cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeted Degradation of Transcription Factors by TRAFTACs: Transcription Factor Targeting Chimeras

Abstract Many diseases, including cancer, stem from aberrant activation and overexpression of oncoproteins that are associated with multiple signaling pathways. Although proteins with catalytic activity are able to be successfully drugged, the majority of other protein families, such as transcription factors, remain intractable due to their lack of ligandable sites. In this study, we report the development of TRAnscription Factor TArgeting Chimeras (TRAFTACs) as a generalizable strategy for targeted transcription-factor degradation. Herein, we show that TRAFTACs, which consist of a chimeric oligonucleotide that simultaneously binds to the transcription-factor of interest (TOI) and to HaloTag fused dCas9 protein, can induce degradation of the former via the proteasomal pathway. Application of TRAFTACs to two oncogenic TOIs, NF-κB and brachyury, suggests that TRAFTACs can be successfully employed for the targeted degradation of other DNA-binding proteins with minor changes to the chimeric oligonucleotide.
Measuring the Multimode Fiber Transmission Matrix from only the Proximal Side

Multimode fibers may serve as narrow-gauge imaging probes that extend the reach of optical imaging, using computational reconstruction and knowledge of the fiber’s single-pass transmission matrix. We propose a method to recover this transmission matrix from round-trip measurements performed on the proximal side only.
Perceptions regarding 100% fruit juice among parents who give them to their children <5 years

Background: 100% fruit juice, the sugar content of which closely approximates that of sodas and several other sugar-sweetened beverages, is commonly consumed by infants and young children, often in amounts that exceed recommended limits. While early introduction and high consumption of fruit juice have both been linked to increased obesity risk, juice is available to families of WIC-enrolled children >1 year, in limited amounts, as an alternative to whole fruit.. The …
Using ethical leadership to reduce job stress and improve performance quality in the hospitality industry

Abstract Given an increased call for examining ethics in the hospitality industry, this research examines how ethical leadership influences the job stress and performance quality of customer-contact employees in the hospitality industry. Results indicate that customer-contact employees’ views of their supervisor’s use of ethical leadership behaviors is related to lower levels of ethical ambiguity and job stress. Ethical ambiguity is positively associated with job stress, which is negatively associated with customer-contact employees’ performance quality. Perceived ethical leadership behaviors positively influence performance quality. Based on the findings, implications are provided for both theory and management, and directions for future research are offered.
Real-time Alerting System for COVID-19 Using Wearable Data

Early detection of infectious disease is crucial for reducing transmission and facilitating early intervention. We built a real-time smartwatch-based alerting system for the detection of aberrant physiological and activity signals (e.g. resting heart rate, steps) associated with early infection onset at the individual level. Upon applying this system to a cohort of 3,246 participants, we found that alerts were generated for pre-symptomatic and asymptomatic COVID-19 infections in 78% of cases, and pre-symptomatic signals were observed a median of three days prior to symptom onset. Furthermore, by examining over 100,000 survey annotations, we found that other respiratory infections as well as events not associated with COVID-19 (e.g. stress, alcohol consumption, travel) could trigger alerts, albeit at a lower mean period (1.9 days) than those observed in the COVID-19 cases (4.3 days). Thus this system has potential both for advanced warning of COVID-19 as well as a general system for measuring health via detection of physiological shifts from personal baselines. The system is open-source and scalable to millions of users, offering a personal health monitoring system that can operate in real time on a global scale.
What Makes a Church Sacred? : Legal and Ritual Perspectives from Late Antiquity

What is the purpose of a church? Who owns a church? Mary K. Farag persuasively demonstrates that three groups in late antiquity were concerned with these questions: Christian leaders, wealthy laypersons, and lawmakers. Conflicting answers usually coexisted, but from time to time they clashed and caused significant tension. In these disputes, juridical regulations and opinions mattered more than has been traditionally recognized. Considering familiar Christian controversies in novel ways, Farag’s investigation shows that scholarship has misunderstood well-known religious figures by ignoring the legal issues they faced. This seminal text nuances vital aspects of scholarly conversations on sacred space, gift giving, wealth, and poverty in the late antique Mediterranean world, making use not only of Latin and Greek sources but also Coptic and Arabic evidence. “This is a book I have long been looking for. Meticulously conceived and argued, it provides the first comprehensive survey and analysis of what made a church sacred in late antiquity. It will likely become a standard reference on the topic for decades to come.” WENDY MAYER, Australian Lutheran College, University of Divinity MARY K. FARAG is Assistant Professor of Early Christian Studies at the Princeton Theological Seminary.
Optimal test functions for boundary accuracy in discontinuous finite element methods

Obtaining accuracy along domain boundaries is often the primary goal of a numerical simulation. In this work, we show how the test space of discontinuous Galerkin (DG) methods can be optimized to achieve enhanced boundary accuracy for linear problems. Given some norm in which accuracy is desired, the optimal test functions render the numerical solution the best approximation to the true solution in that norm. For most norms, these test functions would be global in nature. However, for norms emphasizing boundary accuracy, they can be computed in an element-local manner and represent adjoint solutions for the interface fluxes. The resulting accuracy in these interface fluxes propagates globally, leading to convergence rates on the domain boundaries greater than 2 p + 1 . Indeed, if the test functions and interface fluxes are well-resolved, exact boundary fluxes are obtained. Here, we demonstrate these ideas for several Computational Fluid Dynamics (CFD) simulations, including advection-diffusion and linearized Euler problems in both one and two dimensions. An extension of the theory to nonlinear problems will be presented in a future work. We derive and compute optimal test functions for discontinuous finite element methods.These test functions deliver accuracy in domain-boundary quantities.The resulting "BDPG" method achieves higher flux convergence rates than DG.The method applies to linear PDEs and can be extended to nonlinear equations.
Role of S -adenosyl- L -methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium

The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on "Role of S-Adenosyl-L-Methionine (SAMe) in the Treatment of Alcoholic Liver Disease" in Bethesda, Maryland, September 2001. Alcoholic liver disease (ALD) is a major cause of illness and death in the United States. Oxidant stress plays a key role in pathogenesis of liver disease. S-Adenosyl-L-methionine, a dietary supplement, is the methyl donor for biochemical methylation reactions and a precursor of glutathione, the main hepatocellular antioxidant. S-Adenosyl-L-methionine has been shown to attenuate liver injury caused by alcohol and other hepatotoxins in some animal models. Understanding the mechanisms by which SAMe attenuates liver injury caused by alcohol may provide useful information for full-scale human clinical trials. For this symposium, seven speakers were invited to address the following issues: (1) impaired methionine metabolism in alcoholic liver injury; (2) regulation of liver function by SAMe; (3) folate deficiency, methionine metabolism, and alcoholic liver injury; (4) attenuating effect of SAMe on ALD in experimental animals; (5) SAMe and mitochondrial glutathione depletion in ALD; (6) SAMe and cytokine production in liver injury; and (7) role of SAMe in the prevention of hepatocarcinogenesis. The presentations of this symposium support the suggestion that SAMe may have potential to treat ALD by (1) acting as a precursor of antioxidant glutathione, (2) repairing mitochondrial glutathione transport system, (3) attenuating toxic effects of proinflammatory cytokines, and (4) increasing DNA methylation. Further studies are required to evaluate the safety and effectiveness of SAMe treatment.
The determination of carbon dioxide in fermenting mixtures

In connection with a research on enzymic behavior it was necessary to develop a simple and expeditious method for the determination of the carbon dioxide formed during fermentations. The most suitable method of carbon dioxide analysis appeared to be the procedure evolved by Cain and Maxwell [1] for the determination of carbon in steel. They absorbed the carbon dioxide, formed by combustion, in known volumes of barium hydroxide solution and followed the precipitation of barium carbonate by measurements of the electrical conductivity of the solution. The idea has been applied by Spoehr and McGee [2,3] to the determination of carbon dioxide in their studies on plant respiration. This paper describes the development of this general method so as to render it applicable to studies on fermentation.
Modulation of host defense peptide-mediated human mast cell activation by LPS

Human β-defensin3 (hBD3) and the cathelicidin LL-37 are host defense peptides (HDPs) that directly kill microbes and display immunomodulatory/wound-healing properties via the activation of chemokine, formylpeptide and epidermal growth factor receptors on leukocytes and epithelial cells. A C-terminal 14 amino acid hBD3 peptide with all Cys residues replaced with Ser (CHRG01) and an LL-37 peptide consisting of residues 17-29 (FK-13) display antimicrobial activity but lack immunomodulatory property. Surprisingly, we found that CHRG01 and FK-13 caused Ca(2+) mobilization and degranulation in human mast cells via a novel G protein-coupled receptor known as Mas-related gene-X2 (MrgX2). At local sites of bacterial infection, the negatively charged LPS likely interacts with cationic HDPs to inhibit their activity and thus providing a mechanism for pathogens to escape host defense mechanisms. We found that LPS caused almost complete inhibition of hBD3 and LL-37-induced Ca(2+) mobilization and mast cell degranulation. In contrast, it had no effect on CHRG01 and FK-13-induced mast cell responses. These findings suggest that HDP derivatives that kill microbes, harness mast cell's host defense and wound-healing properties via the activation of MrgX2 but are resistant to inhibition by LPS could be utilized for the treatment of antibiotic-resistant microbial infections.
Conformational analysis of a mitochondrial presequence derived from the F1-ATPase β-subunit by CD and NMR spectroscopy

Abstract Previous studies on mitochondrial targeting presequences have indicated that formation of an amphiphillic helix may be required for efficient targeting of the precursor protein into mitochondria, but the structural details are not well understood. We have used CD and NMR spectroscopy to characterize in detail the structure of a synthetic peptide corresponding to the prequence for the β-subunit of F 1 -ATPase, a mitochondrial matrix protein. Although this peptide is essentially unstructured in water, α-helix formation is induced when the peptide is placed in structure-promoting environments, such as SDS micelles or aqueous trifluoroethanol (TFE). In 50% TFE (by volume), the peptide is in dynamic equilibrium between random coil and α-helical conformations, with a significant population of α-helix throughout the entire peptide. The helix is somewhat more stable in the N-terminal part of the presequence (residues 4–10), and this result is consistent with the structure proposed previously for the presequence of another mitochondrial matrix protein, yeast cytochrome oxidase subunit IV. Addition of increasing amounts of TFE causes the α-helical content to increase even further, and the TFE titration data for the presequence peptide of the F 1 -ATPase β-subunit are not consistent with a single, cooperative transition from random coil to α-helix. There is evidence that helix formation is initiated in two different regions of the peptide. This result helps to explain the redundancy of the targeting information contained in the presequence for the F 1 -ATPase β-subunit.
Radiation Induced Electrical Transients in Strain Gage and Temperature Transducer Circuits in a Pulsed Reactor Environment

Radiation induced electrical transients in strain gage, nickel temperature sensor, silicon temperature sensor, and thermocouple circuits have been studied in the Kukla Prompt Critical Pulsed Reactor environment. Induced signals, which could obscure real data, were observed in many strain gage circuits. It was determined that the observed signals were the result of a voltage appearing between the strain gages and ground when the reactor was pulsed. Circuit arrangements were devised and tested which reduced the magnitude of the induced signals to less than 1 mV. Nickel temperature sensors and spot welded thermocouples operated satisfactorily in the reactor environment. No adverse effects due to transient signals and no changes in calibration were observed. The one type of silicon temperature sensor tested suffered large and permanent increases in resistance when exposed to a reactor pulse.
An Assessment of the Reaction Energetics for Cytochrome P450-Mediated Reactions

Abstract Regioselectivity is used to determine the absolute energetic differences for four different reactions catalyzed by P450. Abstraction of a hydrogen from a benzylic carbon containing a chlorine has a 1.0 kcal/mol lower barrier than abstraction from a simple benzylic carbon, which in turn is 0.4 to 0.9 kcal/mol lower than abstraction from the methyl group of an aromatic ether and 0.1 to 0.6 kcal/mol easier than aromatic hydroxylation. Isotope effects are used to determine if the enzyme–substrate complexes leading to each product, from a given substrate, are in rapid equilibrium. For all enzymes isotopically sensitive branching is observed from the benzylic carbon upon deuterium incorporation at that position to each of the other positions, indicating that each product arises from the same active oxygen species. The energetic differences determined experimentally are accurately reproduced by theoretical hydrogen atom abstractions at both the AM1 semiempirical and DFT levels of theory.
Rapid degradation of oxidation resistant nitrophenols by TAML activator and H2O2

Nitrophenols (NPs) are widely prevalent recalcitrant anthropogenic pollutants. TAML activators in conjunction with peroxides have proven to be effective in the remediation of myriad organic pollutants. In the present study, we have discovered that one of the most reactive TAML activators (1) catalyses the oxidative degradation by H2O2 of mono- and dinitrophenols (including all US-EPA classified priority pollutants) under ambient conditions at pH 8 which is close to pH of environmental waters. Individual nitrophenols as well as mixtures thereof undergo fast decontamination (reaction time ≤45 min) resulting in deep oxidation producing HCO2− and minerals, CO, CO2, NO2−, and NO3− (up to 99% of N and 70% of C). The remarkable efficacy of the 1/H2O2-mediated decontamination process is matched by complete elimination of the toxicity of the nitrophenols (Microtox® assays). Detailed mechanistic studies of the catalyzed oxidation revealed a strong substrate inhibition of the catalytic activity for some nitrophenols, the strongest being observed for 4-nitrophenol. DFT calculations suggest that the inhibition is likely due to reversible binding of nitrophenolate anions to the iron(III) center of the resting state of the 1 catalyst, which compromises its reactivity toward H2O2.
Where to begin human papillomavirus vaccination

The lifetime risk of cervical cancer among African American women is 0·25% higher than in white women (0.94% vs 0.69%). More strikingly these women have a lifetime risk of dying from cervical cancer that is twofold higher than that of white women. Clearly human papillomavirus (HPV) does not affect all groups equally. The timely review by Jeffrey Partridge and Laura Koutsky and the accompanying Leading Edge outlines some of the viruss tendencies as we know them and the need to consider men in prevention efforts. However the work is incomplete with respect to how current knowledge should guide vaccination strategies. Neither piece addresses the preference of HPV to affect one racial subgroup--ie African Americans. Nor do they address possible ways to dramatically reduce the disparity. HPV in African American women is not well understood but understanding the causes of the disparity are not a prerequisite to action. Studies suggest there are socially mediated increased susceptibilities to infection and genetically mediated susceptibilities to oncogenesis. Others point to barriers to care and unequal treatment. Simply knowing that this group is disproportionately affected should lead to targeted vaccination efforts that administer the safe effective three-dose prevention tool to African Americans. (excerpt)
Multiple-contact diffusion-limited-aggregation model.

New diffusion-limited growth models are described in which growth occurs at the site which is first contacted by k (k is a small integer) random walkers launched from outside the growing cluster and adsorbed on contact with the cluster. This model is closely related to the dielectric-breakdown model in which the growth probability is proportional to the kth power of the field gradient at the surface of the growing cluster. For the case k=2 our results for the radius-of-gyration exponent \ensuremath{\beta} are consistent with the theoretical predictions of Turkevich and Sher. However, our results do indicate that the main assumption of the theory of Turkevich and Sher (the formation of a diamond shape on the square lattice) is not correct in this case. The clusters grow into a crosslike shape in which the increase in length and width of the arms of the cross with increasing cluster size are described by different exponents. A similar anisotropy is not observed from the largest clusters which can be grown on hexagonal lattices for the cases k=2, 3, and 4. For k=2 the radius-of-gyration exponent has effective values of about 0.73 and 0.70 for the largest clusters which can be grown on square and hexagonal lattices, respectively.
Physiological changes in the running greyhound (Canis domesticus): influence of race length.

Abstract 1. 1. Racing greyhounds were allowed to run 402 m, 503 m, and 704 m to determine the influence of increased race length on physiological changes during and after exercise. 2. 2. Plasma and whole blood variables that changed significantly with increased race length were [K+], [total protein], [lactate], hematocrit, and arterial pH. 3. 3. Those variables that changed with increased race distance showed no indication of reaching a plateau; thus, the maximum changes that these variables might undergo with longer exercise duration remains unknown.
Characterization of condensed plasmid DNA models for studying the direct effect of ionizing radiation

We have examined the changes in physical properties of aqueous solutions of the plasmid pUC18 that take place on the addition of the cationic oligopeptide penta-arginine. An increase in sedimentation rate and static light scattering, and changes in the nucleic acid CD spectrum all suggest that this ligand acts to condense the plasmid. Dynamic light scattering suggests the hydrodynamic radii of the condensate particles are a few micrometers, ca. 50-fold larger than that of the monomeric plasmid. Condensation of the plasmid also produces a ca. 100-fold decrease in the strand break yield produced by gamma irradiation. This extensive protection against reactive intermediates in the bulk of the solution implies that condensed plasmid DNA may offer a model system with which to study the direct effect of ionizing radiation (ionization of the DNA itself). The use of peptide ligands as condensing agents in this application is attractive because the derivatives of several amino acids (particularly tryptophan and tyrosine) have been shown to modify the radiation chemistry of DNA extensively.
Effects of Change in Social Content of Video Rewards on Response Patterns of Bonnet Macaques

Abstract Three individually housed bonnet macaques, with long-term experience in performing a joystick task with a reward choice of either viewing color video of a single bonnet group or obtaining a banana-flavored food treat, were presented with images of a new group when they chose to view social video. The change produced absolute increases in responding for social video and enhanced preference for viewing social video relative to obtaining the food treat, supporting the view that the monkeys were strongly attending to the social content of the videos.
An integral equation method for dynamic crack growth problems

Within the assumptions of linear elastic fracture mechanics, dynamic stresses generated by a crack growth event are examined for the case of an infinite body in the state of plane strain subjected to mode I loading. The method of analysis developed in this paper is based on an integral equation in one spatial coordinate and in time. The kernel of this equation, i.e., the influence or Green's function, is the response of an elastic half-space to a concentrated unit impulse acting on its edge. The unknown function is the normal stress distribution in the plane of the crack, while the free term represents the effect of external loading. The solution for the stresses is obtained with the assumption that its spatial distribution contains a square root singularity near the tip of the crack, while its intensity is an unknown function of time. Thus, the orginal integral equation in space and time reduces to Volterra's integral equation of the first kind in time. The equation is singular, with the singularity of the kernel being a combined effect of the singularity of the influence function and the singularity of the dynamic stresses at the tip of the crack. Its solution is obtained numerically with the aid of a combination of quadrature and product integration methods. The case of a semi-infinite crack moving with a prescribed velocity is examined in detail. The method can be readily extended to problems involving mode II and mixed mode crack propagation as well as to problems of dynamic external loadings.
Energy and nutrient analyses of a dairy farm in Central Pennsylvania

Abstract This paper analyses energy flows on a dairy farm in Central Pennsylvania, U.S.A. Energy values for all inputs to the agricultural system are calculated and evaluated with respect to alfalfa, corn and milk production. An evaluation of nitrogen and phosphorus flows demonstrates the impact that the use of inorganic fertilizers has on the total energy budget of the farm system. The recycling of nutrients via the application of animal manures provides both a source of fertilizer and significant energy savings in terms of the energy costs necessary to produce a similar quantity of inorganic nutrients. Energy efficiencies appeared to be higher than for previous studies reported in the literature. Energy input—output analysis is introduced as an effective technique for tracing both direct and indirect energy flows within an agricultural system. The interdependency of alfalfa, corn, milk production and the management of animal manures is demonstrated with this analysis and the required inputs of fuels and electricity, goods, and solar energy inputs are calculated.
Geology of a Portion of the Contwoyto Lake Area, Northwest Territories: ABSTRACT

Approximately 24 square miles of Archean (?) igneous and metamorphic rocks have been mapped at a scale of 1 inch equals 1,000 feet in an area centered 5 miles south of the central part of Contwoyto Lake, N.W.T. The oldest rock unit is apparently a quartz-plagioclase-biotite-K-feldspar paragneiss containing numerous pegmatitic segregations of quartz, plagioclase, K-feldspar, and minor amounts of muscovite, tourmaline, and apatite. A sequence of low- to medium-grade meta-sediments overlies the paragneiss. In the northern part of the area, these rocks are largely quartz-chlorite-muscovite phyllites. As the grade of metamorphism increases southward, biotite, almandite, andalusite, cordierite, and staurolite become common. Approximately 20 beds of quartz-hornblende-almandite amphibolite up to 10 feet in width have been mapped in the schist sequence. The phyllites, schists, and amphibolites are believed to be correlative with the Yellowknife group. Two biotite granite bodies approximately one mile in diameter intrude the Yellowknife group metasediments. The sediments are also cut by diabase dikes 20-100 feet in width, and a gabbro stock 3/8 mile in diameter. Pyrrhotite, pyrite, and arsenopyrite are found locally in a few of the amphibolite beds. Gold mineralization is locally present in some of the tightly folded pyrrhotite and arsenopyrite-bearing amphibolites. End_of_Article - Last_Page 520------------
A module-based software system for spindle condition monitoring

Accurate identification of spindle working conditions is one of the key features of the next generation smart machining systems with built-in self-diagnosis capability. This paper presents a module-based software system for online spindle defect identification and localisation through an analytic wavelet envelope spectrum algorithm. The software is designed in accordance with the architectural structure of OSA-CBM, and implemented using the graphical programming language LabVIEW. Spindle condition is displayed online in both a basic window for machine operators and a diagnosis window for advanced analysis. The software provides a user-friendly human-machine interface and contributes to realising a smart machine tool.
Pursuit auditory tracking of dichotically presented tonal amplitudes.

In pursuit auditory tracking tasks subjects match a continuously varying pure tone presented to one ear with a second tone presented to the other ear and controlled by unidimensional movements of p...
A Bidomain Model for the Extracellular Potential and Magnetic Field of Cardiac Tissue

In this brief communication, a bidomain volume conductor model is developed to represent cardiac muscle strands, enabling the magnetic field and extracellular potential to be calculated from the cardiac transmembrane potential. The model accounts for all action currents, including the interstitial current between the cardiac cells, and thereby allows quantitative interpretation of magnetic measurements of cardiac muscle.
Pyelonephritis in pregnancy: once-a-day ceftriaxone versus multiple doses of cefazolin. A randomized, double-blind trial.

Abstract OBJECTIVE: The purpose of this study was to compare the efficacy of a single daily dose of intravenous ceftriaxone with that of multiple-dose cefazolin in the treatment of acute pyelonephritis in pregnancy. STUDY DESIGN: This was a double-blind, randomized, clinical trial. Patients admitted to the hospital with the diagnosis of acute pyelonephritis in pregnancy were enrolled and randomized according to a computer-generated randomization schedule. The study group received a single daily 1 gm dose of ceftriazone intravenously along with two additional doses of normal saline solution. The comparison group received three daily 2 gm doses of cefazolin intravenously. All infusions were given on an 8-hour schedule. Treatments were continued until the patient became afebrile. Each patient was discharged from the hospital on a regimen of appropriate oral antibiotics as directed by urine culture and sensitivities. At follow-up visits test-of-cure cultures were obtained. RESULTS: During the 2 year study period, 178 patients were randomized: 88 received cefazolin and 90 ceftriazone. Patient demographics and presenting signs and symptoms were similar in both groups. No differences were noted between the groups regarding days of febrile morbidity, length of hospital stay, or treatment failures. CONCLUSIONS: Daily single-dose intravenous ceftriazone is as effective as multiple-dose cefazolin in the treatment of patients with acute pyelonephritis during pregnancy.
Air Impingement Cooling by Synthetic Jet

Modern consumer electronic trends point to a demand for thinner and more portable electronic devices. Conventional cooling systems of these portable electronic devices are challenging to miniaturize in thin profile applications that are typically on the order of several millimeters in thickness. In order to overcome some of these challenges, a synthetic jet, which is also considered as micro fluidic device, is developed. This device which operates based on Piezo electricity is called Dual Cooling Jet (DCJ). DCJ disturbs the boundary layer over a hot component and hence increases heat transfer compare to conventional blower. DCJ is typically defined as a device using a partially enclosed cavity with oscillating walls/diaphragms to create alternating suction and ejection of fluid across an interface or orifice. In this work, the results of cooling performance investigation of DCJ are shown and compared with natural convection cooling. Also, several experiments have been done to study the cooling effect of DCJ at different configuration with respect to heat source and the results are compared. At the end, the effects of heat source size is investigated which are helpful to understand how effective DCJ is when used for cooling several size chips. In addition, the results of this work show that DCJ can be combined with low profile heat sink as a promising next generation ultra thin thermal solution module.
Knowledge organisation for a new millennium: principles and processes

All Web sites can be viewed as portals through which users have access to other parts of the Internet, but those Web sites whose primary objective is to guide users through the Internet, such as those of the search engines, shopping bots and other bots, and subject gateways, have a particular responsibility for facilitating the communication process. Those who take responsibility for supporting access to information in electronic environments must support all three stages in the organisation of knowledge, including selection, organisation, and the often neglected de‐selection. To be successful and to encourage users to identify with specific portals, and exhibit some loyalty as a member of the portal’s community, portals need to formulate a clear mission, and define some of the parameters of the community they are in the process of creating. Any processes or tools associated with the organisation of knowledge need to be appropriate to the needs of this community.
Note on the Theory of the Neutral Particle

Majorana has recently shown by using a special set of Dirac matrices that the symmetry properties of the Dirac equations make possible the elimination of the negative energy states in the case of a free particle. We present here a further investigation of this possibility, in a treatment based on an arbitrary Hermitian representation of the Dirac matrices instead of Majorana's special representation. The new procedure is compared with Schroedinger's early attempt to eliminate the negative energy states. The question of Lorentz invariance is discussed, and also the possibility of subjecting the particle to forces; it is found that the only sort of force having a classical analogue which is consistent with Majorana's way of eliminating the negative energy states is the nonelectric force of a scalar potential. The theory is worked through for this case, and it is pointed out that, in spite of the fact that the exclusion of negative energy states is accomplished without the introduction of antiparticles, the formalism still shows the stigmata associated with subtraction theories of the positron: the presence of otiose infinite terms which should be removed by subtraction, and the creation and destruction of pairs of particles. The application of Majorana's formalism to the theory of $\ensuremath{\beta}$-radioactivity is discussed at the end of the paper. Here the physical interpretation is quite different from that of the ordinary theory, since only neutrinos appear instead of the neutrinos and antineutrinos of the usual picture. The results predicted for all observed processes are nevertheless identical with those of the ordinary theory. An experimental decision between the formulation using neutrinos and antineutrinos and that using only neutrinos will apparently be even more difficult than the direct demonstration of the existence of the neutrino.
Sulfur Multicenter Bonding and Distortions in a Hypothetical Polydithioquinone

The electronic properties of polydithioquinone, a hypothetical C4S2 carbon-sulfur polymer related to both tetrathiotetracene and thiothiophthene, are examined using approximate molecular orbital calculations. We focus on a curious pattern of sulfur-sulfur bonding interactions suggested by the band structure calculations, a pattern observed in thiothiophthenes and other molecular analogues of our polymer. The ﷿ system of each C4S2 repeat unit contains eight electrons, consistent with a thiothiophthene-like rather than localized polydithioquinone valence structure. A pairing distortion in the carbon sublattice is implied; furthermore, the half-filled sulfur U bands suggest that the sulfur sublattice is also likely to undergo distortions. Restricting our consideration to those distortions that retain planarity of the polymer, we find deformations of the carbon backbone considerably less favorable energetically than those of the sulfur sublattice. Four nicely bond-localized isomers result from the distortions of both carbon and sulfur sublattices; these all are found to be low bandgap semiconductors. We also examine helical distortions and find a stable isomer with an approximately 10-fold helical axis.
Use of indium trichloride for the separation of native, denatured and single-stranded deoxyribonucleic acid.

A PREVIOUS communication from me1 described the use of indium trichloride for the separation of DNA and RNA. This work has now been extended to the point where it has become possible to separate different molecular species of DNA in the presence of indium chloride and varying concentrations of sodium chloride.
Model Misspecification and Invariance Testing Using Confirmatory Factor Analytic Procedures.

Confirmatory factor analytic procedures are routinely implemented to provide evidence of measurement invariance. Current lines of research focus on the accuracy of common analytic steps used in confirmatory factor analysis for invariance testing. However, the few studies that have examined this procedure have done so with perfectly or near perfectly fitting models. In the present study, the authors examined procedures for detecting simulated test structure differences across groups under model misspecification conditions. In particular, they manipulated sample size, number of factors, number of indicators per factor, percentage of a lack of invariance, and model misspecification. Model misspecification was introduced at the factor loading level. They evaluated three criteria for detection of invariance, including the chi-square difference test, the difference in comparative fit index values, and the combination of the two. Results indicate that misspecification was associated with elevated Type I error ra...
Human papillomavirus types 16 E6 and E7 contribute differently to carcinogenesis.

High-risk human papillomaviruses (HPVs) are etiologically implicated in human cervical cancer. Two viral genes, E6 and E7, are commonly found expressed in these cancer cells. We have previously shown that mice transgenic for the HPV-16 E6 gene or E7 gene, in which the E6 or E7 was expressed in the basal layer of epithelia, developed skin tumors. The spectrum of tumors derived from E6 and E7 mice differed, however; although most tumors derived from the E7-transgenic mice were benign, the majority of the tumors from the E6-transgenic mice were malignant. These findings led us to hypothesize that E6 and E7 play different roles in carcinogenesis. To assess at what stages in carcinogenesis E6 and E7 act, we treated the skin of K14E6- and K14E7-transgenic mice with chemical carcinogens known to contribute to distinct stages in carcinogenesis. Both E6 and E7 were found to synergize with chemical carcinogens in causing tumor formation. E6 was found to act weakly at the promotion stage of carcinogenesis in the formation of benign tumors but strongly at the progression stage which involves the malignant conversion of benign tumors. In contrast, E7 primarily affected the promotion stage of carcinogenesis. These results provide direct evidence that E6 and E7 contribute differently to carcinogenesis; E7 promotes the formation of benign tumors, and E6 acts primarily to accelerate progression of these benign tumors to the malignant stage. Consistent with this model, we found E6 and E7 to cooperate in inducing tumor formation in mice expressing both oncogenes.
The antecedents and effects of national corruption: A meta-analysis

Abstract A meta-analysis of 42 empirical studies was conducted to quantitatively summarize the corruption literature within a holistic theoretical framework. In general, variables within the political/legal, economics, and socio-cultural categories were equally correlated with national corruption; however, there have been twice as many studies examining the causes of corruption than those that examine the effects of corruption. Furthermore, we found that some measures of corruption are more robust than others. Finally, we identified some insights which future researchers might want to explore further. Overall, this study summarizes previous research, and serves as a guide to future research on corruption.
Optical detectors for GaAs MMIC integration - Technology assessment

Fiber optic links are being considered to transmit digital and analog signals in phased array antenna feed networks in space communications systems. The radiating elements in these arrays will be GaAs monolithic microwave integrated circuits (MMIC's) in numbers ranging from a few hundred to several thousand. If such optical interconnects are to be practical it appears essential that the associated components, including detectors, be monolithically integrated on the same chip as the microwave circuitry. The general issue of monolithic integration of microwave and optoelectronic components is addressed from the point of view of fabrication technology and compatibility. Particular attention is given to the fabrication technology of various types of GaAs optical detectors that are designed to operate at a wavelength of 830 nm.
Academic marine scientists and the federal funding system

Abstract This paper addresses one aspect of the academic marine research community in the United States, namely the relationship of that community to the federal funding agencies. Extensive survey and interview data provide the basis for a demographic profile of university marine scientists; these data are followed by descriptions of scientists’ contacts with federal funding agencies, judgments about the health of the funding system in the late 1970s, and perceptions of how well the scientists felt their federal sponsors were carrying out their duties. Two major issues, relative austerity and increased bureaucratization, were identified as having a special importance for the continued health of marine research endeavors.
Immunomodulatory and Physical Effects of Oil Composition in Vaccine Adjuvant Emulsions

Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60°C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60°C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants.
Fodor and Lepore on holism

L'A. reprend les definitions donnees par Fodor et Lepore du holisme semantique, de l'anatomicite des propositions et du molecularisme pour expliquer et discuter les deux conclusions suivantes:- d'une part, si les proprietes semantiques sont typiquement anatomiques avec aucune distinction entre analytique et synthetique, alors le holisme semantique est vrai- d'autre part, il n'y a aucune obligation a supposer que les propositions semantiques soient typiquement anatomiques
Why TV Is Not Our Fault: Television Programming, Viewers, and Who's Really in Control, by By Eileen R. Meehan

The culture industries unfailingly argue that they provide us the news and entertainment that we want. That is, we the people determine what is produced via our attention and, of course, our purcha...
Cyclic tournaments and cooperative majority voting: A solution

A new solution concept is axiomatically characterized for tournaments that represent cooperative majority voting. The predicted set of outcomes lies inside the top-cycle set, the uncovered set, and the Banks set.
The hypothalamus, brain-catecholamines, and drug therapy for gigantism and acromegaly.

Abstract A three-part hypothesis is proposed: (1) chronic hypersecretion of growth-hormone (G.H.) in many cases of gigantism and acromegaly is nonautonomous, and in these cases is under deranged hypothalamic control; (2) the major brain-catecholamines, noradrenaline (norepinephrine) and dopamine, play a crucial role in the hypothalamic mechanisms controlling G.H. release from the anterior pituitary gland; (3) drugs able to interfere with the metabolic cycle of these catecholamines should prove effective in the treatment of those cases of hypersomatotropism in which G.H. hypersecretion is nonautonomous.
Regulation of Connexin26 by Ca2+ and Calmodulin

Gap junction channels are key pathways for direct cell-cell communication that enables the intercellular diffusion of ions, second messengers, small metabolites and electrical coupling. To date, there are over 20 members of the gap junction channel family identified in human and they serve distinct roles in different cells and tissues. Among them, Cx26 is one of the most prominently expressed connexins (including Cx26, 29, 30 and 43) in the cochlea, which is primarily responsible of sound transduction in the inner ear. Over 100 mutations of Cx26 genes account for the 14% of the hearing loss. Here, we report a novel calcium binding pocket conserved in various family of Cxs using our established computer algorithms. In addition, we have also identified a calmodulin regulation site that with many disease mutations reside proximately. using a variety of spectroscopic methods including CD, fluorescence, NMR, we have determined metal binding affinity, stoichiometry, conformational change and binding modes of Ca2+ and Calmodulin.
Biomechanics of a novel minimally invasive lumbar interspinous spacer: effects on kinematics, facet loads, and foramen height.

OBJECTIVE: To study the alteration to normal biomechanics after insertion of a lumbar interspinous spacer (ISS) in vitro by nondestructive cadaveric flexibility testing. METHODS: Seven human cadaveric specimens were studied before and after ISS placement at L1-L2. Angular range of motion, lax zone, stiff zone, sagittal instantaneous axis of rotation (IAR), foraminal height, and facet loads were compared between conditions. Flexion, extension, lateral bending, and axial rotation were induced using pure moments (7.5 Nm maximum) while recording motion optoelectronically. The IAR was measured during loading with a 400 N compressive follower. Foraminal height changes were calculated using rigid body methods. Facet loads were assessed from surface strain and neural network analysis. RESULTS: After ISS insertion, range of motion and stiff zone during extension were significantly reduced (P .18). CONCLUSION: The primary biomechanical effect of the ISS was reduced extension with associated reduced facet loads and smaller decrease in foraminal height. The ISS had little effect on sagittal IAR or on motion or facet loads in other directions.
Expression and Spectroscopic Analysis of Soluble Nicotinic Acetylcholine Receptor Fragments Derived from the Extracellular Domain of the α-Subunit†

To facilitate structural studies of the ligand binding region from the nicotinic acetylcholine receptor (nAChR), we have developed methods for the high-level expression and purification of an important functional portion of the N-terminal extracellular domain (ECD) of the α-subunit. Two soluble receptor fragments comprising residues 143−210 of the Torpedo californica α-subunit were expressed in E. coli: αT68His6, which contains a histidine tag, and αT68M1, which includes the first transmembrane region, M1, of the α-subunit. Both proteins demonstrate saturable, high-affinity α-bungarotoxin (Bgtx) binding with an apparent equilibrium KD (3 nM) that is comparable to the affinities reported for preparations comprising the entire α-subunit ECD. These results demonstrate that the ECD determinants required for Bgtx recognition of the α-subunit are entirely specified by residues 143−210. The binding of small ligands was demonstrated in competition assays with 125I-Bgtx yielding KI values of 58 and 105 μM for d-t...
Observer design for stochastic-parameter systems

Constant-gain linear observer design is utilized to reconstruct the state vector of stochastic systems with both multiplicative and additive noises. It is shown that if the system model is mean square stable, then it is very easy to design an effective estimation scheme