cssi/SciSciGPT-SciSciNet huggingface dataset:
Forced and combined convection of water in a vertical seven-rod bundle with P/D = 1.38

Heat transfer experiments of forced turbulent and laminar, and combined laminar downflows of water are conducted in a uniformly heated, triangularly arranged, seven-rod bundle having a P/D ratio of 1.38. In the forced flow experiments Re ranged from 1200 to 24 800 and Pr from 6.8 to 9.0, while in the combined convection experiments Re varied from 148 to 3800, Grq from 1.3 × 105 to 3 × 106, and Ri from 0.01 to 9. The data in the forced turbulent and the laminar flow regimes are in good agreement with the upflow correlations (within ±10%). Also, the transition between these two regimes, occurring at Re = 3800, is the same as that for the upflow condition. In the laminar flow regime, the flow entering the heated section is hydrodynamically developing while the flow in the heated section is thermally developed. The transition from forced laminar to combined convection occurred at Ri = 0.1, which is an order of magnitude lower than that for upflow. The combined convection data are correlated by superimposing the correlations for forced laminar and natural laminar flows as: NuC,L = [NuF,L3 + NuN,L3]13, for upflow NuC,L = [NuF,L2 + NuN,L2]12, for downflow. These correlations are within ±11 and ±15% of the uplow and downflow data, respectively.
Evaluating a palliative care case management program for cancer patients: the Omega Life Program.

Abstract Purpose: This study evaluated a cancer case management pilot program focusing on palliative care, the Omega Life Program (OLP), by assessing whether the program was associated with reduced hospital utilization. Methods: A retrospective observational study of patients with cancer who enrolled in the OLP (intervention) compared to those who chose not to enroll (comparison) from January 1, 2005 to February 28, 2007. Patients were included in the primary analyses if they died by the end of the study period and were enrolled in the program at least 1 week before death. Patients were followed from the time of referral until death. Outcomes included whether or not the patients had any admissions during this period and, for patients with at least one admission, the total number of inpatient hospital admissions, inpatient days, and hospital costs. Results: Approximately 75% of eligible patients enrolled in the OLP; 60% were older than 50 and 60% were female. Of included patients in the intervention group ...
In vitro Production and Inhibition of Aortic Vasoconstriction by Mercuric, Cadmium, and Other Metal Ions.

SummaryLow concentrations of mercuric ion induced slow steady contractions of spirally-cut strips of thoracic aorta from normal rabbits. The shortening of the strip was 2.5% with 10−7 molar and 21% with 10−4 molar mercuric ion. Such a contraction was preceded by a latent period and followed by spontaneous relaxation, after which the strip was refractory to the original stimulus. Cadmium ions did not induce contractions, but did inhibit those induced by lower concentrations of mercuric ions. Both mercuric and cadmium ions inhibited 1-epinephrine; mercuric, but not cadmium, ions inhibited angiotensin II. Zinc ions were inert. Silver cupric, cuprous, barium, mercurous, and vanadyl ions induced contractions but only in concentrations greater than 10−6 molar, Relatively high concentrations of two sulfhy-dryl-binding agents inhibited contractions induced by the mercuric ion; whereas low concentrations of a chelating agent markedly augmented them.
Manual laterality in anvil use: wild chimpanzees cracking Strychnos fruits.

Wild chimpanzees (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania, smash open the hard-shelled fruits of Strychnos spp. on anvils of stone or woody vegetation. In this food-processing task, most of the apes show exclusive use of one hand or the other, that is, strong individual hand preferences. Such extreme laterality of manual functioning corresponds to Level 3 on a five-level descriptive model of lateralisation that appears to reflect the increasingly skilful demands of object manipulation. There is precise congruence in laterality between anvil use and another subsistence task involving elementary technology-termite fishing-in almost all cases.
Induced Regulatory T cells: Mechanisms of Conversion and Suppressive Potential

Abstract Thymus-derived, naturally occurring CD4+ Forkhead Box P3+ regulatory T cells (nTreg) have suppressive activity that is important for the establishment and maintenance of immune homeostasis in the healthy state. Abundant reports have demonstrated that they can suppress pathogenic processes in autoimmune diseases and inhibit transplant rejection and graft-versus-host disease. Far less is known about induced regulatory T cells (iTreg) that are generated from naive T cells in the periphery or in vitro by directing naive T cells to acquire suppressive function under the influence of transforming growth factor-β and other factors. In this review, we describe mechanisms by which naive T cells are thought to be converted into iTreg. We also discuss the suppressive potential of iTreg, particularly in comparison with their naturally occurring counterparts, focusing on those reports in which direct comparisons have been made. Based on current knowledge, we consider the rationale for using iTreg versus nTreg in clinical trials.
Direct calculation of fluctuation formulae in the microcanonical ensemble

We present simple derivations of the classical microcanonical ensemble formulae for fluctuations which involve the kinetic energy and microscopic pressure function. The new derivations, which confirm earlier results of Lebowitz et al. [1] and Cheung [2], proceed in a direct way from basic microcanonical ensemble theory without recourse to fluctuation expressions of other ensemble theories. The method developed is applicable to shell ensembles in general.
Synthesis and SAR of tolylamine 5-HT6 antagonists.

Abstract The synthesis and SAR of tolylamines with 5-HT6 receptor antagonist activity is presented. The amine, core aromatic, peripheral aromatic, and ether linker moieties of HTS hit 1 were modulated and the effect on potency at 5-HT6 examined. Tolylpiperidine ether 9h was found to possess desirable pharmacokinetic (PK) properties, and was also shown to enhance cognition in the rat novel object recognition paradigm.
High cholesterol content in neurons increases BACE, β-amyloid, and phosphorylated tau levels in rabbit hippocampus

Abstract Epidemiological, cellular, and animal studies suggest that abnormalities in cholesterol metabolism may contribute to the etiology of Alzheimer's disease by increasing the generation of β-amyloid (Aβ). However, the mechanism by which cholesterol increases Aβ levels is not fully understood. In the present study, we demonstrate that feeding rabbits with 1% cholesterol for 7 months causes an increase in cholesterol content in neurons. High cholesterol content in neurons is accompanied by an increase in the level of BACE1, the enzyme that initially cleaves β-amyloid precursor protein to generate Aβ, causing the accumulation of Aβ1–42 peptide. These effects correlate with the phosphorylation of tau and the activation of extracellular signal-regulated protein kinase (ERK). Our data suggest that excessive cholesterol content in neurons, following long-term dietary cholesterol, may underlie the increase in BACE1 and Aβ levels. Increased Aβ levels may in turn trigger the phosphorylation of tau by activating ERK.
Wilderness Wives and Dishwashing Husbands: Comfort and the Domestic Arts of Camping in America, 1880–1910

In the late nineteenth century, many well-off white Americans turned the practice of camping out into a leisure activity. Where camping had existed as a mode of ordinary travel, a staging ground for labor, a necessary skill of foot soldiers, and an activity associated with transients, for some it arose as an appealing vacation alternative to the resort hotel. These campers narrated their travels in the wilderness as prompted by a desire to escape the bonds of modern city life and get back to nature. And yet much of their time and recollections focused on chores: raising tents, making beds, organizing living spaces, building fires, cooking meals. In outdoor magazines, popular guidebooks, and private diaries, campers elevated the domestic arts of camping out. The concept of comfort—and who produced it—emerged as meaningful in the shifting notions of class, gender, and the body in turn-of the-century America. The campers’ wilderness sat, not outside of civilization, but offered a kind of stage for it, a space to audition modern social relationships. Leisure camping offers new frameworks for asking how Americans understood the role of nature in modern culture and accommodated the social changes they attributed to modernity.
Radionuclide content of Las Vegas wash sediments

Abstract The Las Vegas Wash is an excavated waterway channel which drains all surface water and effluent discharge from sewage-treatment facilitates from the greater Las Vegas Metropolitan Area to Lake Mead. Fine and course sediment samples were collected at 100-m intervals and analyzed to determine the distribution of gamma-emitting radionuclides in the lower 5,500 m of the Las Vegas Wash. Results indicate depletion of long-lived fission products in upstream Wash sediments. However, trace levels of 137 Cs measured in downstream sediments suggest the resuspension and transport of radioactive fallout within the Wash. Levels of 40 K, 232 Th, 235 U, and 238 U found in Wash sediments were consistent with levels typically found in southeast Nevada soils.
Impact of the new National Cholesterol Education Program (NCEP) guidelines on patient management.

Purpose To update nurse practitioners (NPs) on the latest National Cholesterol Education Program (NCEP) guidelines for the management of high blood cholesterol in adults. Data Sources The 2001 NCEP Adult Treatment Panel (ATP) III guidelines and supporting scientific reviews and reports of clinical trials related to the evidence upon which the guidelines are based. Conclusions The many new features of the ATP III guidelines include an increased emphasis on the patient with multiple risk factors in order to identify appropriate candidates for primary prevention and on more stringent classifications of elevated lipid/lipoprotein levels. However, elevated levels of low-density lipoprotein (LDL) cholesterol continue to be the focus for both primary and secondary prevention, and 3-hydroxy-3-methylglu-tarylcoenzyme A (HMG-CoA) reductase inhibitors (statins) are clearly the drugs of choice for decreasing LDL cholesterol in most patients. Implications for Practice Because NPs play key roles in optimizing treatment management, it is important that they become familiar with, and be prepared to help implement, these latest guidelines. By embracing the global risk assessment approach of ATP III and aggressively treating all at-risk patients, NPs can take a proactive role in helping to halt the progression of coronary heart disease and its consequences.
Genetic changes that correlate with the pine-oil disinfectant-reduced susceptibility mechanism of Staphylococcus aureus.

Aims: To identify factors associated with the Staphylococcus aureus pine-oil disinfectant-reduced-susceptibility (PDRS) mechanism and to describe one possible PDRS model. Methods and Results: Comparative genomic sequencing (CGS) and microarray analysis were utilized to detect mutations and transcriptome alterations that occur in a S. aureus PDRS mutant. Mutant analysis, antimicrobial gradient plates, growth studies and 3-hydroxy-3-methylglutaryl coenzyme A synthase assays were then performed to confirm the biological consequences of the ‘omics’ alterations detected in a PDRS mutant. CGS uncovered three mutations in a PDRS mutant in a(n): alcohol dehydrogenase (adh), catabolite control protein A (ccpA) and an NADPH-flavin oxidoreductase (frp). These mutations lead to increased growth rates; increased transcription of an NAD-dependent d-lactate dehydrogenase gene (ddh); and increased flux through the mevalonate pathway. PDRS mutants demonstrated reduced susceptibility to bacitracin and farnesol, and one PDRS mutant displayed upregulation of bacA, a bacitracin-resistance gene. Collectively, this evidence demonstrates altered undecaprenol metabolism in PDRS mutants. Conclusions: The PDRS mechanism proposed results from increased catabolic capabilities and increased flux through the mevalonate pathway as well as altered bactoprenol physiology. Significance and Impact of the Study: A novel mechanism that bacteria utilize to overcome the killing effects of PD formulations is proposed that is unique from the PDRS mechanism of the enterobacteraciae.
Reconsidering the International Business Capstone: Capping, Bridging, or Both?

The capstone experience has become ubiquitous in undergraduate education. Originally, it served as a terminal display of academic excellence and bridging experience between study and work; more recently, however, it has been seen in terms of academic completion and consolidation. In times of increased turbulence for new business graduates, and in an international business (IB) landscape where appreciation of sociocultural and communication skills are critical, capstone experiences can provide a valuable means of demonstrating relevant and transferable professional competencies. This article considers the origins and context of the capstone, its evolutionary history, and current potential. It uses an analysis of undergraduate dissertations of non-American students studying at an American college in the Czech Republic to explore capping, bridging, and balanced strategies.
Floristic plant geography: the classification of floristic areas and floristic elements

Floristic plant geography is concerned with narrow timescales, narrow to broad spatial scales and entire floras. A major objective is the identification and classification of floristic areas and fl...
ARTIFICIAL URINARY SPHINCTER FOR POST-RADICAL PROSTATECTOMY URINARY INCONTINENCE: LONG-TERM SUBJECTIVE RESULTS

Purpose: Incontinence affects between 3% and 60% of patients after radical prostatectomy. Insertion of an artificial urinary sphincter is a mainstay therapeutic option available to these patients. We assessed patient satisfaction, outcome and complications long after artificial urinary sphincter implantation.Materials and Methods: From a data bank of 131 patients who underwent artificial urinary sphincter prosthesis insertion we identified 71 with a mean age of 72 years who had also undergone radical prostatectomy and were available for evaluation. This group included 29 patients (40.8%) who received an earlier version of the AMS-800 (American Medical Systems, Minnetonka, Minnesota) and 42 (59.2%) who received the newer narrow back cuff device. Information on surgical procedures and followup were obtained from a computerized database. Patients were also contacted by an impartial reviewer who administered a standard telephone questionnaire on the degree of continence, complications, other means used to hel...
Comparitive study of high-resolution algorithms for multiple point source location via infrared focal plane arrays

There has been a growing interest in employing infrared (IR) detectors to locate and track multiple sources in recent years. Conventional methods of locating point sources such as centroiding are not effective when point sources are closely spaced. In this paper, alternative location finding methods with the potential of resolving closely spaced objects (CSOs) is introduced. Of the three algorithms introduced here, two are based on the eigendecomposition of the input data. The other is predicated on least squares error modeling (LSE) with a Gram- Schmidt orthogonalization step to ensure fast convergence. Resolution capabilities of these algorithms are compared through Monte Carlo simulations at various noise levels. Estimates obtained through the LSE modeling approached the Cramer-Rao lower bound for high signal- to-noise-ratios. The performance of the LSE estimate is severely degraded in the presence of nongaussian noise. An outlier detection scheme that may be used in conjunction with the location and amplitude estimation procedure is described. Its effectiveness is demonstrated through Monte Carlo simulations.
Effect of an electric field on the recovery and recrystallization of Al and Cu

Influence des defauts ponctuels et lineaires sous champ electrique sur les processus de recristallisation et de restauration lors d'un recuit.
Towards automatic conceptual personalization tools

This paper describes the results of a study designed to validate the use of domain competency models to diagnose student scientific misconceptions and to generate personalized instruction plans using digital libraries. Digital library resources provided the content base for human experts to construct a domain competency model for earthquakes and plate tectonics encoded as a knowledge map. The experts then assessed student essays using comparisons against the constructed domain competency model and prepared personalized instruction plans using the competency model and digital library resources. The results from this study indicate that domain competency models generated from select digital library resources may provide the desired degree of content coverage to support both automated diagnosis and personalized instruction in the context of nationally-recognized science learning goals. These findings serve to inform the design of personalized instruction tools for digital libraries.
Multi-Element High-Lift Configuration Design Optimization Using Viscous Continuous Adjoint Method

An adjoint-based Navier‐Stokes design and optimization method for two-dimensional multi-element high-lift configurations is derived and presented. The compressible Reynolds-averaged Navier‐Stokes equations are used as a flow model together with the Spalart‐Allmaras turbulence model to account for high Reynolds number effects. When a viscous continuous adjoint formulation is used, the necessary aerodynamic gradient information is obtained with large computational savings over traditional finite difference methods. The high-lift configuration parallel design method uses a point-to-point matched multiblock grid system and the message passing interface standard for communication in both the flow and adjoint calculations. Airfoil shape, element positioning, and angle of attack are used as design variables. The prediction of high-lift flows around a baseline three-element airfoil configuration, denoted as 30P30N, is validated by comparison with available experimental data. Finally, several design results that verify the potential of the method for high-lift system design and optimization are presented. The design examples include a multi-element inverse design problem and the following optimization problems: lift coefficient maximization, lift-to-drag ratio maximization, and the maximum lift coefficient maximization problem for both the RAE2822 single-element airfoil and the 30P30N multi-element airfoil.
Malignancy rate in thyroid nodules classified as bethesda category III (AUS/FLUS)

Background: The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The “atypia of undetermined significance/follicular lesion of undetermined significance” (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5–15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center. Methods: The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan–Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology. Results: Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was...
Stratigraphy and tectonics of the Virginia–North Carolina Blue Ridge: Evolution of a late Proterozoic–early Paleozoic hinge zone

Late Proterozoic (690-570 Ma) through Ordovician rocks of the Virginia—North Carolina Blue Ridge and Valley and Ridge record the evolution of an eastward-facing passive margin and its subsequent deformation during continent-arc collision (Taconic orogeny). Comparison of Blue Ridge stratigraphy with modern rifts and passive margins suggests that late Proterozoic rifting involved substantial crustal attenuation in the eastern Blue Ridge. The axial zone of the Blue Ridge from central Virginia southward is occupied by a major fault system (Hayesville-Fries-Rock-fish Valley fault). Contrasts between rocks deposited east and west of this fault suggest that it is a reactivated hinge zone, separating highly attenuated continental crust to the east from continental crust of more normal thickness to the west. During rifting, normal faulting and rapid subsidence of attenuating crust in the eastern Blue Ridge produced rift basins in which deep-water clastic and volcanic rocks accumulated (Lynchburg Group, Ashe Formation). Landward of the hinge zone in the western Blue Ridge, mainly terrestrial to shallow-water clastic and volcanic rocks were deposited in a series of subaerial rift basins (Swift Run/Catoctin, Grandfather Mountain, Mount Rogers Formations). The hinge zone not only controlled depositional patterns throughout the rift and passive-margin history, but it was also reactivated during the Taconic collision, when attenuated crust and its cover were thrust westward over the shelf edge. Turbidite-dominated rift sequences of the eastern Blue Ridge are unlike “typical” rift deposits, which are characterized by predominantly subaerial and shallow-water sedimentation. Deep-water rifts may be common on attenuated crust (as in the Bay of Biscay); however, they are poorly known from the stratigraphic record because of their susceptibility to destruction during orogeny.
Refinement Inference for Sequence Diagrams

Refinement is fundamental to software development. An earlier work proposed a refinement relation between sequence diagrams based on their required behaviors. In this paper, we first generalize the refinement relation by taking into account system variable assignment and event hiding, renaming and substitution. We then give an algorithm as a system of inference rules that does not just verify refinement relationship between two sequence diagrams but also derives sufficient conditions under which such a relationship holds. The algorithm makes use of a semantics preserving transformation on sequence diagrams. The usefulness of refinement inference is demonstrated with a case study.
A combined theoretical–semiempirical penetration model of ballistic penetration of thick section composites:

A combined theoretical–semiempirical penetration model of ballistic penetration of thick section composites has been developed. The penetration model is developed by breaking down the penetration e...
Axis Formation in Hydra

A hydra has a simple structure consisting of a head, body column, and foot along a single axis called the oral-aboral axis. The tissue dynamics of a hydra consist of a steady state of production and loss of tissue involving the entire animal. Axis formation and its maintenance is controlled by the head organizer, which is located at the apex of the animal. The head organizer produces two signals, the head activator and head inhibitor, which are transmitted to, and are distributed in, descending gradients among the epithelial cells along the body column. The two gradients control axial patterning along the oral-aboral axis. In the context of the tissue dynamics of the adult hydra, these three elements controlling axis formation and axial patterning are in a steady state of production and loss. The canonical Wnt pathway plays a major role in setting up and maintaining the head organizer.
Endothelial Dysfunction, Isoprostanes, and Copper Deficiency

To the Editor: Following the tradition of using animal experiments to clarify and illustrate human pathology, Lavi et al1 sought similarities between people with ischemic heart disease and animals fed cholesterol. They detected a decreased effect of acetylcholine on coronary arteries in 8 of 20 angiogram patients with minimal coronary artery disease. F2-isoprostanes were higher and extracellular superoxide dismutase activity was lower in those with impaired dilation. Findings were consonant with decreased superoxide dismutase activity associated with myocardial infarction history …
Don't be fazed by PHASER: Beginning exploration of a cyclical motivational system

An earlier article in this journal (Townsend, 1991) reviewed in general terms the PHASER software and manual. The present paper illustrates how PHASER may be used in investigation of a nonlinear dynamic psychological model and exhibits several of PHASER’s facilities and attributes.
Origin of discontinuity surfaces in limestones; isotopic and petrographic data, Pleistocene of Barbados, West Indies

ABSTRACT In order to compare the validity of petrographic and isotopic techniques in determining the depositional and diagenetic history of limestones, both techniques were used on samples from a Pleistocene outcrop on Barbados, where depositional and disgenetic models are relatively simple and have well-documented recent analogues. The outcrop consists of a reasonably homogeneous grainstone cut by a discontinuity surface. The carbonate immediately above and below the discontinuity forms well-cemented layers, but the rest of the grainstone is highly permeable. Only the lower well-cemented layer contains isopachous, bladed cement. Carbon of this layer is isotopically light, and oxygen is slightly heavy. In addition, 18O distinctl changes across the discontinuity. Based on the cement morphology, the lower cemented layer formed as a submarine hardground; however, the isotopic analyses indicate evaporative precipitation of calcite at a subaerial exposure at or just above the submarine hardground following a regression. This regression and following transgression formed the discontinuity. The distinct offset of 18O values across the discontinuity indicates that the limestone above and below the discontinuity underwent mineralogical stabilization in solutions of different isotopic compositions. Diagenesis of the unit below the discontinuity preceded deposition of the unit above. The upper cemented layer resulted from cementation in a perched phreatic environment resting on the discon inuity. We consider these results to be generally applicable to other limestones. Stratigraphic variation in 18O is especially useful in identifying discontinuity surfaces and in mapping individual depositional/diagenetic packages within otherwise similar limestones. Integration of petrographic and isotopic data is necessary to determine the origin of discontinuity surfaces.
Corticosteroid inhibition of ACTH secretion.

THE LEVEL of activity within the adrenocortical system is determined by endogenous (circadian) and exogenous (stress) excitatory inputs, by inhibitory neural modulation and also by corticosteroid negative feedback control. Although corticosteroid feedback on (CRF and) ACTH secretion is easily demonstrated by treatment of mammals with exogenous glucocorticoids and subsequent measurement of either basal or stimulated activity in the system, the physiological role of this negative feedback is not so easily discerned. It is likely that most disagreement about feedback regulation of ACTH secretion has arisen because of three characteristics of the system. First, it now appears that there are at least three distinct time domains in which negative feedback by glucocorticoids on ACTH secretion are exerted. These can be distinguished at the level of the corticotrope in vitro by the different cellular effects of glucocorticoid action. Thus, interpretation of results of in vivo experiments is critically dependent on...
Heterogeneous workstation to STU-III prototype

Secure communications between heterogeneous workstations via the public telephone utility is necessary in the Department of Defense (DOD) and in the civil agency environments. A prototype was developed using two heterogeneous workstations attached to Secure Telephone Unit-IIIs (STU-IIIs). Custom software was developed to provide an interface between the trusted operating system and the STU-III. This custom software controlled the STU-III connections to the operating system. This paper describes the components of the prototype, the operation of the custom STU-III software, and the findings based on this effort. >
Verified elimination of nuclear warheads

No nuclear warheads have yet been eliminated by treaty. This paper examines possibilities for verified dismantlement and elimination of nuclear warheads as called for by possible future nuclear disarmament treaties. After warheads have been removed from missiles, the INF treaty allows each country to retain them, without restrictions.1 According to present expectations similar conditions will apply to the START treaty now under negotiation to reduce numbers of Soviet and American deliverable strategic ballistic missile warheads by half. Nevertheless, given recent advances in cooperative methods verification, as well as progress in technical capabilities of detection and monitoring, it is reasonable to hope and expect that dismantlement of nuclear warheads, not just the means for their delivery, will be called for sometime in the future. This possibility has prompted a number of studies.2 The principal focus of this paper is on procedures to verify that warheads specified by treaty for elimination are, in ...
Structural basis of the cross-reactivity of genetically related human anti-HIV-1 mAbs: implications for design of V3-based immunogens

Summary Human monoclonal antibodies 447-52D and 537-10D, both coded by the VH3 gene and specific for the third variable region (V3) of the HIV-1 gp120, were found to share antigen-binding structural elements including an elongated CDR H3 forming main-chain interactions with the N terminus of the V3 crown. However, water-mediated hydrogen bonds and a unique cation-π sandwich stacking allow 447-52D to be broadly reactive with V3 containing both the GPGR and GPGQ crown motifs, while the deeper binding pocket and a buried Glu in the binding site of 537-10D limit its reactivity to only V3 containing the GPGR motif. Our results suggest that the design of immunogens for anti-V3 antibodies should avoid the Arg at the V3 crown, as GPGR-containing epitopes appear to select for B cells making antibodies of narrower specificity than V3 that carry Gln at this position.
Evidence for a bone-kidney axis regulating phosphate homeostasis

A novel circulation phosphaturic hormone is postulated to regulate systemic phosphate homeostasis. Two new studies reveal that the phosphaturic factor FGF-23 is increased in hypophosphatemic subjects with McCune-Albright syndrome and that secreted frizzled-related protein-4 (sFRP-4), a factor produced by tumors derived from subjects with tumor-induced osteomalacia, also has phosphaturic activity. It remains to be established whether FGF-23 and sFRP-4 represent two distinct phosphatonins or are somehow integrated in a novel phosphate-regulating bone-kidney axis.
Duplex ultrasound criteria for femorofemoral bypass revision.

Purpose This study was conducted to evaluate the impact of duplex ultrasound surveillance on the patency of femorofemoral bypasses performed for symptomatic peripheral arterial occlusive disease (PAOD). Methods A retrospective review was conducted of 108 patients (78 men, 30 women) with a mean age of 62 ± 10 years who underwent femorofemoral prosthetic (n = 100) or vein (n = 8) bypass grafting for symptomatic PAOD (claudication, 38%; rest pain, 41%; tissue loss, 11%; infection, 10%) during a 10-year period. Prior or concomitant inflow iliac artery stenting was performed in 26 patients (24%), and a redo femorofemoral bypass was performed in 19 patients (18%). Duplex ultrasound surveillance of the reconstruction was performed at 6-month intervals to assess patency, graft (midgraft peak systolic flow velocity) hemodynamics, and identify inflow or outflow stenotic lesions. Repair was recommended for a stenosis with a peak systolic velocity (PSV) >300 cm/s and a PSV ratio >3.5. Life-table analysis was used to estimate primary, assisted-primary, and secondary graft patency. Results During a mean 40-month follow-up (range, 2 to 120 months), 31 bypasses (29%) were revised: 19 duplex-detected stenosis involving the inflow iliac artery (n = 15) or anastomotic stenosis (n = 4), or both, 11 for graft thrombosis, and 1 for graft infection. Abnormal inflow iliac (PSV >300 cm/s) hemodynamics or a mid-graft PSV P Conclusions Vascular laboratory surveillance after femorofemoral bypass that included duplex ultrasound imaging of the inflow iliac artery and graft accurately identified failing grafts. A duplex-detected identified stenosis with a PSV >300 cm/s correlated with failure, and repair of identified lesions was associated with excellent 5-year patency.
Insulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cells.

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) can stimulate apoptosis and inhibit cell proliferation directly and independently of binding IGFs or indirectly by forming complexes with IGF-I and IGF-II that prevent them from activating the IGF-I receptor to stimulate cell survival and proliferation. To date, IGF-independent actions only have been demonstrated in a limited number of cells that do not synthesize or respond to IGFs. To assess the general importance of IGF-independent mechanisms, we have generated human IGFBP-3 mutants that cannot bind IGF-I or IGF-II by substituting alanine for six residues in the proposed IGF binding site, Ile56/Tyr57/Arg75/Leu77/Leu80/Leu81, and expressing the 6m-hIGFBP-3 mutant construct in Chinese hamster ovary cells. Binding of both IGF-I and IGF-II to 6m-hIGFBP-3 was reduced >80-fold. The nonbinding 6m-hIGFBP-3 mutant still was able to inhibit DNA synthesis in a mink lung epithelial cell line in which inhibition by wild-type hIGFBP-3 previously had been shown to be exclusively IGF-independent. 6m-hIGFBP-3 only can act by IGF-independent mechanisms since it is unable to form complexes with the IGFs that inhibit their action. We next compared the ability of wild-type and 6m-hIGFBP-3 to stimulate apoptosis in serum-deprived PC-3 human prostate cancer cells. PC-3 cells are known to synthesize and respond to IGF-II, so that IGFBP-3 could potentially act by either IGF-dependent or IGF-independent mechanisms. In fact, 6m-hIGFBP-3 stimulated PC-3 cell death and stimulated apoptosis-induced DNA fragmentation to the same extent and with the same concentration dependence as wild-type hIGFBP-3. These results indicate that IGF-independent mechanisms are major contributors to IGFBP-3-induced apoptosis in PC-3 cells and may play a wider role in the antiproliferative and antitumorigenic actions of IGFBP-3.
TBI ADAPTER: traumatic brain injury assessment diagnosis advocacy prevention and treatment from the emergency room--a prospective observational study.

ABSTRACT There is no standard treatment algorithm for patients who present to the emergency department (ED) with acute traumatic brain injury (TBI). This is in part because of the heterogeneity of the injury pattern and the patient profile, and the lack of evidence-based guidelines, especially for mild TBI in adults. As TBI is seen more and more frequently in the ED, a standardized assessment would be beneficial in terms of efficiency. The authors present their ED approach to mild TBI evaluation in the ED, along with results to date. These data represent a prospective observational cohort study, where each patient provided individual, written informed consent.
Effect of idarubicin and epirubicin on in vitro polymorphonuclear function: diminished superoxide radical formation compared to their parent compounds daunorubicin and doxorubicin.

Anthracyclines are active against a variety of malignancies. The present study examined the effect of epirubicin and idarubicin on in vitro polymorphonuclear (PMN) function including chemotaxis, aggregation, bacteriocidal activity degranulation, and superoxide generation. We also studied the effects of cyclosporin (100 ng/ml) and verapamil (500 ng/ml), two membrane active biological response modifiers, on their potential role in modulating anthracycline-induced oxygen radical formation in the human PMN. Older anthracyclines (doxorubicin and daunorubicin) did not affect superoxide generation in the human PMN. However, the newer anthracyclines, both epirubicin and idarubicin, profoundly inhibited human superoxide generation (P less than .02) and (P less than .01), respectively. This inhibition was not agonist specific but occurred with multiple agonists including FMLP, PMA, A23187, and Zymosan-activated serum (ZAS). Last, cyclosporin and verapamil did not modulate the anthracycline effects of PMN superoxide generation. This study suggests that two of the newest anthracyclines, epirubicin and idarubicin, inhibit more PMN superoxide radical formation compared to their parent compounds. This reduction in oxyradical formation may account in part for their difference in anthracycline cellular cytotoxic activity.
Treatment Options for Type 2 Diabetes in Youth Remain Limited.

The incidence and prevalence of type 2 diabetes (T2D) in youth are steadily increasing. The Centers for Disease Control and Prevention recently published the projected prevalence of T2D in youth using the SEARCH for Diabetes in Youth Study database from 2001 for prevalence and 2002 for incidence. Based on these data and assuming a 2.3% increase annually, it is predicted that the prevalence of T2D in youth could quadruple in 40 years. 1 As in adults with T2D, adolescents develop macrovascular and microvascular complications, including albuminuria, hypertension, and dyslipidemia. These complications occur earlier and appear to be more rapidly progressive in youths than in adults. 2 Thus, prevention and treatment of T2D is paramount. Prevention begins with addressing known risk factors for developing T2D, the most important of which is obesity. Most youths with T2D have a body mass index (BMI) greater than the 85th percentile and are diagnosed between the ages of 10 and 16 years, around the time of puberty and the associated physiologic insulin resistance. 3 Occurrence is familial; 74%100% of adolescents with T2D have an affected first or second degreerelative. 4 OtherriskfactorsfordevelopingT2Darelarge forgestationalageorsmallforgestationalagebirthweightsand high risk ethnicities. American Indians are the most affected, followed in decreasing order by African Americans, Hispanics, Asian/Pacific Islanders, and non-Hispanic Whites. 3 Understanding the pathophysiology of diabetes has led to the development of novel treatments. T2D is due to insulin resistance and a relative insulin deficiency due to beta cell dysfunction with eventual beta cell failure. The time to beta cell failure in youth is more rapid than in adulthood, with the rate of beta cell function declining by � 20% per year in 6 youths who underwent clamp studies. 5 Explanations for the beta cell failure include beta cell exhaustion because of increased insulin secretion to compensate for insulin resistance, desensitization of the beta cell because of hyperglycemia (glucotoxicity), lipotoxicity, and a reduction of beta cell mass from amyloid deposition. 6 At diag
Metabolism and Biology of Tryptophan

The age of 21 years is usually considered the age at which a person becomes an adult. So it is that the International Study Group for Tryptophan Research (ISTRY), which is now 21 years old becomes a mature organization. The first meeting was held 21 years ago here in beautiful and historic Padua organized by Professor L. Musajo and his able assistants Professors G. Allegri C. Costa and A. De Antoni. Intervening triennial meetings were held in Madison, Kyoto, Martinsried, Cardiff, Baltimore, and Nagoya. It is appropriate that this meeting again be in Padua to celebrate the maturity of ISTRY, and we are grateful to Professors Allegri-Filippini and Costa for hosting this conference.
Imaging of the Spine: A Medical and Physical Perspective

This chapter introduces the basic methods of visualization currently used in clinical medical practice for diagnostic imaging of the spine. The different methods of visualization based on physical properties of tissue (imaging modalities) included in this introduction are radiography and fluoroscopy, computed tomography, magnetic resonance imaging, molecular imaging, and ultrasound. The basic physics of each of these techniques for visualization of the anatomy and pathology of the spine is presented, along with current paradigms of application of each in a clinical medical setting. Electronic storage and manipulation of images in a healthcare setting are discussed, with a brief discussion of image noise, resolution, and artifact as a basis of image quality.
How Risky Is Consumption in the Long-Run? Benchmark Estimates from a Robust Estimator

The long-run standard deviation (LRSD) of consumption growth is a key moment in determining risk premiums under Epstein-Zin preferences. Standard estimators of the LRSD are biased downward and have poor confidence interval coverage, making them overreject the long-run risk model. This paper studies a new estimator with smaller bias and accurate confidence intervals. Standard long-run risk calibrations are still rejected in the data. The LRSD of consumption growth in the postwar sample is estimated to be 2.5% per year with an upper bound to the 95% confidence interval of 4.9%. These values can be taken as benchmarks for future calibrations.Received October 29, 2014; accepted February 18, 2016 by Editor Leonid Kogan.
The Fundamentals of Human Virology

Publisher Summary Viruses are molecular pathogens that cause human diseases. A conventional virus is made up of 2 or 3 major components. A nucleic acid genome, which can be Deoxyribonucleic Acid (DNA) or Ribonucleic Acid (RNA), single or double-stranded, contiguous or segmented, contains all the genetic information and encodes all the virus-specific macromolecules of the pathogen. The molecular and pathogenic aspects of their biology are grouped in terms of their genomic organization. Molecular characterization of these pathogens provides an understanding of mechanisms of pathogenesis, rational drug design, molecular signatures that can be used to trace outbreaks of viral disease… An overview of the six families of DNA and 15 families of RNA viruses, based on their molecular properties and life cycles is presented. The utility and issues surrounding the use of molecular forensics and epidemiology to the world of virology are exemplified, for instance, because of rapid sequencing techniques detailed fingerprints of viruses provide important clues about their source. Like other microbial species, the analysis of viral genomic segments can provide important clues as to the relatedness and origins of infections. Given their small size and high rate of evolution, several considerations should be kept in mind when applying comparative molecular forensic analyses to viruses. The tracking of HIV infections exemplifies the successful application of molecular forensics to identify the source of a viral infection. The goal of this chapter is to provide a background in the fundamentals of human virology and provide an overview of the utility and issues surrounding the use of molecular forensics and epidemiology to the world of virology.
Music preferences and perception of loudness.

again. The second ratings were either the same (70%) or different by only one (28%) in almost all cases, so means of these two ratings were used for analysis. On the second procedure, the 10 selections were played again, and the subjects were asked to adjust the loudness of the music to their preferred level using a volume control knob that varied from 0 (softest) to 9 (loudest). Finally, the 10 selections were played again, and each subject was asked to adjust the volume of the music to match the volume of "pink noise" generated by a commercial sound laboratory and played over the same earphones. Subjects were told that the loudness of the pink noise would vary with each music selection, but in fact it remained at a constant level. The subjects were able to switch back and forth from music to pink noise as often as they wished during each 60-sec. music selection as they attempted to match the two, but they had no control over the loudness of the pink noise. The "matched" volume level was recorded for each of the 10 musical selections when the subject indicated the task was completed. In this last procedure, since the volume of the pink noise remained at a constant level, the "matched" volume level for each music selection was interpreted as an indirect measure of how loud the music was perceived. To analyze the data, estimates from all 15 subjects (multiplied by 10 music selections) were pooled to give 150 music ratings (M = 4.2, SD = 1.8, range = 6.0), preferred volumes (M = 3.3, SD=1.6, range=8), and matched volumes (M=l.3, SD=l.3, range=6.5). A significant Pearson correlation of ,484 (df = 148, p .10) between ratings of music and how loud the music was perceived to be. This correlation, although nonsignificant, suggests that well-liked music may be perceived as less loud than music that is not liked. Perhaps another study with a larger number of subjects and a more direct measure of perceived loudness of music will help answer this question.
Brief physician advice for alcohol problems in older adults: a randomized community-based trial.

BACKGROUND Alcohol use in older adults is common. It is associated with depression, hypertension, diabetes, drug interactions, accidents, and increased rates of emergency department visits and hospitalizations. METHODS A controlled clinical trial (Project GOAL--Guiding Older Adult Lifestyles) tested the efficacy of brief physician advice in reducing the alcohol use and use of health care services of older adult problem drinkers. Twenty-four community-based primary care practices in Wisconsin (43 family physicians and internists) participated in the trial. Of the 6073 patients screened, 105 men and 53 women met inclusion criteria and were randomized into a control group (n = 71) or an intervention group (n = 87). Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions that included advice, education, and contracting using a scripted workbook. A total of 146 patients (92.4%) participated in the 12-month follow-up procedure. RESULTS No significant differences were found between the control and intervention groups at baseline in alcohol use, age, socioeconomic status, depression, onset of alcohol use, smoking status, activity level, or use of mood-altering drugs. The older adults who received the physician intervention demonstrated a significant reduction in 7-day alcohol use, episodes of binge drinking, and frequency of excessive drinking (P <.005) compared with the control group at 3, 6, and 12 months after the intervention. There was a 34% reduction in 7-day alcohol use, 74% reduction in mean number of binge-drinking episodes, and 62% reduction in the percentage of older adults drinking more than 21 drinks per week in the intervention group compared with the control group. There were no significant changes in health status. Patterns of health care utilization were not extensively analyzed because of the small number of events. CONCLUSIONS This study provides the first direct evidence that brief physician advice can decrease alcohol use by older adults in community-based primary care practices.