cssi/SciSciGPT-SciSciNet huggingface dataset:
Converting java programs to use generic libraries

Java 1.5 will include a type system (called JSR-14) that supports parametric polymorphism, or generic classes. This will bring many benefits to Java programmers, not least because current Java practice makes heavy use of logically-generic classes, including container classes. Translation of Java source code into semantically equivalent JSR-14 source code requires two steps: parameterization (adding type parameters to class definitions) and instantiation (adding the type arguments at each use of a parameterized class). Parameterization need be done only once for a class, whereas instantiation must be performed for each client, of which there are potentially many more. Therefore, this work focuses on the instantiation problem. We present a technique to determine sound and precise JSR-14 types at each use of a class for which a generic type specification is available. Our approach uses a precise and context-sensitive pointer analysis to determine possible types at allocation sites, and a set-constraint-based analysis (that incorporates guarded, or conditional, constraints) to choose consistent types for both allocation and declaration sites. The technique handles all features of the JSR-14 type system, notably the raw types that provide backward compatibility. We have implemented our analysis in a tool that automatically inserts type parameters into Java code, and we report its performance when applied to a number of real-world Java programs.
T-cell-directed treatment strategies for Type 1 diabetes and the confounding role of inflammation.

Described by Arataeus as “a melting down of flesh and limbs into urine”, the etiology of diabetes long remained a mystery. From the time of Arataeus, approximately 3500 years passed until the disease was controversially linked, at least initially, to malfunction of the pancreas and soon thereafter linked to a failure to produce insulin. The discovery of insulin and the availability of insulin as a therapy changed the fate of millions of patients affected by this condition; however, treatment with exogenous insulin does not provide patients with Type 1 diabetes mellitus (T1DM) protection from long-term morbid complications. In humans and nonobese diabetic (NOD) mice with T1DM, autoimmune T cells infiltrate and destroy insulin-producing β-cells, thereby creating an insulin-deficient state [1]. The hypothesis that pancreas transplantation or, even better, transplantation with insulin-producing β-cells harvested from pancreatic islets represents a better therapeutic solution than exogenous insulin treatment was successfully tested by Paul Lacy [2,3]. Since islets possess both glucose sensors and insulin-secreting cells, tight control of hyperglycemia can often be established with a successful transplant.
Multifocal Interferometric Synthetic Aperture Microscopy

We extend ISAM to OCT data collected with multiple positions of the focal plane. Multifocal ISAM achieves spatially invariant resolution and better signal-to-noise ratio over the entire image than is possible with single-focus ISAM.
Determination of pesticide metabolites in human urine using an isotope dilution technique and tandem mass spectrometry.

A method that measures 12 analytes in urine and reflects possible exposure to pesticides was developed. The sample preparation involves enzyme hydrolysis and solvent extraction through the use of laboratory robotics, followed by phase-transfer catalysis
Electromagnetic modeling of waveguides involving finite-size dielectric regions

A moment method for handling arbitrarily shaped 2-D and 3-D waveguides that involve either conductors, finite-size dielectric regions, or both is presented. A procedure for modeling the dielectric allows 2-D rooftop functions to represent both the 3-D polarization current in the dielectric and the surface current on the conductors, and precludes the presence of fictitious charge within the dielectric. Examples include coaxial, microstrip, and dielectric waveguides. Numerical convergence, consistency with physical principles, and agreement with the literature are demonstrated. >
Pictures, images, and pure alexia: A case study

Abstract A patient with pure alexia was presented with a series of tachistoscopic tests involving words, letters, pictures, and lines. Low level perceptual processing remained intact. A major deficit was revealed in the speed of identifying orthographic material. This deficit extended to the identification of pictures presented at tachistoscopic durations, although no disturbance in the visual identification of pictures or objects was observed in real time. There were frequent reports of visual imagery associated with the perception of written material. These images cannot account for the patient's partial recovery of reading functions; instead, it appears that the abnormal characteristics of the patient's reading arise because, after a visual stimulus is perceived, an abnormally long period of time is required before the patient can identify the stimulus. It is suggested that pure alexia is the behavioral manifestation of a deficit in speed of visual identification which is not specific to orthographic m...
Could She Be Dying? Dis-Orders of Reality around Death in an American Hospital

Dying in an American hospital is a site of conflict among clinicians with competing orders of reality differing from each other and from the patient and family. Anthropological studies of death have often shown that the participants share a cosmology in common. Hospitalized patients may die among strangers, clinicians who exert different forms of control and attempt to make their own meanings out of the dying process. Their efforts can interfere with the patient and family's opportunity to reconnect with their life worlds at the time of death. A particular case from a research project on the dying process in the hospital is used to illustrate these points.
Effect of marinade containing thyme and orange oils on broiler breast fillet and whole wing aerobic bacteria during refrigerated storage

SUMMARY Raw meat typically hosts spoilage organisms and sometimes hosts pathogens; to combat this, natural antimicrobial interventions have gained interest among consumers. In a previous study a marinade containing a thyme-orange essential oils combination (TOC) at the 0.5% level was found to inhibit Salmonella and Campylobacter species. The objective of the current study was to evaluate the effect of a salt-phosphate marinade solution with 0.5% TOC (treatment) or without TOC (control) applied by vacuum tumbling on the shelf life of broiler breast fillets and whole wings. The total aerobic and facultative mesophiles (TAm) occurring naturally on these products during refrigerated storage for 14 d (at 1, 7, 10, and 14 d) were enumerated. A total of 48 (24 for each trial) skinless breast fillets and 48 (24 for each trial) whole wings were used for the 2 trials. For each trial, 12 of the 24 breast fillets or wings were marinated using the control marinade solution and the remaining 12 were marinated in the treatment marinade solution. On d 1, 7, 10, and 14, 3 treatment and 3 control breast fillets and wings were randomly selected for TAm enumeration. Sample rinsates were plated in duplicate and incubated at 35°C for 48 h. Thyme-orange combination marinade significantly reduced TAm numbers on d 1, 7, and 10 compared with the controls. Log reductions of 0.3, 0.9, and 1.1 were recorded on d 1, 7, and 10, respectively. The difference in TAm between the treated and untreated whole wings was not significant. Therefore, 0.5% TOC in marinade can be used as a natural antimicrobial to reduce TAm on skinless breast fillets; however, a higher concentration may be required for skin-on products.
DOUGLAS-FIR GROWTH IN MOUNTAIN ECOSYSTEMS. WATER LIMITS TREE GROWTH FROM STAND TO REGION

The purpose of this work is to understand the nature of growth-climate relationships for Douglas-fir (Pseudotsuga menziesii) across the climatic dimensions of its niche. We used a combination of biophysically informed sampling (to identify sample sites) and dendroclimatology (to identify growth-climate relationships) along a climate gradient in northwestern United States mountain ecosystems from the western Olympic Peninsula, Washington to the eastern Rocky Mountain Front, Montana. We used a multi-scale sampling strategy that accounted for continentality, physiography, and topography as non-climatic factors that could influence climate and alter tree growth. We developed a network of 124 Douglas-fir tree-ring chronologies and explored growth-climate correlations across the sampled gradients. We considered two different spatial scales of monthly and seasonal climate variables as potential controlling factors on tree growth. Annual radial growth in 60-65% of the plots across the region is significantly correlated with precipitation, drought, or water balance during the late summer prior to growth and the early summer the year of growth. In a few plots, growth is positively correlated with cool-season temperature or negatively correlated with snowpack. Water availability is therefore more commonly limiting to Douglas-fir growth than energy limitations on growing season length. The first principal component derived from the chronologies is significantly correlated with independent drought reconstructions. The sensitivity of Douglas-fir to summer water balance deficit (potential evapotranspiration minus actual evapotranspiration) indicates that increases in April to September temperature without increases in summer precipitation or soil moisture reserves are likely to cause decreases in growth over much of the sampled area, especially east of the Cascade crest. In contrast, Douglas-fir may exhibit growth increases at some higher elevation sites where seasonal photosynthesis is currently limited by growing-season length or low growing-season temperature. Life-history processes such as establishment, growth, and mortality are precursors to changes in biogeography, and measurements of climate effects on those processes can provide early indications of climate-change effects on ecosystems.
Peripheral Neuropathy in Diabetic Monkeys

Peripheral neuropathy is a significant complication of human diabetes and a source of morbidity. Appropriate experimental models may aid in understanding its pathogenesis and in developing therapeutic strategies. We sought to determine whether spontaneously diabetic obese adult monkeys developed peripheral neuropathy and whether it occurred early or late in relation to the onset of hyperglycemia. We studied nerve conduction in both motor (peroneal, median, and ulnar) and sensory (median and ulnar) nerves in 13 adult male rhesus monkeys, 4 overtly diabetic and 9 nondiabetic (mean age 21 ± 2 and 16 ± 2 yr, respectively, NS; mean fasting plasma glucose 14.5 ± 3.4 and 4.4 ± 0.6 mM, P = .001). The diabetic animals had significantly reduced motor conduction velocities and prolonged F-wave latencies. Motor-evoked amplitudes did not differ. In the diabetic monkeys, nerve conduction times were increased in motor fibers, which could be identified as early as 2 yr after the onset of hyperglycemia. These abnormalities are similar to those seen in humans and suggest further study of these animals as a primate model of human diabetic neuropathy.
Optimal loading of solids by the boundary element method

Abstract Optimal boundary loading of solids in elastostatics is analyzed within the framework of optimal control problems. First, the necessary conditions of optimality are found by means of calculus of variations. The resulting sets of vector PDE's are then discretized in space by using the boundary element method, while an integral function (the performance index of the control problem) is minimized by the conjugate gradient method of optimization. Numerical results are provided for a thin plate of annular sector.
Social trait judgment and affect recognition from static faces and video vignettes in schizophrenia

article i nfo Social impairment is a core feature of schizophrenia, present from the pre-morbid stage and predictive of outcome, but the etiology of this deficit remains poorly understood. Successful and adaptive social interactions depend on one's ability to make rapid and accurate judgments about others in real time. Our surprising ability to form accurate first impressions from brief exposures, known as "thin slices" of behavior has been studied very extensively in healthy participants. We sought to examine affect and social trait judgment from thin slices of static or video stimuli in order to investigate the ability of schizophrenic individuals to form reliable social impressions of others. 21 individuals with schizophrenia (SZ) and 20 matched healthy participants (HC) were asked to identify emotions and social traits for actors in standardized face stimuli as well as brief video clips. Sound was removed from videos to remove all verbal cues. Clinical symptoms in SZ and delusional ideation in both groups were measured. Results showed a general impairment in affect recognition for both types of stimuli in SZ. However, the two groups did not differ in the judgments of trustworthiness, approachability, attractive- ness, and intelligence. Interestingly, in SZ, the severity of positive symptoms was correlated with higher ratings
Nano-Encrypted Morse Code: A Versatile Approach to Programmable and Reversible Nanoscale Assembly and Disassembly

While much work has been devoted to nanoscale assembly of functional materials, selective reversible assembly of components in the nanoscale pattern at selective sites has received much less attention. Exerting such a reversible control of the assembly process will make it possible to fine-tune the functional properties of the assembly and to realize more complex designs. Herein, by taking advantage of different binding affinities of biotin and desthiobiotin toward streptavidin, we demonstrate selective and reversible decoration of DNA origami tiles with streptavidin, including revealing an encrypted Morse code "NANO" and reversible exchange of uppercase letter "I" with lowercase "i". The yields of the conjugations are high (>90%), and the process is reversible. We expect this versatile conjugation technique to be widely applicable with different nanomaterials and templates.
Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs

β-Adrenergic hyporesponsiveness in congestive heart failure (CHF) is mediated, in part, by nitric oxide (NO). NO and brain natriuretic peptide (BNP) share cGMP as a second messenger. Left ventricul...
Neural programming

An attempt is made to solve difficult AI (artificial intelligence) problems, such as language comprehension, by introducing a novel scheme, the net program. The net program is a programmable net whose components are neural nets and procedural functions. A set of subroutines has been devised for neural programming as an enhancement to the procedural language C. The resulting language, called C/sup +NET/, makes possible and controls modular structuring, training, and activation of nets, and the interaction among nets and procedural functions. C/sup +NET/ has been applied on a model for natural language comprehension. >
Antigenic Relation of Type B H. Influenzae to Type 29 and Type 6 Pneumococci.

ConclusionFour strains of type 6 pneumococci and 4 strains of type 29 pneumococci have been encountered which appear to have one or more capsular antigens in common with 7 strains of type B H. influenzae which have recently beeen recovered from the spinal fluid or blood of infants. This relationship has been demonstrated by the capsular quellung method.
User Interests Identification on Twitter Using a Hierarchical Knowledge Base

Twitter, due to its massive growth as a social networking platform, has been in focus for the analysis of its user generated content for personalization and recommendation tasks. A common challenge across these tasks is identifying user interests from tweets. Semantic enrichment of Twitter posts, to determine user interests, has been an active area of research in the recent past. These approaches typically use available public knowledge-bases (such as Wikipedia) to spot entities and create entity-based user profiles. However, exploitation of such knowledge-bases to create richer user profiles is yet to be explored. In this work, we leverage hierarchical relationships present in knowledge-bases to infer user interests expressed as a Hierarchical Interest Graph. We argue that the hierarchical semantics of concepts can enhance existing systems to personalize or recommend items based on a varied level of conceptual abstractness. We demonstrate the effectiveness of our approach through a user study which shows an average of approximately eight of the top ten weighted hierarchical interests in the graph being relevant to a user’s interests.
Efficacy Observation of the Sequential Therapy of Traditional Chinese Medicine for Hypertensive Cerebral Hemorrhage

OBJECTIVE:To observe the clinical efficacy of traditional Chinese medicine for hypertensive cerebral hemorrhage.METHODS:179 patients with hypertensive cerebral hemorrhage were randomly divided into study group(90 cases)and control group(89 cases).Two groups were treated by routine western medicine,such as to reduce blood pressure and keep the stability of the vital sign during acute phase,rehabilitative exercises during convalescence.Study group was additionally given sequential therapy of traditional Chinese medicine using Tongqiao huoxue decoction of acute phase and Buyang huanwu decoction of convalescence phase as routine therapy.We record the survival status for 90 days,changes of hematoma volume for 14 days,score of neurological impairment before treatment,14 days,30 days and 90 days after treatment,and evaluation of ability of daily living(ADL)for 90 days after treatment.RESULTS:(1)Survival rate of study group and control group were 83.3% and 79.8%(Kaplan Meier method),respectively,Log Rank(Mantel-Cox)χ2 =0.359,P=0.549.(2)Hematoma absorption,reduction,fixation or enlargement were 24 cases,46 cases and 12 cases in study group at 14 days,and 10 cases,56 cases and 14 cases in control group(Z=-2.092,P=0.036).(3)The score of neurological impairment of both groups were decreasing,F=503.114,P=0.000;The decrease of the score of neurological impairment in study group was more significant than control group,F=178.481,P=0.000.The trend of the score of neurological impairment of both groups were not parallel,F=11.816,P=0.000.(4)Possibility of gradeⅠADL in study group was 1.992 times as in control group(Wald χ2 =5.184,P=0.023).CONCLUSION:The sequential therapy of traditional Chinese medicine for hypertensive cerebral hemorrhage could accelerate hematoma absorption,protect nerve cell,and improve ability of daily living.
79 A 21-YEAR-OLD FEMALE WITH POLYCYSTIC OVARY SYNDROME AND HEART FAILURE

Introduction This is a case of a 21-year-old female with a history of polycystic ovary syndrome (PCOS) that was subsequently diagnosed with heart failure. This diagnosis was made on the patient9s history and physical, CXR findings consistent with pulmonary edema, and elevated BNP levels. The patient did not have a family history of heart failure, nor did the patient herself have evidence of ischemic or valvular heart disease or prior viral infection, as determined by coronary angiogram, echocardiogram, and myocardial biopsy. Management The patient was treated successfully with vasodilators and diuretics. Once the patient9s clinical status started improving, an ACE inhibitor was started, and once tolerated, a beta-blocker was started as well. The patient was found, upon further evaluation, to have severe obstructive sleep apnea (OSA). CPAP therapy was instituted, and the patient was eventually discharged home in a much-improved condition with a stable oral heart failure regimen, in addition to a home CPAP device. Discussion In recent years, the presence of OSA has increasingly been linked to the development and progression of heart failure.1OSA has been shown to have a deleterious effect on normal neurohormonal pathways resulting in arrhythmias and myocardial ischemia. Invariably, most patients with PCOS are obese, and thus would be more prone than a non-obese individual to develop OSA. Recent clinical evidence has indicated that patients with PCOS, when compared with weight-matched controls, were significantly more likely to develop OSA.2The underlying reason(s) for why patients with PCOS might exhibit a greater amount of sleep disorders is still being examined. References 1ShaharE, WhitneyCW, RedlineS, et al.. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med2001;163:19-25.2GopalM, DuntleyS, UhlesM, et al.. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med2002;3:401-404.
Upper Cambrian and lowest Ordovician articulate brachiopods from the Arbuckle and Wichita Mountains, Oklahoma

Brachiopods assigned to eight genera and 15 species have been recovered from Upper Cambrian (Franconian and Trempealeauan Stages) and lowest Ordovician strata in the Arbuckle and Wichita Mountains of Oklahoma. Species of Ocnerorthis and Eoorthis occur in the Reagan Sandstone and Honey Creek Limestone of the Timbered Hills Group. Species of Billingsella appear in the Honey Creek and range upward into the overlying Fort Sill and Signal Mountain Limestones of the Arbuckle Group. Species of Cymbithyris, Finkelnburgia, Nanorthis, and Apheoorthis succeed each other upsection in the Signal Mountain Limestone. Five brachiopod zones and one subzone have been established that can be used to correlate the measured sections in the Arbuckle and Wichita Mountains, and to correlate with varying degrees of confidence from Oklahoma to similar brachiopod occurrences in other areas in the United States.
Mossbauer Studies of Ultrathin Magnetic Films of Fe/Ag(100)

Magnetic studies of very thin magnetic films, where only small amounts of material are present and where surface and interface effects may be almost completely dominant, represent a difficult challenge to the experimentalist. The Mossbauer effect utilizing Fe57 has proved to be very useful tool in such investigations, since under favorable circumstances it can provide important information about both the physical and electronic structure of the film as well as the magnetization, spin orientations, and dynamic processes. In contrast to some techniques, the Mossbauer effect generally probes all the Fe57 spins which are present in the film, even those which are not magnetically ordered, and thus makes it possible to determine if some spins are decoupled from the main part of the film. The isomer shift and the quadrupole splitting (in the case of cubic materials) can sometimes be used to infer the location of the atoms being probed (interior, exterior, or at the interface of a film); the magnetic hyperfine field can be related both to the degree of magnetic order as well as to the electronic structure, and the line intensities can be used to determine the orientation of the spins. Broadening of the spectra may also be used to study the nature of the spin dynamics in the film, Ultrathin (< 10 monolayer) Fe/Ag(100) films are particularly interesting for such studies because all of these phenomena prove to be useful in developing our understanding of these near 2-d systems.1,2 For further details concerning applications of the Mossbauer effect see the article by A, Morrish in these proceedings.
Electric field stimulated growth of Zn whiskers

We have investigated the impact of strong (∼104 V/cm) electric fields on the development of Zn whiskers. The original samples, with considerable whisker infestation were cut from Zn-coated steel floors and then exposed to electric fields stresses for 10-20 hours at room temperature. We used various electric field sources, from charges accumulated in samples irradiated by: (1) the electron beam of a scanning electron microscope (SEM), (2) the electron beam of a medical linear accelerator, and (3) the ion beam of a linear accelerator; we also used (4) the electric field produced by a Van der Graaf generator. In all cases, the exposed samples exhibited a considerable (tens of percent) increase in whiskers concentration compared to the control sample. The acceleration factor defined as the ratio of the measured whisker growth rate over that in zero field, was estimated to approach several hundred. The statistics of lengths of e-beam induced whiskers was found to follow the log-normal distribution known previo...
Pressure driven currents near magnetic islands in 3D MHD equilibria: Effects of pressure variation within flux surfaces and of symmetry

In toroidal, magnetically confined plasmas, the heat and particle transport is strongly anisotropic, with transport along the field lines sufficiently strong relative to cross-field transport that the equilibrium pressure can generally be regarded as constant on the flux surfaces in much of the plasma. The regions near small magnetic islands, and those near the X-lines of larger islands, are exceptions, having a significant variation of the pressure within the flux surfaces. It is shown here that the variation of the equilibrium pressure within the flux surfaces in those regions has significant consequences for the pressure driven currents. It is further shown that the consequences are strongly affected by the symmetry of the magnetic field if the field is invariant under combined reflection in the poloidal and toroidal angles. (This symmetry property is called “stellarator symmetry.”) In non-stellarator-symmetric equilibria, the pressure-driven currents have logarithmic singularities at the X-lines. In s...
Western Europe and North America

Out of the ashes of the Second World War, against all the dire predictions, emerged a new and powerful Europe. Nothing set the pattern of Europe’s recovery more than its growing unity. The free movement of people, goods, capital and services, and the introduction of a common commercial policy, began in 1948 with the Benelux customs union between Belgium, the Netherlands and Luxembourg. Political integration began with the establishment of the European Parliamentary Assembly in 1949.1 In 1951, as a result of the initiative of the French statesmen Robert Schumann (1886–1963) and Jean Monnet (1888–1979), there emerged the European Coal and Steel Community).2 Britain, with its traditional mistrust of continental proposals, refused to join. In 1957, under the Treaty of Rome, the European Economic Community (EEC) and the Common Market were established. Again, Britain refused to join. In 1959, Britain countered the EEC, by joining with Austria, Denmark, Norway, Portugal, Sweden, Switzerland, Liechtenstein, Finland and Iceland to form the European Free Trade Association (EFTA). In 1973 Britain, Ireland and Denmark joined the EEC. In 1987 Greece, Portugal and Spain became members.
Predicting Short-Term Cognitive Change from Longitudinal Neuroimaging Analysis

This paper introduces a framework for analyzing longitudinal neuroimaging datasets. We address the problem of detecting subtle, short-term changes in neural structure that are indicative of cognitive decline and correlate with risk factors for Alzheimer’s disease. Previous approaches have focused on separating populations with different risk factors based on gross changes, such as decreasing gray matter volume. In contrast, we introduce a new spatially-sensitive kernel that allows us to characterize individuals, as opposed to populations. We use this for both classification and regression, e.g., to predict changes in a subject’s cognitive test scores from neuroimaging data alone. In doing so, this paper presents the first evidence demonstrating that very small changes in white matter structure over a two year period can predict change in cognitive function in healthy adults.
Mitigating environmental impacts in advance: Evidence of cost and time savings for transportation projects

Abstract The traditional model for mitigating a transportation project’s environmental impacts typically operates project-by-project and delivers the mitigation just-in-time. In contrast, the newer practice of advance mitigation comprehensively assesses and mitigates impacts from one or multiple transportation projects before or during project planning, sometimes long before project construction begins. The practice has gained adherents for its potential to improve ecological outcomes, by better aligning mitigation and conservation goals. Advance mitigation also stands to reduce mitigation costs, an important secondary benefit for transportation agencies with constrained resources. Evidence of cost savings, however, has been piecemeal and anecdotal. This paper advances knowledge of advance mitigation’s financial impacts in two ways. First, it critically assesses the evidence about cost savings realized through advance mitigation, both through avoided up-front costs and reduced project delay. Second, it directly estimates the project time savings that might accrue with advance mitigation of state highway projects in California. Overall, the balance of evidence is encouraging for transportation agencies that would introduce the practice, and general agreement exists on its financial benefits. Considering project delays related only to the environmental process, we estimate advance mitigation could reduce delivery times by 1.3–5.0 months per project. Still, we also identify factors limiting comprehensive analysis. Transportation agencies adopting advance mitigation practices into their operations could use a pilot approach that includes rigorous environmental and mitigation cost accounting; such pilots would build needed empirical evidence of advance mitigation’s financial and ecological outcomes.
The Statistical Design and Interpretation of Microarray Experiments

This chapter reviews major issues related to design and interpretation of microarray experiments. Important aspects of design covered include identification of experimental objectives, treatment of batch effects, selection of replication and pooling levels, determining sample size for class comparison and class prediction, and optimal allocation of samples to arrays and labels in dual label experiments. Aspects of interpretation focus on class prediction issues, including case selection, external vs. internal validation, and pitfalls in cross-validation.
Irofulven binding and inactivation of purified and cellular redox-controlling proteins

1510 Irofulven (hydroxymethylacylfulvene) is a novel pro-apoptotic antitumor drug currently in clinical development. Irofulven reacts with DNA and proteins and both interactions may contribute to its induction of apoptosis. Previous studies demonstrated that treatment of cancer cells with irofulven elicits redox-mediated responses including (i) transient induction of a key redox-controlling protein, thioredoxin (Trx), (ii) activation of redox-dependent transcription factors NF-κB and AP-1, and (iii) pro-oxidative distortion of the cell redox status. Here we examined whether these effects could reflect functional damage to redox controlling proteins. Covalent binding of irofulven to purified human recombinant Trx was demonstrated using [14C]-labeled drug. The high affinity of irofulven for Trx is indicated by the inability of DTT and glutathione (at 25-fold molar excess over Trx) to reduce the level of irofulven-Trx adducts. Irofulven binding is accompanied by the inhibition of Trx reducing activity (IC50=4.5 μM). The drug also binds to and rapidly inactivates the Trx regenerating enzyme, thioredoxin reductase (TrxR), with an IC50 of 20 μM when drug is added directly to the reaction, while a brief (15 min) preincubation of TrxR with 10 μM irofulven resulted in complete inactivation. Purified glutathione-S-transferase is another redox protein that is adducted to and inactivated by irofulven, although this inhibition was weaker than that of Trx and TrxR (IC50 of 45 μM and 10 μM drug without and with a 1 h pre-incubation, respectively). The effects of irofulven on purified redox proteins were corroborated in prostate tumor LNCaP-Pro5 cells. [14C]-irofulven binds to cellular Trx as demonstrated using 2D PAGE of cytosolic extracts followed by autoradiography and Western blotting. Moreover, irofulven decreased the Trx activity in LNCaP-Pro5 cells (40% inhibition by 3 μM drug), despite a transient increase in Trx protein levels. Intracellular activities of TrxR and GST were also reduced by 3 μM drug (by ∼25 and 50%, respectively). In contrast to tumor cells, normal NCM 460 cells remain non-apoptotic even after prolonged treatment with 10 μM irofulven. These cells exhibit approximately 2-fold higher basal activity of Trx than LNCaP-Pro5 cells. Accordingly, treatment of NCM 460 cells with 10 μM irofulven caused only a transient and modest decrease (20%) in Trx activity and had no inhibitory effect on the activity of TrxR and GST. Collectively, the results suggest that targeting and inactivation of the Trx system and other redox-controlling proteins could be a factor in the cellular effects of irofulven, including the differential responses of tumor and normal cells. (Supported by CA78706, CA80936, and MGI Pharma, Inc).
‘Civilization’ and its subalterns

This article reviews Andrew Linklater’s Violence and Civilization in the Western States-Systems. Focusing upon the book’s explanation of the ‘European civilizing process’ in the modern era, it suggests that the account is limited by ‘civilizational isolationism’ and ‘metrocentric diffusion’. These analytic operations serve to minimise the agency and contributions of non-Western, colonial, and postcolonial actors to the global civilizing process. The occlusion of such agency and contributions, however, are not specific to this work, but reflect broader limitations in historical sociology writ large.
Attractiveness as a Function of Skin Tone and Facial Features: Evidence from Categorization Studies

Participants rated the attractiveness and racial typicality of male faces varying in their facial features from Afrocentric to Eurocentric and in skin tone from dark to light in two experiments. Experiment 1 provided evidence that facial features and skin tone have an interactive effect on perceptions of attractiveness and mixed-race faces are perceived as more attractive than single-race faces. Experiment 2 further confirmed that faces with medium levels of skin tone and facial features are perceived as more attractive than faces with extreme levels of these factors. Black phenotypes (combinations of dark skin tone and Afrocentric facial features) were rated as more attractive than White phenotypes (combinations of light skin tone and Eurocentric facial features); ambiguous faces (combinations of Afrocentric and Eurocentric physiognomy) with medium levels of skin tone were rated as the most attractive in Experiment 2. Perceptions of attractiveness were relatively independent of racial categorization in both experiments.
Insights into the Regulation of Collecting Duct Homeostasis by Small Noncoding RNAs

Tubulointerstitial fibrosis is a common, convergent hallmark of progression to renal failure in many forms of CKD. It is characterized by inflammation, tubular injury, loss of vascular integrity, and proliferation of fibroblasts and myofibroblasts, leading to excessive secretion of extracellular
Reverse Mathematics Is Computable for Interval Computations

For systems of equations and/or inequalities under interval uncertainty, interval computations usually provide us with a box whose all points satisfy this system. Reverse mathematics means finding necessary and sufficient conditions, i.e., in this case, describing the set of all the points that satisfy the given system. In this paper, we show that while we cannot always exactly describe this set, it is possible to have a general algorithm that, given \(\varepsilon >0\), provides an \(\varepsilon \)-approximation to the desired solution set.
Adaptive NK Cells Resist Regulatory T-cell Suppression Driven by IL37

Natural killer (NK) cells are capable of fighting viral infections and cancer. However, these responses are inhibited by immune suppressor cells in the tumor microenvironment. Tumor progression promotes the recruitment and generation of intratumoral regulatory T cells (Treg), associated with a poor prognosis in cancer patients. Here, we show that canonical NK cells are highly susceptible to Treg-mediated suppression, in contrast to highly resistant CD57+ FceRγ-NKG2C+ adaptive (CD56+CD3-) NK cells that expand in cytomegalovirus exposed individuals. Specifically, Tregs suppressed canonical but not adaptive NK-cell proliferation, IFNγ production, degranulation, and cytotoxicity. Treg-mediated suppression was associated with canonical NK-cell downregulation of TIM3, a receptor that activates NK-cell IFNγ production upon ligand engagement, and upregulation of the NK-cell inhibitory receptors PD-1 and the IL1 receptor family member, IL1R8 (SIGIRR or TIR8). Treg production of the IL1R8 ligand, IL37, contributed to the phenotypic changes and diminished function in Treg-suppressed canonical NK cells. Blocking PD-1, IL1R8, or IL37 abrogated Treg suppression of canonical NK cells while maintaining NK-cell TIM3 expression. Our data uncover new mechanisms of Treg-mediated suppression of canonical NK cells and identify that adaptive NK cells are inherently resistant to Treg suppression. Strategies to enhance the frequency of adaptive NK cells in the tumor microenvironment or to blunt Treg suppression of canonical NK cells will enhance the efficacy of NK-cell cancer immunotherapy. Cancer Immunol Res; 6(7); 766-75. ©2018 AACR.
Characterization and Modification of Adhesion in Dry and Wet Environments in Thin-Film Parylene Systems

Parylene C is a thin-film polymer used as a biocompatible barrier layer in biomedical implants and implantable MEMS; free-film Parylene C may serve as both the substrate and insulation in polymer-based microdevices, a growing branch of biomedical technology. The adhesion of vapor deposited Parylene C, particularly when exposed to wet, in vivo environments, is a critical determinant of device lifetime for such polymer-based implants. This paper explores several novel strategies for improving the adhesion of multi-layer Parylene structures, including thermal annealing and the use of several chemical interposer layers. Interfacial adhesion of Parylene-Parylene and Parylene-platinum-Parylene films was examined using a standard T-peel test to quantify adhesion and measure film integrity under chronic exposure to saline up to two years. Improved adhesion and barrier properties in Parylene-Parylene films resulted from the inclusion of diamond-like carbon and ethylene glycol diacrylate layers. Thermal annealing improved Parylene film integrity in wet environments but was insufficient for improving the integrity of Parylene-platinum interfaces. A 100-fold increase in adhesive strength at such interfaces was achieved using a commercially available adhesion promoter, and the corresponding improvements in resistance to moisture driven delamination were observed. X-ray diffraction and X-ray photoelectron spectroscopy results are provided to highlight the role of film morphology and surface composition in adhesion integrity. [2018-0076]
Paired bulk organic and individual amino acid δ15N analyses of bivalve shell periostracum: A paleoceanographic proxy for water source variability and nitrogen cycling processes

Abstract Developing high-resolution, well-dated, marine proxies of environmental, climatic, and oceanographic conditions is critical in order to advance our understanding of the ocean’s role in the global climate system. While some work has investigated bulk and compound specific stable nitrogen isotope (δ15N) values in bivalve shells as proxies for environmental variability, the small concentrations of nitrogen found in the organic matrix of the shell calcium carbonate (hereafter carbonate) makes developing high resolution records challenging. This study investigates the potential of using the bulk and amino acid δ15N values of bivalve periostracum, the protein layer on the outside of the shell, as a proxy archive of nitrogen cycling processes and water source variability. Bulk δ15N values were measured on the periostracum, carbonate, and adductor muscle of Arctica islandica shells collected in the Gulf of Maine. Increased variability of isotopic values across growth lines compared to along growth lines support mechanistic reasoning based on growth processes that periostracum is recording changes in δ15N values over the course of the clam’s lifetime (up to 500 years). In addition, the statistically significant relationship between periostracum δ15N values and contemporaneous carbonate δ15N values of the same shell (r = 0.82, p Compound specific δ15N analyses of the periostracum of A. islandica shells were used to determine that the calculated trophic position of the clams in this study (1.4 ± 0.4) did not change significantly between 1783 and 1997. Phenylalanine δ15N values over the last 70 years show similar trends to that of the bulk record, suggesting that changes in bulk δ15N values over that time period are related to changes in baseline δ15N values. Periostracum δ15N values from shells collected in the western Gulf of Maine have decreased by ∼1‰ since the mid-1920s. This trend (−0.008‰/year) is not statistically different from the trend of previously published δ15N values of deep-sea corals from the entrance to the Gulf of Maine over the same time period. This coral record has been shown to indicate a shift in water source in the region and therefore the similarity between the two records suggest that changes in periostracum δ15N values are reflecting broader North Atlantic hydrographic changes. Our study introduces a new, high-resolution, and absolutely dated paleoceanographic proxy of baseline δ15N values, presenting the opportunity for future reconstructions of aspects of nitrogen cycling and water source changes in the global oceans.
Low-dose versus high-dose methadone for the management of neonatal abstinence syndrome

Objectives: The primary objective was to compare median time to symptom relief (time from methadone initiation until two consecutive modified Finnegan [neonatal abstinence syndrome, NAS] scores 0.275 mg/kg/day) methadone. Secondary objectives included assessment of factors associated with symptom relief. Design: Retrospective cross-sectional study. Setting: Ninety-nine bed neonatal intensive care unit within a tertiary-care academic hospital. Participants: Seventy-two neonates who received methadone for NAS over a 7.5-year period. Main outcome measures(s): Kaplan-Meier curves with a log-rank test and a stepwise Cox proportional-hazard model were used to analyze outcomes. Results: The median dose for the low-dose (n = 40) and high-dose (n = 32) groups were 0.19 mg/kg/day (interquartile range [IQR], 0.12-0.24) divided every 6-12 hours and 0.4 mg/kg/day (0.3-0.44) divided every 6-8 hours, respectively. The median time to symptom relief was higher in the low-dose versus high-dose groups, 9.3 (5.8-24.6) versus 6.0 (5.4-12.5) hours, respectively (p = 0.014). Low-dose males had a longer time to symptom resolution than other groups (p = 0.008). Female premature neonates (<37 weeks gestation) had a shorter time to symptom relief than term neonates [adjusted hazard ratio = 2.96 (1.02-8.62)]. The median total duration of methadone was shorter but not statistically significant between high- versus low-dose groups, 17.5 (IQR: 11.0-25.0) versus 21.0 days (IQR: 10.0-28.0), respectively (p = 0.483). Conclusions: Neonates receiving high-dose methadone had a significantly shorter time to symptom relief. Differences in sex were noted in response to therapy with low-dose males having a longer time to symptom relief and premature neonates a shorter time to symptom relief.
Isotropic 3D Super Resolution Imaging with Self-Bending Point Spread Function

We introduce a self-bending point spread function (SB-PSF) based on Airy beams for three-dimensional (3D) super-resolution fluorescence imaging. We designed a side-lobe-free SB-PSF for the incoherent fluorescence emission and implemented a two-channel detection scheme for the SB-PSF to enable unambiguous 3D localization of fluorescent molecules. The lack of diffraction and the propagation-dependent lateral bending make the SB-PSF ideal for precise 3D localization of molecules over a large imaging depth. Using this SB-PSF, we demonstrated super-resolution imaging with isotropic localization precisions of 10-15 nm in all three dimensions over a 3 μm imaging depth without sample scanning.
Edwards Program for Transcatheter Aortic Valve Implantation

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic valve disease. Multiple favorable clinical trial results have led to the expeditious implementation of TAVR across an ever-expanding population of patients. Over time, increasing operator experience and ongoing progress in device design have led to substantial improvements in procedural success. Central to the advancement of TAVR has been the Edwards (Edwards Lifesciences, Irvine, CA) family of transcatheter aortic valve systems, which has been evaluated in many of the major landmark clinical trials of TAVR to date. From the initial experience of balloon-expandable valves with Dr. G. Alain Cribier, Edwards Lifesciences was instrumental in the development balloon-expandable valves, including SAPIEN, SAPIEN XT, and most recently SAPIEN 3. This chapter explores the history of and wealth of data accrued from the Edwards family of transcatheter aortic valve systems.
Exploring Perspectives from Internal Medicine Clerkship Directors in the USA on Effective Narrative Evaluation: Results from the CDIM National Survey.

Clinical performance evaluations play a critical role in determining medical school clerkship grades. This study aimed to provide clarification from clerkship directors in internal medicine on what constitutes an effective and informative narrative description of student performance. In September 2016, the Clerkship Directors in Internal Medicine (CDIM) electronically administered its annual, voluntary, and confidential cross-sectional survey of its US membership. One section of the survey asked six questions regarding the helpful components of an effective narrative evaluation. Respondents were asked to rate the effectiveness of elements contained within narrative evaluations of students. Ninety-five CDIM members responded to the survey with an overall response rate of 74.2%. Descriptions of skills and behaviors were felt to be the most important, followed by a description of the overall synthetic or global assessment level of the student. Descriptions of personality and attitude were the next highest rated feature followed by adjectives describing performance. Length was felt to be the least important component. In free-text comments, several respondents indicated that direct observation of performance and specific examples of skills and behaviors are also desirable. Narrative evaluations of students that explicitly comment on skills, behaviors, and an overarching performance level of the learner are strongly preferred by clerkship directors. Direct observation of clinical performance and giving specific examples of such behaviors give evaluations even more importance. Faculty development on evaluation and assessment should include instruction on these narrative assessment characteristics.