cssi/SciSciGPT-SciSciNet huggingface dataset:
Investigating177Lu-PSMA617 efficacy as function of intra-tumor PSMA heterogeneity

14 Objectives: Radioligand therapy (RLT) with177Lu-PSMA617 is effective in patients with metastatic castration resistant prostate cancer. 177Lu-PSMA617 binds with high affinity to PSMA on prostate cancer cells, and thus delivers ionizing radiation to the tumor. However, it is not known if heterogenous intra-tumoral PSMA expression impacts the effectiveness of PSMA-RLT. Here we investigate (i) the relationship between RLT efficacy and tumor PSMA expression (PSMA per cell), and (ii) if, in a given tumor lesion, a minimum threshold number of PSMA+ cell s exists below which RLT is not effective. Methods: RM1 prostate cancer cells expressing different levels of human PSMA (RM1-PSMA low, medium, high, or RM1-YFP that do not express PSMA) (study 1), or a mix of RM1-YFP and RM1-PSMA high cells at various ratios (study 2) were subcutaneously injected into Nod Scid gamma (NSG) mice on day 0. Mice received 60 MBq 177Lu-PSMA617 (84 GBq/µmol) on day 4. Tumor growth was monitored on the day before treatment and three times per week thereafter using computer tomography (CT) volumetry. In a subset of mice, tumors were resected three days post treatment. Tumor uptake of 177Lu-PSMA617 (%IA/g) and DNA damage (53BP1 foci) were determined by ex vivo gamma-counting and immunohistochemistry, respectively. Results: In study 1 determining RLT efficacy as function of cellular PSMA levels, RLT induced the most pronounced growth retardation in RM1-PSMA high tumors, followed by RM1-PSMA medium tumors (p=0.0008 vs. RM1-PSMA high) which in turn grew slower than RM1-PSMA low tumors (p=0.0016 vs. RM1-PSMA medium). Tumors without PSMA expression did not respond to RLT (p<0.0001 vs. RM1-PSMA low). In agreement with these findings, cell surface PSMA expression positively correlated with achieved 177Lu-PSMA617 tumor doses (R2=0.9994) and with the extend of DNA damage elicited by RLT. Study 2 in which we investigate the efficacy of RLT in relation to the number of PSMA expressing cells in the tumor is ongoing. Conclusions: The extend of PSMA expression per cell is a crucial factor that determines the 177Lu-PSMA 617 tumor dose and the resulting extend of treatment-induce DNA damage in the current model. Higher PSMA levels thus translate into enhanced therapeutic efficacy of RLT against PC. We will report whether the efficacious targeting of PSMA-high cells in a mixed tumor cell population can compensate for the lack of therapeutic effect in PSMA-negative cells.
Megacities and natural disasters: a comparative analysis

Natural disasters are a worsening problem in many of the world's largest cities. Since an increasing majority of the world's population will soon live in cities, and mostly in large cities, the trend towards increasing urban hazard poses serious societal challenges for the future. Beginning in the mid-1990s, the International Geographical Union's Study Group on the Disaster Vulnerability of Megacities undertook a series of case studies of megacities that have been – and are – exposed to major natural disasters. These include: Tokyo, Seoul, Sydney, Lima, Mexico City, Los Angeles, San Francisco, Miami, London and Dhaka. Case studies focused on reviewing the historic record of major disasters in each city and on documenting recent changes in different components of hazard including, risk, exposure, vulnerability and response. It was found that exposure and vulnerability are the components of hazard that are changing fastest and with the gravest implications for urban populations. Because hazards are only one part of the typical urban management agenda, hazards management in large cities should be pursued with careful regard to the context of general urban policy manking and management. Sustainability has become a guiding principle of urban management but the relationship between hazard and sustainability is little understood and little explored. The way lies open for hazard researchers to develop alternative contextualized approaches to the analysis and resolution of urban hazard issues.
Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking.

Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for detoxification the ethanol metabolite acetaldehyde, is recognized as a promising therapeutic target to treat alcohol use disorders (AUDs). Disulfiram, a potent ALDH2 inhibitor, is an approved drug for the treatment of AUD but has clinical limitations due to its side effects. This study aims to elucidate the relative contribution of different organs in acetaldehyde clearance through ALDH2 by using global- (Aldh2−/−) and tissue-specific Aldh2-deficient mice, and to examine whether liver-specific ALDH2 inhibition can prevent alcohol-seeking behavior. Aldh2−/− mice showed markedly higher acetaldehyde concentrations than wild-type (WT) mice after acute ethanol gavage. Acetaldehyde levels in hepatocyte-specific Aldh2 knockout (Aldh2Hep−/−) mice were significantly higher than those in WT mice post gavage, but did not reach the levels observed in Aldh2−/− mice. Energy expenditure and motility were dramatically dampened in Aldh2−/− mice, but moderately decreased in Aldh2Hep−/− mice compared to controls. In the 2-bottle paradigm and the drinking-in-the-dark model, Aldh2−/− mice drank negligible volumes from ethanol-containing bottles, whereas Aldh2Hep−/− mice showed reduced alcohol preference at high but not low alcohol concentrations. Glial cell- or neuron-specific Aldh2 deficiency did not affect voluntary alcohol consumption. Finally, specific liver Aldh2 knockdown via injection of shAldh2 markedly decreased alcohol preference. In conclusion, although the liver is the major organ responsible for acetaldehyde metabolism, a cumulative effect of ALDH2 from other organs likely also contributes to systemic acetaldehyde clearance. Liver-targeted ALDH2 inhibition can decrease heavy drinking without affecting moderate drinking, providing molecular basis for hepatic ALDH2 targeting/editing for the treatment of AUD.
Dynamics of splashed droplets impacting wheat leaves treated with a fungicide.

Wheat is threatened by diseases such as leaf rust. One significant mechanism of disease spread is the liberation and dispersal of rust spores due to rainsplash. However, it is unclear to what exten...
Investor Ideology and the Heterogeneous Stakeholder Approaches of New Firms: A System Justification

Instrumental stakeholder theory proposes firms that manage stakeholder relationships on the basis of social fairness unlock additional potential for attracting investors. Yet, some firms are succes...
Impact of an Internet-Based Lifestyle Intervention on Behavioral and Psychosocial Factors During Postpartum Weight Loss.

Objective This cluster randomized trial tested whether an effective internet-based weight-loss intervention for low-income, postpartum women resulted in greater improvements in targeted social cognitive theory (SCT) constructs and psychosocial outcomes. Methods Fit Moms/Mamas Activas was a 12-month cluster randomized controlled trial of 370 postpartum women at 12 Special Supplemental Nutrition Program for Women, Infants, Children (WIC) clinics that were randomly assigned to intervention or standard WIC. SCT constructs (weight-control behaviors, cognitive restraint, disinhibition, self-efficacy, social support, body image) and psychosocial outcomes (depressive symptoms and stress) were measured at study entry and after 6 and 12 months. Results The intervention versus standard WIC resulted in greater 12-month increases in weight-control behaviors (3.28 points [95% CI: 1.06-5.50]), self-monitoring of weight and eating (2.28 points [1.17-3.40]), and cognitive restraint (1.93 points [0.78-3.08]) (all P ≤ 0.004). The intervention effect was only modestly (ηp 2 = 0.02) mediated by improvements in these factors. No significant group by time effect was observed for disinhibition, self-efficacy, social support, body image, depressive symptoms, or stress. Conclusions Among low-income postpartum women, an effective internet-based weight-loss program resulted in improved weight-control behaviors and cognitive restraint but did not affect other SCT targets and psychosocial outcomes.
Audit committee diversity and financial restatements

Prior research has found that characteristics of the audit committee influence the incidence of financial restatements, as does demographic diversity on boards of directors. We draw upon work team diversity research to examine the impact of relations-oriented and task-oriented diversity in the audit committee on the likelihood of fraud-related and error-related financial restatements, respectively. We argue that these two types of demographic diversity work differently through greater vigilance of the audit committee in reducing the occurrence of financial restatements. Using a matched sample of fraud-restatement, error-restatement and non-restatement U.S. firms between 1996 and 2010, we find that relations-oriented diversity is associated with a lower incidence of fraud-related restatements, while task-oriented diversity is associated with a lower likelihood of error-related restatements. We also find that the involvement of audit committee members on other board committees moderates these relationships. We discuss the important role of work team diversity mechanisms in evaluating the effectiveness of board audit committees.
Functional Deficits in Gut Microbiome of Young and Middle-Aged Adults with Prediabetes Apparent in Metabolizing Bioactive (Poly)phenols.

Background: Gut microbiota metabolize select dietary (poly)phenols to absorbable metabolites that exert biological effects important in metabolic health. Microbiota composition associated with health/disease status may affect its functional capacity to yield bioactive metabolites from dietary sources. Therefore, this study assessed gut microbiome composition and its related functional capacity to metabolize fruit (poly)phenols in individuals with prediabetes and insulin resistance (PreDM-IR, n = 26) compared to a metabolically healthy Reference group (n = 10). Methods: Shotgun sequencing was used to characterize gut microbiome composition. Targeted quantitative metabolomic analyses of plasma and urine collected over 24 h were used to assess microbial-derived metabolites in response to a (poly)phenol-rich raspberry test drink. Results: PreDM-IR compared to the Reference group: (1) enriched Blautia obeum and Blautia wexlerae and depleted Bacteroides dorei and Coprococcus eutactus. Akkermansia muciniphila and Bacteroides spp. were depleted in the lean PreDM-IR subset; and (2) impaired microbial catabolism of select (poly)phenols resulting in lower 3,8-dihydroxy-urolithin (urolithin A), phenyl-γ-valerolactones and various phenolic acids concentrations (p < 0.05). Controlling for obesity revealed relationships with microbial species that may serve as metagenomic markers of diabetes development and therapeutic targets. Conclusions: Data provide insight from multi-omics approaches to advance knowledge at the diet–gut–disease nexus serving as a platform for devising dietary strategies to improve metabolic health.
9.8 A 25mm 2 SoC for IoT Devices with 18ms Noise-Robust Speech-to-Text Latency via Bayesian Speech Denoising and Attention-Based Sequence-to-Sequence DNN Speech Recognition in 16nm FinFET

Automatic speech recognition (ASR) using deep learning is essential for user interfaces on IoT devices. However, previously published ASR chips [4 –7] do not consider realistic operating conditions, which are typically noisy and may include more than one speaker. Furthermore, several of these works have implemented only small-vocabulary tasks, such as keyword-spotting (KWS), where context-blind deep neural network (DNN) algorithms are adequate. However, for large-vocabulary tasks (e.g., $\gt100\mathrm{k}$ words), the more complex bidirectional RNNs with an attention mechanism [1] provide context learning in long sequences, which improve ASR accuracy by up to 62% on the 200kwords LibriSpeech dataset, compared to a simpler unidirectional RNN (Fig. 9.8.1). Attention-based networks emphasize the most relevant parts of the source sequence during each decoding time step. In doing so, the encoder sequence is treated as a soft-addressable memory whose positions are weighted based on the state of the decoder RNN. Bidirectional RNNs learn past and future temporal information by concatenating forward and backward time steps.
Physiological Impact of a Single Serving Slow Absorption Carbohydrate on Metabolic, Hemodynamic, and Performance Markers in Endurance Athletes During a Bout of Exercise

ABSTRACT Davitt, PM, Saenz, C, Hartman, T, Barone, P, and Estremera, S. Physiological impact of a single serving slow absorption carbohydrate on metabolic, hemodynamic, and performance markers in endurance athletes during a bout of exercise. J Strength Cond Res 35(5): 1262-1272, 2021-The purpose of this study was to determine how a slow-absorbing carbohydrate affected markers of metabolism, hemodynamics, and performance in well-trained endurance athletes. We examined total and exogenous carbohydrate oxidation (CHO ox), glucose, and performance after consuming different glucose beverages, before a treadmill run. Ten male runners (32.4 years; Vo2max, 55.9 ml·kg-1·min-1) participated on 3 occasions: slow digestion CHO (S), fast digestion CHO (F), and water (W). Subjects consumed a 50 g dose of either S or F before a 3-hour treadmill run at 57% Vo2max. Variables were assessed at -15, 0, 30, 60, 90, 135, and 180 minutes. Immediately postrun, subjects completed a time-to-fatigue test at 110% Vo2max. There was a significant difference in CHO ox for W vs. F and S (C,1.14; S,1.52; F,1.66 ± 0.2 g·min-1, p < 0.05). Fat ox was significantly higher in S vs. F (S,0.54; F,0.47 ± 0.08 g·min-1, p < 0.05). Exogenous CHO ox was significantly higher in F vs. S (F,0.26; S,0.19 + 0.04 g·min-1, p < 0.05). There was a significant difference in average blood glucose for trial (F,94.5; S,97.1 vs. W,88.4 + 2.1 mg·dl-1) and time × trial for F vs. S (0 minutes, p < 0.05). There were no significant performance differences. Consumption of a single bolus of CHO beverage before a 3-hour run elicits significant alterations in energy metabolism compared with just water, with S CHO oxidizing significantly more fat than a rapidly digested carbohydrate. These findings suggest that slow-digesting modified starch provides a consistent blood glucose level and sustained exogenous energy supply during a sustained, 3-hour endurance run. Significance was set at p < 0.05.
Assortment Optimization with Product Level Demand and Substitution Information

This paper presents a mathematical model for jointly optimizing base stock levels for the multiple items subject to service level goals. The proposed model uses the expected demand and substitution probabilities between products as inputs and has been used to analyze the effects of demand variability on profitability under service level constraint. The results of the analysis demonstrate that neglecting customer-driven substitution or excluding the impacts of variability and correlations in demand leads to significantly inefficient assortments.
Evaluation of VMAT Planning Strategies for Prostate Patients with Bilateral Hip Prosthesis.

Purpose: In this study, we investigate linac volumetric-modulated arc therapy (VMAT) planning strategies for bilateral hip prostheses prostate patients with respect to plan quality and deliverability, while limiting entrance dose to the prostheses. Methods: Three VMAT plans were retrospectively created for 20 patients: (1) partial arcs (PA), (2) 2 full arcs optimized with 500 cGy max prostheses dose (MD), and (3) 2 full arcs optimized with max dose-volume histogram (DVH) constraint of 500 cGy to 10% prostheses volume (MDVH). PA techniques contained 6 PA with beam angles that avoid entering each prosthesis. For each patient, other than prostheses constraints, the same Pinnacle VMAT optimization objectives were used. Plans were normalized with PTV D95% = 79.2 Gy prescription dose. Organ-at-risk DVH metrics, monitor units (MUs), conformality, gradient, and homogeneity indices were evaluated for each plan. Mean entrance prosthesis dose was determined in Pinnacle by converting each arc into static beams and utilizing only control points traversing each prosthesis. Plan deliverability was evaluated with SunNuclear ArcCheck measurements (gamma criteria 3%/2 mm) on an Elekta machine. Results: MD and MDVH had similar dosimetric quality, both improved DVH metrics for rectum and bladder compared to PA. Plan complexities among all plans were similar (average MUs: 441-518). Conformality, homogeneity, and gradient indices were significantly improved in MD and MDVH versus PA (P < .001). Gamma pass rates for MD (99.0 ± 1.2%) and MDVH (99.2 ± 0.99%) were comparable. A significant difference over PA was observed (96.8 ± 1.6%, P < .001). Field-by-field analysis demonstrated 12/20 PA plans resulted in fields with pass rates <95% versus 1/20 plans for MD and none for MDVH. Cumulative mean entrance doses to each prosthesis were 62.9 ± 17.7 cGy for MD plans and 83.4 ± 27.5 cGy for MDVH plans. Conclusion: MD and MDVH plans had improved dosimetric quality and deliverability over PA plans with minimal entrance doses (∼1% of prescription) to each prosthesis and are an improved alternative for bilateral prostheses prostate patients.
Iron Uptake via the Enterobactin System

Iron assimilation by means of the enterobactin (Ent) system of Escherichia coli has served as a paradigm for siderophore-dependent iron uptake in prokaryotes. This chapter briefly reviews well-documented aspects of the Ent system and then concentrates on some remaining major questions concerning Ent-related iron transport. The Ent gene cluster contains six genes (entA to entF) required for Ent biosynthesis. Before biosynthesis of Ent can occur, the Ent-specific precursor dihydroxybenzoic acid (DHB) must be produced. Cells with mutations in entS grow in iron-poor media, but this is attributed to their excretion of Ent breakdown products (DBS monomers, dimers, and trimers), which can act as secondary siderophores. It is likely that our understanding of iron uptake by products of Ent cluster genes has been limited by focusing on Ent, the defining and strongest siderophore of this system; in its basic form, one molecule of Ent is responsible for the import of only one ferric ion. The chapter discusses the results of studies showing that Ent breakdown products as well as at least one Ent precursor (DHB) can serve as siderophores. Ferrienterobactin enters the cell via an unusually complex transport system. Details concerning the regulation of many individual Ent cluster genes are unclear; for instance, the significance of the precisely placed open reading frames (ORFs) upstream of fepB, cir, and entF and the roles of the palindromic repetitive extragenic palindrome (REP) and box C sequences remain to be determined.
Pharmacotherapy of Excessive Sleepiness: Focus on Armodafinil

Excessive sleepiness (ES) is responsible for significant morbidity and mortality due to its association with cardiovascular disease, cognitive impairment, and occupational and transport accidents. ES is also detrimental to patients’ quality of life, as it affects work and academic performance, social interactions, and personal relationships. Armodafinil is the R-enantiomer of the established wakefulness-promoting agent modafinil, which is a racemic mixture of both the R- and S-enantiomers. R-modafinil has a longer half-life and is present at higher circulating concentrations than the S-enantiomer following chronic administration of modafinil and may therefore be the enantiomer predominantly responsible for the beneficial effects of the racemic compound. Armodafinil has been approved by the Food and Drug Administration for the improvement of ES associated with narcolepsy, shift-work disorder, and obstructive sleep apnea following a program of randomized, placebo-controlled clinical trials. This comprehensive medication review discusses the pharmacologic profile of armodafinil and the current evidence regarding its efficacy, safety, and tolerability; appraises patient-reported outcomes data; and suggests additional indications in which armodafinil may be of use.
On the Postoutburst Far Ultraviolet Declines of Wz-Sagittae and V1500-CYGNI

In an earlier paper [1], we demonstrated that the declining ultraviolet flux, observed long after optical quiescence was reached in three dwarf novae, most likely represents the cooling of a white dwarf whose outer layers have been heated by the accretion event. If the observed change in temperature is due to the cooling of the white dwarf surface layers following the intense heating produced in the outburst, then a thermal timescale of the heated portion of the white dwarf is implied, which could yield a rough estimate of the depth of heating into the white dwarf envelope. The thermal timescale is essentially given by the ratio of the internal energy in the affected layers to their luminosity, L.
An Analysis of Price Dynamics, Bidder Networks, and Market Structure in Online Art Auctions

One of the greatest contributions of e-comrnerce and online auctions is their ability to provide detailed bidding records in the form of a bid history. These data sources not only furnish dynamic information regarding the status of auctions, but also capture the essence of auction activities that was not accessible from live auctions. In this chapter, we explore three broad online auction issues from these bidding data: the effects of various factors on price dynamics, effects of inter-bidder interactions on bidder dynamics, and underlying relationships of auctioned objects. From the auction house manager's perspective, insights from issues like how price formation takes place, how competitive bidding among bidders evolves, and which items are perceived as similar and dissimilar by the bidders are vital in setting up future auctions. Here we present results online auctions of fine arts. of the above investigations using data from
Regulation of dopamine D3 receptors by protein-protein interactions

Gαi/o protein-coupled dopamine D3 receptors (D3Rs) are preferentially expressed in the limbic system, including the nucleus accumbens. This situates the receptor well in the regulation of limbic function and in the pathogenesis of various neuropsychiatric and neurodegenerative disorders. The intracellular domains of the receptor, mainly the large third intracellular loop and the intracellular C-terminal tail, interact with multiple submembranous proteins. These interactions are critical for the control of surface expression of the receptor and the efficacy of receptor signaling. Recently, a synapse-enriched protein kinase, Ca2+/calmodulin-dependent protein kinase II (CaMKII), has been found to interact with D3R in the above mentioned interaction model. CaMKII directly binds to the N-terminal of the third loop of D3R. This binding is Ca2+-dependent and is sustained by the autophosphorylation of the kinase. In rat accumbal neurons, the increase in Ca2+ level induces the recruitment of CaMKII to D3R, and CaMKII phosphorylates the receptor at a specific serine site. The CaMKII-induced phosphorylation could inhibit the receptor function and further regulate the behavioral response to the psychostimulant cocaine. These findings reveal a prototypic protein association model between a G protein-coupled receptor and CaMKII. Through the dynamic protein-protein interactions, the abundance, turnover cycle, and function of D3R can be regulated by multiple signals and enzymatic proteins.
A comparative study of ID3 and backpropagation for English text-to-speech mapping

The performance of the error backpropagation (BP) and ID3 learning algorithms was compared on the task of mapping English text to phonemes and stresses. Under the distributed output code developed by Sejnowski and Rosenberg, it is shown that BP consistently out-performs ID3 on this task by several percentage points. Three hypotheses explaining this difference were explored: (a) ID3 is overfitting the training data, (b) BP is able to share hidden units across several output units and hence can learn the output units better, and (c) BP captures statistical information that ID3 does not. We conclude that only hypothesis (c) is correct. By augmenting ID3 with a simple statistical learning procedure, the performance of BP can be approached but not matched. More complex statistical procedures can improve the performance of both BP and ID3 substantially. A study of the residual errors suggests that there is still substantial room for improvement in learning methods for text-to-speech mapping.
Random Permutations from Logarithmic Signatures

A cryptographic system, called pgm, was invented in the late 1970's by S. Magliveras. pgm is based on the prolific existence of certain kinds of factorization sets, called logarithmic signatures, for finite permutation groups. Logarithmic signatures were initially motivated by C. Sims' bases and strong generators. A logarithmic signature α, for a given group G, induces a mapping \(\hat \alpha\) from Z |G| to G. Hence it would be natural to use logarithmic signatures for generating random elements in a group. In this paper we focus on generating random permutations in the symmetric group S n. Random permutations find applications in design of experiments, simulation, cryptology, voice-encryption etc. Given a logarithmic signature α for S n and a seed s 0, we could efficiently compute the following sequence : \(\hat \alpha\)(s 0), \(\hat \alpha\)(s 0 + 1), ..., \(\hat \alpha\)(s 0 + r - 1) of r permutations. We claim that this sequence behaves like a sequence of random permutations. We undertake statistical tests to substantiate our claim.
Critical appraisal of medical devices in the management of cerebrovascular disease

Medical devices may revolutionize the management of acute ischemic stroke and prevention of recurrent events. By comparison with pharmaceuticals, the device approval process and subsequent application of these devices in stroke treatment is founded on a paucity of Class I evidence-based clinical trial data. Thromboembolectomy for acute stroke, stenting of cervical or cerebral arteries for stroke prevention, and percutaneous closure of patent foramen ovale for prevention or recurrent cerebral ischemia are being done with an ever-increasing frequency despite few, if any, randomized clinical trials to confirm the appropriateness of the interventions. The current basis, or lack thereof, for these interventions for cerebrovascular disease is therefore discussed. As such, a critical appraisal of the available clinical data does not support widespread use of medical devices at this time outside of well-designed clinical trials.
OR39 De novo assembly of the major histocompatibility complex using single-molecule real-time sequencing of large contiguous DNA fragments captured by targeted region specific extraction

Aim Utilize our region-specific extraction (RSE), targeted DNA capture methodology to generate large, contiguous DNA fragments (5–60 Kbp) from the MHC for sequencing on the PacBio RSII single molecule real-time sequencing (SMRT) platform to produce long sequenced reads (10–15 Kbp) for de novo assembly and characterization of the MHC. This unique combination of technologies produces long sequenced reads (up to 60 Kbp) that may eventually enable the construction of large, phased haplotype blocks and haplotype resolved de novo assembly of the MHC. Methods Genomic DNA from the homozygous cell line, COX (which has a fully characterized MHC haplotype) was enriched for 4 Mbp of the MHC (chr6: 29618227–33618227) using the RSE DNA capture methodology [1] . DNA fragment lengths were calculated using a BioAnalyzer prior to sequencing. SMRTbell DNA libraries were constructed according to the Pacbio standard protocol “20 kb Template Preparation Using BluePippin Size-selection system”. Libraries were sequenced on the PacBio RS II instrument (P6-C4 chemistry). Computational analysis was carried out using the PacBio SMRT portal HGAP 2 de novo assembly algorithm. Assembled contigs were evaluated using QUAST with the COX haplotype sequence as reference. Results Captured DNA fragments from the MHC were calculated to be ∼12 Kbp on average (ranging from ∼5 to 60 Kbp). The observed read length distribution following PacBio RSII sequencing reveals an average read length of ∼3.5 Kbp, with some reads as long as 60 Kbp. We are able to de novo assemble 91% of the targeted region, with 99.99% accuracy. The N50 and NG50 for the assembly were calculated to be 33,234 bp and 92,824 bp, respectively. The largest contig aligned to the COX reference was found to be ∼ 200Kbp. Conclusions Our targeted resequencing and de novo assembly approach represents a comprehensive method to characterize 4 Mbp of the Human MHC. We demonstrate the unique ability to de novo assemble and fully characterize 91% of the targeted MHC for the homozygous cell line COX with 99.9% accuracy as compared to the annotated COX haplotype reference sequence.
Vertical stability requirements for ARIES-I reactor

The vertical stability of the ARIES-I reactor design is analyzed with the NOVA-W, PSTAB, and TSC codes. A growth rate of approximately 5.7 s/sup -1/ is predicted for a vacuum vessel which is positioned behind the scrapeoff, first wall, and blanket (0.7-m inboard and 0.9-m outboard thickness), and which acts acting as a passive stabilizer. A reactive power of approximately 2 MVA would be required for active feedback coils located outside of the TF (toroidal-field) coils ( approximately 3 m beyond the plasma in the equational plane) to correct a 50-mm vertical displacement of the magnetic axis. A multipole-expansion technique used in the TSC analysis is also used to examine options that minimize stored energy. >
The StrongARM Latch [A Circuit for All Seasons]

i»?The StrongARM latch topology finds wide usage as a sense amplifier, a comparator, or simply a robust latch with high sensitivity. The term âStrongARMâ commemorates the use of this circuit in Digital Equipment Corporationâs StrongARM microprocessor [1], but the basic structure was originally introduced by Toshibaâs Kobayashi et al. [2]. The StrongARM latch has become popular for three reasons: 1) it consumes zero static power, 2) it directly produces rail-to-rail outputs, and 3) its input-referred offset arises from primarily one differential pair. In this column, we study the circuit and its properties.
Heptose-Containing Pentaglycosyl Diglyceride Among the Lipids of Acholeplasma modicum

A pentaglycosyl diglyceride with the tentative structure of galactosyl-galactosyl-mannoheptosyl-glucosyl-glucosyl diglyceride was found to be the major glycolipid in Acholeplasma modicum. The heptose is d-glycero-d-mannoheputose. The diglyceride-terminating moiety possesses the structure O-alpha-d-glucopyranosyl-(1 --> 2)-O-alpha-d-glucopyranosyl-sn-1,2-diglyceride. Other glycolipids occurring in this organism are a diglucosyl diglyceride and a monoglucosyl diglyceride with structures identical to the terminal segments of the pentaglycosyl diglyceride. More fully acylated derivatives of these two glycolipids also occur. The phospholipids are all of the glycerophosphoryl type. The neutral lipids are composed of diglycerides and four polyterpenes. The polyterpenes consist of both colored and colorless carotenoids and become radiolabeled with both [(14)C]acetate and [(14)C]mevalonate.
Campus-Based Organizing: Tactical Repertoires of Contemporary Student Movements

This chapter elaborates on the range of collective action tactics and organizing strategies that today's students invoke to pursue their ambitions for social change.
Overview of Linkage Analysis in Complex Traits

Linkage analysis is a well-established and powerful method for mapping disease genes. While linkage analysis has been most successful when applied to disorders with clear patterns of Mendelian inheritance, it can also be a useful technique for mapping susceptibility genes for common complex diseases. In this unit, we outline the key concepts of complex disease, and how linkage analysis for complex traits differs from simple Mendelian traits. Optimal genetic studies require careful study design, ascertainment strategy, and analysis methods. We describe how disease parameters such as prevalence, heritability estimates, and mode of inheritance should be considered before data is collected. Furthermore, we outline a general strategic approach for conducting linkage analysis of a complex disease, along with several design considerations that can optimize statistical power to detect disease loci and generally improve the quality of a study. Finally, we discuss the benefits and weaknesses of linkage analysis in contrast to genome-wide association studies.
Picloram Stability in a Sample of Forest Soil During Handling and Storage

Picloram (4-amino-3,5,6-trichloropicolinic acid) is a broad-spectrum herbicide used to control a wide variety of broadleaf and woody vegetation. It is particularly important in forestry (Norris et al. 1983). For both research and monitoring purposes, soil samples are frequently collected and analyzed to determine the persistence and mobility of picloram in the environment. Management, regulatory, and judicial decisions depend on these data; therefore it is essential that results are reliable. Unfortunately, although quality-control and quality-assurance programs are important, sample integrity during handling and storage has received little attention. Most managers of monitoring and research programs expect to complete chemical analyses soon after sample collection. In practice, long delays often occur, yet investigators assume that residue levels found at the time of analysis are the same as those present at the time of sample collection.
Strategies for pharmacologic treatment of high functioning autism and Asperger syndrome

The treatment of complex, polymorphous disorders like HFA/AS always brings a particular challenge to pharmacotherapy. Additionally, the specific characteristics presented by HFA/AS introduce unique complications to patient care and place unusual demands on a clinician's skill and experience. To provide safe and effective treatment, the clinician must understand the core features of the disorder and the manifestations of the condition in his or her patient. Furthermore, a thorough understanding of the family, school, and community resources and limitations is necessary. Once an assessment has been made, focusing on target symptoms provides a crucial framework for care. Knowing manifestations of symptoms and characterizing their distribution and behavior in that patient is most important. For patients with HFA/AS it is particularly essential to coordinate behavioral and pharmacologic objectives. The target symptoms should be tracked carefully and placed into a priority system that is based on the risks and disability they create for the patient. The skill of pharmacotherapy also means setting out realistic expectations, keeping track of the larger systems of care at school and home, and collaboration with parents and care providers. There is an expanding range and pace of biologic and intervention research into HFA/AS. The genetic work has produced exciting leads that are likely to be helpful to future generations [82-84], but the task of clinicians is to tend to today's patients. As we discover more about the complex neural circuitry subserving repetitive behaviors, reward systems, and social cognition, there are good reasons to believe our treatments will become more sophisticated and specific. Psychopharmacology is also moving to design medications that target more specific populations of receptor and brain functions. This is likely to produce medicines that have fewer side effects, are more effective, and are more symptom-specific. Pharmacotherapy is not the ultimate treatment for HFA/AS but it has a definite place. Medication can be a critical element in a comprehensive treatment plan. There is a wider range of medications with more specific biologic effects than ever before. For patients with HFA/AS these newer agents are safer and less disruptive. When paired with clinicians who are becoming more skilled at recognizing and managing symptoms, patients have a greater opportunity to reach their potential and lead pleasurable lives.
Aggressive behavior in preschoolers' social networks: Do birds of a feather flock together?

In a preschool setting, the naturally occurring aggressive behavior of sixtyfour 4-year-old children was observed and recorded. Individual differences in gender, behavioral style, social competence, reciprocal friendship, and social clique membership were examined to understand how these variables might be related to children's aggressive behavior. Variations in children's aggressive behavior were found to be associated with behavior style and social competence with peers. Children within social cliques were relatively similar in the frequency of their observed aggressive behavior. The results suggest that efforts to decrease children's aggression might target groups of children rather than individuals.
The Relationship of Affective and Continuance Organizational Commitment with Correctional Staff Occupational Burnout: A Partial Replication and Expansion Study

Finding strategies to prevent burnout is imperative for correctional administrators. Ordinary least squares regression analyses of survey results from 160 employees at a private prison for offender...
Evaluating target cold spots by the use of tail EUDs.

Purpose To propose a new measure of target underdose that can be used in the evaluation and optimization of radiotherapy dose distributions. Methods and Materials We compare various formulations of the equivalent uniform dose (EUD) and introduce a modification of existing EUD definitions, which we call tail EUD . Tail EUD is a measure of “cold spots” below the prescription dose in the target dose distribution, using units of gray (Gy). We investigate the mathematical properties of various target EUD concepts, including tail EUD. We apply the tail EUD measure retrospectively to intensity modulated radiation therapy (IMRT) treatment plans from our plan database. We also use tail EUD as an optimization objective in the optimization of prostate, pancreas, and head-and-neck plans. Results Tail EUD has desirable mathematical properties. In particular, it is convex and it leads to convex level sets ( i.e., no local minima) if the EUD from which it is derived is concave. The tail EUD value is correlated with the subjective degree of target coverage. Constraining tail EUDs to a certain level in plan optimization leads to comparable target coverage in different plans and treatment sites. Conclusions The newly introduced concept of tail EUD appears to be useful for both plan evaluation and optimization. In addition it can potentially be applied in the design of new clinical protocols.
Deleuze's expressionism

One of the most pressing set questions presented by Gilles Deleuze's body of work is that of the expression of differences, of the univocity of being, and of how the relation between the two functi...
PREVALENCE OF BORDETELLA AVIUMINFECTION IN SELECTED WILD AND DOMESTICATED BIRDS IN THE EASTERN USA

Bordetella aviumis the etiologic agent of bordetellosis, a highly contagious upper respiratory disease of young poultry. Its prevalence among domesticated turkeys is well-known, but information on prevalence of this bacterium in other birds is limited. A survey of the prevalence of B. aviumin wild and domesticated birds was conducted from June 1998 to January 2000, using tracheal cultures and serology. Of 237 blood samples from 61 species, 100 individuals from 41 species had antibodies against B. aviumas determined with a microtiter agglutination test. Nine isolates of B. aviumwere cultured from 128 tracheal samples. Ribotype analysis of seven isolates from mallards (Anas platyrhynchos), one from a wild turkey (Meleagris gallopavo), and one from a Canada goose (Branta canadensis) indicated that they represent three strains, two of which were indistinguishable from clinical isolates from domesticated turkeys. Bordetella aviumis present in wild bird populations of multiple species. Transmission from free-li...
Cross-sectional area of flexible tubes

Kresch (1977) presented the results of calculations which determined the cross-sectional shapes assumed by flexible, elastic tubes for varying transmural pressures. Extensions of these results are presented here in the form of graphs of the cross-sectional area as a function of the transmural pressure. Since the circumferential arc length, theX-axis intercept and theY-axis intercept were necessarily computed, and are of interest, graphs of these are also presented.
Modafinil evokes striatal [3H]dopamine release and alters the subjective properties of stimulants

Modafinil is a mild psychostimulant used for the treatment of sleep and arousal-related disorders, and has been considered a pharmacotherapy for cocaine and amphetamine dependence; however, modafinil's mechanism of action is largely unclear. The present study investigated modafinil using drug discrimination and slice superfusion techniques. Rats were trained to discriminate cocaine (1.6 or 5 mg/kg) or amphetamine (0.3 mg/kg) from saline injection for food reinforcement. Modafinil (64–128 mg/kg) substituted partially for both cocaine doses and amphetamine. Pretreatment with a lower modafinil dose (32 mg/kg) augmented the discriminative stimulus properties of cocaine (1.6 mg/kg dose group) and amphetamine. In neurochemical experiments, modafinil (100–300 μM) evoked [3H]overflow from rat striatal slices preloaded with [3H]dopamine in a concentration-dependent manner; however, modafinil was less potent and efficacious than amphetamine and nicotine. The dopamine transporter inhibitor nomifensine (10 μM) blocked modafinil-evoked [3H]overflow, and concentrations of modafinil (< 100 μM) that did not have intrinsic activity attenuated amphetamine (1 and 3 μM)-evoked [3H]overflow. Modafinil-evoked [3H]overflow was not altered by the nicotinic acetylcholine receptor antagonist mecamylamine, and modafinil did not alter nicotine-evoked [3H]overflow, indicating that nicotinic acetylcholine receptors likely are not important for modafinil's mechanism of action. The present results indicate that modafinil evokes dopamine release from striatal neurons and is a psychostimulant that is pharmacologically similar to, but much less potent and efficacious than, amphetamine.
Life Cycle Water Consumption and Wastewater Generation Impacts of a Marcellus Shale Gas Well

This study estimates the life cycle water consumption and wastewater generation impacts of a Marcellus shale gas well from its construction to end of life. Direct water consumption at the well site was assessed by analysis of data from approximately 500 individual well completion reports collected in 2010 by the Pennsylvania Department of Conservation and Natural Resources. Indirect water consumption for supply chain production at each life cycle stage of the well was estimated using the economic input–output life cycle assessment (EIO-LCA) method. Life cycle direct and indirect water quality pollution impacts were assessed and compared using the tool for the reduction and assessment of chemical and other environmental impacts (TRACI). Wastewater treatment cost was proposed as an additional indicator for water quality pollution impacts from shale gas well wastewater. Four water management scenarios for Marcellus shale well wastewater were assessed: current conditions in Pennsylvania; complete discharge; d...
Primitive calc-alkaline and alkaline rock types from the Western Mexican Volcanic Belt

Since the early Pliocene, small volumes of alkaline magmas have erupted in the western Mexican Volcanic Belt (MVB) in close association with the volumetrically dominant calc-alkaline magmas. Both suites include relatively rare “primitive” types, characterized by high Mg#, Cr, and Ni contents. Primitive hypersthene-normative basalts, parental to the calc-alkaline suite, are found along the volcanic front but are absent at greater distances from the trench. The volcanic-front calc-alkaline suites are typically hornblende bearing, indicating relatively high water contents. Associated primitive alkaline magmas at volcanic-front locations also contain hydrous minerals. These nepheline-normative suites include basanites, phlogopite-bearing minettes, and other hornblende-bearing lamprophyres. These are probably the youngest and freshest lamprophyres yet discovered on Earth, and ideal samples for addressing the origin of this exotic class of rocks. On extended MORB-normalized elemental plots, all lamprophyres show patterns similar to the calc-alkaline basalts, but have overall enrichments of 2 to 25X in Ti, K, P, Ba, Sr, light rare earth elements, and other incompatible elements. The lamprophyres show the same strong relative enrichments of Ba, K, and Sr, and depletions in Ti and Nb that characterize the calc-alkaline rocks of western Mexico and all subduction zones. These similarities in relative element abundances support a common source region for all primitive magmas of the western MVB. The primitive calc-alkaline and alkaline rocks of western Mexico show narrow, overlapping ranges in Sr, Nd, and Pb isotopic ratios, also consistent with derivation of all magmas from a common source. The presence of the relatively cold subducted Cocos and Rivera plates below the volcanic front demands that all primitive magmas originated in the depth range 30 to 75 km. These magmas are enriched in Ba, K, Sr, and other elements, probably transported by hydrous fluids rising from the subducted slab. Several lines of evidence support the presence of phlogopite in the source region of western MVB magmas, probably in the form of phlogopite-rich veins cutting asthenospheric peridotite. The first liquids formed upon partial melting of this veined source region will concentrate the vein component and generate the lamprophyres. These lamprophyric melts rarely erupt in arc settings, more commonly forming dikes in the arc crust. Eruption of lamprophyric magmas in the western MVB is favored by through-crustal extensional fracture systems related to active rifting of the Jalisco block from the N. American plate. Larger volumes of calc-alkaline basalt are generated by melting of the same source which dilutes the vein component with larger proportions of peridotitic wall rock.
Real-time dual wavelength polarimetry for glucose sensing

Proper treatment of diabetes includes maintenance of near normal blood glucose levels, which can only be achieved with frequent blood glucose monitoring. Current blood finger-stick methods for glucose sensing are invasive, often resulting in low patient compliance and poor disease control. The development of a noninvasive glucose sensor has the potential to provide optimal management of diabetes. Our proposed noninvasive approach is based on an optical polarimetry system for probing the anterior chamber of the eye. The sensor would eventually be used to measure the aqueous humor glucose concentration as a means to determine the blood glucose concentration. In this report, we present the development of a near real-time (less than 1 second) dual wavelength closed-loop polarimetric system to minimize glucose prediction error in the presence of varying birefringence due to motion artifact. The new dual wavelength polarimetric system and in vitro glucose measurement results will be presented which demonstrate the sensitivity and accuracy of the system in the presence of varying birefringence.