cssi/SciSciGPT-SciSciNet huggingface dataset:
Polymer Modeling Applications of Symbolic Computation

Statistical models are employed to describe (a) the geometry and (b) kinetics of local conformational backbone motions in glassy polymers. First, 13 the chemical shift anisotropy (CSA) tensor line shape of an aromatic C is modeled using a double-well potential with temperature-dependent flips and oscillations modulating the experimental principal components. MACSYMA is used to perform matrix multiplications and subsequent Boltzmann averages. Second, bond-defect diffusion models lead to Levy-stable laws for conformer orientational survival probability densities. MACSYMA assists in the analysis and resummation of series expansions of stable laws needed for data processing.
A Comparison of Diffusion-Conductimetric and Distillation-Titration Methods in Analyzing Ammonium- and Nitrate-Nitrogen in the KCl-Extracts of Georgia Soils

Soil mineral (or inorganic) nitrogen (SMN), which primarily exists as exchangeable and soluble ammonium (NH4+) and the nitrate (NO3−) ions, represents readily available nitrogen for plant growth. O...
Dramatic Improvement of the Mechanical Strength of Silane-Modified Hydroxyapatite-Gelatin Composites via Processing with Cosolvent

Bone tissue engineering (BTE) requires a sturdy biomaterial for scaffolds for restoration of large bone defects. Ideally, the scaffold should have a mechanical strength comparable to the natural bone in the implanted site. We show that adding cosolvent during the processing of our previously developed composite of hydroxyapatite–gelatin with a silane cross-linker can significantly affect its mechanical strength. When processed with tetrahydrofuran (THF) as the cosolvent, the new hydroxyapatite–gelatin composite can demonstrate almost twice the compressive strength (97 vs 195 MPa) and biaxial flexural strength (222 vs 431 MPa) of the previously developed hydroxyapatite–gelatin composite (i.e., processed without THF), respectively. We further confirm that this mechanical strength improvement is due to the improved morphology of both the enTMOS network and the composite. Furthermore, the addition of cosolvents does not appear to negatively impact the cell viability. Finally, the porous scaffold can be easily...
KELCH F-BOX protein positively influences Arabidopsis seed germination by targeting PHYTOCHROME-INTERACTING FACTOR1.

Seeds employ sensory systems that assess various environmental cues over time to maximize the successful transition from embryo to seedling. Here we show that the Arabidopsis F-BOX protein COLD TEMPERATURE-GERMINATING (CTG)-10, identified by activation tagging, is a positive regulator of this process. When overexpressed (OE), CTG10 hastens aspects of seed germination. CTG10 is expressed predominantly in the hypocotyl, and the protein is localized to the nucleus. CTG10 interacts with PHYTOCHROME-INTERACTING FACTOR 1 (PIF1) and helps regulate its abundance in planta . CTG10-OE accelerates the loss of PIF1 in light, increasing germination efficiency, while PIF1-OE lines fail to complete germination in darkness, which is reversed by concurrent CTG10 - OE . Double-mutant ( pif1 ctg10 ) lines demonstrated that PIF1 is epistatic to CTG10. Both CTG10 and PIF1 amounts decline during seed germination in the light but reaccumulate in the dark. PIF1 in turn down-regulates CTG10 transcription, suggesting a feedback loop of CTG10/PIF1 control. The genetic, physiological, and biochemical evidence, when taken together, leads us to propose that PIF1 and CTG10 coexist, and even accumulate, in the nucleus in darkness, but that, following illumination, CTG10 assists in reducing PIF1 amounts, thus promoting the completion of seed germination and subsequent seedling development.
Surgeons have an opportunity to improve teaching quality through feedback provision.

BACKGROUND Medical student evaluations of faculty are increasingly incorporated into promotion and tenure decisions, making it imperative to understand learner perceptions of quality teaching. Prior work has shown that students value faculty responsiveness in the form of feedback, but faculty and students differ in their perceptions of what constitutes sufficient feedback. The innovative minute feedback system (MFS) can quantify responsiveness to students' feedback requests. This study assessed how feedback provision via MFS impacts teaching quality scores. MATERIALS AND METHODS This retrospective observational study compared average faculty teaching quality scores with faculty's percentage response to student feedback requests via the MFS. The data were generated from the core surgical clerkship for third-year medical students at the University of Michigan Medical School. The relationship between average teaching quality scores and response percentage was assessed by weighted regression analysis. RESULTS Two hundred thirty-seven medical students requested feedback via MFS, and 104 faculty were evaluated on teaching quality. The mean faculty feedback response percentage was 55.78%. The mean teaching quality score was 4.27 on a scale of 1 to 5. Teaching quality score was significantly correlated with response percentage (P < 0.001); for every 10% increase in response percentage, average teaching quality score improved by 0.075. Average teaching quality score was not significantly associated with response time (P = 0.158), gender (P = 0.407), or surgical service (P = 0.498). CONCLUSIONS Medical students consider responsiveness to feedback requests an important component of quality teaching. Furthermore, faculty development focused on efficient and practical feedback strategies may have the added benefit of improving their teaching quality.
Monitoring Cardiopulmonary Function and Progression Toward Shock: Oxygen Micro-sensor for Peripheral Tissue

We are developing a robust, minimally invasive device for detecting progression toward hemorrhagic shock in trauma patients. To accomplish this, oxygen micro-sensors are being developed that contain a solution of oxygen-sensitive phosphorescent probes within gas permeable tubing attached to optical fibers. These micro-sensors can be inserted into peripheral tissue to accurately measure tissue oxygenation. As the blood volume decreases (hemorrhage), physiological mechanisms progressively restrict blood flow to “non essential” peripheral tissues, redirecting that flow to the essential internal organs. It is hypothesized that the sensors will detect the shutdown of peripheral blood flow well before the decreasing blood volume reaches the threshold where multi-organ failure begins. Proactive treatment with volume expanders or blood, guided by peripheral oxygen measurements, would significantly reduce multi-organ failure and other complications in trauma cases.
Embedded Triply-Periodic Minimal Surfaces and Related Soap Film Experiments

Some aspects of the modelling of embedded triply-periodic minimal surfaces (ETPMS) by both soap films and plastic models are discussed. Eight new examples of possible ETPMS are introduced. Interference-diffraction patterns obtained by reflecting laser light from soap films with non-zero Gaussian curvature are described.
Autonomy and Death

In this Article, Professor Clark explores the contours of the current debate over physician-assisted death. She beings by focusing on the legal issues raised by statutory attempts to either legalize or criminalize physician-assisted death, with particular emphasis on the constitutional questions that are currently before the United States Supreme Court. She then examines physician-assisted death from both medical and societal perspectives. Professor Clark uses a thought experiment in which assisted death is facilitated by persons other than physicians, and in doing so, questions whether physicians are the proper persons in whom to rest power over assisted death. She points out the irony in a process that would set up physicians as protectors of individual autonomy, and ultimately concludes that by deferring to the medical profession in this process, we risk losing the very autonomy that assisted death is designed to effectuate.
The Humid Tropical and Mountain Ecoregions

Equatorial and tropical air masses largely control the humid tropical group of climates found at low latitudes. Every month of the year has an average temperature above 18°C, and no winter season. In these tropical systems, the primary periodic energy flux is diurnal: the temperature variation from day to night is greater than from season to season (see Figure 4.2, p. 35). Average annual rainfall is heavy and exceeds annual evaporation, but varies in amount, season, and distribution.
Graduate Internship Training of Integrated Behavioral Health in Primary Care (IBHPC)

Graduate programs that train students to operate in team-based integrated care environments are increasingly provided in online platforms and target the development of competencies related to team-based collaborations. Evaluations tied to these and other competencies are making it possible to determine that students can apply the knowledge of team-based work in primary care practice settings. One evaluation tool is presented that proposes a link among behavioral health activities, behavioral anchors, and performance metrics that address each of the three worlds (i.e., clinical, operational, financial) of healthcare practice.
“But I just want a book!” Is your discovery layer meeting your users’ needs?

In January 2016, the University of Toledo Libraries implemented EBSCO Discovery Services (EDS) as its discovery layer. Administrators questioned whether users were able to find consortial material ...
A Naïve Realist Theory of Colour

Philosophical theories of colour are typically sorted into a small number of groups, on the basis of the kinds of property that colours are taken to be. Physicalist theories of colour take colours ...
Resistance, WAPAC: J-Town Collective, Nihonmachi Little Friends—The Goodman Group and Coalitions with Architectural Preservationists

Here the process by which neighbors formed groups to defend themselves and their communities is described. The Japanese community, just returned from the camps, is the first set up for removal in the face of patriotic sacrifice and threats. Attempts to join historic preservation with community preservation begin to appear.
Assessment of the physicochemical and microbiological status of western Niger Delta soil for crude oil pollution bioremediation potential

The physical, chemical and microbiological characteristics of the soil across the western Niger Delta area of Nigeria were determined to assess its potential for natural remediation of crude oil pollution. The pH (oil-producing area, 6.1 ± 1.1; non-oil producing, 5.9 ± 0.9) and temperature (28–35 °C in both areas) were favourable to natural remediation, while the fluctuating moisture (7.7–45.6 %) and the dominant sandy soil textural classes (70 %) were limitations. The carbon nitrogen phosphorus (CNP) ratio markedly exceeded recommended 100:10:1, while the cation exchange capacity was below acceptable range. Counts of heterotrophic bacteria, fungi and hydrocarbon-utilising and nitrogen-fixing bacteria (mean range log10 3.8 ± 1.5–6.52 ± 0.9 cfu/g) were favourable having markedly exceeded the minimum counts required. Crude oil loss was highest in loam soil, but significantly (P = 0.00) increased in all soil textural classes including sandy soils after amendment with cow dung/poultry dropping and manual aeration in laboratory and 8-month field tests as indicated by two-way ANOVA. Thus, the overall assessment is that while CNP can be viewed as the major limiting factor to natural oil pollution remediation in the western Niger Delta soil, its influence can be minimised by the amendment indicated in the study.
Cars and Contemporary Communication| Automobility, Autonomy, and Communication

This article explores the tension between the freedom a self-driving car offers and privacy considerations. Studies of the automobile’s impact on the environment, public health, noise, planning, and development, as well as its appearance in, and inspiration of, popular culture are easy to find. In the field of communication, research on cars as a medium or as a site of communication often falls into the domain of mobilities, as defined by John Urry (2007). Mobilities consider not just the travel of people and objects through space, but also the imaginative, virtual, and communicative travel of messages between people and things. Julia Hildebrand (2017) notes the relationship of mobilities to media ecology and argues that we can understand the exploration of converging media and mobility entities as transportation–information–communication technologies. Furthermore, imaginaries of the autonomous car promote greater freedom for drivers while raising concerns with the necessity of increased connectivity. The automobile is a case for concern in communication studies, particularly around issues of control, freedom, and privacy.
Intermolecular Interactions in Adenine Barbiturate Complexes

Barbiturates are many things to many people. To the pharmacologist they are highly effective sedative-hypnotic agents [1]. To the physiologist they are general metabolic depressants that appear to act as competitive inhibitors in oxidative metabolism [1]. However to the biochemist they are, perhaps, most notable in their resemblance to the nucleic acid bases uracil and thymine.
Tobacco-21 laws and young adult smoking: quasi-experimental evidence.

Aims To estimate the impact of tobacco-21 laws on smoking among young adults who are likely to smoke, and consider potential social multiplier effects. Design Quasi-experimental, observational study using new 2016-17 survey data. Setting United States. Participants/cases A total of 1869 18-22-year-olds who have tried a combustible or electronic cigarette. Intervention and comparators Tobacco-21 laws raise the minimum legal sales age of cigarettes to 21 years. Logistic regressions compared the association between tobacco-21 laws and smoking among 18-20-year-olds with that for 21-22-year-olds. The older age group served as a comparison group that was not bound by these restrictions, but could have been affected by correlated factors. Age 16 peer and parental tobacco use were considered as potential moderators. Measurements Self-reported recent smoking (past 30-day smoking) and current established smoking (recent smoking and life-time consumption of at least 100 cigarettes). Findings Exposure to tobacco-21 laws yielded a 39% reduction in the odds of both recent smoking [odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.42, 0.89] and current established smoking (OR = 0.61; 95% CI = 0.39, 0.97) among 18-20-year-olds who had ever tried cigarettes. This association exceeded the policy's relationship with smoking among 21-22-year-olds. For current established smoking, the tobacco-21 reduction was amplified among those whose closest friends at age 16 used cigarettes (OR = 0.50; 95% CI = 0.29, 0.87), consistent with peer effects moderating the policy's impact on young adult smoking. Conclusions Tobacco-21 laws appear to reduce smoking among 18-20-year-olds who have ever tried cigarettes.
Helping learners as they construct knowledge: How can instructors leverage research findings

The author presents research-based principles that can improve the recall of factual subject matter using existing features in LMS tools, apps, and other methods to meet targeted learning goals.
Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome

Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the Thermus thermophilus 70S ribosome. Our 2.8-A resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomal subunit. Importantly, unlike other tetracyclines, the unique C7 extension of sarecycline extends into the messenger RNA (mRNA) channel to form a direct interaction with the A-site codon to possibly interfere with mRNA movement through the channel and/or disrupt A-site codon-anticodon interaction. Based on our biochemical studies, sarecycline appears to be a more potent initiation inhibitor compared to other tetracyclines, possibly due to drug interactions with the mRNA, thereby blocking accommodation of the first aminoacyl transfer RNA (tRNA) into the A site. Overall, our structural and biochemical findings rationalize the role of the unique C7 moiety of sarecycline in antibiotic action.
Understanding and the listener: Conflicting views.

Skinner’s (1957, 1974) distinction between three senses of the term understanding is presented. For Skinner, a listener understands if she (a) can repeat back to the speaker what he has said; or (b) can respond appropriately; or (c) knows about the controlling variables. Next, a critique of Skinner’s view by Parrott (1984; now L.J. Hayes) is presented. Parrott criticizes the first sense of understanding for simplifying a complex activity; the second for equating understanding with reinforcement mediation; and the third for defining understanding as potential behavior. Next, Parrott’s two alternative views are presented. Understanding is (a) having perceptual responses of things when only their “names” are present, and (b) organizing objects and words into relational networks. Lastly, Skinner’s and Parrott’s views on understanding are evaluated, and Parrott’s views are critiqued.
20 Years for Clearings Your Browser History

In today’s world, average people create and delete massive amounts of digital data every single day. And most of the time people can do so without expecting the Department of Justice to come knocking. But deleting digital data — including clearing browser history — can also result in federal felony obstruction of justice charges under 18 U.S.C. § 1519, the federal anti- shredding statute, which carries a 20-year maximum penalty. It is thus vital that citizens understand what is and is not illegal under § 1519.Unfortunately, understanding what the statute prohibits is an almost impossible task. Indeed, this Article will argue that § 1519 has a vagueness problem. That is, the statute arguably fails “to provide a person of ordinary intelligence fair notice of what is prohibited” and “is so standardless that it authorizes or encourages seriously discriminatory enforcement.” This Article brings attention to § 1519’s vagueness problem and to suggest solutions. Specifically, it recommends that the courts either impose a “nexus requirement” on § 1519 or limit enforcement to the corporate crime context.
Adaptive and multi-path progression signal control under connected vehicle environment

Abstract Through wireless communications, enriched information from connected vehicles (CVs) can describe traffic information near an intersection and would supplement a data source for an effective signal control. This paper proposes an adaptive traffic signal control system in a CV environment. At the intersection level, an adaptive control model is developed to assign optimal green times by minimizing the total vehicle delay. When the CV penetration rate is low, a method depending on limited CV data is presented to estimate the vehicle arrival information. At the corridor level, a real-time optimization model is formulated to design the dynamic progression plan for critical paths (i.e. paths with high flows). These two optimization models are solved by the dynamic programming technique. A real-world arterial is modeled in VISSIM to evaluate the effectiveness and efficiency of the proposed traffic signal control system. Simulations with various CV penetration rates and demand levels are conducted to compare the proposed system with fixed coordination and adaptive signal control systems. Results indicate that the proposed system outperforms both base systems by reducing 15.67% and 13.81% of the average delay, respectively, when the CV penetration rate is relatively high. Moreover, the proposed system can improve the arterial performance under all tested scenarios with various CV penetration rates and demand levels. Since the tested demand scenarios can reflect the real traffic fluctuations, it can be proved that the proposed control system could be applied in the field to boost the overall traffic efficiency along the arterial.
Non-contrast head CT-based thrombolysis for wake-up/unknown onset stroke is safe: A single-center study and meta-analysis.

BackgroundRecent studies have shown that tPA can be safely administered past the standard 4.5 h window with good outcomes when selected with multi-model imaging, which is often lacking outside of c...
Swelling-Induced Symmetry Breaking: A Versatile Approach to the Scalable Production of Colloidal Particles with a Janus Structure

Janus particles are widely sought for applications related to colloidal assembly, stabilization of emulsions, and development of active colloids, among others. Here we report a versatile route to the fabrication of well-controlled Janus particles by simply breaking the symmetry of spherical particles with swelling. When a polystyrene (PS) sphere covered by a rigid shell made of silica or polydopamine is exposed to a good solvent for PS, a gradually increased pressure will be created inside the shell. If the pressure becomes high enough to poke a hole in the shell, the spherical symmetry will break while pushing out the swollen PS through the opening to generate a Janus particle comprised of two distinct components. One of the components is made of PS and its size is controlled by the extent of swelling. The other component is comprised of the rigid shell and remaining PS, with its overall diameter determined by the original PS sphere and the rigid shell. This solution-based route holds promises for the scalable production of complex Janus particles with a variety of compositions and in large quantities.
Channelopathies in fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and the leading monogenic cause of autism. The condition stems from loss of fragile X mental retardation protein (FMRP), which regulates a wide range of ion channels via translational control, protein–protein interactions and second messenger pathways. Rapidly increasing evidence demonstrates that loss of FMRP leads to numerous ion channel dysfunctions (that is, channelopathies), which in turn contribute significantly to FXS pathophysiology. Consistent with this, pharmacological or genetic interventions that target dysregulated ion channels effectively restore neuronal excitability, synaptic function and behavioural phenotypes in FXS animal models. Recent studies further support a role for direct and rapid FMRP–channel interactions in regulating ion channel function. This Review lays out the current state of knowledge in the field regarding channelopathies and the pathogenesis of FXS, including promising therapeutic implications. Ion channel dysfunctions contribute significantly to fragile X pathophysiology. In this Review, Deng and Klyachko discuss the mechanisms underlying the effects of these channelopathies in fragile X syndrome, and the therapeutic potential of pharmacological interventions that target ion channels.
American Diversity in International Arbitration: A New Arbitration Story or Evidence of Things Not Seen (last edit)

I was drawn to the idea of having a longer view of diversity by focusing on the presence of black people in international trade. 1609 then becomes a way station in a process that started over 150 years before that date of Africans being objects in international trade. The best way I found to capture this flow of humans and their labor out of Africa to the New World is in a short video entitled “Transatlantic Slave Trade in Two Minutes, 315 years, 20,528 voyages, millions of lives” which I encourage the reader to watch now before reading further. Once in the New World, the labor of these enslaved Africans was extracted to create wealth which in turn flowed back to international trade in goods such as cotton. I imagine every time there was a dispute between merchants on an American wharf about the quality of the cotton being loaded with an arbitrator coming in to resolve the dispute, some unseen enslaved African picked that cotton, baled it, and put it on some means of transportation to get to that port where the dispute has arisen. This article suggests that the unseen presence of blacks and other underrepresented groups in the shadows of development of international arbitration law in the United States helps us see that diversity – while unrecognized – has been inherent to American international arbitration for hundreds of years.
A Neighborhood Aware Caching and Interest Dissemination Scheme for Content Centric Networks

Content-Centric Networking (CCN) is a promising framework for the next generation Internet architecture that exploits ubiquitous in-network caching to minimize content delivery latency and reduce network traffic. In this paper, we introduce a neighborhood aware mechanism for content caching, named Neighborhood Aware Caching and Interest Dissemination ( NACID ) that accounts for the popularity of contents and how close the content copies are in the neighborhood. We use a very low-overhead, Bloom Filter based dissemination of caching information in the neighborhood. Given the neighborhood cached contents, the proposed scheme decides when and how to handle the additional caching of content and its eviction. Simulation results show that NACID performs substantially better than the existing CCN caching policies. We also study different heterogeneous cache memory allocation strategies and show that the simpler homogeneous allocation strategies work almost as well.
Multinational Firms’ Sourcing Decisions and Wage Inequality: A Dynamic Analysis

This paper uses a two-country dynamic general equilibrium model to consider how, following a trade cost shock, multinational firms’ offshoring decision and the countries’ different factor endowments affect wage inequality between high- and low-skilled workers in the home country. Highlighting task-offshoring, heterogenous firms, and factor proportions, the study sheds light on how offshoring shapes wage inequality along different time horizons. While the paper’s focus is the relationship between the U.S. (home country) and China (foreign country), its findings are more broadly relevant. The three main findings are these: First, both intensive and extensive margins contribute to the widening wage gap, with the latter playing a more important role in the short- to medium- term than it does in the initial stage after the trade cost shock. Second, endogenous firm entry raises wage for both low-skilled and high-skilled workers while also widening the wage gap between the two groups over time. Third, whether firms offshore to a foreign country like Mexico, where the supply of low-skilled laborers is moderately larger than in the home country, or to a country like China, where the supply of low-skilled laborers is vastly larger, makes scant difference to wage inequality in the long term.
Patrimony and Law in Renaissance Italy

Family was a central feature of social life in Italian cities. In the Renaissance, jurists, humanists, and moralists began to theorize on the relations between people and property that formed the 'substance' of the family and what held it together over the years. Family property was a bundle of shared rights. This was most evident when brothers shared a household and enterprise, but it also faced overlapping claims from children and wives which the paterfamilias had to recognize. Thomas Kuehn explores patrimony in legal thought, and how property was inherited, managed and shared in Renaissance Italy. Managing a patrimony was not a simple task. This led to a complex and active conceptualization of shared rights, and a conscious application of devices in the law that could override liabilities and preserve the group, or carve out distinct shares for each member. This wide-ranging volume charts the ever-present conflicts that arose and were a constant feature of family life.
Limitation Riders in the Postreform House: A Test of Procedural Cartel and Conditional Party Government Theories

The theoretical debate over the ability of parties and leaders in the House of Representatives to influence legislative decision-making is at the center of much of the literature on Congress. On the one hand, the Procedural Cartel perspective argues that while the tools used by the majority party leadership to assure the triumph of its preferences may vary depending on the institutional context, the basic ability of the leadership to impact legislative outcomes remains consistent. In contrast, Conditional Party Government (CPG) theory posits that any power the majority party and its leadership possesses over legislative decision-making is directly conditioned upon the amount of agreement within the majority party caucus as to collective goals, as well as the amount of ideological polarization that exists between the majority and minority parties. This thesis provides an original test of these two theoretical perspectives by evaluating their comparative ability to account for the proposal and passage of limitation riders on the House floor during the annual appropriations process since the 1980s. Limitation riders provide a good vehicle to test theories of congressional voting as they often have important policy implications in areas of significant controversy. In addition, the extent to which the individual members or legislative parties are able to successfully utilize limitation riders as a means of making substantive policy is indicative of larger patterns of committee or party domination of
A self-cooled liquid breeder blanket for a laser ife power plant with magnetic intervention

A possible way to address the issue of dry wall survival in a Laser IFE chamber is to use magnetic diversion in order to steer away the ions from the chamber wall (representing ∼25-30% of the yield energy). A cusp magnetic field is imposed on to the chamber; the ions from the micro-explosion are trapped within the magnetic field and are directed to more readily accessible and replaceable dump regions at the equator and poles. A large fraction of the magnetic energy can be dissipated in the chamber walls if an electrically resistive structural material is used. An advanced blanket based on a self-cooled liquid breeder (e.g.Pb-17Li or flibe) and SiC/SiC structure has been proposed for this purpose and a scoping design study performed as part of the High Average Power Laser program effort This paper summarizes the results of this scoping study, and highlights the advantages of such a concept as well as the key issues that need to be addressed by R&D.
EGFR Mutations in Lung Adenocarcinomas: Clinical Testing Experience and Relationship to EGFR Gene Copy Number and Immunohistochemical Expression

Lung adenocarcinomas responsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors possess EGFR mutations and often increased EGFR copy number. We prospectively studied 334 clinical cases using polymerase chain reaction-based assays to detect deletions within exon 19 and the L858R mutation in exon 21, which together account for approximately 90% of EGFR mutations. Seventy-eight (23%) of these tumors had an EGFR mutation, with 55 (71%) exon 19 deletions and 23 (29%) exon 21 L858R mutations. We were able to compare mutant and normal EGFR alleles and found a preferential amplification of the mutant allele. The association of mutations with EGFR amplification (determined by chromogenic in situ hybridization) and EGFR expression (determined by immunohistochemistry) was further examined in a subset of 60 tumors. EGFR amplification (≥5 EGFR signals per nucleus) was seen in 15 of 29 (52%) EGFR-mutated tumors but in only five of 31 (6%) non-mutated tumors (P = 0.006). EGFR overexpression was strongly associated with amplification but was statistically independent of EGFR mutation. Most patients with EGFR mutations (17 of 29, 59%) never smoked compared with 13% (four of 31) of patients lacking such mutations (P = 0.0003). The association of amplification with smoking status was marginal and was nonexistent with EGFR expression. Thus, these results indicate that EGFR amplification, preferentially of the mutant allele, often accompanies EGFR mutation, whereas EGFR immunohistochemical staining associates with amplification but cannot predict EGFR mutation status.
A MAP Kinase-Signaling Pathway Mediates Neurite Outgrowth on L1 and Requires Src-Dependent Endocytosis

The neural cell adhesion molecule L1 mediates the axon outgrowth, adhesion, and fasciculation necessary for proper development of synaptic connections. Mutations of human L1 cause an X-linked mental retardation syndrome termed CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia, and hydrocephalus), and L1 knock-out mice display defects in neuronal process extension resembling the CRASH phenotype. Little is known about the biochemical or cellular mechanism by which L1 performs neuronal functions. Here it is demonstrated that clustering of L1 with antibodies or L1 protein in rodent B35 neuroblastoma and cerebellar neuron cultures induced the phosphorylation/activation of the mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinases 1 and 2. MAPK activation was essential for L1-dependent neurite outgrowth, because chemical inhibitors [2-(2′-amino-3′-methoxyphenyl)-oxanaphthalen-4-one and 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] of the MAPK kinase MEK strongly suppressed neurite outgrowth by cerebellar neurons on L1. The nonreceptor tyrosine kinase pp60 c-src was required for L1-triggered MAPK phosphorylation, as shown in src- minus cerebellar neurons and by expression of the kinase-inactive mutant Src(K295M) in B35 neuroblastoma cells. Phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase p21 rac were identified as signaling intermediates to MAPK by phosphoinositide and Rac–GTP assays and expression of inhibitory mutants. Antibody-induced endocytosis of L1, visualized by immunofluorescence staining and confocal microscopy of B35 cells, was blocked by expression of kinase-inactive Src(K295M) and dominant-negative dynamin(K44A) but not by inhibitors of MEK or PI3-kinase. Dynamin(K44A) also inhibited L1 antibody-triggered MAPK phosphorylation. This study supports a model in which pp60 c-src regulates dynamin-mediated endocytosis of L1 as an essential step in MAPK-dependent neurite outgrowth on an L1 substrate.
Jonathan Lawrence and Justin Vaisse, Integrating Islam: political and religious challenges in contemporary France

The growing Muslim population in Europe has increasingly attracted social scientists’ attention. Jonathan Laurence and Justin Vaisse’s Integrating Islam is a very successful example of books recently written on this issue. As is clear from its publisher, Integrating Islam is primarily a policy study. Although the book does not include an explicit discussion of social science theories, it still has an implicit theoretical background. It mainly refutes essentialism. Essentialism, which takes Islam as a monolithic entity comprised by certain essences that challenge Western values, became popular among certain analysts who have tried to explain terrorism. In his excellent Foreword to Integrating Islam, Olivier Roy summarizes the antiessentialist theoretical stand of the book: ‘In Europe, Islamic fundamentalism is usually the product of a process of alienation and deculturation rather than the ultimate expression of Islamic culture....This noteworthy book...refuses to engage in the often fruitless debate on Islam as an abstract concept. The authors rely on solid documentation to study actual Muslims who live in France (p. xiv-xv)’. Integrating Islam explores both the Muslims’ attitudes in France and the French state’s response to this relatively new public actor, while revealing the interaction between these two. According to Laurence and Vaisse, Islam is only one aspect of the multiculturalist challenge that the French Republic has witnessed. Not only Muslims, but also followers of other religions have certain problems in France due to the French Republic’s ‘sensitivities regarding the presence of religion in the public sphere’ and its goal to ‘“privatize” religious affiliation’ (p. 10). Due to the Cont Islam DOI 10.1007/s11562-007-0036-5
Data quality requirements analysis and modeling

A set or premises, terms, and definitions for data quality management are established, and a step-by-step methodology for defining and documenting data quality parameters important to users is developed. These quality parameters are used to determine quality indicators about the data manufacturing process, such as data source creation time, and collection method, that are tagged to data items. Given such tags, and the ability to query over them, users can filter out data having undesirable characteristics. The methodology provides a concrete approach to data quality requirements collection and documentation. It demonstrates that data quality can be an integral part of the database design process. A perspective on the migration towards quality management of data in a database environment is given. >
Convergence of multiple signaling pathways is required to coordinately up-regulate mtDNA and mitochondrial biogenesis during T cell activation.

The quantity and activity of mitochondria vary dramatically in tissues and are modulated in response to changing cellular energy demands and environmental factors. The amount of mitochondrial DNA (mtDNA), which encodes essential subunits of the oxidative phosphorylation complexes required for cellular ATP production, is also tightly regulated, but by largely unknown mechanisms. Using murine T cells as a model system, we have addressed how specific signaling pathways influence mitochondrial biogenesis and mtDNA copy number. T cell receptor (TCR) activation results in a large increase in mitochondrial mass and membrane potential and a corresponding amplification of mtDNA, consistent with a vital role for mitochondrial function for growth and proliferation of these cells. Independent activation of protein kinase C (via PMA) or calcium-related pathways (via ionomycin) had differential and sub-maximal effects on these mitochondrial parameters, as did activation of naive T cells with proliferative cytokines. Thus, the robust mitochondrial biogenesis response observed upon TCR activation requires synergy of multiple downstream signaling pathways. One such pathway involves AMP-activated protein kinase (AMPK), which we show has an unprecedented role in negatively regulating mitochondrial biogenesis that is mammalian target of rapamycin (mTOR)-dependent. That is, inhibition of AMPK after TCR signaling commences results in excessive, but uncoordinated mitochondrial proliferation. Thus mitochondrial biogenesis is not under control of a single master regulatory circuit, but rather requires the convergence of multiple signaling pathways with distinct downstream consequences on the organelle's structure, composition, and function.
The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected participants.

Background: The pathogenesis of immunodeficiency due to human immunodeficiency virus (HIV)-1 is incompletely understood, but immune activation is believed to play a central role. Immunomodulatory agents that decrease immune activation may be useful in the treatment of HIV-1 infection. Methodology: A randomized, double blind, placebo-controlled pilot study of leflunomide for 28 days was performed in participants with HIV-1 infection who were not receiving antiretroviral therapy. Participants randomized to leflunomide were subsequently treated with cholestyramine until leflunomide levels were below detection limit. Findings: Treatment with leflunomide was well tolerated with mostly low-grade adverse events. Leflunomide administration reduced cycling of CD4 T cells (by ex vivo bromodeoxyuridine uptake and Ki67 expression) and decreased expression of activation markers (HLA-DR/CD38 co-expression) on CD8 T cells in peripheral blood. In addition, decreased expression of HIV-1 co-receptors was observed in both CD4 and CD8 T cells in the leflunomide group. There were no
Alkaline thermolysis of phenyl α- and, β-D-glucopyranosides

Abstract Pyrolysis of phenyl α- and β- D -glucopyranosides in the presence and absence of 5% of sodium hydroxide has been investigated by co-ordinated thermal and chemical methods. The resulting thermograms and kinetic data show that the configurational effects observed for aqueous systems also prevail under the pyrolytic condition, and that the thermolysis of the β- D anomer under alkaline conditions is facilitated by anchimeric assistance of the trans -hydroxyl group at C-2, to provide a quantitative yield of 1,6-anhydro-β- D -glucopyranose.
Oblique tibial osteotomy for Blount's disease (tibia vara)

Nine oblique proximal tibial osteotomies were performed on six children with genu varum, all but one of whom had Blount's disease. The osteotomy was a single-plane cut allowing simultaneous correction of varus and internal rotation and permitting postoperative cast wedging if necessary to improve position. All osteotomies healed within 10 weeks. The major complications were three episodes of weakness of the extensor hallucis longus, two of which resolved in 4 days and one of which resolved only partially. We were able to combine the osteotomy with other procedures, such as epiphyseal bar resection. All nine osteotomies achieved the desired correction of deformity.
Effect of alpha-methyl-para-tyrosine on response to cocaine challenge.

This study evaluated the effect of an acute reduction in catecholamine synthesis produced by alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, on cocaine-induced euphoria. In a blinded, placebo-controlled study, AMPT (1 g p.o. T.I.D.) was given to 10 non-treatment-seeking cocaine abusers prior to intranasal administration of 2 mg/kg cocaine. AMPT, but not placebo, reduced plasma levels of the dopamine metabolite homovanillic acid and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol. AMPT also elevated prolactin levels, indicating inhibition of the tuberoinfundibular dopamine system. AMPT pretreatment produced a trend toward diminished cocaine "high." AMPT also tended to lower heart rate and blood pressure responses to cocaine, but had no effect on serum cocaine levels. Although we cannot rule out the therapeutic potential of the depletion strategy, our results with AMPT alone, at this dose, do not strongly support it.
Recent Advances in Acne Pathogenesis: Implications for Therapy

Acne pathogenesis is a multifactorial process that occurs at the level of the pilosebaceous unit. While acne was previously perceived as an infectious disease, recent data have clarified it as an inflammatory process in which Propionibacterium acnes and innate immunity play critical roles in propagating abnormal hyperkeratinization and inflammation. Alterations in sebum composition, and increased sensitivity to androgens, also play roles in the inflammatory process. A stepwise approach to acne management utilizes topical agents for mild to moderate acne (topical retinoid as mainstay ± topical antibiotics) and escalation to oral agents for more resistant cases (oral antibiotics or hormonal agents in conjunction with a topical retinoid or oral isotretinoin alone for severe acne). Concerns over antibiotic resistance and the safety issues associated with isotretinoin have prompted further research into alternative medications and devices for the treatment of acne. Radiofrequency, laser, and light treatments have demonstrated modest improvement for inflammatory acne (with blue-light photodynamic therapy being the only US FDA-approved treatment). However, limitations in study design and patient follow-up render these modalities as adjuncts rather than standalone options. This review will update readers on the latest advancements in our understanding of acne pathogenesis and treatment, with emphasis on emerging treatment options that can help improve patient outcomes.
Matrix solution for the wall impedance of infinitely long multilayer circular beam tubes

The coupling impedance of beam tubes is a long-standing important topic for particle accelerators that many authors have addressed. The present study was initiated in view of a specific problem, but its novel approach is broadly applicable to the longitudinal and transverse coupling impedances of coated beam tubes or multilayer tubes. The matrix method presented here derives the wall impedance by treating the radial wave propagation of the beam-excited electromagnetic fields in full analogy to longitudinal transmission lines. Starting from the Maxwell equations, the radially transverse magnetic field components are described for monopole and dipole modes by a $2\ifmmode\times\else\texttimes\fi{}2$ matrix. Assuming isotropic material properties within one layer, the transverse field components at the inner boundary of a layer uniquely are determined by matrix transfer of the field components at its outer boundary. By imposing power-flow constraints on the matrix, wave impedance mapping and field matching between layers is enforced and replaced by matrix multiplication. The longitudinal and transverse coupling impedances are derived from the wall impedance at the innermost boundary, and the different procedures for its determination are discussed. The matrix method is demonstrated via selected yet representative examples of the well-documented cases of a stainless-steel tube, and of a graphite collimator.
Design and in silico evaluation of an intraperitoneal–subcutaneous (IP–SC) artificial pancreas

Prandial glucose regulation is a major challenge for the artificial pancreas using subcutaneous insulin (without a feedforward bolus) due to insulin's slow absorption-peak (50-60 min). Intraperitoneal insulin, with a fast absorption peak (20-25 min), has been suggested as an alternative to address these limitations. An artificial pancreas using intraperitoneal insulin was designed and evaluated on 100 in silico subjects and compared with two designs using subcutaneous insulin with and without a feedforward bolus, following the three meal (40-70 g-carbohydrates) evaluation protocol. The design using intraperitoneal insulin resulted in a significantly lower postprandial blood glucose peak (38 mg/dL) and longer time in the clinically accepted region (13%) compared to the design using subcutaneous insulin without a feedforward bolus and comparable results to a subcutaneous feedforward bolus design. This superior regulation with minimal user interaction may improve the quality of life for people with type 1 diabetes mellitus.
Scalable multifolded hypercubes for versatile parallel computers

This paper introduces the family of scalable multifolded hypercube (SMH) architectures for parallel computers. Scalability and versatility at resonable cost are the major characteristics of these architectures. SMHs perform comparable to generalized hypercubes for important classes of algorithms that use regular communication patterns. In addition, they often achieve better performance than the popular direct binary hypercubes because they can emulate efficiently a powerful family of multifolded direct binary hypercubes. Extensive comparison of cost with binary and generalized hypercubes is also included. The hardware cost of SMH's is shown to be even lower than that of fat trees. Therefore, SMH's are viable candidates for the construction of versatile parallel computers.