cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessing regulatory information in developmental gene regulatory networks

Gene regulatory networks (GRNs) provide a transformation function between the static genomic sequence and the primary spatial specification processes operating development. The regulatory information encompassed in developmental GRNs thus goes far beyond the control of individual genes. We here address regulatory information at different levels of network organization, from single node to subcircuit to large-scale GRNs and discuss how regulatory design features such as network architecture, hierarchical organization, and cis-regulatory logic contribute to the developmental function of network circuits. Using specific subcircuits from the sea urchin endomesoderm GRN, for which both circuit design and biological function have been described, we evaluate by Boolean modeling and in silico perturbations the import of given circuit features on developmental function. The examples include subcircuits encoding positive feedback, mutual repression, and coherent feedforward, as well as signaling interaction circuitry. Within the hierarchy of the endomesoderm GRN, these subcircuits are organized in an intertwined and overlapping manner. Thus, we begin to see how regulatory information encoded at individual nodes is integrated at all levels of network organization to control developmental process.
Dysplasias in the Child’s Cervical Spine

Skeletal dysplasias are a diverse group of conditions with altered cartilage and bone development, therefore presenting unique cervical spine pathology and management challenges. A number of findings pose risk of quadriplegia or sudden death as early as the first year of life, necessitating an understanding of the diagnosis and natural history of these various disorders. This chapter aims to provide a framework to assess and manage cervical spine problems of the more common skeletal dysplasias.
Distinct roles for the cell adhesion molecule Contactin2 in the development and function of neural circuits in zebrafish

Contactin2 (Cntn2)/Transient Axonal Glycoprotein 1 (Tag1), a neural cell adhesion molecule, has established roles in neuronal migration and axon fasciculation in chick and mouse. In zebrafish, antisense morpholino-based studies have indicated roles for cntn2 in the migration of facial branchiomotor (FBM) neurons, the guidance of the axons of the nucleus of the medial longitudinal fascicle (nucMLF), and the outgrowth of Rohon-Beard (RB) central axons. To study functions of Cntn2 in later stages of neuronal development, we generated cntn2 mutant zebrafish using CRISPR-Cas9. Using a null mutant allele, we detected genetic interactions between cntn2 and the planar cell polarity gene vangl2, as shown previously with cntn2 morphants, demonstrating a function for cntn2 during FBM neuron migration in a sensitized background of reduced planar cell polarity signaling. In addition, maternal-zygotic (MZ) cntn2 mutant larvae exhibited aberrant touch responses and swimming, suggestive of defects in sensorimotor circuits, consistent with studies in mice. However, the nucMLF axon convergence, FBM neuron migration, and RB outgrowth defects seen in morphants were not seen in the mutants, and we show here that they are likely off-target effects of morpholinos. However, MLF axons exhibited local defasciculation in MZcntn2 mutants, consistent with a role for Cntn2 in axon fasciculation. These data demonstrate distinct roles for zebrafish cntn2 in neuronal migration and axon fasciculation, and in the function of sensorimotor circuits.
Snaps, Selfies, and Shares: How Three Popular Social Media Platforms Contribute to the Sociocultural Model of Disordered Eating Among Young Women.

Abstract The current study aimed to integrate and test the sociocultural model of disordered eating with theories explaining the impact of mass media on the development of disordered eating for use...
Polynomial Time Equilibria in Bottleneck Congestion Games

We consider bottleneck congestion games in an arbitrary graph G where player strategies are flows in G . The player's objective is to select a flow that minimizes the maximum load on any edge, that is, minimize the bottleneck congestion. We consider splittable and unsplittable games with pure strategies. It has been an open problem for many years to determine whether it is possible to compute in polynomial time Nash equilibriums for bottleneck congestion games in arbitrary graphs. For splittable games we provide a polynomial time algorithm to compute a Nash equilibrium which is also a global optimum. The unsplittable game problem is known to be PLS-complete, and so we focus on approximate Nash equilibria where players are approximately stable. For uniform player demands we give an algorithm to compute a O(log m)-approximate unsplittable equilibrium in polynomial time, where m is the number of edges. For non-uniform player demands we give an algorithm to compute a O(ζ log(ζ m))-approximate unsplittable equilibrium in polynomial time, where ζ = O(1 + log (dmax /dmin)) and dmax, dmin are the respective maximum and minimum player demands. To our knowledge, these are the first general results for efficiently computing equilibria of pure bottleneck congestion games in arbitrary graphs, both for the splittable and unsplittable cases.
Palliative Care and Quality Management: The Core Principles of Quality Improvement and their Utility in Designing Clinical Programs for End of Life Care and Complex Case Management Models

Over the past decade, efforts to define, build, and improve palliative care and care for complex chronic illness have been commonplace at both the micro—or organizational—and macro—or healthcare organization, payment, and regulatory policy—levels. Having grown largely out of the hospice movement, palliative care for many represents all that hospice does so well, and by extending hospice’s reach offers a promise of comfortable and compassionate care earlier in the disease process than hospice is often able to. To some, palliative care logically represents the epitome of high quality health care. Ideally palliative care is an “approach that improves the quality of life of patients and their families facing the problem associated with lifethreatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.” (World Health Organization, 2005) The goal of this chapter is to introduce the reader to the role of simple quality improvement methods in the development and enhancement of palliative care and complex case management programs. In addition to
Epidemiologic clues to the causes and routes to prevention of Alzheimer disease.

Identification of epidemiologic risk factors serves many purposes. These include 1) identification of high risk groups as potential targets for interventions; 2) identification of the candidate interventions (when the risk factor is susceptible to modification); and 3) suggestion of previously unsuspected causal mechanisms (when the risk relationship is unexpected and not readily explained by current causal theories). Two possible risk relationships will be discussed — one now well-known and the other novel — that may provide a means of reducing the risk of Alzheimer’s disease (AD). I will also suggest a causal theory that encompasses these epidemiologic observations and other recent data.
Peirce como leitor & leitura como devaneio

Scientific inquirers in the modern sense, those thinkers with whom C. S. Peirce most deeply identified, “have been successful because they have spent their lives not in their libraries and museums but in their laboratories and in the field” (CP 1.34). But, in fact, Peirce spent countless hours engaged in an activity he appears to slight in this and other passages. Indeed, he seems to have misread his life as a reader. The author offers a portrait of Peirce as a reader, but of even greater importance he draws upon Georges Poulet to sketch a phenomenology of reading and upon Elaine Scarry to offer an account of reading as a form of reverie. In addition, he shows how Peirce’s thought underwrites both of these endeavors, paying close attention to Peirce’s synechistic account of mind, consciousness, and subjectivity, but also consideration to the semeiotic categories of diagram, symbol, and to a less degree icons.
It is time to carpe diem with porcine ACTH – A comparison of porcine sequence corticotropin to tetracosactide hexaacetate in testing the hypothalamic pituitary adrenal axis in healthy individuals

Context: Our literature search revealed that the use of porcine sequence corticotropin has not been validated against tetracosactide hexaacetate in a healthy population. Aims: To study the efficacy of using porcine sequence corticotropin in comparison with tetracosactide hexaacetate in the evaluation of hypothalamo pituitary adrenal (HPA) axis. Materials and Methods: Fifteen healthy volunteers were enrolled. Serum cortisol was measured at 0 minute in all subjects and at 30 and 60 minutes after tetracosactide hexaacetate 250 μg intravenously. Four weeks later, serum cortisol level was measured at 0 minute and at 30 and 60 minutes following 24 units of porcine sequence corticotropin given intramuscularly. Results: Mean serum cortisol values with tetracosactide were 30.3 (±7.83) μg/dl and 31.27 (±7.36) μg/dl at 30 and 60 minutes, respectively. The mean cortisol values with porcine sequence corticotropin were 26.33 (±5.47) μg/dl and 31.59 (±6.40) μg/dl at 30 and 60 minutes, respectively. All subjects had a response qualified as normal or adequate at 30 minutes itself. Mean peak serum cortisol response was 32.65 (±7.76) μg/dl in tetracosactide group and 31.59 (±6.4) μg/dl in porcine sequence corticotropin group, and the responses in two groups were comparable (P = 0.686). There were no immediate side effects in both groups, with a lower cost of procedure in the porcine corticotropin group. Conclusion: Our study established the efficacy of porcine sequence corticotropin in testing the adequacy of HPA axis in healthy individuals. Our study also revealed that, the intactness of the HPA axis could be confirmed as early as 30 minutes in healthy individuals.
Spectroscopic evidence for acid-base interaction driven interfacial segregation.

Quantification of interfacial composition and interfacial energy is essential for understanding prevalent phenomena such as purification and adhesion. However, for high-energy planar solid surfaces, traditional approaches for determining both parameters are inadequate. We take advantage of interface-sensitive spectroscopy to calculate the interfacial composition for acetone–chloroform, tetrahydrofuran–benzene, and N,N-dimethylformamide (DMF)–benzene mixtures. We calculate the differences in interfacial energy for the two components of each mixture from the adsorption isotherms and compare with that obtained from acid–base and dispersive interactions. The interfacial energy calculated using interfacial segregation agrees with the interfacial energy calculated by acid–base and dispersive interactions. The comparison illustrates how molecular interactions control macroscopic interfacial segregation. In all three mixtures, acid–base interactions dominate interfacial segregation. Comparing the two approaches for DMF–benzene mixtures leads to evidence of DMF dimerization in benzene. Using the present approach, the interfacial composition and interfacial energy can now be understood for interfacial behaviors including wetting and self-assembly.
A Case for Digital Beamforming at mmWave

Due to the heavy reliance of millimeter-wave (mmWave) wireless systems on directional links, beamforming (BF) with high-dimensional arrays is essential for cellular systems in these frequencies. How to perform the array processing in a power efficient manner is a fundamental challenge. Analog and hybrid BF require fewer analog-to-digital and digital-to-analog converters (ADCs and DACs), but can only communicate in a small number of directions at a time, limiting directional search, spatial multiplexing and control signaling. Digital BF enables flexible spatial processing, but must be operated at a low quantization resolution to stay within reasonable power levels. This decrease in quantizer resolution introduces noise in the received signal and degrades the quality of the transmitted signal. To assess the effect of low-resolution quantization on cellular system, we present a simple additive white Gaussian noise (AWGN) model for quantization noise. Simulations with this model reveal that at moderate resolutions (3-4 bits per ADC), there is negligible loss in downlink cellular capacity from quantization. In essence, the low-resolution ADCs limit the high SNR, where cellular systems typically do not operate. For the transmitter, it is shown that DACs with 4 or more bits of resolution do not violate the adjacent carrier leakage limit set by 3-rd Generation Partnership Project (3GPP) New Radio (NR) standards for cellular operations. Further, this work studies the effect of low resolution quantization on the error vector magnitude (EVM) of the transmitted this http URL fact, our findings suggests that low-resolution fully digital BF architectures can be a power efficient alternative to analog or hybrid beamforming for both transmitters and receivers at millimeter wave.
Interaction Effects of the Amount of Practice, Preferred Cane Technique, and Type of Cane Technique Used on Drop-off Detection Performance:

This study examined the interaction effects of the amount of practice and the cane technique used in drop-off detection with a sample of 32 adults who were blind. The advantage of the constant cont...
LONG DURATION BALLOON PLATFORM

Abstract With the development of large plastic balloons in the early 1950's the use of the balloon as a research tool has increased dramatically. “Zero-pressure” balloons, made of polyethylene materials, and using ballasting techniques to maintain level float have been capable of meeting most of the requirements until recent years. The demand for exposure periods of days, weeks, and months for many scientific experiments, however has prompted the development of large “super-pressure”, globe circling, balloons capable of floating at a near constant altitude without ballasting. The work of the National Scientific Balloon Facility towards the development of a balloon vehicle that will accomplish the goal of sustaining a 250 Kg payload at 40 Km for 100 days is discussed.
Telemetry for Implantable Biosensors

This paper presents the design, fabrication, and test of antennas intended to be used for implantable biosensors. With the rising number of Americans managing chronic diseases, implantable biosensors offer better access to vital information for the management of these diseases. Diabetes, particularly, is managed by many through the means of a finger prick monitor, offering only a snap shot of blood glucose at a particular time without showing trends of a rise or fall in the glucose levels. Implantable sensors not only offer these trends via a continuous monitor, a fully implantable sensor offers these trends without the inconvenience of a monitoring system extending outside of the human body. Such appendages hinder the normal activity of patients monitoring their chronic diseases. Due to their full implantation, the sensor monitor needs to broadcast the analyte date from the human body outward to an external data collector. This broadcast requires an antenna made of a biocompatible antenna that operates on frequency bands allocated for medical telemetry as well as frequency bands allocated for unlicensed communication (e.g. WiFi and Bluetooth). This paper presents antennas designed using a biocompatible material Titanium Nitrite (TiN) for subcutaneous implant. The antennas presented operate on the Wireless Medical Telemetry System (WMTS) frequency band and the 2.4 GHz Industrial, Scientific, and Medical (ISM) frequency band.
Safety and Efficacy of MRI Scans in Patients With Implanted Microvascular Coupling Devices.

Objective To demonstrate the safety and compatibility of microvascular couplers in patients undergoing postoperative magnetic resonance imaging (MRI) scans. Study design Retrospective case series. Methods A consecutive review of 1,252 patients undergoing free tissue transfer for head and neck reconstruction at Oregon Health and Sciences University (OHSU) between 2010 and 2017 who had microvascular coupler Synovis, Baxter Deerfield, IL (Synovis Life Technologies, Saint Paul, MN) implantation were reviewed. One hundred fifteen patients had a subsequent MRI scan, which consisted of a variety of Phillips (Amsterdam, Netherlands) MRI machines ranging from 1.0 to 3.0 Tesla (T) in magnetic strength. Results These 115 patients underwent 121 free flaps with 131 couplers (including 32 flow couplers) utilized for venous anastomoses. Couplers ranged in size from 1.5 to 4.0 mm (3.0 mm [42%] followed by 3.5 mm [21%], 2.5 mm [19%], 2.0 mm [10%], 4.0 mm [6%], and 1.5 mm [2%]. Three hundred fifty-nine MRI scans (2 days to 91 months postoperatively) were obtained with 233 MRIs for cancer surveillance, and the remaining were obtained for neurologic disease, injury, or evaluation for metastases. No complications occurred related to the MRI and the metallic components of the coupler or other metal implants, such as reconstruction bars, vascular clips, or metallic surgical mesh. Additionally, no radiology report commented on MRI distortion due to the coupler placement, which contrasts the distortion seen with the other metallic implants. Conclusion Microvascular couplers and their constitutive stainless-steel pins have not been found to cause any complications in a large series of consecutive patients undergoing multiple MRIs with magnetic strength up to 3 T. The U.S. Food and Drug Administration advocates medical alert notification for patients with couplers; however, hesitation regarding potential MRI scanning for surveillance or otherwise is unwarranted. Level of evidence 4 Laryngoscope, 130:1428-1430, 2020.
The association between weather and the number of daily shootings in Chicago (2012–2016)

Previous studies have linked weather to crime and aggression but have not considered the causal structure of the variables included in the model(s). This cross-sectional study used data from 2012 to 2016 to measure the association between weather and the number of shootings in Chicago. The number of shootings per day was obtained via the Chicago Tribune (2012–2016). Daily high temperature, humidity, wind speed, difference in temperature from historical average, precipitation type and amount, were extracted via The Weather Underground. Weekend, holidays, and other non-school days were also included as possible effect measure modifiers. Causally-adjusted negative binomial regressions were used to evaluate the associations between the exposures of interest and daily number of shootings. A 10-degree (°C) higher temperature was significantly associated with 34% more shootings on weekdays, and 42% more shootings on weekends or holidays. A 10-degree higher temperature than average was also associated with 33.8% higher rate of shootings. In recent years, shootings in Chicago were more likely to happen on warm days and especially during the weekend or holidays. This finding is in-line with studies that have linked crime to higher temperature and also suggests that shootings may be related to when individuals are outside and more likely to encounter violence. Interventions that keep people inside, such as air-conditioning and summer programs for students, might be effective in reducing the number of shootings in Chicago. We believe using a causal structure is useful for understanding the link between weather and shootings.
Predisposing factors for positive D-Xylose breath test for evaluation of small intestinal bacterial overgrowth: a retrospective study of 932 patients.

Predisposing factors for positive D-Xylose breath test for evaluation of small intestinal bacterial overgrowth: A retrospective study of 932 patients
Serum Neurofilament Light Chain Levels are Associated with Lower Thalamic Perfusion in Multiple Sclerosis.

Both perfusion-weighted imaging (PWI) measures and serum neurofilament light (sNfL) chain levels have been independently associated with disability in multiple sclerosis (MS) patients. This study aimed to determine whether these measures are correlated to each other or independently describe different MS processes. For this purpose, 3T MRI dynamic susceptibility contrast (DSC)–PWI and single-molecule assay (Simoa)-based sNfL methods were utilized when investigating 86 MS patients. The perfusion measures of mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were derived for the normal-appearing whole brain (NAWB), the normal-appearing white matter (NAWM), the gray matter (GM), the deep GM (DGM), and the thalamus. The normalized CBV and CBF (nCBV and nCBV) were calculated by dividing by the corresponding NAWM measure. Age- and sex-adjusted linear regression models were used to determine associations between the DSC–PWI and sNfL results. False discovery rate (FDR)-adjusted p-values < 0.05 were considered statistically significant. A greater age and thalamic MTT were independently associated with higher sNfL levels (p < 0.001 and p = 0.011) and explained 36.9% of sNfL level variance. NAWM MTT association with sNfL levels did not survive the FDR correction. In similar models, a lower thalamic nCBF and nCBV were both associated with greater sNfL levels (p < 0.001 and p = 0.022), explaining 37.8% and 44.7% of the variance, respectively. In conclusion, higher sNfL levels were associated with lower thalamic perfusion.
Nucleus accumbens shell Orexin-1 receptors are not needed for single-bottle limited daily access alcohol intake in C57BL/6 mice

Abstract Excessive, binge drinking is a major contributor to the great harm and cost of alcohol use disorder. We recently showed, using both limited and intermittent-access two-bottle-choice models, that inhibiting nucleus accumbens shell (Shell) orexin-1-receptors (Ox1Rs) reduces alcohol intake in higher-drinking male C57BL/6 mice (Lei et al., 2019). Other studies implicate Ox1Rs, tested systemically, for several higher-drinking models, including the single-bottle, Rhodes Drinking-in-the-Dark paradigm. Here, we report studies examining whether Shell Ox1Rs contribute to alcohol intake in male mice using a single-bottle Limited Daily Access (LDA) drinking model modified from drinking-in-the-dark paradigms (2-h access starting 3 h into the dark cycle, 5 days per week). In addition, some previous work has suggested possible differences in circuitry for one- versus two-choice behaviors, and thus other mice first drank under a single-bottle schedule, and then an additional water bottle was included 2 days a week starting in week 3. Surprisingly, at the same time we were determining Ox1R importance for two-bottle-choice models, parallel studies found that inhibiting Shell Ox1Rs had no impact on drinking using the single-bottle LDA model, or when a second bottle containing water was added later during drinking. Furthermore, we have related Shell Ox1R regulation of intake to basal consumption, but no such pattern was observed with single-bottle LDA drinking. Thus, unlike our previous work showing the importance of Shell Ox1Rs for male alcohol drinking under several two-bottle-choice models, Shell Ox1Rs were not required under a single-bottle paradigm, even if a second water-containing bottle was later added. These results raise the speculations that different mechanisms could promote intake under single- versus two-bottle access conditions, and that the conditions under which an animal learns to drink can impact circuitry driving future intake.
Do dual eligible beneficiaries experience better health care in special needs plans

OBJECTIVE Dual Eligible Special Needs Plans (D-SNPs) were intended to provide better care for beneficiaries eligible for both Medicare and Medicaid through better coordination of these two programs. DATA SOURCES 671 913 dual eligible (DE) respondents to the 2009-2019 Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. STUDY DESIGN We compared the 2015-2019 experiences of DE beneficiaries in D-SNPs relative to fee-for-service Medicare (FFS) and non-SNP Medicare Advantage (MA) using propensity-score weighted linear regression. Comparisons were made to 2009-2014. 12 patient experience measures were considered. DATA COLLECTION METHODS Annual mail survey with telephone follow-up of non-respondents. PRINCIPAL FINDINGS More than 65% of DE beneficiaries enrolled in FFS. Of 12 measures, D-SNP performance was higher than non-SNP MA on two (P < .05), lower than non-SNP MA on two (P < .05), and higher than FFS on four (P < .01). DE beneficiaries did not report better coordination of care in D-SNPs. D-SNP performance was often worse than other coverage types in prior periods. CONCLUSIONS Relative to FFS Medicare, DE beneficiaries report higher immunization rates in D-SNPs, but slight or no better performance on other dimensions of patient experience. New requirements in 2021 may help D-SNPs attain their goal of better care coordination.
The string tension of SU(3) representations

I report on the status of a computation of fundamental and some higher representation string tensions in pure gauge SU(3). An order a^2 tadpole improved action and an anisotropic lattice are used. At present, the static quark potentials and the string tensions are calculated by measuring Wilson loops on an 8^3 x 24 lattice. Wilson loops for higher representations are measured in terms of Wilson loops of the fundamental representation. At the small and intermediate distances available, rough agreement with Casimir scaling is observed, and no color screening for the 8 representation is seen.
Protocol for Rapid Assessment of the Efficacy of Novel Wnt Inhibitors Using Zebrafish Models

Summary Dysregulation of Wnt signaling is a hallmark of many cancers, and the development of effective, non-toxic small-molecule Wnt inhibitors is desirable. Off-target toxicities of new compounds are typically tested in mouse models, which is both costly and time consuming. Here, we present a rapid and inexpensive protocol to determine the in vivo toxicity and efficacy of novel Wnt inhibitors in zebrafish using a combination of a fluorescence reporter assay as well as eye rescue and fin regeneration assays. These experiments are completed within 1 week to rapidly narrow drug candidates before moving to more expensive pre-clinical testing. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2020) .
Weighted utility theory with incomplete preferences

Abstract This paper axiomatizes the representations of weighted utility theory with incomplete preferences. These include the general multiple weighted utility representation as well as special cases of multiple utilities or multiple weights only. Some behavioral implications are explored in the context of a portfolio selection problem, which illustrates the potential applicability of such models to a range of problems.
TAPAC Accreditation Reviewers: Tips and Best Practices for the Accreditation Review Preparation, Process, and Report

This special topic session focused on guidelines and tips for current and potential reviewers for the Textile and Apparel Programs Accreditation Commission accreditation process. The session was divided into five components: (1) overview of the accreditation process, (2) planning for the site visit, (3) the site visit, (4) writing the report, and (5) conclusion.
APOE Gene Associated with Cholesterol-Related Traits in the Hispanic Population

Genetic variants in the apolipoprotein E (APOE) gene are associated with lipid metabolism and lipid-related traits in the non-Hispanic population. There have been limited studies regarding the association between the APOE gene and hypercholesterolemia in the Hispanic population; therefore, our aim for this study is to examine the APOE gene’s associations with cholesterol level and its related phenotypes. The APOE gene consists of three different alleles, e2, e3, and e4, with e4 being associated with dementia and cardiovascular diseases. A total of 1,382 subjects were collected from the Texas Alzheimer’s Research and Care Consortium (TARCC, N = 1320) and the Initial Study of Longevity and Dementia from the Rio Grande Valley (ISLD-RGV, N = 62). Questionnaires on demographics, medical history, and blood/saliva samples were collected and APOE genotypes were performed. We observed allele frequencies of the APOE e3 (96.7%), e4 (22.6%) and e2 (6.8%) alleles, respectively. Multivariable logistic regression revealed a significant association between the APOE e4 allele and hypercholesteremia (p = 1.8 × 10−4) in our studied Hispanic population. We prove for the first time, that the APOE e4 allele increases the risk for hypercholesterol in Hispanics. Further research is needed to confirm and supports our current findings.
Initial Angiotensin Receptor Blocker Response in Young Marfan Patients Decreases After 3 Years of Treatment.

Marfan syndrome is caused by mutations of the fibrillin-1 gene, which weakens the connective tissue integrity. Since 2003, bioavailability regulations of TGF-s through fibrillin alterations have been presumed of being the culprit mechanisms for aortic aneurysm development. We present the analysis of our single-center Marfan children and adolescents cohort to assess the influence of age, sex, degree of cardiovascular involvement and dosage on losartan effectivity. This prospective longitudinal registered echocardiographical investigation (EudraCT 2009-016139-36) of 49 patients with an average follow-up of 72 months focused on aortic root z-scores, elasticity, and yearly progression rates. The 33 patients under medication with losartan showed an aortic root z-score reduction during the first 36 months compared to 22 patients without medication presenting constant mild progression. Yet, results diminished under losartan thereafter, adding up to similar progressions over 72 months in both groups (0.07 ± 0.10/year versus 0.04 ± 0.11/year). Although male patients exhibited higher root z-scores, progression with and without medication was comparable to females and not age-dependent. In conclusion, losartan evoked a significant aortic root z-score regression in young Marfan patients over the first 3 years, but this effect mitigated thereafter. The initial improvement concurred with ameliorated elasticity; lower stiffness levels predicted better clinical outcome, but likewise only up to 36 months. Sex differences in dilatation severity were observed but neither age nor sex had significant influence on progression rates. Losartan dosages were gradually increased in more severely affected patients and provided an equal rate of root progression over 72 months in comparison to patients under losartan treatment with lesser baseline dilatation severity.
Chapter 3 Replacement of Y730 and Y731 in the α2 Subunit of Escherichia coli Ribonucleotide Reductase with 3‐Aminotyrosine using an Evolved Suppressor tRNA/tRNA‐Synthetase Pair

Abstract Since the discovery of the essential tyrosyl radical (Y•) in E. coli ribonucleotide reductase (RNR), a number of enzymes involved in primary metabolism have been found that use transient or stable tyrosyl (Y) or tryptophanyl (W) radicals in catalysis. These enzymes engage in a myriad of charge transfer reactions that occur with exquisite control and specificity. The unavailability of natural amino acids that can perturb the reduction potential and/or protonation states of redox‐active Y or W residues has limited the usefulness of site‐directed mutagenesis methods to probe the attendant mechanism of charge transport at these residues. However, recent technologies designed to site‐specifically incorporate unnatural amino acids into proteins have now made viable the study of these mechanisms. The class Ia RNR from E. coli serves as a paradigm for enzymes that use amino acid radicals in catalysis. It catalyzes the conversion of nucleotides to deoxynucleotides and utilizes both stable and transient protein radicals. This reaction requires radical transfer from a stable tyrosyl radical (Y 122 •) in the β subunit to an active‐site cysteine (C 439 ) in the α subunit, where nucleotide reduction occurs. The distance between the sites is proposed to be >35 A. A pathway between these sites has been proposed in which transient aromatic amino acid radicals mediate radical transport. To examine the pathway for radical propagation as well as requirements for coupled electron and proton transfers, a suppressor tRNA/aminoacyl‐tRNA synthetase (RS) pair has been evolved that allows for site‐specific incorporation of 3‐aminotyrosine (NH 2 Y). NH 2 Y was chosen because it is structurally similar to Y with a similar phenolic p K a . However, at pH 7, it is more easily oxidized than Y by 190 mV (≈4.4 kcal/mol), thus allowing it to act as a radical trap. Here we present the detailed procedures involved in evolving an NH 2 Y‐specific RS, assessing its efficiency in NH 2 Y insertion, generating RNR mutants with NH 2 Y at selected sites, and determining the spectroscopic properties of NH 2 Y• and the kinetics of its formation.
Chylomicron metabolism: Chylomicron uptake by bone marrow in different animal species

Previously it was shown in rabbits that 20-40% of the injected dose of chylomicrons was cleared from the plasma by perisinusoidal bone marrow macrophages. The present study was undertaken to determine whether the bone marrow of other species also cleared significant amounts of chylomicrons. Canine chylomicrons, labeled in vivo with [14C]cholesterol and [3H] retinol, were injected into marmosets (a small, New World primate), rats, guinea pigs, and dogs. Plasma clearance and tissue uptake of chylomicrons in these species were contrasted with results obtained in rabbits in parallel studies. The chylomicrons were cleared rapidly from the plasma in all animals; the plasma clearance of chylomicrons was faster in rats, guinea pigs, and dogs compared with their clearance from the plasma of rabbits and marmosets. The liver was a major site responsible for the uptake of these lipoproteins in all species. However, as in rabbits, the bone marrow of marmosets accounted for significant levels of chylomicron uptake. The uptake by the marmoset bone marrow ranged from one-fifth to one-half the levels seen in the liver. The marmoset bone marrow also took up chylomicron remnants. Perisinusoidal macrophages protruding through the endothelial cells into the marrow sinuses were responsible for the accumulation of the chylomicrons in the marmoset bone marrow, as determined by electron microscopy. In contrast to marmosets, chylomicron clearance by the bone marrow of rats, guinea pigs, and dogs was much less, and the spleen in rats and guinea pigs took up a large fraction of chylomicrons. The uptake of chylomicrons by the non-human primate (the marmoset), in association with the observation that triglyceride-rich lipoproteins accumulate in bone marrow macrophages in patients with type I, III, or V hyperlipoproteinemia, suggests that in humans the bone marrow may clear chylomicrons from the circulation. It is reasonable to speculate that chylomicrons have a role in the delivery of lipids to the bone marrow as a source of energy and for membrane biosynthesis or in the delivery of fat-soluble vitamins.
Genetic evidence that NarL function is not required for nitrate regulation of nitrate assimilation in Klebsiella pneumoniae M5al.

Abstract We cloned the narL gene, required for nitrate induction of respiratory nitrate reductase synthesis, from Klebsiella pneumoniae. The E. coli narL gene product shares sequence similarity with the response regulator proteins of two-component regulatory systems. We found that narL(+)-containing plasmids restored nitrate regulation of anaerobic respiratory gene expression in appropriate Escherichia coli hosts. The K. pneumoniae narL region encoded a protein whose migration in Laemmli gels was indistinguishable from that of the narL product of E. coli. We constructed a narL::Km mutant of K. pneumoniae. This mutation abolished nitrate induction of respiratory nitrate reductase synthesis but had no effect on nitrate induction of assimilatory nitrate and nitrite reductase synthesis. We conclude that K. pneumoniae has distinct nitrate-responsive regulators for controlling respiratory and assimilatory gene expression.
Gauge invariance and the quantization of mass (of gravitational charge)

In a previous paper (referred to as I in the text) it was shown that the Weyl principle of gauge invariance leads to the relationshipGm2 =ħc for a particle of inertial massm obeying the Dirac equation, whereG is the Newtonian gravitational constant. Instead of interpreting this equation to mean thatG takes on the extremely large valueħc/m2 inside a particle like an electron (as we did in I), we now write it in the formGm2/c = ħ and treat it as a quantization condition on the square of the gravitational charge √Gm. We show that this same quantization condition can be obtained from an angular-momentum component in the general-relativistic two-body problem as well as from the Machian definition of inertial mass in a rotating universe by using the Dirac-Schwinger procedure for quantizing charge. From this quantization condition we now deduce that the fundamental particle in Nature (the uniton) has an inertial mass equal to about 10-5 g. The possibility of using the uniton to shed light on the mystery of the « missing mass » in the Universe is discussed. Other cosmological implications of the uniton are also discussed and it is suggested that unitons can clear up the solar-neutrino discrepancy.
Herpes simplex-1 DNA polymerase. Identification of an intrinsic 5'----3' exonuclease with ribonuclease H activity.

The herpes simplex virus-1 DNA polymerase is a heterodimer of Mr 190,000 which consists of the products of the UL30 (Pol) and UL42 genes. The 136-kilodalton Pol gene product contains an intrinsic ribonuclease H activity that specifically degrades RNA.DNA heteroduplexes or duplex DNA substrates in the 5'----3' direction. It can therefore catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during herpes DNA replication.
Biodiversity and the World’s Food Crisis

During the next fifty years the world’s population is expected to double. In order to avoid catastrophic famines the world’s food production also must double. Although this is technically possible with present high-input methods, such technology is probably not affordable by poor tropical countries with high population growth. A more environmental friendly, and less demanding but equally productive technology based on time tested, labour intensive, tropical systems must be developed to avoid both famine, landscape deterioration, and biodiversity loss.
Comparison of the New Southern Chinch Bug-Resistant Lines with Commercial Cultivars of St. Augustinegrass

St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] is a warm season turfgrass and is widely used for lawns and landscapes in the southern United States of America. The southern chinch bug (Blissusinsularis Barber) is the most damaging insect of St. Augustinegrass. Use of resistant cultivars is an environmentally sound and sustainable method to control this insect pest. Two newly identified resistant St. Augustinegrass lines (NUF3231 and NUF4872) were compared with three commercial cultivars for turfgrass quality and other important traits. The two lines had turf color and turf visual quality similar to those of Captiva and similar to or better than those of Floratam and Palmetto during the experiment. NUF4872 had higher level of resistance to gray leaf spot than Floratam and Palmetto. Stolon architectures of NUF3231 were similar to those of Captiva whereas NUF4872 had the stolons similar to those of Floratam. The results indicated that the two lines could potentially be released as commercial cul...
Ocean Freight Rates and Economic Development 1730-1913

Revolutionary developments in transport have been an essential feature of the rapiddevelopments in transportgrowth of the past two centuries. Reduction in the cost of carriage has enabled specialization and division of labor on a national and international basis to replace the relatively self-sufficient economies that predominated in the western world two centuries ago. The striking role of the railroad in the nineteenth century is well known. However, it was water transport in which the bulk shipment of commodities began, and it was the development of ocean shipping that was an integral aspect of die growing economic interdependence of the western world, the opening up of the undeveloped continents, and the promotion of the settlement of the “empty lands.” The declining cost of ocean transportation was a process of widening the resource base of the western world. The agriculture of new countries was stimulated (and that of old countries at least temporarily depressed), the specter of famine as a result of crop failure reduced, and the raw materials were provided for industrialization. In short, the radical decline in ocean freight rates was an important part of the redirection of the resources of the western world in the course of the vast development of die past two centuries.
Anti-obesity and metabolic efficacy of the β3-adrenergic agonist, CL316243, in mice at thermoneutrality compared to 22°C.

Objective Mice are typically housed at environmental temperatures below thermoneutrality, whereas humans live near thermoneutrality. This difference affects energy physiology and, potentially, anti-obesity drug efficacy. Here we compare β3-adrenergic agonist treatment at thermoneutrality (30°C) versus room temperature (22°C).
MaxDiff Priority Estimations with and without HB-MNL

Maximum difference (MaxDiff) is a discrete choice modeling approach widely used in marketing research for finding utilities and preference probabilities among multiple alternatives. It can be seen as an extension of the paired comparison in Thurstone and Bradley–Terry techniques for the simultaneous presenting of three, four or more items to respondents. A respondent identifies the best and the worst ones, so the remaining are deemed intermediate by preference alternatives. Estimation of individual utilities is usually performed in a hierarchical Bayesian (HB)-multinomial-logit (MNL) modeling. MNL model can be reduced to a logit model by the data composed of two specially constructed design matrices of the prevalence from the best and the worst sides. The composed data can be of a large size which makes logistic modeling less precise and very consuming in computer time and memory. This paper describes how the results for utilities and choice probabilities can be obtained from the raw data, and instead of HB methods the empirical Bayes techniques can be applied. This approach enriches MaxDiff and is useful for estimations on large data sets. The results of analytical approach are compared with HB-MNL and several other techniques.
Air-fraction modeling for simultaneous Diesel engine NOx and PM emissions control during active DPF regenerations

Abstract This study develops a control-oriented air-fraction model which can accurately predict the air-fraction dynamics for a Diesel engine and the coupled aftertreatment system (mainly Diesel oxidation catalyst (DOC)) during active DPF regenerations. NOx and particulate matter (PM) emissions are the two main concerns for modern Diesel engine development. Diesel particulate filters (DPFs) have become a standard device for reducing the PM emissions from Diesel engine powertrains. To maintain high filtration efficiencies and avoid high back pressures, active DPF regenerations have to be implemented periodically by significantly elevating the exhaust gas temperatures. However, during active DPF regenerations, the selective catalytic reduction (SCR) deNOx performance may be significantly decreased, while the high temperature durability and total hydrocarbon (THC) poisoning of SCRs may be potential issues. To simultaneously meet the NOx emission standard, high-pressure loop EGR needs to be applied. Since in-cylinder NOx reduction relies heavily on the in-cylinder oxygen content, an accurate air-fraction model is necessary, and the effects of recycled THC and CO emissions should be considered. The developed air-fraction model has been experimentally validated to show its capability of capturing the actual air fraction dynamics accurately. Such a model can be instrumental in simultaneous NOx and PM emission control during active DPF regenerations and in advanced combustion mode control.
Feasible itemset distributions in data mining: theory and application

Computing frequent itemsets and maximally frequent item-sets in a database are classic problems in data mining. The resource requirements of all extant algorithms for both problems depend on the distribution of frequent patterns, a topic that has not been formally investigated. In this paper, we study properties of length distributions of frequent and maximal frequent itemset collections and provide novel solutions for computing tight lower bounds for feasible distributions. We show how these bounding distributions can help in generating realistic synthetic datasets, which can be used for algorithm benchmarking.
Human endopeptidase (THOP1) is localized on chromosome 19 within the linkage region for the late-onset Alzheimer disease AD2 locus

A cDNA encoding the rat endopeptidase 24.15 was used to determine the chromosomal localization of the respective human gene. Hybridization to DNA from human-rodent somatic cell hybrids assigned the human gene to chromosome 19. Fluorescence in situ hybridization on human metaphase chromosomes localized the human endopeptidase 24.15 to 19q13.3.
Groundwater flow and capture zone analysis of the Central Passaic River Basin, New Jersey

Delineating capture zones of pumping wells is an important part of safe drinking water and well protection programs. Capture zones or contributing areas of a groundwater extraction well are the parts of the aquifer recharge areas from which the wells draw their water. Their extent and location depend on the hydrogeologic conditions such as groundwater recharge, pumping scenario and the aquifer properties such as hydraulic conductivity, porosity, heterogeneity of the medium and hydraulic gradient. Different methods of delineation can be used depending on the complexity of the hydrogeologic conditions. In this study, a 3-dimensional transient numerical MODFLOW model was developed for the Central Passaic River Basin (CPRB), and used with a MODPATH particle tracking code to determine 3-dimensional transient capture zones. Analytically calculated capture zones from previous studies at the site were compared with the new numerically simulated capture zones. The study results revealed that the analytical solution was more conservative, estimating larger capture zones than the numerical models. Of all the parameters that can impact the size, shape and location of a capture zone, the hydraulic conductivity is one of the most critical. Capture zones tend to be smaller in lower hydraulic conductivity areas.
Wigner Crystals in the lowest Landau level at low filling factors

We report on results of finite-size numerical studies of partially filled lowest Landau level at low electron filling factors. We find convincing evidence suggesting that electrons form Wigner Crystals at sufficiently low filling factors, and the critical filling factor is close to 1/7. At nu=1/7 we find the system undergoes a phase transition from Wigner Crystal to the incompressible Laughlin state when the short-range part of the Coulomb interaction is modified slightly. This transition is either continuous or very weakly first order.