cssi/SciSciGPT-SciSciNet huggingface dataset:
New insights into extracellular vesicle biogenesis and function

It is becoming increasingly evident that most cell types are capable of forming and releasing multiple distinct classes of membrane-enclosed packages, referred to as extracellular vesicles (EVs), as a form of intercellular communication. Microvesicles (MVs) represent one of the major classes of EVs and are formed by the outward budding of the plasma membrane. The second major class of EVs, exosomes, are produced as components of multivesicular bodies (MVBs) and are released from cells when MVBs fuse with the cell surface. Both MVs and exosomes have been shown to contain proteins, RNA transcripts, microRNAs and even DNA that can be transferred to other cells and thereby trigger a broad range of cellular activities and biological responses. However, EV biogenesis is also frequently de-regulated in different pathologies, especially cancer, where MVs and exosomes have been suggested to promote tumor cell growth, therapy resistance, invasion and even metastasis. In this Review, we highlight some of the recent advances in this rapidly emerging and exciting field of cell biology, focusing on the underlying mechanisms that drive MV and exosome formation and release, with a particular emphasis on how EVs potentially impact different aspects of cancer progression and stem cell biology.
Pectoralis Major Rupture in Military Academy Athletes

Background:Pectoralis major ruptures are rare injuries that can occur at several parts of the muscle. Little is known of the pathoanatomic process and performance following pectoralis major rupture...
Community regulation models as a framework for direct and indirect effects of climate change on species distributions

Existing projections of climate change impacts focus primarily on direct abiotic impacts on individuals and populations. However, these models often ignore species interactions, which are vital for determining community composition and structure. To evaluate both direct and indirect effects of climate change on species distributions, we applied the Menge–Sutherland model, which describes the relative role of predation and environmental stress in regulating community structure. Using a space‐for‐time approach, we tested the predictions that (1) predators are more strongly impacted by increasing environmental stress than prey (as described in the Menge–Sutherland model) and (2) incorporating indirect (predator) effects increases our ability to predict impacts of increased temperature on prey distributions. We surveyed vertical distributions of predators (sea stars) and a foundational prey species (mussels) at 20 intertidal sites spanning a thermal gradient along the West Coast of the United States. Using generalized linear models and structural equation models, we found that as temperature increased, the upper limits of foundational prey species decreased (a direct effect), while prey lower limits also shifted downward, due to an indirect effect of temperature on predator distributions. Under future climate change, mussel ranges may undergo vertical shifts toward subtidal habitats, allowing for localized persistence of mussels and associated species. Our model comparisons indicate that this framework—incorporating both direct and indirect environmental stress effects within a classic community regulation model—can improve prediction of responses to warming. Community regulation models could be expanded to inform management and conservation efforts during unprecedented climate and ecological change.
Impact of Rainfall Variation on Slope Made of Expansive Yazoo Clay Soil in Mississippi

Yazoo clay soil is highly expansive in nature and extends over central Mississippi, Alabama, and Southern Louisiana. Shallow slope failure is frequent in embankments constructed using Yazoo clay due to rainfall volume and climatic variation. This study investigates the effect of different intensities and volumes of rainfall on slopes constructed of Yazoo clay soil in Mississippi. The coupled flow-deformation analysis was conducted using the finite element method (FEM) in PLAXIS to investigate the unsaturated hydromechanical behavior of the slopes. Weathered Yazoo clay soil samples were collected and tested in laboratory conditions to investigate the soil index properties, soil strength parameters, and soil water characteristics curve. The historical rainfall pattern of Mississippi from National Oceanic and Atmospheric Administration (NOAA) is evaluated at different intensities (2 to 50 mm/h) and duration of rainfall (30 min to 7 days) based on return periods of 50, 100, and 500 years. Three fill slopes constructed using Yazoo clay soil, with slope ratios of 2H:1V, 3H:1V, and 4H:1V, are investigated. The rainfall pattern is applied to the top boundary of the slope in PLAXIS. The investigation results indicated that rainfall water infiltrated the top part of the slope, near the crest, resulting in the reduction of both the matric suction and the factor of safety of the slope.
Providential Products: Reconciling the American and European Constitutional Experiences

Citizens on both sides of the Atlantic readily compare the European Union experience to date with the United States’ transition from the Articles of Confederation to the Constitution. While many recognize the apparent parallels of merging a “loose confederation” of states and the seeming desirability of a stronger federal union, scholars have not fully uncovered why efforts in Rome failed while those in Philadelphia succeeded. Speaking to American and Continental audiences, this note will seek to assess why the European Union has failed to develop a strong federal constitution by comparing the inherent deviating dynamics that characterize the EU and American experiences John Jay alluded to in The Federalist. Looking to discrete criteria, I hope to reframe the debate through an objective lens. Preliminarily, this note will lie out the early origins of the American colonies and republic vis-a-vis the European Union’s succession of treaties that comprise its adolescent years to provide a basic necessary context. In juxtaposition, I will demonstrate how the “raw materials,” in terms of people, place and history, with which the constitutional framers in America were afforded, were deeply different and more conducive to a single constitutional convention and relatively quick ratification. First among these variables, I consider the unifying concept or vision and theoretical frameworks for integration, both of which demonstrate comparative clarity in the new world versus heated obscurity in the old world. Next, I look to political, religious, and cultural distinctions between political subdivisions and demonstrate how the American experience benefitted from greater cohesion. Finally, I analyze the economic condition and disparities throughout the territories, expressing how a more egalitarian society advantaged early America. Aggregating these factors indicates that while both constitutional ventures experienced some measure of resistance, the American experience reflects far more favorable winds than its European corollary. While many suggest Europe is waiting for its own James Madison to come along, I suggest it might as well be waiting for Godot (or worse). While all politicians are wise to consider the historical contributions of predecessors, European integration presents diametrically different difficulties that necessitate a distinct process with unique solutions.
PROTEOMIC CHARACTERIZATION OF STAGE C AND D HEART FAILURE: IDENTIFICATION OF A CORE PROTEIN SIGNATURE AND EFFECT OF TREATMENT

Proteomics may identify previously unsuspected regulatory pathways in heart failure with reduced ejection fraction (HFrEF). It remains uncertain how the proteome differs between Stages C and Stage D HF or how HF treatment alters the proteome. Following clinical matching of patients between Stages,
Detection of Falsely Elevated Point-of-Care Potassium Results Due to Hemolysis Using Predictive Analytics

Objectives Preanalytical factors, such as hemolysis, affect many components of a test panel. Machine learning can be used to recognize these patterns, alerting clinicians and laboratories to potentially erroneous results. In particular, machine learning might identify which cases of elevated potassium from a point-of-care (POC) basic metabolic panel are likely erroneous. Methods Plasma potassium concentrations were compared between POC and core laboratory basic metabolic panels to identify falsely elevated POC results. A logistic regression model was created using these labels and the other analytes on the POC panel. Results This model has high predictive power in classifying POC potassium as falsely elevated or not (area under the curve of 0.995 when applied to the test data set). A rule-in and rule-out approach further improves the model's applicability with a positive predictive value of around 90% and a negative predictive value near 100%. Conclusions Machine learning has the potential to detect laboratory errors based on the recognition of patterns in commonly requested multianalyte panels. This could be used to alert providers at the POC that a result is suspicious or used to monitor the quality of POC results.
The Changing Board Exam Schedule in the U.S.: Will General Radiologists and Emergency Radiologists Become Synonymous?

Change is a constant in radiology. Yet the visibility of that change depends upon the thing altered. The introduction of a new modality or an advanced technique is readily manifest as it is demonstrated in the production of novel images. Modifications of reimbursement or the announcement of new regulations are usually publicized before their imposition so that while they may be startling, they are not unexpected, at least in the immediate term. In contradistinction, there are profound changes that do not broadcast their arrival as they are the result of gradual alterations of attitude or slowly developing realignments of opportunities or even sometimes the subliminal redirection of perspectives held by regulators policy planners, or competitors. Such new realities are generally perceptible in both their evolution and inevitability by those attuned to look for trends. Yet for most radiologists, they are apt to burst on the scene assertively, belatedly and unheralded.
Predicting cell-to-cell failure propagation and limits of propagation in lithium-ion cell stacks

Abstract Thermal runaway of lithium-ion batteries is a risk that is magnified when stacks of lithium-ion cells are used for large scale energy storage. When limits of propagation can be identified so that systems can be designed to prevent large scale cascading failure even if a failure does occur, these systems will be safer. This work addresses the prediction of cell-to-cell failure propagation and the propagation limits in lithium-ion cell stacks to better understand and identify safe designs. A thermal-runaway model is presented based on recent developments in thermochemical source terms. It is noted that propagating failure is characterized by temperatures above which calorimetry data is available. Results show high temperature propagating failure predictions are too rapid unless an intra-particle diffusion limit is included, introducing a Damkohler number limiter into the rate expression. This new model form is evaluated against cell-to-cell failure propagation where the end cell of a stack is forced into thermal runaway through a nail-induced short circuit. Limits of propagation for this configuration are identified. Results show cell-to-cell propagation predictions are consistent with measurements over a range of cell states of charge and with the introduction of metal plates between cells to add system heat capacity representative of structural members. This consistency extends from scenarios where propagation occurs through scenarios where propagation is prevented.
Physical Stores in the Digital Age: How Store Closures Affect Consumer Churn

In this paper we investigate how consumers derive value from having the option to use physical stores for their transactions focusing on the DVD rental market. We use a large individual and transaction level panel dataset including information from consumers who subscribed to an online-offline video rental service from a leading company that closed a large number of physical store locations during our study period. Our empirical approach is to estimate a conditional logistic panel data model quantifying the extent to which offline store closures induced individuals to terminate their subscriptions with our focal company. We further examine how physical store closures affected consumers’ churn decisions differently for individuals who either heavily or lightly used physical stores for their transactions. Our results show that the closure of a physical store in a zip code increased the churn rate by approximately 50% for heavy users of physical stores and that the increase in the churn rate was essentially zero for light users. Our findings thus show that physical stores substantially increase loyalty for a fraction of consumers, and that there is substantial heterogeneity across consumers regarding how much utility they derive from having the option of using physical stores for their transactions. Our results provide a critical ingredient that managers need to have when formulating their online-offline channel operations strategies.
Faculty That Look Like Me: An Examination of HBCU Accounting Faculty Motivation and Job Satisfaction

Historically black colleges and universities (“HBCU”) provide an academic environment that contributes to increased student success and social mobility. However, this environment introduces unique working conditions for faculty members. The existing academic literature does not provide evidence about the motivation and job satisfaction of HBCU accounting faculty. This study addresses that gap and provides survey evidence on this unique group's motivation and job satisfaction. We find that respondents are motivated by helping others but are not satisfied with institutional operations, research resources, and compensation. We also find that tenured faculty have lower job satisfaction than non-tenured faculty. Demographically, we find that the respondents were older, predominately female, tenured, and have significant practitioner experience. Taken together, these findings identify opportunities for improvement in job satisfaction for HBCU accounting faculty.
Near Field Optical Sensing of Single Cell Activity with Integrated Micro-Ring Resonators

We propose a biohybrid sensor based on optical measurements of transmembrane proteins using micro-ring resonators. The scalability and sensitivity of this geometry could enable optical recording of many individual cells over large physical areas.
Discrepancies between Conference Abstracts and Published Manuscripts in Plastic Surgery Studies: A Retrospective Review.

Background Inconsistency in results and outcomes between presented abstracts and corresponding published articles can negatively affect clinical education and care. The objective of this study was to describe the frequency of clinically meaningful change in results and outcomes between abstracts presented at the American Association of Plastic Surgeons annual conference and the corresponding published articles, and to determine risk factors associated with discrepancies. Methods All abstracts delivered as oral presentations at the American Association of Plastic Surgeons conference (2006-2016) were reviewed. Results and outcomes were compared with those in corresponding articles. We defined clinically meaningful discrepancy as any change in the directionality of an outcome, or a quantitative change in results exceeding 10%. Results Four hundred eighty-six abstracts were identified. Of these, 63% (N = 305) advanced to publication. Of the published studies, 19% (N = 59) contained a discrepancy. In 85% of these (N = 50), discrepancies could not be explained by random variation. Changes in sample size were associated with heightened risk for a discrepancy (OR 10.38, 95% CI 5.16-20.86, P < 0.001). A decrease in sample size greater than 10% increased the likelihood of a discrepancy by 25-fold (OR 24.92, 95% CI 8.66-71.68, P < 0.001), whereas an increase in sample size greater than 10% increased the likelihood of a discrepancy by eight-fold (OR 8.36, CI 3.69-19.00, P < 0.001). Conclusions Most discrepancies between abstract and published article were not due to random statistical variation. To mitigate the possible impact of unreliable abstracts, we recommend abstracts be marked as preliminary, that authors indicate whether sample size is final at time of presentation, and that changes to previously reported results be indicated in final publications.
Reducing respondents’ perceptions of bias in survey research:

Response rates for surveys have declined steadily over the last few decades. During this period, trust in science has also waned and conspiratorial theorizing around scientific issues has seemingly...
Beyond words: Pragmatic inference in behavioral variant of frontotemporal degeneration

Abstract When the message of a speaker goes beyond the literal or logical meaning of the sentences used, a pragmatic inference is required to understand the complete meaning of an utterance. Here we study one example of pragmatic inference, called scalar implicature. Such an inference is required when a weaker term “some” is used in a sentence like “Some of the students passed the exam” because the speaker presumably had a reason not to use a stronger term like “all”. We investigated the comprehension of scalar implicatures in a group of 17 non-aphasic patients with behavioral variant frontotemporal degeneration (bvFTD) in order to test the contribution of non-linguistic decision-making ability and the role of prefrontal cortex in supporting the computation of pragmatic inferences. The results of two experiments point to a deficit in producing alternative interpretations beyond a logical reading. bvFTD patients thus prefer the narrowly literal or logical interpretation of a scalar term when they must generate a possible alternative interpretation by themselves, but patients prefer a pragmatic reading when offered a choice between the logical and the pragmatic interpretation of the same sentence. An imaging analysis links bvFTD patients' spontaneous tendency toward a narrowly logical interpretation with atrophy in ventromedial prefrontal cortex. Our findings are consistent with the pragmatic tolerance hypothesis , which proposes that difficulty generating alternative interpretations of an utterance, rather than a frank inability to compute an inference, affects the comprehension of a scalar term.
Morphological inference from bitext for resource-poor languages

The development of rich, multi-lingual corpora is essential for enabling new types of large-scale inquiry into the nature of language (Abney and Bird, 2010; Lewis and Xia, 2010). However, significant digital resources currently exist for only a handful of the world's languages. The present dissertation addresses this issue by introducing new techniques for creating rich corpora by enriching existing resources via automated processing. As a way of leveraging existing resources, this dissertation describes an automated method for extracting bitext (text accompanied by a translation) from bilingual documents. Digitized copies of printed books are mined for foreign-language material, using statistical methods for language identification and word alignment to identify instances of English-foreign bitext. After parsing the English text and transferring this analysis via the word alignments, the foreign word tokens are tagged with English glosses and morphosyntactic features. Tagged tokens such as these constitute the input to a new algorithm, presented in this dissertation, for performing morphology induction. Drawing on previous work on unsupervised morphology induction which uses the principle of minimum description length to drive the analysis (Goldsmith, 2001), the present algorithm uses a greedy hill-climbing search to minimize the size of a paradigm-based morphological description of the language. The algorithm simultaneously segments wordforms into their component morphemes and organizes stems and affixes into a paradigmatic structure. Because tagged tokens are used as input, the morphemes produced by this induction method are paired with meaningful morphosyntactic features, an improvement over algorithms for unsupervised morphology based on monolingual text, which treat morphemes purely as strings of letters. Combined, these methods for collecting and analyzing bitext data offer a pathway for the automatic creation of richly-annotated corpora for resource-poor languages, requiring minimal amounts of data and minimal manual analysis.
The Book They Held Together

To two old friends, sitting by a window, suddenly came a sense of freedom from all commitments, as if that very evening the future (or whatever was left of it for them) had tangibly moved into the street below. Thinking of this place and the many places in the world where they had been, they were filled with tenderness and peace, and felt enveloped by the unheard music of contentment that flowed all about them and into the distance. The book they held together seemed to confirm and encourage their feeling of abandonment.
Inappropriate Medication Administration to the Acutely Ill Elderly: A Nationwide Emergency Department Study, 1992–2000

Objectives: To determine the national rate and trend of inappropriate medication administration to elderly emergency department (ED) patients. Secondary objectives were to identify risk factors for receiving an inappropriate medication and to determine whether administration is sometimes justified based on diagnosis. Design: Retrospective analysis of ED visits in the 1992–2000 National Hospital Ambulatory Medical Care Survey. Inappropriate medications identified using Beers' 1997 explicit criteria. Setting: EDs of U.S. noninstitutionalized general and short-stay hospitals. Participants: ED survey patients aged 65 and older. Measurements: Magnitude and rate of administration of 36 medications. Results: Inappropriate medications were administered in an estimated 16.1 million (95% confidence interval (CI)=14.9–17.3 million) or 12.6% (95% CI=11.6–13.5%) of elderly ED visits from 1992 to 2000. The rate of inappropriate administration was unchanged throughout the study period (P=.40). Six drugs accounted for 70.8% of inappropriate administration: promethazine (22.2%), meperidine (18.0%), propoxyphene (17.2%), hydroxyzine (10.3%), diphenhydramine (7.1%), and diazepam (6.0%). In multivariate analysis, number of ED medications was the strongest predictor, with an odds ratio for two to three medications of 6.0 (95% CI=5.3–6.7) and for four to six medications of 8.1 (95% CI=7.2–9.2). Diagnoses indicating potentially appropriate uses of these medications were rarely present. For example, only 42.4% of patients receiving diphenhydramine and 7.4% receiving hydroxyzine were diagnosed with an allergic process. Conclusion: Elderly ED patients are frequently administered inappropriate medications. Potentially appropriate uses of generally inappropriate drugs cannot account for such administrations. Inappropriate administration rates remain unchanged despite the 1997 publication of explicit criteria.
Weak lensing of the cosmic microwave background: Power spectrum covariance

We discuss the non-Gaussian contribution to the power spectrum covariance of cosmic microwave background (CMB) anisotropies resulting through weak gravitational lensing angular deflections and the correlation of deflections with secondary sources of temperature fluctuations generated by the large scale structure, such as the integrated Sachs-Wolfe effect and the Sunyaev-Zel’dovich effect. This additional contribution to the covariance of binned angular power spectrum, beyond the well known cosmic variance and any associated instrumental noise, results from a trispectrum, or a four point correlation function, in temperature anisotropy data. With substantially wide bins in multipole space, the resulting non-Gaussian contribution from lensing to the binned power spectrum variance is insignificant out to multipoles of a few thousand and is not likely to affect the cosmological parameter estimation with acoustic peaks and the damping tail. The non-Gaussian contribution to covariance, however, should be considered when interpreting binned CMB power spectrum measurements at multipoles of a few thousand corresponding to angular scales of few arcminutes and less.
Gestational high fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats

In insulin resistance and type II diabetes, there is an elevation of hepatic gluconeogenesis, which contributes to hyperglycaemia. Studies in experimental animals have provided evidence that consumption of high fat (HF) diets by female rats programs the progeny for glucose intolerance in adulthood, but the mechanisms behind the in utero programming remain poorly understood. The present study analysed the effect of a maternal HF diet on fetal gluconeogenic gene expression and potential regulation mechanism related to histone modifications. Dams were fed either a Control (C, 16% kcal fat) or a high-fat (HF, 45% kcal fat) diet throughout gestation. Livers of the offspring were collected on gestational day 21 and analysed to determine the consequences of a maternal HF diet on molecular markers of fetal liver gluconeogenesis. We demonstrated that offspring of HF-fed dams were significantly heavier and had significantly higher blood glucose levels at the time of delivery than offspring of dams fed the C diet. While maternal gluconeogenesis and plasma glucose were not affected by the HF diet, offspring of HF-fed dams had significantly higher mRNA contents of gluconeogenic genes in addition to the elevated plasma glucose. In addition to increased transcription rate, a gestational HF diet resulted in modifications of the Pck1 histone code in livers of offspring. Our results demonstrate that in utero exposure to HF diet has the potential to program the gluconeogenic capacity of offspring through epigenetic modifications, which could potentially lead to excessive glucose production and altered insulin sensitivity in adulthood.
Chapter Five - Recent Studies of Rhenium and Manganese Bipyridine Carbonyl Catalysts for the Electrochemical Reduction of CO2

Abstract The eventual deployment of large-scale systems for the electrochemical reduction of carbon dioxide (CO 2 ) to fuels and commodity chemicals depends on the development of stable, highly active, and selective catalysts. The fac -Re(bpy-R)(CO) 3 X system, originally reported three decades ago, is very efficient for CO 2 reduction to carbon monoxide (CO) even in the presence of proton sources. Recent studies from our group and others that have improved the catalyst activity and significantly expanded the understanding of these catalysts are highlighted in this report. The 4,4′- tert -butyl-substituted complexes fac -Re(bpy- t Bu)(CO) 3 X have been found to be more active than the parent 2,2′-bipyridine complexes. The presence of Bronsted acids increases the activity of these catalysts, with stronger acids leading to more rapid catalysis. The catalytically relevant [Re(bpy-R)(CO) 3 ] − 1 anions have been isolated and studied in order to elucidate their structures and reactivities. X-ray crystallography, quantum chemical calculations, and synchrotron radiation experiments have shown that the electronic structures of the anions are best described as Re 0 (bpy-R) − 1 states, with electron density delocalized over both the metal and the ligand. This delocalized ground state is thought to enable better overlap with CO 2 compared to protons, which explains the selectivity for CO 2 reduction with these types of catalysts even in the presence of acids. Recent reports have also shown that earth-abundant manganese can be substituted for rhenium to yield fac -Mn(bpy-R)(CO) 3 X catalysts that approach the CO 2 reduction activity of the analogous rhenium compounds. Indeed, the anionic [Mn(bpy- t Bu)(CO) 3 ] − 1 species has recently been crystallized and studied, and it possesses a similar structure to the [Re(bpy- t Bu)(CO) 3 ] − 1 anion. Future directions for the study of fac -M(bpy-R)(CO) 3 X catalysts are also discussed.
Probability Models for Live-Load Survey Results

Structural floor load data from five major live-load surveys are analyzed probabilistically in order to determine the accuracy of fitted normal, lognormal, and gamma distributions. Histograms and scaled cumulative graphs are made for every use type from each survey and statistical goodness-of-fit tests made on the assumed distributions. Data from the surveys are combined by occupancy type to compute load levels with high probabilities of nonexceedance, and comparisons are made among conservative levels of observed loads, present design values, and the computed loads. Results indicate that the gamma distribution provides a realistic approximation to the observed data, and in particular yields excellent prediction of observed office load data up to the 99.9% cumulative level. Present design loads for offices, domestic dwellings, and mercantile occupancies appear to approximate the 99.99% cumulative level.
Synthesis of memory-based VLSI architectures for discrete wavelet transforms

We propose novel VLSI architectures for computing the Discrete Wavelet Transforms. The proposed architectures employ a memory-based approach. ROM lookup tables are used for the implementation of complex computational modules. Compared with known architectures that employ traditional hardware computational modules, the proposed architectures are faster and are area-efficient. The memory-based architecture is used to implement the block-based DWT with parallel I/O. The resulting architectures are area-efficient and have high throughput and low latency. These architectures are suitable for low-power single-chip implementations which are useful for DWT-based mobile/visual communication systems.
The Antiapoptotic Protein Bcl-xL Is Dispensable for the Development of Effector and Memory T Lymphocytes

The antiapoptotic protein Bcl-x(L) is induced in activated T lymphocytes upon costimulation through CD28, 4-1BB, and OX40. Bcl-x(L) is also highly enriched in memory T lymphocytes. Based on this body of evidence, it was thought that Bcl-x(L) plays an essential role in the generation of effector and memory T lymphocytes. We report that mice with a conditional deletion of Bcl-x in T lymphocytes develop a normal CD8(+) T cell response to Listeria monocytogenes infection. Furthermore, Bcl-x conditional knockout mice exhibit normal T-dependent humoral immune responses. These results indicate that Bcl-x is dispensable for the generation of effector and memory T lymphocytes and suggest that costimulation of T lymphocytes promotes their survival through a Bcl-x(L) independent mechanism.
Teriparatide treatment in adult hypophosphatasia in a patient exposed to bisphosphonate: a case report.

We describe the case of a woman with hypophosphatasia previously exposed to bisphosphonate and subsequently treated with teriparatide (recombinant human PTH 1-34). A Caucasian woman sustained bilateral femur stress fractures when she was fifty years old, which widened despite use of calcium, vitamin D and risedronate for 2.5 years and required intramedullary rods for stabilization. Hypophosphatasia was diagnosed in the interim due to low serum alkaline phosphatase (ALP) (ALP 20 IU/L; normal (N), 40-150 IU/L) and high pyridoxal 5' phosphate (3400 nmol/L; N 18-175 nmol/L). She was referred for further management. On presentation, she had significant fracture site pain and generalized bone pain (weight bearing and non-weight bearing) - making her walker dependent at home and wheel chair dependent outside home. She could not sleep at night due to discomfort when she moved. Daily teriparatide injections, 20 mcg subcutaneously were prescribed. At 8-weeks follow-up, fracture site pain, weight-bearing and non weight-bearing pain improved significantly allowing ambulation for prolonged periods without assistance. She slept at night without discomfort. Improvement persisted during her entire treatment period. Radiographs taken at 4 and 16 months of treatment demonstrated healing of femur fractures. Biochemically, mean urine cross-link-N-telopeptide increased 11% as compared to her base-line, while bone specific alkaline phosphatase did not increase as expected. In conclusion, we observed an uncoupling of bone formation and resorption markers during her treatment period in the face of notable clinical and radiological improvement. Off-label use of teriparatide may help patients with hypophosphatasia
A Simple Multi-Factor Model of Corporate Bond Prices

We propose a multi-factor structural model of corporate bond prices. Bonds are valued in an arbitrage-free setting. The term structure of credit spreads is a function of a set of observable variables, including the issuer's leverage ratio, the riskfree interest rate and other stochastic factors that proxy for the issuer's likelihood of default. The set of factors may include both systematic and idiosyncratic components. We test the model using prices of Delta Airlines' bonds. Factors included in this empirical analysis are the growth rate of GDP and the volatility on Delta's stock. The root mean squared error between actual credit spreads and model-determined credit spreads decreases from 45 to 40 basis points when these factors are included in the analysis. Several extant models in the literature are special cases of the structure developed here and rejected in the empirical work.
A human lysosomal alpha-mannosidase specific for the core of complex glycans.

A novel lysosomal alpha-mannosidase, with unique substrate specificity, has been partially purified from human spleen by chromatography through concanavalin A-Sepharose, DEAE-Sephadex, and Sephacryl S-300. This enzyme can catalyze the hydrolysis of only 1 mannose residue, that which is alpha(1----6)-linked to the beta-linked mannose in the core of N-linked glycans, as found in the oligosaccharides Man alpha(1----6)[Man alpha(1----3)] Man beta(1----4)GlcNAc and Man alpha(1----6)Man beta(1----4) GlcNAc. The newly described alpha-mannosidase does not catalyze the hydrolysis of mannose residues outside of the core, even if they are alpha(1----6)-linked, and is not active on the other alpha-linked mannose in the core, which is (1----3)-linked. The narrow specificity of the novel mannosidase contrasts sharply with that of the major lysosomal alpha-mannosidase, which is able to catalyze the degradation of oligosaccharides containing diverse linkage and branching patterns of the mannose residues. Importantly, although the major mannosidase readily catalyzes the hydrolysis of the core alpha(1----3)-linked mannose, it is poorly active towards the alpha(1----6)-linked mannose, i.e. the very same mannose residue for which the newly characterized mannosidase is specific. The novel enzyme is further differentiated from the major lysosomal alpha-mannosidase by its inability to catalyze the efficient hydrolysis of the synthetic substrate p-nitrophenyl alpha-mannoside, and by the strong stimulation of its activity by Co2+ and Zn2+. Similarly to the major mannosidase, it is strongly inhibited by swainsonine and 1,4-dideoxy-1,4-imino-D-mannitol, but not by deoxymannojirimycin. The presence of this novel alpha-mannosidase activity in human tissues provides the best explanation, to date, for the structures of the oligosaccharides stored in human alpha-mannosidosis. In this condition the major lysosomal alpha-mannosidase activity is severely deficient, but apparently the alpha(1----6)-mannosidase is unaffected, so that the oligosaccharide structures reflect the unique specificity of this enzyme.
A discrete cell migration model

Migration of vascular smooth muscle cells is a fundamental process in the development of intimal hyperplasia, a precursor to development of cardiovascular disease and a potential response to injury of an arterial wall. Boyden chamber experiments are used to quantify the motion of cell populations in response to a chemoattractant gradient (i.e., cell chemotaxis). We are developing a mathematical model of cell migration within the Boyden chamber, while simultaneously conducting experiments to obtain parameter values for the migration process. In the future, the model and parameters will be used as building blocks for a detailed model of the process that causes intimal hyperplasia. The cell migration model presented in this paper is based on the notion of a cell as a moving sensor that responds to an evolving chemoattractant gradient. We compare the results of our three-dimensional hybrid model with results from a one-dimensional continuum model. Some preliminary experimental data that is being used to refine the model is also presented.
Hierarchical controls on runoff generation: Topographically driven hydrologic connectivity, geology, and vegetation

[1] Understanding the relative influence of catchment structure (topography and topology), underlying geology, and vegetation on runoff response is key to interpreting catchment hydrology. Hillslope-riparian-stream (HRS) water table connectivity serves as the hydrologic linkage between a catchment's uplands and the channel network and facilitates the transmission of water and solutes to streams. While there has been tremendous interest in the concept of hydrological connectivity to characterize catchments, few studies have quantified hydrologic connectivity at the stream network and catchment scales with observational data. Here we examine how catchment topography, vegetation, and geology influenced patterns of stream network HRS connectivity and runoff dynamics across 11 nested headwater catchments in the Tenderfoot Creek Experimental Forest (TCEF), MT. This study builds on the empirical findings of Jencso et al. (2009) who found a strong linear relationship (r2 = 0.91) between the upslope accumulated area (UAA) and the annual duration of shallow groundwater table connectivity observed across 24 HRS transects (146 groundwater recording wells). We applied this relationship to the entire stream network across 11 nested catchments to quantify the frequency distribution of stream network connectivity through time, and quantify its relationship to catchment-scale runoff dynamics. Each catchment's hydrologic connectivity duration curve (CDC) was highly related to its flow duration curve (FDC) and the slope of the relationship varied across catchments. The slope represents the streamflow yield per unit connectivity (Conyield). We analyzed the slope of each catchment's CDC-FDC relationship or Conyield (annual, peak, transition, and base flow periods) in multiple linear regression models with common terrain, land cover vegetation, and geology explanatory variables. Significant predictors (p < 0.05) across 11 catchments included the ratio of flow path distances and gradients to the creek (DFC/GTC), geology, and a vegetation index. The order and strength of these predictors changed seasonally and highlight the hierarchical controls on headwater catchment runoff generation. Our results highlight direct and quantifiable linkages between catchment topography, vegetation, geology, their topology, and hydrologic dynamics.
Associations among late chronotype, body mass index and dietary behaviors in young adolescents.

Associations among late chronotype, body mass index and dietary behaviors in young adolescents
Gi Irks GIRKs

G protein-activated potassium channels (GIRKs), monitored with the temporal and molecular resolution of electrophysiology, play a key role in the study of signal transduction. GIRKs are activated primarily by the Gβγ subunits, but a paper by Peleg et al. (2002)([this issue of Neuron]) demonstrates a role for Gα subunits in suppressing basal activity and supports the idea of a macromolecular complex of G protein, GIRK, and perhaps RGS protein.
EYE-MOVEMENT PATTERNS IN SCANNING NUMERIC DISPLAYS.

Eye movements of three Ss during visual scanning of 15° 2′ 6 × 6 numeric matrices were studied, using a modification of the Mackworth eye-marker apparatus, as a function of frequency of target nume...
RADICAL CROSSOVER IN NITROXIDE MEDIATED LIVING FREE RADICAL POLYMERIZATIONS

The efficiency of exchange between the mediating nitroxide moieties at the termini of growing polymer chains during “living” free radical polymerizations has been probed by a series of crossover experiments using functionalized unimolecular initiators. The design of appropriately substituted initiators permitted the synthesis of specifically functionalized model polymers which could be readily distinguished using high-performance liquid chromatography (HPLC). Using these models, the mixture of macromolecules obtained from a 1:1 combination of disparate initiators was separated and identified. The results reveal that exchange of the mediating nitroxide free radicals is a facile process and at essentially all stages of the polymerization a nearly statistical mixture of crossover products is obtained. The HPLC techniques developed are also useful in evaluating the extent of chain termination in nitroxide mediated “living” free radical polymerizations.
Carbodiimide conjugation of fibronectin on collagen basal lamina analogs enhances cellular binding domains and epithelialization.

To improve the regenerative potential of biomaterials used as bioengineered scaffolds, it is necessary to strategically incorporate biologically active molecules that promote in vivo cellular processes that lead to a fully functional tissue. This work evaluates the effects of strategically binding fibronectin (FN) to collagen basal lamina analogs to enhance keratinocyte functions necessary for complete skin regeneration. We found that FN that was passively adsorbed to collagen–glycosaminoglycan basal lamina analogs enhanced epithelial thickness and keratinocyte proliferation compared with nontreated basal lamina analogs at 3 days of air/liquid (A/L) interface culture. Additionally, we evaluated the availability of FN cellular binding site domains when FN was either passively adsorbed or [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride] conjugated to basal lamina analogs fabricated from collagen–glycosaminoglycan coprecipitate or self-assembled type I collagen. It was found that 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride conjugation of FN significantly enhanced FN binding site presentation as well as epithelial thickness. Overall, the results gained from this study will be used to improve the regenerative capacity of basal lamina analogs for bioengineered skin substitutes as well as the development of bioengineered scaffolds for other tissue engineering applications.
K-Ar dating of the Cima volcanic field, eastern Mojave Desert, California: Late Cenozoic volcanic history and landscape evolution

Thirty-four K-Ar ages and supporting paleomagnetic measurements from flows of the Cima volcanic field provide a detailed volcanic history and a temporal basis for analysis of evolving landforms. The Cima field has undergone three periods of volcanic activity, spanning late Miocene through latest Pleistocene time: (1) 7.6 to 6.5, (2) 4.5 to 3.6, and (3) 1.0 to at least 0.015 m.y. ago. These precisely dated sequences afford a unique opportunity to quantify the long-term effects of pedogenesis and erosion on volcanic landforms in an arid environment. Morphologic and pedologtc data indicate that the most stable geomorphic surfaces in the field occur on flows between 0.25 and 0.75 m.y. old. Younger flows are dominated by eolian aggradation and outcrop rubbling, and older flows are dominated by surface runoff and fluvial dissection. A process-response model involving progressive pedogenesis and a subsequent shift from infiltration to surface runoff is proposed to explain this temporal variation in land-surface stability.
The importance of the effective intermediate principal stress (σ′2) to fault slip patterns

Abstract In normal faulting regimes, the magnitudes and orientations of the maximum and minimum principal compressive stresses may be known with some confidence. However, the magnitude of the intermediate principal compressive stress is generally much more difficult to constrain and is often not considered to be an important factor. In this paper, we show that the slip characteristics of faults and fractures with complex or nonoptimal geometry are highly sensitive to variation or uncertainty in the ambient effective intermediate principal stress ( σ ′ 2 ). Optimally oriented faults and fractures may be less sensitive to such variations or uncertainties. Slip tendency ( T s ) analysis provides a basis for quantifying the effects of uncertainty in the magnitudes and orientations of all principal stresses and in any stress regime, thereby focusing efforts on the most important components of the system. We also show, for a normal faulting stress regime, that the proportion of potential surfaces experiencing high slip tendency (e.g., T s ≥ 0.6) decreases from a maximum of about 38% where σ ′ 2 = σ ′ 3 , to a minimum of approximately 14% where σ ′ 2 is halfway between σ ′ 3 and σ ′ 1 , and increases to another high of approximately 29% where σ ′ 2 = σ ′ 1 . This analysis illustrates the influence of the magnitude of σ ′ 2 on rock mass strength, an observation previously documented by experimental rock deformation studies. Because of the link between fault and fracture slip characteristics and transmissivity in critically stressed rock, this analysis can provide new insights into stress-controlled fault transmissivity.
Multimodal imaging of vascular grafts using time-resolved fluorescence and ultrasound

The translation of engineered tissues into clinic requires robust monitoring of tissue development, both in vitro and in vivo . Traditional methods are destructive, time- and cost- inefficient, and do not allow time-lapse measurements from the same sample or animal. This study reports on the ability of time-resolved fluorescence and ultrasound measurements for non-destructive characterization of explanted tissue engineered vascular grafts. Results show that TRFS and FLIm are able to assess alterations in luminal composition namely elastin, collagen and cellular content via changes in fluorescence lifetime values between normal and grafted tissue. These observations are complemented by structural changes observed in UBM pertaining to graft integration and neo-intimal and neo-medial thickening. These results encourage the future application of a catheter-based technique that combines these imaging modalities for nondestructive characterization of vascular grafts in vivo.
Hydrodynamics of Domain Size Equilibration in Monolayers

Coexisting thermodynamic phases of lipid molecules at the air−water interface often exhibit microscopically observable domains with a variety of sizes and shapes. The size and shape equilibration of these domains generally involve fluid flow in the monolayer as well as in the aqueous subphase. The present work treats the problem of the rate of size equilibration of a circular solid domain surrounded by a liquid composed of the same substance. The pressure at large distances from the domain is maintained constant, so that there is monolayer flow toward or away from the central domain. The central domain accordingly increases or decreases in size until a state of stable or metastable equilibrium is reached. Calculated rates of domain size change are discussed in terms of different experimental conditions, including applied electric fields.