cssi/SciSciGPT-SciSciNet huggingface dataset:
WE‐C‐BRA‐05: Physiological Imaging‐Defined Response‐Driven Subvolumes of a Tumor

Purpose: To develop an image analysis framework to delineate the physiological imaging‐defined subvolumes of a tumor in relating to treatment response and outcome. Methods: Our proposed approach is designed to delineate subvolumes of a tumor based upon its heterogeneous distributions of physiological imaging parameters. The method assigns each voxel a probabilistic membership function belonging to the physiological parameter classes based upon a sample of tumors, and then calculates the related subvolumes for each tumor. We applied our approach to regional cerebral blood volume (rCBV) and Gd‐DTAP transfer constant (Ktrans) images of patients who had brain metastases and were treated by whole brainradiation therapy (WBRT). Forty five lesions were included in the analysis. Changes in the rCBV (or Ktrans)‐defined subvolumes of the tumors from pre RT to 2 weeks (2W) after the start of WBRT were evaluated for differentiation of responsive, stable and non‐responsive tumors using Mann‐Whitney U test. Performance of the newly developed metrics for predicting tumor response to WBRT was evaluated by Receiver Operating Characteristic (ROC) analysis. Results: The percentage decrease in the high‐CBV defined subvolumes of the tumors from pre‐RT to 2W was significantly greater in the group of responsive tumors than in the group of stable and nonresponsive ones (p<0.007). The change in the high‐CBV defined subvolumes of the tumors from pre‐RT to 2W was a predictor for post‐RT response significantly better than the change in gross tumor volume observed during the same time interval (p=0.0124), suggesting the physiological change occurs prior to the volumetric change. Also, Ktrans did not add significant discriminatory information for assessing response with respect to rCBV. Conclusions: The physiological imaging‐defined subvolumes of the tumors delineated by our method have the potential to be a new imaging response‐predictor and a candidate for intensified treatment. NIH grant RO1 NS064973
Use of a folding model and in situ spectroscopic techniques for rational formulation development and stability testing of monoclonal antibody therapeutics

Aggregation is a critical issue that hampers the development of monoclonal antibody therapeutics (Mabs). Traditionally, aggregation is considered a process in which native forms of proteins are transformed into an unstable highly associated form through an intermediate formation step. Here we describe the unfolding of an antiCD40 antibody using a folding model based on Lumry-Eyring nucleated polymerization (LENP) model. This model captures several experimental features of the thermal unfolding of this protein as studied by common in situ biophysical techniques such as circular dichroism, fluorescence spectroscopy, and turbidity measurements. According to this model, the unfolding and aggregation of the antiCD40 antibody is determined by several distinct steps that include conformational change(s) to generate aggregation prone states, reversible oligomer formation, nucleation and growth as well as their kinetics, and the formation of higher order assemblies/aggregates. Furthermore, the loss of monomer is controlled by both thermodynamic (equilibrium unfolding) and kinetic determinants of the unfolding process. This approach captures both of these rate-limiting steps. It can be concluded that this approach is sensitive to formulation conditions such as protein concentration, changes in buffer conditions, and temperature stress. The potential use of this approach in formulation development and stability testing of Mabs is discussed.
P-type and S-type pahoehoe: a study of vesicle distribution patterns in Hawaiian lava flows

Abstract Two main types of Hawaiian pahoehoe lava, P-type (pipe vesicle-bearing) and S-type (spongy), are characterized. Their origin is inferred from features of the vesicle sizes and abundances, particularly in their chilled margins which record, frozen in, the vesicle population at the time and place of solidification. S-type margins are distinctly more vesicular than P-type. Porosity and vesicle size and range in S-type margins are highest at the vent. Vesicle size reaches a minimum in medial areas, and then increases while porosity decreases onto the flatter ground of the coastal terrace. The vesicles are inferred to be part of the complement of bubbles that was present at the vent, modified by loss and coalescence during travel in lava tubes. The minimum porosity occurs on the coastal terrace and is the result of degassing during a longer residence time in lava tubes there. The systematically lower porosity of P-type margins than S-type is attributed to a still longer residence, allowing more time for bubble coalescence and loss. P-type pahoehoe is common only on flatter ground, such as the coastal terrace. It is found where tumuli and lava rises are widespread and where extensive networks of lava-expansion clefts occur through which lava moving below the surface crust can lose gas without significant cooling. Additionally, P-type pahoehoe shows clear evidence that a strong inward movement and growth of bubbles took place from the outermost selvage into an inner selvage concentration zone. A mechanism that might cause this inward movement is surface tension, operating against deforming forces in the steep viscosity gradient of flow margins, causing down-gradient bubble translation. Inward movement does not usually occur in the upper crust of thick (> 2 m ) flow-units because of the absence of strong deforming forces in the shallow velocity gradient there. Many of the larger bubbles that entered the inner selvage rose buoyantly to form pipe vesicles. P-type pahoehoe is characterized by sampled profiles across 20 flow-units. Continued gas loss through surface clefts caused a general overall reduction in vesicle content within each flow-unit to less than that in the upper crust, and the pronounced depletion of vesicles from its lower half is attributed to scavenging by ascending pipe bubbles. In a small proportion of flow-units, overall gas loss was small and a median gas blister fed by pipe bubbles developed instead.
A Fused Floating-Point Three-Term Adder

This paper presents improved architectures for a fused floating-point three-term adder. The fused floating-point three-term adder performs two additions in a single unit to achieve better performance and better accuracy compared to a network of traditional floating-point two-term adders, which is referred to as a discrete design. In order to further improve the performance of the three-term adder, several optimization techniques are applied including a new exponent compare and significand alignment, dual-reduction, early normalization, three-input leading zero anticipation, compound addition/rounding and pipelining. The proposed design is implemented for both single and double precision and synthesized with a 45 nm CMOS standard-cell library. The improved fused floating-point three-term adder reduces the area and power consumption by about 20% and reduces the latency by about 35% compared to a discrete floating-point three-term adder. Based on the data flow analysis, the proposed three-term adder can be split into three pipeline stages. Since the latencies of three pipeline stages are fairly well balanced, the throughput is increased to 2.7 times that of the non-pipelined design.
Pediatrics by the book: pediatricians and literacy promotion.

Change can come slowly in medical practice—unless of course it comes in a sudden and absolute flurry of discovery, evidence-based recommendations, and new standards of care. But the kind of change that is based on consensus, on slowly dawning realization, or just on revamping ingrained habits can be slow indeed—it has not proved easy, for example, or even doable, to get physicians to expand our role by screening regularly and consistently for maternal depression, home firearm safety, or domestic violence.1–7 It can sometimes seem that as regularly as we read articles about the need to incorporate undeniably important issues into pediatric primary care, we then read complimentary studies about how problematic it is for us to do so consistently. Most of the issues around which pediatricians are asked to consider expanding their roles are psychosocial or developmental, though all have clear and demonstrable impacts on the health and well-being of children—in other words, most are slightly outside the traditional boundaries of medical responsibility and a physician’s role.8–10 It is a testament to the flexibility and resilience of the profession that individual pediatricians, research groups, and formally constituted committees of the American Academy of Pediatrics (AAP) are ready to take on the challenges of convincing their colleagues to alter everyday behavior. On the other hand, some of the studies testify to the difficulty of achieving widespread change, even with convincing evidence in an evidence-based climate. Change may come slowly because of inertia and the strength of our established patterns, along with the persistence of the original constraints and imperatives that helped establish those patterns. Sometimes physicians may find it difficult to expand the vision of our role and responsibilities, a vision that already seems so broad and complex and one that already struggles against time …
Preparation of a Floral Initiating Extract from Xanthium

An extract from lyophilized tissue of flowering Xanthium (cocklebur) plants initiates floral development when applied to Xanthium test plants maintained on long-day photoperiodic conditions. Details of the preparation of the extract are described.
Positive integers expressible as a sum of three squares in essentially only one way

Abstract The set S consisting of those positive integers n which are uniquely expressible in the form n = a2 + b2 + c2, a ≧ b ≧ c ≧ 0 , is considered. Since n ∈ S if and only if 4n ∈ S, we may restrict attention to those n not divisible by 4. Classical formulas and the theorem that there are only finitely many imaginary quadratic fields with given class number imply that there are only finitely many n ∈ S with n = 0 (mod 4). More specifically, from the existing knowledge of all the imaginary quadratic fields with odd discriminant and class number 1 or 2 it is readily deduced that there are precisely twelve positive integers n such that n ∈ S and n ≡ 3 (mod 8). To determine those n ∈ S such that n ≡ 1, 2, 5, 6 (mod 8) requires the determination of the imaginary quadratic fields with even discriminant and class number 1, 2, or 4. While the latter information is known empirically, it has not been proved that the known list of 33 such fields is complete. If it is complete, then our arguments show that there are exactly 21 positive integers n such that n ∈ S and n ≡ 1, 2, 5, 6 (mod 8).
Combination antiangiogenic therapy and radiation in head and neck cancers

Tumor angiogenesis is a hallmark of advanced cancers and promotes invasion and metastasis. Over 90% of head and neck squamous cell carcinomas (HNSCC) express angiogenic factors such as vascular endothelial growth factor (VEGF). Several preclinical studies support the prognostic implications of angiogenic markers for HNSCC and currently this is an attractive treatment target in solid tumors. Since radiotherapy is one of the most commonly used treatments for HNSCC, it is imperative to identify the interactions between antiangiogenic therapy and radiotherapy, and to develop combination therapy to improve clinical outcome. The mechanisms between antiangiogenic agents and ionizing radiation are complicated and involve many interactions between the vasculature, tumor stroma and tumor cells. The proliferation and metastasis of tumor cells rely on angiogenesis/blood vessel formation. Rapid growing tumors will cause hypoxia, which up-regulates tumor cell survival factors, such as hypoxia-inducing factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), giving rise to more tumor proliferation, angiogenesis and increased radioresistance. Thus, agents that target tumor vasculature and new tumor vessel formation can modulate the tumor microenvironment to improve tumor blood flow and oxygenation, leading to enhanced radiosensitivity. In this review, we discuss the mechanisms of how antiangiogenic therapies improve tumor response to radiation and data that support this combination strategy as a promising method for the treatment of HNSCC in the future.
Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention?

Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency that affects premature newborns. This disease often has a rapid onset with few, if any, antecedent signs that can be used to reliably predict its occurrence. Its rapid onset and progression to death, as well as its severe morbidity when the infant survives, begs for early diagnostic tools that may be used in determining those infants who would be at greatest risk for development of the disease, and for whom early preventative measures could be targeted. Although studies have suggested efficacy of several techniques such as breath hydrogen, inflammatory mediators in blood, urine or stool, and genetic markers, these all have drawbacks limiting their use. The application of newly developed “omic” approaches may provide biomarkers for early diagnosis and targeted prevention of this disease.
Inhibition of rat neuronal kainate receptors by cis-unsaturated fatty acids

1. Whole-cell recordings from cultured rat hippocampal neurons, from freshly dissociated dorsal root ganglion (DRG) neurons and from human embryonic kidney (HEK) 293 cells expressing the glutamate receptor GluR6 subunit were used to study the modulation of kainate receptor channels by long chain fatty acids. 2. In all three cell types, application of cis-unsaturated fatty acids caused a dose-dependent reduction in whole-cell currents evoked by kainate. Docosahexaenoic acid (DHA), arachidonic acid (AA), linolenic acid and linoleic acid all produced substantial inhibition at a concentration of 50 microM, whereas inhibition by linolenelaidic acid and linolelaidic acid was significantly weaker. Fully saturated fatty acids were essentially inactive. 3. With continuous exposure to active fatty acids, the peak current elicited by kainate declined over a time course of several minutes to reach a steady-state level less than 50 % of the initial amplitude. Recovery was slow in control solution, but was speeded up by exposure to bovine serum albumin (0.5 mg ml-1), a protein that binds fatty acids with submicromolar affinity. The inhibition in neurons was half-maximal with 5-15 microM AA or DHA, but potency was at least 10-fold greater at GluR6 in HEK 293 cells. 4. Inhibition by AA or DHA was unaffected by extracellular nordihydroguaiaretic acid (10 microM), indomethacin (10 microM), 17-octadecynoic acid (30 microM) or 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride (H-7; 10 microM). Furthermore, inclusion of H-7 (100 microM), BAPTA (10 mM), AA (50 microM), antioxidants, or the protein kinase C inhibitor PKC19-36 (20 microM) in the internal solution had little effect on whole-cell currents and did not prevent inhibition of currents by extracellular application of AA or DHA. 5. We conclude that the inhibition produced by cis-unsaturated fatty acids does not require conversion to oxidized metabolites or activation of PKC. Instead, active compounds may interact directly with an extracellular, or intramembraneous, site on kainate receptors.
Benzodiazepine receptors mediate regional blood flow changes in the living human brain

We studied the effects of a high-affinity gamma-aminobutyric acid (GABA)-benzodiazepine-receptor agonist (lorazepam) and an antagonist (flumazenil) in humans, using H2(15)O positron-emission tomography. Administration of lorazepam to healthy volunteers caused time- and dose-dependent reductions in regional cerebral blood flow and self-reported alterations in behavioral/mood parameters. Flumazenil administration reversed these changes. These observations indicated that benzodiazepine-induced effects on regional cerebral blood flow and mood/behavior are mediated at some level through GABA-benzodiazepine receptors, although the specific mechanism remains unclear. The approach described here provides a method for quantifying GABA-benzodiazepine-receptor-mediated neurotransmission in the living human brain and may be useful for studying the role of these receptors in a variety of neuropsychiatric disorders.
Turtlemania: a math game in a distributed environment

This paper is divided into four sections. First an introduction describes the basic goals of the educational math game and the environment chosen. The second section describes the software, showing pictures of the teacher interface (Figure 1) and the Student Interface (Figures 2 and 3). The third section describes the initial classroom experiments introducing the software to K-3 public school teachers and children from Pre-K to 6th grade. The last section presents the preliminary conclusions from using the software and how this type of framework could be used for other educational software.
Type I versus type II lunates: Ligament anatomy and presence of arthrosis

One hundred-seventy embalmed cadaver wrists were dissected. The type of lunate (type I, no medial hamate facet; type II, medial hamate facet), the incidence and location of arthrosis (exposed subchondral bone) in the lunohamate joint, and the anatomic relationship of the volar triquetrocapitate (T-C) and the volar triquetrohamate (T-H) ligaments were identified and measured. The relationship between the T-C and T-H ligaments was classified into 3 types. In type A the T-C ligament was completely separate from the T-H ligament, in type B the T-C ligament overlapped the T-H ligament, and in type C the T-C ligament had an additional ligament from the triquetrum to the proximal pole of the hamate. Eighty-two percent of type I lunates were associated with a type A relationship between the T-C and the T-H ligaments and 96% of type II lunates were associated with a type C relationship between the T-C and the T-H ligaments. Arthrosis at the proximal pole of the hamate was more commonly associated with the type II lunates (49%) and with the type C relationship (57%) of the T-C and T-H ligaments. The incidence of arthrosis in the lunohamate joint was also significantly greater in the type II lunate with a medial facet of 3 mm or more.
Mitomycin C pharmacokinetics in rats - effect of dose size

Abstract The pharmacokinetics of mitomycin C was studied following intravenous administration of the drug at three different dose levels to rats. A rapid high-performance liquid Chromatographic assay was developed for the determination of mitomycin C in plasma and urine. Analysis was performed using a reversed-phase octadecyi silane column and precolumn. The mobile phase consisted of 30% v/v) methanol in water (apparent pH of 4.5) containing 1.0 mM octane sulfonic acid-sodium salt delivered at a rate of 1.0 ml · min −1 . The eluent was monitored at 360 nm. Under the conditions, mitomycin C and the internal standard had capacity factors of 1.6 and 3.0, respectively. Samples (50 μ1) of plasma or urine were prepared by alkalinizing the sample with 50 μl of 0.1 M ohosphate buffer solution and extracting with four volumes of 1:1 (v/v) chloroform: 2-propanol mixture. The detection limit was 0.01 μg · ml −1 . Over the plasma concentration range of 0.01–10.0 μg · ml −1 , the within-day coefficient of variation (CV) ranged from 6 to 16%. The between-day CV ranged from 2 to 18%. The assay was used for pharmacokinetic studies in rats. Logarithm of the olsma concentration-time profiles suggest a biphasic behavior with rapid distribution and dose-dependent elimination phases. At dose levels of 2.5 and 5.0 mg · kg −1 , the effective half-lives, mean residence times and total plasma clearance did not show any significant dose dependency. However, at 10 mg · kg −1 dose level, significant increase in effective half-lives, mean residence times and a significant decrease in total plasma clearance were observed. Only 2–8% of the administered dose appeared as intact drug in the urine, whereas no fecal excretion of the drug was observed. At different dose levels, the disposition is linear with the half-lives becoming longer after the higher doses. This finding may either be attributed to the inhibition of the NADPH-linked cytochrome reductase system or to the rapid tissue uptake followed by slow release of the drug from tissue storage site.
Effect of maternal restraint stress during gestation on temporal lipopolysaccharide-induced neuroendocrine and immune responses of progeny

The impact of gestational dam restraint stress on progeny immune and neuroendocrine temporal hormone responses to lipopolysaccharide (LPS) challenge was assessed. Maternal stress (5-min snout snare restraint stress during days 84 to 112 of gestation) increased (P 0.05) the normalization of proinflammatory cytokines or neuroendocrine hormones produced following LPS. Collectively, these results indicate that maternal stress impacts aspects of the proinflammatory cytokine and stress hormone response in their progeny following LPS dosing of the offspring. This response is potentially responsible in part for the resultant changes to SAA production. Because several of the changes observed here are dependent on pig gender, these results are also the first evidence that inherent epigenetic factors coupled with maternal stress impact the cumulative response to stress and LPS in young pigs.
A micro-device for the mixing of a highly viscous bio-sample with water using micro-channel

A mechanism for controlling the mixing of highly viscous bio-samples at the micro-liter scale is presented. Existing methods for mixing bio-samples using micro-stirrers or shaking micro-wells are only effective for non-highly-viscous materials. The proposed mechanism mixes monoolein, a highly viscous bio-sample, with water in a micro-device called micro-capsule using a micro-channel and centrifugation. To achieve effective mixing, the design of the micro-capsule along with the micro-channel is presented and so is the hydrodynamic model describing the flow of viscous materials in the micro-channel. The mixing process is analyzed according to the Reynolds number of the bio-samples, which is observed during the experiment using digital images for further analysis. Finally, the new approach is verified by X-ray diffraction experiments, which are used to evaluate the effectiveness of mixing. Experimental results not only validate the proposed method but also determine the flow oscillation time in the micro-channel to achieve the efficient mixing.
The mean as the balance point: thought experiments with measuring sticks

This article presents activities to help students establish a connection between the mean and the balance point of a lever. The lever and its law are discussed briefly. Thought experiments with a meterstick are presented to emphasize different properties of the mean and weighted averages.
A model for studying the implications of price-cap regulation of local telephone services

Abstract This paper presents a modeling approach to investigate the practical implications of price-caps for regulating local telephone prices. The model incorporates a stochastic customer choice component, a deterministic pricing component, and a price-cap regulatory component patterned after the Federal Communications Commission's price-cap model. Simulations illustrate the interplay among these components. The analysis is based on input data drawn from 3 months of actual local telephone usage for nearly 2000 households in Ohio. The hypothetical price-cap rule considered in the example is applied to a market basket consisting of the pricing elements for basic local residential telephone services. These price elements are for measured, message and flat rate local calling. The analyses show whether or not prices are currently at Ramsey prices, and how prices change if the telephone company seeks to maximize profits. The impact of the price changes on various demographic groups is presented. A graphic display shows the strength of the economic incentive for the company to operate more efficiently under the hypothetical price-cap rule.
Molecular interstitial skeleton

Abstract The three-dimensional structures of protein molecules, as determined by X-ray crystallography, have been shown to possess packing defects or interior cavities of various sizes. These packing defects have been considered as a possible explanation for how small molecules, such as water and molecular oxygen, gain access to protein interiors. Most previous computational methods for analyzing packing defects use a fixed probe sphere radius or a fixed cube width, and so are limited with regard to the size of the packing defects that they find. Most methods also concentrate on identifying cavities, rather than on finding the tunnels that connect the cavities. The method presented here identifies packing defects of all sizes, and it also delineates the tunnels connecting them to each other and to the protein exterior. In particular, the radius of each tunnel at its narrowest point is determined.
Selectively oxidised vertical cavity surface emitting lasers with 50% power conversion efficiency

Index-guided vertical cavity top-surface emitting laser diodes have been fabricated from an all epitaxial structure with conducting mirrors by selective lateral oxidation of AlGaAs. At low voltage, a 78% slope efficiency, and a 350 mu A threshold current in a single device combine to yield a maximum power conversion efficiency of 50% at less than a 2 mA drive current. The device operates in a single mode up to 1.5 mW. >
A nonmetal die for porcelain jacket crown fabrication

Abstract A technique for making a nonmetal die from a rubber base impression for porcelain jacket crown fabrication has been described. This die material can withstand burnishing and swaging satisfactorily. A method of forming the apron for the matrix is described. This technique eliminates the need for electroplating of rubber base impressions, and avoids the need for making multiple impressions in order to produce a working die with a suitable apron surface.
Endoscopic injection of submucosal bulking agents for the management of incontinent catheterizable channels.

Background: Urinary and fecal continence can be achieved by constructing cathe- terizable continent channels that provide access to the bladder and bowel. Some patients develop persistent stomal leakage. A minimally invasive method of injection with a bulking agent for treatment of stomal incontinence was evaluated.
Wide local excision or abdominoperineal resection as the initial treatment for anorectal melanoma

Abstract Background Anorectal melanoma (AM) is a rare tumor with a poor prognosis. Treatment with abdominoperineal resection (APR) over wide local excision (WLE) is still debated. This study aimed to compare median survival of WLE and APR in patients with AM. Methods A systematic review of the literature was performed. Only series that allowed calculation of median survival were included. Results Fourteen studies met inclusion criteria. Average median survival of stage I WLE patients (N = 34) and stage I APR patients (N = 31) was 44 and 22 months, respectively ( P = .001). For stage II patients, 7 underwent WLE, and 10 underwent APR with an average median survival of 36 and 14 months, respectively ( P = .19). Conclusions This study identified no stage-specific survival advantage to APR in favor of AM. Given that WLE is a more limited intervention associated with at least comparable survival, we propose that it be considered the initial treatment of choice for AM.
Temporal patterns and sources of atmospherically deposited pesticides in Alpine Lakes of the Sierra Nevada, California, U.S.A.

Agricultural pesticides are being transported by air large distances to remote mountain areas and have been implicated as a cause for recent population declines of several amphibian species in such...
Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.

Abstract Background . Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. Methods . Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18°C, and had their circulation arrested (60 minutes) and reperfused at 37°C for 90 minutes (DHCA, n=8); or (2) time-matched normothermic controls on bypass (CPB, n=6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside. Results . In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% ± 2% [ p p p Conclusions . DHCA is associated with endothelial dysfunction in cerebral microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.
A crevalle jack, Caranx hippos (Pisces, Carangidae), with a mandibular calcified connective tissue fibroma

An 84 cm adult crevalle jack, Caranx hippos, was caught on hook and line off Murrill's Inlet, South Carolina, with enlarged bulbous mandibles. Staining and sectioning revealed bony tissue throughout these bulges and ruled out parasitic copepods as possible causal agents of the bulges. The fish was normal in all respects. The tumor was unencapsulated and non-invasive. Radiographs revealed no metastases.
The epidemiology of chemical contaminants of drinking water.

Abstract A number of chemical contaminants have been identified in drinking water. These contaminants reach drinking water supplies from various sources, including municipal and industrial discharges, urban and rural run-off, natural geological formations, drinking water distribution materials and the drinking water treatment process. Chemical contaminants for which epidemiologic studies have reported associations include the following: aluminium, arsenic, disinfection by-products, fluoride, lead, pesticides and radon. Health effects reported have included various cancers, adverse reproductive outcomes, cardiovascular disease and neurological disease. In evaluating epidemiologic studies for risk assessment, considering whether the study design was qualitative (hypothesis generating) or quantitative (hypothesis testing) is important and whether sufficient epidemiologic data of a quantitative nature exists to determine the dose–response curve. Each of the chemical contaminants mentioned are summarized by study designs (qualitative and quantitative) and whether a dose–response curve based on epidemiologic data has been proposed. Environmental epidemiology studies are driven by environmental exposures of interest. For drinking water contaminants, the design of epidemiologic studies and their interpretation should consider the following exposure issues: the source of the contaminant; other sources of the contaminant; the route of exposure; the frequency, duration and magnitude of exposure; the ability to document an actual internal dose; and the ability to document the dose to the target organ. Health effects of concern have other risk factors that must be measured in the conduct of these studies. In evaluating epidemiologic studies, potential errors and biases that may occur must be considered given the very low magnitude of associations (less than 2.0 for either odds ratio or risk ratio). Given the issues, the next generation of drinking water epidemiologic studies should include a multidisciplinary team beyond traditional epidemiologists and statisticians. Study teams will require toxicologists, chemists, engineers and exposure assessors. Arsenic is briefly discussed as an example of the importance of susceptible populations. Disinfection by-products are discussed as an example of epidemiologic studies of mixtures.
Image noise removal using image inpainting

In this paper, new methods are addressed for impulse and speckle noise removal in images. The approach is based on the fusion of noise detection and image inpainting techniques. To avoid destroying the real structures of the image, the noise areas are first recognized to be repaired by an inpainting algorithm, subsequently. To distinguish the impulse noise areas in the image, a Neuro-Fuzzy model is employed and, to extract the speckled regions an algorithm is proposed based on Frost filtering and image resizing. The advantage of inpainting technique over the regular filtering methods is that it will be easier to generalize to all types of noise. Once we detect the damaged pixels in the image, the inpainting algorithm will be able to repair them. Various types of images under three levels of noise are tested using PSNR and SSIM measures. The experimental results demonstrate the great ability of the new approaches to suppress the noise properly, while preserving critical details of the image.
Dynamic Regulation of Contraction by Cardiac Myosin Binding Protein-C

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament associated protein that performs both regulatory and structural roles within cardiac sarcomeres. It is a member of the immunoglobulin (Ig) superfamily of proteins consisting of 8 Ig- and 3 fibronectin (FNIII)-like subdomains along with a unique regulatory sequence referred to as the M-domain whose structure is unknown. Here we used atomic force microscopy (AFM) to probe the structure and mechanical properties of the different subdomains of native and recombinantly expressed cMyBP-C molecules. Results demonstrate that cMyBP-C exhibits complex mechanical behavior under load and contains multiple domains with distinct mechanical properties. The Ig and FNIII-like domains unfold over a range of relatively low forces (50-190 pN), whereas the M-domain is readily extensible at forces <50 pN and is likely to be an intrinsically disordered segment of cMyBP-C. Additional extensible segments of cMyBP-C are likely to include linkers between the Ig domains such as the proline-alanine rich sequence between domains C0 and C1. Taken together these results suggest that cMyBP-C is compliant and readily extensible, potentially conferring structural and functional plasticity to cMyBP-C during the course of a single heart beat. Supported by NIH HL080367.
Heart rate and skin conductance responding during three attention-direction tasks

Subjects were instructed to turn their attention toward: (1) feeling their internal bodily events (BODY task); (2) remembering events that happened to them on the preceding day (COGNITIVE task); and (3) looking at a series of slides (EXTERNAL task). They were assured that no verbal report would be required. Cardiac deceleration occurred during the BODY and EXTERNAL tasks. The BODY task was associated with a decrease on skin conductance measures.
Exploring the relationship between corporate social responsibility and firm innovation

This research investigates the link between corporate social responsibility (CSR) and firm innovation. Drawing upon the literatures on CSR and the knowledge-based view, we conceptualize that a firm's CSR programs enable it to build broader and deeper relationship networks with its stakeholders, facilitating the sharing and exchange of external knowledge of its stakeholders; in turn, stakeholders' external knowledge complements the firm's internal knowledge and promotes firm innovation. Using a large scale data set compiled from various archival sources, our empirical results show that firms with greater CSR activities exhibit higher innovativeness capability and launch more new products. Furthermore, we show that this positive relationship between CSR and firm innovation is stronger for firms with higher R&D investment and firms operating in more competitive markets. This research broadens current understanding of the business returns to CSR, suggesting that CSR can be a catalyst for innovation.
Flapping propulsion using a fin ray

We calculate optimal driving motions for a fin ray in a two-dimensional inviscid fluid, which is a model for caudal fin locomotion. The driving is sinusoidal in time, and consists of heaving, pitching and a less-studied motion called ‘shifting’. The optimal phases of shifting relative to heaving and pitching for maximum thrust power and efficiency are calculated. The optimal phases undergo jumps at resonant combinations of fin ray bending and shear moduli, and are nearly constant in regions between resonances. In two examples, pitching- and heaving-based motions converge with the addition of optimal shifting. Shifting provides an order-one increase in output power and efficiency.
Feasibility of Electromagnetic Transponder Use to Monitor Inter- and Intrafractional Motion in Locally Advanced Pancreatic Cancer Patients

Purpose The primary objective of this study was to determine the feasibility of electromagnetic transponder implantation in patients with locally advanced unresectable pancreatic cancer. Secondarily, the use of transponders to monitor inter- and intrafractional motion, and the efficacy of breath holding for limiting target motion, were examined. Methods and Materials During routine screening laparoscopy, 5 patients without metastatic disease were implanted with transponders peri-tumorally. The Calypso System's localization and tracking modes were used to monitor inter- and intrafractional motion, respectively. Intrafractional motion, with and without breath holding, was also examined using Calypso tracking mode. Results Transponder implantation was well tolerated in all patients, with minimal migration, aside from 1 patient who expulsed a single transponder. Interfractional motion based on mean shifts from setup using tattoos/orthogonal imaging to transponder based localization from 164 treatments was significant in all dimensions. Mean shift (in millimeters), followed by the standard deviation and p value, were as follows: X-axis: 4.5 mm (1.0, p = 0.01); Y axis: 6.4 mm (1.9, p = 0.03); and Z-axis 3.9 mm (0.6, p = 0.002). Mean intrafractional motion was also found to be significant in all directions: superior, 7.2 mm (0.9, p = 0.01); inferior, 11.9 mm (0.9, p p = 0.01); posterior, 2.9 mm (0.5, p = 0.02); left, 2.2 mm (0.4, p = 0.02); and right, 3.1 mm (0.6, p = 0.04). Breath holding during treatment significantly decreased tumor motion in all directions. Conclusions Electromagnetic transponder implantation appears to be safe and effective for monitoring inter- and intrafractional motion. Based on these results a larger clinical trial is underway.
Cortical Map Plasticity Improves Learning but Is Not Necessary for Improved Performance

SUMMARY Cortical map plasticity is believed to be a key substrate of perceptual and skill learning. In the current study, we quantified changes in perceptual ability after pairing tones with stimulation of the cholinergic nucleus basalis to induce auditory cortex map plasticity outside of a behavioral context. Our results provide evidence that cortical map plasticity can enhance perceptual learning. However, auditory cortex map plasticity fades over weeks even though tone discrimination performance remains stable. This observation is consistent with recent reports that cortical map expansions associated with perceptual and motor learning are followed by a period of map renormalization without a decrement inperformance.Our results indicatethatcortical map plasticity enhances perceptual learning, but is not necessary to maintain improved discriminative ability.
Promoting effective transitions of care at hospital discharge: A review of key issues for hospitalists

The period following discharge from the hospital is a vulnerable time for patients. About half of adults experience a medical error after hospital discharge, and 19%-23% suffer an adverse event, most commonly an adverse drug event. This article reviews several important challenges to providing high-quality care as patients leave the hospital. These include the discontinuity between hospitalists and primary care physicians, changes to the medication regimen, new self-care responsibilities that may stress available resources, and complex discharge instructions. We also discuss approaches to promoting more effective transitions of care, including improvements in communication between inpatient and outpatient physicians, effective reconciliation of prescribed medication regimens, adequate education of patients about medication use, closer medical follow-up, engagement with social support systems, and greater clarity in physician-patient communication. By understanding the key challenges and adopting strategies to improve patient care in the transition from hospital to home, hospitalists could significantly reduce medical errors in the postdischarge period.
1.5.1 The C‐17 and BC‐17X: Systems Engineered Transport Aircraft for the World

The USAF and RAF C-17 and the Boeing-funded commercial derivative, the BC-17X, are aircraft with unique requirements. The C-17's capabilities include austere airfield landing, short takeoff and landing capability, and benign loading and unloading. Systems engineering (SE) is applied to the customer-required Producibility Enhancement / Performance Improvement (PE/PI) and to Boeing-initiated projects, such as Must Cost projects to improve aircraft affordability. PE/PI projects include the Dual-Row Airdrop capability. Must Cost examples include the Wheel, Brakes, and Tires Alternate Configuration. Other Boeing-initiated projects include the Extended Range project. BC-17X efforts include commercial certification and the conversion to commercial missions. All of these changes have been accomplished through the fusion of SE and the expediting of changes through the Change Breakthrough Initiative (CBI). The final area of SE application is the development of the Flexible Sustainment system for aircraft support.
Twenty Years Later: Creating a Continuous Improvement Environment for Electrical Safety

This paper discusses demonstrated results from the electrical safety improvement strategy documented in the paper, Creating a Continuous Improvement Environment for Electrical Safety , presented at the 1992 IEEE Industry Applications Society Petroleum and Chemical Industry Conference. Two of the original authors present this follow-up paper with a critique of the continuous improvement strategy outlined in the original paper and discussion of lessons learned from its implementation. The paper shows how this strategy is aligned with leading edge developments in advanced safety management of hazards with high potential for fatality and includes a discussion on applying this strategy to these other hazards.
Polynomial time testability of circuits generated by input decomposition

Considers polynomial time testability of combinational circuits generated by input decomposition, especially those generated by the logic synthesis tool FACTOR. First, the complexity of the fault detection problem in this class of circuits is explored using a stuck-at fault model. An O(2/sup k/m) algorithm for detecting a single stuck-at fault is given that is faster than the O(16/sup k/m), previously reported best algorithm proposed by Fujiwara(1990), where k is the number of inputs in a subcircuit and m the number of signal lines in the circuit. Efficient, polynomial time algorithms are described for generating a test set for all single stuck-at faults in the circuit. The basic strategy is to eliminate backtracks during line justification by constructing tables or vector sets in each subcircuit, which makes the fault propagation procedure very simple and eventually results in an efficient test generation procedure. This presentation of efficient polynomial time test generation algorithms for FACTOR-generated circuits is important, since it shows that it is possible to synthesize circuits that are optimized for area and are polynomial time testable at the same time. >
The 2005 Guidelines for CPR and Emergency Cardiovascular Care: Implications for Emergency Medical Services for Children

In 2005, the American Heart Association published revised guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care. In most emergency medical services systems in this country, these guidelines are used to guide the training of prehospital care providers and also to revise the protocols that these caregivers follow. Therefore, they will have an important impact on emergency medical care of children. The largest impact will be in the way that cardiopulmonary CPR is performed in victims of all ages. The guidelines emphasize the importance of effective uninterrupted chest compressions during CPR. Pediatric-specific changes in the guidelines include the following: when a patient should be identified as a pediatric patient; methods for delivering CPR; and the use of the automated external defibrillator. The guidelines also ask dispatchers and healthcare providers to distinguish between sudden cardiac arrest and asphyxial arrest, and then to base their initial care on the most likely cause of arrest. The goal of the revisions is to guide caregivers to provide the most effective initial care for patients in need of resuscitation.
Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle.

The HIV protease inhibitor indinavir adversely impairs carbohydrate and lipid metabolism, whereas its influence on protein metabolism under in vivo conditions remains unknown. The present study tes...
Drosophila molecular phylogenies and their uses.

Relatively few organisms serve as experimental material for biologists and one could argue that of the several millions of species of plants and animals extant today, no single organism has received more attention as an experimental organism than has Drosophila. In the first part of this century, genetics was the most exciting and new area of biology and, stemming from its use by Morgan and colleagues, Drosophila played a central role in the elucidation of genetic principles. In the middle part of the century, evolutionary genetics and the synthesis of Darwinism with Mendelism represented a major advance in biological thinking; much of the empirical work used to support this synthesis centered around Drosophila as the research organism as exemplified by Dobzhansky’s work. In the latter part of the century, molecular biology and development have become premier research fields and once again Drosophila is playing a major role. The Drosophila embryo is serving as a paradigm for developmental studies (Akam, 1987; Nusslein-Volhard, 1991) as well as a paradigm for genome mapping (Ashburner et al., 1991; Hartl et al., 1992).
Selection for Egg Production Within Crossbred Chickens

Abstract CROSSES of various kinds are used extensively for the production of chickens. It has been generally assumed that crossbred females are undesirable for breeders to produce a terminal generation for maximum egg production. Published data regarding the breeding value of such terminal generation females are limited. Kusner (1957) found a cross between New Hampshire and White Russian gave better production than the backcross to the New Hampshires. Skaller (1954) found 2-way crosses laid 216 eggs and 3-way crosses 210 eggs in experiments extending over a five-year period. Waters (1938) and Maw (1942) suggest that if females from a cross were used as dams the males should be unrelated to the dams. Warren (1953) mentions the common practice of some swine breeders in using crossbreds for dams. He states 3-way crosses are as good as 2-way crosses but no better. Laurent (1953) found vigor to be greater in the 3-way than…