cssi/SciSciGPT-SciSciNet huggingface dataset:
2-Aminoadipic acid is a marker of protein carbonyl oxidation in the aging human skin: effects of diabetes, renal failure and sepsis

We hypothesized that the epsilon-amino group of lysine residues in longlived proteins oxidatively deaminates with age forming the carbonyl compound, allysine (alpha-aminoadipic acid-delta-semialdehyde), which can further oxidize into 2-aminoadipic acid. In the present study, we measured both products in insoluble human skin collagen from n=117 individuals of age range 10-90 years, of which n=61 and n=56 were non-diabetic and diabetic respectively, and a total of n=61 individuals had either acute or chronic renal failure. Allysine was reduced by borohydride into 6-hydroxynorleucine and both products were measured in acid hydrolysates by selective ion monitoring gas chromatography (GC)-MS. The results showed that 2-aminoadipic acid (P<0.0001), but not 6-hydroxynorleucine (P=0.14), significantly increased with age reaching levels of 1 and 0.3 mmol/mol lysine at late age respectively. Diabetes in the absence of renal failure significantly (P<0.0001) increased 2-aminoadipic acid up to <3 mmol/mol, but not 6-hydroxynorleucine (levels<0.4 mmol/mol, P=0.18). Renal failure even in the absence of diabetes markedly increased levels reaching up to <0.5 and 8 mmol/mol for 6-hydroxynorleucine and 2-aminoadipic acid respectively. Septicaemia significantly (P<0.0001) elevated 2-aminoadipic acid in non-diabetic, but not diabetic individuals, and mildly correlated with other glycoxidation markers, carboxymethyl-lysine and the methylglyoxal-derived products, carboxyethyl-lysine, argpyrimidine and MODIC (methylglyoxal-derived imidazolium cross-link). These results provide support for the presence of metal-catalysed oxidation (the Suyama pathway) in diabetes and the possible activation of myeloperoxidase during sepsis. We conclude that 2-aminoadipic acid is a more reliable marker for protein oxidation than its precursor, allysine. Its mechanism of formation in each of these conditions needs to be elucidated.
Analysis of slide exploration strategy of cytologists when reading digital slides

Cytology is the sub-domain of Pathology that deals mainly with the diagnosis of cellular changes caused by disease. Current clinical practice involves a cytotechnologist that manually screens glass slides containing fixed cytology material using a light microscope. Screened slides are then forwarded to a specialized pathologist, a cytopathologist, for microscopic review and final diagnostic interpretation. If no abnormalities are detected, the specimen is interpreted as "normal", otherwise the abnormalities are marked with a pen on the glass slide by the cytotechnologist and then are used to render a diagnosis. As Pathology is migrating towards a digital environment it is important to determine whether these crucial screening and diagnostic tasks can be performed as well using digital slides as the current practice with glass slides. The purpose of this work is to make this assessment, by using a set of digital slides depicting cytological materials of different disease processes in several organs, and then to analyze how different cytologists including cytotechnologists, cytopathologists and cytotechnology-trainees explored the digital slides. We will (1) collect visual search data from the cytologists as they navigate the digital slides, as well as record any electronic marks (annotations) made by the cytologists; (2) convert the dynamic visual search data into a static representation of the observers' exploration strategy using 'search maps'; and (3) determine slide coverage, per viewing magnification range, for each group. We have developed a virtual microscope to collect this data, and this interface allows for interactive navigation of the virtual slide (including panning and zooming), as well as annotation of reportable findings. Furthermore, all interactions with the interface are time stamped, which allows us to recreate the cytologists' search strategy.
Damage Assessment of Historic Earthen Sites after the 2007 Earthquake in Peru

The Pisco earthquake of August 15, 2007 resulted in 519 deaths and 1366 injured, with a total of 650,000 people affected and 80,000 dwellings damaged. Preliminary reports indicated that significant earthen sites were damaged. A few months after the earthquake a rapid assessment to better understand the failure of the affected sites was performed by a multidisciplinary team convened by the Getty Conservation Institute (GCI) in response to a request from the Instituto Nacional de Cultura del Peru (INC). This paper presents the highlights of that evaluation and its implications for the future design and retrofit of earthen buildings.
Advances in memory research: single-neuron recordings from the human medial temporal lobe aid our understanding of declarative memory.

Purpose of reviewTo gain a complete understanding of how the brain functions, both in illness and good health, data from multiple levels of analysis must be integrated. Technical advances have made direct recordings of neuronal activity deep inside the human brain tractable, providing a rare glimpse
Doing radio, making friends, and having fun: Exploring the motivations of independent audio podcasters

This article presents an exploratory, empirical investigation of one under-studied type of user-generated content: independent audio podcasting. While other forms of user-generated content, particularly blogging, have received significant attention from scholars, research on podcasting, particularly on podcasters themselves, is still uncommon. I address this gap through the development of a preliminary profile of independent podcasters and their motivations for podcasting. Results from a web-based qualitative questionnaire indicate that podcasters fit the profile of Pro-Ams (older, educated, professional males) working primarily in the niche markets of the long tail. The study found six major categories of motivations for podcasting: technology/media, content, interpersonal, personal, process, and financial. Comparisons are also drawn between motivations of the podcasters reported in this study and previous research on the motivations of bloggers.
Management of familial hypercholesterolaemia in children and adolescents.

Familial hypercholesterolaemia is a disorder of low-density lipoprotein (LDL) cholesterol metabolism, which is associated with the onset of vascular changes associated with coronary heart disease in childhood. This disorder has co-dominant transmission with a prevalence of one in 500 in the general population. Cascade screening is the most effective method of identifying children. Children in the at-risk group should have their cholesterol levels checked between the age of 2 and 10 years. Children with LDL cholesterol levels = 3.4 mmol/L are likely to suffer from this disorder, although at this level there is a significant false positive rate. Molecular genetic testing is available for the LDL receptor gene, APOB gene and the PCSK9 gene. This is the most specific test for familial hypercholesterolaemia but has a false negative rate of 2050%. Once diagnosed, treatment should be considered in children with an LDL cholesterol level = 4.9 mmol/L. If the child has two other risk factors or a positive family history, this threshold should be lowered to =4.1 mmol/L. Guidelines recommend that treatment should be commenced by the age of 10 years, although some advise waiting until menarche in females. Statin therapy is currently recommended as first line treatment. Randomised placebo trials have shown that statin therapy reduces LDL cholesterol levels by 25% and is not associated with increased risk of adverse events. These are short-term studies, and longer follow-up will be required to definitively prove efficacy and safety.
Influence of cold on liver lipids of rats at different levels of dietary protein.

The effects of feeding diets containing various levels of casein, and of exposure to an environment of 6Â°,on food intake, growth and liver lipid composition of rats were studied. Rats exposed to cold ate more of all diets than rats maintained at normal ambient temperature. The growth rate at 6Â°was greater than at 23.5Â°when they were fed diets containing 5% protein or less, but on diets of 10% protein or more, growth rate was less. Liver triglycA©ride levels rose with decreased dietary protein intake in rats maintained at normal ambient temperature. However, exposing animals to 6Â°had a lipotropic effect. In contrast to the response of liver triglycA©rides, the rise of phospholipid levels, at low protein intake, was not prevented by exposing the animals to 6Â°. J. Nutr. 102: 401-408, 1972.
Oritavancin: A Long-Half-Life Lipoglycopeptide

Oritavancin is a lipoglycopeptide antibiotic that has been shown to be effective for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). This antibiotic has multiple mechanisms of action including inhibiting peptidoglycan cell wall synthesis and disrupting bacterial cell membrane, leading to cell death. Oritavancin is highly active against common gram-positive pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci. The drug is administered as a single intravenous dose of 1200 mg over 3 hours in adult patients, and because of its terminal half-life of 393 hours, repeat dosing is not required in the treatment of ABSSIs. There is a very slow elimination from tissue sites, and no dosing adjustments are required for renal or hepatic insufficiency. Two clinical trials have demonstrated noninferiority compared with vancomycin in the treatment of ABSSSIs. Other than liver enzyme elevation and the occurrence of osteomyelitis, oritavancin has been associated with adverse events similar to those of vancomycin in follow-up for up to 60 days. Patients should be monitored for osteomyelitis and alternate therapy given in the case of confirmed or suspected osteomyelitis. Although oritavancin is an attractive antibiotic to consider in the outpatient area, its efficacy and safety in the treatment of other sites of infection are yet to be established.
Postprandial cholecystokinin release and gastric emptying in patients with bulimia nervosa

This study was designed to investigate the biological underpinnings of the observed deficit in satiety in patients with bulimia nervosa. Eight women with bulimia nervosa and 10 age- and weight-matched control subjects consumed three laboratory meals consisting of 200, 400, and 600 g of a radiolabeled liquid meal. For 1 h after each meal, blood samples were obtained at 10-min intervals for measurement of cholecystokinin concentration and gastric emptying was measured. Subjects also completed perceptual rating scales at 10-min intervals. Compared with control subjects, patients with bulimia nervosa showed a blunting of postprandial cholecystokinin release, particularly with larger meal sizes, as well as delayed gastric emptying. Increasing meal size was associated with increased desire to binge eat in patients but not in control subjects. These data lend support to a model in which increased gastric capacity, perhaps resulting from repeated binge eating, gives rise to delayed gastric emptying and blunted postprandial cholecystokinin release, leading to an impaired satiety response, which tends to perpetuate the illness.
L‐Arginine and Antineutrophil Serum Enable Venular Control of Capillary Perfusion in Hypercholesterolemic Rats

Objective:The purpose of this study was to investigate and counteract dysfunctional control of capillary flow in hypercholesterolemia. Capillary flow is controlled by arteriolar tone, which in turn is influenced by mediators released from closely paired venules in a mechanism that involves nitric oxide (NO). However, venular control of capillary flow is altered with hypercholesterolemia. Methods:Rats were given a normal or high-cholesterol diet before measurements of mesenteric capillary red blood cell velocity. The arteriolar pathway leading to the capillary was videotaped to measure the percent of the surrounding area (within 15 µm) that was occupied by a venule (% pairing). Results:Venule-paired arterioles were significantly smaller in hypercholesterolemia compared with normocholesterolemia, corresponding to slower capillary flow. A positive correlation between capillary velocity and % pairing observed in normocholesterolemia was not observed during NO synthase inhibition or in hypercholesterolemic rat...
Quantitative Assessment of Regional Myocardial Function with MR-Tagging in a Multi-Center Study: Interobserver and Intraobserver Agreement of Fast Strain Analysis with Harmonic Phase (HARP) MRI

Purpose. To assess the reproducibility of Harmonic Phase (HARP) analysis of myocardial MR tagged images acquired in the Multi-Center Study of Atherosclerosis (MESA). Methods. Using the HARP method, three independent observers performed two separate quantitative strain analyses of myocardial cine MR-tagging images blindly in 24 participants. The images were obtained in four different centers and analyzed at a single core lab. Each study comprised 3 short-axis slices subdivided in 12 segments (24 � 3 � 12 = 864 segments), each with three layers. Normal strains (circumferential [Ecc] and radial [Err]), principal strains (Lambda1, Lambda2), and the angle a (between EccLambda2) were calculated. Intraclass correlation coefficient (R) for peak systolic strains, and all pooled systolic and diastolic strain data were used to determine inter- and intraobserver agreement. Two observers also visually graded study quality. R values were related to the image quality in different myocardial regions and layers. Results. Overall, HARP yielded an excellent inter- and intraobserver agreement for peak systolic strain data (for Ecc, R = 0.84 and 0.89, respectively) and all systolic pooled data (for Ecc, interobserver R = 0.82, intraobserver R = 0.69–0.76). Both inter and intraobserver agreement were lower for diastolic pooled data (R = 0.69 and 0.58–0.62, respectively). There was a direct relationship between image quality and performance of the HARP analysis, with increasing inter- and intraobserver R values in studies with longer tag persistence. Both inter- and intraobserver agreement were better in the anterior and septal myocardial regions, and in the midwall layer. The intraobserver agreement was similar among the three observers. Conclusion. Employing the HARP method for quantitative strain analysis of myocardial MR tagged images provides a high inter- and intraobserver agreement. These good results are obtained in case of good to excellent MR image quality.
Evidence for the importance of π-π-attractive interactions in Enantioselective Diels-Alder reactions chiral catalysts of type (RO)2TiCl2

Abstract Reaction of diol 4 with Ti(Oi-Pr) 4 followed by SiCl 4 results in formation of the Ti (IV) complex 5 which is an exceptionally effective catalyst for enantioselective Diels-Alder reactions. The origin of the high enantioselectivities which have been observed (>95 : 5) probably lies in attractive π-π interaction between an aromatic group and the dienophile as indicated in formula 7 .
Constraint and Integer Programming in OPL

In recent years, it has been increasingly recognized that constraint and integer programming have orthogonal and complementary strengths in stating and solving combinatorial optimization applications. In addition, their integration has become an active research topic. The optimization programming language OPL was a first attempt at integrating these technologies both at the language and at the solver levels. In particular, OPL is a modeling language integrating the rich language of constraint programming and the ability to specify search procedures at a high level of abstraction. Its implementation includes both constraint and mathematical programming solvers, as well as some cooperation schemes to make them collaborate on a given problem. The purpose of this paper is to illustrate, using OPL, the constraint-programming approach to combinatorial optimization and the complementary strengths of constraint and integer programming.
Cooperative multihop broadcast for wireless networks

We address the minimum-energy broadcast problem under the assumption that nodes beyond the nominal range of a transmitter can collect the energy of unreliably received overheard signals. As a message is forwarded through the network, a node will have multiple opportunities to reliably receive the message by collecting energy during each retransmission. We refer to this cooperative strategy as accumulative broadcast. We seek to employ accumulative broadcast in a large scale loosely synchronized, low-power network. Therefore, we focus on distributed network layer approaches for accumulative broadcast in which loosely synchronized nodes use only local information. To further simplify the system architecture, we assume that nodes forward only reliably decoded messages. Under these assumptions, we formulate the minimum-energy accumulative broadcast problem. We present a solution employing two subproblems. First, we identify the ordering in which nodes should transmit. Second, we determine the optimum power levels for that ordering. While the second subproblem can be solved by means of linear programming, the ordering subproblem is found to be NP-complete. We devise a heuristic algorithm to find a good ordering. Simulation results show the performance of the algorithm to be close to optimum and a significant improvement over the well known BIP algorithm for constructing energy-efficient broadcast trees. We then formulate a distributed version of the accumulative broadcast algorithm that uses only local information at the nodes and has performance close to its centralized counterpart.
Action of apolipoprotein A-I on lecithin-cholesterol vesicles in model bile

Gallstone disease afflicts 12% of the adult US population and annual medical expenses relating to gallstones are over $2 billion. Understanding the gallstone pathogenic pathway will pave the way for preventive therapies. The primary transporters of cholesterol in bile are the lecithin-cholesterol vesicles. Gallstones are formed due the nucleation of cholesterol from lecithin-cholesterol vesicles of cholesterol-supersaturated bile. The kinetics of cholesterol nucleation is influenced by various biliary species, two of them being Apolipoprotein A-I, an anti-nucleating agent and Phospholipase C, a pro-nucleating agent. In this study, the influence of Apolipoprotein A-I on lecithin-cholesterol vesicles of supersaturated bile is examined in the presence of Phospholipase C. Also, the fundamental understanding gained can be potentially applied to the study of heart disease as both the diseases share a similar mechanistic pathway.
Different Timescales for the Neural Coding of Consonant and Vowel Sounds

Psychophysical, clinical, and imaging evidence suggests that consonant and vowel sounds have distinct neural representations. This study tests the hypothesis that consonant and vowel sounds are represented on different timescales within the same population of neurons by comparing behavioral discrimination with neural discrimination based on activity recorded in rat inferior colliculus and primary auditory cortex. Performance on 9 vowel discrimination tasks was highly correlated with neural discrimination based on spike count and was not correlated when spike timing was preserved. In contrast, performance on 11 consonant discrimination tasks was highly correlated with neural discrimination when spike timing was preserved and not when spike timing was eliminated. These results suggest that in the early stages of auditory processing, spike count encodes vowel sounds and spike timing encodes consonant sounds. These distinct coding strategies likely contribute to the robust nature of speech sound representations and may help explain some aspects of developmental and acquired speech processing disorders.
The Four Pillars of Constitutional Doctrine

Constitutional interpretation, and thus constitutional doctrine, is inevitably controversial. Judges, scholars, lawyers, politicians, and the American public all disagree among themselves, not only about the correct constitutional outcome but even about the right approach to constitutional interpretation. We are unlikely to reach consensus on whether we should read the Constitution as a living and evolving document or instead read it in accordance with a fixed original meaning, much less on whether it does or does not protect campaign contributions, reproductive rights, affirmative action policies, gun ownership, or any of the other contested issues that have recently come before the Supreme Court. Nevertheless, I believe that we can find an important degree of common ground by focusing on the essential elements of sound constitutional doctrine as an abstract matter. Even if we cannot identify standards to evaluate outcomes or approaches, we can at least specify the minimum requirements for sound doctrine. Thus we can come to agreement about how to evaluate the Supreme Court (and its Justices) at some basic level. In this Article, I identify the four necessary pillars underlying sound constitutional doctrine. By doing so, I hope to begin a conversation about the courts and the Constitution that, unlike most such conversations, does not end in a political impasse. The Article proceeds as follows. Part I sketches out the four pillars of constitutional doctrine. Part II provides a practical illustration of these essential principles by using them to test the soundness of a recent little-noticed Supreme Court case that I believe violates all four principles. Part III broadens the focus to examine other recent Supreme Court cases, demonstrating the usefulness of my four pillars to critique judicial output independent of political valence.
Low frequency transcranial magnetic stimulation on the posterior parietal cortex induces visuotopically specific neglect-like syndrome

The visuo-parietal (VP) region of the cerebral cortex is critically involved in the generation of orienting responses towards visual stimuli. In this study we use repetitive transcranial magnetic stimulation (rTMS) to unilaterally and non-invasively deactivate the VP cortex during a simple spatial visual detection task tested in real space. Adult cats were intensively trained over 4 months on a task requiring them to detect and orient to a peripheral punctuate static LED presented at a peripheral location between 0° and 90°, to the right or left of a 0° fixation target. In 16 different interleaved sessions, real or sham low frequency (1 Hz) rTMS was unilaterally applied during 20 min (1,200 pulses) to the VP cortex. The percentage of mistakes detecting and orienting to contralateral visual targets increased significantly during the 15–20 min immediately following real but not sham rTMS. Behavioral deficits were most marked in peripheral eccentricities, whereas more central locations were largely unaffected. Performance returned to baseline (pre-TMS) levels when animals were tested 45 min later and remained in pre-TMS levels 24 h after the end of the stimulation. Our results confirm that the VP cortex of the cat is critical for successful detection and orienting to visual stimuli presented in the corresponding contralateral visual field. In addition, we show that rTMS disrupts a robust behavioral task known to depend on VP cortex and does so for the far periphery of the visual field, but not for more central targets.
Coherent phonon-grain boundary scattering in silicon inverse opals.

We report measurements and modeling of thermal conductivity in periodic three-dimensional dielectric nanostructures, silicon inverse opals. Such structures represent a three-dimensional “phononic crystal” but affect heat flow instead of acoustics. Employing the Stober method, we fabricate high quality silica opal templates that on filling with amorphous silicon, etching and recrystallizing produce silicon inverse opals. The periodicities and shell thicknesses are in the range 420–900 and 18–38 nm, respectively. The thermal conductivity of inverse opal films are relatively low, ∼0.6–1.4 W/mK at 300 K and arise due to macroscopic bending of heat flow lines in the structure. The corresponding material thermal conductivity is in the range 5–12 W/mK and has an anomalous ∼T1.8 dependence at low temperatures, distinct from the typical ∼T3 behavior of bulk polycrystalline silicon. Using phonon scattering theory, we show such dependence arising from coherent phonon reflections in the intergrain region. This is con...
Does family therapy reduce health care costs for more than the identified patient

One of the most intriguing results of the research on the cost effectiveness of family therapy is the possibility that family-based treatment will benefit a number of family members – not just those who are the focus of treatment
Seismic Hazard in the Nation's Breadbasket:

The USGS National Seismic Hazard Maps were updated in 2014 and included several important changes for the central United States (CUS). Background seismicity sources were improved using a new moment...
Desiccating stress-induced disruption of ocular surface immune tolerance drives dry eye disease

Dry eye is an allegedly autoimmune disorder for which the initiating mechanisms and the targeted antigens in the ocular surface are not known, yet there is extensive evidence that a localized T helper type 1 (Th1)/Th17 effector T cell response is responsible for its pathogenesis. In this work, we explore the reconciling hypothesis that desiccating stress, which is usually considered an exacerbating factor, could actually be sufficient to skew the ocular surface's mucosal response to any antigen and therefore drive the disease. Using a mouse model of dry eye, we found that desiccating stress causes a nuclear factor kappa B (NF-κB)- and time-dependent disruption of the ocular surface's immune tolerance to exogenous ovalbumin. This pathogenic event is mediated by increased Th1 and Th17 T cells and reduced regulatory T cells in the draining lymph nodes. Conversely, topical NF-κB inhibitors reduced corneal epithelial damage and interleukin (IL)-1β and IL-6 levels in the ocular surface of mice under desiccating stress. The observed effect was mediated by an augmented regulatory T cell response, a finding that highlights the role of mucosal tolerance disruption in dry eye pathogenesis. Remarkably, the NF-κB pathway is also involved in mucosal tolerance disruption in other ocular surface disorders. Together, these results suggest that targeting of mucosal NF-κB activation could have therapeutic potential in dry eye.
Neural Networks Leverage Corpus-wide Information for Part-of-speech Tagging

We propose a neural network approach to benefit from the non-linearity of corpuswide statistics for part-of-speech (POS) tagging. We investigated several types of corpus-wide information for the words, such as word embeddings and POS tag distributions. Since these statistics are encoded as dense continuous features, it is not trivial to combine these features comparing with sparse discrete features. Our tagger is designed as a combination of a linear model for discrete features and a feed-forward neural network that captures the non-linear interactions among the continuous features. By using several recent advances in the activation functions for neural networks, the proposed method marks new state-of-the-art accuracies for English POS tagging tasks.
Surface faceting and elemental diffusion behaviour at atomic scale for alloy nanoparticles during in situ annealing

The catalytic performance of nanoparticles is primarily determined by the precise nature of the surface and near-surface atomic configurations, which can be tailored by post-synthesis annealing effectively and straightforwardly. Understanding the complete dynamic response of surface structure and chemistry to thermal treatments at the atomic scale is imperative for the rational design of catalyst nanoparticles. Here, by tracking the same individual Pt3Co nanoparticles during in situ annealing in a scanning transmission electron microscope, we directly discern five distinct stages of surface elemental rearrangements in Pt3Co nanoparticles at the atomic scale: initial random (alloy) elemental distribution; surface platinum-skin-layer formation; nucleation of structurally ordered domains; ordered framework development and, finally, initiation of amorphization. Furthermore, a comprehensive interplay among phase evolution, surface faceting and elemental inter-diffusion is revealed, and supported by atomistic simulations. This work may pave the way towards designing catalysts through post-synthesis annealing for optimized catalytic performance.
Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast-enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in a murine model.

We used a transgenic mouse model of breast cancer to investigate contrast enhancement of ductal carcinoma in situ (DCIS) on clinical dynamic contrast material–enhanced (DCE) MR images of the breast, and we have shown via two independent routes—DCE MR imaging and x-ray fluorescence microscopy—that after injection of gadodiamide, there is gadolinium uptake inside ducts distended with murine DCIS.
Thromboxane A2 Receptor Biology and Function of a Peculiar Receptor that Remains Resistant for Therapeutic Targeting

While blood platelets express several G-protein-coupled receptors (GPCRs) that play pivotal roles in their activation, several diseases, for example thrombotic disorders, may develop if these receptors are inappropriately activated. Thus, these receptors have been the subject of investigations to design therapeutic interventions for managing multiple thrombosis-based disease states. One such GPCR, the thromboxane A(2) receptor (TPR), remains resistant to such interventions. The present review provides a critical examination of the binding, structural biology, and signaling of TPRs. The review also provides a rationale for using principles of "drug rediscovery" as an alternative/viable approach for the therapeutic targeting of TPRs. To this end, it is noteworthy that many US Food and Drug Administration (FDA)-approved drugs have been found to selectively (and nonselectively) block TPR-mediated functional responses, for example platelet aggregation, as described in this review. Therefore, while none of the antagonists, thus far developed for targeting TPRs, have made it into clinical use, this peculiar receptor can be antagonized by a large number of drugs used for indications unrelated to thrombosis.
Have you stress tested your assay

Abstract Objectives When a clinical assay is stressed with extraordinarily high volume of specimens over a short period of time, extra caution may be needed to avoid systematic errors and biases. Here we report our experience with a HgbA1c assay used for high volume wellness screening purpose, to illustrate the importance of stress testing during assay validation. Design and Methods Over 15,000 whole blood specimens were tested for HgbA1c in a period of 2 months. HgbA1c was tested by an immunoturbidimetric method on a high through-put automation line. The HgbA1c population distribution in our study was compared to that from the NHANES database. Daily distributions of HgbA1c values ≥6%, means and medians were plotted. Correlation studies were performed between the high through-put immunoturbidimetric assay and a medium through-put HPLC method. Results We observed a shift of HgbA1c distribution to the higher values compared to the NHANES. A bias of 15–20% was noted from further stress testing where large number of samples were batched and tested using the immunoturbidimetric assay. A 5–7% higher bias remained after implementing a cuvette washing program after each HgbA1c sample. We hypothesized this bias was caused by build-up of blood cell fragments in the cuvettes when continuous whole blood samples are run through the system. Our experience suggests stress testing needs to be incorporated early in the test validation process for high volume batched screening applications. This seemingly extra validation step may save significant troubleshooting and retesting efforts down the road.
Patterns of engrailed protein in early Drosophila embryos

By the onset of gastrulation during nuclear cycle 14 of Drosophila embryogenesis, the engrailed gene is expressed in fourteen one-cell-wide stripes. Each stripe defines the anlagen of the posterior compartment of a metameric segment. We report here several observations relating to the role and disposition of the engrailed protein during the embryonic stages that precede cellularization. We demonstrate that in embryos mutant for the engrailed gene, there were characteristic morphological abnormalities as early as the 6th cleavage cycle. In addition, the engrailed protein was detected in pre-cycle-9 embryos by Western blot analysis. When localization of engrailed protein begins during cycle 14, engrailed expression was first present in broad anterior and posterior regions before the fourteen-stripe pattern appeared.
Ubiquilin/Dsk2 promotes inclusion body formation and vacuole (lysosome)-mediated disposal of mutated huntingtin

Ubiquilin proteins contain a ubiquitin-like domain (UBL) and ubiquitin-associated domain(s) that interact with the proteasome and ubiquitinated substrates, respectively. Previous work established the link between ubiquilin mutations and neurodegenerative diseases, but the function of ubiquilin proteins remains elusive. Here we used a misfolded huntingtin exon I containing a 103-polyglutamine expansion (Htt103QP) as a model substrate for the functional study of ubiquilin proteins. We found that yeast ubiquilin mutant (dsk2Δ) is sensitive to Htt103QP overexpression and has a defect in the formation of Htt103QP inclusion bodies. Our evidence further suggests that the UBL domain of Dsk2 is critical for inclusion body formation. Of interest, Dsk2 is dispensable for Htt103QP degradation when Htt103QP is induced for a short time before noticeable inclusion body formation. However, when the inclusion body forms after a long Htt103QP induction, Dsk2 is required for efficient Htt103QP clearance, as well as for autophagy-dependent delivery of Htt103QP into vacuoles (lysosomes). Therefore our data indicate that Dsk2 facilitates vacuole-mediated clearance of misfolded proteins by promoting inclusion body formation. Of importance, the defect of inclusion body formation in dsk2 mutants can be rescued by human ubiquilin 1 or 2, suggesting functional conservation of ubiquilin proteins.
Characterization of Reversibly Immortalized Calvarial Mesenchymal Progenitor Cells.

Background:Bone morphogenetic proteins (BMPs) play a sentinel role in osteoblastic differentiation, and their implementation into clinical practice can revolutionize cranial reconstruction. Preliminary data suggest a therapeutic role of adenoviral gene delivery of BMPs in murine calvarial defect hea
The Doctrine of Implied Limitations to Constitutional Amendments: Painting a Comprehensive Pattern of the Global Practice

In this paper, author, attempts to answer the puzzle about unconstitutional constitutional amendments. In the introductory part, I will state the question whether courts finds implied limitations from within the constitution or from supra-constitutional principles. While raising the question, I will argue that the puzzle is all about the doctrine of Implied limitations that can be seen reduced to the conflict between positivist and natural law approaches. In the second part, I will draw a comprehensive pattern of the judicial practice from the multiple descriptions of the same practice across the world that itself answers the puzzle. In the third part, I will make three specific arguments from the general pattern of the judicial practice. Firstly, the current practice of judicial finding of implied limitations is based on a structural and foundational approach rather than natural law approach. It reflects a shift from positivism to structuralism. Secondly, the structural and foundational approach is based on theories about the distinction between constituent power and amending power. Thirdly, the current practice shows judicial restraint in finding constitutional limitations in natural law. On the basis of the general pattern drawn, the paper underlines the constitutional theories about constituent power propounded by Carl Schmitt, Emmanuel Sieyes, and Bruce Ackerman.
Partnering for New Possibilities: The Development of a Global Learning Certificate

While overseas partnerships are often seen as a facet of the internationalization process, an examination of the literature indicates that partnerships with the goal of the internationalization of campus curricula are much less common between domestic institutions. In 2012, a large research institution, Indiana University (IU), and Indiana’s community college system (Ivy Tech), comprising of 30 campuses in 14 regions, entered into a unique partnership aimed at campus internationalization. The three-year initiative, Global Learning Across Indiana (GLAI), is funded by the US Department of Education’s Undergraduate International Studies and Foreign Language (UISFL) grant. The core aims of this collaborative initiative are to develop a Global Learning Certificate (GLC), to offer Arabic language classes, and to internationalize the curriculum statewide throughout the Ivy Tech campuses. By examining the initial outcomes of this partnership, this study contributes to the conversation on the process of internationalization in higher education and in particular the benefits of collaboration between domestic institutions. Specifically, this study investigates two key questions: To what extent has the initiative served to internationalize curricula on Ivy Tech campuses? Is this a replicable and recommended model for institutions seeking to form partnerships to internationalize? Through attaining the perspectives of faculty associated with the collaborative initiative via survey data and reviewing relevant documents, this study offers insight into collaborations between domestic institutions and the experiences of key stakeholders in their efforts to internationalize the curriculum of their institutions.
Associations: From Actors to Audiences

In Charles Dickens’s Nicholas Nickleby (1838–9), Mr. Pugstyles (possibly modelled on Francis Place) and several other local political activists visit a Westminster address to wait on their MP, the sometime radical Gregsbury, whose situation and speech were much like Sir Francis Burdett’s at the moment the novel was written. ‘“I am very sorry to be here, sir”, said Mr. Pugstyles; “but your conduct Mr. Gregsbury, has rendered this deputation from your constituents imperatively necessary”.’ As the discussion proceeds there follow three questions about past pledges sardonically constructed by Dickens to produce snickering on the part of his readers.
Modulation of Effector Lymphokines

As is now well known, lymphokines are soluble, non-antibody mediators produced by appropriately stimulated lymphocytes. They play important afferent roles with respect to enhancement or suppression of the induction of immunity. They are important in efferent reactions as well. These effector lymphokines, initially described in terms of in vitro bioassays, have been demonstrated in a variety of in vivo situations and, when exogenously administered, have been shown to exert profound effects in vivo (reviewed in 1).
Entrainment Maps: A New Tool for Understanding Properties of Circadian Oscillator Models

Circadian oscillators found across a variety of species are subject to periodic external light-dark forcing. Entrainment to light-dark cycles enables the circadian system to align biological functi...
Reclaiming Instructional Supervision: Using Solution-Focused Strategies to Promote Teacher Development:

To positively affect teacher quality, instructional leaders must engage teachers in ways that support improved practice and seek to empower teachers as creative and knowledgeable risk takers. A collaborative, strengths-based approach that promotes teacher growth, rather than one that conditions teachers to await administrator directive or approval, is warranted. In this conceptual article, we draw from developmental supervision and solution-focused supervision to posit a blended model of instructional supervision that equips aspiring and emerging instructional leaders with strategies to identify and amplify teacher strengths.
Long-Term Incidence and Outcome of BCR-ABL Mutations in Patients (pts) with Chronic Myeloid Leukemia (CML) Treated with Imatinib Mesylate - P-Loop Mutations Are Not Associated with Worse Outcome.

Resistance to imatinib in CML may occur through mutations of the BCR-ABL kinase domain. We investigated the occurrence of mutations in 159 pts treated with imatinib by direct sequencing. Pts had been treated with imatinib for a median of 32 months (mo) (range, 4 to 60 mo). 52 mutations were identified in 49 (31%) pts: 3 pts had 2 different mutations; in 2 of them they appeared simultaneously. Mutations mapped to 23 different amino acid residues, with the most frequent locating to the P-loop (n=19; 39%), and the residues in imatinib binding pocket (n=12; 25%). The single most common mutations were G250E (n=8) and F317L (n=7). At the time imatinib was started, 34 pts (70%) were in chronic phase (CP) (13 previously untreated, 21 post-IFN failure), 14 (28%) in accelerated phase (AP), and 1 (2%) in lymphoid blast phase (BP). Three pts (2 AP, 1BP) had clonal evolution. Best response to imatinib for pts in CP was: cytogenetic (CG) response complete (CGCR) in 13 (38%), partial (CGPR) in 8 (24%), minor in 1 (3%), and hematologic response only in 12 (35%) (11 complete, 1 partial). For pts in AP, best response was: CGCR in 5 (36%), CGPR in 3 (21%), minor in 1 (7%), and hematologic only in 5 (36%). The pt in BP had achieved CGCR. At the time mutations occurred, 47 (96%) pts had lost their hematologic or cytogenetic response, and clonal evolution had occurred in 15 (68%) pts. Among pts who were initially treated in CP, 9 had transformed to AP and 3 to BP. Two pts treated in AP had progressed to BP. In 2 (4%) pts (1 CP, 1 AP) the mutation (F317L, F311I) was identified while in CGCR remission; both pts have remained in CG CR 2 and 4 mo, respectively after the mutations was identified. Five patients died (4 AP, 1 CP) after a median of 7 mo (1–20 mo) following the detection of mutations. Their mutations included F317L (n=2), M244V, F359V, H396R (1 each). Thus, after a median follow-up of 6 mo (range, 1–20 mo) from detection, only 1 of 19 pts with P-loop mutations has died versus 4 of 30 with non-P-loop mutations. The estimated 15-months survival rates were 95% and 83%, respectively (p=0.50). We conclude that 1) mutations occur frequently among pts with acquired resistance to imatinib; 2) in few instances they can be identified in pts in CGCR; and 3) P-loop mutations may not be associated with worse outcome compared to other mutations.
Maximizing coverage in low-power wide-area IoT networks

The Internet of Things (IoT) promises to allow everyday objects to connect to the Internet and seamlessly interact with users and other machines. Essential for the IoT to function is a reliable Internet connection. In 2016 the International Telecommunication Union reports 3.9 billion people - 53% of the world's population are not using the Internet [1]. Projects like Loon (X) and Aquila (Facebook) aim to solve this connectivity gap using atmospheric satellites to deliver 4G-like signals to underserved regions. With the recent interest in low-power wide-area networks (LPWAN) in the license-free ISM bands, we consider using atmospheric satellites to improve coverage in LPWAN networks. We find that LPWAN technologies are compatible with atmospheric satellites and demonstrate that significant connectivity gains are possible by locating an LPWAN base station at altitude from 1 km – 28 km when compared to a typical ground-based base station.
Bright Lines, the Federal Communications Commission's Duopoly Rule, and the Diversity of Voices

One of the stated purposes behind the FCC’s so-called duopoly rule is to foster diversity of programming for the sake of First Amendment interests, as well as to promote programming competition among media outlets in every market. Ironically, the duopoly rule may frustrate these objectives. This Article first argues that so far as diversity is concerned, the multitude of theoretically comparable dimensions that belong to the domain of diversity render it extraordinarily difficult to conceptualize how to regulate “in the public interest.” The Article next reasons that increasing diversity may actually be worse if viewer welfare is the appropriate criterion. Though we readily admit that it is counterintuitive, diversity is not an unambiguous good, and thus should be optimized, not maximized.
An Adaptive and Learning Control System for Underwater Robots

Abstract Underwater robotic vehicles (URVs) have become an important tool for various underwater tasks because they have greater speed, endurance, and depth capability as well as a higher factor of safety than human divers. However, most vehicle control systems were designed based on a simplified vehicle model and they often resulted in poor performance because of the nonlinear, time-varying vehicle dynamics and parameter uncertainties. This paper describes a vehicle control system that has the capability of learning and adapting to changes in the vehicle dynamics and parameters. The control system was compared with conventional linear control system by simulation
Superconducting Thallium Oxide and Mercury Oxide Films

This paper reports on a study to convert electrodeposited Tl-oxide films to Hg-1212 using the cation-exchange process. A two-layer electrodeposition process was used to prepare Tl–Ba–Ca–Cu–O films with Tl-1212 and Tl-2212 stoichiometry. Electrodeposited Tl-films were also deposited with Bi and Sr substituted for the Tl and Ba, respectively and also reacted using cation exchange to attempt formation of Hg-1212. The superconducting transition temperature for the ‘‘non-substituted’’ films improved from 97 to 120 K after the cation-exchange process with a critical current density exceeding 2 � 10 6 at 5 K in zero field. The cation-exchange process for the Bi, Sr substituted films appears to be more difficult with no marked improvement in superconducting properties. 2001 Elsevier Science B.V. All rights reserved.
Guatemalan women achieve ideal family size: Empowerment through education and decision-making

Women's empowerment in family planning strengthens families and communities. Using 2014/2015 Demographic and Health Surveys data from 7,168 Guatemalan women, ages 35 and above with at least one living child, we examined indicators of empowerment in four domains - economic, educational, social, and contraceptive - and their relation to the number of living children compared to the ideal number of children. We reveal our analysis showing that economic, educational, and social empowerment predicted achieving the preferred number of children. Education and control over their own income are two critical empowerment factors for Guatemalan women.
Hazard/Risk Assessment and Ranking

There are various approaches to fire hazard and risk assessment and ranking, from qualitative to quantitative. Detailed discussion of these can be found in many sources, including the SFPE Handbook of Fire Protection Engineering (NFPA 2008), SFPE Engineering Guide on Fire Risk Assessment (SFPE 2006), NFPA 551, Guide for the Evaluation of Fire Risk Assessments (NFPA 2012), textbooks (e.g., Ramachandran and Charters 2011), and in the literature (e.g., Meacham 2004; Meacham et al. 2012).