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At least 415 records · Page 23

Does Breast Density Increase the Risk of Re-excision for Women with Breast Cancer Having Breast-Conservation Therapy?

Background: Women with dense breasts may have less-accurate preoperative evaluation of extent of disease, potentially affecting the achievement of negative margins. The goal of this study is to examine the association between breast density and re-excision rates in women having breast-conserving surgery for invasive breast cancer. Patients and Methods: Women with stage I/II invasive breast cancer treated with breast-conserving surgery between 1/1/2014 and 10/31/2014 were included. Breast density was assessed by two radiologists. The association between breast density and re-excision was examined using logistic regression. Results: Seven hundred and one women were included. Overall, 106 (15.1%) women had at least one re-excision. Younger age at diagnosis was associated with increased breast density (p < 0.001). On univariable analysis, increased breast density was associated with significantly increased odds of re-excision (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.04–1.83), as was multifocal disease, human epidermal growth factor receptor 2 (HER2) positive status, and extensive intraductal component (EIC) (all p < 0.05). On multivariable analysis, breast density remained significantly associated with increased odds of re-excision (OR 1.37, 95% CI 1.00–1.86), as did multifocality and EIC. HER2 positive status was not significantly associated with re-excision on multivariable analysis. Conclusions: Women with dense breasts are more likely to need additional surgery (re-excision after breast-conserving surgery), but increased breast density did not adversely affect disease-free survival in our study. Our findings support the need for further study in developing techniques that can help decrease re-excisions for women with dense breasts who undergo breast-conserving surgery.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [{sup 11}C]raclopride (D{sub 2}/D{sub 3} receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D{sub 2}/D{sub 3} receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

60 APPLIED LIFE SCIENCES↗

Effects of increasing tip velocity on wind turbine rotor design.

A reduction in cost of energy from wind is anticipated when maximum allowable tip velocity is allowed to increase. Rotor torque decreases as tip velocity increases and rotor size and power rating are held constant. Reduction in rotor torque yields a lighter weight gearbox, a decrease in the turbine cost, and an increase in the capacity for the turbine to deliver cost competitive electricity. The high speed rotor incurs costs attributable to rotor aero-acoustics and system loads. The increased loads of high speed rotors drive the sizing and cost of other components in the system. Rotor, drivetrain, and tower designs at 80 m/s maximum tip velocity and 100 m/s maximum tip velocity are created to quantify these effects. Component costs, annualized energy production, and cost of energy are computed for each design to quantify the change in overall cost of energy resulting from the increase in turbine tip velocity. High fidelity physics based models rather than cost and scaling models are used to perform the work. Results provide a quantitative assessment of anticipated costs and benefits for high speed rotors. Finally, important lessons regarding full system optimization of wind turbines are documented.

17 WIND ENERGY↗

IL-17A Increases Doxorubicin Efficacy in Triple Negative Breast Cancer

Due to lack of targetable receptors and intertumoral heterogeneity, triple negative breast cancer (TNBC) remains particularly difficult to treat. Doxorubicin (DOX) is typically used as nonselective neoadjuvant chemotherapy, but the diversity of treatment efficacy remains unclear. Comparable to variability in clinical response, an experimental model of TNBC using a 4T1 syngeneic mouse model was found to elicit a differential response to a seven-day treatment regimen of DOX. Single-cell RNA sequencing identified an increase in T cells in tumors that responded to DOX treatment compared to tumors that continued to grow uninhibited. Additionally, compared to resistant tumors, DOX sensitive tumors contained significantly more CD4 T helper cells (339%), γδ T cells (727%), Naïve T cells (278%), and activated CD8 T cells (130%). Furthermore, transcriptional profiles of tumor infiltrated T cells in DOX responsive tumors revealed decreased exhaustion, increased chemokine/cytokine expression, and increased activation and cytotoxic activity. γδ T cell derived IL-17A was identified to be highly abundant in the sensitive tumor microenvironment. IL-17A was also found to directly increase sensitivity of TNBC cells in combination with DOX treatment. In TNBC tumors sensitive to DOX, increased IL-17A levels lead to a direct effect on cancer cell responsiveness and chronic stimulation of tumor infiltrated T cells leading to improved chemotherapeutic efficacy. IL-17A’s role as a chemosensitive cytokine in TNBC may offer new opportunities for treating chemoresistant breast tumors and other cancer types.

4T1↗

The critical amplifying role of increasing atmospheric moisture demand on tree mortality and associated regional die-off

Drought-induced tree mortality, including large-scale die-off events and increases in background rates of mortality, is a global phenomenon (Allen et al., 2010) that can directly impact numerous earth system properties and ecosystem goods and services (Adams et al., 2010; Breshears et al., 2011; Anderegg et al., 2013). Tree mortality is particularly of concern because of the likelihood that it will increase in frequency and extent with climate change (McDowell et al., 2008, 2011; Adams et al., 2009; McDowell, 2011; Williams et al., 2013). Recent plant science advances related to drought have focused on understanding the physiological mechanisms that not only affect plant growth and associated carbon metabolism, but also the more challenging issue of predicting plant mortality thresholds (McDowell et al., 2013). Although some advances related to mechanisms of mortality have been made and have increased emphasis on interrelationships between carbon metabolism and plant hydraulics (McDowell et al., 2011), notably few studies have specifically evaluated effects of increasing atmospheric demand for moisture (i.e., vapour pressure deficit; VPD) on rates of tree death. In this opinion article we highlight the importance of considering the key risks of future large-scale tree die-off and other mortality events arising from increased VPD. Here we focus on mortality of trees, but our point about the importance of VPD is also relevant to other vascular plants.

54 ENVIRONMENTAL SCIENCES↗

Mobilizing Vacuolar Sugar Increases Vegetative Triacylglycerol Accumulation

Photosynthetically derived sugars provide carbon skeletons for metabolism and carbon signals that favor anabolism. The amount of sugar available for fatty acid (FA) and triacylglycerol (TAG) synthesis depends on sugar compartmentation, transport, and demands from competing pathways. We are exploring the influence of sugar partitioning between the vacuole and cytoplasm on FA synthesis in Arabidopsis by building on our previous finding that reduced leaf sugar export in the sucrose-proton symporter2 (suc2) mutant, in combination with impaired starch synthesis in the ADP-glucose pyrophosphorylase (adg1) mutant, accumulates higher sugar levels and increased total FA and TAG compared to the wild type parent. Here we sought to relocalize sugar from the vacuole to the cytoplasm to drive additional FA/TAG synthesis and growth. Arabidopsis suc2 adg1 was therefore crossed with tonoplast monosaccharide transporter mutants tmt1 and tmt2 and overexpression of the sucrose/proton cotransporter SUC4 in which tmt1 tmt2 impairs sugar transport to the vacuole from the cytoplasm and SUC4 overexpression enhances sugar transport in the reverse direction from the vacuole to the cytoplasm. A resulting homozygous suc2 adg1 tmt1 tmt2 SUC4 line was used to test the hypothesis that increased intracellular carbon supply in the form of sugars would increase both FA and TAG accumulation. The data shows that relative to suc2 adg1, suc2 adg1 tmt1 tmt2 SUC4 significantly increases leaf total FA content by 1.29-fold to 10.9% of dry weight and TAG by 2.4-fold to 2.88%, supporting the hypothesis that mobilizing vacuolar sugar is a valid strategy for increasing vegetative oil accumulation.

59 BASIC BIOLOGICAL SCIENCES↗

Bacterial Volatile Organic Compounds as a Strategy to Increase Drought Tolerance in Maize (Zea mays L.): Influence on Plant Biochemistry

Maize is highly susceptible to drought, which affects growth and yield. This study investigated how bacterial volatile organic compounds (BVOCs) affect maize drought tolerance. Drought reduced shoot size but increased root length, an adaptation for accessing deeper soil moisture. BVOCs from strain D12 significantly increased root length and shoot growth under drought conditions. Drought also altered root biochemistry, decreasing enzyme activity, and increased osmolyte levels. BVOCs from strains F11 and FS4-14 further increased osmolyte levels but did not protect membranes from oxidative damage, while BVOCs from strains D12 and D7 strains reduced osmolyte levels and cell damage. In shoots, drought increased the levels of osmolytes and oxidative stress markers. BVOCs from FS4-14 had minimal effects on shoot biochemistry. BVOCs from D12 and F11 partially restored metabolic activity but did not reduce cell damage. BVOCs from D7 reduced metabolic activity and cell damage. These results suggest that BVOCs can modulate the biochemical response of maize to drought, with some strains evidencing the potential to enhance drought tolerance.

Lopes, Tiago (ORCID:0000000330603315)↗

Sequence Length of HIV-1 Subtype B Increases over Time: Analysis of a Cohort of Patients with Hemophilia over 30 Years

We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and P. In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in env and nef genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction.

59 BASIC BIOLOGICAL SCIENCES↗

NITROGEN CAN LIMIT OVERSTORY TREE GROWTH FOLLOWING EXTREME STAND DENSITY INCREASE IN A PONDEROSA PINE FOREST

Extreme stand density increases have occurred in ponderosa pine forests throughout the western U.S. since the early 20th Century, with adverse implications for growth, physiological functioning, and mortality risk. Identifying primary stressors on large, old overstory trees in dense forests can inform management decisions to promote resilience and survival. We tested the impact of stand density increase on overstory treering growth, and the relative influence of water and nitrogen, in an old-growth ponderosa pine forest subject to variable density increase. We measured annual tree-ring growth and carbon discrimination in trees before stand density increased, in a climatically-similar period post-density increase, and in recent transition to drought. We expected density-driven water stress to drive reduced tree-ring growth in overstory trees in dense stands. We found reduced growth and higher mortality in dense stands, but nitrogen rather than water constrained growth, as determined by carbon isotope discrimination in tree rings, leaf nitrogen concentration, and soil nitrogen supply. In dense stands, less available nitrogen limited photosynthetic rate, leading to reduced assimilation of intracellular 13C and higher discrimination with low tree-ring growth and a reduced relationship with climate. This unexpected result illustrates that a variety of limiting factors can influence forest dynamics, as density-driven nitrogen limitation interacts with water stress to influence tree growth and physiological functioning.

dendroecology, tree-ring width, limiting factors, ↗

Distinct drivers of recent seasonal precipitation increase over Central Asia: roles of anthropogenic aerosols and greenhouse gases

Observational evidence reveals a pronounced wetting trend over Central Asia in recent decades, with the most substantial increases occurring during winter and summer. Yet the extent to which the drivers of these changes differ seasonally remains unknown. Here, we use single-forcing experiments from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP) to examine the effects of various external forcings on winter and summer precipitation across Central Asia and to explore the physical mechanisms underlying seasonal precipitation changes. We find that greenhouse gas (GHG) forcing mainly increases winter precipitation by enhancing atmospheric moisture content through warming. In contrast, in summer, Asian sulfate aerosols enhance precipitation by modulating the westerly jet, which strengthens atmospheric moisture transport into the region. Asian black carbon exerts an opposing influence that partially offsets the sulfate-induced effect. Further attribution analysis based on CMIP6 simulations reinforces these sensitivity results and shows that GHG forcing is the primary driver of winter precipitation increases whereas anthropogenic aerosols dominate summer trends. Future CMIP6 projections suggest that under moderate- to high-emission scenarios, winter precipitation will continue to rise due to increasing GHG concentrations, while summer precipitation may decline across much of Central Asia as a result of reduced aerosol emissions following Asian clean air policies. These findings highlight a distinct seasonality in the drivers of recent precipitation increase and suggest a plausible divergence in future winter and summer precipitation trends.

54 ENVIRONMENTAL SCIENCES↗

AKR signal increases caused by triggering

This paper presents a study of the amplitude increases which accompany the triggering of auroral kilometric radiation (AKR) by type-III solar radio bursts. IMP-8 data were used to determine the signal increases observed during one-hour periods before and after type-III bursts at 100 kHz, 178 kHz, and 500 kHz, and these were compared with similar observations when the type-III bursts were absent. The results indicate that between 8 to 16 pct of the type-III bursts caused statistically significant intensity increases and that infrequent large signal increases of sometimes 20 dB or more tended to characterize the triggered AKR, rather than a large proportion of small increases.

Farrell, W. M.↗

The potential impact on atmospheric ozone and temperature of increasing trace gas concentrations

The response of the atmosphere to emissions of chlorofluorocarbons (CFCs) and other chlorocarbons, and to increasing concentrations of other radiatively active trace gases such as CO2, CH4, and N2O is calculated by a coupled chemical-radiative transport one-dimensional model. It is shown that significant reductions in the ozone concentration and in the temperature are expected in the upper stratosphere as a result of increasing concentrations of active chlorine produced by photodecomposition of the CFCs. The ozone content is expected to increase in the troposphere, as a consequence of increasing concentrations of methane and nitrogen oxides. Due to enhanced greenhouse effects, the Earth's surface should warm up by several degrees. The amplitude and even the sign of future changes in the ozone column are difficult to predict as they are strongly scenario-dependent. An early detection system to prevent noticeable ozone changes as a result of increasing concentrations of source gases should thus be based on a continuous monitoring of the ozone amount in the upper stratosphere rather than on measurements of the ozone column only. Measurements of NOx, Clx, and HOx are also required for unambiguous trend detection and interpretation.

Brasseur, G.↗

Increase of stagnation pressure and enthalpy in shock tunnels

High stagnation pressures and enthalpies are required for the testing of aerospace vehicles such as aerospace planes, aeroassist vehicles, and reentry vehicles. Among the most useful ground test facilities for performing such tests are shock tunnels. With a given driver gas condition, the enthalpy and pressure in the driven tube nozzle reservoir condition can be varied by changing the driven tube geometry and initial gas fill pressure. Reducing the driven tube diameter yields only very modest increases in reservoir pressure and enthalpy. Reducing the driven tube initial gas fill pressure can increase the reservoir enthalpy significantly, but at the cost of reduced reservoir pressure and useful test time. A new technique, the insertion of a converging section in the driven tube is found to produce substantial increases in both reservoir pressure and enthalpy. Using a one-dimensional inviscid full kinetics code, a number of different locations and shapes for the converging driven tube section were studied and the best cases found. For these best cases, for driven tube diameter reductions of factors of 2 and 3, the reservoir pressure can be increased by factors of 2.1 and 3.2, respectively and the enthalpy can be increased by factors of 1.5 and 2.1, respectively.

Bogdanoff, David W.↗

Depth-viewing-volume increase by collimation of stereo 3-D displays

Typical stereo 3-D displays are produced using a single-image-source, which is time-multiplexed, to present disparate, directly-viewed views (stereo pairs) of the visual scene to each eye. However, current stereoscopic viewing techniques impose severe restrictions in the effective viewing-volume of the stereo 3-D display. Recent experiments at Langley Research Center determined that the effective region of stereopsis cuing, the depth-viewing volume, increased with increasing viewer-to-screen distances. This increase was also accompanied by a decrease in the field-of-view of the system. It was postulated that collimation of the display source would dramatically increase the depth-viewing volume, as the effective accommodation distance would be near infinity, while maintaining the field-of-view at required levels. The goal of this proof-of-concept effort was to investigate whether or not a dramatic increase in depth-viewing volume for stereo 3-D displays would be provided by the application of collimated optics to the stereo display source.

Busquets, Anthony M.↗

Increasing levels of assistance in refinement of knowledge-based retrieval systems

The task of incrementally acquiring and refining the knowledge and algorithms of a knowledge-based system in order to improve its performance over time is discussed. In particular, the design of DE-KART, a tool whose goal is to provide increasing levels of assistance in acquiring and refining indexing and retrieval knowledge for a knowledge-based retrieval system, is presented. DE-KART starts with knowledge that was entered manually, and increases its level of assistance in acquiring and refining that knowledge, both in terms of the increased level of automation in interacting with users, and in terms of the increased generality of the knowledge. DE-KART is at the intersection of machine learning and knowledge acquisition: it is a first step towards a system which moves along a continuum from interactive knowledge acquisition to increasingly automated machine learning as it acquires more knowledge and experience.

Baudin, Catherine↗

Increase of carbonyl fluoride (COF2) in the stratosphere and its contribution to the 1992 budget of inorganic fluorine in the upper stratosphere

Volume mixing ratio profiles of COF2 have been derived through most of the stratosphere between 30 deg N and 54 deg S from series of 0.01-/cm resolution infrared solar spectra recorded in the occultation mode by the atmospheric trace molecule spectroscopy (ATMOS) instrument during the ATLAS 1 space shuttle mission of March-April 1992. When compared with similar results obtained from the ATMOS/Spacelab 3 mission of April-May 1985, the cumulative increase in the burden of COF2 in the middle and upper stratosphere was found to be 67% for that 7-year time interval. By combining a subset of these COF2 results with upper stratospheric concentrations of HF also derived from the ATMOS observations, it was further found that the budget of inorganic fluorine above 35 km altitude increased by (60 +/- 10)% over the 1985-1992 time interval, which corresponds to an average exponential rate of increase of (6.7 +/- 1/1)%/yr, or a linear rate of increase reference to 1985 of (8.5 +/- 1.3)%/yr at the 1 sigma confidence level. The total inorganic F atom volume mixing ratio found in the upper stratosphere for 1985 and 1992 and the increase during this perid mirror the rise in man-made fluorine-bearing compounds at the ground during the early to mid 1980s. This demonstrates the negligible impact of natural sources of fluorine, in particular volcanic activity, on the observed change in F in the upper stratosphere. Implications of the present findings and comparison with model results are discussed.

Zander, R.↗

Increase of carbonyl fluoride (COF2) in the stratosphere and its contribution to the 1992 budget of inorganic fluorine in the upper stratosphere

Volume mixing ratio profiles of COF2 have been derived through most of the stratosphere between 30 deg N and 54 deg S from series of 0.01-cm(exp -1) resolution infrared solar spectra recorded in the occultation mode by the atmospheric trace molecule spectroscopy (ATMOS) instrument during the ATLAS 1 space shuttle mission of March-April 1992. When compared with similar results obtained from the ATMOS/Spacelab 3 mission of April-May 1985, the cumulative increase in the burden of COF2 in the middle and upper stratosphere was found to be 67% for that 7-year time interval. By combining a subset of these COF2 results with upper stratospheric concentrations of HF also derived from the ATMOS observations, it was further found that the budget of inorganic fluorine above 35 km altitude increased by (60 +/- 10) % over the 1985-1992 time interval, which corresponds to an average exponential rate of increase of(6.7 +/- 1.1) % /yr , or a linear rate of increase referenced to 1985 of (8.5 +/- 1.3) % /yr at the 1(sigma) confidence level. The total inorganic F atom volume mixing ratio found in the upper stratosphere for 1985 and 1992 and the increase during this period mirror the rise in man-made fluorine-bearing compounds at the ground during the early to mid 1980s. This demonstrates the negligible impact of natural sources of fluorine, in particular volcanic activity, on the observed change of F in the upper stratosphere. Implications of the present findings and comparison with model results are discussed.

Zander, R.↗

Simulated Microgravity Increases Cutaneous Blood Flow in the Head and Leg of Humans

The cutaneous micro-circulation vasodilates during acute 6 deg. head-down tilt (HDT, simulated microgravity) relative to upright conditions, more in the lower body than in the upper body. We expected that relative magnitudes of and differences between upper and lower body cutaneous blood flow elevation would be sustained during initial acclimation to simulated microgravity. We measured cutaneous micro-vascular blood flow with laser-Doppler flowmetry at the leg (over the distal tibia) and cheek (over the zygomatic arch) of eight healthy men before, during, and after 24 h of HDT. Results were calculated as a percentage of baseline value (100% measured during pre-tilt upright sitting). Cutaneous blood flow in the cheek increased significantly to 165 +/- 37% (mean + SE, p less than 0.05) at 9-12 h HDT, then returned to near baseline values by 24 h HDT (114 +/- 29%, NSD), despite increased local arterial pressure. Microvascular flow in the leg remained significantly elevated above baseline throughout 24 h HDT (427 +/- 85% at 3 h HDT and 215 +/- 142% at 24 h HDT, p less than 0.05). During the 6-h upright sitting recovery period, cheek and leg blood flow levels returned to near pre-tilt baseline values. Because hydrostatic effects of HDT increase local arterial pressure at the carotid sinus, baroreflex-mediated withdrawal of sympathetic tone probably contributed to increased microvascular flows at the head and leg during HDT. In the leg, baroreflex effects combined with minimal stimulation of local veno-arteriolar and myogenic autoregulatory vasoconstriction to elicit relatively larger and more sustained increases in cutaneous flow during HDT. In the cheek, delayed myogenic vasoconstriction and/or humoral effects apparently compensated for flow elevation by 24 h of HDT. Therefore, localized vascular adaptations to gravity probably explain differences in acclimation of lower and upper body blood flow to HDT and actual microgravity.

Stout, M. Shannon↗