cssi/SciSciGPT-SciSciNet huggingface dataset:
Rural Food and Physical Activity Assessment Using an Electronic Tablet-Based Application, New York, 2013-2014.

INTRODUCTION A community's built environment can influence health behaviors. Rural populations experience significant health disparities, yet built environment studies in these settings are limited. We used an electronic tablet-based community assessment tool to conduct built environment audits in rural settings. The primary objective of this qualitative study was to evaluate the usefulness of the tool in identifying barriers and facilitators to healthy eating and active living. The second objective was to understand resident perspectives on community features and opportunities for improvement. METHODS Participants were recruited from 4 rural communities in New York State. Using the tool, participants completed 2 audits, which consisted of taking pictures and recording audio narratives about community features perceived as assets or barriers to healthy eating and active living. Follow-up focus groups explored the audit experience, data captured, and opportunities for change. RESULTS Twenty-four adults (mean age, 69.4 y (standard deviation, 13.2 y), 6 per community, participated in the study. The most frequently captured features related to active living were related to roads, sidewalks, and walkable destinations. Restaurants, nontraditional food stores, and supermarkets were identified in the food environment in relation to the cost, quality, and selection of healthy foods available. In general, participants found the assessment tool to be simple and enjoyable to use. CONCLUSION An electronic tablet-based tool can be used to assess rural food and physical activity environments and may be useful in identifying and prioritizing resident-led change initiatives. This resident-led assessment approach may also be helpful for informing and evaluating rural community-based interventions.
Discarnation and interactive variables as conditions for disease

Evidence-based medicine is currently founded in probability-based statistics and attempts to extrapolate what is the case for the collective to individual patient diagnosis and treatment. This study uses fuzzy measures to find structure in individual patient data and suggests that interactions, as they exist in nature as variables that are combinatorialy represented in the unique person, are only captured by fuzzy measures. If pathology and physiology are biologically relevant in the individual patient system, fuzzy measures may be more appropriate, or at least appropriate in addition to statistical analysis for medical clinical studies.
Dependable reconfigurable computing design diversity and self repair

Summary form only given, as follows. We demonstrate the power of reconfigurable computing in enabling cost-effective implementations of dependable systems. New concurrent error detection techniques based on practical implementations of design diversity are presented Field reconfigurability of reconfigurable hardware is utilized to design self-healing systems capable of autonomous recovery and repair from temporary errors and permanent faults. The applicability of these techniques are demonstrated through implementations on commercial reconfigurable hardware platforms. An error detection scheme based on diverse duplication compares the outputs of two "different" implementations of the same function and indicates error when a mismatch occurs. The idea of such a technique is derived from the general concept of design diversity. The conventional notion of design diversity is qualitative and relies on "independent" generation of "different" implementations. A metric to quantify design diversity is presented along with synthesis algorithms to efficiently design systems with error detection based on diverse duplication. In traditional dependable systems using hardware redundancy, fault tolerance is realized by detecting errors and locating the faulty chip or faulty board (Field Replaceable Unit or FRU) to be replaced by field service engineers. For systems designed using reconfigurable hardware, the FRU is very fined-grained such as a logic block or a routing resources (e.g., a pass-transistor based switch or a logic lookup table in Field Programmable Gate Arrays). Thus, in the case of a permanent fault, a cost-effective repair scheme is obtained using an alternative configuration in which the faulty parts are replaced with originally unused resources. A new self-repairing reconfigurable computing architecture based on dual FPGAs with embedded "soft" micro-controllers is presented This architecture allows the implemented system to recover from temporary errors and repair itself from permanent faults with minimum impact on system performance while ensuring very high data integrity and availability without external intervention. These capabilities make this architecture useful for a variety of dependable applications including unmanned remote applications such as deep space exploration.
A TOG:αβ-Tubulin Complex Structure Reveals Conformation-Based Mechanisms for a Microtubule Polymerase

Stu2p/XMAP215/Dis1 family proteins are evolutionarily conserved regulatory factors that use αβ-tubulin–interacting tumor overexpressed gene (TOG) domains to catalyze fast microtubule growth. Catalysis requires that these polymerases discriminate between unpolymerized and polymerized forms of αβ-tubulin, but the mechanism by which they do so has remained unclear. Here, we report the structure of the TOG1 domain from Stu2p bound to yeast αβ-tubulin. TOG1 binds αβ-tubulin in a way that excludes equivalent binding of a second TOG domain. Furthermore, TOG1 preferentially binds a curved conformation of αβ-tubulin that cannot be incorporated into microtubules, contacting α- and β-tubulin surfaces that do not participate in microtubule assembly. Conformation-selective interactions with αβ-tubulin explain how TOG-containing polymerases discriminate between unpolymerized and polymerized forms of αβ-tubulin and how they selectively recognize the growing end of the microtubule.
Changes to inpatient versus outpatient hospitalization: Medicare's 2-midnight rule

Outpatient versus inpatient status determinations for hospitalized patients impact how hospitals bill Medicare for hospital services. Medicare policies related to status determinations and the Recovery Audit Contractor (RAC) program charged with postpayment review of such determinations are of increasing concern to hospitals and physicians. We present an overview and discussion of these policies, including the recent 2-midnight rule, the effect on status determinations by the RAC program, and other recent and pertinent legislative and regulatory activity. Finally, we discuss the future direction of Medicare status determination policies and the RAC program, so that physicians and other healthcare providers caring for hospitalized Medicare beneficiaries may better understand these important and dynamic topics.
The Neuropsychiatric and Motor Profile of GBA-Associated Parkinson's Disease: A Review.

Background Cognitive and motor decline, along with psychiatric symptoms, have a major impact on independence, nursing home admission, caregiver burden, and mortality in Parkinson's disease (PD). The single most common genetic risk factor for developing PD is a mutation in the glucocerebrosidase (GBA) gene. Methods This work is a literature review regarding “GBA” and “Parkinson's disease” as conducted by PubMed search. Results There is a higher prevalence of cognitive decline and more rapid trajectory of disease progression in PD-GBA carriers, compared to noncarriers. PD-GBA carriers also have domain-specific cognitive impairment, particularly in visual memory tasks. PD-GBA carriers may also have a more aggressive motor phenotype than noncarriers. Conclusions Early identification of PD-GBA carriers may lead to targeted therapies and development of new treatments.
Small screen aesthetics: from TV to the internet

A curious researcher or reader might be skeptical of the title of a book that places emphasis on the ‘aesthetics’ of the ‘small screen’. In other words, in what ways can the television image overco...
Monodisperse Poly(lactide‐co‐glycolic acid)‐Based Nanocarriers for Gene Transfection

This contribution describes a simple, aerosol-based method for fabricating monodisperse particles containing mixtures of poly(lactide-co-glycolic acid) [PLGA], protamine sulfate (Prot), and poly(l-lysine) [PLL] as nanocarriers for gene transfection. Aqueous solutions of PLGA, Prot, and PLL were collison-atomized, and the resulting aerosolized droplets were dried "on the fly" to form solid particles, which then were electrostatically size-classified into 50, 100, and 200 nm mobility diameter samples. Measurements of cell viability and transfection reveal that the fabricated nanocarriers have a lower cytotoxicity (>85% in cell viability) and a higher transfection efficiency [>8.7 × 10(5) in relative light units (RLU) mg(-1) ] than does 25 kDa polyethyleneimine (≈50% and 6.8 × 10(5) RLU mg(-1) ).
Omega-phase formation in Beta III titanium alloy

Abstract The kinetics of the formation of the omega phase in the Beta III alloy is followed during aging at 400°C after quenching from 825°C. Electron diffraction patterns indicate that the omega phase forms during the quench. The aging kinetics indicate that the omega particles that form on quenching grow to form ellipsoidal shaped particles during aging. After aging 49 hrs at 400°C the omega phase makes up greater than 90% of the volume of the material. During the first 20 min of aging a heavy grain boundary precipitate is formed which continues to grow as aging progresses.
Lymphocyte signaling: adapting new adaptors

New developments in lymphocyte signaling have revealed insights into the proximal phosphorylation events associated with the T-cell receptor and into the importance of the T-cell adaptor protein Slp-76 and its B-cell homolog in the transduction of the signal from the antigen receptor.
Early to Bed, Early to Rise? An Exploration of Adolescent Sleep Hygiene Practices

Cognition, memory, safety, mental health, and weight are all affected by inadequate sleep. Biological studies indicate significant changes in sleep architecture during adolescence, such as changes in melatonin secretion, and a need for greater total sleep time. Yet, social contexts and cultural values impinge on these changing biological sleep needs making adolescents vulnerable to the dangers of insufficient sleep. Sleep hygiene practices are purported as potential mediating factors between biological sleep needs and the sociocultural context of sleep. The purpose of this literature review is to highlight biological and social factors contributing to insufficient sleep in adolescents, to explore the evidence of several recommended sleep hygiene practices, and to stimulate further research about how adolescents negotiate their shifting biological sleep needs amid increasing social demands.
Enzymes of nucleic acid metabolism as biochemical markers of T cell development in mouse

Abstract The levels of three purine salvage enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and 5′-nucleotidase (5′-N), which are known to be associated with certain immunodeficiency disorders were determined in mouse T lymphocytes. These enzymes showed characteristic changes depending on the stage of T cell development. The activity of ADA was 5-fold higher in thymocytes compared to splenic T cells. On the other hand, the splenic T cells displayed a 2-fold and a 4–8 fold greater activity of PNP and 5′-N, respectively than those of thymocytes. The apparent Km and Vmax values have been determined for all the 3 enzymes in the immature and mature T cells. The data demonstrate that the absolute and relative activity of these enzymes may be used as biochemical markers to characterize the T lymphocytes during different stages of differentiation.
Ovary Transcriptome Profiling via Artificial Intelligence Reveals a Transcriptomic Fingerprint Predicting Egg Quality in Striped Bass, Morone saxatilis

Inherited gene transcripts deposited in oocytes direct early embryonic development in all vertebrates, but transcript profiles indicative of embryo developmental competence have not previously been identified. We employed artificial intelligence to model profiles of maternal ovary gene expression and their relationship to egg quality, evaluated as production of viable mid-blastula stage embryos, in the striped bass (Morone saxatilis), a farmed species with serious egg quality problems. In models developed using artificial neural networks (ANNs) and supervised machine learning, collective changes in the expression of a limited suite of genes (233) representing 90% of the eventual variance in embryo survival. Egg quality related to minor changes in gene expression (<0.2-fold), with most individual transcripts making a small contribution (<1%) to the overall prediction of egg quality. These findings indicate that the predictive power of the transcriptome as regards egg quality resides not in levels of individual genes, but rather in the collective, coordinated expression of a suite of transcripts constituting a transcriptomic “fingerprint”. Correlation analyses of the corresponding candidate genes indicated that dysfunction of the ubiquitin-26S proteasome, COP9 signalosome, and subsequent control of the cell cycle engenders embryonic developmental incompetence. The affected gene networks are centrally involved in regulation of early development in all vertebrates, including humans. By assessing collective levels of the relevant ovarian transcripts via ANNs we were able, for the first time in any vertebrate, to accurately predict the subsequent embryo developmental potential of eggs from individual females. Our results show that the transcriptomic fingerprint evidencing developmental dysfunction is highly predictive of, and therefore likely to regulate, egg quality, a biologically complex trait crucial to reproductive fitness.
Detection of tRNA-like Structure through RNase P Cleavage of Viral Internal Ribosome Entry Site RNAs Near the AUG Start Triplet *

The 9600-base RNA genome of hepatitis C virus (HCV) has an internal ribosome entry site (IRES) in its first 370 bases, including the AUG start triplet at bases 342–344. Structural elements of this and other IRES domains substitute for a 5′ terminal cap structure in protein synthesis. Recent work (Nadal, A., Martell, M., Lytle, J. R., Lyons, A. J., Robertson, H. D., Cabot, B., Esteban, J. I., Esteban, R., Guardia, J., and Gomez, J. (2002) J. Biol. Chem. 277, 30606–30613) has demonstrated that the host pre-tRNA processing enzyme, RNase P, can cleave the HCV RNA genome at a site in the IRES near the AUG initiator triplet. Although this step is unlikely to be part of the HCV life cycle, such a reaction could indicate the presence of a tRNA-like structure in this IRES. Because susceptibility to cleavage by mammalian RNase P is a strong indicator of tRNA-like structure, we have conducted the studies reported here to test whether such tRNA mimicry is unique to HCV or is a general property of IRES structure. We have assayed IRES domains of several viral RNA genomes: two pestiviruses related to HCV, classical swine fever virus and bovine viral diarrhea virus; and two unrelated viruses, encephalomyocarditis virus and cricket paralysis virus. We have found similarly placed RNase P cleavage sites in these IRESs. Thus a tRNA-like domain could be a general structural feature of IRESs, the first IRES structure to be identified with a functional correlate. Such tRNA-like features could be recognized by pre-existing ribosomal tRNA-binding sites as part of the IRES initiation cycle.
Bone Sialoprotein Binding to Matrix Metalloproteinase-2 Alters Enzyme Inhibition Kinetics

Bone sialoprotein (BSP) is a secreted glycophosphoprotein normally restricted in expression to skeletal tissue that is also induced by multiple neoplasms in vivo. Previous work has shown that BSP c...
Correlation of xenon-enhanced computed tomography-defined cerebral blood flow reactivity and collateral flow patterns.

A chronic compromise of cerebral hemodynamics has been shown to identify a group of patients at an increased risk for stroke. Because a "steal phenomenon" induced by a vasodilatory challenge has characterized the group at greatest risk, it was hypothesized that these individuals would also have a severe compromise of primary collaterals and an increased dependence on leptomeningeal collaterals. Twenty-three patients with symptomatic cerebrovascular disease underwent angiography and xenon-enhanced computed tomographic cerebral blood flow studies before and after 1 g IV acetazolamide within 6 months of each other. Cerebral blood flow vasoreactivity was classified by whether cerebral blood flow increased (> 5%) or was unchanged (+/- 5%) (group 1) or fell by > 5% (group 2) in any vascular territory. Angiographic collateralization was classified into four types: normal (type 1), willisian (type 2), ophthalmic (type 3), and leptomeningeal (type 4). Twenty percent (2/10) of group 1 patients and 69% (9/13) of group 2 patients (P = .0009) had leptomeningeal collaterals. A negative flow reactivity is significantly associated with a dependence on leptomeningeal collaterals and implies a state of maximal hemodynamic compromise.
Laser Doppler flowmetry in non-human primate stroke studies: model refinement for pre-clinical development of cerebroprotective strategies.

¶Background. Safety, feasibility, and efficacy trials in non-human primate stroke models are essential to the evaluation of experimental therapies and their translation to humans. Although Laser Doppler Flowmetry has been successfully employed in rodent stroke to continuously monitor cerebral blood flow, it has not been applied in primate studies. This investigation examined the utility of Laser Doppler Flowmetry in refining an existing baboon model of cerebral ischemia/reperfusion. Method. Continuous Laser Doppler Flowmetry monitoring was used, in non-human primates, to document local cerebral blood flow before, during, and after middle cerebral artery territory occlusion. In each baboon (n = 7) a single Doppler probe was placed into the left frontal cortex through a precoronal burr hole. Correlations between Laser Doppler Flowmetry values and latencies to Motor Evoked Potential dropout were compared using a linear regression model. Findings. Placement of the Laser Doppler probe was easily accomplished in all animals. Laser Doppler Flowmetry tracings accurately documented blood flow changes that occurred with each technical manipulation during the procedure. Laser Doppler confirmed decreased perfusion that coincided both regionally and temporally with vessel occlusion. Depth of ischemia as measured by Laser Doppler Flowmetry was associated with Motor Evoked Potential dropout latencies for individual animals. Conclusions. Continuous, single probe Laser Doppler Flowmetry is a reliable method of documenting perfusion changes following middle cerebral artery territory occlusion in a baboon model of reperfused stroke. This advanced intraoperative monitoring technique may lead to more accurate evaluation of acute stroke therapies in pre-clinical trials.
Pre-eclampsia and nasal CPAP: part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: preliminary findings.

Abstract Background Pre-eclampsia is a leading cause of maternal–fetal morbidity and mortality. Significant overlap exists between the risk factors for pre-eclampsia and sleep-disordered breathing. Nasal continuous positive airway pressure (CPAP) has been proposed as therapy for pre-eclampsia. This prospective, longitudinal study was designed to characterize sleep-related breathing patterns in pregnant women with pre-eclampsia risk factors, and to describe the effects of early nasal CPAP therapy in these patients. Methods Twelve pregnant women with pre-eclampsia risk factors underwent polysomnography to characterize sleep-related breathing abnormalities and baseline blood pressure determination. Patients with airflow-limitation underwent nasal CPAP titration and were treated with optimal pressures. Periodic assessments of CPAP compliance and tolerance, sleep quality, and blood pressure control were performed until delivery or pre-eclampsia onset. CPAP retitration was performed between weeks 20 and 22 of pregnancy. Results Mean respiratory disturbance index was 8.5±2.6events/h of sleep, and initial nasal CPAP pressures were 5–6cmH 2 O with an increase to 6–9cmH2O after recalibration. All subjects with chronic hypertension maintained blood pressures below 140/90 with a mean diurnal blood pressure of 122±2.5mmHg over 83±1.5mmHg. Patient characteristics of obesity and prior pre-eclampsia were associated with pregnancies complicated by spontaneous abortion, premature delivery, or pre-eclampsia. Conclusions Early application of nasal CPAP in pregnant women alleviated sleep-related breathing disturbances but was not sufficient to prevent negative pregnancy outcomes. Obesity and prior pre-eclampsia appeared to be important factors and were associated with the worst complications. However, nasal positive pressure may still be beneficial to decrease severity of outcomes, particularly if individualized to patient risk factors, more particularly hypertension at pregnancy onset.
Research on technology standards: Accomplishment and challenges

Abstract In this paper, we organize the fragmented management literature on technology standards according to a meta-theoretical scheme originally proposed by Astley and Van de Ven. We review over 89 relevant papers in influential journals in management, marketing and management-related disciplines. We observe that cumulative research streams on this topic have stayed within a single central perspective, that the development of research across the four central perspectives has been uneven, and that works incorporating multiple central perspectives have been few. We argue for complex models that take into account the two boundary conditions—technological complexity and institutional environment—that have been implicit in the extant literature. We also argue for theoretically grounded works in the collective action and strategic choice views, but the greatest opportunity lies in integrative works that will take us one step closer to a comprehensive view of technology standards.
Enhancing physical well-being and overall quality of life among underserved Latina-American cervical cancer survivors: feasibility study

Introduction Evidence for the effectiveness of behavioral interventions are lacking for cervical cancer survivors (CCS). Disparities in survivorship outcomes exist for CCS, especially Latina-Americans. This study assessed the feasibility of implementing a culturally sensitive intervention delivered in a telephonic format.
MARANGONI BUBBLE MOTION PHENOMENON IN ZERO GRAVITY

The Marangoni phenomenon is shown to be the primary mechanism for the movement of a gas bubble in a nonisothermal liquid in a low-gravity environment. In such a two-phase system, local variations in surface tension at the bubble surface are caused by a temperature gradient in the liquid. Shearing stresses thus generated at the bubble surface lead to convection in both media, as a result of which the bubble moves. A mathematical model consisting of the Navier-Stokes and thermal energy equations, together with the appropriate boundary conditions for both media, is presented. Parameter perturbation theory is used to solve this boundary value problem, with the expansion parameter being the Marangoni number. The zeroth, first- and second-order approximations for the velocity, temperature and pressure distributions in the liquid and in the bubble, and the deformation and terminal velocity of the bubble are determined. Experimental zero-gravity data for a nitrogen bubble in ethylene glycol, ethanol, and silicone...
Rabies-specific antibodies: measuring surrogates of protection against a fatal disease.

Antibodies play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies, the Fc- and complement-dependent activities of these multifunctional proteins may also be critical in their ability to provide protection against most viruses. Protection against viral pathogens in vivo is complex, and while virus neutralization—the ability of antibody to inactivate virus infectivity, often measured in vitro—is important, it is often only a partial contributor in protection. The rapid fluorescent focus inhibition test (RFFIT) remains the “gold standard” assay to measure rabies virus–neutralizing antibodies. In addition to neutralization, the rabies-specific antigen-binding activity of antibodies may be measured through enzyme-linked immunosorbent assays (ELISAs), as well as other available methods. For any disease, in selecting the appropriate assay(s) to use to assess antibody titers, assay validation and how they are interpreted are important considerations—but for a fatal disease like rabies, they are of paramount importance. The innate limitations of a one-dimensional laboratory test for rabies antibody measurement, as well as the validation of the method of choice, must be carefully considered in the selection of an assay method and for the interpretation of results that might be construed as a surrogate of protection.
The effects of visual contact and aggressor identification on interpersonal aggression

Groups of four Ss were ordered by the E to respond in a simple reaction time (RT) task in a way which (allegedly) would lead to the delivery of painful shock to a human “victim.” It was found that compliance with these orders declined under conditions where the victim was given the specific identity of the potential harmer. However, compliance was not directly influenced by whether or not the victim and potential harmer were in visual contact.
TU-C-T-6E-02: A Computational Algorithm for Independent Planar Dose Verification of IMRT

Purpose: The purpose of this work is to develop a computational algorithm for independent planar dose verification of IMRT plans delivered with an MLC as part of the IMRTquality assurance procedure. Method and Materials: A pencil beam convolution method was adopted for the algorithm. The general scheme of the calculation consists of three parts. The first part calculates the delivered fluence in air based on the positions of the leaves and jaws specified in the RTP file. We employed a modified three‐source model to obtain the planar fluence at the detector plane based on the projected source integration on the source plane shaped by the combined positions of the jaws and MLC. In the second part, dose kernel in phantom was determined by fitting the convolution results with a series of square‐field profiles. Thirdly, the mid‐leaf and interleaf transmissions, rounded leaf end, and tongue‐and‐groove effects were considered to improve the accuracy of the algorithm. All of these effects were taken into account by semi‐empirical methodology and the parameters were obtained by fits to measured data. To verify the accuracy of the algorithm, we compared the calculation results with the MapCHECK measurements. Results: The accuracy of the algorithm was verified by comparing the calculations with the MapCHECK measurements for several head‐and‐neck cases. The passing rate for most of the cases is above 95% with the 2% in absolute dose or 2‐mm distance‐to‐agreement criteria. The agreement was better than the agreement between the results from a commercial planning system (Pinnacle3, version 7.0g) and MapCHECK measurements for all the cases tested. Conclusion: An algorithm has been developed for independent planar dose verification of IMRT plans as part of the IMRTquality assurance procedure. Our methods could be implemented on other kinds of machines with minor modifications.
Interpreting and Projecting: Two Elements of the Self as Moral Agent

THIS ESSAY WILL focus upon essential structures of the self which are presupposed in moral agency.' Its method is phenomenological in the broad sense of that term.2 Its purpose is to untangle some of the puzzles to which the following kinds of questions refer: What is the moral life? What are its elementary forms? How is it constituted? What powers of the self does it presuppose? Is it a clearly delineated aspect of human being? Careful description can at least begin to clarify some of these questions.3 When we look at patterns of action and response in the social world, it is easy to observe that human behavior exhibits routinization.4 We do not have to attend to every situation afresh, for we possess a reservoir of knowledge and
A photoionization instability in the early intergalactic medium

It is argued that any fairly uniform source of ionizing photons can be the cause of an instability in the pregalactic medium on scales larger than a photon path length. Underdense regions receive more ionizing energy per atom and reach higher temperature and entropy, driving the density down still further. Fluctuations created by this instability can lead to the formation of structures resembling protogalaxies and intergalactic clouds, obviating the need for gas clouds or density perturbations of earlier cosmological provenance, as is usually assumed in theories of galaxy and structure formation. Characteristic masses for clouds produced by the instability, with log mass in solar units plotted against log radius in kpc, are illustrated.
An unusual presentation of scabies infestation in a patient with Darier's disease. The use of ivermectin as an adjunctive scabicide

Darier's disease is an inherited condition of defective keratinization in which patients are predisposed to the development of severe viral infections and have an increased susceptibility to bacterial and mycotic infections. We describe a patient with Darier's disease who had a severe form of scabies infestation which responded to treatment with permethrin in combination with ivermectin. The tendency of patients with Darier's disease to develop severe forms of cutaneous infections and infestations may reflect a common underlying mechanism, and their management may require more aggressive therapeutic approaches.
Formamide and dimethylformamide: reproductive assessment by continuous breeding in mice.

Abstract Reproductive toxicity in Swiss mice, during chronic exposure to formamide (FORM) or dimethylformamide (DMF), was evaluated using the Reproductive Assessment by Continuous Breeding Protocols. FORM administered in drinking water at 0, 100, 350, and 750 ppm (∼20 to 200 mg/kg/d) reduced fertility and litter size in F0 animals without generalized toxicity at 750 ppm FORM. Crossover matings suggested that females were the affected sex. After F1 mating, FORM reduced F2 litter size, increased days to litter, reduced relative ovarian weight, and lengthened estrous cycles at 750 ppm. The No-Observed-Adverse-Effect-Level for generalized toxicity was 750 ppm for the F0 and 350 ppm for the F1 generation. Reproductive performance was normal at 350 ppm for both F0 and F1 mice. Chronic exposure to DMF in drinking water at 0, 1000, 4000, and 7000 ppm (∼200 to 1300 mg/kg/d) reduced fertility by the first litter at 4000 ppm, reduced body weight in F0 females at 7000 ppm, and increased liver weights at all doses in both sexes. A crossover mating at 7000 ppm identified F0 females as the affected sex. F1 postnatal survival was reduced at ≥4000 ppm DMF. F1 mating reduced F2 litter size and live pup weight at ≥1000 ppm. At necropsy, body weight of F1 males and females was reduced at ≥4000 ppm. DMF-treated pups (both Fl and F2) and Fl adults had cranial and sternebral skeletal malformations. Only DMF caused overt developmental toxicity. A No-Observed-Adverse-Effect-Level for DMF was not established.
Crystal Clear: A Unique Clue to Diagnosis in a Patient With Recurrent Nausea and Vomiting

Question: A 36-year-old African-American woman with a history of hypertension, asthma, and ongoing tobacco use presented to our hospital with abdominal pain, nausea, vomiting, and intermittent diarrhea. She had recently been treated for a breast abscess with trimethoprim/ sulfamethoxazole and subsequently admitted to another hospital for acute pancreatitis with lipase of 1314 U/L. Her symptoms improved on discharge; however, she continued to have diarrhea. On admission to our hospital 3 days later, her physical examination was only notable for moderate abdominal tenderness to palpation in the epigastric region without peritoneal signs, and her lipase was elevated at 582 U/L. She was also noted to have a peripheral eosinophilia of 11.3% (total white blood cell count, 7.96 K/mm; absolute eosinophil count, 900 K/mm), initially attributed to recent sulfa exposure, which had been hypothesized to cause her pancreatitis given normal hepatobiliary imaging and no history of alcohol intake. The patient’s nausea and vomiting improved with limited oral intake. She did, however, experience intermittent loose bowel movements. Stool studies for ova and parasites were sent. A trichrome stain of stool is shown in Figure A. What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
ON THE NATURE OF THE INTERDEPENDENCE OF THE ADRENAL CORTEX, NON-SPECIFIC STRESS AND NUTRITION IN THE REGULATION OF NITROGEN METABOLISM*

IT IS now widely recognized that the adrenal cortex is concerned in some fundamental way with the ability of the organism to respond to injury in a characteristic fashion. However, the precise mechanism by which the steroids of the adrenal cortex participate in the metabolic response to injury still remains speculative. Earlier studies in this area led to the concept which is still widely held that certain of the metabolic alterations after injury in the healthy organism are a direct consequence of hypersecretion of adrenal cortical steroids (Selye 1946). However, later work (see Engel, 1951a and b for a review of the literature) has cast doubt on such a simple causal relationship and relatively few investigators active in this field accept this concept any longer. The best evidence against it is found in the report of Ingle, Ward and Kuizenga (1947) who showed that the characteristic negative nitrogen balance which follows fractures in normal,
Reactive oxygen species: the unavoidable environmental insult?

Reactive oxygen species (ROS) are generated by a variety of sources from the environment (e.g., photo-oxidations and emissions) and normal cellular functions (e.g., mitochondrial metabolism and neutrophil activation). ROS include free radicals (e.g., superoxide and hydroxyl radicals), nonradical oxygen species (e.g., hydrogen peroxide and peroxynitrite) and reactive lipids and carbohydrates (e. g., ketoaldehydes, hydroxynonenal). Oxidative damage to DNA can occur by many routes including the oxidative modification of the nucleotide bases, sugars, or by forming crosslinks. Such modifications can lead to mutations, pathologies, cellular aging and death. Oxidation of proteins appears to play a causative role in many chronic diseases of aging including cataractogenesis, rheumatoid arthritis, and various neurodegenerative diseases including Alzheimer's Disease (AD). Our goal is to elucidate the mechanism(s) by which oxidative modification results in the disease. These studies have shown that (a) cells from old individuals are more susceptible to oxidative damage than cells from young donors; (b) oxidative protein modification is not random; (c) some of the damage can be prevented by antioxidants, but there is an age-dependent difference; and (d) an age-related impairment of recognition and destruction of modified proteins exists. It is believed that mechanistic insight into oxidative damage will allow prevention or intervention such that these insults are not inevitable. Our studies are also designed to identify the proteins which are most susceptible to ROS damage and to use these as potential biomarkers for the early diagnosis of diseases such as AD. For example, separation of proteins from cells or tissues on one- and two-dimensional gels followed by staining for both total protein and specifically oxidized residues (e.g., nitrotyrosine) may allow identification of biomarkers for AD.
Observing the continuous transformation of a four level laser into a two level system

Photoassociation of Ca-Ar-Kr trios results in lasing in Cs at 852.1 nm and allows one to observe the transition of a four level laser into a two level system.
Role of sterol structure in the thermotropic behavior of plasma membranes of Saccharomyces cerevisiae

Abstract Plasma membranes from Saccharomyces cerevisiae were prepared by a new procedure involving lyticase treatment of the yeast cells. The plasma membranes were right-side-out, closed vesicles of uniform appearance with a sterol to phospholipid molar ratio of 0.365. The thermotropic behavior of these plasma membranes from wild-type yeast and from sterol mutants was examined by differential scanning calorimetry, fluorescence anisotropy and Arrhenius kinetics of plasma membrane enzymes. While differential scanning calorimetry failed to demonstrate any lipid transition, fluorescence anisotropy data indicated that lipid transitions were occurring in the plasma membranes of the yeast sterol mutants but not the sterol wild-type. The temperature dependence of the plasma membrane enzymes, chitin synthase and Mg 2+ -ATPase, was also investigated. The Arrhenius kinetics of chitin synthase did not reveal any transitions in either the sterol mutant or wild-type plasma membranes, yet the Arrhenius kinetics of the Mg 2+ -ATPase suggested that lipid transitions were occurring in both cases.
Quantifying distortions in soft lithography

This article describes a moire technique for determining distortions in soft lithography. We use the technique to investigate distortions when soft lithography is performed in a variety of configurations; a method is identified for limiting maximum distortions to less than 1 μm over areas ∼1 cm2. We also suggest an approach for actively controlling these distortions, and we demonstrate in a simple way its feasibility.
Quantitative and qualitative analysis of RNA synthesis in stage 6 and stage 4 oocytes of Xenopus laevis.

Abstract RNA synthesis has been studied in oocytes taken from Xenopus laevis females which have not recently ovulated. Such females contain a population of large (stage 6) oocytes which exhibit white equatorial bands and which are considered to represent the terminal stage of oocyte development. Rates of RNA synthesis in these “banded” oocytes were measured by analyzing the kinetics of incorporation of 3 H-guanosine into acid-precipitable, alkaline-labile material, and changes in precursor pool (GTP) specific activity during incubations. In additional experiments, rates of RNA synthesis were measured after 3 H-GTP was injected directly into stage 6 oocytes. For comparison, rates of RNA synthesis were measured in lampbrush chromosome stage oocytes (stage 4; 0.5–0.6 mm diameter). The results show that, under the in vitro conditions employed, stage 6 oocytes are not metabolically dormant, but synthesize total RNA at a rate at least as great as the stage 4 oocytes. Qualitative studies on newly synthesized RNA in the two oocyte classes have been performed using sucrose density gradient centrifugation and acrylamide gel electrophoresis. Both stage 4 and stage 6 oocytes exhibited similar patterns, and the bulk of the RNA synthesized and accumulated during 12-hr pulses appears to be ribosomal. These observations are discussed in terms of existing concepts concerning synthetic activity in stage 6 oocytes.
Methods for kinetic analysis of methane fermentation in high solids biomass digesters

Methods are presented for kinetic analysis of anaerobic biomass reactors. In some cases, assumptions implicit in kinetic analysis techniques developed for conventional dilute digestion modes are not applicable to systems operating at high rates and/or high solids concentrations. As a result, modified definitions are presented for CST digester retention times and first order kinetic coefficients. Procedures are presented for converting biogas data to standard conditions. Two novel methods for quantifying mass removals, based on direct measurement of reactor mass losses and on biogas production, allow rapid determination of mass removal rates and detection of gas leakage. The use of a per unit mass basis for reporting concentrations and kinetics is recommended.
Specificity of arginine binding by the Tetrahymena intron.

L-Arginine competitively inhibits the reaction of GTP with the Tetrahymena ribosomal self-splicing intron. In order to define this RNA binding site for arginine, Ki's have now been measured for numerous arginine-like competitive inhibitors. Detailed consideration of the Ki's suggests a tripartite binding model. The dissociation constants of the inhibitors can be consistently interpreted if the guanidino group of arginine binds in the GTP site by utilizing the H-bonds otherwise made to the N1-H and 2 NH2 of the guanine pyrimidine ring. The positive charge of the arginine guanidino group also enhances binding. A second requirement is for the precise length of the aliphatic arm connecting the guanidino with the alpha-carbon. The positive charge of the alpha-amino group is the third feature essential to effective inhibition. The negative carboxyl charge of arginine inhibits binding, and the substituents on the alpha-carbon are probably oriented, with the alpha-amino group near the phosphate backbone of the RNA. This orientation contributes strongly to the L stereoselectivity of the amino acid site on the RNA. When spaced optimally, net contribution to the free energy of binding is of the same order for the guanidino group and for the arginine alpha-carbon substituents, but the guanidino apparently contributes more to binding free energy. Taken together, these observations extend the previous binding model [Yarus, M. (1988) Science (Washington, D.C.) 240, 1751-1758]. The observed dependence of binding on universal characteristics of amino acids suggests that RNA binding sites with other amino acid specificities could exist.
Evolutionary conservation of motif constituents in the yeast protein interaction network

Understanding why some cellular components are conserved across species but others evolve rapidly is a key question of modern biology 1–3 . Here we show that in Saccharomyces cerevisiae, proteins organized in cohesive patterns of interactions are conserved to a substantially higher degree than those that do not participate in such motifs. We find that the conservation of proteins in distinct topological motifs correlates with the interconnectedness and function of that motif and also depends on the structure of the overall interactome topology. These findings indicate that motifs may represent evolutionary conserved topological units of cellular networks molded in accordance with the specific biological function in which they participate.
Inhibition of the membrane-bound Mg++ -ATPase of chloroplasts by lipophilic chelators.

Summary The lipophilic iron chelators, bathophenanthroline and TTFA inhibit the membrane-bound light-activated and sulfhydryl-pendent Mg ++ -ATPase of spinach chloroplasts, but not the trypsin-activated Ca ++ -ATPase of the solubilized enzyme. Phosphorylation was also inhibited by both chelators. Under these conditions BP acts as an electron transport inhibitor, not an energy transfer inhibitor, i.e. the inhibition was not reversed by uncouplers. TTFA on the other hand showed the classical energy transfer inhibition pattern, the inhibition being reversed by uncouplers. The chelators also make the membranes more leaky toward H + ions. This alone does not seem to account for the inhibition of energy transduction, i.e. the chelators are not simply uncouplers. The data are consistent with the concept that a metal ion may be intimately involved in energy transduction.
Targeted drug delivery to tumors: myths, reality and possibility.

The ultimate goal of drug delivery research is to help patients by developing clinically useful formulations. During the last several decades controlled drug delivery technology has advanced significantly, leading to the development of various clinical formulations improving patient compliance and convenience [1]. Current technologies allow delivery of drugs at desired release kinetics for extended periods of time ranging from days to years. Oral and transdermal drug delivery systems routinely deliver drugs for 24 h, substantially improving drug efficacy and minimizing side effects. Implantable systems can locally deliver drugs for months, even years. While significant advances have been made, there are still areas where substantial improvements need to be made to reach the next level of clinical relevance. One such area is targeted drug delivery to solid tumors. The clinically significant impact of targeted drug delivery lies in the ability to specifically target a drug or drug carrier to minimize drug-originated systemic toxic effects. Successful translation (from bench to bedside) of potential cancer and gene therapies, particularly small interfering RNA (siRNA) delivery, will largely depend on targeted drug delivery strategies. Overcoming the many challenges of identifying a successful targeted drug delivery strategy requires an understanding of events involving transport of drug or drug carrier to a target site after intravenous (i.v.) administration as well as issues relevant for specific target diseases and the body’s response toward a drug delivery system. The current lack of clear recognition of problems facing the drug delivery field can be anticipated to result in only marginal advances in targeted drug delivery technologies in the coming years. The current unmet needs and challenges in this area were summarized by Professor Alexander T. Florence who is one of the few who raised awareness on the exaggerated claims of the nanoparticle-based drug targeting [2,3]. They need to be better appreciated and understood for achieving greater success in drug targeting to tumors. Thus, it would be profitable to address a variety of issues and factors that could affect the development of improved targeted drug delivery systems. Many terms have been used to describe nano-sized drug delivery systems, and here the term “nanoparticle” is used to represent a spectrum of systems, including nanocarrier, nanovehicle, nanosystem, nanostructure, and other terms used in the literature.
Interference alignment with asymmetric complex signaling

It has been conjectured that complex Gaussian interference channels with constant channel coefficients have only one degree-of-freedom (DoF) regardless of the number of users. While several examples are known of constant channels that achieve more than 1 DoF, these special cases only span a subset of measure zero. In other words, for almost all channel coefficient values, it is not known if more than 1 DoF is achievable. In this paper, we settle this conjecture in the negative. We show that at least 1.2 DoF are achievable for all values of complex channel coefficients except for a subset of measure zero. To establish the achievability of 1.2 DoF we introduce the novel idea of asymmetric complex signaling — i.e., the inputs are chosen to be complex but not circularly symmetric. It is shown that unlike Gaussian point-to-point, multiple-access and broadcast channels where circularly symmetric complex Gaussian inputs are optimal, for interference channels optimal inputs are in general asymmetric. In addition, with this idea, we also show that 4/3 DoF can be achieved for 2 user X channel with constant, complex channel coefficients.