cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of copper–nickel alloys fabricated using laser metal deposition and blended powder feedstocks

In the current study, the feasibility of fabricating copper–nickel alloys by using laser metal deposition and blended powder feedstocks was investigated through material characterization. Material fabricated from the blended powder mixtures containing elemental nickel was seen to possess large amounts of gas and shrinkage porosity. Due to this porosity, elemental nickel powder was deemed to be an unviable modular feedstock. Instead, Delero-22, a high nickel content alloy, was identified as a viable substitute for elemental nickel. The silicon and boron alloy additions in Delero-22 alloy were identified to be crucial in overcoming the porosity prevalent when using elemental nickel. Counterparts to commercially available copper–nickel alloys were then fabricated using blended elemental copper and Delero-22 alloy powders. Thus, fabricated alloys were characterized using X-ray diffraction, scanning electron microscopy, Vickers hardness testing, energy-dispersive X-ray spectroscopy, and mini-tensile testing. Analyses revealed that the deposited material was formed with homogenous microstructure and the resultant compositions were close to as-blended feedstocks. The results from tensile testing showed an increase in strength caused by solid solution strengthening upon addition of copper to nickel. The addition of copper also increased the ductility of the material. Analysis of the fracture surface revealed changes in the fracture mechanism from transgranular to ductile with an increase in copper content. Variation in scan speed during laser metal deposition resulted in a change in average secondary dendrite arm spacing and variability in tensile performance.
Superconductivity in the Narrow‐Gap Semiconductor CsBi4Te6.

Centimeter-sized crystals of the title compound are prepared by reaction of Bi2Te3 with Cs in the vapor phase at 670 °C followed by melting and slow cooling.
Epidural Anesthesia is Associated With Increased Complications in Cystectomy Patients: A NSQIP Analysis.

Abstract Objective To identify differences in short-term outcomes and readmission rates in cystectomy patients managed with general anesthesia compared to those undergoing general anesthesia and adjuvant epidural anesthesia. Methods Utilizing the National Surgical Quality Inpatient Program database, patients who underwent a cystectomy with ileal conduit between 2014 and 2017 were included. Patients were further subdivided based on additional anesthesia modality; general anesthesia vs general anesthesia plus epidural anesthesia. Propensity score-matching was used to adjust for baseline differences between cohorts using 1:1 caliper width of 0.15 for the propensity score through the nearest neighbor. Stepwise multivariable logistic regression was used to identify preoperative and intraoperative predictors associated with 30-day procedure related readmission, complications, and length of stay. Results About 2956 patients met our inclusion and exclusion criteria and eligible for propensity score matching. Compared to general anesthesia, adjuvant epidural anesthesia showed an increased odds of procedure related complications (adjusted Odds Ratio (aOR): 1.264, 95% CI: 1.019-1.567, P = .033). There was an increased trend for development of pulmonary emboli (13 [1.8%] vs 4 [0.5%], P = .051) in the adjuvant epidural cohort. Combined general with epidural anesthesia demonstrated no difference in length of stay, readmission, or reoperation rate in comparison to general anesthesia alone. Conclusion Cystectomy patients who underwent general anesthesia plus epidural anesthesia demonstrated a higher percentage of any procedural related complication without change in postoperative stay, reoperation rate, or readmission rate compared to patients undergoing general anesthesia alone.
Postcumulus and subsolidus equilibration of chromite and coexisting silicates in the Eastern Bushveld Complex

Analyses of chromite and coexisting olivine or bronzite in various textural associations in the Critical Zone of the Eastern Bushveld Complex are examined for evidence of the extent and nature of postcumulus or subsolidus equilibration of chromite and Fe-Mg silicates. Sub-solidus equilibration of chromite inclusions in bronzite and olivine is indicated, and postcumulus or subsolidus equilibration of chromite with postcumulus bronzite is indicated in mottled anorthosite of the H unit. Compositional zoning of cumulus bronzite is inferred to be due to equilibration with cumulus chromite during the postcumulus stage. The main pattern of variation in Mg/Fe ratio and A12O3 content of chromite with modal per cent chromite is inferred, however, to have been produced during the cumulus stage. The data are consistent with control of chromite precipitation and composition by the oxygen fugacity of the magma, but the effects of changes in pressure or other variables of the magma system on chromite stability and composition are still largely unknown.
The influence of humor on workplace mentoring and employee attitudes

Organizations are under continual pressure to cultivate an environment in which employees feel valued and committed, and mentoring provides one channel through which this may be achieved. In particular, the dynamics characterizing the mentoring relationship are of paramount importance. In the current study of 108 direct-care staff at a psychiatric hospital, we investigated the influence of 2 aspects of these dynamics—mentor humor style and the frequency with which humor is used—on protege satisfaction with the mentoring relationship and on several key work-related outcomes (i.e., organizational commitment, job satisfaction, and turnover intentions). Overall, mentor humor style and frequency were both positively associated with proteges’ mentoring satisfaction. Furthermore, mentoring satisfaction favorably influenced proteges’ affective organizational commitment and job satisfaction, both of which were inversely related to their turnover intentions. Theoretical and practical implications of these results, along with the role of indirect effects, are discussed.
Science, Context, and Gender Fluidity in Public Policy

This interdisciplinary essay combines science, social sciences, and the humanities to argue in favor of a less rigid understanding of the traditional gender binary of male and female. Relying on re...
Lectures On Black Hole Evaporation and Information Loss

Trieste Spring School Lectures describing the author's opinions about black hole evaporation and information loss. The remnant, or cornucopion scenario for the endpoint of Hawking evaporation is described in detail. In this picture information can be lost to the original asymptotic observer without violating the rules of quantum mechanics, because a black hole remnant is viewed as a large space connected onto our own by an almost pointlike opening. It does not behave like an elementary particle. Objections to remnants are refuted and the (remote) possibility of testing this scenario experimentally is discussed. Also included is a brief description of Susskind's picture of the stringy origin of Bekenstein-Hawking entropy. An attempt is made to argue that the cornucopion picture and Susskind's model of the states responsible for black hole entropy are compatible with each other. Information is lost to the asymptotic observer in Hawking evaporation, but the information encoded in the BH entropy remains in causal contact with him and is re-emitted with the Hawking radiation.
Defeating Cache Timing Channels with Hardware Prefetchers

Editor’s note: This article proposes a framework to mitigate cache timing attacks. The framework identifies attacks and targets by monitoring the cache access pattern and counteracts them by injecting noise using hardware prefetcher. — Rosario Cammarota, Intel Labs — Francesco Regazzoni, University of Amsterdam and Universita della Svizzera Italiana
Annealing Accelerator for Ising Spin Systems based on In-memory Complementary 2D FETs.

Metaheuristic algorithms such as simulated annealing (SA) has been implemented for optimization in combinatorial problems, especially for discreet problems. SA employs a stochastic search, where high-energy transitions ("hill-climbing") are allowed with a temperature-dependent probability to escape local optima. Ising spin glass systems have properties such as spin disorder and "frustration" and provide a discreet combinatorial problem with high number of metastable states and ground-state degeneracy. In this work, we exploit subthreshold Boltzmann transport in complementary two-dimensional (2D) field effect transistors (p-type WSe2 and n-type MoS2 ) integrated with analog, non-volatile, and programmable floating-gate memory stack to develop in-memory computing primitives necessary for energy and area efficient hardware acceleration of SA for the Ising spin systems. We experimentally demonstrate > 800X search acceleration for 4 × 4 ferromagnetic, antiferromagnetic, and a spin glass system using SA compared to an exhaustive search using brute force trial at miniscule total energy expenditure of ∼120 nJ. Our hardware-realistic numerical simulations further highlight the astounding benefits of SA in accelerating the search for larger spin lattices. This article is protected by copyright. All rights reserved.
A Framework for Reconsidering the Lake Wobegon Effect

The Lake Wobegon Effect (LWE) describes the potential measurement-error bias introduced into survey-based analyses of education issues. Although this effect potentially applies to any student-report variable, the systematic overreporting of academic achievements such as grade point average is often of preeminent concern. This concern can be easily circumvented if official records data are available; however, many researchers can only access student-reported data. In this article, the authors examine whether using student-survey data in place of official records data meaningfully biases regression estimates. They motivate their contribution by noting a useful statistical feature of overreporting on bounded variables such as grade point average. Specifically, the misreports will be negatively correlated with the true grade point average, yielding a form of nonclassical measurement error that actually counteracts the bias. The authors connect this observation to reliability ratios used in labor economics, wh...
Quasi-Conical Free Interaction in Fin-Induced Shock Wave/Laminar Boundary-Layer Interactions

A numerical study was performed on the three-dimensional interaction between a laminar boundary layer and the shock wave induced by a sharp, unswept fin mounted perpendicularly on a flat plate at f...
Instrumented Wave Gliders for Air-Sea Interaction and Upper Ocean Research

Over the last several years, the Air-Sea Interaction Laboratory at Scripps Institution of Oceanography has developed a fleet of wave-powered, uncrewed Wave Gliders (Liquid Robotics) specifically designed and instrumented for state-of-the-art air-sea interaction and upper ocean observations. In this study, measurement capabilities from these platforms are carefully described, compared, and validated against coincident measurements from well-established, independent data sources. Data collected from four major field programs from 2013 to 2020 are considered in the analysis. Case studies focusing on air-sea interaction, Langmuir circulations and frontal processes are presented. We demonstrate here that these novel, instrumented platforms are capable of collecting observations with minimal flow-structure interaction in the air-sea boundary layer, a region of crucial current and future importance for models of weather and climate.
Cellular perception of growth rate and the mechanistic origin of bacterial growth laws

Cells organize many of their activities in accordance to how fast they grow1-4. Yet it is not clear how they perceive their rate of growth, which involves thousands of reactions. Through quantitative studies of E. coli under exponential growth and during growth transitions, here we show that the alarmone ppGpp senses the rate of translational elongation by ribosomes, and together with its roles in controlling ribosome biogenesis and activity5-9, closes a key regulatory circuit that enables the cell to perceive the rate of its own growth for a broad class of growth-limiting conditions. This perception provides the molecular basis for the emergence of simple relations among the cellular ribosome content, translational elongation rate, and the growth rate, as manifested by bacterial growth laws2,10-13. The findings here provide a rare view of how cells manage to collapse the complex, high-dimensional dynamics of the underlying molecular processes to perceive and regulate emergent cellular behaviors, an example of dimension reduction performed by the cells themselves.
Too Big Not to Fail: Federalism and the Failure of Local Urban Redevelopment Policies

Although Congress continues to pass urban redevelopment programs and local actors attempt to use these policies to address urban problems, many policies do not live up to initial expectations. Urban policy scholars tend to focus on local political or economic arrangements to explain this phenomenon, while public policy scholars emphasize the role of special interest or bureaucratic influence on policy success or failure. Neither approach studies the ideas and institutional arrangements motivating urban policy, nor do they do so over time. In this paper, I suggest a new framework for exploring urban redevelopment policy: intercurrence, which is a theoretical framework and analytical lens used in the subfield of American Political Development (APD). Using the Community Reinvestment Act (CRA) as a case study and congressional hearings as my unit of analysis, I argue that challenges to successful policy implementation can best be appreciated by understanding how ideological commitments to certain ideas and institutional arrangements inherent to American principles of separation of powers and federalism circumscribe policy creation and implementation at the local level.
Magnetic resonance imaging in the quantitative assessment of gouty tophi

Measurements of tophus size can be important in monitoring the course of gout therapy, as tophus resolution is proposed as one measure of success of treatment. This multicentre study assessed the intra- and interreader reproducibility of quantitative tophus volume measurements from magnetic resonance images (MRI) in subjects with palpable gouty tophi. Subjects first underwent radiographic imaging of a selected tophus followed by MRI before and at <or=5, 10 and 20-min after gadolinium administration. After choosing optimal parameters, subjects underwent pre- and postgadolinium-enhanced MRIs of a selected tophus on two occasions separated by 5-10 days. Unenhanced spin-echo images provided satisfactory tophi images and were less subject to interfering artefacts than gadolinium-enhanced gradient-echo images. Intrareader reproducibility was excellent, with no statistically significant difference in mean tophus volume between visits (mean difference - 0.05 +/- 0.97 cm3). A small but statistically significant difference in interreader mean tophus volume was detected (mean difference 0.89 +/- 2.05 cm3; p < 0.05). MRI can quantify tophus size in gout and deserves further comparison with other techniques for tophus size monitoring in assessing effects of gout therapy.
Secretion of atrial natriuretic factor-(1-98) by primary cardiac myocytes

Previous studies have demonstrated that primary cultures of cardiac myocytes maintained in a complete serum-free medium contain a precursor to atrial natriuretic factor (ANF-(1-126]. The cultured cells secrete this precursor unless maintained in the presence of glucocorticoids wherein the known circulating form derived from the C-terminal of ANF (ANF-(99-126] is secreted. The present study was designed to determine the fate of the N-terminal region of the ANF precursor during secretion from myocytes maintained in glucocorticoids. A radioimmunoassay (RIA) was developed using synthetic ANF-(1-16); the antiserum demonstrated cross-reactivity toward ANF-(1-126) and ANF-(1-98)-like peptides but did not cross-react with ANF-(99-126). Coupling this RIA with an ANF-(99-126)-specific RIA and reversed phase, size exclusion, and ion exchange high performance liquid chromatography (HPLC), it was shown that primary cultures of atrial myocytes maintained in dexamethasone contained ANF-(1-126) and secreted ANF-(99-126) and a peptide that was chromatographically indistinguishable from ANF-(1-98). Isolated perfused rat hearts were also shown by RIA and HPLC to secrete similar peptides. The primary cells were labeled with [35S]methionine, and the secreted N-terminal ANF-related material was immunoprecipitated with the ANF-(1-16) antiserum. HPLC, tryptic peptide mapping, and radiosequencing demonstrated that this peptide possessed an N-terminal structure identical to that of ANF-(1-126). When the cells were labeled with [3H] leucine and the secreted N-terminal ANF-related material was immunoprecipitated and analyzed by tryptic mapping, it was shown to possess labeled tryptic peptides consistent with the structure of ANF-(1-98). Tryptic mapping of [3H]arginine-labeled N-terminal ANF-related material demonstrated the presence of all peptides consistent with the ANF-(1-98) structure, including ANF-(92-98). These studies demonstrate that primary atrial myocytes contain ANF-(1-126) and in the presence of dexamethasone secrete both ANF-(1-98) and ANF-(99-126), the two major circulating forms of the hormone.
Peak Shaving through Resource Buffering

We introduce and solve a new problem inspired by energy pricing schemes in which a client is billed for peak usage. At each timeslot the system meets an energy demand through a combination of a new request, an unreliable amount of free source energy (e.g. solar or wind power), and previously received energy. The added piece of infrastructure is the battery , which can store surplus energy for future use. More generally, the demands could represent required amounts of energy, water, or any other tenable resource which can be obtained in advance and held until needed. In a feasible solution, each demand must be supplied on time, through a combination of newly requested energy, energy withdrawn from the battery, and free source. The goal is to minimize the maximum request. In the online version of this problem, the algorithm must determine each request without knowledge of future demands or free source availability, with the goal of maximizing the amount by which the peak is reduced. We give efficient optimal algorithms for the offline problem, with and without a bounded battery. We also show how to find the optimal offline battery size, given the requirement that the final battery level equals the initial battery level. Finally, we give efficient H n -competitive algorithms assuming the peak effective demand is revealed in advance, and provide matching lower bounds.
Acute sensitization to opioid antagonists.

Abstract Acute morphine pretreatment sensitizes rats to the response rate-decreasing effects of opioid antagonists naloxone and naltrexone. The effect appears to be mu-opioid receptor specific, as pretreatment with non-mu-selective oipiod agonists results in less pronounced sensitization. In the present study, food-deprived rats were trained to respond for food reinforcement on a FI 3-min schedule (9.5 min) with multiple trials. Doses of opioid antagonists were administered cumulatively before each trial of a session following 4-h pretreatment with either vehicle or morphine (3.0 mg/kg). Morphine pretreatment sensitized rats to naltrexone, lowering its ED50 from 20 to 0.03 mg/kg. It also sensitized rats to naloxone and to diprenorphine, another pure antagonist. Morphine-induced sensitization was stereoselective among the optical isomers of the benzomorphans, cyclazocine, pentazocine, and N-allylnormetzocine. In addition, acute morphine pretreatment resulted in sensitization to the mixed agonist/antagonist nalorphine, but not to buprenorphine or nalbuphine. The results extend previous findings concerning the importance of the mu-opioid receptor in the development of sensitization to opioid antagonists.
A 3-query PCP over integers

A classic result due to Haastad~hastad established that for every constant e > 0, given an overdetermined system of linear equations over a finite field Fq where each equation depends on exactly 3 variables and at least a fraction (1-e) of the equations can be satisfied, it is NP-hard to satisfy even a fraction (1/q+e) of the equations.In this work, we prove the analog of Hastad's result for equations over the integers (as well as the reals). Formally, we prove that for every e,δ > 0, given a system of linear equations with integer coefficients where each equation is on 3 variables, it is NP-hard to distinguish between the following two cases: (i) There is an assignment of integer values to the variables that satisfies at least a fraction (1-e) of the equations, and (ii) No assignmenteven of real values to the variables satisfies more than a fraction δ of the equations.
Hierarchical MapReduce Programming Model and Scheduling Algorithms

We present a Hierarchical MapReduce framework that gathers computation resources from different clusters and runs MapReduce jobs across them. The applications implemented in this framework adopt the Map-Reduce-Global Reduce model where computations are expressed as three functions: Map, Reduce, and Global Reduce. Two scheduling algorithms are introduced: Compute Capacity Aware Scheduling for compute-intensive jobs and Data Location Aware Scheduling for data-intensive jobs. Experimental evaluations using a molecule binding prediction tool, Auto Dock, and grep demonstrate promising results for our framework.
Reason and Culture: Debating the Foundations of Morals in a Pluralist World

Masolo takes as his starting point a dinnertime discussion between two teenagers on the role of tradition, a discussion that led into a debate on the merits of the idea of autonomous reason. The author was struck by their cosmopolitan multiculturalism and by the transient nature of the communities from which people source their points of view, allowing them to question the rationality of opposing views. This article expands such theoretical concerns and applies them to an assessment of Kant’s culture-free moral principles against a communitarian view of the resources of reason.
Utilization of in vivo liver perfusion to prevent pulmonary damage following regional ischemia

Abstract A 4-hour period of extremity ischemia in dogs produces intravascular coagulation and results in 50 per cent mortality at 24 hours. Hemorrhagic atelectasis of the lungs is produced, and microemboli can be identified within the pulmonary arterioles. Portacaval transposition followed by the regional ischemia preparation results in no gross or microscopic abnormality in the lungs or liver, although there is a significant elevation of SGOT values. The mortality of the combined procedure is 7 per cent. The importance of the RE system to recovery from shock is emphasized.
The convective liquidus in a solidifying magma chamber - A fluid dynamic investigation

An experimental study of the solidification of a layer of paraffin cooled from above is reported. When the fluid is superheated, convection sets in at the beginning of cooling but rapidly decreases in intensity. Once the layer has lost its superheat, convection ceases and further cooling is by conduction. The interior temperature then remains constant until encountered by the upper crust. The convective liquidus is defined as the temperature threshold below which convection is very weak or nonexistent. In natural basaltic systems the convective liquidus, although strictly unknown, may be very close to the true liquidus. Rapid convection may therefore not be a dominant process during the crystallization of many magmna chambers; instead, convection is part of an overall intimate balance between phase equilibria, crystal growth, and heat transfer.
Exacerbation of a lupus-erythematosus-like syndrome during treatment of non-C1-esterase-inhibitor-dependent angioedema with danazol

A 70-yr-old man presented with symptoms of angioedema and a lupus erythematosus-like syndrome. Because initial studies showed a functional deficiency of C1 esterase inhibitor and low C4 levels, he was treated with danazol, an attenuated androgen that has proven to be effective in the treatment of angioedema associated with C1 esterase inhibitor deficiency. After treatment, the patient's C4 levels returned to normal and his angioedema resolved, but concurrently he experienced clinical and laboratory exacerbations of his lupuslike illness. Specifically, on two occasions after danazol treatment he developed arthralgias, myalgias, hematuria, and pleuritic chest pain, accompanied by increased titers of antinuclear antibodes and circulating immune complexes. Serum testosterone levels were decreased during these episodes. Because treatment with danazol was temporally associated with recurrent exacerbations of a lupuslike illness and low serum testosterone levels, we believe that this case is an example of sex hormonal modulation of a lupuslike disease in man.
Rare earth element complexation behavior in circumneutral pH groundwaters: Assessing the role of carbonate and phosphate ions

Rare earth element (REE) concentrations were determined in circumneutral pH (7 ≤ pH ≤ 9) groundwaters from south-central Nevada and the Mojave Desert in eastern California, U.S.A. The inorganic speciation of the REEs in these water were evaluated primarily to assess the relative importance of carbonate (LnHCO32+, LnCO3+ and Ln(CO3)2−) and phosphate (LnH2PO42+, LnHPO4+, Ln(HPO4)2− and LnPO40) complexes. Other REE complexes with sulfate, hydroxyl, chloride, and fluoride ions were also assessed, as was the significance of the free metal ion species (i.e., Ln3+). Our speciation calculations indicate that REE-carbonate complexes dominate and typically account for more than 99% of each REE in solution. Moreover, carbonato complexes (LnCO3+) were predicted to be the dominant species for the light REEs and dicarbonato complexes (Ln(CO3)2−) were predicted to increase in importance with increasing atomic number. All other complexes were predicted to be negligible. Furthermore, the combined percentage of all REE-phosphate complexes never accounted for more than 0.1% of the dissolved REEs, and generally much less than 0.1%. Phosphate complexes can not compete with carbonate complexes in these groundwaters because of the low ∑PO43− concentrations (< 0.3–1.58 μmol/kg), the much lower concentrations of the free phosphate ion (i.e., [PO43−]F = 10−9−10−6 μmol/kg), due to ion pair formation with Ca2+ and Mg2+, and the much higher free carbonate ion concentrations ([CO32−]F = 0.32−87 μmol/kg).
What's an Oscar worth?

This article examines the impact of an Academy Award nomination and award for best picture, best actor/actress, and best supporting actor/actress on a film's (i) market share of theaters, (ii) average revenue per screen, and (iii) its probability of survival. The model is estimated using weekly box-office data for a matched sample of nominated and non-nominated films. The results indicate substantial financial benefits for a nomination and award for best picture and best actor/actress. The structure of rewards is consistent with that found in two-stage, single-elimination tournaments.
An alternating selection strategy for cloning phage display antibodies

Phage display is a powerful technique that can be used to develop antibodies to target molecules. One approach for antibody phage display is to select phage from a large naive library of antibody immunoglobulin variable region fragments (Fv) expressed on the surface of phage. Phage that display antibody fragments of interest are selected by their ability to bind the target antigen immobilized on a solid support surface. A major difficulty often encountered with this approach is that phage that bind to additional antigens that are present during the phage selection steps are also selected. We have developed an alternating selection approach to minimize selection of unwanted phage. In the alternating selection approach, two selection methods are used. Each selection method contains different contaminating antigens. This approach was used to select phage that bind a phosphoryated form of the E47 transcription factor. Phage were selected based on their ability to bind a phospho-peptide in solution and alternatively a phospho-protein coated on a polyvinyl micortiter plate. This approach proved significantly better than selection with only one method. With one selection technique, 2 of 48 (4%) selected clones bound to the target antigen. With another selection technique, 15 of 48 (31%) selected clones bound to the target antigen. With alternating selection, 71 of 93 (76%) of the clones bound to the target antigen.
The Use of Buproprion in Reducing Cravings after Cessation of Cocaine Use

(1995). The Use of Buproprion in Reducing Cravings after Cessation of Cocaine Use. Substance Abuse: Vol. 16, No. 3, pp. 181-182.
Persistent IR spectral hole-burning in chalcogenide glasses

Abstract All persistent spectroscopic effects observed to date in glassy hosts have involved electronic excitation of the defect center, with the hole-burning attributed either to photochemical modification of the defect itself, or to rearrangement of the host atoms around the defect. Here we describe the production of persistent infrared spectral holes in the vibrational spectrum of molecules doped into chalcogenide glasses, the first observation of non-electronic spectral persistence in a glassy host.
Density fluctuations in a fluid mixture of hard spheres

Time-dependent phase-space density correlation functions in a fluid mixture of hard spheres are analyzed using a coupled set of generalized Boltzmann equations. The matrix of memory functions is expressed explicitly as static, direct-collision, and cross-collision contributions. Low-order matrix elements of the memory functions are calculated, and the results used to discuss the hydrodynamics of the system and to construct kinetic models. Numerical spectra of density fluctuations are presented to illustrate the effects due to dynamical correlations in a mixture.
Predictive biomarkers in colorectal cancer: usage, validation, and design in clinical trials

As cancer treatment development has shifted its attention to targeted therapies, it is becoming increasingly important to provide tools for selecting the right treatment for an individual patient to achieve optimal clinical benefit. Biomarkers, identified and studied in the process of understanding the nature of the disease at the molecular pathogenesis level, have been increasingly recognized as a critical aspect in more accurate diagnosis, prognosis assessment, and therapeutic targeting. Predictive biomarkers, which can aid treatment decisions, require extensive data for validation. In this article, we discuss the definition, clinical usages, and more extensively the clinical trial designs for the validation of predictive biomarkers. Predictive biomarker validation methods can be broadly grouped into retrospective and prospective designs. Retrospective validation utilizes data from previously conducted prospective randomized controlled trials. Prospective designs include enrichment designs, treatment-by-marker interaction designs, marker-based strategy designs, and adaptive designs. We discuss each design with examples and provide comparisons of the advantages and disadvantages among the different designs. We conclude that the combination of scientific, clinical, statistical, ethical, and practical considerations provides guidance for the choice of the clinical trial design for validation of each proposed predictive biomarker.
Salt-Finger convection in the surface discharge of heated saline jets

Experimental investigations of the surface discharge of two-dimensional heated saline jets into surroundings with stable, constant salt gradients were carried out. The discharge conditions were par...
A VISCOSITY MODEL FOR A COOKING DOUGH

A five parameter semi-empirical model is developed describing the apparent viscosity of a cooking dough as a function of applied shear rate, temperature, and time-temperature history. Such a model will be useful in the mathematical simulation of the extrusion cooking process. Other factors which can affect the apparent viscosity of a cooking dough are also discussed. The viscosity model is verified and the constants evaluated for a typical dough by combining the results of Amylograph and capillary viscometer experiments.
Altered function and histology in guinea pigs after inhalation of diesel exhaust

Health effects of inhaled diesel engine exhaust were evaluated in infant guinea pigs following 4 and 8 weeks of exposure. Animals were exposed to 1 part exhaust diluted by 13 parts clean air for 20 hr/day, 7 days/week. Lung function, electrocardiogram, growth rate, and histopathology were assessed following exposure. After 4 weeks, animals exposed to irradiated exhaust, showed a 35% increase in pulmonary air flow resistance, and a small but significant decrease in heart rate. Necropsy, after 8 weeks, showed exhaust exposed animals to have black discoloration of the lungs and increased lung to body weight ratios. Microscopic examination of the lungs from these animals revealed black particulate material in the cytoplasm of alveolar macrophages and in draining lymph nodes.
The effect of tagging upon the fatty acid metabolism of juvenile pink salmon.

Abstract 1. 1. Wild juvenile pink salmon were captured at sea, tagged with a Dennison internal anchor tag and retained in sea water for 32 days. 2. 2. Mortality of tagged salmon was significantly higher than in untagged salmon. 3. 3. Liver lipid percentage increased from 5·9 per cent in untagged salmon to 10·4 per cent in tagged salmon and these changes were accompanied by diminutions in muscle weight and increases in liver weight. 4. 4. Extensive mobilization of specific fatty acids from muscle to liver tissues occurred in tagged salmon. These fatty acids were primarily of the monounsaturated and saturated types.
Towards computer-aided configuration design for the life cycle

In modern design, life-cycle concerns such as recycling and service are receiving increased attention. The configuration design phase, where the product and component structure is established, is of particular importance when designing for the life cycle. In this paper, the foundation for a CAD system supporting configuration design for the life cycle is presented. A prototypical CAD system, called CODA (Configuration Design of Assemblies), is under development based on this foundation. A discussion on the supported product and component representation is given, followed by a portrayal of some of the capabilities to support life-cycle design. Specifically, requirements are identified for the information needed to support design for assembly, disassembly, service, recycling, and reuse. A case study involving the (re)design of a hand-held tape recorder with respect to improved disassemblability and recyclability is utilized to highlight some of the capabilities of the current system. With the new product and component representation embodied in CODA, improved support over current CAD systems is provided for configuration design and life-cycle design assessments.
Hyperfine structure of 2 3 P levels of heliumlike ions

A systematic calculation of the hyperfine structure of 2${\mathrm{}}^{3}$P levels of heliumlike ions is presented. Reduced matrix elements of the magnetic-dipole hyperfine operator between substates of the 2${\mathrm{}}^{1,3}$P states are evaluated using relativistic configuration-interaction wave functions that account for both Coulomb and Breit interactions. These matrix elements, together with the energy intervals \ensuremath{\Delta}${\mathrm{E}}_{10}$=E(2${\mathrm{}}^{3}$${\mathrm{P}}_{1}$)-E(2${\mathrm{}}^{3}$${\mathrm{P}}_{0}$), \ensuremath{\Delta}${\mathrm{E}}_{20}$=E(2${\mathrm{}}^{3}$${\mathrm{P}}_{2}$)-E(2${\mathrm{}}^{3}$${\mathrm{P}}_{0}$), and \ensuremath{\Delta}${\mathrm{E}}_{\mathrm{st}}$=E(2${\mathrm{}}^{1}$${\mathrm{P}}_{1}$)-E(2${\mathrm{}}^{3}$${\mathrm{P}}_{0}$), are tabulated for ions with nuclear charges in the range Z=2--100. For Z=2, the matrix elements are in close agreement with precise nonrelativistic variational calculations, but as Z increases from 2 to 10, the present values deviate smoothly from the variational values owing to relativistic corrections. Applications are given to determine the hyperfine structure of $^{3}\mathrm{He}$, $^{6,7}\mathrm{Li}^{+}$, $^{9}\mathrm{Be}^{2+}$, and $^{19}\mathrm{F}^{7+}$. Hyperfine quenching rates of 2${\mathrm{}}^{3}$${\mathrm{P}}_{0}$ states are calculated using a radiation-damping formalism for all stable isotopes in the range Z=6--92. Quenching rates of 2${\mathrm{}}^{3}$${\mathrm{P}}_{2}$ states are also calculated for selected ions. For Z=9--29, the 2${\mathrm{}}^{3}$${\mathrm{P}}_{0}$ quenching rates are in good agreement with relativistic 1/Z calculations. For Zg40, the diagonal hyperfine matrix elements disagree in sign with previously published multiconfiguration Dirac-Fock values. In view of these differences, the present matrix elements are used to reevaluate the fine-structure intervals \ensuremath{\Delta}${\mathrm{E}}_{10}$ inferred from hyperfine quenching experiments for the ions ${\mathrm{Ni}}^{26+}$, ${\mathrm{Ag}}^{45+}$, and ${\mathrm{Gd}}^{62+}$.
S-RNase and SLF determine S-haplotype-specific pollen recognition and rejection

Self-incompatibility (SI) is a genetically determined system for recognition and rejection of self-pollen and pollen from closely related plants. Recognition specificity is controlled by the S -locus. This locus is complex in the sense that it contains multiple genes: one controls specificity on the
The validity of self-reports of alcohol consumption: state of the science and challenges for research.

Aims To review three topics pertaining to the validity of alcohol self-reports: factors that influence response accuracy; the relative merits of different self-report approaches; and the utility of using alternative measures to confirm verbal reports. Findings Response behavior is influenced by the interaction of social context factors, respondent characteristics, and task attributes. Although research has advanced our knowledge about self-report methods, many questions remain unanswered. In particular, there is a need to investigate how task demands interact with different patterns of drinking behavior to affect response accuracy. There is also a continuing need to use multiple data sources to examine the extent of self-report response bias, and to determine whether it varies as a function of respondent characteristics or assessment timing. Conclusion Self-report methods offer a reliable and valid approach to measuring alcohol consumption. The accuracy of such methods, however, can be improved by research directed at understanding the processes involved in response behavior.
An Iterative Thresholding Algorithm for Image Segmentation

A thresholding technique is developed for segmenting digital images with bimodal reflectance distributions under nonuniform illumination. The algorithm works in a raster format, thus making it an attractive segmentation tool in situations requiring fast data throughput. The theoretical base of the algorithm is a recursive Taylor expansion of a continuously varying threshold tracking function.
Non-histone protein phosphorylation in normal and neoplastic rat liver chromatin☆

Abstract Hepatectomy or exposure of rats to a hepatocarcinogenic azo dye, N,N-dimethyl-p-(m-tolylazo)-aniline or 3′ MDAB resulted in a sharp increase of the activity of cytoplasmic and chromatin-bound phosphoprotein kinases in liver. While in the regenerating rat liver both enzyme groups increased nearly equally, in the 3′-MDAB-treated animals, there was much greater increase of the cytoplasmic kinases as compared with the chromatin-bound enzymes. The activation of phosphoprotein kinases was accompanied by an increase of the ability of liver chromatin to template for the in vitro RNA synthesis. This transcriptional activation was attributed to a partial destabilization of chromatin, resulting probably from the increased phosphorylation of chromatin proteins. The phosphorylation patterns of non-histone proteins differed in the liver chromatins of sham-operated, regenerating and 3′-MDAB-treated rats.
Creating Fluid Supported Lipid Bilayers with High Amounts of Phosphatidylethanolamine

Phosphatidylethanolamine (PE) comprises 20-50% of overall phospholipid content in human cell membranes and constitutes 70-80% of the membranes in gram-negative bacteria. Its presence is specifically required for the proper folding of numerous membrane proteins, the function of active transport systems, cell division, fusion, blood coagulation, and may play a role in neurodegenerative diseases. Unfortunately, it is hard to work with this lipid in model systems like supported lipid bilayers and there is correspondingly less information known about its basic physical properties in bilayers. Specifically, the role of PE in lipid raft formation, vesicle fusion, cholesterol interactions, ion binding, and lipid flip-flop needs to be elucidated to understand its part in cell membrane function and disease pathways. To this end, my research has two goals. First, I have developed supported lipid bilayer systems that can operate with high mole percentages of PE. Second, I have begun to exploit such systems to explore the properties and functions of PE in membranes.
Synthetic studies of the nargenicins: synthesis of the oxa-bridged octalin nucleus

Abstract An efficient, stereocontrolled entry to the 11-oxatricyclo[4.4.1 1,6 .0 2,7 ] undecene system of the nargenicin antibiotics is presented.
Ultracold atom-molecule collisions with fermionic atoms

Elastic and inelastic properties of weakly bound $s$- and $p$-wave molecules of fermionic atoms that collide with a third atom are investigated. Analysis of calculated collisional properties of $s$-wave dimers of fermions in different spin states permit us to compare and highlight the physical mechanisms that determine the stability of $s$-wave and $p$-wave molecules. In contrast to $s$-wave molecules, the collisional properties of $p$-wave molecules are found to be largely insensitive to variations of the $p$-wave scattering length, and these collisions will usually result in short molecular lifetimes. We also discuss the importance of this result for both theories and experiments involving degenerate Fermi gases.
A calorimetric examination of the effect of myotoxin a on the thermotropic phase behavior of model lipid membranes.

The effect of myotoxin a on the thermotropic phase behavior of aqueous dispersions of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylserine (DMPS) was examined using differential scanning calorimetry (DSC). Myotoxin a significantly altered the normal phase behvior of DMPC in a concentration dependent fashion. This effect is perturbed by Cae+ and is sensitive to ionic strength and pH. High concentrations of toxin eliminate the characteristic pretransition associated with the polar head group of DMPC. They also increase the temperature of the main gel-to-liquid crystal transition from 23°C to 32–235°C. At low concentrations of toxin, the first visible effect is upon the pretransition which is split into two components that diminish with time. The main transition is less affected at low toxin concentrations, although the magnitude of the transition is reduced while it is simultaneously shifted to higher temperatures. The main transition is also split into multiple components. The toxin also had pH specific effects on the phase behavior of DMPS. Above physiological pH (8.5) the normal transition of DMPS at 36–38°C was split in the presence of myotoxin a and new components appeared centered at 31°C and 35°C. These observations are consistent with reports that the skeletal muscle membrane system is the major site of the myonecrotic effect of myotoxin a.
Chemistry of the male mandibular gland secretion of the ant, Camponotus clarithorax

Abstract The male mandibular gland secretion of Camponotus clarithorax contains 2, 6-dimethyl-5-hepten-1-ol and 2-phenylethanol as the major concomitants of six new arthropod natural products. The exudate also contains n-octanoic, n-nonanoic, citronellic, and geranic acids. A novel series of the esters of the two alcohols and n-octanoic and n-nonanoic acids further distinguishes this secretion from any known blend of formicine natural products. The probable significance of sex-specific secretions within a genus is discussed.
Role of Muscle in Regulating Extracellular (K)

There is a positive association between diets rich in potassium, control of blood pressure, and prevention of stroke. Extracellular [K+] is regulated closely to maintain normal membrane excitability by the concerted regulatory responses of muscle and kidney. Although kidney is responsible for ultimately matching K+ output to K+ intake each day, muscle contains more than 90% of the body's K+ and can buffer changes in extracellular fluid [K+] by either acutely taking up extracellular fluid K+ or releasing intracellular fluid K+ from muscle. It long has been assumed that the changes in muscle K+ transport are a function of sodium pump (Na,K-adenosine triphosphatase [Na, K-ATPasel]) abundance, especially that of the alpha2 isoform, which predominates in skeletal muscle. To test the physiologic significance of changes in muscle Na,K-ATPase expression, we developed the K+ clamp, which measures insulin-stimulated cellular K+ uptake in vivo in the conscious rat. By using the K+ clamp we discovered that significant insulin resistance to cell K+ uptake occurs as follows: (1) early in K+ deprivation before a decrease in muscle sodium pump pool size, and (2) during glucocorticoid treatment, which increases muscle Na,K-ATPase alpha2 levels greater than 50%. We also discovered that adaptation of renal and extrarenal K+ handling to altered K+ balance often occurs without changes in plasma [K+], supporting a feedforward mechanism involving K+ sensing in the splanchnic bed and adjustment of K+ handling. These findings establish the advantage of combining molecular analyses of Na,K-ATPase expression and activity with systems analyses of cellular K+ uptake and excretion in vivo to reveal regulatory mechanisms operating to control K+ homeostasis.
Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: summary statement of a first National Institutes of Health/Office of Rare Diseases conference.

Researchers and clinicians with expertise in autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF) and related fields met on May 5-6, 2005, on the National Institutes of Health (NIH) campus for a 1.5-day symposium sponsored by the NIH Office of Rare Diseases, the National Human Genome Research Institute (NHGRI), and in part by the ARPKD/CHF Alliance. The meeting addressed the present status and the future of ARPKD/CHF research.