in the time-frequency domain and in the time-delay domain. It also produces singular vectors that are used with a broad-band propagation model to form back-propagation images in the range, depth, frequency or range, depth, time domain. The analysis shows that the limiting factors in this data set arise from 1) motion that causes a lack of time-invariance, 2) additive noise and 3) the independent transmission scheme. The lack of time invariance is shown to spread the echo energy into several singular indices. Additive noise is shown to contaminate the singular values and back-propagation images. The particular transmission scheme used, time division multiplexed LFMs, is shown to create large side lobes in the time domain. Alternative transmission sequences, as well as alternative source and receiver orientations, are discussed
The inverse problem of the calculus of variations for scalar fourth-order ordinary differential equations

A simple invariant characterization of the scalar fourth-order ordinary differential equations which admit a variational multiplier is given. The necessary and sufficient conditions for the existence of a multiplier are expressed in terms of the vanishing of two relative invariants which can be associated with any fourth-order equation through the application of Cartan’s equivalence method. The solution to the inverse problem for fourth-order scalar equations provides the solution to an equivalence problem for secondorder Lagrangians, as well as the precise relationship between the symmetry algebra of a variational equation and the divergence symmetry algebra of the associated Lagrangian.
The development of live load for long span bridges

The available live load models were developed for short and medium span bridges. This paper deals with the development of live load for long span structures. Loads are considered as random variables, with regard to magnitude and frequency of occurrence. In contrast to short and medium spans, a long span live load must include the multiple trucks being present. Based on the analysis of traffic records (weigh-in-motion and videos) taken on selected bridges, the design live load has been developed and a recommended design live load has been formulated for consideration in the bridge design code.
The promise of xenografting.

Advances in understanding the rejection of foreign tissues has renewed enthusiasm about the possibility of overcoming the present organ shortage by transplanting porcine kidneys into humans. Currently, three known forms of organ rejection stand as obstacles to xenotransplantation as a clinical reality—hyperacute rejection, acute vascular rejection, and cellular rejection. Progress in the knowledge of xenoreactive antibodies and of complement, along with new transgenic technologies, have enabled researchers to overcome hyperacute rejection in xenografts. The advances have brought into focus such issues as the ability of the porcine kidney to replace the physiologic functions of the human kidney and the risk associated with the potential transmission of infectious agents from animals to humans. Despite the remaining hurdles to clinical application of xenotransplantation, the rapid pace of research and emerging technologies would seem to make xenotransplantation a renal replacement therapy of great promise.
Sustainable Competitive Advantage of Internet Firms - A Strategic Framework and Implications for Global Marketers

– At the core of an international marketing strategy is the internet firm's goal of building and sustaining a competitive advantage. The purpose of this paper is to present an integrative framework to explain the role that customer behavior and customer relationship management (CRM) play in developing a profitable, sustainable competitive advantage for internet companies., – The integrative framework utilizes existing theoretical concepts from the areas of strategy and internet marketing and develops a framework to provide firms with insights into how they can gain the competitive advantage., – This paper links global customer behavior to the firms' business value chain and provides guidelines for strategic implications. In this conceptual paper, it is discussed that understanding consumer decision‐making behavior on the web and managing these relationships are critically important to achieve a superior performance., – This is not empirical research. A theoretical model is presented for future testing by researchers using statistical techniques such as structural equation modeling., – The framework provides managerial insights into building and sustaining a competitive advantage using a consumer‐centric approach, coupled with CRM technology on a global scale. Managerial value is derived by providing an understanding of the link between a sustainable competitive advantage, customer‐focused strategies, consumers' needs and wants, the firm's performance, and shareholder value., – It is important for global marketers to understand how consumer decision‐making on the web affects strategic and financial performance. This paper extends the current literature by integrating consumer decision behavior on the web, CRM, and the firms' performance. This framework explains the creation of a sustainable competitive advantage using customer‐focused strategies to develop customer loyalty for superior firm performance.
Carbohydrates in Food—An Introduction

Carbohydrates are organic compounds containing carbon, hydrogen, and oxygen, and they may be simple or complex molecules. Historically, the term “carbohydrate” has been used to classify all compounds with the general formula C n (H2O) n as the hydrates of carbon. Important food carbohydrates include simple sugars, dextrins, starches, celluloses, hemicelluloses, pectins, and gums. They are an important source of energy or fiber in the diet, and they are also important constituents of foods because of their functional properties. Carbohydrates may be used as sweeteners, thickeners, stabilizers, gelling agents, and fat replacers.
Solar CO2 Reduction Using Surface-Immobilized Molecular Catalysts

This review article summarizes recent work in developing hybrid photocatalysts by grafting molecular catalysts on solid-state surfaces for solar CO2 reduction. Several surface-immobilized systems are discussed to examine effects of ligand derivatization and surface characteristics on the activities of hybrid photocatalysts. This article also describes the extensive use of spectroscopic techniques in studying hybrid photocatalysts, and briefly introduces research efforts in constructing artificial photosynthetic assemblies based on surface-immobilized CO2-reduction catalysts.
90 nm CMOS RF technology with 9.0 V I/O capability for single-chip radio

In this article, an industry leading 21 mask count 90nm CMOS SoC technology with integrated RF, analog, dense memory, low power or high-speed logic, and high-voltage DEMOS options is demonstrated. RF and analog characteristics with high on-chip voltage capability enable single chip radio design as well as many additional SoC applications.
Cloned alpha and beta C-protein antigens of group B streptococci elicit protective immunity

Abstract Streptococcus agalactiae (group B streptococci [GBS]) is the leading cause of neonatal sepsis and meningitis in the United States. The surface-associated C proteins of GBS play a role in immunity, but their number, size, structure, function, and virulence properties have not been well characterized. A recombinant library of DNA fragments from GBS strain A909 (type Ia/C) was prepared in the plasmid pUX12, a specially constructed Escherichia coli expression vector. The library was screened with a rabbit antiserum shown to be protective for passive immunity to GBS infection in a mouse lethality model. Clones were divided into two distinct groups on the basis of DNA-DNA cross-hybridization, restriction enzyme analysis, and the expression of antigenic proteins in E. coli. A characteristic clone from each group was chosen for further study. Clone pJMS23 expresses gene products that biochemically and immunologically correspond to the trypsin-resistant, C-protein alpha antigen. Clone pJMS1 expresses a gene product that binds to immunoglobulin A and is similar to the trypsin-sensitive, C-protein beta antigen. Antisera raised in rabbits against E. coli containing each of the plasmid clones were able to elicit protective immunity in mice challenged by GBS strains carrying the C proteins but not by non-C-protein-bearing strains. Southern blot analysis shows no DNA homology between the clones, and there is no immunological cross-reactivity between the antigens they express. Therefore, pJMS23 and pJMS1 encode two different C proteins that define unique protective epitopes.
Enhanced Smith-Purcell radiation from a bigrating surface through multiplasmon excitation.

A theory is presented of the Smith-Purcell diffraction radiation from a beam of point charges passing over a finitely conducting bigrating surface, with arbitrary orientation of the beam relative to the bigrating axes. The beam's field can resonantly excite one or more surface-plasmon polaritons, which the bigrating can then decouple into a single outward radiating wave at any given angle and frequency. This radiation, arising from the collective motion of the electrons in a surface plasmon, has been shown theoretically to enhance the radiated power by two or three orders of magnitude in the peak direction. Numerical implementation of the present theory has shown that there is an optimal grating height at which this surface-plasmon-enhanced radiation peak is at a maximum. This work has also shown that a sinusoidal bigrating, forming a rectangular lattice, can yield an added enhancement, through two-plasmon excitation, when compared to the radiation from a classical grating (periodic in one direction).
IEDF control using multifrequency harmonic drive

Multi-frequency RF power delivery for IEDF control has become commonplace in semiconductor manufacturing, particularly in plasma etch applications.1 Recently, two frequency drives where the higher drive frequency is a harmonic of the lower drive frequency have shown interesting influence on IEDF's with phase acting as an additional tuning knob for control.2 In this work, an RF sheath model that assumes a matrix sheath condition and known electron density is used to compare the influence of multiple frequencies over transient sheath parameters, specifically the time dependent potential across the powered sheath. Using this time dependent potential, ion energies incident on the plasma facing surface are calculated using an ion transit time dependent dampening term.3 Ion energy distribution functions are obtained for dual frequency conditions where the two frequencies are integer multiples of each other and compared to the more typical case where the frequencies are not integers of each other. Control of the distribution width is identical with respect to relative RF current from two sources for both the integer and non-integer case. The integer frequency drive produces (n−1) intermediate peaks in the distribution between the maximum and minimum energies whose energy and magnitude can be controlled with the relative phase of the two waveforms. Manipulation of the phase and amplitude of these two power sources can also produce some unique distribution functions, in some cases mimicking distributions that are normally achieved outside of the range of frequencies used to drive the sheath potential, and lend an additional level of IEDF control not achievable with comparable non-integer dual frequency drives. This work will present a brief review of dual frequency IEDF control and present a model that captures the effects of both frequency mixing and phase of integer multiple frequency drives.
Broad-Spectrum Antiviral Therapeutics

Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.
Ultrasonic Evaluation of Bolted Connections in Satellites

Prolonged periods from conception to deployment of a satellite can undermine a time dependent mission. Currently, the timeline for a new satellite to reach deployment is on the order of years. The need for a more efficient process is evident and has lead to innovations at every aspect of satellite design and pre-launch testing. One such example is the development of panels and components that are prefabricated for space flight and capable of assembly in a variety of configurations. However, all final systems regardless of component qualification must be validated for space flight. Current qualification testing can take weeks to years. An ultrasonic technique based on the energy of a transmitted wave across the connection is intended either as an alternative to traditional vibration/qualification testing or as a precursor to in-situ monitoring of panel-to-panel connections. Transmitted elastic wave energy is used to assess the integrity of the connection in reference to an initially established baseline. A...
GAMMA IRRADIATION OF THE TOBACCO BUDWORM: STERILIZATION, COMPETITIVENESS, AND OBSERVATIONS ON REPRODUCTIVE BIOLOGY.

Both sexes of adult tobacco budworms, Heliothis virescens (F.), were completely sterilized by 45 kilorads (krad) of gamma irradiation; 35 krad resulted in less than 1% egg hatch. Sterile females laid about ⅔ as many eggs as the control, and longevity of both sexes was reduced 0-10%. The mating ability of males sterilized as adults or pupae was not significantly less than that of the control males in most tests, the females sterilized as adults mated as frequently as the controls. Normally, neither sex mates more than once a night as determined by transfer of spermatophores. Males sterilized as pupae or adults were not fully competitive with untreated males as measured by egg hatch from ratio tests with untreated males and females. However, in a test in which the mating of sterile males was determined by labeling spermatophores with C14, males were found to be fully competitive in mating females. Females alternately mated to sterile and untreated males usually remained fertile after mating with an untreated male followed by a sterile male, or became fertile about 50% of the time if mated with a sterile male followed by an untreated male. Thus when mating to both types of males occurred, the female was more likely to be fertile than sterile. It was observed also that when second matings altered fertility, the alteration was complete—the result of sperm displacement, not sperm mixing. Sterile males mated to untreated females resulted in about 25% fewer eggs per female than controls.
Unifying ideas for non-parametric linkage analysis

Objectives: Non-parametric linkage analysis (NPL) exploits marker allele sharing among affected relatives to map genes influencing complex traits. Computational barriers force approximate analysis on large pedigrees and the adoption of a questionable perfect data assumption (PDA) in assigning p values. To improve NPL significance testing on large pedigrees, we examine the adverse consequences of missing data and PDA. We also introduce a novel statistic, Q-NPL, appropriate for NPL analysis of quantitative traits. Methods: Using simulated and real data sets with qualitative traits, we compare NPL analysis results for four testing procedures and various degrees of missing data. The simulated data sets vary from all nuclear families, to all large pedigrees, to a mix of pedigrees of different sizes. We implemented the Kong and Cox linear adjustment of p values in the software packages Mendel and SimWalk. We perform similar analysis with Q-NPL on quantitative traits of various heritabilities. Results: The Kong and Cox extension for significance testing is robust to realistic missing data patterns, greatly improves p values in approximate analyses, and works equally well for qualitative and quantitative traits and small and large pedigrees. The Q-NPL statistic is robust to missing data and shows good power to detect linkage for quantitative traits with a wide spectrum of heritabilities. Conclusions: The Kong and Cox extension should be a standard tool for calculating NPL p values. It allows the combination of exact and estimated analyses into a single significance score. Q-NPL should be a standard statistic for NPL analysis of quantitative traits. The new statistics are implemented in Mendel and SimWalk.
Observations on biochemical abnormalities in hereditary angioneurotic edema

Abstract Serum specimens collected from patients with hereditary angioneurotic edema showed low titers for inhibitors of serum kallikrein, and, when obtained shortly after an episode of edema, were deficient in available substrate for kallikrein activity. Patients were more sensitive to intradermal injection of serum kallikrein than normal controls. Serum also showed an abnormally low content of inhibitor for activated C′1-esterase, and the capacity of C′1-esterase to cause severe permeability-increasing reactions in human skin, and with special intensity in patients' skin, was demonstrated. Other skin tests suggested the possible participation in the edematous process of PF/Dil. The exact role of these permeability factors and the precise identity of the specific inhibitor(s) which are lacking or deficient remain uncertain.
Fast sparse regression and classification

Abstract Many present day applications of statistical learning involve large numbers of predictor variables. Often, that number is much larger than the number of cases or observations available for training the learning algorithm. In such situations, traditional methods fail. Recently, new techniques have been developed, based on regularization, which can often produce accurate models in these settings. This paper describes the basic principles underlying the method of regularization, then focuses on those methods which exploit the sparsity of the predicting model. The potential merits of these methods are then explored by example.
A study of the mixed Na1−xLix zeolite A system by powder X-ray diffraction

Abstract A simple analysis of the ratios of selected X-ray powder diffraction intensities from anhydrous sodiumlithium zeolite A samples, Na 12− x Li x Si 12 Al 12 O 48 , shows that Li replaces Na in site I for 0 ≤ x ≤ 8. This result is discussed in relation to previously reported 29 Si NMR data and a model is presented for the cation ordering scheme in the anhydrous mixed material with x = 4. Changes in the X-ray pattern with external water vapor pressure are also described.
Neural-net computing for real-time control of a ship's dynamic positioning at sea

Abstract Dynamic positioning or station-keeping of vessels is a technique which uses ship-mounted propulsors and lateral thrusters to counteract environmental forces acting on the vessel due to wind, waves and currents, thereby maintaining it as closely as possible at some desired position in the horizontal plane. This paper reports on an exploration of the feasibility of using a neural-net model which takes measurements of wave motion and provides estimates of forces exerted on the ship. Dynamic positioning was demonstrated with simulation. A training data acquisition scheme is also described.
Enantioselective Enzyme-Catalyzed Aziridination Enabled by Active-Site Evolution of a Cytochrome P450

One of the greatest challenges in protein design is creating new enzymes, something evolution does all the time, starting from existing ones. Borrowing from nature’s evolutionary strategy, we have engineered a bacterial cytochrome P450 to catalyze highly enantioselective intermolecular aziridination, a synthetically useful reaction that has no natural biological counterpart. The new enzyme is fully genetically encoded, functions in vitro or in whole cells, and can be optimized rapidly to exhibit high enantioselectivity (up to 99% ee) and productivity (up to 1,000 catalytic turnovers) for intermolecular aziridination, demonstrated here with tosyl azide and substituted styrenes. This new aziridination activity highlights the remarkable ability of a natural enzyme to adapt and take on new functions. Once discovered in an evolvable enzyme, this non-natural activity was improved and its selectivity tuned through an evolutionary process of accumulating beneficial mutations.
Modeling of the thermal effects of heat generating devices in close proximity on vertically oriented printed circuit boards for thermal management applications

The localized thermal interactions between adjacent devices on vertically orientated circuit boards in natural convection are predicted using experimentally validated computational fluid dynamics models. The effects of power density, device proximity, device geometry, circuit board material, board packing density and board separation distance on the steady state operating temperatures are investigated and incorporated into mathematical models which can be used to design packages which minimize thermal interactions. The separation distance beyond which the devices do not thermally influence each other is identified and the influence of various parameters on this distance is studied. The parametric study is designed using Design of Experiments methodology and therefore can be used to interpret the interaction between independent parameters. The developed models and methodology can easily and quickly be applied to other packaging situations to help minimize negative thermal interactions as one consideration in board layout design.
Our Modern Foreign Language Trinity: Language, Literature, Civilization1

The importance of modern foreign language study for any well-balanced curriculum: it provides not only practical training but a critical sense and humanistic perspectives especially needed at the present time. The triune approach: language, literature, and civilization: examples and suggestions for integrating these at all stages of study. Multiplicity of contacts and objectives, far from being a weakness of our subject, is its greatest value as an educational agent. Its richness and uniqueness in this respect.)
Lineage-specific defect in gene expression in human platelet phospholipase C-β2 deficiency

Phospholipase C (PLC)–β2 plays a major role in platelet activation. Previous studies have described a unique patient with impaired receptor-mediated platelet aggregation, secretion, calcium mobilization, and phospholipase C (PLC) activation associated with a selective decrease in platelet PLC-β2 isozyme. To identify the mechanisms leading to the defect, platelet RNA from the patient and healthy subjects was subjected to reverse transcription–polymerase chain reaction (RT-PCR) and the products sequenced. The PLC-β2 cDNA sequence in the patient showed no abnormalities. Platelet PLC-β2 and β-actin (internal control) mRNA levels were assessed by RT-PCR; the ratio of PLC-β2 to β-actin mRNA levels was 0.80 to 0.95 in 4 healthy subjects and 0.28 in the patient. PLC-β2 mRNA levels were similarly reduced compared with GPIIb and Gαq mRNA levels. PLC-γ2 and platelet factor 4 mRNA levels were normal. Calcium mobilization was studied in neutrophils upon activation with formyl-Met-Leu-Phe (fMLP), adenosine diphosphate (ADP), platelet-activating factor (PAF), interleukin-8 (IL-8), C5a, and leukotriene B4 (LTB4), and it was normal. Neutrophil elastase secretion upon activation with fMLP, ADP, PAF, IL-8, C5a, and LTB4 was normal, as were neutrophil PLC-β2 mRNA and PLC-β2 on immunoblotting. Thus, responses to activation, PLC-β2 protein, and PLC-β2 mRNA are decreased in patient platelets but not in neutrophils, providing evidence for a hitherto undescribed lineage (platelet)–specific defect in PLC-β2 gene expression. These studies provide a physiologically relevant model to delineate regulation of PLC-β2 gene and its tissue-specific expression.
Age Differences in the Interpretation of Probability Expressions: Implications for Clinicians

Age Differences in the Interpretation of Probability Expressions: Implications for Clinicians
Evaluation of EUV toroidal diffraction gratings for SOHO/Coronal Diagnostic Spectrometer

ABSTRACT Verification ofcomponent specification and EUV optical performance for the diffraction gratings of the normal incidence BUY spectrograph of SOHO/CDS is discussed. This discussion includes: a comparison of experimentally obtained EUV spectral images of a point source with corresponding ray trace analysis, in-band Lyman alpha leak determination, verification of toroidal radii of curvature,verification of blaze direction by calculation and VUV measurement, and zero order efficiency at 124nm. 1. INTRODUCTION The Coronal Diagnostic Spectrometer (CDS) is an instrument on board the Solar and Heliospheric Observatory (SOHO) spacecraft. Its objective is to obtain intensity ratios of selectedextreme ultraviolet line pairs with spatial and temporal scales appropriate to the fine scale features ofthe solar atmosphere. Researchers will use density and temperature information derived from theintensity ratios to study the energy and mass balance of the solar atmosphere. This information will
Stimulation of rat liver adenylate cyclase by halothane.

Abstract Rat liver membranes prepared by a modification of the procedure of Neville were exposed to clinical and toxic concentrations of the general anesthetic, halothane, for 10 minutes. Basal, glucagon (5 × 10 −5 M) and sodium fluoride (20 mM) stimulated adenylate cyclase activity was assayed. Clinical and toxic concentrations of halothane augmented basal adenylate cyclase activity. Glucagon and sodium fluoride stimulated adenylate cyclase activity was enhanced at greater than clinically useful halothane concentrations only. The study provides direct evidence that halothane stimulates adenylate cyclase, the extent of augmentation of enzyme activity is halothane concentration dependent, and modified by other drugs.
Applying Values and Lifestyles Psychographics to Parental Involvement in College and University Orientation

The authors suggest that college and university planners and advisors shift from a student-centered to a parentlstudent-centered freshman orientation. Planning significant events for parents not only improves the quulity of orientation but also offers excellent public relations opportunities. While careful orientation for students will enhance adjustment to college life, a good orientation for parents will benefit parents, students, and the school. By applying a psychographic typology known as Values and Lifestyles (VALS), schools can create a choice of activities attractive to parents from different market segments. Zncreclsed student retention will be a major benefit. For parents as well as students, the freshman year is a rite of passage. In the four years to come, at no time will parental interest in the educational institution be likely to be as intense as it is during orientation for the freshman year. At no other time will the educational institution have as good a chance to secure the solid parental backing so critical to student retention and academic success.
Estradiol induction of proenkephalin messenger RNA in hypothalamus: dose-response and relation to reproductive behavior in the female rat

Abstract Hormone effects on proenkephalin (PE) mRNA allow an opportunity to compare a brain region-specific molecular change with a quantifiable behavior. Slot blots were used to measure PE mRNA levels in the ventromedial hypothalamus (VMN) and preoptic area (POA) as a function of the dose of estrogen administered to ovariectomized rats. Every rat used had been characterized for the ability to display lordosis behavior. Estradiol treatment led to a monotonic dose-dependent increase in PE mRNA level in VMN, while only a small effect was observed in POA at the higher estradiol doses. Lordosis behavior, assessed manually and in mating tests, also increased monotonically with estradiol dose. The data indicate that an apparent ‘threshold’ level of PE mRNA in VMN coincided with display of behavior, and suggest further that high levels of PE mRNA, alone, are not sufficient for lordosis. While the exact relationship of the eventual product, Met-enkephalin, to female reproductive behavior remains to be determined, the parallel changes in PE mRNA level and behavior encourage further analysis.
The mechanism of insulin action

Insulin was isolated over 70 years ago, but the intracellular transduction of the insulin signal has not been elucidated. Significant progress has been made, particularly in the last 10 years, with the characterization of the insulin receptor and its intrinsic tyrosine kinase. However, no mechanism has been proposed that accounts for all the actions of insulin. Furthermore, all the mechanisms discussed in this brief overview contain major inadequacies. Despite these gaps in our knowledge, substantial evidence indicates that receptor tyrosine kinase activity is essential for insulin action and multiple pathways almost certainly participate. Hopefully, continued dissection of the signalling pathways will soon yield the mechanism of insulin action.