cssi/SciSciGPT-SciSciNet huggingface dataset:
Artificial neural networks: a science in trouble

This article points out some very serious misconceptions about the brain in connectionism and artificial neural networks. Some of the connectionist ideas have been shown to have logical flaws, while others are inconsistent with some commonly observed human learning processes and behavior. For example, the connectionist ideas have absolutely no provision for learning from stored information, something that humans do all the time. The article also argues that there is definitely a need for some new ideas about the internal mechanisms of the brain. It points out that a very convincing argument can be made for a "control theoretic" approach to understanding the brain. A "control theoretic" approach is actually used in all connectionist and neural network algorithms and it can also be justified from recent neurobiological evidence. A control theoretic approach proposes that there are subsystems within the brain that control other subsystems. Hence a similar approach can be taken in constructing learning algorithms and other intelligent systems.
Enhancement of aster‐induced furrowing activity by a factor associated with the nucleus

The purpose of this investigation was to determine whether asters that develop in the absence of nuclear material have the normal ability to cause surface contraction and furrows. Experimental cells were confined in silicone rubber tubes with flattened lumens. The lumen roof was thin enough to permit deformation or perforation of the contained eggs by pressure with glass tools. When a flattened, elongate egg was perforated at its midpoint with a relatively large glass ball before nuclear membrane breakdown, the positions of the asters and nucleus were determined by chance. When the nucleus and asters were on the same side of the perforation, normal furrows developed. When the nucleus was separated from the aster pair, only ephemeral furrows developed. When the asters straddled the perforation so that only one of the asters was associated with the nucleus, ephemeral furrowing activity was most pronounced at the nucleated end of the cell. The asters of cells that were kneaded before insertion in the flattened capillary were often farther apart than normal, and the nucleus was more closely associated with one aster than the other. Constrictions developed in the planes of both asters, but only those associated with the aster closest to the nucleus persisted to produce two aster-containing cells, only one of which contained a nucleus. In subsequent division cycles, asters reproduced and developed in both cells, but only the progeny of the nucleated cell formed permanent furrows. The normal furrow-inducing capacity of the asters appears to depend in part on the presence of a factor associated with the nucleus.
Guild-specific responses of bats to landscape composition and configuration in fragmented Amazonian rainforest

Summary 1 Habitat loss and fragmentation are serious threats to biodiversity, especially in the Amazon Basin, where biodiversity is greatest and deforestation is continuing at an alarming rate. Nonetheless, little is known about the responses of biotas to spatially explicit aspects of landscape structure. 2 Bats are a promising indicator group for studying consequences of forest fragmentation in the Neotropics. Therefore, population- and assemblage-level responses of bats to landscape composition and configuration were quantified at each of three focal scales (circles of 1-, 3-, and 5-km radii) at 14 sites in lowland Amazonia. 3 Responses to landscape characteristics were scale-dependent. Abundance and richness were higher in moderately fragmented forest than in continuous forest. Moreover, the abundance of each of nine frugivorous species decreased with increasing forest cover. 4 The abundance of frugivores probably responded to landscape composition (e.g. percentage forest, mean patch density) because of an increase in early successional fruits and flowers in areas with reduced canopy cover. In contrast, abundances of gleaning animalivores responded to landscape configuration (e.g. edge density), probably by exploiting low-contrast edges (i.e. closed canopy forest patches embedded in secondary forest) while foraging and travelling between higher quality resource patches. 5 Synthesis and applications. Species- and ensemble-specific responses to aspects of landscape structure suggest that both compositional and configurational aspects need to be managed effectively in conservation planning. However, conservation decisions based on associations of biodiversity metrics (e.g. richness, diversity and rarity) with landscape structure may be problematic as they are composite characteristics that mask individual responses and potentially reflect only patterns of the dominant species or groups.
A new bone to pick: osteoblasts and the haematopoietic stem-cell niche.

Two recent publications highlight the role of bone-forming cells, the osteoblasts, in controlling the development of neighboring haematopoietic stem cells (HSCs).1,2 Using two distinct transgenic mouse models, one using the conditional deletion of the Bone Morphogenetic Protein Receptor 1A (BMPR1A) gene, the other using over-expression of an active PTH/PTHrP receptor (PPR) mutant within osteoblasts, the authors show parallel, concordant increases in the generation of trabecular osteoblasts and the number of HSCs. In situ staining showed that rarely cycling HSCs sporadically attach to endosteal osteoblasts, while in vitro assays indicated that ligation of Jag1 on osteoblasts by Notch1 on HSCs promotes HSC proliferation. These two independent works have revived and revitalized the notion that osteoblasts are a major, defining component of the HSC niche within the bone marrow (BM). This minireview discusses these results in the context of other recent studies of mesenchymal cells within the BM microenvironment, presents one potential unified model of the functional anatomy of the BM HSC niche, and highlights new questions raised by these and other studies of osteoblasts and HSCs. BioEssays 26:595–599, 2004. © 2004 Wiley Periodicals, Inc.
Crystal structure of the RIM2 C2A-domain at 1.4 Å resolution

RIMs are large proteins that contain two C2-domains and are localized at presynaptic active zones, where neurotransmitters are released. RIMs play key roles in synaptic vesicle priming and regulation of presynaptic plasticity. A mutation in the RIM1 C2A-domain has been implicated in autosomal dominant cone-rod dystrophy (CORD7). The RIM C2A-domain does not contain the full complement of aspartate residues that commonly mediate Ca 2+ binding at the top loops of C2-domains, and has been reported to interact with SNAP-25 and synaptotagmin 1, two proteins from the Ca 2+ -dependent membrane fusion machinery. Here we have used NMR spectroscopy and X-ray crystallography to analyze the structure and biochemical properties of the RIM2 C2A-domain, which is closely related to the RIM1 C2A-domain. We find that the RIM2 C2A-domain does not bind Ca 2+ . Moreover, little binding of the RIM2 C2A-domain to SNAP-25 and to the C2-domains of synaptotagmin 1 was detected by NMR experiments, suggesting that as yet unidentified interactions of the RIM C 2A-domain mediate its function. The crystal structure of the RIM2 C2A-domain using data to 1.4 A resolution reveals a‚-sandwich that resembles those observed for other C2-domains, but exhibits a unique dipolar distribution of electrostatic charges whereby one edge of the ‚-sandwich is highly positive and the other edge is highly negative. The location of the mutation site implicated in CORD7 at the bottom of the domain and the pattern of sequence conservation suggest that, in contrast to most C2-domains, the RIM C2A-domains may function through Ca 2+ -independent interactions involving their bottom face.
On-line extraction of soft decoding information and applications in VLSI turbo decoding

In this paper, a set of variables which can be easily computed in the course of iterative decoding of turbo decoders named turbo decoding metrics (TDMs) are introduced. TDMs are measured twice per iteration. According to the measured values, a lot of information other than the signal-to-noise ratio (SNR) in the received data, such as how good (or bad) the current decoding block is and how close to the convergence the current decoding is, can be obtained. Detailed discussions are provided regarding why these variables are considered. Based on the measured TDMs after the first iteration, an approximate channel reliability value (denoted as L/sub c/) can be obtained for MAP-based turbo decoders. Simulation results show that there is no performance degradation if approximated L/sub c/ values are used instead of using exact values. It is also shown that the adaptive decoding approach employing TDMs is more efficient than all existing methods in terms of hardware and latency. Other applications of TDMs are also pointed out.
Foreign Exchange Budgets in Latin America

T HE CONCEPT of a foreign exchange budget and the use which may be made of it are not so well known or so generally understood as are the more common types of budget, such as the corporation or national budget.' The use of foreign exchange budgets in various Latin American countries during recent years is reviewed by the present study. Without expressing any judgment on the desirability of exchange controls and restrictions, the study attempts merely to explain the role of exchange budgets where such restrictions exist. The actual use and operation of such budgets in Latin America vary widely, the purpose ranging from a simple statistical control to the application of severe restrictions. A body of literature on this subject has yet to be developed. The objectives of an exchange budget could be more effectively realized if the experiences and techniques of various countries were carefully analyzed, and the results of the analysis made generally available to those responsible for the preparation and implementation of the budget. Exchange budgets are prepared in most countries where there is a need for controls or restrictions in the foreign exchange market, but also in some countries where there is a substantial measure of exchange freedom. The present review concentrates particularly on those countries where restrictions are so extensive that the role played by the foreign exchange budget is of great importance. It does not cover all the situations in which exchange budgets are used in Latin America, nor does it discuss exhaustively the role of the budget in each particular case.
Theory and Evidence on the Dynamic Interactions between Sovereign Credit Default Swaps and Currency Options

Using sovereign CDS spreads and currency option data for Mexico and Brazil, we document that CDS spreads covary with both the currency option implied volatility and the slope of the implied volatility curve in moneyness. We propose a joint valuation framework, in which currency return variance and sovereign default intensity follow a bivariate diffusion with contemporaneous correlation. Estimation shows that default intensity is much more persistent than currency return variance. The market price estimates on the two risk factors also explain the well-documented evidence that historical average default probabilities are lower than those implied from credit spreads.
Satellite and Surface Observations of Strong Wind Zones Accompanying Thunderstorms

Abstract This paper describes how the strength of thunderstorm gut fronts can frequently be determined from the satellite-derived speed of the clouds associated with the gust front and the appearance of the cloud patterns on the visible and enhanced IR satellite imagery. Rapidly moving gust fronts are generally associated with strong surface wind speeds, with the strongest winds located in the portion of the arc boundary closest to the most vigorous convection. The region of most vigorous convection can be pinpointed by the cloud-edge gradients and the appearance of the anvil cirrus on enhanced infrared imagery. The relationship between cloud patterns and gust front strength was obtained by plotting surface wind data on 1 and 2 km resolution visible satellite imagery. The speeds of the clouds associated with the gust fronts were determined using an image analyzer with a video disk capable of storing images and displaying them in motion.
Implementation, capabilities, and benchmarking of Shift, a massively parallel Monte Carlo radiation transport code

This work discusses the implementation, capabilities, and validation of Shift, a massively parallel Monte Carlo radiation transport package authored at Oak Ridge National Laboratory. Shift has been developed to scale well from laptops to small computing clusters to advanced supercomputers and includes features such as support for multiple geometry and physics engines, hybrid capabilities for variance reduction methods such as the Consistent Adjoint-Driven Importance Sampling methodology, advanced parallel decompositions, and tally methods optimized for scalability on supercomputing architectures. The scaling studies presented in this paper demonstrate good weak and strong scaling behavior for the implemented algorithms. Shift has also been validated and verified against various reactor physics benchmarks, including the Consortium for Advanced Simulation of Light Water Reactors' Virtual Environment for Reactor Analysis criticality test suite and several Westinghouse AP1000? problems presented in this paper. These benchmark results compare well to those from other contemporary Monte Carlo codes such as MCNP5 and KENO.
Abstract 4149: Pathway-based serum microRNA profiling and late-stage non-small cell lung cancer survival

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer mortality in the world. Nearly half of NSCLC patients are diagnosed with late-stage (stage III or stage IV) disease with an overall 5-year survival rate of less than 15%. Deregulation of microRNAs (miRNAs) is involved in cancer development, progression, and prognosis. Circulating miRNAs have been suggested as promising biomarkers for early detection, diagnosis, and prognosis of cancer. This ongoing study is to utilize a pathway-based approach to screen and validate serum miRNA profiles as predictors of survival using a large patient cohort of 348 late-stage NSCLC patients. In the testing set, pre-treatment serum miRNA profiles of four good- (survival time > 24 months) and four poor-survival (survival time −6 ). The 2-year overall survival rate in patients with high serum miR-93-3p expression was significantly lower than that in those with low expression with an adjusted HR of 1.59 (95% CI, 1.24 - 2.03) (P = 2x10 −4 ). In contrast, serum level of let-7g, that targets SMAD2, TGFBR1 and the activin A receptor family was significantly lower in the poor-survival group than in the good-survival group (P = 7x10 −4 ), and patients with high serum let-7g expression was associated with a significantly better two-year survival (HR=0.48, 95% CI, 0.37 - 0.62, P = 1x10 −8 ). Our results suggest that serum miR-30d, miR-93-3p and let-7g may become valuable biomarkers for survival in late-stage NSCLC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4149. doi:1538-7445.AM2012-4149
A Decision-making Structure for Price Decisions:

Pricing practice remains largely intuitive and routine. To gain insight as to why, the author examines critically some of the trends and gaps in the literature and practice. A comprehensive and sys...
Economic analysis of dyspepsia

A variety of organic and non-organic diseases can present with symptoms of dyspepsia or upper abdominal pain, and a large diagnostic and therapeutic armamentarium is available to manage symptoms of dyspepsia. How extensively should a diagnostic search be conducted; and where does the best path run through the maze of potential combinations of tests and therapies? Physicians have hoped that economic and medical decision analyses would help them to find the most cost-effective and most efficacious means to deal with dyspepsia. Because of the large variety of potential diagnoses, diagnostic procedures and therapeutic means, however, it is very doubtful that a single most effective or least expensive strategy can ever be developed to apply to every patient with dyspepsia. Following the lines of common medical sense is probably more cost-effective than observing a rigid regimen derived from an economical analysis.
Revealing hidden helix propensity in Aβ peptides by molecular dynamics simulations.

Using all-atom explicit solvent model and exhaustive replica exchange molecular dynamics simulations we studied the conformational ensembles of several amino-truncated Aβ peptides. In our simulatio...
Prevalence of Pancreatic Steatosis at a Pediatric Tertiary Care Center.

OBJECTIVES Pancreatic steatosis in adults has been proposed to be associated with obesity; however, data on pancreatic steatosis in children are lacking. Our study aimed to measure the prevalence of pancreatic steatosis in children and to examine its association with obesity and nonalcoholic fatty liver disease. METHODS This is a retrospective chart review study of 232 patients 2 to 18 years old who underwent abdominal computed tomographic imaging in the emergency department or inpatient ward within a 1-year time span and from whom demographics, anthropometrics, and medical history were obtained. Our radiologist determined mean Hounsfield unit (HU) measurements for the pancreas, liver, and spleen. A difference of -20 between the pancreas and spleen (psHU) and between the liver and spleen was used to determine fatty infiltration. RESULTS Of the 232 patients, 11.5% had a psHU less than -20. The prevalence of pancreatic steatosis was more than double among obese children (19%) than that in nonobese groups (8%). There is a significant correlation between the psHU and liver-spleen HU (r = 0.50, P < 0.001). CONCLUSIONS Pancreatic steatosis was identified in 10% of the study population and is associated with obesity. Also, pancreatic steatosis is significantly associated with nonalcoholic fatty liver disease. This is the first study assessing the prevalence of pancreatic steatosis in children.
The Analysis of the Construction of Chinese Ethnic Minority's Physical laws

Based on the literature review in this area,this paper analyzes the current situation and problems of the construction of Chinese minority's physical laws and regulations.For instance,there has been little physical laws and regulations about the ethnic minority as well as their propaganda,and the local physical laws has ignored the real content of the ethnical minority itself.In order to further the development of the construction of the laws and regulations,some suggestions,such as detail the specific laws and spread their propaganda,are promoted at last.
Phenolic compounds from Nymphaea odorata.

Assay-guided fractionation of the ethanol extract of Nymphaea odorata resulted in the identification of two lignans, one new (1) and one known (2), together with six known flavonol glycosides (3−8). The structures of 1−8 were established by spectroscopic analysis as nymphaeoside A (1), icariside E4 (2), kaempferol 3-O-α-l-rhamnopyranoside (afzelin, 3), quercetin 3-O-α-l-rhamnopyranoside (4), myricetin 3-O-α-l-rhamnopyranoside (myricitrin, 5), quercetin 3-O-(6‘ ‘-O-acetyl)-β-d-galactopyranoside (6), myricetin 3-O-β-d-galactopyranoside (7), and myricetin 3-O-(6‘ ‘-O-acetyl)-β-d-galactopyranoside (8). Compounds 3, 4, and 7 showed marginal inhibitory effect against fatty acid synthase with IC50 values of 45, 50, and 25 μg/mL, respectively.
Properties of myofibril-bound calpain activity in longissimus muscle of callipyge and normal sheep.

Properties of the calpain bound to myofibrils in longissimus muscle from callipyge or noncallipyge sheep were examined after 0, 1, 3, and 10 d of postmortem storage at 4 degrees C. Western analysis has shown that most of this calpain is mu-calpain, although the sensitivity of the antibodies used in the earlier studies could not eliminate the possibility that up to 10% of the calpain was m-calpain. The calpain is bound tightly, and very little is removed by washing with the detergent Triton X-100; hence, it is not bound to phospholipids in the myofibril. Over 25% of total mu-calpain was bound to myofibrils from at-death muscle, and this increased to approximately 40% after 1 d postmortem. The amount of myofibril-bound mu-calpain increased only slightly between 1 and 10 d of postmortem storage. The percentage of autolyzed mu-calpain increases with time postmortem until after 10 d postmortem, when all myofibril-bound mu-calpain is autolyzed. The specific activity of the myofibril-bound calpain is very low and is only 6 to 13% as high as the specific activity of extractable mu-calpain from the same muscle. It is unclear whether this low specific activity is the result of unavailability of the active site of the myofibril-bound calpain to exogenous substrate. The myofibril-bound calpain degrades desmin, nebulin, titin, and troponin T in the myofibrils, and also releases undegraded alpha-actinin and undergoes additional autolysis when incubated with Ca(2+); all these activities occurred slowly considering the amount of myofibril-bound calpain. Activity of the myofibril-bound calpain was partly (58 to 67%) inhibited by the calpain inhibitors, E-64 and iodoacetate; was more effectively inhibited by a broader-based protease inhibitor, leupeptin (84 to 89%); and was poorly inhibited (43 to 45%) by calpastatin. Release of undegraded alpha-actinin and autolysis are properties specific to the calpains, and it is unclear whether some of the myofibril-bound proteolytic activity originates from proteases other than the calpains or whether the active site of myofibril-bound calpain is shielded from the inhibitors. Activities and properties of the myofibril-bound calpain were identical in longissimus muscle from callipyge and normal sheep, although previous studies had indicated that the "normal" longissimus was much more tender than the callipyge longissimus. Hence, it seems unlikely that the myofibril-bound calpain has a significant role in postmortem tenderization of ovine longissimus.
Hamdan v. Rumsfeld - U.S. Supreme Court decision on legality of military commissions established by President Bush

Hamdan v. Rumsfeld. 126 S.Ct. 2749. United States Supreme Court, June 29, 2006. In Hamdan v. Rumsfeld, the U.S. Supreme Court found that the military commissions established by President George W. Bush were unauthorized by law and inconsistent with both the Uniform Code of Military Justice (UCMJ) and the 1949 Geneva Conventions. Rejecting jurisdictional challenges to its resolving the legality of the tribunals, the Court found the military commission proceedings against Hamdan to violate the “uniformity” requirement of the UCMJ, under which military commissions must be governed by the same standards as courtsmartial except where impracticable. The Court also found the tribunals to violate the Geneva Conventions as incorporated by Article 21 of the UCMJ, because the commissions did not qualify as “regularly constituted courts” as required under Common Article 3.
Arguments en faveur de la double origine des Nématodes néarctiques du genre Heligmosomoides Hall, 1916

1) Description d’une nouvelle espece : Heligmosomoides douglasi parasite d’un Cricetide Reithrodontomys raviventris, originaire de Californie (U.S.A.). Cette espece est caracterisee par des spicules courts et un nombre eleve de cretes cuticulaires. Ses caracteres morphologiques la rapprochent des autres Heligmosomoides nearctiques. Le seul point particulier est sa presence chez un Cricetide et non un Microtide.2) Contrairement a l’opinion generalement admise Heligmosomoides polygyrus polygyrus (Dujardin, 1845) (= Nematospiroides dubius Baylis, 1926), parasite d’Apodemus sylvaticus en Europe occidentale, n’a pas ete retrouve chez les Rongeurs d’Amerique du Nord. Ce sont 2 sous-especes du polygyrus morphologiquement distinguables, que l’on rencontre chez les Rongeurs de la region nearctique :a)H. polygyrus bakeri n. sub. sp., parasite de Mus musculus (Murides) et de Reithrodontomys megalotis et Reithrodontomys raviventris (Cricetides), est caracterise par une augmentation relative du nombre des cretes cuticulaires par rapport a la longueur du corps, comme chez H. p. corsicus. Mais il se distingue du precedent par 2 caracteres : la bourse caudale est plus developpee et la cote 4 gauche est presqu’aussi longue que la cote 5. b)H. polygyrus americanus n. sub. sp., parasite de Phenacomys intermedius (Miorotide) est caracterise par une diminution relative du nombre des cretes cuticulaires par rapport a la longueur du corps. En outre les cotes 8 presentent une branche interne a leur extremite proximale et les spicules sont plus longs.La presence de ces 2 sous-especes peut s’expliquer, nous semble-t-il, par un double phenomene de capture : Le polygyrus europeen aurait ete introduit en Amerique du Nord par les Souris grises Mus musculus et aurait subi une legere sub-speciation pour donner H. p. bakeri. A partir de cette forme, la sous-espece du Phenacomys se differencie avec une forte sub-speciation (allongement des spicules, diminution des cretes cuticulaires).Dans notre conception, l’introduction des Heligmosomoides en Amerique du Nord s’est donc produite de 2 facons :a )L’introduction d’un premier groupe, essentiellement infeode aux Microtides, a eu lieu au Pleistocene et s’est effectuee par le detroit de Bering correlativement au passage des hotes. b )L’introduction d’un second groupe, connu actuellement par 2 sous-especes du polygyrus europeen, a du se produire beaucoup plus recemment lorsque Mus musculus est arrivee en Amerique du Nord par passage sur bateau a travers l’Atlantique (fig. 5).3) Heligmosomoides montanus Durette-Desset 1967, parasite primitivement decrit chez Microtus longicaudus d’Alaska, a ete trouve pour la premiere fois chez Microtus californicus en Californie.
You Can Lead a Horse to Water, But Can You Pay to Make Him Drink? An Ethical Analysis of Research on Using Incentives to Promote Patient Health

In the mid 1980s, advances in vaccine technology led to the development of a safe and highly effective vaccine for the prevention of hepatitis B virus (HBV) infection (Zajac 1986; Andre 1989; Szmun...
Cryptosporidium infection in solid organ transplantation

Diarrhea is a common complication in solid organ transplant (SOT) recipients and may be attributed to immunosuppressive drugs or infectious organisms such as bacteria, viruses or parasites. Cryptosporidium usually causes self-limited diarrhea in immunocompetent hosts. Although it is estimated that cryptosporidium is involved in about 12% of cases of infectious diarrhea in developing countries and causes approximately 748000 cases each year in the United States, it is still an under recognized and important cause of infectious diarrhea in SOT recipients. It may run a protracted course with severe diarrhea, fluid and electrolyte depletion and potential for organ failure. Although diagnostic methodologies have improved significantly, allowing for fast and accurate identification of the parasite, treatment of the disease is difficult because antiparasitic drugs have modest activity at best. Current management includes fluid and electrolyte replacement, reduction of immunosuppression and single therapy with Nitazoxanide or combination therapy with Nitazoxanide and other drugs. Future drug and vaccine development may add to the currently poor armamentarium to manage the disease. The current review highlights key epidemiological, diagnostic and management issues in the SOT population.
Prescriptions for a New Age

Here, Michael Genovese presents his agenda to reform the war powers in light of the new demands of a new age. He calls for slightly more presidential authority, and a different form of accountability for the president’s decisions on war. Arguing that the eighteenth-century Constitution is not well suited for a twenty-first-century superpower facing the threat of terrorism, Genovese calls for a more muscular presidency, but one still enchained by congressional accountability.
The Self as Discovery and Creation in Western and Indian Philosophy

Two inscriptions were carved on the facade of the temple of Apollo at Delphi: “Know thyself” and “Nothing in excess” These admonitions were not unrelated. Man was advised to know himself — yet in his knowing he was to avoid extremes. One extreme was the attempt to go beyond his finitude, to act as though he were a god. “Hybris” — the term used to designate this extreme, meant an outrage against the nature of things. Originally it denoted the offspring of the union of a wild boar and a domestic sow. The other extreme was the attempt to act as though he were not a member of society. The Greeks held that man is a city animal. He who lived outside the polis was called a private being. “Idios” was the term for such a being. At Delphi, then, the Greeks were reminded of their natural and social contingencies: “Know yourself, but in your knowing don’t become a hybrid or an idiot !”
A Pragmatic Teaching Philosophy

Patricia M. Shields is the recipient of the 2002 NASPAA Excellence in Teaching Award, given “in recognition of outstanding contributions to education for public service through excellence in teaching.”
Generative mechanistic explanation building in undergraduate molecular and cellular biology

When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of mo...
Kant on Extension and Force: Critical Appropriations of Leibniz and Newton

In the history of modem philosophy Kant is often described as the arch-epistemologist, taking a “Critical turn” through the construction of a grand synthesis of the rationalist and empiricist traditions, which emphasise either reason or the senses (respectively) as the exclusive source of knowledge, by arguing that “[w]ithout sensibility, no object would be given to us, and without understanding none would be thought... Only from their unification can cognition arise” (Kant, Critique of Pure Reason [CPR], A51/B75).1 As apt as this description of Kant qua pure epistemologist may be, it is clear that it must be supplemented in many ways. In addition to his revolutionary work outside theoretical philosophy in ethics and aesthetics, Kant is particularly interested in physics throughout his career. Although Kant’s epistemology influences his physics in significant ways2, it is important to consider questions that arise at the level of physics in order to see that his epistemology does not contribute to the resolution of all such questions all by itself.
Discovering scientific influence using cross-domain dynamic topic modeling

We describe an approach using dynamic topic modeling to model influence and predict future trends in a scientific discipline. Our study focuses on climate change and uses assessment reports of the Intergovernmental Panel on Climate Change (IPCC) and the papers they cite. Since 1990, an IPCC report has been published every five years that includes four separate volumes, each of which has many chapters. Each report cites tens of thousands of research papers, which comprise a correlated dataset of temporally grounded documents. We use a custom dynamic topic modeling algorithm to generate topics for both datasets and apply cross-domain analytics to identify the correlations between the IPCC chapters and their cited documents. The approach reveals both the influence of the cited research on the reports and how previous research citations have evolved over time. For the IPCC use case, the report topic model used 410 documents and a vocabulary of 5911 terms while the citations topic model was based on 200K research papers and a vocabulary more than 25K terms. We show that our approach can predict the importance of its extracted topics on future IPCC assessments through the use of cross domain correlations, Jensen-Shannon divergences and cluster analytics.
Metaphoric extension, relational categories, and abstraction

We propose that concepts exist along a continuum of abstraction, from highly concrete to highly abstract, and we explore a critical kind of abstract category: relational abstractions. We argue that...
Ldb1 mediates trans enhancement in mammals

Singular olfactory receptor (OR) gene expression coincides with the formation of a multi-chromosomal enhancer hub that associates with the only transcribed OR allele in each cell. This hub consists of converging transcriptional enhancers, or Greek Islands, defined by stereotypic binding of Lhx2 and Ebf on a shared, composite DNA motif. How this multi-chromosomal hub, or any other genomic compartment, assembles is unknown, and so is the significance of compartmentalization in transcription. Here, we report that LIM domain binding protein 1 (Ldb1), which is recruited by Lhx2 and Ebf to Greek Islands, promotes robust and specific trans interactions between these enhancers. In addition to disrupting Greek Island hubs, Ldb1 deletion also causes significant downregulation of OR transcription. Thus, our data provide insight to the formation of genomic compartments, confirm the essential role of interchromosomal interactions in OR gene choice, and establish trans enhancement as a mechanism for mammalian gene activation.
Ideal Cardiovascular Health and Adiposity: Implications in Youth.

Background The American Heart Association set 2020 Strategic Impact Goals that defined cardiovascular risk factors to be included in the concept of ideal cardiovascular health (ICH). The prevalence of ICH among differing levels of adiposity in youth, especially severe obesity, is uncertain. Methods and Results The cross‐sectional study measured ICH metrics in 300 children and adolescents stratified by adiposity: normal weight, overweight/obese, and severely obese. ICH incorporates 7 behavioral and health metrics, and was characterized as poor, intermediate, or ideal. Individual ICH metrics were transformed into standardized sample z ‐scores; a summary ICH sample z ‐score was also calculated. Multivariable linear regression models were used to estimate differences in ICH sample z ‐scores by adiposity status. Of the 300 participants, 113 were classified as having normal weight, 87 as having overweight/obesity, and 100 as having severe obesity (mean age 12.8 years, SD 2.7; 48% female). No participants met the criteria for ICH; 80% of those classified as having normal weight, 81% of those with overweight/obesity, and all of those with severe obesity were in poor cardiovascular health. After multivariable adjustment, those with overweight/obesity (sample z ‐score: −1.35; 95% confidence interval, −2.3, −1.1) and severe obesity (sample z ‐score: −1.45; 95% confidence interval, −2.9, −0.92) had lower overall ICH sample z ‐scores compared with participants with normal weight. Results were similar for individual ICH metrics. Conclusions Poor cardiovascular health was highly prevalent in youth; ICH sample z ‐scores increased across levels of adiposity. Youth with obesity, particularly those with severe obesity, remain a rich target for primary prevention efforts. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01508598.
Direct-acting antiviral agents in patients with hepatitis C cirrhosis.

Patients with cirrhosis who are infected with hepatitis C virus (HCV) are the most in need of antiviral treatment. Virologic cure improves fibrosis and quality of life while reducing liver-related morbidity and mortality. In mid-2011, the addition of direct-acting antiviral agents (DAAs)—the protease inhibitors boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex)—to pegylated interferon α-2a/b and ribavirin revolutionized the treatment of HCV infection by increasing cure rates across all fibrosis scores in patients with genotype 1 HCV infection. However, patients with advanced fibrosis or cirrhosis are the most difficult to treat, and the addition of DAAs increases treatment side effects as well as potency. Five phase III DAA trials have been published to date, but they contain limited data on patients with cirrhosis. This review will examine the available data and will describe the evolution of HCV therapy in patients with cirrhosis from the standard-of-care therapy of the past decade into the new era of DAAs.
Airborne Measurements of Electric Charging of Marine Fog

Measurements of electric field strength in the vicinity of a straight and distinct edge of an extensive 60 m marine fog show a region of enhanced field over the clear area adjacent to the edge. Also discussed is the new airborne field mill used for these measurements. This instrument, a rotating capacitive plate type is particularly small and light for aircraft nose boom mounting. Use of modern microelectronic circuitry allows the signal processing to be done beneath the 0.15 m long by 0.05 m diameter capacitive plates. Output from the processor, rotating with the plates, is digital and is transmitted optically to the stationary frame.
Critical Values and Transforming Data: Teaching Statistics with Social Justice

Despite the dearth of literature specifically on teaching statistics using social justice, there is precedent in the more general realm of teaching using social justice, or even in teaching mathema...
Abstract 552: PEPD is an essential regulator of p53 tumor suppressor

Peptidase D (PEPD), also known as prolidase among other names, is an enzyme that hydrolyzes dipeptides with proline or hydroxyproline at the carboxy terminus and is believed to be important for collagen metabolism, as proline and hydroxyproline are very abundant in collagen. Interestingly, we recently found that eliminating cellular PEPD causes cell death and tumor regression due to p53 activation. Here, we show that PEPD binds to and suppresses over half of nuclear and cytoplasmic p53 under normal conditions, independent of its enzymatic activity. PEPD binds to the proline-rich domain in p53, which inhibits phosphorylation of nuclear p53 and MDM2-mediated mitochondrial translocation of nuclear and cytoplasmic p53. Indeed, PEPD competes with MDM2 for p53 binding. However, the PEPD-p53 complex is critical for p53 response to stress, as stress signals doxorubicin (DOX) and hydrogen peroxide each must free p53 from PEPD in order to achieve robust p53 activation, which is mediated by reactive oxygen species. Thus, PEPD stores p53 for stress response, but this also renders cells dependent on PEPD for survival as it suppresses p53. Our results reveal a major p53 regulatory mechanism and a critical physiological function of PEPD. The p53-PEPD system likely operates in most if not all cells, since both p53 and PEPD are expressed ubiquitously. Disrupting PEPD suppression of p53 may be an important therapeutic strategy in cancer, as our data show that PEPD knockdown by RNA interference in tumors in mice causes p53 activation in the tumor tissues and tumor regression. Our study also reveals a previously unrecognized anticancer mechanism of DOX. We show that the key step in DOX-induced p53 activation is the disruption of p53 association with PEPD via reactive oxygen species. This finding also raises the intriguing question of whether other stress-inducing anticancer agents also disrupt the PEPD-p53 complex for p53 activation and suggests that antioxidants may inhibit the anticancer activity of DOX and other agents by inhibiting p53 separation from PEPD. This work is supported by NCI grants and Roswell Park Alliance Foundation Grants. Citation Format: Lu Yang, Yun Li, Arup Bhattacharya, Yuesheng Zhang. PEPD is an essential regulator of p53 tumor suppressor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 552.
Climate mobilizations and democracy: the promise of scaling community energy transitions in a deliberative system

Climate mobilizations to address the rapidly accelerating impacts of climate change are now an imperative; but can these processes be accomplished democratically? This paper shows how climate mobil...
Risk factors for reoperation, readmission, and early complications after below knee amputation.

Abstract Background Many patients undergoing below knee amputations (BKA) return for subsequent unplanned operations, hospital readmission, or postoperative complications. This unplanned medical management negatively impacts both patient outcomes and our healthcare system. This study primarily investigates the risk factors for unplanned reoperation following BKA. Methods Below knee amputations from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database from the years 2012–2014 were identified by CPT code 27880 for amputation through the tibia and fibula. Our query identified 4631 BKA cases, including 30 day complications. Multivariate logistic regression modeling was performed on several patient demographic and disease factors to assess for independent predictors of unplanned reoperation. Secondary outcomes of unplanned and related readmissions (related to the procedure), major complications, minor complications, and mortality were also included in the analysis. Results Of 4631 BKAs identified, 9.63% (446/4631) underwent unplanned reoperations and 8.75% (405/4631) had unplanned and related readmissions. Major complications were experienced by 12.8% (593/4631) and minor complications by 8.7% (401/4631). Thirty day mortality rate was 5.14% (238/4631). The most common procedures for unplanned operations were thigh amputations (128/446, 28.7%), debridement/secondary closure (114/446, 25.6%), and revision leg amputations (46/446, 10.32%). Factors associated with an increased risk of unplanned reoperation included patients transferred from another facility (Adjusted Odds Ratio [AOR] = 1.28; p = .04), recent smokers (AOR = 1.34; p = .02), bleeding disorder (AOR = 1.30; p = .02), and preoperative ventilator use (AOR = 2.38; p = .01). Conclusion Patients that were ongoing/recent smokers, had diagnosed bleeding disorders, required preoperative ventilator use, or were transferred in from another facility were associated with the highest risks of reoperation following BKA. This patient population experiences high rates of reoperation, readmission, complication, and mortality.
The Effect of Various Doses of Oral Vitamin D3 Supplementation on Gut Microbiota in Healthy Adults: A Randomized, Double-blinded, Dose-response Study.

BACKGROUND/AIM To investigate the effects of vitamin D3 supplementation on gut microbiota. PATIENTS AND METHODS Twenty adults with vitamin D insufficiency/deficiency [25(OH)D <30 ng/ml] were enrolled and given 600, 4,000 or 10,000 IUs/day of oral vitamin D3 Stool samples were collected at baseline and 8 weeks for identifying gut microbiota using 16S rRNA gene amplification and sequencing. RESULTS Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (p<0.05). After the intervention, we observed a dose-dependent increase in relative abundance of Bacteroides with a significant difference between the 600 IUs and the 10,000 IUs groups (p=0.027), and Parabacteroides with a significant difference between the 600 IUs and the 4,000 IUs groups (p=0.039). CONCLUSION Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria. A dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity was observed after vitamin D3 supplementation.
Does objectively-assessed sleep moderate the association between history of major depressive disorder and task-switching?

Abstract Background Executive function and psychomotor speed are consistently impaired in patients with major depressive disorder (MDD). Persistent cognitive impairments after depression remission are thought to reflect “scarring” from the neurotoxic effects of hypothalamic-pituitary-adrenal axis activity during a depressive episode. As sleep also deteriorates with depression and restores daytime executive functions, we examined whether adequate sleep could be protective against task-switching and psychomotor impairments associated with a history of MDD. Methods This cross-sectional study tested task-switching associations with MDD history, sleep, and their interaction to determine whether sleep continuity and sleep duration moderate the relationship between MDD history and task-switching performance. Results After adjusting for age, sex, education, current depressive symptoms, and use of anti-depressants, a history of MDD, particularly recurrent MDD, was associated with slower response speed and disproportionately lower accuracy on repetition trials compared to switch trials, reflecting impaired adoption of a task-set. Regardless of MDD history, higher wake after sleep onset and shorter total sleep time were associated with slower response times, but neither sleep measure moderated the association between depression history and task-switching performance. Limitations This cross-sectional study cannot assess the causal direction of associations. One night of sleep in the laboratory was used to assess sleep and a single task-switching paradigm was used to assess executive function. Conclusions These results suggest that longer, more continuous sleep is associated with greater psychomotor speed across healthy controls and those with a history of MDD, but MDD-task-switching associations are not mitigated by longer or more continuous sleep.
Graphene Activation Explains the Enhanced Hydrogen Evolution on Graphene-Coated Molybdenum Carbide Electrocatalysts.

Molybdenum carbides (MoxC) have shown high catalytic activities toward hydrogen evolution reaction (HER) when coupled with graphene. Herein, we use density functional theory (DFT) calculations in c...
Protein–Antibody Conjugates (PACs): A Plug-and-Play Strategy for Covalent Conjugation and Targeted Intracellular Delivery of Pristine Proteins

We report here on protein-antibody conjugates (PACs) that are used for antibody-directed delivery of protein therapeutics to specific cells. PACs have the potential to judiciously combine the merits of two prolific therapeutic approaches-biologics and antibody-drug conjugates. We utilize spherical polymer brushes to construct PACs using the combination of two simple and efficient functionally orthogonal click chemistries. In addition to the synthesis and characterization of these nanoparticles, we demonstrate that PACs are indeed capable of specifically targeting cells based on the presence of target antigen on the cell surface to deliver proteins. The potentially broad adaptability of PACs opens up new opportunities for targeted biologics in therapeutics and sensing.