cssi/SciSciGPT-SciSciNet huggingface dataset:
Experiments on fluid flow induced by melting around a migrating heat source

A series of melting experiments with a moving horizontal cylindrical heat source at constant surface heat flux have been performed. The heat source was designed in such a way that it could descend under its weight while melting the phase-change material (n-octadecane) surrounding it. The heat-source velocity was measured and the motion and shape of the solid–liquid interface were determined photographically. The effects of the surface heat flux, the density and initial position of the heat source, and the initial subcooling of the solid were investigated and are discussed. Conduction was found to be the dominant heat-transfer mechanism around the lower stagnation point and controlled the terminal velocity of the source. The fluid motion in the melt pool above the heat source was mainly induced by the descent of the source, while natural convection played only a relatively minor role in the motion.
Time Past, Time Present, Time Future The Alzheimer's Disease Sufferer as Stern's Unitas Multiplex

Two case studies of Alzheimer's disease sufferers are presented and analyzed in terms of William Stem's `Science of Personalistics'. Despite a plethora of deficits in cognitive function as measured by standardized tests, the afflicted persons discussed herein show striking evidence of having goals of the autotelic and heterotelic variety, and the need to entertain such goals. Furthermore, the application of Stem's concepts of the `personal present', `convergence', `assimilation', and the like, to the discourse of the afflicted permits us to understand the experience of the afflicted with a clarity not allowed by neuropsychological tests. Stem's approach to the study of persons is thus seen as an important addition to our understanding of cognitive life.
Mouse chromosome 11.

A consensus linkage map of Chr 11 was constructed based on several multilocus genetic crosses, and the remainder of the loci were placed on this foundation (Buchberg et al. 1991). This report expands on the previous consensus map (Buchberg et al. 1991) and includes over 20 new loci that have been recently mapped on Chr 11. The cytogenetic characterization of mouse Chr 11 and the linkages of the human homologs of the genes mapping to mouse Chr 11 are summarized in this report. The resulting consensus linkage map is intended to be used as a guide for genetic, physical, and molecular analyses of Chr 11.
Burden of cardiovascular morbidity and mortality following humanitarian emergencies: a systematic literature review.

Background The global burden of cardiovascular mortality is increasing, as is the number of large-scale humanitarian emergencies. The interaction between these phenomena is not well understood. This review aims to clarify the relationship between humanitarian emergencies and cardiovascular morbidity and mortality. Methods With assistance from a research librarian, electronic databases (PubMed, Scopus, CINAHL, and Global Health) were searched in January 2014. Findings were supplemented by reviewing citations of included trials. Observational studies reporting the effect of natural disasters and conflict events on cardiovascular morbidity and mortality in adults since 1997 were included. Studies without a comparison group were not included. Double-data extraction was utilized to abstract information on acute coronary syndrome (ACS), acute decompensated heart failure (ADHF), and sudden cardiac death (SCD). Review Manager 5.0 (Version 5.2, The Nordic Cochrane Centre; Copenhagen Denmark,) was used to create figures for qualitative synthesis. Results The search retrieved 1,697 unique records; 24 studies were included (17 studies of natural disasters and seven studies of conflict). These studies involved 14,583 cardiac events. All studies utilized retrospective designs: four were population-based, 15 were single-center, and five were multicenter studies. Twenty-three studies utilized historical controls in the primary analysis, and one utilized primarily geographical controls. Discussion Conflicts are associated with an increase in long-term morbidity from ACS; the short-term effects of conflict vary by study. Natural disasters exhibit heterogeneous effects, including increased occurrence of ACS, ADHF, and SCD. Conclusions In certain settings, humanitarian emergencies are associated with increased cardiac morbidity and mortality that may persist for years following the event. Humanitarian aid organizations should consider morbidity from noncommunicable disease when planning relief and recuperation projects. Hayman KG , Sharma D , Wardlow RD II , Singh S . Burden of Cardiovascular Morbidity and Mortality Following Humanitarian Emergencies: A Systematic Literature Review. Prehosp Disaster Med. 2015;30(1):1-9 .
Syndrome of Inappropriate Antidiuretic Hormone in Association with Amiodarone Therapy: A Case Report and Review of Literature

Background: Amiodarone is a class III antiarrhythmic agent that is widely used in the treatment of a variety of arrhythmias. Several different systemic side effects are reported after use of this medication. In this article, we report a case that had developed syndrome of inappropriate antidiuretic hormone (SIADH) after starting treatment with this agent. Case report: The patient is a 66-year-old male with past medical history of hypertension, hyperlipidemia, coronary artery disease, and class III New York Heart Association congestive heart failure who presented with monomorphic nonsustained ventricular tachycardia. A loading dose of amiodarone followed by maintenance dose was started. Baseline serum sodium of 138 mmol/L on admission decreased to 119 mmol/L by day 7, and a diagnosis of SIADH was made. The patient was not taking any other medication known to cause SIADH, nor had any such comorbidity to explain it. Serum sodium increased to 133 and 138 mmol/L, respectively, after 16 and 33 days from discont...
Probing and wire bonding of aluminum capped copper pads

Microelectronics manufacturing has started to develop and, in some cases, ramp wafer fabrication processes using copper interconnects as the preferred metallurgy. Since bare copper wire bonding has not been accepted as a reliable and high throughput process, integrated circuit manufacturers are applying an aluminum cap on top of the copper to facilitate bonding. Past studies carried out on aluminum-based silicon wafers concluded that scrub damage on bond pads due to multiprobe testing should be minimized in order to maintain high assembly yields and a robust bond process. Texas Instruments has carried out an experimental study that compares wire-bonding characteristics of probed aluminum capped and etched aluminum bond pads. Wafers were probed multiple times to generate pads with measured damage ranging from 10-45% of total pad area. Analyses on bonded units include percent of Au-Al intermetallics formed, ball shear, wire pull, and underlying pad damage. The paper will highlight the differences found between the two methodologies and recommend basic changes that will enhance the assembly process of Al-capped copper bond pads.
Developmental changes within the core of artifact concepts.

Three experiments addressed the relative importance of original function and current function in artifact categorization. Subjects were asked to judge whether an artifact that was made for one purpose (e.g. making tea) and was currently being used for another purpose (e.g. watering flowers) was a teapot or a watering can. Experiment 1 replicated the finding by Hall (1995) (unpublished manuscript) that adults rely on the original function of an artifact over a current function in their kind judgments. Experiments 2 and 3 revealed that whereas the kind judgments of 6-year-olds, like those of adults, patterned with the original function, those of 4-year-olds did not. Four-year-olds were influenced by the order in which the functions were mentioned in the story. Further, in their justifications 6-year-olds and adults referred to the origin of the objects, whereas 4-year-olds virtually never did. We conclude that 6-year-olds have begun to organize their understanding of artifacts around the notion of original function, and that 4-year-olds have not. The data are discussed as they bear on children's understanding of the design stance (Dennett, D. C. (1987). The intentional stance. Cambridge, MA: MIT Press).
RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund-Thomson syndrome

Rothmund-Thomson syndrome (RTS) is a heterogeneous disease, associated with increased prevalence of osteosarcoma in very young patients with a mutated RECQL4 gene. In this study, we tested the ability of RECQL4 deficient fibroblasts, derived from a RTS patient to recover from hydrogen peroxide (H(2)O(2))-induced oxidative stress/damage. Immunoperoxidase staining for 8-oxo-deoxyguanosine (8-oxo-dG) formation in RTS and normal human fibroblasts were compared to assess DNA damage. We determined DNA synthesis, cell growth, cell cycle distribution, and viability in RTS and normal human fibroblasts before and after H(2)O(2) treatment. H(2)O(2) induces 8-oxo-dG formation in both RTS and normal fibroblasts. In normal human fibroblasts, RECQL4 was predominantly localized to cytoplasm; nuclear translocation and foci formation occurred in response to oxidant stimulation. After recovery from oxidant exposure, viable RTS fibroblasts showed irreversible growth arrest compared to normal fibroblasts. DNA synthesis decreased significantly in treated RTS cells, with concomitant reduction of cells in the S-phase. These results suggest that enhanced oxidant sensitivity in RECQL4 deficient fibroblasts derived from RTS patients could be attributed to abnormal DNA metabolism and proliferation failure. The ramifications of these findings on osteosarcoma prevalence and heterogeneity in RTS are discussed.
Can Natural Language Processing Improve the Efficiency of Vaccine Adverse Event Report Review

Background: Individual case review of spontaneous adverse event (AE) reports remains a cornerstone of medical product safety surveil-lance for industry and regulators. Previously we developed the Vaccine Adverse Event Text Miner (VaeTM) to offer automated information extraction and potentially accelerate the evaluation of large volumes of unstructured data and facilitate signal detection. Objective: To assess how the information extraction performed by VaeTM impacts the accuracy of a medical expert’s review of the vaccine adverse event report. Methods: The “outcome of interest” (diagnosis, cause of death, second level diagnosis), “onset time,” and “alternative explanations” (drug, medical and family history) for the adverse event were extracted from 1000 reports from the Vaccine Adverse Event Reporting System (VAERS) using the VaeTM system. We compared the human interpretation, by medical experts, of the VaeTM extracted data with their interpretation of the traditional full text reports for these three variables. Two experienced clinicians alternately reviewed text miner output and full text. A third clinician scored the match rate using a predefined algorithm; the proportion of matches and 95% confidence intervals (CI) were calculated. Review time per report was analyzed. Results: Proportion of matches between the interpretation of the VaeTM extracted data, compared to the interpretation of the full text: 93% for outcome of interest (95% CI: 91– 94%) and 78% for alternative explanation (95% CI: 75 – 81%). Extracted data on the time to onset was used in 14% of cases and was a match in 54% (95% CI: 46 – 63%) of those cases. When supported by structured time data from reports, the match for time to onset was 79% (95% CI: 76 – 81%). The extracted text averaged 136 (74%) fewer words, resulting in a mean reduction in review time of 50 (58%) seconds per report. Conclusion: Despite a 74% reduction in words, the clinical conclusion from VaeTM extracted data agreed with the full text in 93% and 78% of reports for the outcome of interest and alternative explanation, respec -tively. The limited amount of extracted time interval data indicates the need for further development of this feature. VaeTM may improve review efficiency, but further study is needed to determine if this level of agreement is sufficient for routine use.
Understanding and motivating health care employees: integrating Maslow's hierarchy of needs, training and technology.

Aim This paper applies Maslow's Hierarchy of Needs Model to the challenges of understanding and motivating employees in a rapidly changing health care industry. Background The perspective that Maslow's Model brings is an essential element that should be considered as the health care arena is faced with reorganization, re-engineering, mergers, acquisitions, increases in learning demands, and the escalating role of technology in training. Evaluation This paper offers a new perspective related to how Maslow's Model, as used in business/organizational settings, can be directly related to current workforce concerns: the need for security and freedom from stress, social belongingness, self-esteem, self-actualization, altered work/social environments, and new opportunities for learning and self-definition. Key issues Changes in health care will continue at an accelerated pace and with these changes will come the need for more and more training. The use of technology in training has heightened access, faster distribution, innovation and increased collaboration. However, with this technology come attendant challenges including keeping up with the technology, the increased pace of training, depersonalization, and fear of the unknown. The Maslow model provides a means for understanding these challenges in terms of universal individual needs. Conclusion How does one motivate employees in the face of increased demands, particularly when they are being asked to meet these demands with fewer resources? The answer is, in large part, to make the employee feel secure, needed, and appreciated. This is not at all easy, but if leaders take into consideration the needs of the individual, the new technology that provides challenges and opportunities for meeting those needs, and provides the training to meet both sets of needs, enhanced employee motivation and commitment is possible.
Preferential denervation of the adductor muscles of the equine larynx. I: Muscle pathology.

Summary The terminal branches of the recurrent laryngeal nerve (RLN) of three normal ponies and six horses with sub-clinical laryngeal disease were examined qualitatively and quantitatively in an attempt to explain the preferential denervation of the laryngeal adductor muscles in the neuropathy of idiopathic laryngeal hemiplegia (ILH). The myelinated fibre spectra of all the motor nerve fibres in the left and right abductor and adductor branches of the RLN in three normal ponies were measured. The density of myelinated fibres was also calculated. There was no significant difference between the larger group of myelinated fibres in the adductor or abductor branches. In the six horses with laryngeal hemiparesis, however, there was a marked preferential loss of the medium/large size myelinated fibres in the left adductor branch, although nerve fibre densities were not significantly different. While no simple morphometrical feature was found to explain the selective muscle denervation, the greater loss of large diameter myelinated fibres in the adductor branches confirms the earlier observation of adductor muscle susceptibility in the neuropathy of ILH.
Effects of Prescribed Fire and Herbicide Application on Cattle Grazing and Herbage Production from Yellow Bluestem Pastures1

Forage management practices influence the quantity and quality of forage available to grazing cattle. The objectives of this experiment were to determine the effects of prescribed fire or herbicides on the density of forbs, the production and nutritive value of the herbage, and the performance of beef steers grazing Yellow bluestem [Bothriochloa ischaemum (L.) Keng var. ischaemum (Hack.) Celarier and Harlan] pastures. The experiment was conducted in northwestern Oklahoma from 1998 through 2000, and the untreated pastures (control) were not burned or sprayed. The prescribed-fire treatment (PFT) occurred annually between March 27 and April 10. The herbicide treatment (HT) consisted of an annual application of 0.9 kg of 2,4-dichlorophenoxyacetic acid and 2.8 g of metsulfuron methyl per hectare. Compared with the control, forb densities were or tended to be decreased (P < 0.13) in PFT and HT pastures only in May and June of 1998; forb densities were not affected (P ≥ 0.45) in later months or years. Dry matter production of Yellow bluestem in August was not affected (P ≥ 0.10) by treatment, but CP concentration and in vitro OM disappearance were greater (P ≤ 0.05) in herbage collected early in the grazing season from PFT pastures than in that from control and HT pastures. Over the 92-d grazing period that started May 30 (initial stocking rate, 1.93 steers/ha), ADG and BW gain per hectare did not differ (P ≥ 0.74) among treatments. Forb control with prescribed fire or the herbicides used in this experiment did not improve the performance of beef cattle grazing Yellow bluestem pastures even though prescribed fire improved forage quality early in the grazing season.
Coronary air embolism: incidence, severity, and suggested approaches to treatment

Because no well-controlled study of inadvertent coronary air embolism has been done to truly quantify the incidence of this cardiac catheterization complication, we wanted to determine its incidence and severity in an active teaching medical center and assess approaches to treatment. We retrospectively reviewed 3,715 coronary angiogram and PTCA reports performed over 32 months. Further, we classified severity based on angiographic findings and symptoms as minimal, mild, moderate, and massive. Two independent angiographers reviewed 764 consecutive cines performed in the first 2 months of training of each new fellow and 740 cines performed in the last 2 months of training. We found that during the first 2 months of training the overall incidence for significant intracoronary air embolism was 0.19% (7 documented cases) compared with 0.2% (3 cases) for non-reported, minimal asymptomatic air embolism. The estimated incidence for total air emboli events was 0.27% (10/3,715). We did not find coronary air emboli in the 740 cines performed at the end of fellowship training. Additionally, the incidence of coronary air emboli during PTCA training was much higher compared with coronary angiography training (0.84 vs. 0.24%). Although there is no best technique to restore blood flow after blockage by air emboli, we suggest as options aspirating the air or forcefully injecting saline, with auxiliary supportive measures like 100% oxygen, IABP, CPR, and DC cardioversion.
Bolted Connections with Varied Hole Diameters

The effect of oversize holes on the slip resistance and ultimate strength of bolted joints is evaluated. Tests were performed on 47 different lap and butt joints. The average slip coefficient of the friction-type butt or lap joint using 3/4 in. and 7/8-in. A325 high-strength bolts was not signficantly reduced with an oversize up to 3/16 in. when a washer is placed under the turned element. When the oversize was increased to 1/4 in. the bolthead had very little contact with the plate and it was difficult to obtain the minimum tension in the bolt. The ultimate shear strength of the bearing-type butt or lap joint using 3/4 in. and 7/8-in. A325 high-strength bolts was not reduced by any significant amount with an oversize of upt o 3/16 in. Upon increasing hte oversize to 1/4 in., the boltheads cut into the plate to such a great extent that the heads almost pulled through the holes.
A Stationary Reaction Current Effect in Mesoporous Pt/ZrO2 System Under H2/O2 Environment

There have been many works analyzing thermionic currents and chemicurrents generated on various electrolyte-free metal/semiconductor nanostructures. More recently, the chemicurrent phenomenon was reported for mesoporous Pt/semiconductor systems adept at converting surface-released chemical energy into a stationary electrical signal at room-temperature conditions. The present work points out the existence of an entire class of such surface-driven functional nanosystems. Here, the reaction current generation of Pt/ZrO2 systems was studied at room temperature under exposure to oxyhydrogen environments for mesoporous zirconia; this nanostructure was capable of the continuous oxidation of hydrogen, producing a long-standing stationary current. Synthesis parameters during the anodization process were manipulated to control sample pore density and the average pore diameter. Deposited via wide-angle PVD sputtering, the Pt phase forms an electrically continuous topographical nanomesh layer, and thus the Pt/ZrO2/gas interface is regulated through the manipulation of zirconia porosity. We observed reaction current enhancements with increasing porosity due to the lengthening of the Pt/ZrO2 interface. The most porous sample was significantly more sensitive to initial hydrogen additions, pointing toward the spillover of positive ionic charge across the Pt/ZrO2 interface as the origin of the observed electromotive force.
Acetylcholine and acetylcholine receptor subtypes in REM sleep generation.

Publisher Summary This chapter discusses the acetylcholine and acetylcholine receptor subtypes in rapid eye movement (REM) sleep generation. REM sleep is characterized by the simultaneous presence of tonic components, such as cortical desynchronization, atonia of antigravitory muscles, hippocampal theta rhythm, and phasic components, such as REM and ponto-geniculo occipital spikes. Cholinergic stimulation of the brainstem is capable of eliciting a state that is behaviorally and polygraphically indistinguishable from naturally occurring REM sleep, and specific sites within the brainstem are capable of inducing a selective increase of one of the components as well. The cholinergic stimulation of a number of brain regions can increase either slow-wave sleep or REM sleep. A cholinergic hypnogenic pathway is presented, including the hypothalamus, amygdala, hippocampus, the medial anterior preoptic area, temporal and cingulate cortex, and some areas of the brainstem where the medial pontine reticular formation is relevant. REM sleep is induced by the administration of a solution of acetylcholine bromide in the caudal mesencephalon and in the medulla of freely moving cats. The main pharmacological tool in the analysis of cholinergic control of REM sleep is carbachol, a mixed cholinergic receptor agonist.
Conformational Dependence of Electronic Coupling Across Peptide Bonds: A Ramachandran Map

Electronic coupling across peptide bonds has been determined throughout the peptide bond conformational space. Using the side chains of tyrosine (Tyr) and tryptophan (Trp) as donors (D) and acceptors (A), respectively, a plot of the electronic coupling matrix element HDA versus (ϕ,ψ) torsional angles has been constructed for Trp-peptide-Tyr molecules. The HDA values were obtained using the generalized Mulliken−Hush approach with electronic transition energies, permanent and transition dipole parameters derived from semiempirical quantum mechanical electronic structure calculations (INDO/S). The computed HDA values and the corresponding electron transfer (ET) rates show that specific helical peptide conformations situated in a narrow ϕ region of the full HDA-(ϕ,ψ) map play a significant role in developing strong electronic coupling for promoting ET. The HDA-(ϕ,ψ) map clearly defines the angular regions in space, where strong Trp-peptide-Tyr coupling occurs and peptide-mediated ET results, as well as region...
Nutrition and aging.

Aging is multifactorial and is dependent on genetic, life-style, and environmental factors. Successful aging relies upon a nutritionally complete diet and adequate exercise to counteract some of the physiologic changes related to age. A nutritionally sound diet for wellness in normal elderly is outlined which usually does not require additional vitamin supplements. Protein-calorie malnutrition is very prevalent in older patients with chronic disease, living alone, and receiving low income. Nutritional assessment and early intervention in the hospitalized elderly patient is extremely important to reduce the morbidity associated with this disease.
Some Properties of Castle's Intrinsic Factor

SummaryExposure of normal human gastric juice to pH 10 for 30 minutes destroys peptic activity without materially affecting intrinsic factor. Pepsinogen containing 28 mg. N was inert when administered parenterally. Eighty cc. of normal juice collected by Greenspon's technique was inert but when added to 80 gm. of boiled liver accentuated the hematopoietic effect of the liver.
Characterization of dermatopathology fellowship applicants: a 5-year single institution experience.

Background Although much data have been documented on the characteristics of medical school applicants for dermatology and pathology residency programs in the United States and select medical and surgical fellowship applicants through the National Residency Matching Program, little is known about the dermatopathology applicant demographics. Methods We examined a 5-year pool of dermatopathology fellowship applicants from a single institution (University of Arkansas for Medical Sciences) and compiled background profile data of the applicants to characterize an 'average dermatopathology fellow' applicant. Results A total of 229 applicants over a 5-year period were included in the assessment. The majority were of pathology background with medical school and residency training based in the southern United States. One-third of the applicants had original research publications, case reports or had given an oral or poster presentation in the field of dermatopathology. Conclusions Knowledge regarding the average applicant statistics for a dermatopathology fellowship will allow prospective applicants to evaluate their own applications for strengths and weaknesses. This will also provide institutions information regarding anticipated statistics for a competitive applicant pool.
Integrating Soiological Research and Theory with Community-Oriented Policing: Bridging the Gap between Academics and Practice

Over 70 percent of police agencies indicate that they have put the community-oriented policing (COPS) philosophy into practice, but some critics claim that they are failing to do it well. In this paper, we examine three core components of community policing (community involvement, problem solving, and organizational decentralization) and employ lessons from the academic sociological literature on these topics to inform how to improve the fit between philosophy and practice. We argue that applying lessons from sociology will make the implementation and practice of community policing more successful in meeting community needs, including reducing crime and fear of crime.
Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. Here, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Using this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS-specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens.
A Spotlight on Reward.

Research published in this issue of Neuron from McGinty et al. (2016) suggests that attention may help bind information about value to specific options in economic choice. Responses of orbitofrontal neurons are strongly modulated by the distance from gaze to the position of a reward-predicting target.
Talk versus Action: Comparing the Narratives and Behaviors of Diabetes Self-Management in Latino Caregiving Dyads.

PurposeThe purpose of this longitudinal qualitative study was to explore Latino caregiving dyads’ experiences with managing diabetes in the home.MethodsThe authors used Sebern’s Shared Care construct as a framework for understanding the realities that some Latino older adults and their caregivers face in managing diabetes. Twelve caregiving dyads completed a semistructured interview followed by weekly participant observation in their homes over 3 to 4 months. Data were analyzed using a grounded theory approach.ResultsDiet was the most commonly discussed and observed aspect of diabetes care and also a source of strain within dyads. Dyads talked and acted congruently about food preparation and the challenges of diet adherence but had conflicting views on whether the care receiver’s diabetes was under control. Analysis also revealed a discordance between views and observed actions of diabetes care related to monitoring blood glucose levels.ConclusionFindings suggest that caregivers or other key family member...
CHEMODYNAMICS AND ENVIRONMENTAL TOXICOLOGY OF CONTROLLED RELEASE ORGANOTIN MOLLUSCICIDES

The efficacy of controlled release trialkyl organotin molluscicides has been amply demonstrated under field conditions at over 40 test sites in Africa, Asia and South America (1,2). Cost/benefit ratios appear to be extremely favorable. The major impediment to large scale usage of the three commercially available materials is the need to establish benefit/risk ratios for various environmental conditions Basically the need is to assess the degree of environmental hazard involved. It is believed that the organotins, under foreseeable use conditions, impose less ecological burden than conventional molluscicides now in extensive use. Our present task is to supply convincing evidence to the World Health Organization and a multitude of public health agencies that: 1. Controlled release molluscicides are safe in toxicological terms, and 2. That the destruction of the snail host is a superior approach to disease intervention than the use of highly hazardous drugs in medical therapy.
A New Carbon-Activity Meter for High-Temperature Sodium

ABS>A metering system has been devised and tested which utilizes a solid- electrolyte oxygen-activity meter to measure the carbon activity in high- temperature sodium. The activity of the carbon is related to the activity of oxygen by the reactions: C + C0/sub 2/ in equilibrium 2CO; 2C0 + O/sub 2/ in equilibrium 2C0/sub 2/. Good agreement was obtained between actual calibration points and values calculated from thermodynamic considerations. (auth)
Punishment and Moral Risk

For every interesting moral question, we should have at least some doubt that we know the right answer. Legal theorists ignore this moral uncertainty at their peril. To take one important example, for retributivists to inflict punishment, they must believe not only that a defendant is guilty but that all other prerequisites for deserved punishment are satisfied as well. They must believe offenders have free will, even though philosophers have debated the topic for centuries. They must believe offenders can be punished proportionally, even though no one has convincingly determined how to assess proportionality. And they must believe it appropriate to make offenders suffer as a response to the suffering they caused, even though some find this view barbaric.These retributivist commitments, along with several others, are clearly controversial. One would be hard-pressed to believe a single one — let alone the conjunction — with the 95% or 99% confidence frequently attributed to the beyond-a-reasonable doubt standard used to assess guilt. Reasonable retributivists, I argue, face too much uncertainty to justify punishment under the standard of proof they would likely set for themselves. Consequentialists, by contrast, are less vulnerable to this challenge. They can accept greater risk when punishing because they face countervailing risk by failing to adequately punish.More generally, I argue that we hold not just beliefs but “portfolios of beliefs” that can exacerbate or hedge moral risks. These portfolios sometimes do a better job of explaining our moral and legal views than existing theories, and I show how “epistemic hybrid” theories that combine retributivism and consequentialism can avoid the inconsistencies facing current hybrid theories. We are not necessarily retributivists or consequentialists but, say, 60%-retributivists or 90%-consequentialists. Portfolios of beliefs can also help us understand other areas of law and morality, such as the perplexities of threshold deontology and the puzzles of tort law. Indeed, portfolios of beliefs may not only explain our beliefs but also offer normatively appealing alternatives to our existing theories that fail to take moral risk into account.
The design and validation of novel exposure surrogates for past environmental exposures.

B47 The opportunity to measure relevant (i.e. past) exposures to environmental carcinogens has been lost to time, impeding establishing causal relationships, and underscoring the need to develop exposure surrogates. This study is based on the hypothesis that environmental exposures occur from polluted drinking water emanating from groundwater leaching off hazardous waste sites which occurred decades ago, consistent with the latency period of the disease under investigation. I constructed the surrogates using governmental records of hazardous waste sites. A hazard density score, HDS, (the number of hazardous waste sites per square mile), and the chemical contamination index (CCI), designed to reflect exposures to individual chemicals prevalent in waste sites, were constructed on a per water-district basis. The CCI was derived by comparing the total square footage of all waste sites in a water district with its size in square miles, representing the percentage of the water district9s contaminated surface area. Water districts were chosen as the exposure boundary, as opposed to zip codes, as better reflecting relevant exposures. Nassau County, New York, was the test site area for validation. The county derives all of its drinking water from ground water, has an unusually high incidence of breast cancer and records of well measurements currently exist. The most frequently detected chemicals in Nassau County waste sites were: perchloroethylene, (PCE) trichloroethylene (TCE), dichloroethylene, (DCE) and trichloroethane (TCA). The same chemicals were found in drinking wells -- in identical order of detection, frequency and prevalence, indicating reliability of the HDS. The study also demonstrated that two pollutants, TCE and DCE, infiltrated wells at high levels, up to two orders of magnitude higher than TCA. An 86% correlation was found between the CCI for DCE (considered a high correlation by the scientific community) and heavily contaminated wells, while no correlation was found between heavily contaminated wells and TCA, indicating that TCA if found at all in drinking wells, did so at very low levels. The correlation between heavily contaminated wells and TCE/PCE was moderate. It appears that DCE in waste sits infiltrates wells at the highest levels of concentration; TCE and PCE, also found in wells at high levels were related to waste site content - but to a lesser degree, and TCA, while present in waste sites, did not infiltrate wells to any significant degree. The investigation of a dose response relationship with the prevalent exposurues, using contamination per square mile as the dose index, can now be undertaken. Further, more effective exposure surveillance through targeted drinking well testing and better groundwater detection can be implemented.
A Stapled p53 Helix Targets HDMX to Overcome Nutlin-3 Resistance and Reactivate the p53 Tumor Suppressor Pathway in Cancer

p53 is a transcription factor that induces cell cycle arrest or apoptosis in response to DNA damage and cellular stress, and thereby plays a critical role in protecting cells from malignant transformation. The E3 ubiquitin ligase HDM2 controls p53 levels through a direct binding interaction that neutralizes the transactivation activity of p53 and targets it for degradation via the ubiquitylation-proteasomal pathway. Whereas the HDM2-homologue HDMX lacks ubiquitin ligase function, it participates in regulating the p53 axis by heterodimerizing with HDM2 and sequestering p53 through protein interaction. Loss of p53 activity, either by deletion, mutation, or HDM2/HDMX overexpression, is the most common defect in human cancer. Tumors expressing wild type p53 are rendered vulnerable by pharmacologic approaches that stabilize and upregulate p53. In this context, HDM2 and HDMX have emerged as independent therapeutic targets for restoring p53 activity and resensitizing cancer cells to apoptosis in vitro and in vivo . The small molecule nutlin-3 is an effective antagonist of the p53-HDM2 interaction. However, several studies have demonstrated the inability of nutlin-3 to disrupt the p53-HDMX complex, rendering tumor cells that overexpress HDMX nutlin-3-resistant. We have previously described the synthesis and characterization of a hydrocarbon-stapled alpha-helical p53 peptide (SAH-p53-8) that binds HDM2 with low nanomolar affinity, targets HDM2 in situ , and reactivates the p53 tumor suppressor pathway in HDM2-overexpressing osteosarcoma cells. We now report that SAH-p53-8 binds HDMX with even higher affinity, co-immunoprecipitates with endogenous HDMX, and induces apoptosis and cell cycle arrest in nutlin-3-resistant cancer cells that overexpress HDMX. Thus, by inserting a chemical staple into a peptide fragment of the p53 transactivation domain, we have generated the first bifunctional inhibitor of HDM2 and HDMX, enabling the investigation and pharmacologic modulation of both targets in human cancer.
9 Bim suppresses the development of sle by limiting macrophage inflammatory responses

Background and aims There are numerous endogenous Bcl-2 antagonists that share similar homology, structure, topology and expression pattern, yet only the loss of Bim in mice is sufficient to lead to the development of a systemic autoimmunity. Methods We investigated the contribution of Bim in monocytes/macrophages and its effect on systemic autoimmunity by establishing conditionally Bim-deleted mice in the monocyte/macrophage compartment (Cre LysM Bim fl/fl mice) and examined the development of lupus-like disease over time. Results Patients with lupus display decreased expression of Bim in circulating monocytes and reduced Bim expression in kidney macrophages. Cre LysM Bim flox/flox mice develop a lupus-like disease that mirrors aged Bim -/- mice including loss of the marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies including anti-DNA IgG, and a type I interferon signature as compared to control mice. Cre LysM Bim flox/flox mice also exhibit increased mortality attributed to immune complex deposition and increased numbers of kidney macrophages all of which contribute to glomerulonephritis. The loss of Bim in macrophages is sufficient to break tolerance as adoptive transfer of wild-type lymphocytes into Cre LysM Bim flox/flox Rag -/- mice leads to systemic autoimmunity. We also identified that the loss of TLR signalling adaptor protein TRIF but not MyD88 is essential for progression to GN phase but is dispensable for systemic autoimmunity. RNA seq analysis of sorted kidney macrophages revealed a novel Bim and lupus specific signatures. Conclusions These data add another facet to the conventional dogma that Bim’s central role in autoimmune disease is to prevent the escape of autoreactive lymphocytes from apoptosis. Thus, Bim may be a novel therapeutic target for treating SLE.
Trans responses to Adichie: challenging cis privilege in popular feminism

In recent years, Chimamanda Ngozi Adichie, author of several award-winning, bestselling novels has gained recognition for centering a strong African feminist perspective in her work. In 2012, Adich...
Enteral Feeding during Induced Hypothermia after Intracerebral Hemorrhage (P3.200)

Introduction. Therapeutic moderate hypothermia (MH, Tcore33-34°C) is being studied as a treatment option for spontaneous intracerebral hemorrhage (ICH). Early enteral nutrition (EN) is associated with improved outcomes. However, few studies have evaluated feeding during hypothermia, and EN initiation is often deferred until the rewarming phase. The purpose of this study was to evaluate the safety and tolerance of EN during MH after ICH. Methods. During a Phase-IIa/b clinical-trial (TTM-ICH, clinicaltrials.gov: NCT01607151), patients presenting with ICH within 18 hours of onset were randomized to 72 hours of either MH or normothermia (NT; 36-37°C). Gastric feeding tubes were placed at bedside. Semi-elemental EN was initiated at 20mL/hr for MH patients. Data were collected on the occurrences of feeding intolerance (gastric residuals >250mL, emesis), GI-related adverse events (bowel necrosis, perforation, ileus) and ventilator-associated pneumonia (VAP). Chi-square test and t-test were used to analyze outcomes between groups. Results. In total, 13 ICH patients participated in this study: 6 MH, 7 NT. Median age 57 years (IQR 22), 55[percnt] women, 66[percnt] Black, median GCS 7 (IQR 4), median ICH score 2 (IQR 1). Mean time to initiate EN was 29.9 (MH) vs 18.4 hours (NT) (p=0.046). Average daily EN calories received during first 4 days were 398 for MH group vs 1006 for NT group (p=0.0014). Half (3/6) of MH patients experienced high gastric residuals requiring pro-kinetics whereas 1/7 NT patient experienced emesis. Other than a mild ileus noted in 1 MH patient, there were no GI-related adverse or VAP events. Conclusions. Patients receiving MH for ICH are more likely to experience delayed EN initiation and high gastric residuals and receive less EN calories though these are not significantly associated with adverse events. Future studies should focus on EN initiation within 24 hours, advanced EN rates and post pyloric feeds during hypothermia. Disclosure: Dr. Dobak has nothing to disclose. Dr. Rincon has nothing to disclose.
Advanced Microscopy Techniques

Resolution of current controversies regarding the nature and functional roles of the oligomeric forms of G-protein coupled receptors (GPCRs) demands that experimental methods are both quantitative – i.e., they allow determination of size, geometry and stability of oligomers under varying experimental conditions – and applicable to receptors within their cellular milieu. Standard microscopy methods based on light do not provide the resolution necessary to resolve membrane receptor complexes, while techniques based on other contrast mechanisms (e.g., electron microscopy or atomic force microscopy) require sample destruction and fixation. Fortunately, techniques that exploit physical properties of fluorescent molecules, such as their ability to transfer excitations to an unexcited nearby fluorescent molecule (as in FRET spectrometry) and spatial or temporal fluctuations in the fluorescence intensity (fluorescence correlation spectroscopies and photon counting histograms) driven by aggregation and diffusion are capable of increasing the spatial and temporal resolution of all optical microscopies by several orders of magnitude. In this chapter, we overview the physical principles underlying such techniques, their comparative advantages and limitations, as well as their application to quantitative analysis of GPCR oligomerization in living cells.
Understaffed?: A Case Study in Empowering a User Community to Get a Large Project Done

The University of Minnesota Duluth made the decision to transition the majority of its websites into Drupal, a content management system (CMS). Additionally, during the process the university's website underwent a complete redesign as well as a content overhaul. Prior to the move to Drupal, there were few technical, design, or brand standards being enforced; each department or unit took its own unique approach to web design, development, and maintenance. Tight budgets meant that there were no staff available to commit full time to the project. The historical approach of letting units manage their websites however they wished also meant a huge cultural shift for members of the campus community. In this paper, we will address how through the formation of user and technical groups, we built trust, harnessed technical expertise, addressed bugs and feature requests, created training opportunities, developed documentation, provided viable channels for feedback, and successfully united a previously fragmented campus community to successfully get the job done.
Chronic Lead Exposure Induces Cochlear Oxidative Stress and Impairs Hearing

Oxidative stress plays a pivotal role in mediating hearing loss induced by exposure to a number of environmental risk factors. Elevated levels of lead is one of the commonly encountered risk factor in the urban environment. Though lead exposure damages the sensory, vascular, and neuronal components of the cochlea, it is not known whether oxidative stress mediates its ototoxic effects. The aim of this study is to delineate the redox mechanism underlying lead-induced auditory dysfunction. Young-adult C57BL/6 mice were exposed to: 1) control conditions or 2) 2 mM lead acetate in drinking water for 28 days. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS), lead-induced cochlear oxidative stress was assessed using targeted gene arrays, and hearing thresholds were assessed by recording auditory brainstem responses. Lead exposure significantly increased the blood lead levels to 293 ± 67 ppb. However, the body weight, appearance, and behavior of the lead-exposed mice were similar to that of the controls. This suggested that the exposure level was probably moderate for young-adult mice, and was not capable of inducing severe toxic effects. Nevertheless, lead exposure at this level downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. In addition, exposure to lead induced 8-12 dB shifts in hearing thresholds. Collectively, these findings suggest that chronic exposure to even moderate levels of lead induces cochlear oxidative stress and causes hearing loss.