cssi/SciSciGPT-SciSciNet huggingface dataset:
Testing for Interaction in Two‐Way Random and Mixed Effects Models: The Fully Nonparametric Approach

Summary. In a recent paper, Gaugler and Akritas (unpublished manuscript) considered testing for no main effect in a two-factor mixed effects design when the traditional assumptions do not hold. Here we extend the nonparametric modeling to the random effects design and consider the problem of testing for no interaction effect. The new models for these designs allow for dependence among the random effects, heteroscedasticity in the error and interaction terms, and do not require normality. At a more systemic level, these models differ from the classical ones in that they do not consider the random interaction term as an additional, extraneous source of variability. The proposed test procedure applies to settings where the random factor in the case of the mixed model or at least one of the random factors in the case of the random effects model has many levels. The number of replications can be small and possibly unbalanced. Moreover, the model and test procedure are general enough to accommodate data missing at random (MAR), provided the missingness mechanism is the same for each level of the random effect. The limiting distribution of the test statistic is normal. Extensive simulations indicate that our test procedure, with or without missing data, maintains the nominal Type I error rate in all simulation settings. On the contrary, the standard procedures (the F -test of PROC GLM in SAS ,a nd theML and REML methods of PROC MIXED in SAS), as well as the exact F -test of Khuri, Mathew, and Sinha (1998 in Statistical Tests for Mixed Linear Models), are extremely liberal in heteroscedastic settings, while under homoscedasticity and normality, the proposed test procedure is comparable to them. An analysis of a dataset from the Mussel Watch Project is presented.
Thrust and Efficiency Optimization of a Harmonically Deforming Thin Airfoil for MAV Design

This article presents analytical and numerical approaches to optimizing thrust and thrust efficiency of a harmonically deforming thin airfoil. An unsteady aerodynamic model for a deforming thin airfoil undergoing harmonic oscillations has been developed previously. Here the thrust and efficiency functions are presented in a quadratic form in terms of the deformation design variables. A zero leading-edge suction constraint is developed which can be used to avoid leading edge separation in thin airfoils. Pareto fronts in terms of thrust magnitude and efficiency are generated showing optimum deformation conditions (magnitude and phase) at various reduced frequencies for various constraints.
Sentinel lymph node biopsy in staging of differentiated thyroid cancer: a critical review.

Abstract Sentinel lymph node biopsy has recently been utilized to map tumor lymphatics in patients with differentiated thyroid carcinoma. Currently, controversy centers around the feasibility and future role of this technique in the management of differentiated thyroid cancer patients. A review of the current literature in which sentinel lymph node biopsy was performed on patients with a diagnosis of differentiated thyroid cancer was undertaken. Sentinel lymph node biopsy has been carried out on thyroid cancer patients utilizing a vital dye technique, a radiotracer technique, and a combination of both techniques. In the current literature the average rate of sentinel node identification is 91% (range 66–100%) and when identified, the sentinel node accurately predicts the disease status of the neck in most patients (range 80–100%). Limitations to carrying out the sentinel node biopsy on thyroid cancer patients include staining of parathyroid glands, identification of lymph nodes draining into the mediastinum, and the ‘shine through' effect. Sentinel lymph node biopsy is technically feasible, but for a disease in which nodal metastases are of debatable prognostic value, the clinical utility of sentinel lymph node biopsy in the management of patients with differentiated thyroid cancer appears less than promising.
Vertebrate paleontology of the Cloverly Formation (Lower Cretaceous), I: faunal composition, biogeographic relationships, and sampling

ABSTRACT The vertebrate fauna of the Cloverly Formation has been studied for more than 75 years, but remains poorly sampled and incompletely understood. We undertook an extensive survey of the formation that resulted in the discovery of several new, highly productive vertebrate microfossil bonebeds (VMBs). Comprehensive sampling of these and other sites has nearly doubled the known vertebrate diversity of the Cloverly Formation. In addition to the comparatively well-known dinosaurs, this augmented faunal list includes hybodontoid sharks, numerous bony fishes, three lissamphibian lineages, lizards, multiple crocodylians, and several new mammal occurrences. The known Cloverly vertebrate fauna now more closely resembles those of other late Early Cretaceous formations in North America, indicating broad similarities across wide geographic areas at this time. In addition, this work underscores the important role VMBs can play in areas previously studied primarily through surface prospecting and quarrying, espec...
Total body irradiation with an arc and a gravity-oriented compensator.

Purpose To deliver uniform dose distributions for total-body irradiation (TBI) with an arc field and a gravity-oriented compensator. This technique allows the patient to be treated lying on the floor in a small treatment room. Methods and materials Through the sweeping motion of the gantry, a continuous arc field can deliver a large field to a patient lying on the floor. The dose profile, however, would not be uniform if no compensator were used, due to the effects of inverse square variation of beam intensity with distance as well as the slanted depth in patient. To solve this problem, a gravity-oriented compensator made of cerrobend alloy was designed. This compensator has a cross-section of an inverted isosceles triangle, with the apex always pointing downward, due to gravity. By properly selecting the thickness of the compensator, the width of the base, and the distance between the pivots to the base, the difference in the path length through the compensator can be made just right to compensate the effects of inverse-square and slanted depth, thus producing a uniform dose profile. Results Arc fields with a gravity-oriented compensator were used for 6, 10, 15, and 18 MV photon beams. The arc field can cover a patient with a height up to 180 cm. The field width was chosen from 32 to 40 cm at the machine isocenter. The optimal thickness of the compensator was found to be 2.5 cm, and its base was 25 cm wide. The distance from the pivot points to the flat surface of the compensator proximal to the beam ranges from 13 to 14 cm for different beam energies. The dose uniformity at a depth of 10 cm is within +/-5% for all beam energies used in this study. Conclusions Highly uniform dose profiles for TBI treatments can be delivered with an arc and a gravity-oriented compensator. The proposed technique is simple and versatile. A single compensator can be used for all energies, because the amount of compensation can be adjusted by changing the distance to the pivot and/or the field size.
Cellular localization of tissue kallikrein and kallistatin mRNAs in human kidney

Cellular localization of tissue kallikrein and kallistatin mRNAs in human kidney. The renal kallikrein-kinin system has been implicated in the regulation of blood pressure and sodium/water excretion. The activity of renal kallikrein is controlled by a number of factors in vivo . Kallistatin is a newly identified serine proteinase inhibitor (serpin) which binds to tissue kallikrein and inhibits its enzymatic activity in vitro . To understand the role of kallistatin in modulating tissue kallikrein's function in vivo , we examined the anatomical relationship between human tissue kallikrein and kallistatin in the kidney by in situ hybridization histochemistry. Tissue kallikrein and kallistatin gene transcripts were identified using digoxigenin-labeled riboprobes at the cellular level. Antisense and sense riboprobes corresponding to the 3′ region of the human kallikrein and kallistatin mRNAs were synthesized by in vitro transcription and used for hybridization. Using an antisense kallikrein riboprobe, sites of kallikrein synthesis were localized in the distal tubules, collecting ducts and Henle's loops of the kidney. To a lesser degree, juxtaglomerular cells were also stained. Kallistatin mRNA was found at the same sites where kallikrein mRNA was localized. The most intense signals of both kallikrein and kallistatin were seen in the distal tubules and collecting ducts. Hybridization was specific for the target mRNA since sense kallikrein or kallistatin riboprobe did not bind to the sections. Immunoreactive human renal kallikrein and kallistatin levels were measured in the kidney and urine by immunoassays using specific antibodies. Co-localization of kallikrein and kallistatin mRNA in the kidney suggests a potential role of kallistatin in regulating tissue kallikrein's function.
Relationship of changes in spontaneous motor activity to spontaneous circling in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra.

Abstract Two unilateral injections of 6-hydroxydopamine into the substantia nigra and ventral tegmental area of adult rats pretreated with desmethylimipramine produced severe unilateral depletions of limbic and striatal dopamine. These animals sustained global deficits in spontaneous motor activity with no recovery evident from 1 to 14 weeks postoperative. The frequency of spontaneous circling increased during the 1 st few weeks postoperative and then remained stable during the last 2 months of observation. The changes in circling were independent of changes in global spontaneous motor behaviors. Biochemical determinations indicated an increased dopamine turnover in residual limbic and striatal dopamine neurons but with substantially changed dihydroxyphenylacetic acid:homovanillic acid ratios. The absence of functional recovery of both normal and asymmetric motoric behavior indicates that severe uncompensated deficits in motoric function produced by unilateral 6-hydroxydopamine lesions can provide a useful animal model for the study of dopaminergic contributions to movement disorders.
Seismic risk mitigation of building structures: The role of risk aversion

ABSTRACT Risk mitigation decisions for civil infrastructure exposed to rare natural and manmade hazards are often impacted by risk aversion, a behavioral phenomenon in which the decision maker's perception and judgment of risk are systematically distorted, resulting in decisions that might be viewed as excessively conservative when compared to those from a traditional minimum expected cost analysis. Risk aversion is believed to be especially significant if the decision maker is confronted with a low-probability event with catastrophic consequences. Most consequence-based decision models, including those based on minimum expected lifecycle cost, have supported engineering decisions in many contexts but address the influence of risk perception on those decisions only to a limited degree. This study is aimed at exploring how decisions regarding structural safety are affected by the attitudes of the decision-maker toward risk using decision models, such as cumulative prospect theory, that allow risk-averse behaviors to be modeled. The nature of risk aversion is highlighted through two examples, the first involving seismic retrofit and the second related to aseismic design of a frame.
Fecal and Urinary Excretion of Six Iodothyronines in the Rat

Fecal and urinary excretion rates of six iodothyronines were assessed in the rat maintained under normal steady state physiological conditions, to gain a more comprehensive understanding of the mechanisms of control of normal thryoid hormone economy and metabolism. Groups of young adult male rats were injected with trace doses of T4, T3, rT3, 3,3′-diiodothyronine (T2), 3′,5′-T2, or 3′-monoiodothyronine, each labeled with 125I, and feces and urine were collected separately for up to 10 days. Pooled fecal pellets were homogenized in saline, extracted in ethanol, evaporated under vacuum, and reconstituted in NaOH. Fecal extracts and urine were chromatographed on Sephadex G25 columns under conditions providing quantitative separations of components of interest. A new technique was also developed, based on a model of the in vitro extraction and measurement process, to correct chromatographic results for possible variable recoveries and possible artifactious degradation of radioactively labeled components. No i...
GVL for ATL

In this issue of Blood , Itonaga and colleagues report the outcomes of and discuss treatment options for patients with relapse of adult T-cell leukemia (ATL) after allogeneic hematopoietic stem cell transplantation (HSCT). Their findings suggest an association of postrelapse induction of a graft-
Casimir effects: an optical approach I. Foundations and examples

Abstract We present the foundations of a new approach to the Casimir effect based on classical ray optics. We show that a very useful approximation to the Casimir force between arbitrarily shaped smooth conductors can be obtained from knowledge of the paths of light rays that originate at points between these bodies and close on themselves. Although an approximation, the optical method is exact for flat bodies, and is surprisingly accurate and versatile. In this paper we present a self-contained derivation of our approximation, discuss its range of validity and possible improvements, and work out three examples in detail. The results are in excellent agreement with recent precise numerical analysis for the experimentally interesting configuration of a sphere opposite an infinite plane.
Techniques for Matching Laser TEM(00) Mode to Obscured Circular Aperture.

The performance of an optical telescope system with a centrally obscured aperture illuminated by a laser operated in the TEM00 mode is analyzed in terms of antenna gain. This permits calculation of power budgets for optical radar and communication systems by substitution into the microwave range equations in common use. Practical techniques for increasing the antenna gain using conical axicons and aspheric lenses are presented. For example, if 0.25 of the aperture area is obscured, increases in the antenna gain of two times have been obtained using a conical axicon. The analysis also indicates that this approaches the maximum theoretical gain obtainable from an obscured aperture. The optimum method of interfacing the laser output with the obscured optical system and experimental results are also presented.
Growth, photosynthesis, nitrogen fixation and carbohydrate production by a unicellular cyanobacterium, Synechococcus sp. (Cyanophyta)

A polymer-producing strain of unicellular cyanobacteria, Synechococcus sp., was isolated from a coastal lagoon in Florida. This strain, designated BG0011, excreted a highly viscous polysaccharide. Maximum observed growth rates for BG0011 were 2.5 div. day-2. BG0011 also exhibited nitrogen fixation (nitrogenase) activity under aerobic conditions and grew at near maximum rates in medium lacking reduced nitrogen. Growth and carbohydrate production were enhanced by carbon dioxide enrichment. Rheological study of the extracellular polysaccharide revealed a viscosity versus shear rate curve similar in shape to that of xanthan gum. Maximum observed rate of carbohydrate production was 1 g dry weight liter-1 month-1.
Biological Effects of Power-Frequency Fields As They Relate to Carcinogenesis:

There is a widespread public perception that exposure to electricity is linked to cancer. The public concern stems largely from epidemiological studies which appear to show a relationship between cancer incidence and exposure to power-frequency electromagnetic fields. This review will discuss the biophysics of power-frequency electromagnetic fields as it relates to biological effects, summarize the current state of the cancer epidemiology, and then concentrate on the laboratory studies that are relevant to addressing the possibility that power-frequency fields are carcinogenic. Review of the epidemiological evidence shows that the association between exposure to power-frequency fields and cancer is weak and inconsistent, and generally fails to show a dose-response relationship. The laboratory studies of power-frequency fields show little evidence of the type of effects on cells or animals that point towards power-frequency fields causing or contributing to cancer. Finally, from what is known about the biophysics of power-frequency fields, there is no reason to even suspect that they would cause or contribute to cancer. Application of "Hill's criteria" to epidemiological and laboratory studies shows that the evidence for a causal association between exposure to power-frequency fields and the incidence of cancer is weak.
Structural and Biochemical Analysis of the Obg GTP Binding Protein

The Obg nucleotide binding protein family has been implicated in stress response, chromosome partitioning, replication initiation, mycelium development, and sporulation. Obg proteins are among a large group of GTP binding proteins conserved from bacteria to man. Members of the family contain two equally and highly conserved domains, a C-terminal GTP binding domain and an N-terminal glycine-rich domain. Structural analysis of Bacillus subtilis Obg revealed respective domain architectures and how they are coupled through the putative switch elements of the C-terminal GTPase domain in apo and nucleotide-bound configurations. Biochemical analysis of bacterial and human Obg proteins combined with the structural observation of the ppGpp nucleotide within the Obg active sight suggest a potential role for ppGpp modulation of Obg function in B. subtilis.
Structural properties of vapor deposited silicon nitride

Some of the chemical and physical properties of silicon nitride films have been studied to determine the effects of deposition process variables and wafer preparation prior to deposition. The boat temperature and the reaction gas mixture were changed to optimize the quality of the silicon nitride films. This resulted in amorphous films free of pinholes, cracks, and impurities, together with good electrical properties such as an effective barrier against sodium ions and a low fast and fixed surface state density. Most of the work has been done on silicon nitride deposited over silicon dioxide films or silicon dioxide steps on a siliconsubstrate. The silane-ammonia and the silicon tetrachloride-ammonia reactions resulted in silicon nitride of comparable physical and chemical properties. Cleaning procedures are most effective if they include an etching step to take off 50 to 100A of the oxide prior to nitride deposition. The influence of subsequent heat treatments (up to 1200°C) on cracking and etch rates of the silicon nitride films has been studied. Films thicker than 2000A deposited over oxide steps were found to crack after heat treatments above 1000°C. Films in the lower thickness range of 500 to 1000A are most suitable because they have good resistance against cracking after heat treatments up to 1200°C, do not need excessively long etch times, and are still an excellent barrier against a heavy sodium contamination applied at 535°C.
Development of an intelligent knowledge base for heat stress evaluation

An intelligent knowledge base system for heat stress evaluation is described. The evaluation of heat stress is a particularly difficult problem, utilizing a variety of sometimes contradictory heat stress indices, and thus is naturally suited for computer aided design. The present system uses an expert system approach and can be used either as a stand along design tool or as one of the lower level models for larger ergonomic expert systems such as ALFIE. Simulations of a variety of environmental conditions were performed. A large diversity in predictive capabilities was found, depending on the assumptions used for each component index. For maximum efficiency with novice users, further explanations and on-line assistance need to be implemented within the system.
Plasma triglycerides predict incident albuminuria and progression of coronary artery calcification in adults with type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes Study.

Background Coronary artery disease and diabetic nephropathy, which are thought to share pathogenic mechanisms, remain the most common causes of mortality in type 1 diabetes (T1D). Data from basic and clinical studies indicate that hypertriglyceridemia plays an important role in the pathogenesis of vascular complications, but the role of triglycerides (TG) in the normal range remains unresolved in T1D. Objective We hypothesized that fasting TG would independently predict cardiorenal disease in adults with T1D and normal-to-low levels of TG. Methods Subjects (N = 652) were 19 to 56 years old at baseline and reexamined 6 years later. Urinary albumin excretion was measured, and categorized as microalbuminuria or greater. Progression of coronary artery calcification (CACp), measured using electron beam computed tomography, was defined as a change in the square root transformed CAC volume ≥2.5. The association of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, non–HDL-C, natural log triglyceride (lnTG), ln(TG/HDL-C) ratio with CACp and incident albuminuria were examined in logistic regression. The models were adjusted for age, sex, T1D duration, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, blood pressure medications, statins, and smoking status. Integrated discrimination index and net reclassification improvement were used to examine prediction performance. Results Incident albuminuria was independently associated with CACp. lnTG independently predicted both incident albuminuria (odds ratio: 1.53, 1.02–2.30, P = .04) and CACp (1.41, 1.11–1.80, P = .006). The addition of lnTG to ABC risk factors (HbA1c, systolic blood pressure, diastolic blood pressure, and LDL-C) moderately improved discrimination and reclassification of CACp and incident albuminuria. Conclusion In adults with T1D, fasting TG independently predicted cardiorenal disease over 6 years and improved reclassification of risk by conventional risk factors.
Comparison of optic afferents to primary visual and polysensory areas of cat neocortex

Abstract Optic projections to cortical polysensory areas were examined in cats anesthetized with chloralose. Photically evoked responses in polysensory areas persisted after removal of diencephalon exclusive of the lateral geniculate body (LGB), and ablation of visual cortex. Electrical stimulation of optic nerve, tract or radiations elicited long-latency responses from the same cortical areas. The long delay of the electrically elicited responses appeared to occur between LGB and cerebral cortex, but not within cortex. Thresholds of responses in polysensory areas to optic tract stimulation were higher than those in visual cortex. Photically evoked responses in polysensory areas were either unaffected or potentiated by tetanization of optic nerve or tract at voltages sufficient to depress responses in visual cortex. Responses in polysensory areas were more resistant to retinal hypoxia than those in visual cortex. Exploration of the visual field with punctiform photic stimuli revealed that stimulation of central retina was more effective than peripheral, for eliciting responses in polysensory areas. The data suggest a system of small fibers in optic nerve, tract and radiations, mediating optic input to polysensory areas. This system would be relatively independent of the primary visual system.
Novel approaches to inhibitor design for the p110β phosphoinositide 3-kinase

Phosphoinositide (PI) 3-kinases are essential regulators of cellular proliferation, survival, metabolism, and motility that are frequently dysregulated in human disease. The design of inhibitors to target the PI 3-kinase/mTOR pathway is a major area of investigation by both academic laboratories and the pharmaceutical industry. This review focuses on the Class IA PI 3-kinase p110β, which plays a unique role in thrombogenesis and in the growth of tumors with deletion or loss-of-function mutation of the Phosphatase and Tensin Homolog (PTEN) lipid phosphatase. Several p110β-selective inhibitors that target the ATP-binding site in the kinase domain have been identified. However, recent discoveries regarding the regulatory mechanisms that control p110β activity suggest alternative strategies by which to disrupt signaling by this PI 3-kinase isoform. This review summarizes the current status of p110β-specific inhibitors and discusses how these new insights into p110 regulation might be used to devise novel pharmacological inhibitors.
Transfer matrix spectrum for the finite-width Ising model with adjustable boundary conditions: Exact solution

Using the spinor approach, we calculate exactly the complete spectrum of the transfer matrix for the finite-width, planar Ising model with adjustable boundary conditions. Specifically, in order to control the boundary conditions, we consider an Ising model wrapped around the cylinder, and introduce along the axis a “seam” of defect bonds of variable strength. Depending on the boundary conditions used, the mass gap is found to vanish algebraically or exponentially with the size of the system. These results are compared with recent numerical simulations, and with random-walk and capillary-wave arguments.
Molecular underpinnings of Aprataxin RNA/DNA deadenylase function and dysfunction in neurological disease.

Abstract Eukaryotic DNA ligases seal DNA breaks in the final step of DNA replication and repair transactions via a three-step reaction mechanism that can abort if DNA ligases encounter modified DNA termini, such as the products and repair intermediates of DNA oxidation, alkylation, or the aberrant incorporation of ribonucleotides into genomic DNA. Such abortive DNA ligation reactions act as molecular checkpoint for DNA damage and create 5′-adenylated nucleic acid termini in the context of DNA and RNA-DNA substrates in DNA single strand break repair (SSBR) and ribonucleotide excision repair (RER). Aprataxin (APTX), a protein altered in the heritable neurological disorder Ataxia with Oculomotor Apraxia 1 (AOA1), acts as a DNA ligase “proofreader” to directly reverse AMP-modified nucleic acid termini in DNA- and RNA-DNA damage responses. Herein, we survey APTX function and the emerging cell biological, structural and biochemical data that has established a molecular foundation for understanding the APTX mediated deadenylation reaction, and is providing insights into the molecular bases of APTX deficiency in AOA1.
Effect of Azithromycin on Lipid Accumulation in Immortalized Human Meibomian Gland Epithelial Cells

Meibomian gland dysfunction (MGD) is believed to be the leading cause of dry eye disease (DED), which afflicts tens of millions Americans (1). Of particular interest, the most common pharmaceutical treatment for the management of MGD in the United Statesis the off-label use of topical azithromycin (2). This macrolide antibiotic is presumed to be effective because of its anti-inflammatory and anti-bacterial actions, which may suppress the MGD-associated posterior blepharitis and growth of lid bacteria (3). However, there are no published, peer-reviewed data demonstrating that azithromycin has the ability to act directly on the human meibomian gland to enhance this tissue’s function, and to ameliorate the pathophysiology of MGD. We hypothesize that azithromycin can act directly on human meibomian gland epithelial cells to stimulate their differentiation, enhance the quality and quantity of their lipid production, and promote their holocrine secretion. Our purpose was to begin to test our hypothesis.
Vegetation along hydrologic, edaphic, and geochemical gradients in a high-elevation poor fen in Canaan Valley, West Virginia

Wetland plant community composition and pattern are regulated by a host of abiotic/environmental gradients and biotic factors. We used multivariate analyses to classify wetland plant communities and determine the relation of hydrologic, edaphic, and geochemical gradients on community composition and spatial distribution among 18 vegetation, hydrology, and soil sampling points in Abe Run, a botanically unique poor fen in northeastern West Virginia. We also examined the interactions of disturbance with the physical environment and species composition. A total of 179 vascular plant species were identified from sample plots. Vegetative composition and structure, dominant soil texture, and hydrology lacked the distinct concentric zonation of northern peatlands; instead, all were patchy and varied considerably over short distances. Graminoid-forb meadows with primarily silt-loam mineral horizons, greater depth to groundwater, and fewer days of inundation characterized the lower reaches of the wetland. These plots were more acidic, with absent or shallow O horizons, and lower concentrations of soil base cations (Ca, Mg, K). In the upper reaches of the wetland, mixed herb-shrub-tree dominated communities were structurally and compositionally more complex; here, organic horizons were much more prominent, peat depth ranged from 80 to 100 cm, and the average depth to water table was 10 cm less than for wells in the lower reaches of the wetland. Plots from upper transects (3–6) tended to have more shrub and tree cover, and higher concentrations of soil base cations. Much of the variability among plots in the upper and lower reaches of the wetland are consistent with beaver inundation of a large portion of the wetland during the 1980s. Multiple-response permutation procedures verified the difference (P < 0.0001) between vegetation of plots in the lower and upper reaches of the watershed. Because fens are connected to groundwater, these habitats are particularly vulnerable to disturbances, particularly those that alter existing land use and land cover. Minimization of disturbances in the surrounding watershed, controls on an excessive deer population, removal of exotic, non-native species, and control on foot traffic are all integral to maintaining the integrity of this high-value wetland.
AUTONOMOUS DEVELOPMENTAL CONTROL OF HUMAN EMBRYONIC GLOBIN GENE SWITCHING IN TRANSGENIC MICE

The mechanisms by which expression of the beta-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (epsilon) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human epsilon-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human epsilon-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of epsilon gene expression in definitive erythroid cells suggests that the developmental regulation of the epsilon-globin gene depends only on the presence of the LCR and the epsilon-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of epsilon-globin gene developmental control distinguishes it from the competitive mechanism of regulation of gamma and beta-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.
Size and rate of growth of crystals on aluminium oxide films

The sizes of crystals on aluminium oxide films formed by exposing commercial aluminium (2S) and two nickel- and iron-containing alloys to pure water at high temperature were determined by measuring and counting crystals on electron micrographs of surface replicas. The mean crystal size was determined for eight different times at five temperatures over the range 150–350°. The increase in crystal size followed a law of the type D = Ain and the values of n found were in the range 0.18–0.26. The size distributions for various times at 300° and for various temperatures after 7 h. of exposure are discussed.
Methodology for bounding calculations of nuclear criticality of fissile material accumulations external to a waste container at Yucca Mountain, Nevada

Abstract The possibility of nuclear criticality, however remote, in the vicinity of the proposed repository at Yucca Mountain, Nevada generates justified concerns and may impact the performance of the repository. A heuristic approach is presented here for determining the amount, spatial distribution and other characteristics of fissile material accumulation in the rock beneath a waste package that could contribute to such an event. This study is concerned primarily with waste packages containing special spent fuel from the Department of Energy and high-level nuclear waste glass. Mixing with less alkaline waters and the subsequent drop in pH is the mechanism that is most efficient for precipitating fissile material from the waste package internal leachate, in contrast to natural deposits in which redox changes are the main precipitation driver. External accumulation size is determined by (1) computing the chemical composition of the leachate leaving a package as its internal materials degrade (with the batch geochemical code EQ3/6), (2) determining precipitation of fissile material into mineral phases (using the 1D geochemical code PHREEQC) as the effluent mixes with percolation water, and (3) heuristically scaling results to a 3D volume and computing the criticality coefficient (using the code MCNP). Loci for accumulation are the multiple lithophysal cavities and the fracture system. A bounding conservative approach is used by necessity in Step 3. Nuclear criticality is sensitive to small variations in the distribution of fissile material and parameters of natural systems vary by orders of magnitude. Because the most likely combinations of parameters are not conducive to nuclear criticality, this study focuses on extreme values of parameter probabilistic distributions, such as limited flow into the package associated with a large percolation rate, combinations of material degradation rates favoring actinide release, and very high host-rock porosity values. By considering these combinations, most favorable to criticality but unlikely, it was concluded that external nuclear criticality is not a concern at the proposed repository.
The Mechanism of Hydrotrope Action of a Dicarboxylic Acid

Abstract The mechanism of the hydrotrope action of a dicarboxylic acid monosoap was investigated by determination of the change in order parameter of the amphiphile in a lamellar liquid crystal. The results showed addition of the hydrotrope considerably to reduce the order while addition of a surfactant had no effect.
Report of a Meeting; Molecular Basis of Cancer Therapy

There has been an explosive increase in information relevant to the pathways that determine growth signal transduction, regulation of the cell cycle, mechanism of action of oncogenes and tumor suppressors, and mechanisms of programmed cell death (apoptosis). Additional information is needed to determine the targets for anticancer therapy that are most likely to lead to cancer cell death and/or growth cessation. Current experimental clinical approaches are directed toward killing cells with unique cancer-related phenotypes, such as cell surface antigens or growth factor receptors, or altering the host immune system to attack cancer cells. The following major therapeutic targets were identified during the course of this conference: 1) Reduce activity of gene products associated with stimulation of cell growth and increase activity of gene products that inhibit growth. The major principle here is that genes known to be sufficient for malignant transformation (such as Ras, Raf, and Bcr-Abl) and genes whose expression is necessary, but not sufficient, for malignant transformation (such as some cyclins) both may be important targets for anticancer drugs. The reason genes necessary but not sufficient for cell growth are targets is that progression through the cell cycle is based on a series of "on-off" switches whose activation depends on critical levels of specific kinases and phosphatases. Subtle differences in concentration or activity of these regulators, as may be found in cancer cells, could profoundly influence the position of the switch. There are many ways to affect activity of gene products, including use of anti-sense or ribozyme targeting of mRNAs; manipulation of regulatory controls (i.e., state of phosphorylation of Raf and p53; effect of SOS and GAP on Ras, etc.); alteration of essential covalent modifications (i.e., farnesylation of Ras which is essential for its association with the plasma membrane); and various forms of gene therapy to introduce genes (i.e., addition of wild-type p53) or to reduce activity of genes essential for growth (i.e., dominant negative receptor mutants). 2) Interfere with protein-protein or DNA-protein interactions that are needed for the activity of oncogenes and/or growth factors or the transcription factors essential for cell growth. This approach has been demonstrated to work in vitro to interfere with SH2-tyrosine phosphate interactions (i.e., Grb-2 and EGF receptor) and Ras-Raf interactions using specific peptides (J. Downward), but to be useful therapeutically it must be possible to introduce stable low-molecular-weight drugs into cells to affect these interactions.(ABSTRACT TRUNCATED AT 400 WORDS)
Electrocatalytic oxygen reduction at polyoxometalate/Au-nanoparticle hybrid thin films formed by layer-by-layer deposition

Abstract We report the fabrication of stable Au nanoparticle/polyoxometallate modified glassy carbon electrodes using layer-by-layer (LbL) assembly. These hybrid films were formed by the sequential deposition of poly(diallyldimethylammonium) chloride (PDDA) stabilized Au-nanoparticles (NPs) and transition metal substituted POMs, and were employed as electrocatalysts for the oxygen reduction reaction (ORR). The LbL approach allows the film thickness, metal NP and POM to be varied systematically in order to optimize catalyst performance. Rotating electrode measurements were used to study ORR kinetics at a series of GC/{M-POM/Au-NP} n (M = Ru, Co, W) electrodes. POM co-catalysts containing more labile M–O bonds were found to be better ORR co-catalysts than POMs containing more stable M–O bonds.
Measurement and calculation of Josephson junction device inductances

We have measured the inductances of various structures used in Josephson junction devices and circuits by means of a novel differential inductance measurement technique. The structures measured include a single superconductor strip line, multisuperconductor strip lines, a single superconductor strip line crossing a ground plane hole, and two coupled superconductor strip lines crossing a ground plane hole. All measured inductances are compared with inductances calculated from various inductance formulas and two numerical inductance calculation programs. Very good agreements are found between the measured inductances and the calculated results for most cases.
Thermal Activation Energies and Peak Temperatures in Thermoluminescence of LiF (Mg, Ti) and CaF2:Mn at Low Temperatures

Low temperature thermoluminescence (TL) ofl LiF (TLD-100) and CaF2:Mn is studied. The TLD-100 is dosimetry grade LiF manufactured by Harshaw-Filtrol Partnership. It is believed that it contains about 200 ppm Mg and 7 ppm Ti as impurities. In each case the glow curve shows several peaks. Some of these peaks are quite strong and develop with dose. Others are weak. Kinetic parameters are calculated for the former using the initial rise method and Chen's modified formula. The two sets of values are found to be different. Some authors have suggested empirical formulae connecting peak temperature, Tm and activation energy, E. The empirical relations are tried for the values of E calculated, as well as those available in literature (for Tm above room temperature). It is found that a fairly reasonable relation existed between E and Tm. Niedertemperatur-Thermolumineszenz (TL) Von LiF (TLD-100) and CaF2:Mn wird untersucht. Das Material TLD-100 ist dosimetrisch reines LiF Von der Harshaw-Filtrol Partnership. Es wird angenommen, das es etwa 200 ppm Mg und 7 ppm Ti als Verunreinigungen enthalt. In jedem Falle enthalt die Glowkurve mehrere Maxima. Einige dieser Maxima sind ziemlich stark und ent-wickeln sich mit der Dosis. Andere sind schwach. Die kinetischen Parameter fur die ersteren werden mit der Anfangsanstiegsmethode und der modifizierten Formel Von Chen berechnet. Es wird ge-funden, das sich beide Wertsatze voneinander unterscheiden. Einige Autoren haben empirische Formeln vorgeschlagen, die die Maximumtemperatur Tm und die Aktivierungsenergie E verknup-fen. Es wird versucht, sowohl mit den empirischen Beziehungen E zu berechnen, als auch mit ande-ren aus der Literatur bekannten (fur TL oberhalb Zimmertemperatur). Es wird gefunden, das eine vernunftige Beziehung zwischen E und Tm existiert.
Unexpected μ-oxo five-member ring intermediates for oxygen atom transfer between osmium complexes

The reaction mechanisms for oxygen atom transfer between O = OsL3 and OsL3 with ligands of different sizes (L = NMe, NPh, Nmes, NAr) were studied by using density functional theory. In contrast to a previously proposed transition state with a linear Os–O–Os structure, an unexpected μ-oxo five-member diosmium ring with an N–N bonded structure is discovered as an intermediate for the transfer of oxygen. An isomeric five-member ring structure with an N–O bond is also found. Computational results indicate that the steric effects of bulky ligands play an important role in the geometry of dimetal complexes, and strongly affect the reaction kinetics.
Glutathione in fibroblasts from normal and cystinotic children

Abstract Intracellular levels of GSH and GSSG were compared in fibroblasts initiated from skin biopsies from normals and cystinotics. The concentration of GSH was essentially the same in both cell lines. However, the intracellular GSSG in cystinotic cells averaged less than half of that in normal cells. The ratio of intracellular GSH:GSSG was 10.6 in cells from cystinotics as compared with 4.7 in cells from normals. A significant distortion in the ratio of GSH:GSSG serves as another marker of the derangement of sulfur-amino acid metabolism in cystinosis. Whether this effect is primary or secondary remains to be elucidated.
Effectiveness of exercise versus normal activity on acute low back pain: an integrative synthesis and meta-analysis.

Abstract There are a variety of protocols used to treat acute low back pain in adults. Therapies currently prescribed include bed rest, normal activity, and exercise therapy. The effectiveness of each of these treatments is controversial. The purpose of this study is to compare the effectiveness of exercise therapy with normal activity in the treatment of employed adults with acute low back pain through an integrative synthesis and meta-analysis of published research. The integrative synthesis and meta-analytical results support the hypothesis that employed adults diagnosed with acute low back pain will have fewer number of days absent from work after exercise therapy when compared to number of days absent from work after normal activity. This study's weighted P is 0.0000003109. The weighted effect size D is 0.4785 and this is a strong effect of exercise on number of days absent from work. This study concluded that exercise therapy should be prescribed for the treatment of adults with acute low back pain to expedite recovery. The results of this study allow the health care provider to confidently prescribe exercise therapy for acute low back pain. This study can be used to support exercise therapy as an evidence based care protocol for health care providers.
Specificity of IHS Criteria in Childhood Headache

We prospectively assessed the relative specificity of the International Headache Society (IHS) criteria in 30 children referred to a pediatric neurologist. An important cause of headache, including raised intracranial pressure with slit ventricle syndrome, would have been missed in 4 children if one had relied on IHS criteria alone. Specific revisions have been proposed to minimize misclassification and further enhance the relevance of the IHS document for children.
Molecular mechanics (MM3) study of the lactones of endo‐bicyclo[2.2.2]oct‐5‐ene‐2‐carboxylic acid

endo-Bicyclo[2.2.2]oct-5-ene-2-carboxylic acid, in acidic solution, cyclizes to give a mixture of three isomeric lactones. These three isomers have different stabilities and are partly interconvertible, but their simultaneous decomposition makes the experimental study of these equilibria difficult. In the present work, these three lactones were studied using MM3. The relationship between the O—C(O)—C bond angles and the CO stretching frequencies of these compounds was investigated. Based partly on the thermodynamic data calculated by MM3, the mechanism of the interconversion of the three lactones was proposed. Copyright © 1999 John Wiley & Sons, Ltd.
The Effect of Functional Knee Bracing on the Anterior Cruciate Ligament in the Weightbearing and Nonweightbearing Knee

We investigated the effect of functional bracing on anterior cruciate ligament strain in humans by arthroscopic implantation of a differential variable reluctance transducer on the ligament and measurement of its strain behavior. Strains were measured while "injury mechanism" loads were applied to the weightbearing and nonweightbearing knees for both braced and unbraced conditions. For the unbraced knee, there was a significant increase in ligament strain values when subjects went from a seated position (minimal shear and compressive loads across the knee) to a standing posture (substantial shear and compressive loads across the knee). Similar strain values were found between these same seated and standing postures when a 140-N anterior-directed load was applied to the tibia. This indicates that the ligament is strained during weightbearing and demonstrates that the compressive load across the knee produced during weightbearing does not significantly reduce ligament strain values in comparison with the unweighted joint with relaxed muscles for the 140-N load limit of our anterior shear test. Bracing produced a protective effect on the ligament by significantly reducing the strain values for anterior-directed loading of the tibia up to 140 N with the knee in both weightbearing and nonweightbearing conditions. Likewise, bracing produced a protective effect on the ligament by significantly reducing strain values in response to internal-external torque of the tibia up to 6 N-m with the knee nonweightbearing. The brace strap that contacts the tibia just distal to the insertion of the patellar tendon was instrumented with a load sensor, allowing us to measure the posterior-directed loads applied by the brace to the tibia. Adjustment of strap tension between low and high settings did not modulate the protective effect of the brace on the ligament.
An infinite dimensional quadratic theory for linear delay systems

A quadratic optimal control theory is presented for linear delay systems which are represented by "infinite dimensional" linear differential difference equations. The closed-loop optimal control is given by use of a feedback operator obtained from solving a linear Fredholm integral equation.
Wildfires increasing in size and frequency across the U.S. West

Since 1984, wildfires have increased in size and frequency, correlating with higher drought severity across the western United States. Dennison et al. looked at remotely sensed data from the U.S. government's Monitoring Trends in Burn Severity project from the years 1984−2011, focusing on fires larger than 400 hectares in nine ecoregions that included mountains, plains, and deserts. The authors found that not only are wildfires becoming more frequent—by an estimated seven large fires per year—but they are also burning more total area, increasing by about 355 square kilometers per year.