cssi/SciSciGPT-SciSciNet huggingface dataset:
Clockless, Continuous-Time Analog Correlator Using Time-Encoded Signal Processing Demonstrating Asynchronous CDMA for Wake-Up Receivers

A clockless, continuous-time (CT) analog correlator circuit realization is presented based on time-encoded analog signal processing. Voltage-controlled oscillators (VCOs) transform the analog voltage signals into time-encoded analog signals and, in the process, perform signal integration; CT, digital-style delay cells combined with phase-frequency detectors followed by capacitive summers implement a CT matched filter. The correlator prototype designed in 65-nm CMOS-LP technology consumes 37 nW from 0.54 V and is used in the baseband of a wake-up receiver to despread asynchronous code-division multiple access (CDMA) codes and demonstrate code-domain filtering for an 11-bit Barker code. The wake-up receiver’s sensitivity is enhanced by 2 dB to −80.9 dBm for a missed detection ratio of 10−3, and its selectivity is improved by 5 dB, thanks to the use of the correlator. Simultaneous wake-up using CDMA is demonstrated with selective responses of the receiver to different desired codes in the presence of an undesired code.
Prevalence of Ophidiomyces ophiodiicola, the Causative Agent of Snake Fungal Disease, in the Interior Plateau Ecoregion of Tennessee, USA

The fungal pathogen Ophidiomyces ophiodiicola, the causative agent of snake fungal disease, has been implicated in declines of North American snake populations since 2006 and the geographic range of this pathogen is still not fully known. In Tennessee, US, O. ophiodiicola has been detected since 2012, but large portions of the state have not been surveyed for this pathogen. Our primary objective was to monitor the prevalence of O. ophiodiicola in the Interior Plateau ecoregion of Tennessee by swabbing all snakes that were encountered during road cruising survey efforts in 2017 and 2018. Eleven snakes of four species, copperhead (Agkistrodon contortrix), common water snake (Nerodia sipedon), black kingsnake (Lampropeltis nigra), and smooth earthsnake (Virginia valeriae), tested positive for the presence of O. ophiodiicola. Overall, 9.2% (11/120) of snakes sampled tested positive for the presence of O. ophiodiiola, and we further observed a seasonal trend in detections with summer months having the greatest frequency of detections. Our results extend the known geographic range of O. ophiodiicola in Tennessee by adding four previously unconfirmed O. ophiodiicola-positive counties. Further sampling will need to be conducted across west Tennessee because this is the most data-deficient region of the state. Our results offer additional evidence of the presence of this pathogen in Tennessee and will help researchers further understand the geographic distribution and host range.
Predicting differentiated developmental trajectories of prosocial behavior: A 12-year longitudinal study of children facing early risks and vulnerabilities:

The current study examined the heterogeneity in the development of school-based prosocial behavior from Grades 1 to 12 and the role of multiple early childhood antecedents in predicting heterogeneo...
Intergenerational and transgenerational effects of environmental factors and a role for the epigenome

Abstract In this chapter, studies that examine the relationship between exposure to chemicals and health effects across multiple generations are highlighted. A variety of environmental contaminants associated with intergenerational affects are discussed. Studies that relate predominantly to intergenerational inheritance as well as some that exemplify true transgenerational inheritance are detailed. Finally, the prevailing mechanistic theories tying exposure to toxicants during the prenatal periods to later-in-life health outcomes are provided.
Life Cycle Management of Micra Transcatheter Pacing System: Data From a High‐Volume Center

Background Data on the management of Micra transcatheter pacing system (TPS) at the time of an upgrade or during battery depletion is limited. Objective We sought to evaluate the management patterns of patients implanted with a Micra TPS during long-term follow-up. Methods We retrospectively identified patients who underwent Micra implantation from April 2014 to November 2019. We identified patients who underwent extraction (n = 11) or had an abandoned Micra (n = 12). Results We identified 302 patients who received a Micra during the period of the study. Mean age was 72.7 ± 15.4 years, 54.6% were men, and left ventricular ejection fraction was 51.9 ± 5.2%. Mean follow-up was 1105.5 ± 529.3 days. Procedural complications included pericardial tamponade (n = 1) treated with pericardiocentesis, significant rise in thresholds (n = 6) treated with reimplantation (n = 4), and major groin complications (n = 2). Indications for extraction included an upgrade to cardiac resynchronization therapy (CRT) device (n = 3), bridging after extraction of an infected transvenous system (n = 3), elevated thresholds (n = 3), and non-Micra-related bacteremia (n = 2). The median time from implantation to extraction was 78 days (interquartile range: 14-113 days), with the longest extraction occurring at 1442 days. All extractions were successful, with no procedural or long-term complications. Indications for abandonment included the need for CRT (n = 6), battery depletion (n = 2), increasing thresholds/failure to capture (n = 3), and pacemaker syndrome (n = 1). All procedures were successful, with no procedural or long-term complications. Conclusion In this large single-center study, 6% of patients implanted with a Micra required a system modification during long-term follow-up, most commonly due to the requirement for CRT pacing. These patients were managed successfully with extraction or abandonment.
To screen or not to screen: Assessing caregiver comfort with social determinants of health screening

Background: Screening for social determinants of health (SDOH), defined as social circumstances affecting patient health, is recommended by the AAP for all children. While research has shown that SDOH screening can improve health, ethical considerations of screening must also be addressed. In particular, caregiver comfort with SDOH screening specifically where, how, and by whom screening occurs is unclear. Objective: To develop and pilot a survey asking caregivers where, how, and …
The Effects of Adverse Childhood Experiences and Gender on Developmental Trajectories of Internalizing and Externalizing Outcomes

Adverse Childhood Experiences (ACEs) are linked to problematic outcomes, but it remains unclear how ACEs affect developmental patterns of harmful behavior, and whether this varies by gender. This s...
Investigating the indoor environmental quality of different workplaces through web-scraping and text-mining of Glassdoor reviews

The analysis of occupants’ perception can improve building indoor environmental quality (IEQ). Going beyond conventional surveys, this study presents an innovative analysis of occupants’ feedback a...
Decreased transfusion requirements with use of acute normovolemic hemodilution in open aortic aneurysm repair.

Abstract Objective Acute normovolemic hemodilution (ANH) is an operative blood conservation technique involving the removal and storage of patient blood after the induction of anesthesia, with maintenance of normovolemia by crystalloid and/or colloid replacement. Developed and used predominately in cardiac surgery, ANH has been applied to the vascular surgery population. However, data regarding the effects on transfusion requirements in this population are limited. The objective of the present study was to compare the transfusion requirements and coagulopathy for patients who had undergone open abdominal aortic aneurysm repair (oAAAR) using ANH to those for patients who had received only product replacements, as clinically indicated. Methods We performed a retrospective review of patients who had undergone elective oAAAR at a quaternary aortic referral center from 2017 to 2019. Those eligible for ANH, with no active cardiac ischemia, no valvular disease, normal left ventricular and right ventricular function, chronic kidney disease stage 38%, and a normal coagulation profile were included in the present study. Patient demographics and characteristics and operative variables, including aneurysm extent, clamp site, visceral and renal ischemia time, operative time, and transfusion requirements, were collected. Postoperative morbidity, mortality, and length of stay were analyzed. The patients with and without ANH were matched and compared. Continuous measures were analyzed using Wilcoxon rank sum tests and t tests. Results During the study period, 209 oAAARs had been performed. Of the 209 patients, 76 had met the inclusion criteria. Of these 76 patients, 27 had undergone ANH and 49 had not. The patients with ANH had required fewer PRBC transfusions intraoperatively (median, 0 U; interquartile range [IQR], 0-1 U; median, 1 U; IQR, 0-2 U; P = .02), at 24 hours (median, 0 U; IQR, 0-1 U; vs median, 1 U; IQR, 0-2 U; P = .008), at 48 hours (median, 0 U; IQR, 0-1 U; vs median, 1 U; IQR, 0-2; P = .007), and throughout the admission (median, 0 U; IQR, 0-1 U; vs median, 2 U; IQR, 0-2 U; P = .011). No difference was found in the number of intraoperative platelet or cryoprecipitate transfusions. At 48 hours, the ANH group had had significantly greater platelet counts (142 ± 35.8 × 103/μL vs 124 ± 37.6 × 103/μL; P = .044), lower partial thromboplastin time, and lower international normalized ratio. No difference in myocardial infarction, return to the operating room, or mortality (one death overall). The ANH patients had a shorter length of stay (7.0 ± 2.7 vs 8.8 ± 4.8 days; P = .041). Conclusions The use of ANH during oAAAR resulted in fewer intraoperative and postoperative PRBC transfusions with improved coagulation parameters and a shorter hospital length of stay.
Strategic Release of Information in Platforms: Entry, Competition, and Welfare

Besides their role in reducing frictions and facilitating trade, two-sided platforms increasingly collect and process data, e.g., supply and demand forecasts, that can further affect market outcomes. This paper studies how a platform may choose to disclose its information about future demand to maximize its profits and the resulting implications for the welfare of its market participants. By strategically designing its information disclosure policy, a platform can influence the entry and pricing decisions of its potential suppliers, thereby increasing profits. In general, it is optimal for the platform to disclose its information partially to either "nudge'' entry when it is a priori costly for suppliers to join or, conversely, discourage it when suppliers do not have access to attractive alternatives. Although platforms can boost their profits significantly by strategically communicating their forecasts to market participants, this may come at the expense of consumers, who end up having fewer trading options or facing higher prices.
Spina bifida: a biopsychosocial perspective

Abstract Spina bifida is the most common congenital birth defect of the central nervous system, affecting multiple domains of functioning. This chapter provides an overview of spina bifida and describes its neurological, physical, cognitive, and psychosocial features. This includes examining the epidemiology of spina bifida, its different types, and possible causal and preventative mechanisms. This chapter also describes neuropsychological domains, such as intellectual functioning and attention, and psychosocial domains, such as peer relationships and psychological functioning. Variability in illness severity and degree of impairment in spina bifida are discussed, as well as how impairment can change as a function of development. The current literature indicates that disease and environmental factors can both curtail and worsen the degree of impairment. Interventions for affected domains are reviewed and areas for future research are discussed.
Fundamental Thermal Analysis

This chapter presents the fundamental equations governing the physical behavior of PCMs in melting and solidification . The classical Stefan problem is discussed, along with the way in which natural convection present in the melting phase can change the motion of the melt front. Various methods are presented to account for changes in effective thermal conductivity when foams and nanoparticles are used.
Query processing in multidatabase systems

A novel algorithm to efficiently process a query in a multidatabase environment is devised. The proposed approach reduces data movement between sites and local processing time by allowing local selection and projection for a user query. Also, the algorithm efficiently removes null values incurred due to an outer join by generating the results as a set of sets, gives users more accurate information by presenting all data values for an overlap part, and gives users flexibility by enabling them to define their own processing strategy at a query time. >
Role of membrane organization and membrane domains in endocytic lipid trafficking.

Lipid compositions vary greatly among organelles, and specific sorting mechanisms are required to establish and maintain these distinct compositions. In this review, we discuss how the biophysical properties of the membrane bilayer and the chemistry of individual lipid molecules play a role in the intracellular trafficking of the lipids themselves, as well as influencing the trafficking of transmembrane proteins. The large diversity of lipid head groups and acyl chains lead to a variety of weak interactions, such as ionic and hydrogen bonding at the lipid/water interfacial region, hydrophobic interactions, and van-der-Waals interactions based on packing density. In simple model bilayers, these weak interactions can lead to large-scale phase separations, but in more complex mixtures, which mimic cell membranes, such phase separations are not observed. Nevertheless, there is growing evidence that domains (i.e., localized regions with non-random lipid compositions) exist in biological membranes, and it is likely that the formation of these domains are based on interactions similar to those that lead to phase separations in model systems. Sorting of lipids appears to be based in part on the inclusion or exclusion of certain types of lipids in vesicles or tubules as they bud from membrane organelles.
Limited-information Goodness-of-fit Testing of Hierarchical Item Factor Models

In applications of item response theory, assessment of model fit is a critical issue. Recently, limited-information goodness-of-fit testing has received increased attention in the psychometrics literature. In contrast to full-information test statistics such as Pearson's X(2) or the likelihood ratio G(2) , these limited-information tests utilize lower-order marginal tables rather than the full contingency table. A notable example is Maydeu-Olivares and colleagues'M2 family of statistics based on univariate and bivariate margins. When the contingency table is sparse, tests based on M2 retain better Type I error rate control than the full-information tests and can be more powerful. While in principle the M2 statistic can be extended to test hierarchical multidimensional item factor models (e.g., bifactor and testlet models), the computation is non-trivial. To obtain M2 , a researcher often has to obtain (many thousands of) marginal probabilities, derivatives, and weights. Each of these must be approximated with high-dimensional numerical integration. We propose a dimension reduction method that can take advantage of the hierarchical factor structure so that the integrals can be approximated far more efficiently. We also propose a new test statistic that can be substantially better calibrated and more powerful than the original M2 statistic when the test is long and the items are polytomous. We use simulations to demonstrate the performance of our new methods and illustrate their effectiveness with applications to real data.
Ionic Mechanism of Ouabain-Induced Concurrent Apoptosis and Necrosis in Individual Cultured Cortical Neurons

Energy deficiency and dysfunction of the Na+, K+-ATPase are common consequences of many pathological insults. The nature and mechanism of cell injury induced by impaired Na+, K+-ATPase, however, are not well defined. We used cultured cortical neurons to examine the hypothesis that blocking the Na+, K+-ATPase induces apoptosis by depleting cellular K+ and, concurrently, induces necrotic injury in the same cells by increasing intracellular Ca2+ and Na+. The Na+, K+-ATPase inhibitor ouabain induced concentration-dependent neuronal death. Ouabain triggered transient neuronal cell swelling followed by cell shrinkage, accompanied by intracellular Ca2+ and Na+ increase, K+ decrease, cytochrome c release, caspase-3 activation, and DNA laddering. Electron microscopy revealed the coexistence of ultrastructural features of both apoptosis and necrosis in individual cells. The caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD-FMK) blocked >50% of ouabain-induced neuronal death. Potassium channel blockers or high K+ medium, but not Ca2+ channel blockade, prevented cytochrome c release, caspase activation, and DNA damage. Blocking of K+, Ca2+, or Na+ channels or high K+ medium each attenuated the ouabain-induced cell death; combined inhibition of K+ channels and Ca2+ or Na+ channels resulted in additional protection. Moreover, coapplication of Z-VAD-FMK and nifedipine produced virtually complete neuroprotection. These results suggest that the neuronal death associated with Na+, K+-pump failure consists of concurrent apoptotic and necrotic components, mediated by intracellular depletion of K+ and accumulation of Ca2+ and Na+, respectively. The ouabain-induced hybrid death may represent a distinct form of cell death related to the brain injury of inadequate energy supply and disrupted ion homeostasis.
A HOL Mechanisation of the Axiomatic Semantics of a Simple Distributed Programming Language

This paper presents the axiomatic semantics for a simple distributed language, and its mechanization in HOL. The constructs of this language include those basic to a very simple sequential programming language in addition to asynchronous send and synchronous receive statements. The language has the appearance of a system programming language that supports sequential execution extended with message passing, and would be a suitable basis for coding distributed operating systems and applications. Included in the mechanization are functions which generate the goals associated with the verification of sequences of simple statements in the language. In contrast to Gordon's work on the HOL mechanization of programming logics, the starting point for our work is an axiomatic (rather than denotational definition) of the language, in the style of Schlichting's definition of message passing.
Asset Allocation Dynamics in the Hedge Fund Industry

This paper examines asset allocation dynamics of hedge funds through conducting optimal change point test on an asset class factor model. Based on the average F-test and the Bayesian Information Criterion (BIC), we find that more dynamic hedge funds exhibit significantly better quality than less dynamic funds, signaled by lower return volatility, stricter share restrictions, and high water mark provision. In particular, a higher degree of dynamics is shown to be associated with better risk-adjusted performance at the individual fund level. We find that the degree of a fund’s dynamics is closely related to share restrictions. However, the outperformance of highly dynamic funds is robust even after controlling for share restrictions. Subperiod analysis suggests that the superiority of asset allocation dynamics is mostly driven by performance during earlier time periods before the peak of the technology bubble. Fund flow analysis suggests that abnormal returns in the hedge fund industry are diminishing as capital flows in and arbitrage opportunities are not infinitely exploitable.
T Cell Repertoire in Mice with Alopecia Areata

It has become clear that skin infiltrating autoreactive CD4 + T helper cells play a crucial role in the initiation of alopecia areata. However, the natures of the pathogenic T cell clones as well as of the skin antigen they recognize remain obscure. Here, we analyzed the T cell receptor repertoire expressed in the spleen of diseased mice. We consistently observed the dominant expansion of a limited set of T cell clones expressing Vβ38.2/Jβ2.5 T cell receptor rearrangement. We conclude that T cell response in mice alopecia areata is markedly oligoclonal; a feature that may permit the design of selective immunotherapy.
Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease

How stage-specific enhancer dynamics modulate gene expression patterns essential for organ development, homeostasis and disease is not well understood. Here, we addressed this question by mapping chromatin occupancy of GATA4--a master cardiac transcription factor--in heart development and disease. We find that GATA4 binds and participates in establishing active chromatin regions by stimulating H3K27ac deposition, which facilitates GATA4-driven gene expression. GATA4 chromatin occupancy changes markedly between fetal and adult heart, with a limited binding sites overlap. Cardiac stress restored GATA4 occupancy to a subset of fetal sites, but many stress-associated GATA4 binding sites localized to loci not occupied by GATA4 during normal heart development. Collectively, our data show that dynamic, context-specific transcription factors occupancy underlies stage-specific events in development, homeostasis and disease.
Discrete simulation of the dynamics of spread of extreme opinions in a society

Abstract We propose a discrete model for how opinions about a given “extreme” subject, about which various groups of a population have different degrees of enthusiasm for or susceptibility to, such as fanaticism, extreme social and political positions, and terrorism, may spread. The model, in a certain limit, is the discrete analogue of a deterministic continuum model suggested by others. We carry out extensive computer simulation of the model by utilizing it on lattices with infinite- or short-range interactions, and on symmetric and hierarchical (or directed) Barabasi–Albert scale-free networks. Several interesting features of the model are demonstrated, and comparison is made with the deterministic continuum model.
STOCK SPLITS AND MARKET ANOMALIES

Previous studies of market efficiency have reported conflicting results when examining stock splits. Recent studies reporting market inefficiencies have made several methodological improvements, but have failed to control for the possible confounding effects of “unexpected” changes in corporate earnings announced near the stock split event. Stock splits are often issued around the time that firms experience large increases in corporate earnings. Therefore, an explicit treatment of earnings announcements in an event study of stock splits may yield further insights. This study found no market inefficiencies associated with splitting securities that experienced moderate changes in corporate earnings. However, anomalies were associated with splitting securities that experienced large increases in corporate earnings. These results suggest that previous findings of market inefficiencies, attributable solely to the stock split event, may be due in part to unexpected changes in corporate earnings.
Intrinsically Disordered C-Terminal Tails of E. coli Single-Stranded DNA Binding Protein Regulate Cooperative Binding to Single-Stranded DNA

The homotetrameric Escherichia coli single-stranded DNA binding protein (SSB) plays a central role in DNA replication, repair and recombination. E. coli SSB can bind to long single-stranded DNA (ssDNA) in multiple binding modes using all four subunits [(SSB)65 mode] or only two subunits [(SSB)35 binding mode], with the binding mode preference regulated by salt concentration and SSB binding density. These binding modes display very different ssDNA binding properties with the (SSB)35 mode displaying highly cooperative binding to ssDNA. SSB tetramers also bind an array of partner proteins, recruiting them to their sites of action. This is achieved through interactions with the last 9 amino acids (acidic tip) of the intrinsically disordered linkers (IDLs) within the four C-terminal tails connected to the ssDNA binding domains. Here, we show that the amino acid composition and length of the IDL affects the ssDNA binding mode preferences of SSB protein. Surprisingly, the number of IDLs and the lengths of individual IDLs together with the acidic tip contribute to highly cooperative binding in the (SSB)35 binding mode. Hydrodynamic studies and atomistic simulations suggest that the E. coli SSB IDLs show a preference for forming an ensemble of globular conformations, whereas the IDL from Plasmodium falciparum SSB forms an ensemble of more extended random coils. The more globular conformations correlate with cooperative binding.
New distributional records of ticks from Southeast Asia and the Pacific (Metastigmata : Argasidae, Ixodidae)

The following 11 species of ticks are recorded for the first time from various countries in Southeast Asia and the Pacific: Argas (Persicargas) robertsi (Indonesia), Amblyomma nitidum (West Irian),...
A paradoxical stimulatory effect of berberine on guinea-pig ileum contractility: Possible involvement of acetylcholine release from the postganglionic parasympathetic nerve and cholinesterase inhibition

Abstract The effects of berberine on guinea-pig ileum contractility were studied in both transmurally-stimulated and unstimulated preparations. Transmural stimulation (80 V, 0.5 ms, 0.05 Hz) of the guinea-pig ileal segments produced a twitch response. Berberine (10−8–10−5 M) enhanced this response dose-dependently. Atropine (10−7 M), but not mecamylamine (10−5 M), abolished this response. Acetylcholine (3 × 10−9 and 10−8 M) also enhanced the response to transmural stimulation. Pretreatment with hemicholinium (3 × 10−5 M) antagonized the effect of berberine but failed to change that of acetylcholine. Berberine (10−5 M) also antagonized the α2-adrenoceptor agonist xylazine (10−8 and 10−7 M)-induced inhibition of the twitch response to transmural stimulation. In unstimulated ileal preparations, berberine (10−5 M) produced contractile responses. In these preparations, atropine (10−6 M), but not mecamylamine (10−4 M), abolished the response to berberine. Furthermore, berberine (10−6 – 10−4 M) inhibited dose-dependently the cholinesterase activity of the guinea-pig blood. The results suggest that berberine increase ileal contractility by: 1) increasing acetylcholine release from the postganglionic parasympathetic nerve terminal, 2) increasing acetylcholine retention through an inhibition of cholinesterase activity, and 3) blocking α2-adrenoceptors, possibly in the postganglionic parasympathetic nerve.
Molecular analysis of microbial communities in mobile deltaic muds of Southeastern Papua New Guinea.

A culture-independent examination of microbial diversity in mobile deltaic sediments from the Gulf of Papua, Papua New Guinea, was conducted by sequence analysis of 16S rDNA clone library. Universal small subunit primers were used to amplify DNA extracted from the sediment. Of 91 clones randomly selected from the library, 33 contained unique non-chimeric sequences. Analysis of these unique sequences showed that the majority of them belonged to bacteria (94.5%), with proteobacteria being the dominant division (74.8%). One sequence belonging to Crenarchaeota and another to Euryarchaeota were found as well. Bacterial sequences belonging to the following major divisions were identified: Cytophaga–Flexibacter–Bacteroides (5.5%), low GC Gram-positives (1.1%), Nitrospira group (3.3%), OP8 candidate division (2.2%), OS-K candidate division (2.2%), Planctomyces (1.1%), α, δ, γ and ϵ-subdivisions of Proteobacteria (4.4, 20.9, 19.8 and 23.1%, respectively) and Spirochaetales (4.4%). The composition of 16S rDNA library of the Gulf of Papua sediments is similar to those for deepwater sediments from around the Japanese Islands, indicating a possible cosmopolitan nature of microbial communities in suboxic and anoxic sediments of the Pacific. It appears that many Papua/New Guinea sequences are loosely affiliated with bacteria involved in sulfur cycling, thus supporting the hypothesis that the sulfur cycle may be important in early diagenesis of suboxic sediments.
UBIQUITIN-PROTEASOME-DEPENDENT DEGRADATION OF APOLIPOPROTEIN B100 IN VITRO

Abstract Apolipoprotein B100 (apoB) is a large secretory protein that forms very low density lipoprotein in liver. An in vitro degradation assay was developed using rabbit reticulocyte (RR) lysate in order to investigate the mechanism of intracellular degradation of newly synthesized apoB by the ubiquitin-proteasome pathway. [3H]apoB, isolated from [3H]leucine pulsed/chased Hep G2 cells, was degraded 51% when incubated for 2 h at 37°C in an assay mixture that included RR lysate (source of the ubiquitin conjugation system and proteasome) and an exogenous ATP regenerating system. ApoB degradation was ATP-dependent and degradation fragments were not observed suggesting that the very large apoB molecule was extensively degraded. ApoB degradation was decreased to 50% when potent proteasome inhibitors, clasto-lactacystin β-lactone (10 μM) or MG-132 (50 μM), were added to the reaction mixture, but was not affected by the cysteine protease inhibitor, E-64, or the serine protease inhibitor, phenylmethylsulfonyl fluoride. ApoB degradation was inhibited by the mutant ubiquitin protein K48R and by ubiquitin aldehyde, an inhibitor of ubiquitin-protein isopeptidases. During incubation ubiquitination of apoB increased even as apoB was being degraded. These results suggest that in vitro degradation of apoB, a large secretory protein that is normally found in the endoplasmic reticulum (ER) lumen or associated with the ER membrane, was proteasome-dependent and involved both ubiquitination and deubiquitination steps.
The first muscular branch of the deep inferior epigastric artery: an anatomical study and clinical applications.

BACKGROUND Reconstruction of distal lower extremity defects often necessitates free tissue transfer. Because of its reliable vascular anatomy, pedicle length, and vessel size, the free rectus abdominis flap is widely used for this purpose. To minimize donor-site morbidity, several authors have described a segmental, or "partial," free rectus abdominis flap. METHODS After an initial study in cadavers, measurements of the vascular anatomy of the first muscular branch of the deep inferior epigastric artery were recorded during abdominal wall dissections in 18 patients undergoing free rectus abdominis reconstruction. The partial rectus muscle free flap or "rectus plug" was then used in seven patients to reconstruct lower extremity defects. RESULTS The first muscular branch was seen in all 20 dissections. The mean distance to the branch point from the origin of the deep inferior epigastric artery was 53.60 ± 9.63 mm. The branch point occurred before the deep inferior epigastric artery passed under the lateral border of the rectus in five dissections and deep to the muscle in 15. The mean length of the muscular branch was 20.85 ± 4.04 mm, and the mean total pedicle length was 77.0 ± 8.46 mm. The supplied portion of muscle was used successfully to reconstruct lower extremity defects in seven patients; at 1-year follow-up, all had healed with good contour and without donor- or recipient-site complications. CONCLUSION The free rectus plug has minimal donor-site morbidity and a reliable anatomy, and should be considered for coverage of lower extremity defects smaller than 25 cm2. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, V.
Mechanisms of anabolic androgenic steroid modulation of α1β3γ2L GABAA receptors

Modulation of GABA(A) receptors induced by both anabolic androgenic steroids (AAS) and the benzodiazepine (BZ) site agonist, zolpidem, show equivalent dependence upon gamma subunit composition suggesting that both compounds may be acting at a shared allosteric site. Here we have characterized modulation induced by the AAS, 17alpha-methyltestosterone (17alpha-MeT), for responses elicited from alpha(1)beta(3)gamma(2L) GABA(A) receptors and compared it to modulation induced by the BZ site agonists, zolpidem and diazepam. For responses elicited by brief pulses of 20 microM GABA, both the AAS and the BZ site compounds significantly increased the peak current amplitudes and total charge transfer, although 17alpha-MeT was an appreciably weaker agonist than either diazepam or zolpidem at alpha(1)beta(3)gamma(2L) receptors. Neither class of modulator enhanced peak current amplitudes for responses elicited by mM concentrations of GABA. BZ site compounds altered time constants of deactivation, desensitization, and recovery from desensitization, however 17alpha-MeT had no overall effect on these parameters. Experiments in which 17alpha-MeT and BZ site ligands were applied concomitantly indicated that potentiation elicited by 17alpha-MeT and zolpidem were additive and that potentiation by 17alpha-MeT could be elicited in the presence of concentrations of flumazenil that blocked BZ potentiation. Finally, kinetic modeling suggests that while effects of 17alpha-MeT can be simulated by altering receptor affinity, the data for these alpha(1)beta(3)gamma(2L) receptors were best fitted by simulations in which 17alpha-MeT increases transitions into the singly liganded open state. Taken together, our results suggest that 17alpha-MeT does not act at the high-affinity BZ site, but may elicit some of its effects at the low affinity BZ site or at a novel site.
VACCINATED — Visual analytics for characterizing a pandemic spread VAST 2010 Mini Challenge 2 award: Support for future detection

Given a set of hospital admittance and death records, the challenge was to characterize the spread of a pandemic in terms of the attack and mortality rates, spatiotemporal patterns of onset and the recovery time. We began the analysis by preprocessing the hospital admittance records using the University of Pittsburgh's CoCo classifier [1]. CoCo is a text classification software that takes hospital admittance fields and classifies them into chief complaint categories (Botulinic, Constitutional, Gastrointestinal, Hemorrhagic, Neurological, Rash, Respiratory, and Other). The choice of the CoCo classifier was based on its online availability as well as its well documented classification performance metrics, see [1]. Once the data was classified, we utilized and extended work done by the Purdue University Visual Analytics Center on healthcare analysis [2]. Our system consists of a combination of linked views, showing time series views of syndromes and death rates through line graph views (Figure 1 — Top), stacked graph views showing deaths (Figure 1 — Bottom), geographical map views showing the impact by country (not illustrated in this paper), and summary windows providing statistical breakdowns of the data (not illustrated in this paper). All views are linked through an interactive time slider that allows users to explore the data over time. Extensions to our previous work [2] include the stacked graph view, summary windows, new control chart methods, and an interactive ‘tape measure’ tool.
How obligatory is anaerobiosis

Historically many bacteria have been classified as obligate anaerobes. They have been construed as wholly intolerant of oxygen, a feature that was originally ascribed to their lack of superoxide dismutases and catalases. Clostridial species were regarded as classic examples. We now know that this view is quite wrong: enzymes that scavenge superoxide, hydrogen peroxide and even oxygen itself abound in anaerobes. In the current issue of Molecular Microbiology, Hillmann et al. demonstrate that full production of these proteins can allow Clostridium acetobutylicum to survive and even grow in oxygenated culture medium. Evidently, oxidative defences in anaerobes can be robust. In all likelihood, they are critical for the movement of bacteria through aerobic environments to new anaerobic habitats.
Drug discrimination in rats: evidence for amphetamine-like cue state following chronic haloperidol.

Abstract Two groups of male Sprague-Dawley rats were trained to discriminate which of two levers to press for milk reinforcement on a VI-20 sec schedule of reinforcement on the basis of whether they were injected intraperitoneally with d-amphetamine (0.50 mg/kg or 1.50 mg/kg) or saline 15 min prior to daily 30 min training sessions. Following acquisition of the discrimination, dose-response functions were generated for both training-dose groups during 5 min test sessions. All subjects were then injected with 1.0 mg/kg of haloperidol for ten consecutive days and retested on either saline or intermediate doses of amphetamine on days 1,2,4 and 7 following the final haloperidol injection. The results indicated that chronic haloperidol enhanced the discriminative stimulus properties of amphetamine in both training groups. More importantly, when tested on saline, subjects in both training groups made significantly more responses on the d-amphetamine lever than observed prior to chronic haloperidol. On the basis of linear regression analysis of the dose-response curves it was shown that rats in both groups responded as though they had been injected with 0.18 mg/kg of d-amphetamine. In a second experiment this increase in amphetamine-lever responding when animals were tested with saline following chronic haloperidol was replicated and in addition it was observed that chronic amphetamine had the opposite effect on this measure.
MECHANISMS OF THE EPITHELIAL-MESENCHYMAL TRANSITION BY TGF-BETA

The formation of epithelial cell barriers results from the defined spatiotemporal differentiation of stem cells into a specialized and polarized epithelium, a process termed mesenchymal-epithelial transition. The reverse process, epithelial-mesenchymal transition (EMT), is a metastable process that enables polarized epithelial cells to acquire a motile fibroblastoid phenotype. Physiological EMT also plays an essential role in promoting tissue healing, remodeling or repair in response to a variety of pathological insults. On the other hand, pathophysiological EMT is a critical step in mediating the acquisition of metastatic phenotypes by localized carcinomas. Although metastasis clearly is the most lethal aspect of cancer, our knowledge of the molecular events that govern its development, including those underlying EMT, remain relatively undefined. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that oversees and directs all aspects of cell development, differentiation and homeostasis, as well as suppresses their uncontrolled proliferation and transformation. Quite dichotomously, tumorigenesis subverts the tumor suppressing function of TGF-beta, and in doing so, converts TGF-beta to a tumor promoter that stimulates pathophysiological EMT and metastasis. It therefore stands to reason that determining how TGF-beta induces EMT in developing neoplasms will enable science and medicine to produce novel pharmacological agents capable of preventing its ability to do so, thereby improving the clinical course of cancer patients. Here we review the cellular, molecular and microenvironmental mechanisms used by TGF-beta to mediate its stimulation of EMT in normal and malignant cells.
Demonstration of 300?kA CHI-startup current, coupling to transformer drive and flux savings on NSTX

Discharges formed by transient coaxial helicity injection (CHI) in the National Spherical Torus Experiment (NSTX) have attained peak currents of 300 kA for the first time. CHI-started discharges are coupled to induction, and ramped up to over 1 MA. Up to an additional 400 kA of toroidal current is produced, compared with discharges with the same inductive drive without CHI. These CHI-inductively coupled discharges demonstrate flux savings over standard NSTX inductive-only discharges, requiring significantly less transformer flux to reach 1 MA of toroidal current, as well as exhibiting higher elongation and lower internal inductance. These results indicate the potential for substantial current generation capability by CHI in NSTX and in future toroidal devices.
Electroosmotic flow-based pump for liquid chromatography on a planar microchip.

An electroosmotic flow (EOF)-based pump, integrated with a sol−gel stationary phase located in the electric field-free region of a microchip, enabled the separation of six nitroaromatic and nitramine explosives and their degradation products via liquid chromatography (LC). The integrated pump and LC system were fabricated within a single quartz substrate. The pump region consisted of a straight channel (3.0 cm × 230 μm × 100 μm) packed with 5-μm porous silica beads. The sol−gel stationary phase was derived from a precursor mixture of methyltrimethoxy- and phenethyltrimethoxysilanes and was synthesized in the downstream, field-free region of the microchip, resulting in a stationary-phase monolith with dimensions of 2.6 cm × 230 μm × 100 μm. Fluid dynamic design considerations are discussed, especially as they relate to integrating the EOF pump with the LC system. Pump and separation performance, as characterized by flow rate measurements, injection, elution, separation, and detection, point to a viable ana...
Effects of dietary protein restriction on the progression of advanced renal disease in the modification of diet in renal disease study

Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group. The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease. A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology. The average follow-up was 2.2 years. Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m2 who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded. The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d). Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death. Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d). In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease. A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected. If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure. Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease. In patients with GFR less than 25 mL/min/1.73 m2, we suggest a prescribed dietary protein intake of 0.6 g/kg/d.
Transfer of Alcohols and Ureas Across the Oral Mucosa Measured Using Streaming Potentials and Radioisotopes

Abstract The permeability of the oral mucosa to an alcohol and a urea series was studied using radioisotope transfer and the measurement of streaming potentials. Both methods yielded similar quantitative estimates of permeability. The rate of transfer of the smallest member of both series (methanol and urea) was greater than the second member (ethanol and methylurea). In the alcohol series, permeability increased as the chain length increased from ethanol to butanol. In contrast, the permeability of the oral mucosa to ethylurea and propylurea was less than to methylurea. However, butylurea had a greater rate of transfer than either propylurea or ethylurea.
A Study of Near-Surface Winds in Marine Cyclones Using Multiple Satellite Sensors

Abstract Synoptic-scale surface wind fields are developed using data from two Special Sensor Microwave/Imager (SSM/1) passive radiometers and the European Remote Sensing Satellite-1 (ERS-1) scatterometer for the lifetime of two northern Pacific winter storms. The data are merged with surface wind output from a planetary boundary layer (PBL) model. The inputs to the PBL model are from the European Centre for Medium-Range Weather Forecasts (ECMWF) global analyses. A method for interpolating these analyses to the time of the satellite passage, while preserving fundamental storm characteristics, was developed. Composite wind fields are constructed each time one or more of the satellites views the storms. These composite wind fields are compared to the near-surface wind fields from ECMWF analyses within the storm domain and to buoy wind data on a point-by-point basis. Comparison with ECMWF analyses shows that the composite winds are slightly higher and contain more mesoscale variability. Comparison with buoy d...
The Accelerated Phase of Chediak-Higashi Syndrome. An Expression of the Virus-Associated Hemophagocytic Syndrome?

The clinical and pathologic findings of four patients with Chediak-Higashi syndrome in the accelerated phase were studied in order to clarify the nature of this enigmatic process. Fever, lymphadenopathy, hepatosplenomegaly, and cytopenias were present in every patient. All cases demonstrated extensive parenchymal infiltrates in many organs composed of benign-appearing histiocytes manifesting hemophagocytosis accompanied by lymphocytes and plasma cells. Studies in one patient suggested a viral etiology with the findings of a low blood lymphocyte OKT4 to OKT8 ratio, acquired loss of lymphocyte response to mitogens, the presence of Epstein-Barr virus genome in the mononuclear cells of lymph node, blood, and bone marrow, and possible clinical responses to acyclovir. It is concluded that the accelerated phase of Chediak-Higashi syndrome may be the clinicopathologic expression of the virus-associated hemophagocytic syndrome.