cssi/SciSciGPT-SciSciNet huggingface dataset:
Are cultured liver cells the right tool to investigate mechanisms of liver disease or hepatotoxicity

Microarray technology allows the simultaneous analysis of mRNA expression levels of thousands of genes. In the field of toxicogenomics, this technology could help to identify potentially unsafe compounds based on the changes in mRNA expression patterns they induce. Rodent in vivo and in vitro systems are currently the experimental models of choice for predictive toxicology, especially in early phases of development. This study characterizes several hepatic in vitro systems based on mRNA expression profiles, comparing them to gene expression in liver tissue. The in vitro systems investigated comprise two rat liver cell lines (BRL3A and NRL clone 9), primary hepatocytes in conventional monolayer or in sandwich culture, and liver slices. The results demonstrate that liver slices exhibit the strongest similarity to liver tissue regarding mRNA expression, whereas the two cell lines are quite different from the whole liver. We were able to identify genes with strong changes in expression levels in all or at least one of the in vitro systems relative to whole liver. In particular, for some cytochrome P450s the differences observed on the mRNA expression level were paralleled by protein expression and enzymatic activity. In addition, the effect of time in culture was assessed. We were able to show a profound effect of the duration of culture. Expression patterns change most rapidly soon after cell isolation and culture initiation and stabilize with time in culture. The findings are discussed with respect to the usefulness of the various hepatic in vitro systems for microarray-based toxicological testing of compounds.
Bromide transport under sprinkler and flood irrigation for no-till soil condition

Abstract Understanding the influence of irrigation methods on solute transport is essential to properly manage chemical use in agricultural soils. In this study, we compare the transport of a conservative solute (bromide) under sprinkler and flood irrigations on a sandy clay loam (mixed Ustollic Haplargid) under no-till condition. After spraying 148.8 kg/ha of KBr on the surface, ≈25 cm of irrigation water was applied in six increments over two months as flood irrigation on one plot and as sprinkler irrigation on another plot. The net applied water (NAW=irrigation+precipitation−evaporation) was similar for both plots, which allowed the comparison of the Br profiles for the two types of irrigation. Water content and Br concentration were sampled at 5, 19, 34, and 68 days after chemical application. The recovered mass of Br and the location of center of mass were comparable for the two types of irrigation. The spread around the center of mass, however, was higher for the flood-irrigated plot. On the flood-irrigated plot, more mass leached below the depth of 90 cm, with the differences being statistically significant. The velocity of the Br center of mass was consistently 10%–20% larger than the piston displacement velocity. Dispersion and velocity coefficients varied substantially between sampling time. A recent quasi-steady solution of the convection–dispersion equation [M.H. Nachabe, L.R. Ahuja, Quasi-analytical solution for predicting the redistribution of surface-applied chemicals. Trans. ASAE 39(5) (1996) 1659–1664], which accounts for variable flow and dispersion, simulates the Br profiles fairly well.
Synaptotagmin I is necessary for compensatory synaptic vesicle endocytosis in vivo

Neurotransmission requires a balance of synaptic vesicle exocytosis and endocytosis. Synaptotagmin I (Syt I) is widely regarded as the primary calcium sensor for synaptic vesicle exocytosis. Previous biochemical data suggest that Syt I may also function during synaptic vesicle endocytosis; however, ultrastructural analyses at synapses with impaired Syt I function have provided an indirect and conflicting view of the role of Syt I during synaptic vesicle endocytosis. Until now it has not been possible experimentally to separate the exocytic and endocytic functions of Syt I in vivo. Here, we test directly the role of Syt I during endocytosis in vivo. We use quantitative live imaging of a pH-sensitive green fluorescent protein fused to a synaptic vesicle protein (synapto-pHluorin) to measure the kinetics of endocytosis in sytI-null Drosophila. We then combine live imaging of the synapto-pHluorins with photoinactivation of Syt I, through fluorescein-assisted light inactivation, after normal Syt I-mediated vesicle exocytosis. By inactivating Syt I only during endocytosis, we demonstrate that Syt I is necessary for the endocytosis of synaptic vesicles that have undergone exocytosis using a functional Syt I protein.
What do color blind children really see? Guidelines for clinical prescreening based on recent findings☆

Abstract Recent research on classical red-green blind observers has shown that complete dichromacy may be present only under conditions where the viewing angle is small. For viewing angles greater than about 4°, both rods and an anomalous cone have been shown to underlie a weak form of trichromacy. The conditions for rod or anomalous cone mediation of this trichromacy have also been shown to depend on the overall viewing luminance. These data taken together prompt a rethinking of the classical view of red-green dichromacy and lead to new considerations of the color discrimination performance of dichromatic candidates. In this paper we review the recent research on the presence of trichromatic abilities in classical dichromats and we relate these findings to the needs of the clinician, especially in the screening of young children.
Wildfire Effects on Understory Vegetation, Natural Regeneration, and Forest Floor Fuels in a Sierran Mixed Conifer Stand

Wildfire effects on understory shrubs and herbs, regeneration of the seedling and sapling size classes, and downed and dead fuels were assessed in a mixed conifer stand located in the Lake Tahoe Basin in which California white fir (Abies concolor var. lowiana [Gord.] Lemm.) was most abundant but with Jeffrey pine (Pinus jeffreyi Grev. & Balf.) also prevalent. In burned and unburned stand portions, prefire measurements served as a basis of comparison for the postfire measurements pertinent to each study component. Fire severely suppressed the understory vegetation, which was dominated by shrubs such as bush chinquapin (Chrysolepis sempervirens [Kellogg] Hjelmqvist) and antelope bitterbrush (Purshia tridentata [Pursh] DC.), while a tepid postfire recovery of most of the preexisting species in the burned stand portion was augmented by new ones, including shrubs such as snowbrush (Ceanothus velutinus Douglas ex Hook.) and whitethorn (Ceanothus cordulatus Kellogg) ceanothus and herbs such as Holboell's rockcre...
Phase diagram in an external magnetic field beyond a mean-field approximation

The phase structure of the Polyakov loop-extended chiral quark-meson model is explored in a nonperturbative approach, beyond a mean-field approximation, in the presence of a magnetic field. We show that by including meson fluctuations one cannot resolve the qualitative discrepancy on the dependence of the crossover transition temperature in a nonzero magnetic field between effective model predictions and recent lattice results [1]. We compute the curvature of the crossover line in the $T\ensuremath{-}{\ensuremath{\mu}}_{B}$ plane at a nonzero magnetic field and show that the curvature increases with increasing magnetic field. On the basis of QCD inequalities, we also argue that, at least in the large ${N}_{c}$ limit, a chiral critical end point and, consequently, a change from crossover to a first-order chiral phase transition are excluded at zero baryon chemical potential and nonzero magnetic field.
The Highest Form Of The Geographer's Art

Abstract Geography is an integrative discipline to which society has assigned responsibility for the study of areas. It is expected to satisfy human curiosity about how much of what is where, and why it is there, in an organized manner that will facilitate comprehension and retention. Geography must be both an art and a science, because understanding the meaning of area cannot be reduced to a formal process. The discipline deals with an enormous range of phenomena and must provide a congenial home for many different kinds of practitioners. Geography has survived repeated misguided attempts to “make it into a Science” by amputating vital parts of the discipline. Systematic geography generates theories to facilitate an understanding of regions, and regional geography is the proving ground where theories are rested empirically. The idea of the region provides the essential unifying theme that integrates the diverse subdisciplines of geography. The highest form of the geographer's art is the production of evo...
The mushroom habitat as an ecological arena for global exchange of Wolbachia

Wolbachia infect a variety of arthropod and nematode hosts, but in arthropods, host phylogenetic relationships are usually poor predictors of strain similarity. This suggests that new infections are often established by horizontal transmission. To gain insight into the factors affecting the probability of horizontal transmission among host species, we ask how host phylogeny, geographical distribution and ecology affect patterns of Wolbachia strain similarity. We used multilocus sequence typing (MLST) to characterize Wolbachia strain similarity among dipteran hosts associated with fleshy mushrooms. Wolbachia Supergroup A was more common than Supergroup B in Diptera, and also more common in mycophagous than non-mycophagous Diptera. Within Supergroup A, host family within Diptera had no effect on strain similarity, and there was no tendency for Wolbachia strains from sympatric host species to be more similar to one another than to strains from hosts in different biogeographical realms. Supergroup A strains differed between mycophagous and non-mycophagous Diptera more than expected by chance, suggesting that ecological associations can facilitate horizontal transmission of Wolbachia within mycophagous fly communities. For Supergroup B, there were no significant associations between strain similarity and host phylogeny, biogeography, or ecology. We identified only two cases in which closely related hosts carried closely related Wolbachia strains, evidence that Wolbachia-host co-speciation or early introgression can occur but may not be a major contributor to overall strain diversity. Our results suggest that horizontal transmission of Wolbachia can be influenced by host ecology, thus leading to partial restriction of Wolbachia strains or strain groups to particular guilds of insects.
Auditor compensation, disclosure quality, and market liquidity: Evidence from the stock market

Abstract Previous studies on the effects of auditor compensation on disclosure quality have focused on accounting measures, such as earnings management, discretionary accruals, and restatements. In contrast, we investigate the impact of fees paid for audit and non-audit services on a market-based measure of disclosure quality and stock market liquidity. Based on a large sample of NYSE-traded S&P 1500 stocks, we find only weak evidence to support the argument that auditor compensation lowers firm disclosure quality and market liquidity. This finding is robust to alternative measures of bid-ask spreads and asymmetric information costs of trading. In addition, we find some evidence to suggest that the adverse effects of auditor compensation on market liquidity are concentrated in firms with weak corporate governance mechanisms. Our results underscore the need to revisit the rationale and scope of restrictions on non-audit services imposed recently by the Sarbanes-Oxley Act.
Knowledge in the policy process: Incorporating new environmental information in natural resources policy making

Efforts by both natural and social scientists have brought significant new bodies of information to bear on natural resources policy making. Among these have been new insights in conservation biology and landscape ecology, new methods for valuing intangible resource benefits, and new frameworks for resource accounting. The use of these new sources of information is analyzed from a Lasswellian policy process perspective, with illustrations from recent experience with U.S. national forest planning. A distinction is made between the impact of new information on ‘ordinary’ as contrasted to ‘constitutive’ policy making. This experience suggests that these new sources of information may increase emphasis on sustainable, multiple benefit use of resources, but they can also shift power away from non-expert actors, undermine rights arguments, polarize debates over appropriate resource use, and delay timely decisionmaking.
Some Recent Developments In The Fabrication Of Variably-Spaced Linear And Circular Diffraction Gratings

Recent and continuing developments in laser positional measurement interferometers and computer control make it possible to rule high quality,linear diffraction gratings of variable spacing. One application of such gratings is for testing cylindrical optics. A natural progression from this was the construction an interferometrically controlled rotary ruling engine for the production of precision circular, reflection gratings which may be used for testing optics that have axial symmetry. The construction and operation of this engine will be described, along with earlier practical results with cylindrical and prototype circular gratings.
Virtual Knowledge-Sharing Communities of Practice at Caterpillar: Success Factors and Barriers.

This article reports the results of a qualitative study of success factors and barriers to the development of virtual knowledge-sharing communities of practice at Caterpillar Inc., a Fortune 100 multinational corporation. The study identified several prerequisites for successful knowledge management through virtual communities of practice: knowledge sharing as a key element of the corporate culture; employees regarding knowledge as a public good belonging to the whole organization, and not as their individual asset; communities self-organizing around specific performance-related problems or areas of professional interest of their members; and communities supported by volunteer managers and active core groups of experts. At the same time, the study has identified a number of important barriers to virtual community development. Specifically, even when employees give the highest priority to the interests of the organization, they tend to shy away from contributing knowledge for a variety of other reasons not related to information hoarding. In addition, corporate security considerations and concerns about the accuracy of the information and the potential information overload could clash with the need to promote spontaneous generation of information. Suggestions for overcoming the identified barriers, future research directions, and implications for HRD professionals are formulated.
Gamma Ray Astronomy

Recent observations have marked the transition of gamma ray astronomy from a discovery phase to an exploratory one. This has been the result of the development of a number of very sophisticated sensitive telescopes and the opportunity to place them on space platforms. A survey of the instruments developed for this research is given together with a brief summary of the current status of the observational results. These include the studies of galactic gamma ray emission, the diffuse, presumably extragalactic, gamma radiation and localized gamma ray sources. The study of the spatial distribution of galactic gamma radiation is beginning to provide a new means for the study of galactic structure and dynamics. The diffuse emission may provide evidence of gamma ray emission in the cosmological past, although improved observations must be obtained before the picture can be clarified. The study of localized sources has shown NP0532, the Crab radio pulsar, to be a gamma ray pulsar also and strong emission from Vela may be due to supernova produced cosmic rays interacting with the remnant gas.
SCRAP: A Statistical Approach for Creating a Database Query Workload Based on Performance Bottlenecks

With the tremendous growth in stored data, the role of database systems has become more significant than ever before. Standard query workloads, such as the TPC-C and TPC-H benchmark suites, are used to evaluate and tune the functionality and performance of database systems. Running and configuring benchmarks is a time consuming task. It requires substantial statistical expertise due to the enormous data size and large number of queries in the workload. Subsetting can be used to reduce the number of queries in a workload. An existing workload subsetting technique selected queries based on similarities of the ranks of the queries for low-level characteristics, such as cache miss rates, or based on the execution time required in different computer systems. However, many low-level characteristics are correlated, produce similar behaviors. Also, raw execution time as a metric is too diffuse to capture important performance bottlenecks. Our goal is to select a subset of queries that can reproduce the same bottlenecks in the system as the original workload. In this paper, we propose a statistical approach for creating a database query workload based on performance bottlenecks (SCRAP). Our methodology takes a query workload and a set of system configuration parameters as inputs, and selects a subset of the queries from the workload based on the similarity of performance bottlenecks. Experimental results using the TPC-H benchmark and the PostgreSQL database system, show that the reduced workload and the original workload produce similar performance bottlenecks, and the subset accurately estimates the total execution time.
Uncovering tropical diversity: six sympatric cryptic species of Blepharoneura (Diptera: Tephritidae) in flowers of Gurania spinulosa (Cucurbitaceae) in eastern Ecuador

Diversification of phytophagous insects is often associated with changes in the use of host taxa and host parts. We focus on a group of newly discovered Neotropical tephritids in the genus Blepharoneura, and report the discovery of an extraordinary number of sympatric, morphologically cryptic species, all feeding as larvae on calyces of flowers of a single functionally dioecious and highly sexually dimorphic host species (Gurania spinulosa) in eastern Ecuador. Molecular analyses of the mitochondrial cytochrome oxidase-I gene from flies reared from flowers of G. spinulosa reveal six distinct haplotype groups that differ by 7.2–10.1% bp (uncorrected pairwise distances; N = 624 bp). Haplotype groups correspond to six distinct and well-supported clades. Members of five clades specialize on the calyces of flowers of a particular sex: three clades comprise male flower specialists; two clades comprise female flower specialists; the sixth clade comprises generalists reared from male and female flowers. The six clades occupy significantly different morphological spaces defined by wing pigmentation patterns; however, diagnostic morphological characters were not discovered. Behavioural observations suggest specific courtship behaviours may play a role in maintaining reproductive isolation among sympatric species. Journal compilation © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 93, 779–797. No claim to original US government works.
Statistical feedback control of a plasma etch process

This paper presents the methodology developed for the automatic feedback control of a silicon nitride plasma etch process. The methodology provides an augmented level of control for semiconductor manufacturing processes, to the level that the operator inputs the required process quality characteristics (e.g. etch rate and uniformity values) instead of the desired process conditions (e.g., specific RF power, pressure, gas flows). The optimal equipment settings are determined from previously generated process/equipment models. The control algorithm is driven by the in-situ measurements, using in-line sensors monitoring each wafer. The sensor data is subjected to Statistical Quality Control (SQC) to determine if deviations from the required process observable values can be attributed to noise in the system or are due to a sustained anomalous behavior of the equipment. Once a change in equipment behavior is detected, the process/equipment models are adjusted to match the new state of the equipment. The updated models are used to run subsequent wafers until a new SQC failure is observed. The algorithms developed have been implemented and tested, and are currently being used to control the etching of wafers under standard manufacturing conditions. >
It's Logic in Practice, My Dear Watson: An Imaginary Memoir from Beyond the Grave

In diesem Artikel sollen – unter Anwendung des Verfahrens des imaginaren Memoirs – die logischen und die semiotischen Grundlagen einer empirischen Untersuchung von Bedeutung naher erlautert werden. Ich bediene mich der Stimme von Sherlock Holmes, um einige kritische Fragen bei der Anwendung konkreter Logik in der qualitativen Forschung sichtbar zu machen. Ausgehend von einem vertieften Verstandnis der Logik bei der Anwendung der Forschungsmethode mache ich auserdem Vorschlage fur die Modifikation der derzeitigen qualitativen Forschungspraxis. URN: urn:nbn:de:0114-fqs010191
Fast full wave analysis of PCB via arrays with model-to-hardware correlation

This paper applies a methodology based on a mostly-analytical Foldy-Lax full wave scattering model to analyze via arrays in a multilayered printed circuit board. We have demonstrated good model-to-hardware correlation up to 20 GHz by simulating and measuring 8×8 via arrays including 29 signal vias and 35 ground vias in a 18-layer test board. The required CPU in the 64-via case is 4 seconds which is more than four orders of magnitude faster than the market leading general-purpose 3D full wave solver.
High power 20GHz photodiodes with microwave tuning circuits

Modified uni-travelling-carrier (MUTC) photodiodes (PDs) with microwave open and shorted stubs having RF output power (PRF_out) of 23 dBm and 21.6 dBm, respectively, at 20 GHz are demonstrated.
Illustrating transparent surfaces with curvature-directed strokes

Transparency can be a useful device for simultaneously depicting multiple superimposed layers of information in a single image. However, in computer-generated pictures-as in photographs and in directly viewed actual objects-it can often be difficult to adequately perceive the three-dimensional shape of a layered transparent surface or its relative depth distance from underlying structures. Inspired by artists' use of line to show shape, we have explored methods for automatically defining a distributed set of opaque surface markings that intend to portray the three-dimensional shape and relative depth of a smoothly curving layered transparent surface in an intuitively meaningful (and minimally occluding) way. This paper describes the perceptual motivation, artistic inspiration and practical implementation of an algorithm for "texturing" a transparent surface with uniformly distributed opaque short strokes, locally oriented in the direction of greatest normal curvature, and of length proportional to the magnitude of the surface curvature in the stroke direction. The driving application for this work is the visualization of layered surfaces in radiation therapy treatment planning data, and the technique is illustrated on transparent isointensity surfaces of radiation dose.
Insertable stereoscopic 3D surgical imaging device with pan and tilt

In this paper, we present an insertable stereoscopic 3D imaging system for minimally invasive surgery. It has been designed and developed toward the goal of single port surgery. The device is fully inserted into the body cavity and affixed to the abdominal wall. It contains pan and tilt axes to move the camera under simple and intuitive joystick control. A polarization-based stereoscopic display is used to view the images in 3D. The camerapsilas mechanical design is based upon a single camera prototype we have previously built. We have run calibration tests on the camera and used it to track surgical tools in 3D in real-time. We have also used it in a number of live animal tests that included surgical procedures such as appendectomy, running the bowel, suturing, and nephrectomy. The experiments suggest that the device may be easier to use than a normal laparoscope since there is no special training needed for operators. The Pan/Tilt functions provide a large imaging volume that is not restricted by the fulcrum point of a standard laparoscope. Finally, the 3-D imaging system significantly improves the visualization and depth perception of the surgeon.
The Chemistry-Biology-Medicine Continuum and the Drug Discovery and Development Process in Academia

Admirable as it is, the drug discovery and development process is continuously undergoing changes and adjustments in search of further improvements in efficiency, productivity, and profitability. Recent trends in academic-industrial partnerships promise to provide new opportunities for advancements of this process through transdisciplinary collaborations along the entire spectrum of activities involved in this complex process. This perspective discusses ways to promote the emerging academic paradigm of the chemistry-biology-medicine continuum as a means to advance the drug discovery and development process.
Biodegradation of Nitrated Munition Compounds and Herbicides by Obligately Anaerobic Bacteria

Research performed during the 1970s (15, 18) generally indicated that complete biomineralization of 2,4,6-trinitrotoluene (TNT) and similar highly nitrated compounds did not occur. Biological reductions (R-NO2 → R-NO → R-NHOH → R-NH2) and polymerization reactions appeared to occur, but actual degradation of aromatic nuclei was not observed. However, this work involved studies of aerobic systems such as activated sludge and thermophilic composts, and pure cultures of aerobic fungi and bacteria such as pseudomonads. Pure cultures of some anaerobic bacteria such as Veillonella alcalescens (35) were examined, with similar results. Boopathy and Kulpa (2) recently isolated a Desulfovibrio that used TNT as a sole source of nitrogen, producing toluene as an end product. A Pseudomonas that produced dinitrotoluene, mononitrotoluene, and toluene from TNT, perhaps by hydride additions, was isolated by Duque et al. (10). These are still incomplete degradations of the parent molecule. Since the Desulfovibrio strain required obligately anaerobic conditions to produce toluene from TNT, and the Pseudomonas did so aerobically, the TNT transformation process may be mechanistically different in the two microorganisms. This should be a fruitful area for future research.
Pairing in mallards and American black ducks: a new view on population decline in American black ducks

Data on mating systems suggest that mate choice and dominance advantages by mallard (Anas platyrhynchos) males are not sufficient to explain declines in American black ducks (Anas rubripes). Courtship and pairing of mallards and American black ducks overwintering at a site on the Chesapeake Bay were studied from 1976–1993, during October–March. Mallards declined relative to American black ducks during this period at the study site. Courtship groups and pairs (one exception) consisted of conspecific individuals. Mallards and American black ducks segregated when courting but not when resting. Hybrid males joined courting groups of either species but did not pair successfully with either parental species. Handraised American black ducks hatched from eggs, imprinted on humans, and fledged at the study site, paired with American black ducks even though they were initially the rarer species. Handraised American black ducks avoided pairing with siblings. American black ducks and mallards pair assortatively and hybrids are selected against on the Chesapeake Bay. American black ducks may be declining due to human disturbance rather than due to direct interactions with mallards. Mallards may be increasing because they tolerate human disturbance and through direct release by humans into the American black duck's breeding range.
In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine

The reversible S-nitrosation and inhibition of mitochondrial complex I is a potential mechanism of cardioprotection, recruited by ischemic preconditioning (IPC), S-nitrosothiols, and nitrite. Previously, to exploit this mechanism, the mitochondrial S-nitrosating agent S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) was developed, and protected perfused hearts and isolated cardiomyocytes against ischemia-reperfusion (IR) injury. In the present study, the murine left anterior descending coronary artery (LAD) occlusion model of IR injury was employed, to determine the protective efficacy of SNO-MPG in vivo. Intraperitoneal administration of 1 mg/kg SNO-MPG, 30 min prior to occlusion, significantly reduced myocardial infarction and improved EKG parameters, following 30 min occlusion plus 2 or 24 h reperfusion. SNO-MPG protected to the same degree as IPC, and notably was also protective when administered at reperfusion. Cardioprotection was accompanied by increased mitochondrial protein S-nitrosothiol content, and inhibition of complex I, both of which were reversed after 2 h reperfusion. Finally, hearts from mice harboring a heterozygous mutation in the complex I NDUSF4 subunit were refractory to protection by either SNO-MPG or IPC, suggesting that a fully functional complex I, capable of reversible inhibition is critical for cardioprotection. Overall, these results are consistent with a role for mitochondrial S-nitrosation and complex I inhibition in the cardioprotective mechanism of IPC and SNO-MPG in vivo.
Demonstration of Starter Unit Interprotein Transfer from a Fatty Acid Synthase to a Multidomain, Nonreducing Polyketide Synthase

The pathway for substrate transacylation between a fungal type I fatty acid synthase (FAS) and a nonreducing polyketide synthase (NR-PKS) was determined by in vitro reconstitution of dissected domains. System kinetics were influenced by domain dissections, and the FAS phosphopantetheinyl transferase (PPT) monodomain exhibited coenzyme A selectivity for the post-translational activation of the FAS acyl carrier protein (ACP).
The toxicity of some halomethanes in mice.

Abstract The acute toxicity of trichloromethane, bromodichloromethane, dibromochloromethane, and tribromomethane was studied in mice following administration by gastric gavage. Gross pathological changes included fatty infiltration of the liver and signs of hemorrhage in the kidneys, adrenals, lungs, and brain. Median lethal doses (LD50) were also calculated. Generally, the males were more sensitive to each of the compounds than females.
Science Signaling Podcast: 3 July 2012

This Podcast features an interview with Christopher Garcia, senior author of a Research Article published on 31 May 2012 in Science Express. Wnt signaling plays an important role in many developmental and homeostatic processes as well as in several types of cancer. Despite intensive study for many years, the structure of Wnts and information about how Wnts bind to their receptors, the Frizzled (Fz) proteins, have remained elusive. Garcia’s group has solved the crystal structure of a Wnt-Fz complex. The Wnt ligand formed a pincer-like two-domain structure that contacts opposite sides of Fz. Wnt ligands are lipidated, and the crystal structure also revealed that the lipid moiety covalently attached to Wnt participates in binding to Fz and could play an important role in ligand-receptor docking.
Refining Reputation to Truly Select High-QoS Servers in Peer-to-Peer Networks

Peer-to-peer networks (P2Ps) use reputation systems to provide incentives for nodes to offer high quality of service (QoS) and thwart the intentions of dishonest or selfish nodes. Existing reputation systems have two problems. First, they directly regard node reputation as trust. Reputation represents the opinion formed by others about a node's QoS behavior, while trust represents a node's honesty and willingness to cooperate. In addition to trust, factors such as node capacity and lifetime also influence reputation. Due to the heterogeneous and time-varying attributes of these factors, reputation actually cannot directly reflect a node's trust or current QoS. Second, existing reputation systems guide a node to select the server with the highest reputation, which may not actually select the highest QoS server and would overload the highest-reputed nodes. This work aims to accurately reflect node trust and provide accurate guidance for high QoS server selection. Through experimental study, we find that node trust, available capacity and lifetime positively affect node reputation. Based on this observation, we first propose a manual and an automatic trust model that removes the influence of additional factors on reputation to truly reflect node trust. We then propose a high-QoS server selection algorithm that separately considers node trust, current available capacity, and lifetime. Simulation results demonstrate the effectiveness of the trust models in accurate node trust reflection. Moreover, the server selection algorithm dramatically increases the success rate of service requests and avoids overloading nodes.
An Exploratory Investigation of Analogical Reasoning in International Marketing Based on Single Instances

There is reason to believe that when faced with new and complex situations people tend to use the similarity of that situation with a single prior instance, in making analogical predictions. This may be done at the cost of more objective and relevant information. Since international marketers entering new markets also face new and complex situations, there is a possibility that they too may rely heavily on single instances. An exploratory experiment found that people do seem to rely on subjective, less relevant but vivid information, compared to more objective evidence. Implications for international marketers are discussed.
Identifying unmet informational needs in the inpatient setting to increase patient and caregiver engagement in the context of pediatric hematopoietic stem cell transplantation

Background Patient-centered care has been shown to improve patient outcomes, satisfaction, and engagement. However, there is a paucity of research on patient-centered care in the inpatient setting, including an understanding of unmet informational needs that may be limiting patient engagement. Pediatric hematopoietic stem cell transplantation (HSCT) represents an ideal patient population for elucidating unmet informational needs, due to the procedure’s complexity and its requirement for caregiver involvement. Methods We conducted field observations and semi-structured interviews of pediatric HSCT caregivers and patients to identify informational challenges in the inpatient hospital setting. Data were analyzed using a thematic grounded theory approach. Results Three stages of the caregiving experience that could potentially be supported by a health information technology system, with the goal of enhancing patient/caregiver engagement, were identified: (1) navigating the health system and learning to communicate effectively with the healthcare team, (2) managing daily challenges of caregiving, and (3) transitioning from inpatient care to long-term outpatient management. Discussion We provide four practical recommendations to meet the informational needs of pediatric HSCT patients and caregivers: (1) provide patients/caregivers with real-time access to electronic health record data, (2) provide information about the clinical trials in which the patient is enrolled, (3) provide information about the patient’s care team, and (4) properly prepare patients and caregivers for hospital discharge. Conclusion Pediatric HSCT caregivers and patients have multiple informational needs that could be met with a health information technology system that integrates data from several sources, including electronic health records. Meeting these needs could reduce patients’ and caregivers’ anxiety surrounding the care process; reduce information asymmetry between caregivers/patients and providers; empower patients/caregivers to participate in the care process; and, ultimately, increase patient/caregiver engagement in the care process.
Rational Design of High-Number dsDNA Fragments Based on Thermodynamics for the Construction of Full-Length Genes in a Single Reaction

Gene synthesis is frequently used in modern molecular biology research either to create novel genes or to obtain natural genes when the synthesis approach is more flexible and reliable than cloning. DNA chemical synthesis has limits on both its length and yield, thus full-length genes have to be hierarchically constructed from synthesized DNA fragments. Gibson Assembly and its derivatives are the simplest methods to assemble multiple double-stranded DNA fragments. Currently, up to 12 dsDNA fragments can be assembled at once with Gibson Assembly according to its vendor. In practice, the number of dsDNA fragments that can be assembled in a single reaction are much lower. We have developed a rational design method for gene construction that allows high-number dsDNA fragments to be assembled into full-length genes in a single reaction. Using this new design method and a modified version of the Gibson Assembly protocol, we have assembled 3 different genes from up to 45 dsDNA fragments at once. Our design method uses the thermodynamic analysis software Picky that identifies all unique junctions in a gene where consecutive DNA fragments are specifically made to connect to each other. Our novel method is generally applicable to most gene sequences, and can improve both the efficiency and cost of gene assembly.
Epitaxial Growth of TbSi2 on Si(111)

We describe the epitaxial growth of TbSi2. In this study, terbium metal is evaporated onto (111) silicon and annealed to form terbium suicide, where the pressure during all procedures is maintained below 5×10-10 Torn The interdiffusion of terbium with silicon occurs at room temperature as determined by in-situ Auger electron spectroscopy. Low energy electron diffraction shows a sharp pattern of the hexagonal suicide after an 850°C anneal. Rutherford backscattering analysis indicates single-crystal growth with a channeling minimum yield of 7–8% for 120A thick suicide films annealed to 800–900°C. These metal reacted films have pinholes with an average size of less than 0.5 μm and a fault structure along (220) silicon. Electrical measurements show metallic conduction with a room temperature resistivity of 110 μΩ-cm and evidence of magnetic ordering at 38K.
Depressive symptoms are associated with worsened severity of the metabolic syndrome in African American women independent of lifestyle factors: A consideration of mechanistic links from the Jackson heart study

Abstract Background Depression and the metabolic syndrome (MetS) are both risk factors for cardiovascular disease and type 2 diabetes mellitus. Prior studies in predominantly White populations demonstrated that individuals with depressive symptoms at baseline are more likely to develop future MetS. We tested the hypothesis that depressive symptoms would contribute to a more pronounced increase in MetS severity among African Americans in the Jackson Heart Study (JHS). Methods We used repeated-measures modeling among 1743 JHS participants during Visits 1–3 over 8 years of follow-up to evaluate relations between depressive symptom score (Center for Epidemiologic Survey-Depression (CES-D)) at baseline and a sex- and race/ethnicity-specific MetS severity Z-score at each visit. Results 20.3% of participants had a CES-D score ≥16, consistent with clinically-relevant depressive symptoms. Higher depressive-symptom scores were associated with higher MetS severity in women but not men (p = 0.005 vs. p = 0.490). There was no difference by depressive symptom score with rate of change in MetS severity over time. Both depressive-symptom score and MetS severity Z-score were associated with lower levels of physical activity and higher levels of C-reactive protein; however, addition of these to the regression model did not attenuate the association between depressive symptoms and MetS severity. Conclusion African American women but not men in the JHS exhibit relationships between baseline depressive symptoms and MetS severity over an 8-year period. These data may have implications for targeting of MetS-associated lifestyle changes among individuals with depressive symptoms.
Simple subgroup approximations to optimal treatment regimes from randomized clinical trial data

We consider the use of randomized clinical trial (RCT) data to identify simple treatment regimes based on some subset of the covariate space, A. The optimal subset, A, is selected by maximizing the expected outcome under a treat-if-in-A regime, and is restricted to be a simple, as it is desirable that treatment decisions be made with only a limited amount of patient information required. We consider a two-stage procedure. In stage 1, non-parametric regression is used to estimate treatment effects for each subject, and in stage 2 these treatment effect estimates are used to systematically evaluate many subgroups of a simple, prespecified form to identify A. The proposed methods were found to perform favorably compared with two existing methods in simulations, and were applied to prehypertension data from an RCT.
Positive Surgical Margins at Radical Prostatectomy: Importance of the Apical Dissection

Positive margins were analyzed in 189 clinical stage B radical retropubic prostatectomies. Margins were identified by serially blocking the entire specimens in planes selected for optimum demonstration of capsule surface. Positive margins were divided into 2 categories: 1) those associated with capsular penetration of cancer and 2) those caused by inadvertent surgical incisions through the capsule into intracapsular cancer. Data were analyzed separately at each of 6 anatomical sites. Frequency of positive margins was related to the volume of cancer. Cancer of greater than 12 cc constituted a distinctive category in which seminal vesicle invasion, lymph node metastases and multiple positive margins were found in the majority of cases, signifying minimal possibility of cure. However, 31 positive margins occurred among 136 patients (23%) who were potentially curable by the criteria of normal seminal vesicles and absence of pelvic lymph node metastases; 17, of these 31 surgically positive margins (55%) occurred at the apex. Positive capsular penetration margins at the apex were volume-related, while negative margins were not. Site specific recommendations for avoiding positive and negative capsular penetration margins are suggested. The prostate apex, rectal and lateral surfaces, bladder neck and superior pedicles accounted for 48, 24, 16 and 10% of all positive margins, respectively. Dissection of the apical prostate and Denonvilliers' fascia require modifications of current surgical techniques if positive margins are to be avoided. Serum levels of prostate specific antigen may require as long as 5 years to become detectable when only 1 positive margin is the only evidence of nonorgan-confined disease.
Ammonia supply chains: A new framework for renewable generation with a case study for Minnesota

Abstract This work addresses the introduction of renewable ammonia plants with hydrogen obtained from wind-powered electrolysis into a region’s ammonia supply chain. A supply chain optimization problem is fomulated to decide where to build new renewable plants, how large they should beand how much ammonia should be transported between conventional plants, renewable plants, distribution centers, and demand centers to meet local demand. A multiobjective optimization problem is also formulated to analyze tradeoffs between economic and environmental objectives. The developed framework is applied to a case study in Minnesota utilizing cost data from a pilot renewable plant in Morris, MN. The base case establishes that it is economically optimal to build a single new renewable plant that supplies 27% of the state’s ammonia. New renewable plants are selected for construction in 48% of Monte Carlo trials. A carbon tax analysis is also performed to analyze the carbon emissions of the supply chain. The analysis shows that a modest carbon tax of just $35/t cuts emissions by 65% and promotes the construction of 3 new renewable plants.
A novel human-specific splice isoform alters the critical C-terminus of Survival Motor Neuron protein

Spinal muscular atrophy (SMA), a leading genetic disease of children and infants, is caused by mutations or deletions of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to skipping of exon 7. SMN2 predominantly produces SMNΔ7, an unstable protein. Here we report exon 6B, a novel exon, generated by exonization of an intronic Alu-like sequence of SMN. We validate the expression of exon 6B-containing transcripts SMN6B and SMN6BΔ7 in human tissues and cell lines. We confirm generation of SMN6B transcripts from both SMN1 and SMN2. We detect expression of SMN6B protein using antibodies raised against a unique polypeptide encoded by exon 6B. We analyze RNA-Seq data to show that hnRNP C is a potential regulator of SMN6B expression and demonstrate that SMN6B is a substrate of nonsense-mediated decay. We show interaction of SMN6B with Gemin2, a critical SMN-interacting protein. We demonstrate that SMN6B is more stable than SMNΔ7 and localizes to both the nucleus and the cytoplasm. Our finding expands the diversity of transcripts generated from human SMN genes and reveals a novel protein isoform predicted to be stably expressed during conditions of stress.
Adecuación de la teriparatida y grado de aceptación de las recomendaciones farmacoterapéuticas en un área de gestión sanitaria

Objective: To analyse the suitability of teriparatide prescriptions for osteoporosis treatment in a health management area, as well as the level of acceptance of pharmacotherapeutic recommendations made to physicians. Design: A prospective interventional study conducted from february 2015 to june 2015. Setting: South Seville Health Management Area. Participants: Patients receiving teriparatide. Main measurements: Suitability of teriparatide prescriptions according to Clinical Practice Guidelines and level of acceptance of pharmacotherapeutic recommendations. Results: Teriparatide prescriptions were unsuitable in 45 patients (68.2%); 11 due to no indication, 17 patients did not have previous treatments with first-line drugs, 6 due to contraindications and 9 patients were treated for more than 24 months with the drug. Besides, 4 prescriptions were unsuitable because of combination with other therapies. The acceptance of pharmacotherapeutic recommendations was 64.4%, leading to teriparatide discontinuation in 21 patients (72.4%), and a switch to alendronate or ibandronate in another 8 patients. Conclusions: A high percentage of teriparatide prescriptions is unsuitable in our health care management area, but it has decreased after pharmacist intervention.