cssi/SciSciGPT-SciSciNet huggingface dataset:
Knowledge Encapsulation Framework for Collaborative Social Modeling.

This paper describes the Knowledge Encapsulation Framework (KEF), a suite of tools to enable knowledge inputs (relevant, domain-specific facts) to modeling and simulation projects, as well as other domains that require effective collaborative workspaces for knowledge-based task. This framework can be used to capture evidence (e.g., trusted material such as journal articles and government reports), discover new evidence (covering both trusted and social media), enable discussions surrounding domain-specific topics and provide automatically generated semantic annotations for improved corpus investigation. The current KEF implementation is presented within a wiki environment, providing a simple but powerful collaborative space for team members to review, annotate, discuss and align evidence with their modeling frameworks. The novelty in this approach lies in the combination of automatically tagged and user-vetted resources, which increases user trust in the environment, leading to ease of adoption for the collaborative environment.
On the front line: first choice pharmacotherapeutics for chronic lymphocytic leukemia.

ABSTRACTIntroduction: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with a highly variable clinical course. Frontline treatments include cytotoxic chemotherapies, immunother...
Time-domain Spectral Element Method for Impact Identification of Frame Structures using Enhanced GAs

This paper develops an Enhanced Genetic Algorithm (GA) strategy in conjunction with a time-domain Spectral Finite Element Method (SFEM) for impact identification of framed structures. For this purpose, a spatial truss spectral element is proposed for impact response simulation. In this regard, Gauss-Lobatto-Legendre quadrature rules and points configuration are adopted to construct a diagonal matrix and to gain an optimum computational demands. A decimal and a mixed GA coding system are implemented to locate and re-construct the impact features, respectively. An improved GA-based fitness assessment is designed to significantly accelerate the convergence rate of the optimization strategy. The impact identification of two frame structures is investigated taking into account the influence of externally applied loading. It is concluded that, the proposed mixed coding GA strategy effectively overcomes the main drawbacks of classical GA approach. The developed SFEM is superior to conventional FEM because of its high order interpolation and integration rules. For large structures, impact localization is successfully accomplished very fast, which provides the excellent ability in developing an on-line health monitoring system. It is included that, the robustness of the proposed SFEM lies on the considerably higher computational efficiency in achieving the most accurate results with the less computational costs.
CHAPTER 10 – Interferometry and Photography

This chapter focuses on the use of interferometry and photographic imaging in optical diagnostics. Interferometry can be important in diagnostics in three ways. Standaloneinterferometers can serve as spectroscopic instruments that analyze light collected from a reactor. Interference effects can occur within a physical structure, such as a thin film or multiple films, and this interference can serve as the basis of a diagnostic. The gas-phase medium in a reactor can be placed within an arm of an interferometer, as is done in CVD fluid dynamics measurements of density and temperature. In each of these three cases, interferometry compares the optical path length integrated along a ray in the reactor or film.
The Effect of Breathing Retraining Using Metronome-Based Acoustic Feedback on Exercise Endurance in COPD: A Randomized Trial.

During exercise-training patients with chronic obstructive pulmonary disease (COPD) can entrain their breathing pattern to visual-feedback cues as to achieve a slower respiratory rate and prolong exhalation. The result is an improvement in exercise tolerance and a reduction in dynamic hyperinflation. Acoustic stimuli, including metronome-generated acoustic stimuli, can entrain human movements. Accordingly, we hypothesized that exercise duration and dynamic hyperinflation would be less after exercise-training plus breathing-retraining using a metronome-based acoustic-feedback system than after exercise-training alone. Of 205 patients with COPD [FEV1 = 44 ± 16% predicted (± SD)] recruited, 119 were randomly assigned to exercise-training plus breathing-retraining using acoustic feedback (n = 58) or exercise-training alone (n = 61). Patients exercised on a treadmill thrice-weekly for 12 weeks. Before and at completion of training, patients underwent constant-load treadmill testing with inspiratory capacity measures every 2 min. At completion of training, improvements in exercise duration in the breathing-retraining plus exercise-training and exercise-training alone groups were similar (p = 0.35). At isotime, inspiratory capacity increased (less exercise-induced dynamic hyperinflation) by 3% (p = 0.001) in the breathing-retraining plus exercise-training group and remained unchanged in the exercise-alone group. The between-group change in inspiratory capacity, however, was not significant (p = 0.08). In patients with COPD, breathing-retraining using a metronome-based acoustic feedback did not result in improved exercise endurance or decreased dynamic hyperinflation when compared to exercise-training alone. Trial registry: ClinicalTrials.gov; No.: NCT NCT01009099; URL: http://www.clinicaltrials.gov
Biological, Medical, and Other Tissue Variables Affecting Biospecimen Utilization

Bioresources are critical resources that support biomedical research because of their ability to appropriately collect, process, store, and distribute a wide range of high-quality biospecimens that meet the needs of specific investigators. Of note, some biorepositories are concerned by their growing inventories and their low rates of tissue utilization. This review discusses the technical characteristics of biospecimens that can cause morphological and molecular variability and/or limit the usefulness of biospecimens in research. This article also describes current challenges related to biospecimen characteristics that may affect biospecimen utilization. These include inadequate awareness of investigators about the availability of biospecimens with specific morphologic and molecular features, donor variability, preanalytical variables, technical problems inherent with an investigator's request for biospecimens, limited tissue availability from a biorepository based on requested sizes and/or numbers of available biospecimens, effects of times of warm and cold ischemia, damage of tissues during surgery, and molecular changes during storage. To ensure maximal biospecimen utilization of all types of biospecimens requires continual education of investigators from diverse fields, particularly on factors that cause variability in the morphological and molecular characteristics of tissues. The investigators' requests for biospecimens and associated data should be reviewed carefully, including by a bioresource-associated pathologist. Queries arising from the request/application form should be resolved by bioresource personnel directly with the investigator.
Hybrid Electric Propulsion Using Doubly Fed Induction Machines

This paper considers a hybrid electric propulsion architecture where most of the electric power is transmitted from the generator to the motors without conversion. Doubly fed induction machines are...
Abstract CN07-03: Recombinant immunotoxins for hematologic malignancies

Recombinant immunotoxins are composed of fragments of monoclonal antibodies (Mabs) and protein toxins, enabling the toxin to bind to a target cell recognized by the antibody, and the toxin to kill the cell after internalization. Recombinant immunotoxins are similar to but distinct from growth-factor fusions toxins like denileukin diftitox and Tagraxofusp, FDA-approved in 1999 and 2018, respectively. Unlike chemical conjugates, Recombinant immunotoxins have a peptide that links the cell-binding to the toxin domains. After proteolytic cleavage, the toxin separates from the binding domain, undergoes intracellular trafficking and enters the cytosol, resulting in apoptotic cell death. Recombinant immunotoxins containing Pseudomonas exotoxin A contain an Fv or Fab fragment of a Mab replacing the native cell-binding toxin domain. The first recombinant immunotoxin we made contained an anti-CD25 single-chain Fv fused to a 38 kDa fragment of Pseudomonas exotoxin called PE38. Anti-CD25 recombinant immunotoxin LMB-2 was active in several hematologic malignancies, notably hairy cell leukemia (HCL) and adult T-cell leukemia (ATL). LMB-2 achieved a high complete remission (CR) rate in ATL when combined with chemotherapy to reduce immunogenicity and progression between cycles. Improved targeting of HCL was achieved with anti-CD22 recombinant immunotoxin Moxetumomab Pasudotox (Moxe) that was stabilized with a disulfide bond in the Fv and has a high affinity for CD22. Moxe achieved investigator-assessed CR rates of 51-64% in relapsed/refractory HCL in Phase 1 and 3 trials, leading to FDA-approval in 2018. Minimal residual disease (MRD) was negative in most CRs. On the phase I trial, which had adequate follow-up, MRD eradication by the most sensitive standard assay, flow cytometry of the bone marrow aspirate (BMA), was associated with longer CR duration. Extra or ‘consolidation’ cycles past documentation of CR was also associated with longer CR duration. To detect MRD with higher sensitivity, patient specific immunoglobulin heavy chain (IgH) rearrangements were cloned and real-time quantitative PCR (RQ-PCR) performed. Using patient-specific primers and probe, 1 HCL cell could be detected in 106 normal cells. We found that phase 1-3 patients achieving MRD-free CR by blood RQ-PCR had significantly prolonged CR duration (p Citation Format: Robert Kreitman, Daniel Gorelik, Maryalice Stetler-Stevenson, Constance M Yuan, Hao-Wei Wang, Hong Zhou, Katherine Potocka, Erin Fykes, Evgeny Arons, Ira Pastan. Recombinant immunotoxins for hematologic malignancies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr CN07-03. doi:10.1158/1535-7163.TARG-19-CN07-03
Positive predictive value and screening performance of GoCheck Kids in a primary care university clinic.

Purpose To determine the positive predictive value (PPV) of GoCheck Kids, a smartphone-based photoscreener, to detect refractive amblyopia risk factors (ARFs) in children 3-48 months of age. Methods The medical records of all children ≤48 months of age who failed GoCheck Kids photoscreening at a University of California, San Francisco, pediatric clinic between February 2017 and August 2018 and subsequently examined at the pediatric ophthalmology clinic were reviewed retrospectively. The PPV of GoCheck Kids was determined, where a true positive represents an abnormal cycloplegic refractive error according to the 2013 American Association of Pediatric Ophthalmology and Strabismus Vision Screening Committee criteria. For patients ≤12 months of age, refractive error thresholds were based on the 2017 American Academy of Ophthalmology Preferred Practice Patterns Pediatric Eye Evaluation guidelines. Results A total of 2,963 children were screened with GoCheck Kids. Of these, 172 (5.8%) failed the screening, of whom 115 (67%) were evaluated in the pediatric ophthalmology clinic. The mean age was 24.9 ± 11.1months (range, 3-48). Fifty-seven patients met ARF criteria yielding a PPV of 50% (95% CI, 41%-60%). The PPV was higher in patients of Latino/hispanic ethnicity (75%; 95% CI, 57%-100%; P Conclusions Modifying refractive error thresholds based on patient age and prevalence of ARFs in a population may improve the PPV of GoCheck Kids in a community-based screening program.
High Schmidt number “Washout” of a soluble contaminant downstream of a backward-facing step

Abstract We compute two-dimensional high Schmidt number mass transfer downstream of a backward-facing step in a laminar flow, in which a nonreactive solute is initially confined to a region adjacent to the step, with square cross-section and dimensions equal to the height of the step. For Reynolds numbers (Re; based on step height and far-field velocity) of 10 and 100, and for Schmidt numbers (Sc) of 7, 500, and 2650, we present concentration distributions in the fluid and on the surface, in addition to time histories for the maximum concentration in the domain and the amount of solute remaining upstream of various points in the domain. We show that the rate of removal of solute decreases strongly as the Schmidt number increases from 7 to 2650. For R e = 100 and S c = 500 and 2650, there is a time in the washout process when the location of the maximum concentration shifts from the relatively inaccessible bottom corner behind the step, to a point in the interior of the recirculation zone downstream of the step. When the washout process is approximated by a single exponential in each of three temporal ranges, that shift is seen to be accompanied by a dramatic reduction in the rate at which the maximum concentration decays. The joint effects of the Reynolds and Schmidt numbers on the washout process are discussed.
Fano-interference-enhanced optical chirality and helicity-dependent optical forces in dielectric metasurfaces

Due to the intrinsically weak chirality of biomolecules, discriminating between enantiomers, i.e., chiral molecules of opposite handedness, in low-concentrated solutions by an optical means is one of the unsolved problems in nano-optics. It is even more challenging to separate chiral objects at the nanoscale by optical forces. The key to alleviating the fundamental difficulty of these tasks is to construct an optical field, preferentially in the ultraviolet (UV) region, that carries intense optical chirality with comparable contributions from its electric and magnetic components. However, this requirement has not been met in nanophotonic structures, predominantly because of the lack of magnetic responses in plasmonic materials and the insufficient field enhancement by dielectrics. Innovative designs are highly desired to overcome the limitations from materials. In this work, we systematically investigate the resonance modes in a dielectric metasurface as well as their evolution and interplay as the design variables are engineered. We show that, based on two different mechanisms, 100-fold enhancement of optical chirality can be achieved at near-UV wavelengths with different linewidths. The first one arises from the sharp Fano interference between two distinct magnetic resonances of the unit cell of the metasurface, both of which are enhanced by the coupling across the lattice. The second one originates solely from the magnetic dipole resonance, whereas the chiral hotspots spatially overlap the electric counterparts, forming ideal sites to exert helicity-dependent optical forces on chiral objects at the nanoscale. Our findings pave the way towards practical solutions to the ultimate challenges of chiral optics.
Histamine-dependent interactions between mast cells, glia, and neurons are altered following early-life adversity in mice and humans.

Early-life adversity contributes to the development of functional bowel disorders later in life through unresolved mechanisms. Here, we tested the hypothesis that early-life adversity alters anatomical and functional interactions between mast cells and enteric glia. The effects of early-life stress were studied using the neonatal maternal separation (NMS) stress mouse model. Anatomical relationships between mast cells and enteric glia were assessed using immunohistochemistry and mast cell reporter mice (Mcpt5Cre;GCaMP5g-tdT). Immunohistochemistry was used to assess the expression of histamine, histamine 1 (H1) receptors, and glial fibrillary acidic protein. Functional responses of glia to mast cell mediators were assessed in calcium imaging experiments using Sox10CreERT2;GCaMP5g-tdT mice and cultured human enteric glial cells. NMS increases mast cell numbers at the level of the myenteric plexus and their proximity to myenteric ganglia. Myenteric glia respond to mediators released by activated mast cells that are blocked by H1 receptor antagonists in mice and humans and by blocking neuronal activity with tetrodotoxin in mouse tissue. Histamine replicates the effects of mast cell supernatants on enteric glia, and NMS increases histamine production by mast cells. NMS reduces glial responses to mast cell mediators in mouse tissue, while potentiating responses in cultured human enteric glia. NMS increases myenteric glial fibrillary acidic protein expression and reduces glial process length but does not cause neurodegeneration. Histamine receptor expression is not altered by NMS and is localized to neurons in mice, but glia in humans. Early-life stress increases the potential for interactions between enteric glia and mast cells, and histamine is a potential mediator of mast cell-glial interactions through H1 receptors. We propose that glial-mast cell signaling is a mechanism that contributes to enteric neuroplasticity driven by early-life adversity.NEW & NOTEWORTHY Early-life adversity places an individual at risk for developing functional gastrointestinal disorders later in life through unknown mechanisms. Here, we show that interactions between mast cells and glia are disrupted by early-life stress in mice and that histamine is a potential mediator of mast cell-glial interactions.
Imprecise assessment of mask use may obscure associations with SARS-CoV-2 positivity

Abstract Masks are effective measures to prevent the transmission of SARS-CoV-2, however, lack of a national mandate coupled with poor adherence has led to suboptimal levels of transmission reduction. Although data has suggested that mask adherence is high, few studies have captured details on how mask wearing changes with activities and how these behaviors are associated with SARS-CoV-2 positivity. We recruited an online sample of 3,058 respondents from three US states (MD, FL, IL; n∼1000/state) between September 16 - October 15, 2020. The median age of the sample was 47; 53% were female, 56% were white and 22% were working outside the home. Seventy three percent of the sample reported always wearing a mask indoors and outdoors based on local guidelines, however, 78% of participants who reported always wearing a mask reported taking their mask off when outside the home. While overall masking according to guidelines was not significantly associated with SARS-CoV-2 positivity, sometimes, often or always removing a mask during activities were significantly associated with SARS-CoV-2 positivity (adjusted odds ratio for always vs never removing mask: 9.92; 95% CI: 1.16 – 85.1). These findings suggest that masks were most effective when worn without removal reflecting the need for consistent use.
Idelic zeta functions

In this chapter, we present an idelic formulation of zeta functions associated to central simple algebras over global fields and we prove that they have analytic continuation and functional equation.
Boreal Forest Hazards and Adaptations: The Present

This chapter is based on observations made by the author over a period of 5 years of more or less constant association with the Ojibwa and Cree Indians of northern Ontario and northern Manitoba, Canada. Most of this time was spent in Indian villages, but an appreciable amount of observation was done in the bush under working conditions.* The central contention of this chapter is that, contrary to popular Western belief, cold is not a particularly significant environmental hazard to the native populations of the Canadian boreal forest, but that drowning and fire† are serious hazards. Cold is not perceived to be especially dangerous by the Northern Algonkians, and they are entirely justified in holding this belief. On the other hand, they also fail to see drowning and fire as important environmental hazards, and while their attitudes are to some degree understandable given the historical and cultural context, they are not supported by statistics.
A 12 b 5 MS/s two-step CMOS A/D converter

A 12 b 5 MHz fully differential two-step ADC (analog-to-digital converter) is described which is integrated in a 1- mu m CMOS technology, uses both analog and digital correction, and dissipates 200 mW. The ADC architecture and timing diagram are shown. >
The Origin of Prominences and Their Hemispheric Preference for the Skew of Overlying X-ray Loops

Abstract I review a “head-to-tail” linkage model for the formation, evolution, and eruption of solar filaments. The magnetic field structure of the model is based upon the observation that filaments form exclusively in filament channels with no apparent magnetic connections low above the polarity inversion line. The formation of a filament in this configuration is driven by flux convergence and cancellation, which produces loop-like filaments segments with a half-turn. Filament segments of like chirality may connect and form long quiescent filaments. I analyze the topology of the field in and around filaments formed through “head-to-tail” linkage and find consistency with the observed hemispheric preference for the skew of the X-ray emitting loops that vault the prominence, contrary to what one would expect from differential rotation.
Solvent-Assisted Diastereoselective Tri­meth­ylsilyl Cyanide Additions to Cyclic α-Fluoro Ketones

This paper describes the solvent-assisted addition of trimethylsilyl cyanide (TMSCN) to cyclic α-fluorinated ketones. In DMF, this method gives TMS-protected cyanohydrins in good yields (70–95 %) and with good selectivities (dr up to 22:1), and the products are readily reduced to the corresponding fluorinated 1,2-amino alcohols.
FTY720 preserved islet β-cell mass by inhibiting apoptosis and increasing survival of β-cells in db/db mice.

Background FTY720, an analogue of sphingosine-1-phosphate, has shown potential in the treatment of several autoimmune diseases, such as multiple sclerosis, type 1 diabetes and systemic lupus erythematosus. It prevents development or cure of autoimmune diabetes in animal models. Recently, we reported that FTY720 also prevents development of diabetes in db/db mice by β-cell regeneration in vivo. This study investigated the effect of FTY720 on apoptosis in β-cells in db/db mice treated with FTY720 16 weeks. Methods Six week old female db/db mice were divided into control and FTY720 groups. FTY720 (10 mg/kg) was orally administrated daily. Body weights and fasting glucose levels were measured once a week after overnight fasting. After 16 weeks of treatment, oral glucose and insulin tolerance tests were performed, serum insulin levels and insulin contents in pancreas were determined, and then all mice were subjected to physiological and histological analyses. Results FTY720-treated mice showed normal fasting glucose levels, improved glucose tolerance with normal insulin sensitivity and restored β-cell function to produce and secret insulin. Pancreas histology revealed that FTY720 prevented islet damage and preserved β-cell mass by inhibiting apoptosis and increasing β-cell survival in pancreatic islets. Conclusions We concluded that early intervention with FTY720 in db/db mice can prevent development of diabetes through preserving β-cell mass by inhibiting apoptosis and increasing survival of islet β-cells. Copyright © 2012 John Wiley & Sons, Ltd.
Experimental therapy of human endometrial cancers with a targeted cytotoxic bombesin analog AN-215: low induction of multidrug resistance proteins.

Abstract In this study we have investigated the efficacy and toxicity of targeted cytotoxic bombesin (BN) analog AN-215 and its effects on the expression of three multidrug resistance proteins in experimental human endometrial cancers. Nude mice bearing HEC-1A, RL-95-2 and AN3CA tumours were treated with AN-215 and its cytotoxic radical (AN-201). The BN receptor expression in tumours was followed by RT-PCR analysis and radioligand binding assays. Expression of drug resistance proteins MDR-1, MRP-1 and BCRP were measured by realtime PCR. AN-215 significantly (P
Dynamics of the ssDNA Recognition by the RepA Hexameric Helicase of Plasmid RSF1010: Analyses Using Fluorescence Stopped-Flow Intensity and Anisotropy Methods

The kinetic mechanism of the single-stranded DNA (ssDNA) recognition by the RepA hexameric replicative helicase of the plasmid RSF1010 and the nature of formed intermediates, in the presence of the ATP nonhydrolyzable analog, beta,gamma-imidoadenosine-5'-triphosphate (AMP-PNP), have been examined, using the fluorescence intensity and anisotropy stopped-flow and analytical ultracentrifugation methods. Association of the RepA hexamer with the ssDNA oligomers that engage the total DNA-binding site and exclusively the strong DNA-binding subsite is a minimum four-step mechanism [formula: see text]. Extreme stability of the RepA hexamer precludes any disintegration of its structure, and the sequential character of the mechanism indicates that the enzyme exists in a predominantly single conformation prior to the association with the nucleic acid. Moreover, the hexameric helicase possesses a DNA-binding site located outside its cross channel. The reaction steps have dramatically different dynamics, with rate constants differing by 2-3 orders of magnitude. Such behavior indicates a very diverse nature of the observed transitions, which comprises binding steps and large conformational transitions of the helicase, including local opening of the hexameric structure. Steady-state fluorescence anisotropies of intermediates indicate that the entry of the DNA into the cross channel is initiated from the 5' end of the bound nucleic acid. The global structure of the tertiary complex RepA-ssDNA-AMP-PNP is very different from the structure of the binary complex RepA-AMP-PNP, indicating that, in equilibrium, the RepA hexamer-ssDNA-AMP-PNP complex exists as a mixture of partially open states.
Intracranial blood flow changes after extracranial carotid artery stenting.

BACKGROUND Carotid artery stenting is an endovascular treatment option for patients with extracranial carotid stenosis. However, intracranial blood flow changes following stenting have not been established. OBJECTIVE To determine the effects of stenting on intracranial blood flow. METHODS Records of patients who underwent stenting at our institution between 2004 and 2012 and had flow rates obtained pre- and poststenting by the use of quantitative magnetic resonance angiography were retrospectively reviewed. Percentage stenosis, stenosis length, and minimum vessel diameter were measured from cerebral angiography images. RESULTS Eighteen patients were included. Mean age was 65 years with 67% presenting with symptomatic stenosis. Degree of stenosis ranged from 60% to 90%. Internal carotid artery (ICA) mean flow improved significantly poststenting from 174.9 ± 83.6 mL/min to 250.7 ± 91.2 mL/min (P = .011). Ipsilateral middle cerebral artery (MCA) flow, however, was not significantly altered poststenting (107.8 ± 41.6 mL/min vs 114.3 ± 36.3 mL/min; P = .28). Univariate analysis revealed that improved minimum vessel diameter after stenting, but not percentage stenosis (P = .18) or stenosis length (P = .45), is significantly associated with increased ICA flow (P = .02). However, improved percentage stenosis, stenosis length, minimum vessel diameter, and ICA flow poststenting were not significantly associated with increased MCA flow (P = .64, .38, .13, .37, respectively). CONCLUSION ICA flow was compromised at baseline, improving 43% on average poststenting. Increased minimum vessel diameter was the factor most significantly associated with increased flow. Conversely, MCA flow was not significantly compromised at baseline nor altered after stenting, suggesting compensatory intracranial collateral supply prestenting that redistributes following ICA revascularization.
Hyperuricemia facilitates the prediction of maternal and perinatal adverse outcome in patients with severe/superimposed preeclampsia.

Objective. Hyperuricemia has received much attention and debate recently with regard to its utility as a marker for preeclampsia and as a predictor of adverse maternal–fetal outcome. This investigation was undertaken in patients with severe/superimposed preeclampsia to determine whether the maternal uric acid (UA) level at initial hospital admission is a useful predictor of subsequent adverse maternal and/or perinatal outcomes.Methods. Retrospective analysis of all patients diagnosed with severe preeclampsia, superimposed preeclampsia or HELLP syndrome during 2005 at the University of Mississippi Medical Center (UMMC). Clinical and laboratory data were collected, entered and stored electronically in a password protected, secure system.Results. Adverse maternal outcomes occurred in 15.3% of 258 patients in the cohort. Mean UA concentration in the absence of adverse maternal outcomes was 342.6 ± 77.3 compared to 396.1 ± 117.2 μmol/l in pregnancies with complications (p < 0.001). The positive likelihood rati...
In situ observations of foraging, feeding, and escape behavior in three orders of oceanic ctenophores: Lobata, Cestida, and Beroida

The foraging, feeding, and escape behaviors of members of four genera of oceanic ctenophores were studied by direct observation in the field during the summer of 1987 (7 July to 7 September) on R. V. “Oceanus” Cruise 191 to the Northern Sargasso and Slope water, in an area bounded by 34° to 39°N and 67° and 74°W. Patterns of water movement around these ctenophores were studied using fluorescein dye. Bolinopsis infundibulum forages vertically, capturing prey with mucus-covered oral lobes. Species of Ocyropsis forage horizontally and produce a reduced wake, due to the extreme compression of the body and the aboral location of the ctene rows. Prey are trapped by the muscular oral lobes and ingested by the prehensile mouth. In both genera, the auricles are held rigidly, and apparently are used both to reduce the pressure wave as they forage and to startle prey onto the surfaces of the oral lobes. Cestum veneris also forages horizontally, but continually reverses direction. Prey startled by the turbulent wake produced in the previous pass are captured by tentilla that stream over the sides of the body. All three species of Beroe studied swim in a spiral while foraging and produce similar wakes. Prey are ingested by the negative pressure produced by the rapid expansion of the mouth, and with the macrocilia that line the oral portion of the stomodaeum. The escape behavior of species of Bolinopsis, Ocyropsis, and Cestum appears to function primarily to elude nonvisual predators such as Beroe spp. Species of Beroe bend and swim rapidly during the escape response, and will turn themselves inside-out when repeatedly stimulated. The types of prey captured depend in part on an interplay of foraging and feeding mechanisms.
Lake Ontario Basin (U.S.A.-Canada) runoff modeling

Abstract An interdependent tank-cascade model of basin runoff is described; it employs analytical solutions of climatological considerations relevant for large watersheds. The mass balance is coupled with physically-based concepts of linear reservoir storages, partial-area infiltration, complementary evapotranspiration and evapotranspiration opportunity based on available supply and heat-balance determinations of snowmelt and net supply. Daily air temperature, precipitation and runoff data are required for calibration of the nine parameters; data are grouped for 15 watersheds about Lake Ontario as well as for the entire basin above Elevator, New York and Kingston, Ontario. The model is applied to the Lake Ontario Basin in both lumped- and distributed-parameter approaches; eleven subbasins and two basins are modeled for 7- and 30-day mass-balance computation intervals. Parameter values are interpreted for physical meaning and relation to data errors and computation intervals. Temporal and spatial integration effects are analyzed with respect to error reduction, modelling information and resolution, and cost trade-offs. Result summaries are given depicting model applications and validity. Extensions and improvements are discussed. The model is an accurate, fast representation of weekly or monthly runoff volumes from large watersheds with simple calibration and data requirements. Parameter values have physical significance and appear reasonable and consistent.
Crystallographic studies and model building of ATP at the active site of hexokinase

Abstract The structure of a complex of 8-bromoadenosine monophosphate with hexokinase in crystal form BIII has been determined from a 3 A resolution difference electron density map. The ribose is anti relative to the adenine moiety, and the sugar pucker is C-2′-endo. In a model constructed to fit this map, the adenine is situated in a shallow depression on the surface of the large lobe of the enzyme at the entrance to its deep cleft. Atom N-7 is hydrogen-bonded to the backbone carbonyl oxygen of residue 396. The 2′ and 3′-ribose hydroxyls are hydrogen-bonded to Asx317 and Ser319, respectively. There is no difference electron density corresponding to the phosphate. The three phosphates of ATP and the essential metal ion have been model built into the active site using the known crystal structure of tripolyphosphato tetraamine cobalt (III) (Merritt et al. , 1978), the position of 8-bromoadenosine monophosphate, and the position of a sulfate ion bound to these crystals. In our model for ATP the β and γ-phosphates are hydrogen-bonded by Ser393 and a backbone nitrogen of Ser212, and the cobalt ion interacts with Ser212. In the closed conformation of hexokinase which is induced by the binding of glucose, model building suggests there would be additional contacts between the small enzyme lobe and the metal ion. This could explain the observed synergism in ATP and glucose binding to hexokinase in solution. Since the γ-phosphate of the ATP in our model is nearly 6 A from the 6-hydroxyl of glucose, an additional conformational change must occur in the enzyme upon formation of the ternary complex.
Linking Tumor Mutations to Drug Responses via a Quantitative Chemical–Genetic Interaction Map

There is an urgent need in oncology to link molecular aberrations in tumors with therapeutics that can be administered in a personalized fashion. One approach identifies synthetic-lethal genetic interactions or emergent dependencies that cancer cells acquire in the presence of specific mutations. Using engineered isogenic cells, we generated a systematic and quantitative chemical-genetic interaction map that measures the influence of 51 aberrant cancer genes on 90 drug responses. The dataset strongly predicts drug responses found in cancer cell line collections, indicating that isogenic cells can model more complex cellular contexts. Applied to triple-negative breast cancer, we report clinically actionable interactions with the MYC oncogene including resistance to AKT/PI3K pathway inhibitors and an unexpected sensitivity to dasatinib through LYN inhibition in a synthetic-lethal manner, providing new drug and biomarker pairs for clinical investigation. This scalable approach enables the prediction of drug responses from patient data and can be used to accelerate the development of new genotype-directed therapies.
LONGITUDINAL STUDY OF PERSISTENT GENERALISED LYMPHADENOPATHY IN HOMOSEXUAL MEN: RELATION TO ACQUIRED IMMUNODEFICIENCY SYNDROME

Abstract 42 homosexual or bisexual men with persistent generalised lymphadenopathy not attributable to an identifiable cause have been followed longitudinally since February, 1981. Lymphadenopathy was accompanied by fatigue, low-grade fever and/or night sweats (57%), splenomegaly (29%), leucopenia (40%), hypergamma-globulinaemia (76%), and diminished proportion and absolute numbers of helper T cells (95%). Of the 26 patients who had lymph node biopsy, all showed benign reactive hyperplasia. After 15-30 (median 22) months, 8 patients have met criteria for the diagnosis of acquired immunodeficiency syndrome (AIDS). This outcome was associated with previous heavy nitrite inhalant use, with the presence of night sweats, with leucopenia, and with the triad of constitutional symptoms, splenomegaly, and leucopenia. In addition, a lower mean absolute helper T cell count and an increased frequency of anergy to mumps intradermal antigen and of herpes simplex virus isolation distinguished these patients from those remaining in the cohort, who seem to be stable and in some cases to have improved.
Comparison of Direct and Indirect Measurement of LDL-C in HIV-Infected Individuals: ACTG 5087

AbstractBackground: Hypertriglyceridemia is common in HIV-infected individuals on antiretroviral therapy. Triglyceride (TG) levels >400 mg/dL interfere with the accurate determination of low-density lipoproteins (LDL-C) by the Friedewald equation, making it difficult to assess coronary heart disease risk. Objective: The objective of this study is to compare the agreement of the direct LDL-C assay and the Friedewald equation with a reference ultracentrifugation method in the estimation of LDL-C concentrations. Method: Samples from ACTG 5087 were assayed by ultracentrifugation and a direct enzymatic assay and calculated using the Friedewald equation. Results: In subjects with TG <400 mg/dL (n = 271), 90% of the direct LDL-C values and Friedewald calculations were within 30 mg/dL and 32 mg/dL of the ultracentrifugation values, respectively. With TG ⩾400 mg/dL (n = 186), 90% of the direct assay and Friedewald observations were within 68 mg/dL and 120 mg/dL of the ultracentrifugation results, respectively. Onl...
Should Tamoxifen Be Used in Breast Cancer Prevention

Breast cancer is the most commonly diagnosed cancer in women. The risk of developing breast cancer can be lowered by maintaining a healthy bodyweight and avoiding long-term use of combined estrogen and progestogen replacement after menopause. However, many women are at an increased risk of developing breast cancer secondary to age, early menarche, a family history of breast cancer or a personal history of benign breast disease. These women may now be offered tamoxifen as a chemoprevention therapy. Five years of tamoxifen treatment results in a reduction in the relative risk of developing estrogen receptor-positive breast cancer of 48%. This benefit outweighs the risk of tamoxifen-related adverse events for many healthy women. However, the benefit-risk ratio of tamoxifen chemoprevention varies for individual women. The randomized clinical trials evaluating standard-dose tamoxifen versus placebo as chemoprevention therapy are reviewed and analyzed to determine which particular women are most likely to benefit and least likely to experience a tamoxifen-related adverse event. Tamoxifen decreases the risk of breast cancer associated with aging, having a first-degree relative with disease, and a personal diagnosis of atypical ductal hyperplasia or lobular carcinoma in situ. Women who have had a hysterectomy and are at low risk of a thromboembolic event have a decreased risk of adverse effects associated with tamoxifen therapy. The strengths and weaknesses of the Gail model (frequently used to assess an individual’s risk of developing invasive breast cancer over the next 5 years) are highlighted. A method for assessing the benefit-risk ratio for an individual woman is presented. Alternative breast cancer chemoprevention strategies are considered, including the use of aromatase inhibitors. This article discusses the pros and cons of these various preventive therapies and concludes that at this time, tamoxifen remains the gold standard for breast cancer prevention.
Phosphorescence imaging system using an acousto-optic filter-based charge coupled device

Abstract We are reporting for the first time the development of an imaging spectrometer for solid surface room temperature phosphorimetry based on an acousto-optic tunable filter. A HeCd laser was employed as the excitation source, and a cooled two-dimensional charge coupled device was used as the detector. The spectral characterization and imaging capability of the new system were evaluated with two well known phosphorescent compounds. The phosphorescence emissions of pyrene and 1,2,3,4-dibenzanthracene adsorbed on chromatography paper treated for background reduction were investigated. Thallium(I) acetate was employed as a phosphorescence enhancer. Based on the performance of the proposed instrument, several potential applications are discussed.
Calcium as a permissive factor but not an initiation factor in DNA synthesis induction in cultured rat hepatocytes by the peroxisome proliferator ciprofibrate

Abstract The non-genotoxic hepatocarcinogen and peroxisome proliferating agent, ciprofibrate, is a liver mitogen both in vivo and in cultured adult rat hepatocytes, but the mechanisms of its mitogenicity have not been elucidated. We previously observed that ciprofibrate rapidly increased hepatocyte free intracellular Ca 2+ concentration ([Ca 2+ ] i ), suggesting that this effect may play a role in the initiation of DNA synthesis. In the present study, we have identified a relationship between Ca 2+ and the stimulation of hepatocyte DNA synthesis by ciprofibrate. Exposure of cultured adult rat hepatocytes to ciprofibrate (200 μM) for 48 hr increased DNA synthesis by approximately 2-fold, and this response was attenuated in a Ca 2+ -deficient medium and by the Ca 2+ channel blockers nicardipine and verapamil. To examine the relationship between the stimulation of hepatocyte DNA synthesis and increases in [Ca 2+ ] i by ciprofibrate, the intracellular Ca 2+ chelator 5,5′-dimethyl-1,2-bis(2-aminophenoxyethane)- N , N , N ′, N ′-tetraacetic acid (dimethyl-BAPTA) was employed. Pretreatment of hepatocytes with dimethyl-BAPTA blocked ciprofibrate-induced [Ca 2+ ] i increase, but did not block ciprofibrate-induced hepatocyte DNA synthesis. Dimethyl-BAPTA was only effective in reducing ciprofibrate-induced DNA synthesis when present during the latter 24 hr of a 48-hr cultured period. These data suggest that the early mobilization of hepatocyte [Ca 2+ ] i by ciprofibrate does not play an initiating role in the induction of hepatocyte DNA synthesis but rather may operate as a permissive factor for the entry of ciprofibrate-treated adult rat hepatocytes into S-phase.
Adaptation of a Pocket PC for use as a wearable voice dosimeter.

This article deals with the adaptation of a commercially available Pocket PC for use as a voice dosimeter, a wearable device that measures the vocal dose of teachers or other individuals on the job...
Development and validation of a simple estimating tool to predict heating and cooling energy demand for attics of residential buildings

Abstract The application of attic radiant barriers as a residential building energy conservation tool has received considerable attention in recent years. Quantifying the benefits of radiant barrier is complicated because the energy savings provided by this system depend on various factors including local climate, geometry, and other building parameters. Therefore, the objective of this study is to develop a simple estimating tool that may be used by homeowners and designers to assess the effectiveness and economic benefits of radiant barrier under different climatic conditions in the US. The developed tool is based on transient three-dimensional finite element models that were validated based on the results of an experimental field study. The results of the finite element models were used to develop a set of regression equations to predict the thermal performances of radiant barriers under a wide range of operating conditions. Although the theoretical basis behind this tool is robust and accurate, the developed tool is simple, flexible, and user-friendly to encourage its use among practitioners and homeowners with minimal background about this system and heat transfer mechanisms. It is anticipated that the developed tool will facilitate the integration of energy efficiency in residential design and construction.
Nicking by transesterification: the reaction catalysed by a relaxase

DNA relaxases play an essential role in the initiation and termination of conjugative DNA transfer. Purification and characterization of relaxases from several plasmids has revealed the reaction mechanism: relaxases nick duplex DNA in a site- and strand-specific manner by catalysing a transesterification. The product of the reaction is a nicked double-stranded DNA molecule with a sequestered 3'-OH and the relaxase covalently bound to the 5' end of the cleaved strand via a phosphotyrosyl linkage. The relaxase-catalysed transesterification is isoenergetic and reversible; a second transesterification ligates the nicked DNA. However, the covalent nucleoprotein complex is relatively long-lived, a property that is likely to be essential for its role as an intermediate in the process of conjugative DNA transfer. Subsequent unwinding of the nicked DNA intermediate is required to produce the single strand of DNA transferred to the recipient cell. This reaction is catalysed by a DNA helicase, an activity intrinsic to the relaxase protein in some, but not all, plasmid systems. The first relaxase-catalysed transesterification is essential for initiation of conjugative strand transfer, whereas the second is presumably required for termination of the process. The relaxase, in conjunction with several auxiliary proteins, forms the relaxation complex or relaxosome first described nearly 30 years ago as being associated with conjugative and mobilizable plasmids.
Potential and Viscous Interactions for a Multi-Blade-Row Compressor

A computationally efficient time-accurate vortex method for unsteady incompressible flows through multiple blade row systems is presented. The method represents the boundary surfaces using vortex systems. A local coordinate system is assigned to each independently moving blade row. Blade shed vorticity is determined from two generating mechanisms and convected using the Euler equation. The first mechanism of vorticity generation is a potential mechanism from a nonlinear unsteady pressure-type Kutta condition applied at the blade trailing edges. The second mechanism is a viscous mechanism from a viscous wake vorticity (VWV) model implemented to simulate the viscous shear layers on the blade pressure and suction sides. Two different two-blade-row compressor systems, a rotor/stator (R/S) system and a stator/rotor (S/R) system, were used to investigate the interaction forces on each blade row. Computational results of the potential and viscous interaction forces are presented and compared to measurements. The comparison suggests that the viscous wake interaction accounts for 25–30% of the peak loading for an axial spacing of 10% chord length between the blade rows. The efficient computational method is particularly attractive for blade indexing study. Therefore a three-blade-row rotor/stator/rotor (R1/S/R2) compressor system is used to demonstrate the indexing calculations between the two rotor positions. Resultant forces on each blade row are presented for ten rotor indexing positions and three axial gap sizes for the gaps between R1 and S and between S and R2. The unsteady peak-to-peak force can reach 10–15% of inflow dynamic head for the gap spacing investigated. The minimum-to-maximum variation of the unsteady force can account for 40–50% of averaged unsteady force.Copyright © 2003 by ASME