cssi/SciSciGPT-SciSciNet huggingface dataset:
The PI3K/Akt pathway is present and functional in the preimplantation mouse embryo.

The PI3K/Akt signal transduction pathway is a well-known mediator of growth promoting and cell survival signals. While the expression and function of this pathway have been documented during early and late stages of the reproductive process, currently, there is no evidence demonstrating either the presence or function of the PI3K/Akt pathway in murine preimplantation embryos. We found, using confocal immunofluorescent microscopy and Western blot analysis, that the p85 and p110 subunits of PI3K and Akt are expressed from the 1-cell through the blastocyst stage of murine preimplantation embryo development. These proteins were localized predominantly at the cell surface from the 1-cell through the morula stage. At a blastocyst stage, both PI3K and Akt exhibited an apical staining pattern in the trophectoderm cells. Interestingly, phosphorylated Akt was detected throughout murine preimplantation development, and its presence at the plasma membrane is a reflection of its activation status. Inhibition of Akt activity had significant effects on the normal physiology of the blastocyst. Specifically, inhibition of this pathway resulted in a reduction in insulin-stimulated glucose uptake. In addition, inhibiting Akt activity resulted in a significant delay in blastocyst hatching, a developmental step facilitating implantation. Finally, we established the presence of this pathway in trophoblast stem (TS) cells, a potentially useful in vitro model to study this signaling cascade. Taken together, these data are the first to demonstrate the presence and function of the PI3K/Akt pathway in mammalian preimplantation embryos.
Introduction to John Wild’s “Marxist humanism and existential philosophy”

1 In their The Promise of Phenomenology (2006: 269), Sugarman and Duncan mention that Wild ‘‘almost certainly’’ had given an undergraduate course on ‘‘Marxism and Existentialism’’ in the fall of 1966 when I began my post-doctoral fellowship in philosophy at Yale with the intention of studying phenomenology in earnest with Wild. I wonder if they tried to check with the Yale registrar’s office to make this fact certain. In the fall of 1966, I remember sitting only in his seminar on ‘‘Freedom and Responsibility’’ where I read Wild’s book Existence and the World of Freedom (1963) with utmost care.
Mechanism of reduction in titers from lentivirus vectors carrying large inserts in the 3'LTR.

Self-inactivating (SIN) lentiviruses flanked by the 1.2-kb chicken hypersensitive site-4 (cHS4) insulator element provide consistent, improved expression of transgenes, but have significantly lower titers. The mechanism by which this occurs is unknown. Lengthening the lentiviral (LV) vector transgene cassette by an additional 1.2 kb by an internal cassette caused no further reduction in titers. However, when cHS4 sequences or inert DNA spacers of increasing size were placed in the 3′-long terminal repeat (LTR), infectious titers decreased proportional to the length of the insert. The stage of vector life cycle affected by vectors carrying the large cHS4 3′LTR insert was compared to a control vector: there was no increase in read-through transcription with insertion of the 1.2-kb cHS4 in the 3′LTR. Equal amount of full-length viral mRNA was produced in packaging cells and viral assembly/packaging was unaffected, resulting in comparable amounts of intact vector particles produced by either vectors. However, LV vectors carrying cHS4 in the 3′LTR were inefficiently processed following target-cell entry, with reduced reverse transcription and integration efficiency, and hence lower transduction titers. Therefore, vectors with large insertions in the 3′LTR are transcribed and packaged efficiently, but the LTR insert hinders viral-RNA (vRNA) processing and transduction of target cells. These studies have important implications in design of integrating vectors.
Estimation of myocardial perfusion using deuterium nuclear magnetic resonance.

A technique to estimate regional and/or global myocardial perfusion in-vivo was developed using deuterium nuclear magnetic resonance measurement of perdeuterated saline washout from the myocardium of 9 dogs. Washout data were fitted to a one-component plus baseline Kety-Schmidt exponential model. To assess the ability of this technique to reliably measure changes in perfusion during change in myocardial workload, norepinephrine (1 μg/kg/min) was infused and hypoxia was induced (by increasing the inspired ratio of N2O2 to obtain a PAO2 of 20–30 mmHg) in separate interventions. Myocardial work, as determined by heart rate × systolic blood pressure, increased during both interventions. To support this increased workload, myocardial perfusion increased during both physiological interventions. These data indicate that myocardial perfusion can now be reliably estimated with a non-radioactive, non-toxic (in the concentrations used) tracer, perdeuterated saline. The technique can be used for repeated real-time measurements of perfusion during sequential physiological interventions.
Prime-based mimic functions for the implementation of covert channels

A novel method for design and implementation of a covert channel using a prime-based mimic function is presented. The main idea is to map the production rules of a context-free grammar onto a set of prime numbers, and encode messages using primes as factors so that the generated data fits the statistical properties of a given language. The method's performance is assessed through different metrics such as language perplexities, secret-to-cover ratio, and transmission bit-rates. A set of experiments shows that prime-based mimic functions provide an efficient method for implementing a covert channel with a competitive secret-to-cover ratio and low perplexities.
Total-Body Irradiation and Manganese Metabolism

IN a previous communication1 it was reported that glucocorticoid hormones produced a specific metabolic alteration of manganese in mice. This manifested itself chiefly by a marked change in the partition of manganese-54 between the liver and the rest of the body: under treatment with glucocorticoids the concentration of manganese-54 decreased while the carcass concentration of the radioisotope increased at a much faster rate than in control animals. Mineralocorticoids did not produce this effect. None of the corticoids tested influenced the metabolism of another intracellular transition metal, namely, zinc-65.
Effects of maturation and aging on calmodulin and calmodulin-regulated enzymes in various regions of mouse brain

Components of the calmodulin system (i.e., calmodulin levels and activities of the following calmodulin-dependent enzymes: Ca2+ + Mg2+-ATPase, adenylate and guanylate cyclases, cyclic AMP and cyclic GMP phosphodiesterases, and Ca2+-dependent protein kinase were studied in the following brain regions from immature (25-day-old), mature (3-month-old) and aged (22-month-old) mice: striatum, cortex, cerebellum, diencephalon and medulla + pons. Both maturation and advanced aging were associated with significant changes in calmodulin content and in enzyme activities. The study provides evidence for important changes in the activity of this fundamental cell regulatory system in the brain during the processes of maturation and aging.
Observations of Predation and Anti-Predator Behavior of Rubythroated Hummingbirds During Migratory Stopover

Abstract Predation is not thought to contribute significantly to adult hummingbird mortality in temperate areas, where most reported cases of mortality are the result of accidents (e.g., window collisions and spider webs). However, the hazards encountered during migration, including the threat of predation, can impact hummingbirds while on stopover. We present one account of predation upon Archilochus colubris (Ruby-throated Hummingbird) by Accipiter striatus (Sharp-shinned Hawk) and one account of a Ruby-throated Hummingbird displaying anti-predator behavior by mobbing a Falco sparverius (American Kestrel). All observations took place in coastal Alabama during stopover in autumn.
The relationship between sleep disturbance and pulmonary function in stable pediatric cystic fibrosis patients.

Background Cystic fibrosis (CF) is the most common inherited disease affecting northern European populations. It is characterized by a progressive clinical course that causes diurnal and nocturnal pulmonary and gastrointestinal symptoms. Objectives To determine whether clinically stable pediatric patients with CF have lower sleep efficiency than healthy control subjects, and to examine the relationship between sleep efficiency and pulmonary function. Methods Forty-four CF patients and 40 control subjects completed 5 days of actigraphy recordings. Additionally, sleep questionnaires were independently completed by all study participants and their parents. Pulmonary function testing was performed in all patients with CF. Multiple regression analysis was used to measure the independent correlation between sleep variables and pulmonary function. Results CF patients had significantly lower sleep efficiency than control subjects. The FEV 1 of these patients correlated positively with sleep duration and efficiency, and negatively with the number and duration of nocturnal awakenings, age, and body mass index (BMI). The independent effect of FEV 1 on sleep was first examined. Age and FEV 1 were the only variables that predicted sleep duration ( R 2 = 0.3; p=0.0007), while FEV 1 was the only variable predicting sleep efficiency ( R 2 = 0.28; p=0.0002). When the independent effect of sleep on FEV 1 was analyzed, sleep efficiency, BMI percentile, and gender predicted FEV 1 ( R 2 = 0.46; p ≤ 0.0001). The frequency of nocturnal cough reported by patients and their parents was an independent predictor of FEV 1 . Conclusions Pediatric patients with CF and stable pulmonary function have lower sleep efficiency and more frequent nocturnal awakenings than do healthy control subjects. After adjustment for demographic characteristics, there was an independent and significant correlation between sleep parameters and FEV 1 , when either sleep variables or FEV 1 were used as dependent variables. These findings suggest a bidirectional relationship between sleep disturbance and CF lung disease.
Toward a Networked Urbanism: Hugh Ferriss, Rockefeller Center, and the “Invisible Empire of the Air”

The metaphor of networking informed practices of urban spectatorship in New York City in the 1920s and 1930s. Hugh Ferriss famously represented a future Manhattan in his book The Metropolis of Tomorrow as a careful grouping of distinct nodes unified by the perspective of an individual spectator. In his drawings, a lone figure seems to assemble the disparate parts of the city into a comprehensible whole. The networked urbanism to which Ferriss alluded was first explored in the built environment during the long construction process of the midtown Manhattan development Rockefeller Center. By focusing on its construction plans, public artwork, and publicity, this essay traces the development of early networked urbanism in New York City. It investigates the rhetoric of the network in real space and imagined and explores how this metaphor influences the relationship between the urban spectator and the developing urban landscape.
Correlates of Social Participation: a Comparison of the Ethnic Community and Compensatory Theories*

The ethnic community and compensatory theories of Black social participation are compared by analyzing affective correlates (political efficacy and self-esteem) of participation for 712 residents of Nashville, Tennessee in 1969. The instrumental-expressive typology of participation is utilized in addition to total participation. Participation and the affective variables are significantly correlated for Blacks, but only weakly correlated for Anglos, lending support to both theories. The relationship between participation, the affective variables, and the controlled background factors is briefly discussed, and problems and directions for future research are outlined.
Bacterial lipopolysaccharide induces endothelial cells to synthesize a degranulating factor for neutrophils

Enzymes and other factors secreted by degranulating neutrophils (polymorphonuclear leukocytes, PMNs) mediate endothelial injury, thrombosis, and vascular remodeling. In bacteremia and sepsis syndrome and their consequent complications (including acute respiratory distress syndrome and systemic ischemia-reperfusion resulting from septic shock), neutrophil degranulation is an important mechanism of injury. In related studies, we found that human endothelial cells regulate neutrophil degranulation and that inflammatory cytokines induce synthesis of degranulating factors by human endothelial cells. Here we show that lipopolysaccharides (LPS) from gram-negative bacteria were the most potent agonists for release of degranulating activity by endothelial cells when compared to several cytokines and stimulatory factors. LPS also induced the release of degranulating signals for PMNs from a human endothelial cell line, EA.hy 926. Interleukin 8 (IL-8) is synthesized by endothelial and EA.hy 926 cells in response to LPS and induces neutrophil degranulation. However, complementary strategies using receptor desensitization, translation of messenger RNA by Xenopus laevis oocytes, and purification and analysis of factors from conditioned supernatants demonstrated that degranulating factors distinct from IL8 are generated in response to LPS. The characteristics of a partially purified degranulating factor isolated from conditioned supernatants distinguished it from known chemokines and other factors that induce PMN degranulation and are generated by endothelial cells in response to LPS. Thus, cultured human endothelial cells and endothelial cell lines synthesize several unique signaling molecules that can trigger neutrophil granular secretion. If produced in vivo in response to LPS or other pathologic agonists, these degranulating signals may activate PMNs in combination or in sequence, initiating or propagating vascular damage.
Rehabilitation medicine approach to cancer pain

Cancer pain may benefit from interventions that focus on function. Pain and mobility may be improved by strengthening, stretching, and the use of assistive devices. Physical, occupational, and speech therapy may all be needed to help manage pain in the cancer patient. Pain may be due to the cancer itself or secondary to immobility and debilitation.
DEVELOPMENTAL ASPECTS AND FACTORS INFLUENCING THE SYNTHESIS AND STATUS OF ASCORBIC ACID IN THE PIG

� Abstract Ascorbic acid synthesis in the pig occurs at mid-pregnancy, but activity of the enzyme L-gulono-γ -lactone oxidase (GLO) declines thereafter during gestation and remains low when the pig nurses the sow. During late gestation the ascorbic acid concentration in the fetus increases, but serum and liver ascorbic acid concentration in the sow declines without affecting the dam’s liver GLO activity. It is presumed that as gestation progresses an increased amount of maternal ascorbic acid is transferred to the fetus and to the mammary gland. Colostrum and milk are rich sources of the vitamin and supply the nursing pig with ascorbic acid. The available data suggest that high amounts of ascorbic acid appear to suppress liver GLO activity in the pig. Upon weaning, when exogenous vitamin C is generally not provided, liver GLO activity and serum ascorbic acid increases. During the initial periods postweaning, some reports have indicated growth benefits of supplemental vitamin C. Body tissues differ in their concentrations of ascorbic acid, but tissues of high metabolic need generally have greater concentrations. The corpus luteum in the female, the testis in the male, and the adrenal glands in all pigs contain greater concentrations of the vitamin. Knockout genes preventing ascorbic acid synthesis in pigs have demonstrated poor skeletal and collagen formation and poor antioxidant protection. Under periods of stress ascorbic acid declines in the adrenal, but the pig rapidly recovers to its resting state once the stressor agent is removed. Although there are periods when supplemental vitamin C has been shown to promote pig performance (e.g., during high environmental stress and early postweaning), supplemental vitamin C has not been shown to routinely enhance pig performance.
Evaluation of the Hepatitis C Virus–Infected Patient: The Initial Encounter

Deaths from hepatitis C virus (HCV)-related disease are increasing, now exceeding those from human immunodeficiency virus. Up to 7 million Americans (2.3%) may be infected with HCV, and more than half are undiagnosed. Proposed expansion of hepatitis C screening to include all persons born between 1945 and 1965 will lead to many new diagnoses, and infectious diseases physicians have a unique opportunity to be part of managing these patients. Apart from a liver-focused history and examination, the initial evaluation includes determination of the liver function via serum tests and assessment of liver fibrosis and necroinflammation through biopsy or noninvasive means. Patients with cirrhosis require screening for esophageal varices and for liver cancer. Nonimmune patients need vaccinations against hepatitis A and B, and alcohol abstinence is critical. Initial counseling on therapy emphasizes viral cure rates of currently 70%-80% as well as expected side effects. New treatments with fewer side effects and potentially higher cure rates are currently in development.
Functional parallelism in an operand state saving computer

Multiple, high-level operators are assigned to a general operand. The operators are implemented with individual micro-processors and are "attached" dynamically to the memory location representing the "current" value of the operand. The operators then asynchronously use each new operand value as it is stored and perform their operations in parallel. The proposed architecture represents a true M I S D (Multiple Instruction Stream - Single Data Stream) computer. Its architecture can provide effective parallelism and reduced programming complexity for a large class of both numeric and non-numeric computer problems.
Nano-Particle Polymer Composite MEMS corrosion

This paper presents the concept, design, and diffusion experiments of a new type of MEMS corrosion sensor based on Nano-Particle Polymer Composites as the sensing element. The concept of using MEMS for in-situ corrosion sensing for long-term applications have been proposed recently by our research lab. Past developments in the microfabrication of polymers have enabled the ability to pattern micro- and nano-particles embedded into elastomers such as polyurethanes and silicones. By using metallic particles embedded into varying types of polymers, a tailorable MEMS corrosion sensor is currently being developed. The underlying principle of this sensor is based on the direct sensing of the corrosion of specific target material (embedded particles) instead of indirect environmental measurements. The polymer matrix provides the ability to control the diffusion of corrosion agents, absorption/desorption kinetics, and the oxidation of the metallic particles. A reference sensor consisting of noble particles is then used to provide the degradation information of the polymer matrix itself, thus the effects of the metal corrosion can be extracted using this differential sensor arrangement.
Autophagy and p62 in Cardiac Proteinopathy

Rationale:Recent studies suggest an important role of autophagy in protection against αB-crystallin-based (CryABR120G) desmin-related cardiomyopathies (DRC), but this has not been demonstrated in a...
A software package for computer-aided robotics education

The kinematics of robot manipulators is a corner stone in the study of robotics in general. The computational complexity of the kinematics quite often prevents robotics instructors from using robots of general structure in their illustrative examples and assignments. The software discussed in this article, developed from recent research to support an undergraduate course in robotics, offers computational relief to educators and students in the study of robot manipulators with revolute joints and renders their use as classroom examples possible. Five or six revolute joints robot manipulators of general architecture can be solved easily with the help of this software.
System analysis of flight and passenger trip delays in the National Airspace System (NAS)

The primary objective of the National Airspace System (NAS) is the transportation of passengers and cargo. It is no surprise, therefore, that passenger trip time performance is positively correlated with passenger satisfaction, airfare elasticity, and airline profits. Regulatory consumer information available to airline passengers provides measures of trip performance using only flight data (and not passenger trip data). Previously, researchers, using a small set of proprietary airline data, demonstrated that trip delays experienced by passengers due to missed connections, cancelled flights, and delayed flights are not negligible. Further they showed that flight delay data cannot be used as a proxy for passenger trip delays. This paper describes a comparative statistical analysis between flight delay data and passenger trip delay data for one year's worth of flights on the 1030 single segment routes between the OEP-35 airports. The passenger trip data is derived from publicly available data-bases and accounts for delays experienced by passengers on single segment routes due to cancelled flights as well as delayed flights. The statistical analysis indicates that: (i) the percentage of on-time flights is statistically equivalent to the percentage of on-time passengers, (ii) the average passenger trip delay was 34 minutes in excess of the average flight delay, and (iii) average passenger trip delay for the worst 5% of delayed passengers was 150 minutes in excess of the flight delay. The implications of these results for consumers and consumer protection are discussed.
Determining the peer resource contributions in a P2P contract

In this paper we study a scheme called P2P contract which explicitly specifies the resource contributions that are required from the peers. In particular, we consider a P2P file sharing system in which when a peer downloads the file it is required to serve the file to up to N other peers within a maximum period of time T. We study the behavior of this contribution scheme in both centralized and decentralized P2P networks. In a centralized architecture, new requests are forwarded to a central server which hands out the contract along with a list of peers from where the file can be downloaded. We show that a simple fixed contract (i.e., fixed values of N and T) is sufficient to create the required server capacity which adapts to the load. Furthermore, we show that T, the time part of the contract is a more important control parameter than N. In the case of a decentralized P2P architecture, each new request is broadcast to a certain neighborhood determined by the time-to-live (TTL) parameter. Each server receiving the request independently doles out a contract and the requesting peer chooses the one which is least constraining. If there are no servers in the neighborhood, the request fails. To achieve a good request success ratio, we propose an adaptive scheme to set the contracts without requiring global information. Through both analysis and simulation, we show that the proposed scheme adapts to the load and achieves low request failure rate with high server efficiency.
The effects of temperature settings on cycling rates for bang-bang controllers

An analytical method for determining the effects of temperature differentials on cycling rates for a bang-bang controller in a solar collector loop is presented. The method is an extension of previously published numerical results. The collector thermal capacitance is included in the analysis.
Sensitivity comparison for detection of respiratory bovine coronaviruses in nasal samples from feedlot cattle by ELISA and isolation with the G clone of HRT-18 cells

A monoclonal antibody-based capture enzyme-linked immunosorbent assay (ELISA) was developed to detect respiratory bovine coronavirus (RBCV) antigens in nasal swabs collected from cattle showing signs of respiratory tract disease following shipping. These samples had been previously tested for RBCV by inoculation of G clone cultures of human rectal tumor cells (HRT-18G) and for bovine herpes virus 1, parainfluenza virus 3, bovine adenovirus, bovine respiratory syncytial virus, and bovine viral diarrhea virus on other specifically permissive cell cultures. RBCV has not previously been recognized as an important etiological factor in the bovine respiratory disease complex of feedlot cattle. Thirty of 100 samples tested positive for RBCV antigen by capture ELISA in contrast to 38 of 100 samples that yielded RBCV isolates in G clone cells. Samples yielding other bovine respiratory viruses in the absence of RBCV were negative in the capture ELISA, which was based on the use of a single monoclonal antibody that recognizes one RBCV epitope on the S glycoprotein with the broadest reactivity with different strains of RBCV tested. Some RBCV strains may not be detected by this ELISA, which may account for the higher percentage of RBCV-infected cattle detected by RBCV isolation. However, the ELISA was simple to perform, sensitive, and specific and was more rapid than virus isolation. This assay will be useful for processing large numbers of field samples in future epidemiologic and diagnostic studies of RBCV infections of cattle.
Determination of finite-difference weights using scaled binomial windows

The finite-difference method evaluates a derivative through a weighted summation of function values from neighboring grid nodes. Conventional finite-difference weights can be calculated either from Taylor series expansions or by Lagrange interpolation polynomials. The finite-difference method can be interpreted as a truncated convolutional counterpart of the pseudospectral method in the space domain. For this reason, we also can derive finite-difference operators by truncating the convolution series of the pseudospectral method. Various truncation windows can be employed for this purpose and they result in finite-difference operators with different dispersion properties. We found that there exists two families of scaled binomial windows that can be used to derive conventional finite-difference operators analytically. With a minor change, these scaled binomial windows can also be used to derive optimized finite-difference operators with enhanced dispersion properties.
Sensory cross-finger pedicle graft.

Experience gained on a series of fourteen patients upon whom a sensory pedicle flap from the dorsum of the index finger was used to resurface defects of the thumb has been analyzed.
Re-Defining CSR: Through the lens of a data scientist

The term corporate social responsibility (CSR) has been a continuously evolving concept over the past half century as a strategy to signify social and environmental conscience. However, this philanthropic strategy has become a new paradigm of competitive advantage across many industries. As this strategy continues to progress, the definition is warranted to best capture the essence of the term. Through the review of literature coupled with personal expertise and personal value assessment, a data scientist presents a conceptual definition for CSR in the 21st century.
The Polarization of Light at Sea

A polarizing prism properly oriented was found to darken the sea relative to the sky, to reduce the brilliance of the sun path and to render the horizon more distinct. In bright weather it increased the visibility of objects against the sea background. Attaching polarizing prisms to a sextant and to binoculars improved these instruments in certain cases. Measurements of the light of the sea ruffled by a breeze from several hundred yards from the observer out to the horizon several miles away showed that the light was often more, and rarely less, than 2/3 polarized with electric vector mainly horizontal but tilted up under certain conditions, e.g., tilted up 30° for the sun bearing 90° and at 45° altitude. From the observations and theory it came out that the sea light was the light of the sky at about 25° to 35° above the horizon reflected by the sea, the reflecting facets of the sea surface being most frequently at about 15° to the horizontal. The width of the sun path calculated from this was in agreement with the observed width of about 6°, 14° and 18° in moderate weather for the sun at altitudes 10°, 20° and 30°, respectively. The explanation is given of a number of breezy sea reflection phenomena.
Story/story

This paper starts with an introductory essay stating the issues and discussing the notion of metafiction. Then it continues in an online hypertext narrative demonstration of the interweaving of story and meta-story. The hypertext attempts to show in action how seemingly unified narratives and narrative voices are surrounded and influenced by other voices and meta-stories. No narrative is un-mediated and no narrative voice is alone. The hypertext concludes with some musings on the complexities of narrative reading and writing, also with counterpoint voices. Throughout, the text comments on issues about the reading and writing of hypertext narratives.
Pregnancy Interventions or Behaviors and Cardiometabolic Biomarkers: a Systematic Review

While normal pregnancy is characterized by changes in serum glucose and lipid levels, overweight and obese women exhibit marked alterations in the trajectory of these changes. Reviews have been published assessing the efficacy of behavioral interventions for weight management during pregnancy. No reviews, however, have examined the metabolic impact of such lifestyle changes/behaviors. We conducted this systematic review summarizing evidence to July 2015 from both trials and observational studies examining the impact of lifestyle interventions or healthy behaviors (diet and/or exercise) among pregnant women on cardiometabolic biomarkers measured during pregnancy. We found that studies are conflicting and have small sample sizes. A better understanding of the underlying mechanisms that may mediate the effects of nutrition and physical activity on gestational weight gain, pregnancy complications, and long-term cardiometabolic outcomes is needed with particular focus on high-risk groups of overweight and obese women.
Changing the Paradigm of Imaging Through Immersive Media Experiences

Recent developments of imaging systems have created rich immersive data sets that allow for new forms of media. We will explore new computational imaging capabilities in the area of multi-camera systems and interactive visual experiences.
Estrogen-Induced Hypospadias in the Female Rat.

SummaryThe administration of very large doses of estrogens to pregnant rats has caused a permanent hypospadias and lack of development of the most caudal portion of the vagina, in the female offspring. The abnormality represents an arrest of development so that conditions similar to those found in the 21-day fetus are retained.
Clinical Trial Design Issues in Systemic Sclerosis: an Update

Systemic sclerosis (scleroderma, SSc) is a multisystem disease characterized by vasculopathy, autoimmunity, and fibrosis. SSc has the highest disease-related mortality rate among the rheumatologic illnesses. In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations. It can be difficult to discern disease activity from damage. SSc is highly heterogeneous, with multiple different phenotypes, and predicting who will have progressive disease is not currently well understood. Biomarkers are in early stages of development and do not represent surrogate outcomes at this time. Given that SSc is uncommon, studies of similar disease aspects or populations can lead to competition for patients. This review will focus on current issues in SSc clinical trial design.
Ultraflexible nanostructures and implications for future nanorobots

Several high aspect ratio nanostructures have been made by capillary force directed self-assembly including polymeric nanofiber air-bridges, trampoline-like membranes, microsphere-beaded nanofibers, and intermetallic nanoneedles. Arrays of polymer air-bridges form in seconds by simply hand brushing a bead of polymeric liquid over an array of micropillars. The domination of capillary force that is thinning unstable capillary bridges leads to uniform arrays of nanofiber air-bridges. Similarly, arrays of vertically oriented Ag2Ga nanoneedles have been formed by dipping silvercoated arrays of pyramidal silicon into melted gallium. Force-displacement measurements of these structures are presented. These nanostructures, especially when compressively or torsionally buckled, have extremely low stiffnesses, motion due to thermal fluctuations that is relatively easily detected, and the ability to move great distances for very small changes in applied force. Nanofibers with bead-on-a-string structure, where the beads are micron diameter and loaded with magnetic iron oxide (maghemite), are shown to be simply viewable under optical microscopes, have micronewton/ m stiffness, and have ultralow torsional stiffnesses enabling the bead to be rotated numerous revolutions without breaking. Combination of these high aspect ratio structures with stretched elastomers offer interesting possibilities for robotic actuation and locomotion. Polydimethylsiloxane loaded with nanomaterials, e.g. nanotubes, graphene or MoS2, can be efficiently heated with directed light. Heating produces considerable force through the thermoelastic effect, and this force can be used for continuous translation or to trigger reversible elastic buckling of the nanostructures. The remote stimulation of motion with light provides a possible mechanism for producing cooperative behavior between swarms of semiautonomous nanorobots.
Activation of activating protein 1 during hepatic acute phase response

During an acute phase response following inflammatory stimuli, specific changes occur in the synthesis and secretion of many hepatic proteins. Because the expression of differentiated function requires the coordinated regulation of many genes, we investigated the activity of general and tissue-specific transcription factors using a rat liver model of the acute phase response induced by Freund9s adjuvant. Nuclear extracts and RNAs were prepared throughout a 48-h posttreatment period. Mobility shift assays revealed increased binding activity by nuclear factor-kappa B, interleukin-6 (IL-6) responsive element binding protein, and activating protein 1 (AP-1). Two AP-1 complexes were induced during the acute phase response, and correlation between their presence and transcription activity was demonstrated by transfection studies. Elevated binding activity of AP-1 also correlated with elevated levels of c-jun, junD, junB, and c-fos mRNAs. Western blots showed elevated hepatic levels of c-Jun but not c-Fos proteins during the acute phase response. In addition, IL-6, tumor necrosis factor-alpha, and IL-1 beta, cytokine regulators of the acute phase response, stimulated expression of an AP-1 responsive reporter gene introduced by DNA-mediated transfection into adult rat hepatocytes in primary culture. These findings demonstrate the complexity of AP-1 hepatic transcription factor responses to humoral regulators with direct hepatocellular effects.
Silent ischemia: Clinical relevance

Myocardial ischemia can occur without overt symptoms. In fact, asymptomatic (or silent) ST-segment depression during ambulatory electrocardiogram monitoring occurs more often than symptomatic ST-segment depression in patients with coronary artery disease. Initial studies documented that silent ischemia provided independent prediction of adverse outcomes in patients with known and unknown coronary artery disease. The ACIP (Asymptomatic Cardiac Ischemia Pilot Study) enrolled patients in the 1990s and found that revascularization was better than medical therapy in reducing silent ischemic episodes and possibly cardiovascular (CV) events. However, the more recent COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found similar CV event rates between patients treated with optimal medical therapy alone and those treated with optimal medical therapy plus percutaneous revascularization. Therefore, in the current era, medical therapy appears to be as effective as revascularization in suppressing symptomatic ischemia and preventing CV events. COURAGE was not designed to evaluate changes in the frequency of silent ischemia. Therefore, silent ischemia may persist despite current-era treatment and might still identify patients with increased risk of CV events. Also, silent ischemia is likely to occur frequently in heart transplant patients with denervated hearts and coronary allograft vasculopathy, and future study aimed at improving the management of silent ischemia in this population is warranted. Additionally, future research is warranted to study the effect of newer medical therapies such as ranolazine or selected use of revascularization (for example, guided by fractional flow reserve) in those patients with persistent silent ischemia despite optimal current-era medical therapy.
The importance of counties: Examining the predictive validity of a state juvenile risk assessment instrument

ABSTRACTRisk assessments have been touted by researchers as a key component of best-practices in corrections; however, there remain issues with the inconsistent predictive validity of these tools across different offender samples. To explore this issue, this study investigated the predictive validity of a juvenile risk assessment across 33 counties in Ohio. The results indicated that while the tool was predictive at the state level, there was significant variation across the counties. Further analyses showed that the instrument could predict recidivism in counties on which it was not originally designed and that it performed significantly better in counties with higher crime rates.
Usefulness of lymphoid granulomatous inflammation culture obtained by endobronchial ultrasound-guided transbronchial needle aspiration in a fungal endemic area.

Background and Objectives: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the procedure of choice for the evaluation of mediastinal/hilar lymph node enlargements. Granulomatous inflammation of the mediastinal/hilar lymph nodes is often identified on routine histology. In addition, mediastinal lymphadenopathy may be present with undiagnosed infection. We sought to determine the usefulness of routine cultures and histology for infectious etiologies in a fungal endemic area when granulomatous inflammation is identified. Materials and Methods: We identified 56 of 210 patients with granulomatous inflammation on EBUS-TBNA biopsies from October 2012 through October 2014. An onsite cytologist evaluated all biopsies and an additional TBNA pass for microbiologic stains and cultures were obtained in those with granulomatous inflammation. Results: Of the 56 patients with granulomatous inflammation, 20 patients had caseating (necrotizing) granulomas while noncaseating (nonnecrotizing) granulomas were detected in 36 of the remainder patients. In patients with caseating granulomas, fungal elements were identified in 6 of 20 (30%) patients (histoplasma; N = 5, blastomyces; N = 1) on Grocott methenamine silver (GMS) stain. Lymph node cultures identified 3 of 20 (20%) patients as being positive for Mycobacterium tuberculosis (N = 1), Histoplasma capsulatum (N = 1), and Blastomyces dermatitidis (N = 1). Among patients with noncaseating granulomas, only 2 out of 36 (5%) were positive for fungal elements on GMS stain, identified as Histoplasma, although the lymph node cultures remained negative. Conclusion: The incidence of granulomatous inflammation of mediastinal lymph nodes was 26.6% in our series. Of these patients, noncaseating granulomas were more common (64% vs. 36%). Infectious organisms, fungal or acid-fast bacilli (AFB), on either staining or lymph node culture were rarely identified in noncaseating granulomas, 5% and none, respectively. Caseating granulomas were more commonly associated with positive lymph node fungal stain and culture, 35% and 15%, respectively. In a fungal endemic area, lymph node staining and culture can be considered in cases with caseating granulomatous inflammation, if known at the time of biopsy.
Louis D. Brandeis and the Making of Regulated Competition, 1900–1932: Learning from Railroad Regulation

Brandeis formulated a blueprint for a federal trade commission from his experience with railroad regulation. He learned about the limits of progressivism and applied economics when he became involved in a series of Interstate Commerce Commission (ICC) rate cases between 1910 and 1914. Although he was a partisan participant, and his side won, Brandeis came to see railroad regulation as a failure. Instead of realizing the progressive promise to autonomy, legitimacy, and objectivity, applied economic science led to stalemate and paralysis. Brandeis proposed an alternative, which I call cultivational administration. Although the ICC did not take up his proposal, it became the basis for his Federal Trade Commission design and, as we shall see in Chapter 4, a third way to organize a commission. This chapter explains what Brandeis learned from railroad regulation and outlines his alternative. Brandeis's relationship with the engineers flourished in railroad regulation, where they taught him new ways to think about efficiency and regulation. He consulted them on matters of railroad efficiency, enlisted their service as expert witnesses, and drew on their expertise to craft an alternative design for railroad regulation. And as he did, he deepened the chasm between the way engineering and economics approached the construction of knowledge. He learned four lessons from the engineers, which would reshape his understanding of economic efficiency and regulation. First, railroad cost accounting practices short-circuited improvement, because they prized volume over all other ends. Second, the economists who designed railroad rate regulation mistakenly reified railroad accounting practices as scientific law.
Dispersed-fluorescence spectroscopy of jet-cooled calcium ethoxide radical (CaOC2H5)

Abstract Dispersed fluorescence (DF) spectra of the calcium ethoxide radical (CaOC 2 H 5 ) have been obtained by pumping the A 1 2 A ′ ← X 2 A ′ and the A 2 2 A ′ ′ ← X 2 A ′ origin bands in its laser-induced fluorescence spectrum. Dominant transitions in the vibrationally resolved DF spectra are well reproduced using Franck-Condon factors predicted by complete active space self-consistent field (CASSCF) calculations. Collision-induced population transfer between the A 1 2 A ′ and the A 2 2 A ′ ′ states results in additional peaks in the experimental DF spectra. Differences between the intensities of vibronic bands in the A 1 2 A ′ → X 2 A ′ and the A 2 2 A ′ ′ → X 2 A ′ DF spectra are attributed to different symmetries of the two excited electronic states.
Pre Transplantation MGUS and Transformation to Multiple Myeloma in Kidney Transplantation: A Single Center Experience.

Background: Monoclonal gammopathy of undetermined significance (MGUS) is reported in 3 to 5 percent of population, with the prevalence increasing with advancing age. Patients with MGUS are at increased risk for progression to multiple myeloma or other plasma cell dyscrasias. There is a paucity of information on clinical outcomes of patients with MGUS undergoing renal transplantation. A retrospective study was performed to determine wether MGUS is a contraindication to renal transplantation. Methods: Data was collected from both the kidney transplant and MGUS database. The diagnosis of MGUS was made on the basis of either serum protein electrophoresis (SPEP) or immunofixation after excluding multiple myeloma, amyloidosis and monoclonal immunoglobulin deposition disease. Results: Between 1977 and 2004, 3518 patients underwent kidney transplantation of whom 23 patients had a preexisting monoclonal gammopathy of undetermined significance (MGUS). Fourteen (61%) of these patients were males. The median age at the time of transplant was 59 ±12 years. Ten patients (43.5%) had IgG Kappa (GK), 7 (30.4%) had IgG Lambda (GL), 2 (8.7%) had IgA Lambda (AL), 1 (4.3%) had IgA Kappa (AK), 2 (8.7%) had IgM Lambda (ML). One patient had a biclonal gammopathy GL and ML. Patients were monitored with either SPEP or immunofixation for median duration of 1542 days after transplantation. Thirteen patients had either no change or stable monoclonal protein, 6 had a decrease in their paraprotein level. Two patients had a mild increase in their paraprotein. Two patients with GK developed into biclonal gammopathy (GK and AK). The median follow up of this cohort after the renal transplant was 1783 days. Twelve (52%) patients remained alive at the time of the study. A patient with GK prior to the transplant who underwent kidney transplantation twice developed a biclonal gammopathy and was found to have increased plasma cells (20%) in bone marrow after 14 years. On follow up for 6 years, his M-protein remained stable. Another patient was found to have 17% plasma cells around the time of kidney transplantation. He had a stable M-protein at follow-up, but underwent a stem cell transplant for recurrent immunotactoid glomerulonephritis. Two (9%) patients developed more than 15% plasma cells in their bone marrow with a stable M-protein. None of the patients with a preexisting MGUS evolved into multiple myeloma. Conclusion: In this small study, the presence of MGUS prior to kidney transplantation did not appear to have increased the incidence of multiple myeloma post transplant. Therefore, MGUS by itself should not be considered as an absolute contraindication for renal transplantation.
CNN and al Jazeera’s Media Coverage of America’s War in Afghanistan

From the vantage point of the United States, it seems that one unified reaction swelled in the hearts of the public, politicians, and media in the aftermath of the September 11 attack on America. The American public saw horrific scenes of the Twin Towers collapsing and smoldering wreckage from the Pentagon, followed by painful images of celebration by anti-American protesters in many countries in the Middle East. As American policy makers decided on a course of action in response to these attacks, the selling of the plan unfolded in the American media, including in CNN television coverage. Simultaneously, the U.S. military response was broadcast to the Arab world through a variety of Middle Eastern media sources, including al Jazeera television.
Measuring differential treatment benefit across marker specific subgroups: the choice of outcome scale

Abstract Clinical and epidemiological studies of anticancer therapies increasingly seek to identify predictive biomarkers to obtain insights into variation in treatment benefit. For time to event endpoints, a predictive biomarker is typically assessed using the interaction between the biomarker and treatment in a proportional hazards model. Interactions are contrasts of summaries of outcomes and depend upon the choice of the outcome scale. In this paper, we investigate interaction contrasts under three scales — the natural logarithm of hazard ratio, the natural logarithm of survival probability, and survival probability at a pre-specified time. We illustrate that we can have a non-zero interaction on survival or logarithm of survival probability scales even when there is no interaction on the logarithm of hazard ratio scale. Since survival probabilities have clinically useful interpretation and are easier to convey to patients than hazard ratios, we recommend evaluating a predictive biomarker using survival probabilities. We provide empirical illustration of the three scales of interaction for evaluating a predictive biomarker using reconstructed data from a published melanoma study.