cssi/SciSciGPT-SciSciNet huggingface dataset:
Structural and thermodynamic studies on mutant RNA motifs that impair the specificity between a viral replicase and its promoter.

The 3'-end region of the genomic RNA of brome mosaic virus forms a tRNA-like structure that is critical for its replication. Previous studies have shown that in this region, a stem-loop structure, called SLC, is necessary and sufficient for the binding of the RNA replicase, and for RNA replication. Recently, we determined the high-resolution NMR structure of SLC, which demonstrated that a 5'-AUA-3' triloop region is an important structural element for the enzymatic recognition. We proposed that the 5'-adenine of the triloop, which is rigidly fixed ("clamped") to the stem, is a key recognition element for the replicase. To elucidate the role of this "clamped base motif" for the enzymatic recognition, we have now investigated the solution conformations of several stem-loop molecules with mutant triloops, 5'-UUA-3', 5'-GUA-3', 5'-CUA-3' and 5'-UUU-3', that destroy the enzymatic recognition. For the GUA and UUA mutants, we have obtained high-resolution solution structures using 2D NMR. All four mutants have very similar thermodynamic stabilities, and all have the same secondary structures, a triloop with a five base-paired stem helix. In addition, they have quite similar sugar puckering patterns in the triloop region. The NMR structures of the GUA and UUA show that the 5' nucleotide of the triloop (G6 in GUA or U6 in UUA) lacks the strong interactions that hold its base in a fixed position. In particular, the U6 of UUA is found in two different conformations. Neither of these two mutants has the clamped base motif that was observed in the wild-type. While UUA also shows global change in the overall triloop conformation, GUA shows a very similar triloop conformation to the wild-type except for the lack of this motif. The absence of the clamped base motif is the only common structural difference between these two mutants and the wild-type. These results clearly indicate that the loss of function of the UUA and GUA mutants comes mainly from the destruction of a small key recognition motif rather than from global changes in their triloop conformations. Based on this study, we conclude that the key structural motif in the triloop recognized by the replicase is a solution-exposed, 5'-adenine base in the triloop that is clamped to the stem helix, which is called a clamped adenine motif.
Modeling the cost of shut-in production and the value of information in the Gulf of Mexico

Weather delay is a common risk in offshore energy production, and in the Gulf of Mexico, the occurrence of tropical storms and hurricanes regularly force operators to shut-down production, cease drilling and construction activities, and evacuate personnel. In physical terms, shutting-in a well will usually not cause a loss of the hydrocarbon resource, but in financial terms, the impact of deferred production can have a significant economic effect. Improved ocean observation systems in the Gulf of Mexico are expected to enhance the reliability and accuracy of hurricane forecasting, lowering the probabilities of false positives, and positively impacting the economic and human life consequences. Improved information reduces risk, and to the extent that operators are risk averse, enhanced information increases welfare. The purpose of this paper is to provide a methodological framework to estimate the cost of shut-in production due to extreme weather, and to provide a first-order lower-bound estimate of the market value of improved weather forecasting. Shut-in production is modeled using various recovery scenarios and valued in terms of the cash flow analysis over the life of the asset. A description of the valuation model and the nature of production recovery is outlined and illustrated through stylized examples.
Abstractions for fault-tolerant global computing

Global computing (WAN programming, Internet programming) distinguishes itself from local computing (LAN computing) by the fact that it exposes some aspects of the network to the application, rather than seeking to hide them with network transparency, as in LAN programming. Global computing languages seek to provide useful abstractions for building applications in such environments. The lqp(ċ)-calculus is a family of programming languages that use the abstraction of logs to specify application-specific protocols for distributed agreement and fault tolerance in global applications. Reflecting the motivation for global computing, the abstraction of logs isolates the communication requirements of such protocols. Two specific instances of the lqp(ċ)-calculus are provided, the lqp(dc)-calculus and the lqp(dcu)-calculus. These are intended as kernel programming languages for fault-tolerant distributed programming. The calculi incorporate various abstractions for fault tolerance, from which several forms of distributed transactions and optimistic computation may be built. As an example application, a calculus of atomic failures is presented, the atf-calculus, and its encoding in the lqp(dc)-calculus used to verify a correctness property.
Diagnostic ramifications of ocular vascular occlusion as a first thrombotic event associated with factor V Leiden and prothrombin gene heterozygosity.

Aim This study aimed to assess the diagnostic ramifications of vascular occlusion of the ocular vein and artery as a first thrombotic event associated with factor V Leiden (FVL) and/or prothrombin gene (PTG) heterozygosity.
Volatile fractionation and tektite source material

In discounting the possibility that vapor fractionation played a part in the origin of bediasites, it has been assumed that Na and K are lost to the vapor phase. Experimental work shows, however, that, under oxidizing conditions, neither Na nor K exhibit particularly volatile behavior. Indeed, the compositional variations exhibited by bediasites are very similar to those obtained during experimental high-temperature vapor fractionation of a high-silica melt.
Commonality Analysis: Partitioning Variance to Facilitate Better Understanding of Data:

In early intervention, researchers often are interested in interpretation aids that can help determine the relative importance of variables when multiple regression models are used, and that facilitate deeper insight into prediction dynamics. Commonality analysis is one approach for helping researchers understand the contributions independent or predictor variables make in a given regression model. The purposes of the present paper are to (a) provide a general overview of multiple regression analysis and its application in early intervention research, (b) explain how to conduct a commonality analysis, and (c) illustrate how commonality analysis might be used as an interpretation aid in an early intervention research context.
US oil/gas production cost : recent changes

Abstract Since 1984, US oil development cost has decreased, but only as the movement down along a curve shifting toward higher cost. In contrast, the non-associated gas cost curve has shifted favourably.
Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases

Abstract Caspases are implicated in neuronal death in neurodegenerative and other central nervous system (CNS) diseases. In a rat model of human immunodeficiency virus type 1 (HIV-1) associated neurocognitive disorders (HAND), we previously characterized HIV-1 envelope gp120-induced neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In this model, neuronal apoptosis occurred probably via gp120-induced reactive oxygen species (ROS). Antioxidant gene delivery blunted gp120-related apoptosis. Here, we studied the effect of gp120 on different caspases (3, 6, 8, 9) expression. Caspases production increased in the rat caudate-putamen (CP) 6 h after gp120 injection into the same structure. The expression of caspases peaked by 24 h. Caspases colocalized mainly with neurons. Prior gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1) into the CP before injecting gp120 there reduced levels of gp120-induced caspases, recapitulating the effect of antioxidant enzymes on gp120-induced apoptosis observed by TUNEL. Thus, HIV-1 gp120 increased caspases expression in the CP. Prior antioxidant enzyme treatment mitigated production of these caspases, probably by reducing ROS levels.
Risk Analysis of Terrorist Attacks

A quantitative probabilistic/systems analysis model is described which is useful for allocating resources to safeguard valuable documents or materials in either a fixed-site facility or a moving convoy against an overt terrorist attack. The model is also useful for ranking the sensitive areas at a site according to their survivability of a given hypothesized terrorist attempt. To compare various defense strategies and security configurations, the probability of a successful terrorist activity is computed based on event tree models of the site/security configuration. This calculation incorporates a realistic engagement model (in the event a guard force engages the terrorists prior to completion of their objective) and information on barrier penetration times (for example, distribution of the time to defeat a chain link fence or vault door, traverse an open area, and so forth). Two security analyses are described to illustrate the methodology. One example considers a terrorist attack on a convoy transporting a missile from a storage to a launch facility. The second example involves an attack on a munitions storage facility.
Carbohydrate vaccines as immunotherapy for cancer

Carbohydrates have established themselves as the most clinically relevant antigens of those tested and subsequently developed for vaccines against infectious diseases. However, in cancer patients, many of the defined carbohydrate antigens are really altered 'self' antigens and for unclear reasons, the body does not react to them immunologically. Although these self antigens have been found to be potentially suitable targets for immune recognition and killing, the development of vaccines for cancer treatment is actually more challenging compared with those for infectious diseases mainly because of the difficulty associated with breaking the body's immunological tolerance to the antigen. These antigens lack the inherent immunogenicity associated with bacterial antigens and, therefore, methods to enhance immunological recognition and induction of immunity in vivo are under investigation. These include defining the appropriate tumour-associated antigen, successfully synthesizing the antigen to mimic the original molecule, inducing an immune response, and subsequently enhancing the immunological reactivity so that all components can work together. This has been successfully accomplished with several glycolipid and glycoprotein antigens using carriers such as keyhole limpet haemocyanin (KLH) together with a saponin adjuvant, QS-21. Not only can high titre IgM and IgG antibodies be induced, which are specific for the antigen used for immunization, but the antibodies can mediate complement lysis. The approaches for synthesis, conjugation, clinical administration and immunological potential are discussed.
Dynamic fracture toughness

Dynamic fracture toughness versus crack velocity relations of Homalite-100, polycarbonate, hardened 4340 steel and reaction bonded silicon nitride are reviewed and discrepancies with published data and their probable causes are discussed. Data scatter in published data are attributed in part to the observed fluctuations in crack velocities. The results reaffirmed our previous conclusion that the dynamic fracture toughness versus crack velocity relation is specimen dependent and that the dynamic arrest stress intensity factor is not a unique material property.
Pathogenesis of Malignant Mesothelioma

Malignant mesothelioma (MM) is a very aggressive tumor that is caused by environmental, biologic, and genetic factors. Among these factors, asbestos plays a major role. The link between asbestos and MM has been firmly established through numerous epidemiologic studies conducted during the past 40 years. However, the causal role of chrysotile asbestos compared with crocidolite asbestos in MM, the method of correctly establishing asbestos exposure, the amount of asbestos necessary to cause MM, and the mechanisms of asbestos tumorigenicity are still being debated. Along with asbestos, Simian virus 40 (SV40), a DNA monkey virus, has recently been implicated in the etiology of MM. Simian virus 40 large T antigen (Tag) and small t antigen (tag) are largely responsible for the carcinogenicity of the virus, and it is possible that SV40 and asbestos are cocarcinogens. Finally, a genetic factor identified in 3 villages in Cappadocia, Turkey, where 50% of individuals die of MM, appears to be the cause of a high incidence of the disease. In these villages, genetic predisposition for MM works together with erionite, a nonasbestos fiber found in the stones used in construction of houses. The diagnosis of MM is made histologically and confirmed through electron microscopy and immunohistochemistry. Currently available therapies for MM prolong survival by a few months at most. An SV40 vaccine is being developed for human use and it is hoped that it may reduce the incidence of MM in asbestos workers.
The Evaluation of a Modified Chrome Oxide Based High Temperature Solid Lubricant Coating for Foil Gas Bearings

This paper describes the friction and wear performance of PS304, a modified chrome oxide based coating, for foil gas bearings. PS304 contains 60 wt% NiCr binder, 20 wt% Cr2O3 hardener, and 10 wt% each Ag, and BaF2/CaF2 lubricants. For evaluation, the coating is plasma spray deposited onto test journals which are slid against a superalloy partial arc foil bearing. The test load was 10 KPa (1.5 psi) and the bearings were run under start/stop cyclic conditions. The data show good wear performance of the bearing, especially at temperatures above 25 deg. C. Bearing friction was moderate (micron approx. or equal to 0.4) over the entire temperature range. Based upon the results obtained, the PS304 coating has promise for high temperature, oil-free turbomachinery applications.
Imaging macrophages with nanoparticles

Nanomaterials have much to offer, not only in deciphering innate immune cell biology and tracking cells, but also in advancing personalized clinical care by providing diagnostic and prognostic information, quantifying treatment efficacy and designing better therapeutics. This Review presents different types of nanomaterial, their biological properties and their applications for imaging macrophages in human diseases, including cancer, atherosclerosis, myocardial infarction, aortic aneurysm, diabetes and other conditions. We anticipate that future needs will include the development of nanomaterials that are specific for immune cell subsets and can be used as imaging surrogates for nanotherapeutics. New in vivo imaging clinical tools for noninvasive macrophage quantification are thus ultimately expected to become relevant to predicting patients' clinical outcome, defining treatment options and monitoring responses to therapy.
Relationship between Occupational Fantasies and College Majors

In this study the associations of expressed occupational fantasies and selection of college majors for 66 college students were analyzed. Implications for career counseling are discussed.
Interferon‐γ induced cell death in a cultured human salivary gland cell line

Increased levels of several cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), have been demonstrated in the salivary gland microenvironment of patients with Sjogren's syndrome (SS). How these cytokines may be contributing to the pathogenesis of the disease is not well understood. This study examined the role of IFN-gamma +/- TNF-alpha on cellular death in a cultured human salivary gland cell line (HSG). Cells treated long-term with IFN-gamma +/- TNF-alpha demonstrate a profound antiproliferative effect with a decrease in cell number to below that initially plated. Treatment of HSG cells with TNF-alpha alone did not have any significant effects on growth but did increase the expression of the IFN-gamma receptor. Cells labelled with propidium iodide and anti-digoxigenin dUTP/dATP were examined by flow cytometry to determine the percentage of cells exhibiting low DNA content and DNA strand breaks. The percentage of cells exhibiting subdiploid DNA and DNA strand breaks increased with increased time of exposure to the cytokines. The maximum percentage of cells exhibiting DNA degradation at 12 days was 58% for cells treated with IFN-gamma + TNF-alpha, 31% for IFN-gamma treated cells, and < 5% for TNF-alpha-treated and untreated cells. The cells with subdiploid ( < 2n) DNA were subsequently demonstrated to represent two populations, both with evidence of increased DNA strand breaks but with differing light scatter characteristics. One population had features of cells undergoing necrosis, whereas the second population exhibited features of apoptosis. These findings were confirmed by transmission electron microscopy. Cells not exposed to cytokines did not exhibit significant evidence of either death process. We conclude that long-term exposure of a human salivary gland epithelial cell line to IFN-gamma +/- TNF-alpha leads to increased DNA degradation and subsequent cell death. This suggests a potential SS disease mechanism and implicates the role of the epithelial cell in this disease as an important area for future study.
Biochemical Studies of Bacterial Sporulation and Germination XXII. ENERGY METABOLISM IN EARLY STAGES OF GERMINATION OF BACILLUS MEGATERIUM SPORES

Spore and vegetative cell adenylate kinases of Bacillus subtilis proved indistinguishable by polyacrylamide gel electrophoresis DEAE cellulose chromatography
Covalent cross-linking of duplex DNA using 4-thio-2′-deoxyuridine as a readily modifiable platform for introduction of reactive functionality into oligonucleotides

Full details of the template-directed covalent cross-linking of duplex oligodeoxynucleotides are presented. 4-Thio-2'-deoxyuridine was incorporated synthetically into a 17mer oligodeoxynucleotide, and the thiocarbonyl group of the modified base was alkylated with a variety of alpha-bromoacetyl-derivatized diamines. Covalent cross-linking was initiated by annealing the electrophilic probe oligomers with their complementary sequences, where a dG base was targeted at the position complementary to the modified 4-thio-2'-deoxyuridine. The sequence selectivity of cross-link formation as a function of tether topology and rigidity was examined, and the thermal stability of the modified duplexes was measured by UV melting experiments.
Intravascular ultrasound-guided treatment for angiographically indeterminate left main coronary artery disease: A long-term follow-up study

Objectives The purpose of this study was to evaluate the efficacy of an intravascular ultrasound (IVUS)-guided strategy for patients with angiographically indeterminate left main coronary artery (LMCA) disease. Background The assessment of LMCA lesions using coronary angiography is often challenging; IVUS provides useful information for assessment of coronary disease. Methods Intravascular ultrasound was performed on 121 patients with angiographically normal LMCAs to determine the lower range of normal minimum lumen area (MLA), defined as the mean − 2 SD. We conducted IVUS studies on 214 patients with angiographically indeterminate LMCA lesions, and deferral of revascularization was recommended when the MLA was larger than this predetermined value. Results The lower range of normal LMCA MLA was 7.5 mm2. Of the patients with angiographically indeterminate LMCAs, 83 (38.8%) had an MLA Conclusions Intravascular ultrasound is an accurate method to assess angiographically indeterminate lesions of the LMCA. Furthermore, deferring revascularization for patients with a minimum lumen area ≥7.5 mm2appears to be safe.
Battery/supercapacitor hybrid via non-covalent functionalization of graphene macro-assemblies

Binder-free, monolithic, high surface area graphene macro-assemblies (GMAs) are promising materials for supercapacitor electrodes, but, like all graphitic carbon based supercapacitor electrodes, still lack sufficient energy density for demanding practical applications. Here, we demonstrate that the energy storage capacity of GMAs can be increased nearly 3-fold (up to 23 W h kg−1) by facile, non-covalent surface modification with anthraquinone (AQ). AQ provides battery-like redox charge storage (927 C g−1) without affecting the conductivity and capacitance of the GMA support. The resulting AQ-GMA battery/supercapacitor hybrid electrodes demonstrate excellent power performance, show remarkable long-term cycling stability and, by virtue of their excellent mechanical properties, allow for further increases in volumetric energy density by mechanical compression of the treated electrode. Our measured capacity is very close to the theoretical maximum obtained using detailed density functional theory calculations, suggesting nearly all incorporated AQ is made available for charge storage.
Artificial intelligence modelling of control systems

The field of control systems simulation needs artificial intelligence technology as much as expert systems need systems simulation tools. A functional approach for the design of Expert Systems that perform model generations and simulations is proposed. A differential games simulator design is chosen to exemplify the above ideas. The discrete-event approach, based on the geometry of the game is proposed. Results are comparable with the simu lation results obtained using the imperative approach, but the interrogative approach offers faster execution and clearer sim ula tor definition. Knowledge representation of the differential games models is described using Semantic Networks. The model genera tion methodology is a blend of several problem-solving para digms, and the hierarchical dynamic goal system construction serves as the basis for model generation. Prolog-based imple mentation of the system is suggested.
High-performance Si microwire photovoltaics

Crystalline Si wires, grown by the vapor–liquid–solid (VLS) process, have emerged as promising candidate materials for low-cost, thin-film photovoltaics. Here, we demonstrate VLS-grown Si microwires that have suitable electrical properties for high-performance photovoltaic applications, including long minority-carrier diffusion lengths (Ln ≫ 30 µm) and low surface recombination velocities (S ≪ 70 cm·s−1). Single-wire radial p–n junction solar cells were fabricated with amorphous silicon and silicon nitride surface coatings, achieving up to 9.0% apparent photovoltaic efficiency, and exhibiting up to ∼600 mV open-circuit voltage with over 80% fill factor. Projective single-wire measurements and optoelectronic simulations suggest that large-area Si wire-array solar cells have the potential to exceed 17% energy-conversion efficiency, offering a promising route toward cost-effective crystalline Si photovoltaics.
Open Learning in the Suffolk TVEI Programme

T h e Suffolk TVEI project commissioned a curriculum group which was charged with the task of developing an Integrated Technology course. Members included representatives from Education with over 25 years collective experience of Teaching Technology and Industry. The reality of integrating the many facets of Design and Technology soon began to emerge, and an Open Learning system was considered the ideal vehicle to effect this change. The following factors were felt should be taken in t o account:- 1 . The need to move away from didactic learning approaches, especially in the secondary sector . 2. CDT embraces the philosophy of pupil centred, independent l earning. 3 . Secondary curriculum organisation based on areas of experience, and the disappearance of subjects as they are traditionally perceived within the next ten years. The development of Technology as a core ninth area of experience.4 . The radical change in attitude and approach required to succesfully implement GCSE. 5. The nature of existing staff and their expertise, f o r example in D~gn and Technology as opposed to 'Craft' based subjects. 6. The shortage of skilled teachers in Design and Technology and other related areas. 7. The need t o support and underpin Technology with sound Design practice.8. The use of Open Learning material as a form of 'hidden curriculum' In-Service training. Most authorities a r e not in a position to respond to the massive demand for INSET anticipated in subjects which are changing content radically. 9. The rapid l y increasing use of Open Learning systems post sixteen.
Mechanism of Rhodopsin Kinase Activation

The role of the cytoplasmic loops and C-terminal region of bovine rhodopsin (Rho) in binding and activating rhodopsin kinase was investigated. The ability of various enzymatically truncated forms of photolyzed rhodopsin (Rho*) to stimulate rhodopsin kinase activity was quantified. Following endopeptidase Asp-N cleavage of all phosphorylation sites on the C-terminal, the resulting truncated Rho* (329G-Rho*) was not phosphorylated by rhodopsin kinase. This suggests that rhodopsin kinase only phosphorylates C-terminal sites of Rho*. However 329G-Rho* could bind rhodopsin kinase and stimulate phosphorylation of exogenous peptide. Kinase stimulation was investigated for other truncated forms of Rho* in which the C-terminal region was either partially or completely eliminated, and the V-VI loop was either cleaved or left intact (339K-Rho*, 341E239E-Rho*, 329G239E-Rho*, 327P240S-Rho*). Results suggest that the V-VI loop is crucial for kinase binding (similar to the binding of GT). Mastoparan, a model peptide for G-protein-coupled receptors, was found to stimulate rhodopsin kinase in a mechanism similar to that of truncated Rho*. We conclude that rhodopsin kinase binds to the cytoplasmic loops of Rho* to cause a stimulation of its catalytic activity.
Isentropic Analysis of Convective Motions

This paper analyzes the convective mass transport by sorting air parcels in terms of their equivalent potential temperature to determine an isentropic streamfunction. By averaging the vertical mass flux at a constant value of the equivalent potential temperature, one can compute an isentropic mass transport that filters out reversible oscillatory motions such as gravity waves. This novel approach emphasizes the fact that the vertical energy and entropy transports by convection are due to the combination of ascending air parcels with high energy and entropy and subsiding air parcels with lower energy and entropy. Such conditional averaging can be extended to other dynamic and thermodynamic variables such as vertical velocity, temperature, or relative humidity to obtain a comprehensive description of convective motions. It is also shown how this approach can be used to determine the mean diabatic tendencies from the three-dimensional dynamic and thermodynamic fields. A two-stream approximation that partitions the isentropic circulation into a mean updraft and a mean downdraft is also introduced. This offers a straightforward way to identify the mean properties of rising and subsiding air parcels. The results from the two-stream approximation are compared with two other definitions of the cloud mass flux. It is argued that the isentropic analysis offers a robust definition of the convective mass transport that is not tainted by the need to arbitrarily distinguish between convection and its environment, and that separates the irreversible convective overturning fromoscillations associated with gravity waves.
Compliance with International Court Judgments and Decisions

Often we speak as if international courts were a form of enforcement: we assume that once a legal regime acquires a court, it has teeth. Both within national and international legal systems, however, implementation of adjudicated decisions is itself an enforcement problem. Compliance is not always a straightforward or likely outcome. It is the product of an uncertain and at times lengthy process shaped by political and social dynamics. All the more so in the international realm, wherein courts still lack purse and sword, but are more loosely linked to the executive branches and other actors on which they ultimately depend for the efficacy of their judgments. This chapter explores when and how the rulings of international adjudicative bodies receive compliance. What do recent studies in social science and law reveal about when and how international courts achieve compliance, and what impact, in turn, does compliance " or its absence " have on international courts?
Concomitant Clostridium difficile colitis and cytomegalovirus colitis in an immunocompetent elderly female.

A 78-year-old Japanese woman with diarrhoea and abdominal pain was admitted for PCR test (PCR)-proven Clostridium difficile colitis. The patient9s symptoms persisted despite multiple courses of antibiotics including intravenous metronidazole, oral vancomycin and oral fidaxomicin. She underwent a stool transplant without improvement. Biopsies from a colonoscopy revealed concomitant cytomegalovirus (CMV) infection. The patient was immediately started on intravenous ganciclovir. Unfortunately, she developed sepsis secondary to colitis, and underwent definitive treatment with a total colectomy. Although CMV is a rare colonic pathogen in the immunocompetent patient, it should be considered in patients with severe or refractory C difficile colitis.
STAPHYLOCOCCAL VIROLYSIN, A PHAGE-INDUCED LYSIN ITS DIFFERENTIATION FROM THE AUTOLYSIN OF NORMAL CELLS

Virolysin is a lysin which appears in Staphylococcus aureus K 1 cells infected with phage P 14 ; together with phage, virolysin is released from phage-infected cells at the time of lysis. Autolysin is a lysin formed by uninfected cells of the K 1 strain; autolysin is released from uninfected cells by autolysis. They show the following similarities: Both agents act within the genus Micrococcus . They lyse cells only after the cell has been subjected to a damaging or "sensitizing" treatment, such as heat, bacteriophage, acetone, or ultraviolet irradiation. The course of lysis of heated cells by both lysins has been found to proceed in a similar manner. A constant percentage of cells is lysed, independent of the concentration of lysin; the residual cells remain resistant to either lysin. Lysis proceeds logarithmically with time, and the velocity constants K are proportional to the lysin concentration. K increases with increasing temperature. Both lysins are unaffected by antiserum to the phage. They are inhibited alike by a number of chemicals, including known enzyme inhibitors. Both agents are destroyed by proteolytic enzymes and are precipitated by 40 per cent saturation with (NH 4 ) 2 SO 4 . Both lysins are very thermolabile. The two lysins differ with respect to their pH optimum, antigenic relationship and specificity for Micrococcus lysodeikticus . These results suggest that (1) both lysins have many properties associated with enzymes, (2) the lysis of heated cells, which they produce, has some of the characteristics of a chemical reaction, (3) the lysin from the phage-infected cell is clearly different from the lysin of the uninfected cell.
The Use of Solid-Phase Microextraction—Gas Chromatography in Forensic Analysis

A thorough review of the application of solid-phase microextraction (SPME) combined with gas chromatography for the analysis of forensic specimens is presented, including experimental results for several recent applications. The SPME applications covered in this comprehensive review include ignitable liquid residues (also referred to as accelerants), explosive traces, drugs and poisons from biological specimens, and other forensic applications. Recently developed SPME methods are also presented, including the analysis of ignitable liquid residues on human skin, odor signatures, and several drug applications such as free-fraction antipsychotic drug levels, blood alcohol casework, drink-tampering analysis, and gamma-hydroxybutyrate identification without the need for derivatization. SPME is shown to be an inexpensive, rapid, and sensitive method for the analysis of a variety of forensic specimens.
Sphingosine 1-phosphate rescues canine LPS-induced acute lung injury and alters systemic inflammatory cytokine production in vivo.

S1P has been demonstrated to protect against the formation of lipopolysaccharide (LPS)-induced lung edema when administered concomitantly with LPS. In the current study, we sought to determine the effectiveness of S1P to attenuate lung injury in a translationally relevant canine model of ALI when administered as rescue therapy. Secondarily, we examined whether the attenuation of LPS-induced physiologic lung injury after administration of S1P was, at least in part, caused by an alteration in local and/or systemic inflammatory cytokine expression. We examined 18, 1-year-old male beagles prospectively in which we instilled bacterial LPS (2–4 mg/kg) intratracheally followed in 1 h with intravenous S1P (85 μg/kg) or vehicle and 8 h of high-tidal-volume mechanical ventilation. S1P attenuated the formation of Q s /Q t (32%), and both the presence of protein (72%) and neutrophils (95%) in BAL fluid compared with vehicle controls. Although lung tissue inflammatory cytokine production was found to vary regionally throughout the LPS-injured lung, S1P did not alter the expression pattern. Similarly, BAL cytokine production was not altered significantly by intravenous S1P in this model. Interestingly, S1P potentiated the LPS-induced systemic production of 3 inflammatory cytokines, TNF-α (6-fold), KC (1.2-fold), and IL-6 (3-fold), without resulting in end-organ dysfunction. In conclusion, intravenous S1P reduces inflammatory lung injury when administered as rescue therapy in our canine model of LPS-induced ALI. This improvement is observed in the absence of changes in local pulmonary inflammatory cytokine production and an augmentation of systemic inflammation.
Intraocular cholesterol crystals.

Intraocular cholesterol crystals (cholesterolosis) present as multiple refractile particles suspended within the intraocular environment. There are a number of causes leading to cholesterolosis that the clinician should be aware of. We describe a case of Coats disease in a 2-year-old male child who, following treatment, developed cholesterolosis of the posterior and anterior segments in the affected eye (figures 1 and 2). Figure 1 Photograph of the right eye posterior segment showing multiple refractile particles within the vitreous cavity. Access the article online to view this figure in colour. Figure 2 Anterior segment photograph of the right eye showing multiple refractile particles suspended within the anterior chamber. Access the article online to view this figure in colour. A 2-year-old male child was referred to the eye clinic with a 2-month history of an intermittent right divergent squint and a whitish pupillary reflex, first noted by the …
Lattice‐fluid equation of state with hydrogen‐bond cooperativity

Hydrogen bonding plays an important role in thermodynamic properties of polar fluids. Existing equations of state that include h-bonding cannot accurately predict the phase behavior for polar fluids. In the theories for h-bond-chain forming molecules, h-bonding strength is considered a constant at a given temperature and pressure. Infrared spectroscopy and ab initio calculations show that the h-bonding strength depends on whether or not the molecule was previously h-bonded at other sites. When an h-bond is formed between an already hydrogen-bonded species and a free species, the second h-bond has different energetic characteristics from the primary h-bond. In the case of l-alkanol self-h-bonding, the equilibrium constant for the second h-bond is ten times that for the primary h-bond. This phenomenon called h-bond cooperativity was incorporated in a lattice-fluid-hydrogen-bonding equation of state. Calculations for pure l-alkanols, show that the theory can be improved significantly by the incorporation of h-bond cooperativity. Agreement with the phase behavior and spectroscopic h-bonding data improves using cooperativity, without any additional adjustable parameters. Heat of mixing calculations agree well with the experimental data.
Dysproteinemias and Kidney Disease

Dysproteinemia is characterized by the presence of a monoclonal protein. Dysproteinemia can be associated with malignant conditions such as multiple myeloma (MM) or can be benign as in monoclonal gammopathy (MG) of undetermined significance. These terms unfortunately apply only to the proliferative properties of the clone. Independent of the proliferative potential of the clone, MGs can result in kidney disease, and are increasingly recognized as a cause for acute kidney injury as well as chronic kidney disease. A number of mechanisms have been identified for kidney injury from dysproteinemia including protein deposition, and protein-mediated tubular obstruction and complement activation. Protein deposition can be further divided by the nature of deposits, that is, organized versus non-organized deposits. These different pathologic mechanisms result in different histopathologic features and clinical presentations that can be used to separate these kidney diseases from those without MG. Confirming the association of kidney disease with MG is essential and treatment is geared toward elimination of the clone.
Mutant Rad50-mediated cisplatin chemosensitization for the treatment of human head and neck cancer

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 3314 In 2006, there were 40,000 new cases of head and neck squamous cell carcinoma (HNSCC) and 11,000 deaths in the US. Survival from HNSCC has not improved over many decades. Cisplatin is the mainstay of adjuvant treatment. Escalating cisplatin dose to overcome drug resistance leads to severe systemic toxicity. Repair of DNA double-strand breaks (DSBs) by the Mre11, Rad50, and Nbs1 (MRN) complex contributes to resistance. With the goal of developing molecular therapies to enhance the cytotoxicity of cisplatin and, thus, improve therapeutic outcome in the treatment of HNSCC, we have created a novel, recombinant adenoviral vector containing a mutant Rad50 gene (Ad-Rad50). Ad-Rad50 interrupts the function of the MRN DNA repair complex, thereby sensitizing HNSCC cells to cisplatin-induced damage. Cell proliferation assay showed that Ad-Rad50, with cisplatin, produced significantly slower cancer cell growth than any other treatment group. Neutral comet assay demonstrated a higher number of DNA DSBs in the Ad-Rad50 with cisplatin group, versus all other groups (P<0.01). Ad-Rad50, through impairment of MRN-mediated DNA repair, permits lethal cell damage to accumulate in cisplatin-treated cells. It has been demonstrated that 90% of HNSCC tumor cells achieve immortality through telomerase activation. MRN is required for telomerase function. Telomere shortening beyond a critical threshold causes cellular senescence. PNA-FISH telomere length analysis showed significantly shorter telomeres in the Ad-Rad50 with cisplatin group, relative to all other groups (P<0.01), contributing to enhanced cisplatin cytotoxicity. Cisplatin induces dose-dependent G2/M cell cycle arrest. Flow cytometry revealed that, at tested doses, cisplatin did not increase the proportion of cells in G2/M arrest. The addition of Ad-Rad50 produced G2/M arrest in the majority of HNSCC cells (P<0.005). Abrogation of MRN function by Ad-Rad50 may allow cisplatin-induced damage to accumulate, producing arrest. An animal model of human HNSCC was used to further investigate the feasibility of this novel treatment strategy. Mice, treated with Ad-Rad50 and cisplatin in combination, had significantly smaller tumors than untreated controls, cisplatin alone, or Rad50 alone groups. Preliminary data suggests that low-dose cisplatin, with Ad-Rad50, results in smaller tumors than a higher cisplatin dose, used as the standard in clinical applications. Our study demonstrates that Ad-Rad50 enhances the cytotoxicity of cisplatin in HNSCC by increasing DNA DSBs, telomere shortening, and enhancing G2/M cell cycle arrest. This translates to tumor volume reduction in vivo. The implications are considerable as sensitizing HNSCC to cisplatin with Ad-Rad50 may allow for the use of lower cisplatin doses, clinically. This work is supported by FAMRI.
Symmetry of horizontal and sagittal condylar path angles: an in vivo study.

The specific aims of the study were to determine (1) the mean condylar path inclination (CP) and Bennett angles (BA) in occlusally healthy dentate subjects and (2) whether there was right-left asymmetry of CP and BA. Eccentric movements of three mm and five mm from reference positions were recorded for 45 subjects using a Cadiax system. The mean right CP angles: 48.8±8° (three mm) and 48.2±7° (five mm); the mean left CP angles: 48.8± 8° (three mm) and 49.5±70 (5mm) were steeper than suggested means for setting articulators. The mean right BA: 7.7±3° (3mm) and 7.9±4° (five mm); and the mean left BA: 8.1±4° (three mm) and 8.5±4° (five mm) were lower than suggested means for setting articulators. Paired-t-tests showed no significant differences between right-left CP and right-left BA. These results suggest that current recommended average settings for semi-adjustable articulators for dentate individuals need to be reassessed.
Caseload Burdens and Jurisdictional Limitations: Some Observations from the History of the Federal Courts

This article examines the history of federal courts and the repeated efforts made over the centuries to reshape their jurisdiction to meet the press of continually growing caseloads. Identifying various methods used in the past to expand judicial capacities and restrict the influx of new cases, it addresses the fundamental normative question that should guide all efforts to reshape federal jurisdiction: What kinds of cases should the federal courts hear, and which kinds of cases should command the highest priority? The article argues that neither the Constitution nor any other authoritative legal source provide adequate answers to those questions. The challenge of meeting the problem of expanding caseloads is unavoidably political, it maintains, and all efforts at reform have been and will continue to be shaped largely by the nation’s evolving politics. The article draws on history to suggest some reasons to be hopeful about the possibilities for wise jurisdictional reform in the future, and it concludes by identifying the protection of individual rights against governmental actions as, in the words of Judge Jon O. Newman, the “pure gold” of the American judicial system and the most important function of the federal courts.
Prediction of Hydrodynamic Forces and Moments for Underwater Vehicles Using Overset Grids

This paper describes the addition of an overset mesh capability to existing twoand three-dimensional Reynolds-averaged Navier-Stokes (RANS) solvers that share a cellcentered, finite volume, structured multiblock formulation. The calculation and processing of the overset interpolations are handled by leveraging third-party software. Specifically, the cell-centered, overset interpolation stencils for the two-dimensional and three-dimensional grids are generated using a structured, unstructured and generalized overset grid assembler (SUGGAR). Overset grid compatibility is then added to the RANS solvers by incorporating a library to handle the donor interpolation receptor transactions (DiRTlib). The software for integrating the hydrodynamic forces and moments on overlapping surface grids is new, so much of the paper is devoted to the description of that method. The approach that is described generates a unique surface using ranked polygons (USURP). Finally, surface pressures and the predicted forces and moments are shown to be in good agreement with measurements for DARPA SUBOFF and with more recent measurements for various configurations of the ONR Body-1 submarine model.
Process modeling, joint virtual testing and construction of joint connectors for mechanical fastening by flow-drilling screws

In this work, a computational approach is proposed in order to help establish the effect of various flow-drilling screw process and material parameters on the quality and the mechanical performance of the resulting flow-drilling screw joints. Toward that end, a sequence of three distinct computational analyses is developed. These analyses include the following: (a) finite element modeling and simulations of the flow-drilling screw process; (b) determination of the mechanical properties of the resulting flow-drilling screw joints through the use of three-dimensional, continuum finite element–based numerical simulations of various mechanical tests performed on the flow-drilling screw joints and (c) determination, parameterization and validation of the constitutive relations for the simplified flow-drilling screw connectors, using the results obtained in (b) and the available experimental results. The availability of such connectors is mandatory in large-scale computational analyses of whole-vehicle crash or...
Diagnostic Utility of the Social Skills Improvement System Performance Screening Guide

Researchers investigated the diagnostic utility of the Social Skills Improvement System: Performance Screening Guide (SSIS-PSG). Correlational, regression, receiver operating characteristic (ROC), and conditional probability analyses were run to compare ratings on the SSIS-PSG subscales of Prosocial Behavior, Reading Skills, and Math Skills, to report card grades for conduct, reading, and math, respectively. Respective subscales were all statistically significantly correlated with one another. In addition, all regressions indicated significant predictions for the SSIS-PSG to respective report card grades. ROC analyses for SSIS-PSG Math with math grades and SSIS-PSG Reading with reading grades were statistically significant and described as fair. ROC analysis for SSIS-PSG Prosocial Behavior with conduct grades was not significant and described as poor. In a conditional probability analysis, the variable of concern for screeners concerns false negative ratios; all estimates for this fell within the targeted...
CD63 is a component of Weibel-Palade bodies of human endothelial cells.

Weibel-Palade bodies are secretory granules of vascular endothelial cells specialized in the storage of von Willebrand factor (vWF) and P- selectin, two adhesion proteins that can be rapidly mobilized to the cell surface by exocytosis in response to thrombin or other agonists. In this study, we attempted to identify additional components of Weibel- Palade bodies by raising monoclonal antibodies to these granules, purified by cell fractionation. One antibody, 2C6, was found to be specific for CD63, a membrane glycoprotein previously described in the lysosomes of platelets and other cell types. The immunopurified 2C6 antigen was recognized by an anti-CD63 reference antibody, 2.28, by Western blotting. Also, the biosynthetic profile of the 2C6 antigen in endothelial cells showed a nascent molecular mass and a glycosylation pattern identical to that of CD63. Immunofluorescence staining with 2C6 showed the lysosomes, and also elongated structures identified as Weibel-Palade bodies by their shape, distribution, and positive staining with anti-vWF antibodies, CD63 was also found by Western blotting of subcellular fractions highly enriched in Weibel-Palade bodies. Our results indicate that CD63 colocalizes with vWF and P- selectin in the Weibel-Palade bodies of endothelial cells, and together with these adhesion proteins it could be rapidly expressed on the cell surface in areas of vascular injury and inflammation.