cssi/SciSciGPT-SciSciNet huggingface dataset:
Restriction digest screening facilitates efficient detection of site-directed mutations introduced by CRISPR in C. albicans UME6.

Introduction of point mutations to a gene of interest is a powerful tool when determining protein function. CRISPR-mediated genome editing allows for more efficient transfer of a desired mutation into a wide range of model organisms. Traditionally, PCR amplification and DNA sequencing is used to determine if isolates contain the intended mutation. However, mutation efficiency is highly variable, potentially making sequencing costly and time consuming. To more efficiently screen for correct transformants, we have identified restriction enzymes sites that encode for two identical amino acids or one or two stop codons. We used CRISPR to introduce these restriction sites directly upstream of the Candida albicans UME6 Zn2+-binding domain, a known regulator of C. albicans filamentation. While repair templates coding for different restriction sites were not equally successful at introducing mutations, restriction digest screening enabled us to rapidly identify isolates with the intended mutation in a cost-efficient manner. In addition, mutated isolates have clear defects in filamentation and virulence compared to wild type C. albicans. Our data suggest restriction digestion screening efficiently identifies point mutations introduced by CRISPR and streamlines the process of identifying residues important for a phenotype of interest.
High-Isolation Multimode Multifunction 24-/60-GHz CMOS Dual-Bandpass Filtering T/R Switch

Fully integrated 24-/60-GHz dual-band transmit/receive (T/R) switch capable of bandpass filtering and switching operations in single bands and concurrent dual band, coupled with simultaneous transmission and reception, is developed using a 0.18- $\mu \text{m}$ SiGe BiCMOS process. The developed bandpass filtering switch can also function as a diplexer with switching functions. The measured insertion losses of the T/R switch are 2.9 and 8.7 dB at 24 and 60 GHz in single-band modes and 3/8.8 dB at 24/60 GHz in concurrent dual-band mode, respectively. The measured isolations are 53 and 43 dB at 24 and 60 GHz in single-band modes and 50/57 dB at 24/60 GHz in concurrent dual-band mode, respectively. The measured inputs $P_{1-\text {dB}}$ are 20.6 and 16.4 dBm at 24 and 60 GHz in single-band modes and 15.9/13 dBm at 24/60 GHz in concurrent dual-band mode, respectively. The measured inputs IP3 are 23.2 and 22.5 dBm at 24 and 60 GHz in corresponding single-band modes, respectively. The total chip size is $1480~\mu \text{m}\times 520~\mu \text{m}$ excluding all the RF and dc pads.
Lead Isotope Mapping of Crustal Reservoirs within the Grenville Superterrane: II. Adirondack Massif, New York

Grenville age basement rocks of the eastern U.S.A. occur as discrete massifs both within the dominantly Paleozoic Appalachian orogen, and as the Adirondack massif (Rankin et. al, 1983). These rocks record a complex history of magmatism and metamorphism that often obscures the original petrogenetic and tectonic setting Abundant petrologic and geochronologic data are now available to emphasize the protracted (1400-1000 m.y.) history of these rocks (Davidson, 1995; Jamieson et. al, 1992; McLelland et. al, 1988; Mezger et. al, 1993, and Windley, 1989), but given the complexity of the geologic record, it is still difficult to emphasize the relationship of the massifs to each other in terms of terranes. However, recent advances in characterization of isotope reservoirs in crustal blocks have permitted a more comprehensive assessment of the distinctiveness of terranes (Zartman, 1969, 1974; Bennett and DePaolo, 1987; Wooden et al, 1988, Liew et. al, 1994 and Sinha et. al, 1996) and provide an opportunity to characterize the tectonic evolution of different fragments of the crust.
Integrating Psychosocial Research and Practice in a Pediatric Hospital

This chapter describes how psychosocial research and practice can be integrated in a pediatric hospital setting. We begin with background on the integration of psychology and pediatrics generally and then provide an overview of the social ecological approach that guides our work. The conceptual background, development and implementation of services, and changes over 11 years (1986–1997) of the Psychosocial Services Program in the Division of Oncology at the Children’s Hospital of Philadelphia are then described in detail. The Psychological Services Program is a multidisciplinary program providing comprehensive mental health services for children with cancer and their families and conducting research related to the adjustment of children with cancer and their families. While our comments are focused on pediatric cancer within an academic setting, we have highlighted ways in which our efforts may be generalized to other clinical settings. In particular, we focus on the advantages of integrating research with clinical practice and the problems specific to medical settings, as well as proposed solutions.
The Novel Bromodomain and Extraterminal Domain Inhibitor INCB054329 Induces Vulnerabilities in Myeloma Cells That Inform Rational Combination Strategies.

Purpose: Bromodomain and extraterminal domain (BET) proteins regulate the expression of many cancer-associated genes and pathways; BET inhibitors have demonstrated activity in diverse models of hematologic and solid tumors. We report the preclinical characterization of INCB054329, a structurally distinct BET inhibitor that has been investigated in phase I clinical trials. Experimental Design: We used multiple myeloma models to investigate vulnerabilities created by INCB054329 treatment that could inform rational combinations. Results: In addition to c-MYC, INCB054329 decreased expression of oncogenes FGFR3 and NSD2/MMSET/WHSC1, which are deregulated in t(4;14)-rearranged cell lines. The profound suppression of FGFR3 sensitized the t(4;14)-positive cell line OPM-2 to combined treatment with a fibroblast growth factor receptor inhibitor in vivo. In addition, we show that BET inhibition across multiple myeloma cell lines resulted in suppressed interleukin (IL)-6 Janus kinase–signal transducers and activators of transcription (JAK–STAT) signaling. INCB054329 displaced binding of BRD4 to the promoter of IL6 receptor (IL6R) leading to reduced levels of IL6R and diminished signaling through STAT3. Combination with JAK inhibitors (ruxolitinib or itacitinib) further reduced JAK–STAT signaling and synergized to inhibit myeloma cell growth in vitro and in vivo. This combination potentiated tumor growth inhibition in vivo, even in the MM1.S model of myeloma that is not intrinsically sensitive to JAK inhibition alone. Conclusions: Preclinical data reveal insights into vulnerabilities created in myeloma cells by BET protein inhibition and potential strategies that can be leveraged in clinical studies to enhance the activity of INCB054329.
Data-driven online learning and reachability analysis of stochastic hybrid systems for smart buildings

ABSTRACTAnalysis and design of cyber physical systems (CPS) relies typically on detailed dynamical models. Identifying parametric models of complex CPS such as smart buildings is very hard because of the heterogeneity and complexity of components as well as uncertainty and variability. Alternatively, data availability can potentially support the use of machine learning techniques to develop nonparametric models, which can be used for prediction, analysis, and control. In this paper, we present a data-driven methodology to learn a nonparametric stochastic hybrid system from the observed data in an online fashion. The model uses Gaussian processes and periodic Markov chains to represent the coupled continuous and discrete dynamics respectively. Moreover, we propose a reachability analysis algorithm that represents the reachable states for a receding finite horizon using mixtures of Gaussian processes. The reachability analysis algorithm provides an efficient multi-step prediction for SHS, which can be used ...
Synthesis of C‐4 substituted pyrimidine nucleoside analogs. Preparation of several 4‐(2‐oxoalkylidene)‐2(1H)‐pyrimidinone ribonucleosides

A series of 4-(1-alkynyl)-2(1H)-pyrimidinone ribonucleosides were synthesized from the Pd-catalyzed coupling of terminal alkynes to the 4-chloropyrimidin-2-one ribonucleoside (2). These compounds were hydrated, using three different methods, to afford the 4-(2-oxoalkylidene)-2(1H)-pyrimidinones. The 4-enol-pyrimidin-2-one structure of the title compounds offers functional groups with the potential for Watson-Crick hydrogen bonding.
Associations of adolescent lifestyle behaviors with body mass index within a nationally representative sample of US adolescents: a quantile regression analysis.

Abstract Objectives The purpose of this study was to examine the associations between lifestyle behavior variables such as physical activity, television watching, computer use, and school night sleep duration with body mass index percentile (BMI%) using quantile regression within a representative sample of adolescents who completed the 2017 US National Youth Risk Behavior Survey. Study design The study design was a cross-sectional study. Methods A multistage cluster sampling procedure obtained a representative sample of US adolescents. The number of sampled adolescents submitting questionnaires with BMI% data was 13,146. To examine the associations between lifestyle behaviors and BMI%, simultaneous quantile regression was used. Results When relationships were modeled at every 10th percentile, more precise parameter estimates were observed at higher percentiles. Across the interquartile range, physical activity associated with lower BMI% at the 50th and 75th percentiles (brange = −2.27% to −5.24%, P Conclusions Higher levels of physical activity associated with lower BMI% and longer time watching television, school night sleep durations less than 8 h, and school night sleep durations of 10 h or more at higher quantiles associated with higher BMI% in adolescents. Estimates of association were more precise within higher quantiles.
Is oblique scanning laser ophthalmoscope applicable to human ocular optics? A feasibility study using an eye model for volumetric imaging.

Oblique scanning laser ophthalmoscopy (oSLO) is a novel imaging modality to provide volumetric retinal imaging without depth sectioning over a large field of view (FOV). It has been successfully demonstrated in vivo in rodent eyes for volumetric fluorescein angiography (vFA). However, engineering oSLO for human retinal imaging is challenging because of the low numerical aperture (NA) of human ocular optics. To overcome this challenge, we implement optical designs to (a) increase the angle of the intermediate image under Scheimpflug condition, and (b) expand the magnification in the depth dimension with cylindrical lens to enable sufficient sampling density. In addition, we adopt a scanning-and-descaning strategy, resulting in a compact oSLO system. We experimentally show that the current setup can achieve a FOV of ~3 × 6 × 0.8 mm3 , and the transverse and axial resolutions of 7 and 41 μm, respectively. This feasibility study serves an important step for future in vivo human retinal imaging.
Detecting the Presence of Fog Using Low-cost Proximity Sensors

ABSTRACT A new, low-cost device that detects the presence of fog has been developed for applications such as the activation of fog sampling equipment and the monitoring of fog’s spatial or temporal evolution. This fog presence detector (FPD) offers an inexpensive alternative to visibility monitors and other specialized fog or cloud microphysical instruments that have typically been used for these purposes. The FPD utilizes a VCNL4200 proximity sensor (Vishay Intertechnology, Inc.), which operates as an infrared backscatter detector and was intended to detect proximity in cars, buildings, and personal electronics. An FPD with six individual sensors was evaluated in the field from 19 August 2019 through 4 November 2019. Over the course of the study, the FPD was able to distinguish between foggy and clear conditions. The output values from the individual sensors closely tracked one another and were strongly correlated with extinction coefficient measurements from a collocated visibility monitor. However, the study revealed that a more powerful, external infrared emitting diode (IRED) was necessary for reliable fog detection when sunlight was present. With the inclusion of an external IRED, the agreement between the FPD and visibility monitor averaged 91% when indicating the presence of fog during fog events. Both the FPD and visibility monitor were found to be susceptible to insects and spider webs located in or near the optical sensing volume during foggy and non-foggy periods.
Interobserver Variability in the Assessment of Tumor Budding in pT 3/4 Colon Cancer: Improvement by Supporting Immunohistochemistry?

The prognostic significance of tumor budding in colon cancer is unequivocally documented, and the recommendations of the International Tumor Budding Consensus Conference (ITBCC) are currently the accepted basis for its assessment. Up to now, it is unknown whether the general use of a supporting cytokeratin immunohistochemistry can improve the interobserver variability and prognostic significance. Six investigators with different levels of experience reassessed 229 cases of colon carcinoma (pT3/4, N+/−, M0) with a supporting cytokeratin immunohistochemistry. The results were compared to previous assessments, which have been performed only on H & E. Bd3 was significantly associated with the occurrence of distant metastases according to the assessments of three out of six investigators (p < 0.05). Only one single investigator reached significant results concerning the cancer specific survival (p = 0.01). The pairwise kappa values range between a poor and moderate level of agreement (range 0.17–0.45; median 0.21). In conclusion, the results show no superiority of the use of an additional cytokeratin immunohistochemistry compared to the conventional analysis on sole H & E slides. Therefore, the general supporting use of a cytokeratin immunohistochemical staining seems to be inadvisable in colon cancer in consideration of necessary resources and costs.
Hydroxychloroquine prescription practices after 2016 AAO recommendations

Unstructured Abstract: Among 6539 outpatient hydroxychloroquine prescriptions in 2018, the prevalence of excess dosing based on 2016 AAO recommendations (≤5 mg/kg actual body weight) was 27%. Lower weight and dermatologist prescriber were associated with excessive dosing.
Recalculate the social cost of carbon

The science is ripe to update estimates of CO2 emissions costs. Calls to scrap the calculation are misguided.
The Making of Samuel Beckett’s Endgame and Molloy

Under prolonged confinement in a tight shelter, an overtaxed orderly threatens to desert the invalids withering in his under-resourced care. Time feels suspended, rations are dwindling, everything ...
Algebraic Geometry: A Problem Solving Approach

Algebraic Geometry has been at the center of much of mathematics for hundreds of years. It is not an easy field to break into, despite its humble beginnings in the study of circles, ellipses, hyperbolas, and parabolas. This text consists of a series of exercises, plus some background information and explanations, starting with conics and ending with sheaves and cohomology. The first chapter on conics is appropriate for first-year college students (and many high school students). Chapter 2 leads the reader to an understanding of the basics of cubic curves, while Chapter 3 introduces higher degree curves. Both chapters are appropriate for people who have taken multivariable calculus and linear algebra. Chapters 4 and 5 introduce geometric objects of higher dimension than curves. Abstract algebra now plays a critical role, making a first course in abstract algebra necessary from this point on. The last chapter is on sheaves and cohomology, providing a hint of current work in algebraic geometry. This book is published in cooperation with IAS/Park City Mathematics Institute.
The Procedural Safeguards of Federalism

In the article giving rise to this Symposium, I argued that the Supremacy Clause safeguards federalism by conditioning supremacy on adherence to precise lawmaking procedures prescribed elsewhere in the Constitution.1 These procedures were designed to preserve the governance prerogatives of the states both by making federal law relatively difficult to adopt and by assigning lawmaking solely to actors subject to the political safeguards of federalism.2 The Supremacy Clause recognizes only three sources of law as “the supreme Law of the Land”—the “Constitution,” “Laws,” and “Treaties” of the United States.3 Not coincidentally, the Constitution prescribes precise procedures to govern the adoption of each of these sources of law, and all of these procedures specifically require the participation of the Senate or the states.4 These procedural safeguards of federalism were central to the crucial compromise reached between the small and large states at the Convention concerning the structure of the new Constitution.
Buffer Sizing for Crosstalk Induced Delay Uncertainty

On-chip feature size scaling has aggravated the importance of crosstalk among interconnect lines. The effect of crosstalk on the delay of signals propagating along interconnect lines is investigated in this paper. It is shown that delay uncertainty is proportional to the amount of coupling among interconnect lines. A methodology to reduce delay uncertainty by increasing the size of interconnect buffers is presented. In addition, the effect of increasing buffer size on the power dissipation is discussed. A power efficiency metric is introduced that characterizes the trade off between the reduction in delay uncertainty and the increase in power dissipation.
The Philosophy of Biology: Evolution and Heredity from Darwin to the Rise of Genetics

Introduction In the Descent of Man , Darwin admitted that, in his enthusiasm for what appeared to him a major discovery, he had perhaps overstressed the importance of natural selection. He now sees that there may be changes in the biota that are merely “chemical” – we would say, neutral – but, as he has always recognized, only adaptations are subject to natural selection. Still, Darwin's theory was, in his view, basically a theory of natural selection. Yet, paradoxically, as we noticed earlier, although the Origin persuaded many of the fact of descent with modification, it did not convince so many of natural selection as the chief agency of change. The Darwinism, or “Darwinismus,” of the Origin's first fifty years is certainly evolutionary, but it is scarcely recognizable as Darwin's theory. With respect to this period, Peter Bowler has written both of “the eclipse of Darwinism” (an expression introduced by Julian Huxley in his Evolution: The Modern Synthesis [Huxley 1942]) and of a “non-Darwinian revolution” (Bowler 1983; 1988). However, the situation is more complicated than that. Before we move on to the evolutionary synthesis of the 1930s to 1950s and the philosophical questions associated with it, we need to identify some strands in that complex story. Again, as with Darwin, we will have to select a few points from a very rich subject-matter. Indeed, we are already restricting our account of the nineteenth century severely by focusing on evolution – let alone Darwinian evolution – and neglecting such topics as vitalism or the growth of the cell theory.
A state estimator with reduced sensitivity to sensor quantization

The authors present a simple method to reduce measurement quantization effects in state estimation. The work addresses a practical problem in industrial electronics, where many modern electronic sensors produce quantized outputs (e.g. incremental encoder), or are sampled with finite quantization in digital control applications (e.g. N-bit analog-to-digital converter). Classical methods often describe quantization error as a random process, but the authors' approach is motivated by stability considerations from nonlinear systems analysis. Lyapunov stability analysis shows that the effect of quantization is greatly reduced by embedding the nonlinear quantization characteristic within the state estimator in a deterministic fashion. Several simulation examples complement the theoretical analysis. To the authors' knowledge, the contribution is unique among recent works for its simplicity in addressing the case of large quantization error.
The effect of treatment time in locally advanced cervical cancer in the era of concurrent chemoradiotherapy.

BACKGROUND: This study sought to determine if treatment time impacts pelvic failure (PF), distant failure (DF), or disease-specific mortality (DSM) in patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: A retrospective review was performed of 113 consecutive eligible patients with stage IB2 to IIIB cervical cancer. All patients received whole-pelvis radiation with concurrent chemotherapy and consolidative intracavitary brachytherapy (BT) to the cervix, followed by an external beam parametrial boost when appropriate. The effect of treatment time on PF, DF, and DSM was examined with univariate and multivariate analyses. Characteristics of patients with and without treatment prolongation were compared to explore reasons for treatment prolongation. RESULTS: The median time to completion of BT was 60 days, and the median time to complete all RT was 68 days. The 3-year cumulative incidence of PF, DF, and DSM were 18%, 23%, and 26%, respectively. On multivariate analysis, time to completion of BT >56 days was associated with increased PF (hazard ratio, 3.8; 95% confidence interval, 1.2-16; P = .02). The 3-year PF for >56 days versus ≤56 days was 26% versus 9% (P = .04). Treatment time was not associated with DF or DSM. Treatment prolongation was found to be associated with delay in starting BT and higher incidence of acute grade 3/4 toxicities. CONCLUSIONS: In the setting of CCRT, treatment time >56 days is detrimental to pelvic control but is not associated with an increase in DF or DSM. To maximize pelvic control, we recommend completing BT in 8 weeks or less. Cancer 2013. © 2012 American Cancer Society.
Cognitive Approaches to the Memory Disorders of Demented Patients

Dementia is primarily (but not solely) an affliction of the elderly, with the prevalence increasing dramatically with age to include almost a third of the population over 85 (Mahandra, 1984). Because of the change in population demographics that has been brought about by increases in life expectancy, dementia has in recent years been elevated from an issue of relative obscurity and neglect to one of the utmost interest and importance. Although this increased attention may create the impression that the study of dementia is of relatively recent origin, interest in this topic in fact dates back to antiquity. The term dementia was probably coined in the first century A.D., but was for the next millennium or so generally ill-defined and often used (along with delirium) to refer to insanity in general (Lipowski, 1981; Mahandra, 1984). It is also likely that no real distinction was made between dementia and the changes in cognitive function associated with normal aging (Mahandra, 1984).
Suicide Ideation and Attempts in Hispanics and Non‐Hispanic Whites: Demographic and Psychiatric Disorder Issues

This study examined the lifetime prevalence of suicide ideation and attempts in a community sample of 1,425 Hispanics and 1,309 non-Hispanic whites. The relationship between psychiatric disorder (as assessed by the Diagnostic Interview Schedule, or DIS) and suicide ideation and attempts was also examined. Fewer Hispanics reported suicide ideation (8.8% vs. 18.9%; p less than .001) and suicide attempts (3.2% vs. 5.1%; p less than .001) than non-Hispanic whites. More women of both ethnic groups reported suicide attempts than men of either ethnic group (p less than .001). Disrupted marital bonds were typically associated with higher rates of ideation and attempts. Individuals with any DIS diagnosis were more than four times as likely to think about killing themselves (p less than .01) and more than seven times as likely to attempt suicide (p less than .01) as those without a psychiatric disorder.
A Regular Fault-Tolerant Architecture for Interconnection Networks

A regular communication architecture for large distributed systems is presented. The system topology consists of n = rm nodes, r ≥2, m ≥ 2, with internode connectivity of (r − 1) m. The system is fault tolerant of (r − 1)m −1 node failures for m ≥ 3.
Using 3’-Bridging Phosphorothiolates to Isolate the Forward DNA Cleavage Reaction of Human Topoisomerase IIα

The ability to cleave DNA is critical to the cellular and pharmacological functions of human type II topoisomerases. However, the low level of cleavage at equilibrium and the tight coupling of the cleavage and ligation reactions make it difficult to characterize the mechanism by which these enzymes cut DNA. Therefore, to establish a system that isolates topoisomerase II-mediated DNA scission from ligation, oligonucleotide substrates were developed that contained a 3'-bridging phosphorothiolate at the scissile bond. Scission of these substrates generates a 3'-terminal -SH moiety that is a poor nucleophile relative to the normal 3'-terminal -OH group. Consequently, topoisomerase II cannot efficiently ligate phosphorothiolate substrates once they are cleaved. The characteristics of topoisomerase IIalpha-mediated cleavage of phosphorothiolate oligonucleotides were identical to those seen with wild-type substrates, except that no ligation was observed. This unidirectional accumulation of cleavage complexes provided critical information regarding coordination of the protomer subunits of topoisomerase IIalpha and the mechanism of action of topoisomerase II poisons. Results indicate that the two enzyme subunits are partially coordinated and that cleavage at one scissile bond increases the degree of cleavage at the other. Furthermore, anticancer drugs such as etoposide and amsacrine that strongly inhibit topoisomerase II-mediated DNA ligation have little effect on the forward scission reaction. In contrast, abasic sites that increase levels of cleavage complexes without affecting ligation stimulate the forward rate of scission. Phosphorothiolate substrates provide significant advantages over traditional "suicide substrates" and should be valuable for future studies on DNA scission and the topoisomerase II-DNA cleavage complex.
Bacterial activity in sediments of shallow marine bays

Abstract Complete mineralization of organic matter results from a multitude of complex bacterial activities which must involve more than one species of bacteria. The diverse bacterial activities influence the pH, redox potential, production of gases and their resulting disfiguration of the sediment, concentration of certain elements, precipitation and solution of carbonates, diagenesis of silicates, the production of complex organic compounds such as surface-active agents and many other properties of sediments. The bacterial activities are not constant but proportional to the amount of organic matter, pH, sediment particle size, temperature, sequence of physical changes caused by the bacteria in the sediment and the sequence of the production of organic by-products during decomposition.
Development of a proficiency testing program for molecular diagnosis of influenza viruses.

Abstract Background The Molecular Virology Proficiency Testing Program at the Wadsworth Center began the assembly and distribution of influenza virus panels to US public health labs (PHLs) in 2008. The program was created to assist PHLs in assessing their performance and in meeting CLIA regulations for mandated proficiency testing (PT). Objectives To design and distribute proficiency testing panels containing influenza A virus subtypes H1N1 and H3N2, and influenza B; when H1N1pdm09 emerged it also was incorporated into the panels. A secondary objective was to determine the best matrix for long term storage of the molecular PT samples. Study design Viruses were quantitated using TCID50 and quantitative real-time RT-PCR. Reference laboratories were enlisted to verify viral identity in the panels and to help determine viral titers to be used in the PT panels sent to PHLs. Results and conclusions Of the 29 laboratories that participated the first year, 27 were able to correctly identify all of the virus types in the panel. Fifty-one PHLs participated in the program the second year when pandemic H1N1 was added, and 45 were able to correctly detect, type and subtype all of the viruses in the panel. In the program's third year, 60 laboratories participated; 58 correctly detected and subtyped all of the viruses in the panel. Annual surveys of assay techniques showed that the PHLs had shifted their extraction methods and PCR-thermocycler instrumentation to meet FDA-approved methods. The degradation study revealed that frozen viral stocks were stable for at least 30 months, thus allowing ample time to prepare and pre-test panels.
Function of nAChRs Containing Alpha5 Subunits

Neuronal nicotinic acetylcholine receptors (nAChRs) are abundantly expressed in the central nervous system. Neurons in several brain regions co-express alpha5, alpha4 and beta2 subunits. Changes in the receptor composition and stoichiometry of alpha4 and beta2 containing nAChRs are pertinent to disease states. Several genome-wide association and candidate gene studies have identified polymorphisms in the gene for the alpha5 subunit that are linked to an increased risk for nicotine addiction, alcohol addiction and lung cancer. However more information is required about the functional effects of incorporating a normal or mutated alpha5 subunit into the alpha4beta2 receptor pentamer. Here we examine differences in I-V relationships and dose-response relations between alpha4beta2 receptors and alpha4beta2 receptors including alpha5 subunits containing various mutations to the M2 domain expressed in Xenopus oocytes.
A reusable Ada package for scientific dimensional integrity

Abstract -- Our recent experience in operations Desert Shield and Desert Storm has clearly demonstrated the criticality of software reliability end that truly reliable software Is indeed possible. One tool we can employ to enhance our software reliability is the classic scientific computational reliability technique of dimensional integrity, or unite checking. The Ads programming language makes it easy to implement units checking. A PHYSICAL_QUANTITY type Is declared which ham entries for both the floating point numeric value of s variable, and Integer entries for exponents of the fundamental physical unite of mass, length, and time. The Ads feature of "operator overloading" allows creation of symbols to porters arithmetic and relational operations on these variables . For example, the multiplication operation "*" ie overloaded eo that the numeric values of the two operande are multiplied, and the exponents of their fundamental units are added. An ASSIGN function Is then written to check that the units computed in an expression are equal to the units of the variable to which s new numeric value is assigned. Further reliability ie added by "information hiding" through limited private types, and reusability and modifiability are added by making the package generic. For scientific software, this generic package is as reusable as package Standard.
Integration of Continuous Flow Reactors and Online Raman Spectroscopy for Process Optimization

The pharmaceutical industry has great need to reduce costs and improve manufacturing efficiency while consistently manufacturing quality drug product. Continuous flow reactors (CFRs) offer an option for a flexible, leaner, and cleaner process. CFRs are flow cells optimized for the continuous production of a target compound. Small-volume CFRs avoid some of the reaction control problems associated with scale-up to large-batch chemistry, while still allowing for process intensification through modular scale-out. Compared to batch reactors, CFRs are more energy efficient due to their superior mixing schemes and heat transfer properties. Reactions typically proceed much faster than in batch and require less excess solvent. Currently, CFRs are limited by the technologies available for online monitoring, which require product stream sampling and off-line analytics. This work addresses the analytical challenges inherent to CFRs by demonstrating the ability to assess the quality of product from a reactor stream rapidly, using effective online sampling and monitoring systems. Additionally, following the Quality by Design paradigm, techniques such as statistically based design of experiments, process analytical technologies, and multivariate statistical modeling methods were implemented to facilitate enhanced product and process understanding. An online sampling system that is able to interface with CFRs was developed, with custom software to monitor and control process variables using online analytics. Knowledge of these in-process parameters, combined with appropriate online process analytical technologies, provided a complete understanding of both the physical and chemical system. These improvements reduced the time and effort required to develop and optimize a chemical reaction for large-scale continuous production.
Electrodermal activity and clinical status in chronic schizophrenia

The present study investigated the association between electrodermal nonresponsiveness and clinical state in schizophrenia. Sixty-three patients with a DSM-III diagnosis of chronic schizophrenia served as subjects. Clinical status was assessed using multiple measures, including age of onset, symptom severity, illness duration, hospitalization history, global functioning, and occupational functioning. Electrodermal hypoactivity was found to be associated with poorer functioning and a more severe form of illness. In addition, hyporesponsive patients displayed more conceptual disorganization and alogia.
Comment on Weinberg's “Lindesmith on Addiction”

John F. Galliher repond aux critiques adressees par Darin Weinberg a l'encontre de la theorie de la toxicomanie d'Alfred Lindesmith. Il souligne, contre l'affirmation de Weinberg, que Lindesmith s'est toujours efforce de souligner la dimension culturelle, humaine de la toxicomanie. Il rappelle que selon Lindesmith la prohibition de la drogue induit un cout social, economique, psychologique tres lourd pour les toxicomanes. Ceci conduit Lindesmith a defendre la depenalisation de la toxicomanie. Darin Weinberg replique a Galliher. Il reconnait que les travaux de Lindesmith constituent une alternative a la vision reductionniste psychologique et biologique de la toxicomanie. Il estime que la distinction entre perception brute et perception mentale manifeste une vision dualiste du rapport entre corps et esprit. Il affirme, a l'encontre de Lindesmith, que la toxicomanie ne derive pas de l'apprentissage symbolique de sensations physiques provoquees par la drogue mais de l'utilisation de la drogue en tant que ressource dans l'action pratique. Il rejette le volontarisme de Lindesmith qui evacue toute notion d'apprentissage social
Deactivation of hydrodechlorination catalysts: I. Experiments with 1,1,1-trichloroethane

Abstract In order to understand the cause(s) of catalyst deactivation, microreactor studies were carried out on the catalytic hydrodechlorination (HDC) of 1,1,1-trichloroethane (111-TCA) using a fixed-bed reactor divided into three segments. The catalysts studied were: ηδ-alumina, α-alumina, Pt/α-alumina, Pt/η-alumina, and Pt/ηδ-alumina. Experiments were carried out at atmospheric pressure over a temperature range of 423–623 K and at H 2 /111-TCA molar ratios between 10 and 99. Only the Pt-containing catalysts were able to remove all three Cl atoms from 111-TCA. However, increasing amounts of partially-dechlorinated compounds were formed as the Pt/ηδ-alumina and the Pt/η-alumina catalysts deactivated. The only product with ηδ-alumina was 1,1-dichloroethylene (11-DCE). The conversion of 111-TCA decreased more rapidly with time for Pt/ηδ-alumina than for ηδ-alumina without Pt. Much larger quantities of coke were formed on the Pt/ηδ-alumina than on the ηδ-alumina, at similar conditions. The ηδ-alumina was essentially completely regenerated by heating in flowing He at 773 K. The Pt/η-alumina was only partially regenerated by this technique. The apparent stability of the Pt/ηδ-alumina catalysts increased with increasing Pt concentration. Poisoning by hydrochloric acid, a reaction product, did not cause significant deactivation of either the ηδ-alumina or the Pt/ηδ-alumina catalysts.
Synthesis of monoclinic monazite, LaPO4, by direct precipitation

The direct synthesis of LaPO4 and La0.96Sr0.04PO4monazite using nitrates and phosphoric acid to produce uniform and non-agglomerated monazite powders without the formation of any intermediate hydrated rhabdophane phase (LaPO4·½H2O) is described.
An Experimental Investigation of Uneven Turn Water and Acetone Oscillating Heat Pipes

An experimental investigation of a new three dimensional oscillating heat pipe (OHP) with uneven turn design was conducted in order to develop a gravity-independent OHP. Different from other OHPs, the OHPs investigated herein have uneven turns. In the evaporator, the total turn number is 20 and in the condenser 14, i.e., 14 full turns and 6 half turns, which were constructed using copper tubing with an inner diameter of 1.65 mm. The water OHP was filled with water at a 62.5% filling ratio and the acetone OHP filled with acetone at a 62.7% filling ratio. Experimental results show that the uneven turn OHP developed herein can start the oscillating motion in the negative vertical position, i.e., the evaporator being above the condenser and demonstrate that the uneventurn OHPs can significantly reduce the gravity effect on the heat transport capability in an OHP. In addition, it is found that although at low power inputs the uneven turn OHP in the negative vertical position is not good as that in the positive vertical position (the evaporator being below the condenser), at high power inputs the uneven OHP in negative vertical position has similar heat transfer performance as in the positive vertical position. The uneven turn OHP achieved a thermal resistance of 0.135 °C/W with an operating temperature of 36 °C in the negative vertical position.
The effects of gaseous environments on polymers

Abstract The effect of inert gases on the mechanical properties of polymers is very general. There are certain areas which have not been explored, such as fatigue and crack propagation. The pressure range above one atmosphere has not been observed. The effects of stress on the diffusion of these gases are not known. The question of how much is a surface effect and how much is subsurface plasticization is not clear. The effects of gases other than N2, Ar, O2, and CO2 have not been determined.
COMPUTER GENERATION OF COUPLED-CLUSTER EQUATIONS

A Maple V computer program for obtaining conventional algebraic representations of coupled-cluster equations is described and its use illustrated. The program is available on the World Wide Web. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 75: 593–597, 1999
A comparative analysis of solubility, segregation, and phase formation in atomized and cryomilled Al–Fe alloy powders

Bulk nanostructured and ultrafine-grained binary Al–Fe alloys have been studied in the past for their remarkable strength, hardness, and thermal stability. These properties have been attributed to a combination of solid solution strengthening, precipitate strengthening, and grain boundary strengthening. However, to date, no systematic investigation has been performed to address the factors that govern the evolution of the various metastable and equilibrium precipitates that form as a result of thermal exposure. In this study, Al–2at.%Fe and Al–5at.%Fe powders were synthesized via helium gas atomization and argon gas atomization, respectively. Cooling rates upwards of 106 K s−1 were achieved resulting in an intermetallic-free starting structure, and a map of the structure as a function of cooling rate was established. Electron backscatter diffraction analysis revealed the presence of a larger number of low-angle grain boundaries relative to high-angle grain boundaries, which influenced nucleation and precipitation of the metastable Al6Fe phase. Cryomilling of the atomized powder was subsequently performed, which led to grain refinement into the nanometer regime, dispersion of the Fe-containing phases, and forcing of 2at.%Fe into solution within the Al matrix compared to negligible Fe in solution in the as-atomized state. Finally, differential scanning calorimetry was utilized to elucidate the metastable Al6Fe precipitation temperature (~300 °C) and subsequent phase transformation to the equilibrium Al13Fe4 phase (~400 °C). An activation energy analysis utilizing the Kissinger method revealed three important factors, in order of importance, for ease of Al6Fe precipitation: segregated regions containing iron, availability of nucleation sites, and the number of diffusion pathways.
A preproinsulin-like pseudogene from Neurospora crassa

A segment of DNA was amplified from the Neurospora crassa genome by the polymerase chain reaction using several oligonucleotides coding for highly conserved domains in proinsulin as primers and probe. A genomic clone corresponding to this segment was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of a part of this segment bears remarkable resemblance to preproinsulin, but lacks several requirements for transcription or translation and must therefore be considered to be a pseudogene.
Nonoperative Management of Adult Flatfoot Deformities

Managing those with adult flatfoot deformities can be quite challenging, and the methods and devices used are wide-ranging based on the experience of the managing physician and the experience of the provider of the orthotic devices. A thorough biomechanical assessment is paramount to provide the most successful treatment due to the wide range of pathologic abnormalities and pathomechanics that lead to this painful disorder. Taking away pain while improving function for any patient is a rewarding aspect of clinical foot care, and the information covered in this article should arm the practitioner, or surgeon, with viable alternatives to surgical management.
Instructional case: Choices and dilemmas in accounting for stock-based compensation

Abstract Corporations often seek to motivate managers to think and act long-term by including stock options as part of their compensation. This leads to several interesting consequences. For example, how should the stock options be valued and reported in the financial statements? What types of conflicts of interests (for example, between the CEO and shareholders) does the use of stock options attempt to resolve? Which types of firms would be more likely to use stock options? Would certain firms be penalized in the market if they were forced to disclose the often sizable value of stock options in CEO compensation packages? This case provides a framework for valuing stock options to determine their effect on CEO compensation and corporate net income. Such an analysis helps illustrate that understanding and selecting a GAAP has ‘managerial’ as well as ‘financial’ accounting implications.
A comparison of the affordances of a digital desk and tablet for architectural image tasks

The physical context of architectural design includes large workspaces, typically drafting tables covered with piles of images and sketches. We are investigating if and how a large computerized workspace can be integrated usefully into such a design environment. To this end, we compared a large computerized desktop (digital desk) to a standard desktop computer and a small tablet environment for two typical architecture design tasks: sketching and image sorting. For the sketching task, the participants' preferences were evenly divided between the digital desk and the tablet. For the image sorting task, the desk was the least preferred environment, and produced significantly higher sorting times and more mistakes. Investigation into the causes of this difference yielded several interesting findings, including: the height of the participant was significantly associated with their speed on the sorting task, the larger image size available on the desk compensated for its poorer resolution in subjective preferences, and the quality of the alignment of the pen was an important factor both for preference and scoring results in the sketching task. Highly responsive pen input devices seem critical for user satisfaction not only for sketching, but also for image sorting; the effects of large display spaces are difficult to isolate from the limitations of input device. This paper elaborates on these findings and considers the implications for the design of user interfaces for image manipulation, in particular interaction techniques appropriate to using pen-input with large display surfaces.
Modification of ghrelin receptor signaling by somatostatin receptor-5 regulates insulin release

Both ghrelin and somatostatin (SST) inhibit glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells, but how these independent actions are regulated has been unclear. The mechanism must accommodate noncanonical ghrelin receptor (GHS-R1a)–G-protein coupling to Gαi/o instead of Gαq11 and dependence on energy balance. Here we present evidence for an equilibrium model of receptor heteromerization that fulfills these criteria. We show that GHS-R1a coupling to Gαi/o rather than Gαq11 requires interactions between GHS-R1a and SST receptor subtype 5 (SST5) and that in the absence of SST5 ghrelin enhances GSIS. At concentrations of GHS-R1a and SST5 expressed in islets, time-resolved FRET and bioluminescence resonance energy transfer assays illustrate constitutive formation of GHS-R1a:SST5 heteromers in which ghrelin, but not SST, suppresses GSIS and cAMP accumulation. GHS-R1a–G-protein coupling and the formation of GHS-R1a:SST5 heteromers is dependent on the ratio of ghrelin to SST. A high ratio enhances heteromer formation and Gαi/o coupling, whereas a low ratio destabilizes heteromer conformation, restoring GHS-R1a–Gαq11 coupling. The [ghrelin]/[SST] ratio is dependent on energy balance: Ghrelin levels peak during acute fasting, whereas postprandially ghrelin is at a nadir, and islet SST concentrations increase. Hence, under conditions of low energy balance our model predicts that endogenous ghrelin rather than SST establishes inhibitory tone on the β-cell. Collectively, our data are consistent with physiologically relevant GHS-R1a:SST5 heteromerization that explains differential regulation of islet function by ghrelin and SST. These findings reinforce the concept that signaling by the G-protein receptor is dynamic and dependent on protomer interactions and physiological context.
In our best interests: Experience and workings of an ethics review committee

Revue de 11 cas presentes devant le comite d'ethique compte-tenu d'une discordance entre le souhait des parents de ne pas traiter ou d'interrompre le traitement en cours et l'avis des medecins de traiter. Discussion sur la qualite et le fonctionnement des comites d'ethique
Note on the nature of cosmic rays

The recent experiments of Bothe and Kolhoerster(1) have led to an important and interesting conclusion. The ionization phenomena, by means of which cosmic rays are measured, are produced by highly penetrating corpuscular rays. It remains, however, an open question whether this corpuscular radiation is identical with the cosmic rays themselves, or is secondary in its nature, produced by primary rays of an electromagnetic character. Bothe and Kolhoerster admit both possibilities, but they seem to lean toward the first, owing to the fact that their corpuscular rays show a penetration of the same order of magnitude as that of the cosmic rays themselves.
Separating Agency From Deeds in Immoral Neurological Patients: A Potential Challenge to the ADC Model

Dubljevic and Racine (2014) present an interesting and comprehensive attempt to explain moral judgments using the agency–deeds–consequences (ADC) model, highlighting the need for impartiality to pa...