cssi/SciSciGPT-SciSciNet huggingface dataset:
Facilitating Chromophore Formation of Engineered Ca2+ Binding Green Fluorescent Proteins

Abstract Green fluorescent protein (GFP) containing a self-coded chromophore has been applied in protein trafficking and folding, gene expression, and as sensors in living cells. While the “cycle3” mutation denoted as C3 mutation (F99S/M153T/V163A) offers the ability to increase GFP fluorescence at 37 °C, it is not clear whether such mutations will also be able to assist the folding and formation of the chromophore upon the addition of metal ion binding sites. Here, we investigate in both bacterial and mammalian systems, the effect of C2 (M153T/V163A) and C3 (F99S/M153T/V163A) mutations on the folding of enhanced GFP (EGFP, includes F64L/S65T) and its variants engineered with two types of Ca2+ binding sites: (1) a designed discontinuous Ca2+ binding site and (2) a grafted continuous Ca2+ binding motif. We show that, for the constructed EGFP variants, the C2 mutation is sufficient to facilitate the production of fluorescence in both bacterial and mammalian cells. Further addition of the mutation F99S decreases the folding efficiency of these variants although a similar effect is not detectable for EGFP, likely due to the already greatly enhanced mutation F64L/S65T from the original GFP, which hastens the chromophore formation. The extinction coefficient and quantum yield of purified proteins of each construct were also examined to compare the effects of both C2 and C3 mutations on protein spectroscopic properties. Our quantitative analyses of the effect of C2 and C3 mutations on the folding and formation of GFP chromophore that undergoes different folding trajectories in bacterial versus mammalian cells provide insights into the development of fluorescent protein-based analytical sensors.
The sensitivity of contrast echocardiography in detecting intracardiac shunts

While contrast echocardiography has been shown to delineate intracardiac shunts, no information is available concerning the sensitivity of the method. This study establishes the relative sensitivity of the technique in detecting and localizing shunts by comparing the contrast echocardiograms with the simultaneously recorded cardiogreen dye curves in 26 children during cardiac catheterization. The echocardiograms substantiated isolated intracardiac shunting as small as 5%. There were no false-positive or false-negative echocardiograms in patients with or without shunt defects. This report demonstrates the contrast echocardiographic technique to be extremely sensitive in detecting intracardiac communications. It reviews the diagnostic patterns necessary for diagnosis and proposes the technique as a sensitive, safe, and accurate alternate method of study in the cardiac catheterization laboratory.
An empirical investigation of the market duration of repossessed single‐family houses

Purpose – The purpose of this paper is to determine if lender experience in disposing of repossessed single‐family houses in the local market is significantly related to the probability a property will sell. In addition, other factors that are significantly related to the market duration of repossessed houses are identified.Design/methodology/approach – The Cox proportional hazard model is used to analyze transaction data for 2,099 single‐family houses in Dayton, Ohio. Title to each of these properties was obtained by lenders through foreclosure. The study period approximates the first three years of the subprime mortgage crisis in the USA: 2007‐2009.Findings – The marketing efforts of lenders with more local property disposition experience are found to be superior to the efforts of less experienced lenders. The results also indicate that the selling rate function increased over the study period, and there is seasonality in the data which is consistent with lenders attempting to limit holding costs.Resear...
A three-dimensional atmospheric radiative transfer model based on the discrete-ordinates method

Abstract A three-dimensional, radiative transfer model based on the discrete-ordinates method for application to atmospheric radiation and remote sensing is developed. The model has the capabilities to address one-, two- and three-dimensional rectangular parallelepiped geometries containing nonhomogeneous, absorbing, emitting, anisotropically scattering media. Various boundary conditions including collimated and isotropic radiant sources are incorporated in the model. Where possible, the model takes advantage of symmetric and periodic boundary conditions to reduce the size of the solution domain. The model yields the radiant intensity field as a function of spatial location and direction within the solution domain and for any outward going direction. The model is extensively validated for one-, two- and three-dimensional geometries. The validation is performed through comparison of results from the model against those in the literature. Broken-cloud intensity fields are presented to demonstrate the capabilities of the model.
Female workers' acceptance in traditionally male-dominated blue-collar jobs

This study examined possible differential treatment by and negative attitudes of civilian male co-workers and male supervisors toward civilian female workers in traditionally male-dominated blue-collar jobs. Surveys were completed by 53 male supervisors and 327 male co-workers of four departments of a large government agency. Male supervisors indicated they would not treat female employees differently than they have treated male employees. Male co-workers, however, reported they have treated other male co-workers more favorably than they would treat female co-workers. In addition, supervisors, compared with male co-workers, reported more favorable attitudes toward female workers.
Isolation and partial characterisation of a xyloglucan from the cell walls of Phaseolus coccineus

Abstract Cell-wall material from Phaseolus coccineus was fractionated by successive extraction with aqueous inorganic solvents. From the 4 m KOH-soluble fraction, a polymer composed of l -arabinose (4.2%), l -fucose (6.0%), d -galactose (9.3%), d -xylose (34.1%), and d -glucose (46.4%) was isolated and purified by ion-exchange and cellulose column chromatography; the product was homogeneous by moving-boundary electrophoresis and ultracentrifugation. The S20,wo and Dobs were 2.92 S and 1.7 × 10−7, respectively, and the molecular weight was ∼110,000. Methylation analysis suggested a (1→4)-linked glucan backbone with ∼3 out of 4 glucosyl residues substituted through O-6 with xylose or oligosaccharides terminating in galactose, fucose, and arabinose. Limited acetolysis gave several di- and tri-saccharide derivatives of which four [ d -Galp-(1→2)- d -Xylp, d -Glcp-(1→4)- d -Glcp, l -Fucp-(1→2)- d -Galp-(1→2)- d -Xylp, and d -Glcp-(1→4)- d -Glcp-(1→4)- d -Glcp] were tentatively identified. Specific glycosidases were used to determine the configuration of the glycosidic linkages. The backbone was shown to be a (1→4)-β- d -glucan and the l -fucosyl groups were α. Neither α- nor β- d -galactosidase removed d -galactose. The structure of the xyloglucan is discussed in relation to other cell-wall polymers, especially cellulose.
IPSILATERAL URETEROURETEROSTOMY FOR SINGLE URETERAL REFLUX OR OBSTRUCTION IN A DUPLICATE SYSTEM

AbstractPurpose: The traditional treatment for obstruction or reflux involving a single ureter in a duplicated system has been common sheath reimplantation. More recently, ipsilateral ureteroureterostomy has been suggested as an alternative treatment. We reviewed cases with duplicate systems that were treated with ipsilateral ureteroureterostomy at our institution to determine the acceptability of this operation as an alternative to common sheath reimplantation.Materials and Methods: A total of 22 patients with 24 duplicate systems underwent ipsilateral ureteroureterostomy between March 1986 and December 1996. Patient charts were reviewed and analyzed for patient age, sex, ureteral and renal anatomy, initial presentation, the clinical situation necessitating operation, and the occurrence of early and late complications. Patients were followed for a mean period of 41.4 months.Results: Two adults and 20 children 10 years old or younger presented with urinary tract infection (13), hydronephrosis on maternal ...
Geometric and electronic structure of epitaxial NbxTi1−xO2 on TiO2(110)

Abstract We have investigated the detailed geometric and electronic structure of MBE-grown Nb x Ti 1− x O 2 on TiO 2 (110) by means of high-resolution transmission electron microscopy, X-ray photoelectron diffraction, ultraviolet and X-ray photoemission and electron energy loss spectroscopy. We find no measurable change in the NbO bond length relative to that for TiO bonds in TiO 2 in the dilute limit ( x = 0.05), and that the epitaxial layers remain strained and coherent with the substrate for x ⩽ ≈ 0.3. However, significant dislocation generation occurs for x > ≈ 0.3. Nb substitution for Ti in the lattice introduces an additional valence electron per atom. The resulting density of states falls in the valence band region, but no new state density occurs in the either the band gap or conduction band. This result is in contrast to what occurs in the very dilute limit (parts per thousand), where Nb electrons occupy a shallow donor level near the conduction band minimum. Based on the electron counting rule, the extra Nb electrons form a non-bonding band which is degenerate with the valence band. The significance of these results for enhanced thermal and photochemistry on Nb x Ti 1− x O 2 surfaces vis a vis TiO 2 is discussed.
Differential partitioning of tRNAs between micellar and aqueous phases: A convenient gel filtration method for separation of tRNAs

Partition coefficients (Kp) of phenylalanine, glutamic acid-II and tyrosine tRNAs between water and micellar cetyltrimethylammonium chloride (CTACl) have been determined to be 5600, 520 and 3100, respectively, by gel filtration on Sephadex G-100-120. Equations for obtaining Kp values from quantitative gel filtration have also been derived. The use of this method for the separation of tRNAs is demonstrated.
The analysis and interpretation of cognitive interviews for instrument development

Cognitive interviews assess respondents' understanding of questionnaire items and are increasingly used to improve instrument design. Although investigators have described the contributions of cognitive interviews for instrument development, few guidelines are available for analyzing data from cognitive interviews when they are used for that purpose. In this article we address the development and application of analytic strategies for summarizing, interpreting, and using data from cognitive interviews that were conducted during the process of creating a measure of parental management of childhood chronic conditions. We discuss the contribution of cognitive interviews to establishing content validity and address the importance of developing standardized guidelines for analyzing and interpreting cognitive interviews in order to maximize their usefulness for instrument development.
Why Field Measurements Differ from Model Estimates: Analysis Framework for Capacity and Level-of-Service Analysis of Unsignalized Intersections:

Several questions are considered relating to the variability between field measurements and model forecasts, with a focus on the need to moderate user expectations about this variability. Considered first are the degree of variability observed in field measurements of delay and the stochastic effects in delay estimates produced by microscopic simulation. Examined next are the structure of the models of two-way stop-controlled (TWSC) intersection capacity and delay and how this structure might cause differences between field measurements and model estimates. How much the end user can moderate these differences using backcalculations, observation, and calibration and a "correct" perspective for the end user regarding these differences and variability are also discussed. These questions are considered using data collected as part of the NCHRP project used to develop the TWSC intersection capacity and level-of-service procedures contained in the Highway Capacity Manual models.
Fractionation of synaptic membranes with sodium diatrizoate.

Abstract Synaptic membranes from rat brain cortex were obtained in high yield by a short procedure based on osmotic shock of synaptosomes (P 2 B fraction) followed by fractionation of the membranes on a discontinuous gradient of sodium diatrizoate. Four membrane fractions and the mitochondrial pellet were characterized by morphology, an eight-enzyme profile, serological activity, bungarotoxin binding, RNA content, and polypeptide composition determined by gradient slab-gel electrophoresis. The membrane fractions with lowest density had little or no contamination by microsomes, myelin, or mitochondria, and appeared to be predominantly of presynaptic origin.
Nanosized Au4Pd32(CO)28(PMe3)14 Containing a Highly Distorted Encapsulated Au4 Tetrahedron: Proposed Multi-Twinned Growth-Pattern from Two Deformed Au-Centered Double Icosahedral-Based Fragments*

As part of an extensive effort to synthesize a variety of nanosized gold–palladium carbonyl phosphine clusters, the neutral Au4Pd32(CO)28(PMe3)14 (1) was isolated and unambiguously characterized by low-temperature CCD X-ray diffraction and IR measurements. This nanosized Au4Pd32 cluster was prepared in low yields (<5%) from the room-temperature reaction of Pd10(CO)12(PMe3)6 (2) with Au(SMe2)Cl in THF/acetone. The heretofore unknown molecular geometry of 1 of pseudo-D2 (222) symmetry (without methyl substituents) may be viewed to arise from a relatively strong (Au–Au)-bonded linkage (2.64 A (av)) of two pentagonal-bipyramidal (μ5-Au)(μ5-Pd)Pd5 polyhedra; this generated 14-atom Au2Pd12 unit may be considered as a markedly deformed part of a 19-atom Au-centered double icosahedron without the inner pentagon (corresponding to five missing inner atoms). In turn, two Au2Pd12 units form a central composite-twinned Au4Pd22 kernel via vertex-fusion of two common Pd atoms along with additional formation of four Pd–Pd bonding, four Au–Pd bonding, and two weaker secondary Au–Au bonding interactions at 2.90 A (av) (versus the other two diagonal Au–Au nonbonding ones at 3.51 A (av)); this resulting Au4Pd22P8 kernel is augmented by the addition of two triangular Pd3P core-fragments and four exopolyhedral PdP groups to give the Au4Pd32P14 framework of 1. This cluster is stabilized by 28 bridging COs, of which 20 are doubly bridging and 8 triply bridging. The largest metal-core diameter of 1 along one pseudo C2 axis is 1.1 nm. This new type of multi-twinned metal cluster has direct relevance to both ligated and non-ligated (naked) non-crystalline metal nanoparticles, many of which possess multiple twinning and/or disorder.
Exploring a consensual instructional communication strategy with elder adult development

The ability of senior citizens to structure and deliver real life stories in an educational yet entertaining manner for elementary school children was of critical importance to the success of an applied intergenerational developmental project. Recognizing the importance of collaboration in the elder adult learning process, a consensual instructional communication strategy was employed to develop the storytelling skills of senior citizens. Elders were videotaped telling real‐life stories prior to and following four weeks of instruction. The behaviors and attitudes of the elders during instructional sessions, and the final reactions of the children, teachers, administrators, and elders, all provide evidence of a successful intergenerational project. The consensual instructional strategy was felt to have played a major role by all involved. Both observational and data‐based comparisons of performances prior to and following instruction indicated significant positive improvements in performance content, deliv...
Sonographic evaluation of knee cartilage defects implanted with preconditioned scaffolds.

OBJECTIVES The purpose of this study was to develop a novel method for creating an acellular bioactive scaffold, to prove its efficacy in vivo and in vitro for the augmentation of biological repair, and to confirm that sonographic microscopy is a viable modality for monitoring the healing process of osteochondral defects implanted with preconditioned bioactive scaffolds. METHODS Rabbit marrow stromal cells were retrovirally transduced with either bone morphogenetic protein 7 (BMP-7) or insulinlike growth factor 1 (IGF-1) genes, cultured for 9 weeks in nonwoven poly-L-lactic acid scaffolds, and then frozen and lyophilized. The knees were evaluated at 3, 6, and 12 weeks after surgery using 20-MHz ultrasound and then prepared for routine histologic analysis. B-scans of the extracellular matrix defects were compared to histologic results. RESULTS Control defects showed a void or a mixture of fibrocartilage tissue. Both types of scaffolds resulted in a higher percentage (both P< .001) of primarily hyaline cartilage tissue with intact articular surfaces. The osteochondral defects were clearly observed in each sonographic signature. There were no differences between images of scaffolds treated with IGF-1 or BMP-7. Extracellular matrix regrowth was found to closely parallel (R(2) = 0.968; P < .003) the histologic images. A 3-mm defect depth and a 2.5-mm scaffold thickness were measured on the sonograms, comparing well to actual dimensions. CONCLUSIONS There was a gradual increase in healing bordering the defects for the 3-, 6-, and 12-week samples. Also, we have shown that sonography can aid in monitoring implantation of preconditioned scaffolds in osteochondral defects and thus assessing the healing process and cartilage/bone quality.
Women with viral STIs face dilemmas in negotiating condom use and would like direct safe sex advice from clinicians

Commentary on: Cook C . ‘Nice girls don't’: women and the condom conundrum. J Clin Nurs 2012; 21 :535–43. The study highlights experiences of high-risk women in communicating condom use with their partners and discussing with healthcare providers the impact of a sexually transmitted infection (STI) on their intimate relationships. Clinicians’ views on the effective sexual health communication with their female patients were also examined. The study focused on women diagnosed with genital herpes simplex virus (HSV) and …
Computer Usage and Labour Regulation in India's Retail Sector

Abstract A recent survey of 1,948 retail stores in India conducted by the World Bank's Enterprise surveys shows that 19 per cent of all stores use computers. In the state of Kerala, the figure is as high as 40 per cent. Using this survey, we estimate the effect of computer usage on labour employment. Our findings show that this effect depends on the stringency of the underlying labour laws. Stricter labour laws magnify the labour displacing effect of computers significantly.
Heuristics in decision making

Heuristics are simple rules of thumbs for problem solving that follow a logic that is quite different from consequential logic. They have long been regarded, as an inferior technique for decision making that is the source of irrational decision behavior. Recently, decision making researchers have demonstrated that some heuristics are highly efficient and can compete with complex decision models in some application domains. This paper explores the different streams of research, summarizes the state of the art decision making model, and discusses its implications for complex decisions in engineering and technology management.
Differential Base Rate Training Influences Detection of Novel Targets in a Complex Visual Inspection Task

We studied the effects that multiple levels of signal probability (known as base rate) have on the transfer of learning in an airline luggage screening task. Participants (n = 33) were presented with three base rates during the acquisition (training) phase: 100%, 50%, or 20%; at transfer, all participants detected novel targets at a base rate of 20%. Performance was measured by hit rates, false alarm rates, sensitivities, and detection times. Results revealed that participants receiving higher base rates during training obtained higher hit rates at transfer compared to participants encountering lower base rates. However, increasing the training base rate also increased the incidence of false alarms, leading to a low overall level of sensitivity during transfer. Relatively higher base rates had mixed effects on response times. These results have implications for improving training modules for individuals in complex visual inspection tasks.
SOCIAL DIMENSIONS IN CERAMIC ANALYSIS: A case study from peripheral Tikal

This paper examines the evidence for status and wealth differentiation within the peripheral areas of Tikal, Guatemala, and intersite areas north and south of Tikal. Frequency counts of differing major shape classes show that large groups had significantly higher frequency of serving forms and more associated pottery. The technique of multidimensional scaling is used to see whether there are any qualitative differences in pottery reflecting higher status or wealth. Results of the analysis indicate that qualitative differences are present only for Ik Complex vases. There are also indications of a special relationship between central Tikal and the minor center of Navahuelal located beyond the edges of the Tikal settlement zone.
Experimental study of the stability of heated laminar boundary layers in water

Linear sinusoidal disturbances are introduced into the boundary layer over a heated flat plate of uniform surface temperature using a vibrating ribbon. The experiment is performed in a low turbulence water tunnel with free-stream turbulence intensities of 0[sdot ]1–0[sdot ]2%. Measurements are made using temperature-compensated hot-film anemometry. Neutral-stability characteristics obtained for the unheated case agree favourably with previous results obtained both in water and in air. Neutral-stability and spatial disturbance-growth-rate characteristics measured for wall temperatures up to 8°F above the free-stream temperature verify trends established by parallel-flow solutions of the disturbance momentum and energy equations. Disturbance growth rates and the band of amplified disturbance frequencies both decrease as wall heating is increased. The experimentally observed increase in the minimum critical Reynolds number Re c min with increased wall heating agrees with the trend predicted by theory. However, effects of non-parallel flow act to reduce the measured values of Re c min by about 120 units compared with predicted parallel-flow values independent of the level of wall heating.
Spectroscopic and Computational Studies of Ground State Thermodynamic Equilibrium of s-Trans and s-Cis Conformers in trans,trans-1,4-Diphenyl-1,3-butadiene

At excitation wavelengths in the extreme red onset region of the trans,trans-1,4-diphenyl-1,3-butadiene (DPB) absorption spectrum, observed fluorescence spectra are mixtures of contributions from s-trans and s-cis conformers. Quantitative separations of the spectral mixtures by use of a chemometric method make it possible to determine relative fluorescence contributions and fluorescence quantum yields of DPB conformers as a function of temperature. Enthalpy differences of 1.9 and 2.3 kcal/mol are obtained for the ground state conformational equilibrium of DPB in methylcyclohexane and toluene, respectively. In computational studies, conformational energies and geometries of DPB are evaluated in terms of an ab initio method. The calculated s-cis−s-trans energy difference is in surprisingly good agreement with the experimental results.
Pseudouridine synthase 1: a site-specific synthase without strict sequence recognition requirements

Pseudouridine synthase 1 (Pus1p) is an unusual site-specific modification enzyme in that it can modify a number of positions in tRNAs and can recognize several other types of RNA. No consensus recognition sequence or structure has been identified for Pus1p. Human Pus1p was used to determine which structural or sequence elements of human tRNA(Ser) are necessary for pseudouridine (Ψ) formation at position 28 in the anticodon stem-loop (ASL). Some point mutations in the ASL stem of tRNA(Ser) had significant effects on the levels of modification and compensatory mutation, to reform the base pair, restored a wild-type level of Ψ formation. Deletion analysis showed that the tRNA(Ser) TΨC stem-loop was a determinant for modification in the ASL. A mini-substrate composed of the ASL and TΨC stem-loop exhibited significant Ψ formation at position 28 and a number of mutants were tested. Substantial base pairing in the ASL stem (3 out of 5 bp) is required, but the sequence of the TΨC loop is not required for modification. When all nucleotides in the ASL stem other than U28 were changed in a single mutant, but base pairing was retained, a near wild-type level of modification was observed.
Letting context speak: the use of co-creative, design-led, and user-centered design methods in the design of complex public communications

This paper discusses how co-creative, design-led, and user-centered design methods are being utilized to gain insight into the factors that influence the communication of food recalls. It looks at the role of designer and public in these methods and considers the value of these methods for other settings.
Behavior of period-altered circadian rhythm mutants of Drosophila in light: Dark cycles (Diptera: Drosophilidae)

Adults of Drosophila melanogasterhad their locomotor activity monitored under conditions of cycling light and dark (12 h each per cycle). The elementary behavior of wild-type flies under these “LD” conditions fluctuated between levels of high and levels of low activity. Two high-activity peaks occurred within a given cycle: one at about dawn; the other, at around dusk. Such accentuated activity levels gradually subsided to troughs in the middle of the day and of the night, after which the flies anticipated the next environmental transition by gradually becoming more active. Descriptions of these activity profiles were augmented by newly developed formal analyses of the “diel rhythm” phases (based in part on digital filterings of the raw behavioral data). The applications of these analyses led to objective, automated determination of when in the morning and the evening the flies' activity peaks occur. This normal diel behavior was compared to the locomotor activity and phase determinations for a series of rhythm variants. Most of these involved mutations at the period (per)locus and germ-line transformants bearing normal or altered forms of DNA cloned from this “clock gene.” Such genetic variants have been shown previously to exhibit, in constant darkness, strain-specific circadian periods ranging from about 19 to about 29 h. We now show that the phases of the evening peaks of activity under LD conditions were correspondingly earlier than normal for the short-period mutants and later than normal for those with long circadian cycle durations. The morning peaks, however, moved (in comparison to the normal phase position) minimally under the influence of a given pervariant.
Inflammatory Mechanisms of Stroke

Basic and clinical research provides evidence that inflammatory mechanisms play a central role in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers such as high-sensitivity C-reactive protein have been identified as predictors of first stroke and prognosis after stroke. The value of high-sensitivity C-reactive protein and other markers may depend on the characteristics of the study population; their utility may be less among populations with high vascular risk. A recent randomized, clinical trial suggests that the use of rosuvastatin therapy in otherwise healthy patients with high-sensitivity C-reactive protein >2 mg/dL can reduce the risk of a first stroke by 50%. The prognostic role of high-sensitivity C-reactive protein among patients after stroke, however, is less clear, and other biomarkers, including lipoprotein-associated phospholipase A(2), may provide complementary information about the risk of stroke recurrence. Infections, moreover, may contribute to inflammation and stroke risk. Although no single infectious organism is likely to be identified as the direct cause of atherosclerosis, summary measures of multiple chronic infectious exposures, or "infectious burden," have been associated with the risk of stroke and atherosclerosis affecting the carotid arteries. Acute infections have also been found to serve as stroke triggers in epidemiologic studies. Recommendations to vaccinate patients with cardiovascular disease against influenza represent the first specific anti-infective strategy to be used in vascular prophylaxis. Further studies are needed to determine the role of treatment of inflammation and infection in stroke prevention.
Computer and intrusion forensics [Book Review]

Reviewed In This Issue: George Mohay et al., Computer and Intrusion Forensics, Artech House Computer Security Series, 2003, ISBN 1-58053-369-8, 395 pages, US$79
Opposing roles of p38 and JNK in a Drosophila model of TDP-43 proteinopathy reveal oxidative stress and innate immunity as pathogenic components of neurodegeneration

Pathological aggregation and mutation of the 43-kDa TAR DNA-binding protein (TDP-43) are strongly implicated in the pathogenesis amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 neurotoxicity has been extensively modeled in mice, zebrafish, Caenorhabditis elegans and Drosophila, where selective expression of TDP-43 in motoneurons led to paralysis and premature lethality. Through a genetic screen aimed to identify genetic modifiers of TDP-43, we found that the Drosophila dual leucine kinase Wallenda (Wnd) and its downstream kinases JNK and p38 influenced TDP-43 neurotoxicity. Reducing Wnd gene dosage or overexpressing its antagonist highwire partially rescued TDP-43-associated premature lethality. Downstream of Wnd, the JNK and p38 kinases played opposing roles in TDP-43-associated neurodegeneration. LOF alleles of the p38b gene as well as p38 inhibitors diminished TDP-43-associated premature lethality, whereas p38b GOF caused phenotypic worsening. In stark contrast, disruptive alleles of Basket (Bsk), the Drosophila homologue of JNK, exacerbated longevity shortening, whereas overexpression of Bsk extended lifespan. Among possible mechanisms, we found motoneuron-directed expression of TDP-43 elicited oxidative stress and innate immune gene activation that were exacerbated by p38 GOF and Bsk LOF, respectively. A key pathologic role for innate immunity in TDP-43-associated neurodegeneration was further supported by the finding that genetic suppression of the Toll/Dif and Imd/Relish inflammatory pathways dramatically extended lifespan of TDP-43 transgenic flies. We propose that oxidative stress and neuroinflammation are intrinsic components of TDP-43-associated neurodegeneration and that the balance between cytoprotective JNK and cytotoxic p38 signaling dictates phenotypic outcome to TDP-43 expression in Drosophila.
Sound methods and effective tools for engineering modeling and analysis

Modeling and analysis is indispensable in engineering. To be safe and effective, a modeling method requires a language with a validated semantics; feature-rich, easy-to-use, dependable tools; and low engineering costs. Today we lack adequate means to develop such methods. We present a partial solution combining two techniques: formal methods for language design, and package-oriented programming for function and usability at low cost. We have evaluated the approach in an end-to-end experiment. We deployed an existing reliability method to NASA in a package-oriented tool and surveyed engineers to assess its usability. We formally specified, improved, and validated the language. To assess cost, we built a package-based tool for the new language. Our data show that the approach can enable cost-effective deployment of sound methods by effective tools.
Connections And Connectivity And In China; Guanxi And The Explosion Of Instant Messaging - The Marriage Of Relational Diads, Group Membership, And Web Based Communications

This research explores the reasons behind the phenomenal growth in the use of instant messaging (IM) in China. The paper proposes that one explanation might lie in the high collectivism, high context communication and the cultural practice of guanxi in China. On the one hand, current cross cultural research related to China on mobile telephony seems to provide a strong basis for this contention. On the other hand, the discussion within the literature examining IM within Chinese society appears to be much less robust. However, one could argue that IM provides a unique vehicle for communication within guanxiwang which deserves consideration, especially considering its huge popularity in China. A cursory examination of initial evidence suggests that instant messaging provides the possibility of high context communication and efficient information gathering which facilitates relationship building and maintenance within the relational dyads as well as group characteristics of a guanxiwang. One could argue that instant messaging is perfectly suited to the communication needs of these particularistic and personal hyper-social networks in China.
Influence of the Parameters of Feed Water of the WWER-1000 Reactors on the Corrosion-Electrochemical Behavior of 08KH18N10T Steel

We study the influence of the temperature and composition of the feed water of ammonia–hydrazine control on the corrosion-electrochemical behavior of 08Kh18N10T stainless steel. It is shown that, as temperature increases from 25 to 300°С, the corrosion currents increase by more than an order of magnitude for hydrazine concentrations of 0–2.0 mg/kg, by 1.5–2 orders of magnitude depending on the concentration of chlorides, and by two orders of magnitude within the рН range 6.9–9.0. We plot the dependences of the susceptibility of steel to pitting and repassivation on temperature, on the concentrations of hydrazine and chloride ions, and on the рН value. It is shown that, for a content of chloride ions of 2.0 mg/kg and рН 6.9, the analyzed steel is most susceptible to the initiation of pits within the range 25–300°С.
Simple approaches to improve restoration of coastal sage scrub habitat in Southern California.

ABSTRACT Much of the coastal sage scrub habitat in Southern California that existed prior to European settlement has been developed for human uses. Over the past two to three decades, public agencies and land conservation organizations have worked to acquire some of the remaining lands for preservation. Many of these lands are degraded by past intensive livestock grazing, farming, and frequent fires, and the native flora has been replaced by weedy, exotic annual grasses and forbs, mostly of Mediterranean origin. Restoration of native flora is challenging and there are few successful examples to provide guidance on effective methods. Cost is also an important and prohibitive factor. Competition from weeds is one of the most difficult impediments to establishing native vegetation, which often persists in the seedbank. We compared annual applications of the nonselective herbicide glyphosate over multiple years, followed by a final year with the grass-specific fluazifop, as a simple, low cost method of reduci...
Life Cycle Water Consumption and Water Resource Assessment for Utility-Scale Geothermal Systems: An In-Depth Analysis of Historical and Forthcoming EGS Projects

This report is the third in a series of reports sponsored by the U.S. Department of Energy Geothermal Technologies Program in which a range of water-related issues surrounding geothermal power production are evaluated. The first report made an initial attempt at quantifying the life cycle fresh water requirements of geothermal power-generating systems and explored operational and environmental concerns related to the geochemical composition of geothermal fluids. The initial analysis of life cycle fresh water consumption of geothermal power-generating systems identified that operational water requirements consumed the vast majority of water across the life cycle. However, it relied upon limited operational water consumption data and did not account for belowground operational losses for enhanced geothermal systems (EGSs). A second report presented an initial assessment of fresh water demand for future growth in utility-scale geothermal power generation. The current analysis builds upon this work to improve life cycle fresh water consumption estimates and incorporates regional water availability into the resource assessment to improve the identification of areas where future growth in geothermal electricity generation may encounter water challenges.
Mourning Absences, Melancholic Commemoration, and the Contested Public Memories of the National September 11 Memorial and Museum

This essay extends the interdisciplinary work that exists on the dialectic between mourning and melancholia as a way of analyzing the rhetorical effect of the 9/11 Memorial and Museum. We argue that while previous research on this site has often underscored the reverential and mourning functions of this space, few have studied the darker, more melancholic features of these hallowed grounds. By investigating the melancholic dimensions of public memory, and by illustrating how national communities can strategically take advantage of these dimensions, we affirm the importance of resilience, mourning, and recovery for commemorative efforts.
Chemical fog dispersal with ground equipment for mosquito control.

Fogging for mosquito control has long been centered around the thermal fog and non-thermal fog. Recently a new concept in mosquito control called a chemical fog was reported by Stokes (1967, Proc. Calif. Mosquito Contr. Assoc. 35 : 122). Stroud & Stevens (1968, Mosquito News 28: 569–71) reported the effectiveness of this method as a ground application with propoxur and fenthion. An aerial application technique and the description of the chemical reaction was described by Knapp (1968, Mosquito News 28 : 516–24). Basically, this consists of hydrated silicon dioxide (SiO2) particles impregnated with the insecticides in association with a fog of ammonium chloride (NH4Cl) particles. These 2 products are formed by a chemical reaction resulting from combining silicon tetrachloride (SiCl4) and 5% ammonia water mixed in the atmosphere [SiCl4 + 4NH3 + 2H2O-SiO2(s) + 4NH4Cl(s)].
MYXEDEMA COMA WITH MYXEDEMA HEART DISEASE

Myxedema heart disease is a rare and potentially fatal disease entity. A high index of suspicion in cases of unexplained heart failure with early administration of thyroxine can be potentially lifesaving. A 58 year old woman was admitted with three days of worsening volume overload and marked
Spodoptera frugiperda (Lepidoptera: Noctuidae): Deterrence of Oviposition by Aqueous Homogenates of Fall Armyworm and Corn Earworm Larvae Applied on Whorl-Stage Corn

Aqueous homogenates of terminal-instar larvae of fall armyworm, Spodoptera frugiperda (J. E. Smith), and corn earworm, Heliothis zea (Boddie), were evaluated against field populations of S. frugiperda in whorl-stage field corn near Tifton, Ga. The number of fall armyworm egg masses oviposited on corn treated with either 1.0 or 0.1 larval equivalent per plant of either fall armyworm or corn earworm was significantly lower than that of controls. Multiple applications of 1.0 larval equivalent per plant of fall armyworm and corn earworm reduced the subsequent establishment of fall armyworm larvae by 66.5 and 63.6%, respectively. Plots treated one, two, or three times weekly with 1.0 fall armyworm larval equivalent per plant all received significantly fewer fall armyworm egg masses than did the control plants. Plots treated two or three times weekly contained significantly fewer subsequent fall armyworm larvae-infested plants than did plots treated once weekly. Although deterrent mechanisms have not been specifically identified, semiochemicals associated with terminal-instar larvae of fall armyworm and corn earworm and/or their byproducts may be responsible for inducing fall armyworm females (and, to a lesser extent, newly emerged fall armyworm larvae) to seek uncontaminated sites for oviposition and establishment, respectively.
Species differences in the reaction of the mammalian skeleton to estrogens.

SummaryEstrogenic steroid hormones stimulate endosteal bone formation and inhibit bone resorption in mice. In young growing rats, the same substances do not produce endosteal bone but interfere with endochondral ossification by inhibiting resorption of cartilage matrix and new bone. In other rodents, such as hamsters, guinea pigs, and rabbits, and also in cats and dogs, there is no apparent specific effect of estrogens upon formation of bone.
Multiple customer order decoupling points within a hybrid MTS/MTO manufacturing supply chain with uncertain demands in two consecutive echelons

For decades, manufacturers have dealt with uncertain demands, and many solutions—such as manufacturing semi-finished products–have been presented to help manage the uncertainties. This paper considers the demand uncertainties in two echelons of a supply chain, unlike most of the field research, which has focused on the final customers’ demand uncertainty. In order to decrease the operating costs of a manufacturer, a model is proposed to use hybrid manufacturing in two levels of a supply chain with two echelons of manufacturers. The output of the presented model is the quantity of semi-finished products ordered to the decoupling point upstream manufacturer. The number of processes that must be done based upon Make to Stock, the order quantity of the decoupling point downstream manufacturers, and the order quantity of the final customers are obtained by the presented model as well. A numerical example and a vast sensitivity analysis are presented to better show the applicability of the presented model.
Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors

The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase, but resistance arises rapidly, most frequently owing to the secondary T790M mutation within the ATP site of the receptor. Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant, but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond. All current EGFR TKIs target the ATP-site of the kinase, highlighting the need for therapeutic agents with alternative mechanisms of action. Here we describe the rational discovery of EAI045, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor. The crystal structure shows that the compound binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of the kinase. The compound inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays. However, as a single agent it is not effective in blocking EGFR-driven proliferation in cells owing to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state. We observe marked synergy of EAI045 with cetuximab, an antibody therapeutic that blocks EGFR dimerization, rendering the kinase uniformly susceptible to the allosteric agent. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR(L858R/T790M) and by EGFR(L858R/T790M/C797S), a mutant that is resistant to all currently available EGFR TKIs. More generally, our findings illustrate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors.
The Quest for National Identity

“You will be my next hero,” says a drunk person to an Indian who just entered the saloon, somewhere in the American West. “An Indian treasure will be the subject of my next book”, the same person says a few moments later, just before he loses control of his body and his head bangs against the saloon counter. The drunkard turns out to be Karl May and the scene came from the film Der Schuh des Manitou (Manitou’s Shoe), a parody of Karl May films, released in 2001. More than 8.85 million people saw the film in just two months after its release, which surpassed even Otto-der Film (1985), a film virtually unknown in North America, the most popular film in German history prior to 2001.1
Cyclic Nucleotides and Cell Function

The “second messenger” function of the cyclic nucleotides, CA MP and CG MP, through which external stimuli arriving at the cell membrane are made internally effective, is thought to depend on their ability to activate a class of enzymes known as protein kinases. These then set in motion a cascade of biochemical processes that modulate and enormously amplify the metabolic activities carried on within the cell.
Barbarism and Criminality

The barbarisation of warfare on the Eastern Front was the consequence of a number of interrelated factors, such as the brutality of the fighting itself, the harsh living conditions at the front, the susceptibility of the junior officers and probably of many of the soldiers to Nazi ideology, and the constant political indoctrination of the troops. The most direct cause for the criminal activities of the German army in the East and the resulting brutalising effect that they had on the individual soldier, however, were the so-called ‘criminal orders’. This complex of commands, issued by the OKW and OKH on the eve of the invasion of Russia, determined to a large extent the brutal conduct of the troops at the front by providing them with a pseudo-legal and disciplinary framework. The ‘criminal orders’ were composed of four sets of instructions: (1) Regulations concerning the activities of the Einsatzgruppen of the SS and SD, which enabled these murder squads to operate with relative freedom within the areas controlled by the army groups under the direct command of Reinhard Heydrich. (2) The curtailment of military jurisdiction (Die Einschrankung der Kriegsgerichtsbarkeit), which stipulated that guerrillas, and civilians suspected of assisting them, were to be shot by the army, and that in case no guilty party could be found, collective measures were to be taken against the civilian population in the area. (3) The Commissar Order, which called for the shooting of any Red Army political commissar captured by the troops. (4) The ‘Guidelines for the Conduct of the Troops in Russia’, which ordered ruthless measures against ‘Bolshevik agitators, guerrillas, saboteurs and Jews’ and called for the complete elimination of any active or passive resistance.1
Exploratory Factor Analysis and Reliability of the Child Welfare Trauma-Informed Individual Assessment Tool

This article presents the development and psychometric analysis of the Child Welfare Trauma-Informed Individual Assessment Tool, an instrument designed to measure the extent to which child welfare service providers employ trauma-informed practices with the children and families that they serve. Using the responses of 213 front-line child welfare workers, exploratory factor analysis was used on a seventeen-item scale, resulting in a four-factor model. Based on the results of this analysis, implications for potential uses of the instrument are discussed, and specifications for additional evaluation of the measure's validity are outlined.