The effect of environmental chemicals on the tumor microenvironment

PubMed Central

Casey, Stephanie C.; Vaccari, Monica; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Barcellos-Hoff, Mary Helen; Brown, Dustin G.; Chapellier, Marion; Christopher, Joseph; Curran, Colleen S.; Forte, Stefano; Hamid, Roslida A.; Heneberg, Petr; Koch, Daniel C.; Krishnakumar, P.K.; Laconi, Ezio; Maguer-Satta, Veronique; Marongiu, Fabio; Memeo, Lorenzo; Mondello, Chiara; Raju, Jayadev; Roman, Jesse; Roy, Rabindra; Ryan, Elizabeth P.; Ryeom, Sandra; Salem, Hosni K.; Scovassi, A.Ivana; Singh, Neetu; Soucek, Laura; Vermeulen, Louis; Whitfield, Jonathan R.; Woodrick, Jordan; Colacci, Anna Maria; Bisson, William H.; Felsher, Dean W.

2015-01-01

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis. PMID:26106136

New methods for evaluating physical and thermal comfort properties of orthotic materials used in insoles for patients with diabetes.

PubMed

Lo, Wai Ting; Yick, Kit Lun; Ng, Sun Pui; Yip, Joanne

2014-01-01

Orthotic insoles are commonly used in the treatment of the diabetic foot to prevent ulcerations. Choosing suitable insole material is vital for effective foot orthotic treatment. We examined seven types of orthotic materials. In consideration of the key requirements and end uses of orthotic insoles for the diabetic foot, including accommodation, cushioning, and control, we developed test methods for examining important physical properties, such as force reduction and compression properties, insole-skin friction, and shear properties, as well as thermal comfort properties of fabrication materials. A novel performance index that combines various material test results together was also proposed to quantify the overall performance of the insole materials. The investigation confirms that the insole-sock interface has a lower coefficient of friction and shearing stress than those of the insole-skin interface. It is also revealed that material brand and the corresponding density and cell volume, as well as thickness, are closely associated with the performance of moisture absorption and thermal comfort. On the basis of the proposed performance index, practitioners can better understand the properties and performance of various insole materials, thus prescribing suitable orthotic insoles for patients with diabetic foot.

Plantar pressure with and without custom insoles in patients with common foot complaints.

PubMed

Stolwijk, Niki M; Louwerens, Jan Willem K; Nienhuis, Bart; Duysens, Jacques; Keijsers, Noël L W

2011-01-01

Although many patients with foot complaints receive customized insoles, the choice for an insole design can vary largely among foot experts. To investigate the variety of insole designs used in daily practice, the insole design and its effect on plantar pressure distribution were investigated in a large group of patients. Mean, peak, and pressure-time-integral per sensor for 204 subjects with common foot complaints for walking with and without insoles was measured with the footscan® insole system (RSscan International). Each insole was scanned twice (precision3D), after which the insole height along the longitudinal and transversal cross section was calculated. Subjects were assigned to subgroups based on complaint and medial arch height. Data were analyzed for the total group and for the separate subgroups (forefoot or heel pain group and flat, normal or high medial arch group). The mean pressure significantly decreased under the metatarsal heads II-V and the calcaneus and significantly increased under the metatarsal bones and the lateral foot (p<0.0045) due to the insoles. However, similar redistribution patterns were found for the different foot complaints and arch heights. There was a slight difference in insole design between the subgroups; the heel cup was significantly higher and the midfoot support lower for the heel pain group compared to the forefoot pain group. The midfoot support was lowest in the flat arch group compared to the high and normal arch group (p<0.05). Although the insole shape was specific for the kind of foot complaint and arch height, the differences in shape were very small and the plantar pressure redistribution was similar for all groups. This study indicates that it might be sufficient to create basic insoles for particular patient groups.

Nonlinear Insolation Forcing: A Physical Mechanism for Climate Change

NASA Technical Reports Server (NTRS)

Liu, H. S.

1998-01-01

This paper focuses on recent advances in the understanding of nonlinear insolation forcing for climate change. The amplitude-frequency resonances in the insolation variations induced by the Earth's changing obliquity are emergent and may provide a physical mechanism to drive the glaciation cycles. To establish the criterion that nonlinear insolation forcing is responsible for major climate changes, the cooperative phenomena between the frequency and amplitude of the insolation are defined as insolation pulsation. Coupling of the insolation frequency and amplitude variations has established an especially new and interesting series of insolation pulses. These pulses would modulate the insolation in such a way that the mode of insolation variations could be locked to generate the 100-kyr ice age cycle which is a long-time geophysical puzzle. The nonlinear behavior of insolation forcing is tested by energy balance and ice sheet climate models and the physical mechanism behind this forcing is explained in terms of pulse duration in the incoming solar radiation. Calculations of the solar energy flux at the top of the atmosphere show that the duration of the negative and positive insolation pulses is about 2 thousand years which is long enough to prolong glaciation into deep ice ages and cause rapid melting of large ice sheets in the high latitudes of the northern hemisphere. We have performed numerical simulations of climate response to nonlinear insolation forcing for the past 2 million years. Our calculated results of temperature fluctuations are in good agreement with the climate cycles as seen in the terrestrial biogenic silica (BDP-96-2) data as well as in the marine oxygen isotope (delta(sup 18)O) records.

Lipophilic Compound-Mediated Gene Expression and Implication for Intervention in Reactive Oxygen Species (ROS)-Related Diseases: Mini-review

PubMed Central

Nakamura, Yukiko K.; Omaye, Stanley T.

2010-01-01

In addition to exhibiting antioxidant properties, conjugated linoleic acid (CLA) and vitamin E may modulate gene expression of endogenous antioxidant enzymes. Depending on cellular microenvironments, such modulation reflects either antioxidant or prooxidant outcomes. Although epidemiological/experimental studies have indicated that CLA and vitamin E have health promoting properties, recent findings from clinical trials have been inconclusive. Discrepancies between the results found from prospective studies and recent clinical trials might be attributed to concentration-dependent cellular microenvironment alterations. We give a perspective of possible molecular mechanisms of actions of these lipophilic compounds and their implications for interventions of reactive oxygen species (ROS)-related diseases. PMID:22254050

Spatiotemporal Co-variability of Surface Climate for Renewable Energy across the Contiguous United States: Role of the North Atlantic Subtropical High

NASA Astrophysics Data System (ADS)

Doering, K.; Steinschneider, S.

2017-12-01

The variability of renewable energy supply and drivers of demand across space and time largely determines the energy balance within power systems with a high penetration of renewable technologies. This study examines the joint spatiotemporal variability of summertime climate linked to renewable energy production (precipitation, wind speeds, insolation) and energy demand (temperature) across the contiguous United States (CONUS) between 1948 and 2015. Canonical correlation analysis is used to identify the major modes of joint variability between summer wind speeds and precipitation and related patterns of insolation and temperature. Canonical variates are then related to circulation anomalies to identify common drivers of the joint modes of climate variability. Results show that the first two modes of joint variability between summer wind speeds and precipitation exhibit pan-US dipole patterns with centers of action located in the eastern and central CONUS. Temperature and insolation also exhibit related US-wide dipoles. The relationship between canonical variates and lower-tropospheric geopotential height indicates that these modes are related to variability in the North Atlantic subtropical high (NASH). This insight can inform optimal strategies for siting renewables in an interconnected electric grid, and has implications for the impacts of climate variability and change on renewable energy systems.

The effect of insoles on foot pain and daily activities.

PubMed

Amer, Ahmed O; Jarl, Gustav M; Hermansson, Liselotte N

2014-12-01

Foot pain decreases individuals' ability to perform daily activities. Insoles are often prescribed to reduce the pain which, in turn, may promote return to normal activities. To evaluate the effects of insoles on foot pain and daily activities, and to investigate the relationship between individuals' satisfaction with insoles and actual use of them. A 4-week pre-post intervention follow-up. Brief Pain Inventory, International Physical Activity Questionnaire and Lower Extremities Functional Status were used as outcome measures. Client Satisfaction with Device was used in the follow-up. A total of 67 participants answered the questionnaires (81% women). Overall, a reduction in Pain Severity (p = 0.002) and Pain Interference (p = 0.008) was shown. Secondary analyses revealed a significant effect only in women. No changes in daily activities (Walking, p = 0.867; Total Physical Activity, p = 0.842; Lower Extremities Functional Status, p = 0.939) could be seen. There was no relation between Client Satisfaction with Device measures and duration of insole use. A difference in sex was shown; women scored higher than men on Pain Severity. Insoles reduce pain and pain interference with daily activities for women with foot pain. Satisfaction with the insoles is not a predictor of actual insole use. The effect of insoles on activity performance needs further study. This study provides evidence for prescribing insoles to people with foot pain. Nonetheless, insoles are not enough to increase their physical activity level in the short term. Satisfaction with insoles and duration of use are not correlated and cannot be inferred from each other. © The International Society for Prosthetics and Orthotics 2013.

Evaporation of ice in planetary atmospheres - Ice-covered rivers on Mars

NASA Technical Reports Server (NTRS)

Wallace, D.; Sagan, C.

1979-01-01

The existence of ice covered rivers on Mars is considered. It is noted that the evaporation rate of water ice on the surface of a planet with an atmosphere involves an equilibrium between solar heating and radiative and evaporative cooling of the ice layer. It is determined that even with a mean Martian insolation rate above the ice of approximately 10 to the -8th g per sq cm/sec, a flowing channel of liquid water will be covered by ice which evaporates sufficiently slowly that the water below can flow for hundreds of kilometers even with modest discharges. Evaporation rates are calculated for a range of frictional velocities, atmospheric pressures, and insolations and it is suggested that some subset of observed Martian channels may have formed as ice-choked rivers. Finally, the exobiological implications of ice covered channels or lakes on Mars are discussed.

Effect of a novel insole on the subtalar joint of patients with medial compartment osteoarthritis of the knee.

PubMed

Toda, Y; Segal, N; Kato, A; Yamamoto, S; Irie, M

2001-12-01

To assess the efficacy of a lateral wedge insole with elastic strapping of the subtalar joint for conservative treatment of osteoarthritis (OA) of the knee. The efficacy of a novel insole with elastic subtalar strapping and a traditional shoe insert wedge insole was compared. Ninety female outpatients with OA of the knee were treated with wedge insoles for 8 weeks. Randomization was performed according to birth date. Standing radiographs with unilateral insole use were used to analyze the femorotibial and talar tilt angles for each patient with and without their respective insole. Visual analog scale (VAS) score for subjective knee pain at the final assessment was compared with that at baseline in both groups. Participants wearing the elastically strapped insole (n = 46) had significantly decreased femorotibial angle (p < 0.0001) and talar tilt angle (p = 0.005) and significantly improved VAS pain score (p = 0.045) in comparison with baseline assessments. These significant differences were not found in the group with the inserted insole (n = 44). The novel strapped insole leads to valgus angulation of the talus, resulting in correction of the femorotibial angle in patients with knee OA with varus deformity, and may have a therapeutic effect similar to that of high tibial osteotomy.

Using an optimization approach to design an insole for lowering plantar fascia stress--a finite element study.

PubMed

Hsu, Yu-Chun; Gung, Yih-Wen; Shih, Shih-Liang; Feng, Chi-Kuang; Wei, Shun-Hwa; Yu, Chung-Huang; Chen, Chen-Sheng

2008-08-01

Plantar heel pain is a commonly encountered orthopedic problem and is most often caused by plantar fasciitis. In recent years, different shapes of insole have been used to treat plantar fasciitis. However, little research has been focused on the junction stress between the plantar fascia and the calcaneus when wearing different shapes of insole. Therefore, this study aimed to employ a finite element (FE) method to investigate the relationship between different shapes of insole and the junction stress, and accordingly design an optimal insole to lower fascia stress.A detailed 3D foot FE model was created using ANSYS 9.0 software. The FE model calculation was compared to the Pedar device measurements to validate the FE model. After the FE model validation, this study conducted parametric analysis of six different insoles and used optimization analysis to determine the optimal insole which minimized the junction stress between plantar fascia and calcaneus. This FE analysis found that the plantar fascia stress and peak pressure when using the optimal insole were lower by 14% and 38.9%, respectively, than those when using the flat insole. In addition, the stress variation in plantar fascia was associated with the different shapes of insole.

A longitudinal investigation into the functional and physical durability of insoles used for the preventive management of neuropathic diabetic feet.

PubMed

Paton, Joanne S; Stenhouse, Elizabeth; Bruce, Graham; Jones, Ray

2014-01-01

Insoles are commonly used to assist in the prevention of diabetic neuropathic foot ulceration. Insole replacement is often triggered only when foot lesions deteriorate, an indicator that functional performance is comprised and patients are exposed to unnecessary ulcer risk. We investigated the durability of insoles used for ulcer prevention in neuropathic diabetic feet over 12 months. Sixty neuropathic individuals with diabetes were provided with insoles and footwear. Insole durability over 12 months was evaluated using an in-shoe pressure measurement device and through repeated measurement of material depth at the first metatarsal head and the heel seat. Analysis of variance was performed to assess change across time (at issue, 6 months, and 12 months). Analyses were conducted using all available data (n = 43) and compliant data (n = 18). No significant difference was found in the reduction of mean peak pressure tested across time (P < .05). For both sites, significant differences in insole depth were identified between issue and 6 months and between issue and 12 months but not between 6 and 12 months (P < .05). Most insole compression occurred during the initial 6 months. Visual material compression does not seem to be a reliable indicator of insole usefulness. Frequency of insole replacement is best informed by a functional review of effect determined using an in-shoe pressure measurement system. These results suggest that insoles for diabetic neuropathic patients can be effective in maintaining peak pressure reduction for 12 months regardless of wear frequency.

Shear-reducing insoles to prevent foot ulceration in high-risk diabetic patients.

PubMed

Lavery, Lawrence A; LaFontaine, Javier; Higgins, Kevin R; Lanctot, Dan R; Constantinides, George

2012-11-01

To enhance the learner's competence with knowledge of the effectiveness of shear-reducing insoles for prevention of foot ulceration in patients with high-risk diabetes. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Demonstrate knowledge of foot ulceration risk, risk factors, incidence, and prevention.2. Apply knowledge gained from reviewing this study and a literature review about the use of shear-reducing insoles to patient scenarios. The objective of this study was to evaluate the effectiveness of a shear-reducing insole compared with a standard insole design to prevent foot ulceration in high-risk patients with diabetes. A total of 299 patients with diabetic neuropathy and loss of protective sensation, foot deformity, or history of foot ulceration were randomized into a standard therapy group (n = 150) or a shear-reducing insole group (n = 149). Patients were evaluated for 18 months. Standard therapy group consisted of therapeutic footwear, diabetic foot education, and regular foot evaluation by a podiatrist. The shear-reducing insole group included a novel insole designed to reduce both pressure and shear on the sole of the foot. Insoles were replaced every 4 months in both groups. The primary clinical outcome was foot ulceration. The authors used Cox proportional hazards regression to evaluate time to ulceration. There were 2 significant factors from the Cox regression model: insole treatment and history of a foot complication. The standard therapy group was about 3.5 times more likely to develop an ulcer compared with shear-reducing insole group (hazard ratio, 3.47; 95% confidence interval, 0.96-12.67). These results suggest that a shear-reducing insole is more effective than traditional insoles to prevent foot ulcers in high-risk persons with diabetes.

A 2-year follow-up of a study to compare the efficacy of lateral wedged insoles with subtalar strapping and in-shoe lateral wedged insoles in patients with varus deformity osteoarthritis of the knee.

PubMed

Toda, Y; Tsukimura, N

2006-03-01

This study was conducted in order to assess the effect of wearing a lateral wedged insole with a subtalar strap for 2 years in patients with osteoarthritis varus deformity of the knee (knee OA). The setting was an outpatient clinic. The efficacies of the strapped insole and a traditional shoe insert wedged insole (the inserted insole), as a positive control, were compared at the baseline and after 2 years of treatment. Randomization was performed according to birth date. The 61 female outpatients with knee OA who completed a prior 6-month study were asked to wear their respective insoles continuously as treatment during the course of the 2-year study. The femorotibial angle (FTA) was assessed by standing radiographs obtained while the subjects were barefoot and the Lequesne index of the knee OA at 2 years was compared with those at baseline in each insole group. There were 61 patients in the original study, but 13 patients (21.3%) did not want to wear the insole continuously and five (8.2%) withdrew for other reasons. The 42 patients who completed the 2-year study were evaluated. At the 2-year assessment, participants wearing the subtalar strapped insole (n=21) demonstrated significantly decreased FTA (P=0.015), and significantly improved Lequesne index (P=0.031) in comparison with their baseline assessments. These significant differences were not found in the group with the traditional shoe inserted wedged insole (n=21). Only those participants using the subtalar strapped insole demonstrated significant change in the FTA in comparison with the baseline assessments. If the insole with a subtalar strap maintains FTA for more than 2 years, it may restrict the progression of degenerative articular cartilage lesions of knee OA.

Impact of soft and hard insole density on postural stability in older adults.

PubMed

Losa Iglesias, Marta Elena; Becerro de Bengoa Vallejo, Ricardo; Palacios Peña, Domingo

2012-01-01

A significant predictor of falls in the elderly population is attributed to postural instability. Thus, it is important to identify and implement practical clinical interventions to enhance postural stability in older adults. Shoe insoles have been identified as a mechanism to enhance postural control, and our study aimed to evaluate the impact of 2 shoe insoles on static standing balance in healthy, older adults compared with standing posture while barefoot. We hypothesized that both hard and soft shoe insoles would decrease postural sway compared with the barefoot condition. Indeed, excursion distances and sway areas were reduced, and sway velocity was decreased when wearing insoles. The hard insole was also effective when visual feedback was removed, suggesting that the more rigid an insole, the greater potential reduction in fall risk. Thus, shoe insoles may be a cost-effective, clinical intervention that is easy to implement to reduce the risk of falling in the elderly population. Copyright © 2012 Mosby, Inc. All rights reserved.

The Effect of Arch Height and Material Hardness of Personalized Insole on Correction and Tissues of Flatfoot.

PubMed

Su, Shonglun; Mo, Zhongjun; Guo, Junchao; Fan, Yubo

2017-01-01

Flat foot is one of the common deformities in the youth population, seriously affecting the weight supporting and daily exercising. However, there is lacking of quantitative data relative to material selection and shape design of the personalized orthopedic insole. This study was to evaluate the biomechanical effects of material hardness and support height of personalized orthopedic insole on foot tissues, by in vivo experiment and finite element modeling. The correction of arch height increased with material hardness and support height. The peak plantar pressure increased with the material hardness, and these values by wearing insoles of 40° were apparently higher than the bare feet condition. Harder insole material results in higher stress in the joint and ligament stress than softer material. In the calcaneocuboid joint, the stress increased with the arch height of insoles. The material hardness did not apparently affect the stress in the ankle joints, but the support heights of insole did. In general, insole material and support design are positively affecting the correction of orthopedic insole, but negatively resulting in unreasonable stress on the stress in the joint and ligaments. There should be an integration of improving correction and reducing stress in foot tissues.

[Use of insoles made of antimicrobial materials as prophylactic means in foot mycoses].

PubMed

Sedov, A V; Vazhbin, L B; Odtarzhevskaia, N D; Astaf'eva, I P; Poliakova, L A; Karpov, V V; Ashurova, E I; Lazareva, N M; Mikhaĭlov, O R

1994-01-01

Stationary dermatologic examination covered 32 sufferers from epidermophytosis of soles, who used 3 types of antimicrobial insoles chosen through laboratory investigations. Clinical trials proved that antimicrobial insoles, if applied during 2 weeks, result in considerably decreased occurrence of causal fungus in the patients' surface skin scarring. The results proved fungicidal and bactericidal activity of insoles including furagin, nitrofurilacroleine, polyhexamethylene guanidine, so such insoles could be recommended as prophylactic measure for mycoses of soles.

21 CFR 880.6280 - Medical insole.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical insole. 880.6280 Section 880.6280 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES....6280 Medical insole. (a) Identification. A medical insole is a device intended for medical purposes...

21 CFR 880.6280 - Medical insole.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical insole. 880.6280 Section 880.6280 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES....6280 Medical insole. (a) Identification. A medical insole is a device intended for medical purposes...

21 CFR 880.6280 - Medical insole.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical insole. 880.6280 Section 880.6280 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES....6280 Medical insole. (a) Identification. A medical insole is a device intended for medical purposes...

21 CFR 880.6280 - Medical insole.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical insole. 880.6280 Section 880.6280 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES....6280 Medical insole. (a) Identification. A medical insole is a device intended for medical purposes...

21 CFR 880.6280 - Medical insole.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical insole. 880.6280 Section 880.6280 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES....6280 Medical insole. (a) Identification. A medical insole is a device intended for medical purposes...

Insolation at Carterville, Illinois

Treesearch

Peter Y. S. Chen

1981-01-01

Insolation measured with a precision spectral pyranometer, was recorded near Carterville, Illinois, for 1 year. the pyranometer was tilted at an angle of 25 degrees in summer, 50 degrees in winter, and 37.5 degrees in spring and fall. the insolation measured in winter was found to be significantly larger than the insolation estimated on a horizontal surface.

The Effect of Arch Height and Material Hardness of Personalized Insole on Correction and Tissues of Flatfoot

PubMed Central

Su, Shonglun; Mo, Zhongjun; Guo, Junchao

2017-01-01

Flat foot is one of the common deformities in the youth population, seriously affecting the weight supporting and daily exercising. However, there is lacking of quantitative data relative to material selection and shape design of the personalized orthopedic insole. This study was to evaluate the biomechanical effects of material hardness and support height of personalized orthopedic insole on foot tissues, by in vivo experiment and finite element modeling. The correction of arch height increased with material hardness and support height. The peak plantar pressure increased with the material hardness, and these values by wearing insoles of 40° were apparently higher than the bare feet condition. Harder insole material results in higher stress in the joint and ligament stress than softer material. In the calcaneocuboid joint, the stress increased with the arch height of insoles. The material hardness did not apparently affect the stress in the ankle joints, but the support heights of insole did. In general, insole material and support design are positively affecting the correction of orthopedic insole, but negatively resulting in unreasonable stress on the stress in the joint and ligaments. There should be an integration of improving correction and reducing stress in foot tissues. PMID:29065655

Effect of Foot Progression Angle and Lateral Wedge Insole on a Reduction in Knee Adduction Moment.

PubMed

Tokunaga, Ken; Nakai, Yuki; Matsumoto, Ryo; Kiyama, Ryoji; Kawada, Masayuki; Ohwatashi, Akihiko; Fukudome, Kiyohiro; Ohshige, Tadasu; Maeda, Tetsuo

2016-10-01

This study evaluated the effect of foot progression angle on the reduction in knee adduction moment caused by a lateral wedged insole during walking. Twenty healthy, young volunteers walked 10 m at their comfortable velocity wearing a lateral wedged insole or control flat insole in 3 foot progression angle conditions: natural, toe-out, and toe-in. A 3-dimensional rigid link model was used to calculate the external knee adduction moment, the moment arm of ground reaction force to knee joint center, and the reduction ratio of knee adduction moment and moment arm. The result indicated that the toe-out condition and lateral wedged insole decreased the knee adduction moment in the whole stance phase. The reduction ratio of the knee adduction moment and the moment arm exhibited a close relationship. Lateral wedged insoles decreased the knee adduction moment in various foot progression angle conditions due to decrease of the moment arm of the ground reaction force. Moreover, the knee adduction moment during the toe-out gait with lateral wedged insole was the smallest due to the synergistic effect of the lateral wedged insole and foot progression angle. Lateral wedged insoles may be a valid intervention for patients with knee osteoarthritis regardless of the foot progression angle.

The effects of shoe-worn insoles on gait biomechanics in people with knee osteoarthritis: a systematic review and meta-analysis.

PubMed

Shaw, Kathryn E; Charlton, Jesse M; Perry, Christina K L; de Vries, Courtney M; Redekopp, Matthew J; White, Jordan A; Hunt, Michael A

2018-02-01

The effect of shoe-worn insoles on biomechanical variables in people with medial knee osteoarthritis has been studied extensively. The majority of research has focused specifically on the effect of lateral wedge insoles at the knee. The aim of this systematic review and meta-analysis was to summarise the known effects of different shoe-worn insoles on all biomechanical variables during level walking in this patient population to date. Four electronic databases were searched to identify studies containing biomechanical data using shoe-worn insole devices in the knee osteoarthritis population. Methodological quality was assessed and a random effects meta-analysis was performed on biomechanical variables reported in three or more studies for each insole. Twenty-seven studies of moderate-to-high methodological quality were included in this review. The primary findings were consistent reductions in the knee adduction moment with lateral wedge insoles, although increases in ankle eversion with these insoles were also found. Lateral wedge insoles produce small reductions in knee adduction angles and external moments, and moderate increases in ankle eversion. The addition of an arch support to a lateral wedge minimises ankle eversion change, and also minimises adduction moment reductions. The paucity of available data on other insole types and other biomechanical outcomes presents an opportunity for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Custom therapeutic insoles based on both foot shape and plantar pressure measurement provide enhanced pressure relief.

PubMed

Owings, Tammy M; Woerner, Julie L; Frampton, Jason D; Cavanagh, Peter R; Botek, Georgeanne

2008-05-01

The purpose of this study was to determine whether custom insoles tailored to contours of the barefoot pressure distribution and shape of a patient's foot can reduce plantar pressures in the metatarsal head (MTH) region to a greater extent than conventional custom insoles. Seventy regions of elevated barefoot pressures (mean peak 834 kPa under MTHs) were identified in 20 subjects with diabetes. Foam box impressions of their feet were sent to three different orthotic supply companies for fabrication of custom insoles. One company was also given plantar pressure data, which were incorporated into the insole design. Measurements of in-shoe plantar pressures were recorded during gait for the three custom insoles in a flexible and a rocker-bottom shoe. Peak pressure and force-time integral were extracted for analysis. In 64 of 70 regions, the shape-plus-pressure-based insole in the flexible shoe achieved superior unloading compared with the two shape-based insoles. On average, peak pressure was reduced by 32 and 21% (both P

An Apparatus to Quantify Anteroposterior and Mediolateral Shear Reduction in Shoe Insoles

PubMed Central

Belmont, Barry; Wang, Yancheng; Ammanath, Peethambaran; Wrobel, James S.; Shih, Albert

2013-01-01

Background Many of the physiological changes that lead to diabetic foot ulceration, such as muscle atrophy and skin hardening, are manifested at the foot–ground interface via pressure and shear points. Novel shear-reducing insoles have been developed, but their magnitude of shear stiffness has not yet been compared with regular insoles. The aim of this study was to develop an apparatus that would apply shear force and displacement to an insole’s forefoot region, reliably measure deformation, and calculate insole shear stiffness. Methods An apparatus consisting of suspended weights was designed to test the forefoot region of insoles. Three separate regions representing the hallux; the first and second metatarsals; and the third, fourth, and fifth metatarsals were sheared at 20 mm/min for displacements from 0.1 to 1.0 mm in both the anteroposterior and mediolateral directions for two types of insoles (regular and shear reducing). Results Shear reduction was found to be significant for the intervention insoles under all testing conditions. The ratio of a regular insole’s effective stiffness and the experimental insole’s effective stiffness across forefoot position versus shear direction, gait instance versus shear direction, and forefoot position versus gait instance was 270% ± 79%, 270% ± 96%, and 270% ± 86%, respectively. The apparatus was reliable with an average measured coefficient of variation of 0.034 and 0.069 for the regular and shear-reducing insole, respectively. Conclusions An apparatus consisting of suspended weights resting atop three locations of interest sheared across an insole was demonstrated to be capable of measuring the insole shear stiffness accurately, thus quantifying shear-reducing effects of a new type of insole. PMID:23567000

A comparison of customised and prefabricated insoles to reduce risk factors for neuropathic diabetic foot ulceration: a participant-blinded randomised controlled trial

PubMed Central

2012-01-01

Background Neuropathic diabetic foot ulceration may be prevented if the mechanical stress transmitted to the plantar tissues is reduced. Insole therapy is one practical method commonly used to reduce plantar loads and ulceration risk. The type of insole best suited to achieve this is unknown. This trial compared custom-made functional insoles with prefabricated insoles to reduce risk factors for ulceration of neuropathic diabetic feet. Method A participant-blinded randomised controlled trial recruited 119 neuropathic participants with diabetes who were randomly allocated to custom-made functional or prefabricated insoles. Data were collected at issue and six month follow-up using the F-scan in-shoe pressure measurement system. Primary outcomes were: peak pressure, forefoot pressure time integral, total contact area, forefoot rate of load, duration of load as a percentage of stance. Secondary outcomes were patient perceived foot health (Bristol Foot Score), quality of life (Audit of Diabetes Dependent Quality of Life). We also assessed cost of supply and fitting. Analysis was by intention-to-treat. Results There were no differences between insoles in peak pressure, or three of the other four kinetic measures. The custom-made functional insole was slightly more effective than the prefabricated insole in reducing forefoot pressure time integral at issue (27% vs. 22%), remained more effective at six month follow-up (30% vs. 24%, p=0.001), but was more expensive (UK £656 vs. £554, p<0.001). Full compliance (minimum wear 7 hours a day 7 days per week) was reported by 40% of participants and 76% of participants reported a minimum wear of 5 hours a day 5 days per week. There was no difference in patient perception between insoles. Conclusion The custom-made insoles are more expensive than prefabricated insoles evaluated in this trial and no better in reducing peak pressure. We recommend that where clinically appropriate, the more cost effective prefabricated insole should be considered for use by patients with diabetes and neuropathy. Trial registration Clinical trials.gov (NCT00999635). Note: this trial was registered on completion. PMID:23216959

Tumor-associated macrophages: implications in cancer immunotherapy.

PubMed

Petty, Amy J; Yang, Yiping

2017-03-01

Tumor-associated macrophages (TAMs), representing most of the leukocyte population in solid tumors, demonstrate great phenotypic heterogeneity and diverse functional capabilities under the influence of the local tumor microenvironment. These anti-inflammatory and protumorigenic macrophages modulate the local microenvironment to facilitate tumor growth and metastasis. In this review, we examine the origin of TAMs and the complex regulatory networks within the tumor microenvironment that facilitate the polarization of TAMs toward a protumoral phenotype. More extensively, we evaluate the mechanisms by which TAMs mediate angiogenesis, metastasis, chemotherapeutic resistance and immune evasion. Lastly, we will highlight novel interventional strategies targeting TAMs in preclinical studies and in early clinical trials that have significant potential in improving efficacy of current chemotherapeutic and/or immunotherapeutic approaches.

The feasibility study on fabrication customized orthotic insole using fused deposition modelling (FDM)

NASA Astrophysics Data System (ADS)

Yarwindran, M.; Ibrahim, M.; Raveverma, P.

2017-04-01

There are many important roles of the orthotic insoles, such as for the convenience purpose of diabetic patient's foot problem, and also to enhance athlete's performance in sports. Therefore, highly customised insoles were in demand, where it has to be fabricated by moulding plaster of Paris on the person's leg to customise the insole. The main purpose of the paper is to study the ability to implement additive manufacturing technology in the fabrication process of customised orthotics insole. The recent invention of flexible material (Filaflex) in Fused Deposition Modelling is the most significant reason that makes this fabrication process possible. By implementing a new approach to the 3D scanning of the foot, we produced the computer-aided drafting (CAD) drawing which was able to modify to desired shape and dimension. After the editing has been completed, the file was converted to Stereolithography format file (STL) as to enable it to be printed using Makerware or any other related software by sending command (G-code) to Flashforge 3D printer. The printed insole was tested its fit, form and function (also known as 3F). In the end, printed insole performs the function test which measures the plantar pressure of the foot compared with bare foot. The results show that the insole distributes pressure well throughout the foot surface, in which it reduced the peak pressure to half from 218KPa to 109KPa. Hence, it is concluded that the method proposed in this paper can produce a functional insole so that it can be the alternative way to make customised orthotic insoles.

The effect of textured ballet shoe insoles on ankle proprioception in dancers.

PubMed

Steinberg, Nili; Waddington, Gordon; Adams, Roger; Karin, Janet; Tirosh, Oren

2016-01-01

Impaired ankle inversion movement discrimination (AIMD) can lead to ankle sprain injuries. The aim of this study was to explore whether wearing textured insoles improved AIMD compared with barefoot, ballet shoes and smooth insoles, among dancers. Forty-four adolescent male and female dancers, aged 13-19, from The Australian Ballet School were tested for AIMD while barefoot, wearing ballet shoes, smooth insoles, and textured insoles. No interaction was found between the four different footwear conditions, the two genders, or the two levels of dancers in AIMD (p > .05). An interaction was found between the four different footwear conditions and the three tertiles when tested in ballet shoes (p = .006). Although significant differences were found between the upper tertiles and the lower tertiles when tested with ballet shoes, barefoot and with smooth insoles (p < .001; p < .001; p = .047, respectively), when testing with textured insoles dancers in the lower tertile obtained similar scores to those obtained by dancers in the upper tertile (p = .911). Textured insoles improved the discrimination scores of dancers with low AIMD, suggesting that textured insoles may trigger the cutaneous receptors in the plantar surface, increasing the awareness of ankle positioning, which in turn might decrease the chance of ankle injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of custom-made and prefabricated insoles before and after an intense run

PubMed Central

2017-01-01

Each time the foot contacts the ground during running there is a rapid deceleration that results in a shock wave that is transmitted from the foot to the head. The fatigue of the musculoskeletal system during running may decrease the ability of the body to absorb those shock waves and increase the risk of injury. Insoles are commonly prescribed to prevent injuries, and both custom-made and prefabricated insoles have been observed to reduce shock accelerations during running. However, no study to date has included a direct comparison of their behaviour measured over the same group of athletes, and therefore great controversy still exists regarding their effectiveness in reducing impact loading during running. The aim of the study was to analyse the acute differences in stride and shock parameters while running on a treadmill with custom-made and prefabricated insoles. Stride parameters (stride length, stride rate) and shock acceleration parameters (head and tibial peak acceleration, shock magnitude, acceleration rate, and shock attenuation) were measured using two triaxial accelerometers in 38 runners at 3.33 m/s before and after a 15-min intense run while using the sock liner of the shoe (control condition), prefabricated insoles and custom-made insoles. No differences in shock accelerations were found between the custom-made and the control insoles. The prefabricated insoles increased the head acceleration rate (post-fatigue, p = 0.029) compared to the control condition. The custom-made reduced tibial (pre-fatigue, p = 0.041) and head acceleration rates (pre-fatigue and post-fatigue, p = 0.01 and p = 0.046) compared to the prefabricated insoles. Neither the stride nor the acceleration parameters were modified as a result of the intense run. In the present study, the acute use of insoles (custom-made, prefabricated) did not reduce shock accelerations compared to the control insoles. Therefore, their effectiveness at protecting against injuries associated with elevated accelerations is not supported and remains unclear. PMID:28245273

A six-month followup of a randomized trial comparing the efficacy of a lateral-wedge insole with subtalar strapping and an in-shoe lateral-wedge insole in patients with varus deformity osteoarthritis of the knee.

PubMed

Toda, Yoshitaka; Tsukimura, Noriko

2004-10-01

To assess the effect of a lateral-wedge insole with elastic strapping of the subtalar joint on the femorotibial angle in patients with varus deformity of the knee. The efficacy of a wedged insole with subtalar straps and that of a traditional wedged insole shoe insert were compared. Sixty-six female outpatients with knee osteoarthritis (OA) were randomized (according to birth date) to be treated with either the strapped or the traditional inserted insole. Standing radiographs with unilateral insole use were used to analyze the femorotibial angles for each patient. In both groups, the baseline and 6-month visual analog scale (VAS) scores for subjective knee pain and the Lequesne index scores for knee OA were compared. The 61 patients who completed the 6-month study were evaluated. At baseline, there was no significant difference in the femorotibial angle (P = 0.66) and the VAS score (P = 0.75) between the 2 groups. At the 6-month assessment, the 29 subjects wearing the subtalar-strapped insole demonstrated a significantly decreased femorotibial angle (P < 0.0001) and significantly improved VAS scores (P = 0.001) and Lequesne index scores (P = 0.033) compared with their baseline assessments. These significant differences were not observed in the 32 subjects assigned to the traditional shoe-inserted wedged insole. These results suggest that an insole with a subtalar strap maintained the valgus correction of the femorotibial angle in patients with varus knee OA for 6 months, indicating longer-term clinical improvement with the strapped insert compared with the traditional insert. Copyright 2004 American College of Rheumatology

Virtually optimized insoles for offloading the diabetic foot: A randomized crossover study.

PubMed

Telfer, S; Woodburn, J; Collier, A; Cavanagh, P R

2017-07-26

Integration of objective biomechanical measures of foot function into the design process for insoles has been shown to provide enhanced plantar tissue protection for individuals at-risk of plantar ulceration. The use of virtual simulations utilizing numerical modeling techniques offers a potential approach to further optimize these devices. In a patient population at-risk of foot ulceration, we aimed to compare the pressure offloading performance of insoles that were optimized via numerical simulation techniques against shape-based devices. Twenty participants with diabetes and at-risk feet were enrolled in this study. Three pairs of personalized insoles: one based on shape data and subsequently manufactured via direct milling; and two were based on a design derived from shape, pressure, and ultrasound data which underwent a finite element analysis-based virtual optimization procedure. For the latter set of insole designs, one pair was manufactured via direct milling, and a second pair was manufactured through 3D printing. The offloading performance of the insoles was analyzed for forefoot regions identified as having elevated plantar pressures. In 88% of the regions of interest, the use of virtually optimized insoles resulted in lower peak plantar pressures compared to the shape-based devices. Overall, the virtually optimized insoles significantly reduced peak pressures by a mean of 41.3kPa (p<0.001, 95% CI [31.1, 51.5]) for milled and 40.5kPa (p<0.001, 95% CI [26.4, 54.5]) for printed devices compared to shape-based insoles. The integration of virtual optimization into the insole design process resulted in improved offloading performance compared to standard, shape-based devices. ISRCTN19805071, www.ISRCTN.org. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia: implications for disease pathogenesis and treatment

PubMed Central

ten Hacken, Elisa; Burger, Jan A.

2015-01-01

Chronic Lymphocytic Leukemia (CLL) is a malignancy of mature B lymphocytes which are highly dependent on interactions with the tissue microenvironment for their survival and proliferation. Critical components of the microenvironment are monocyte-derived nurselike cells (NLCs), mesenchymal stromal cells, T cells and NK cells, which communicate with CLL cells through a complex network of adhesion molecules, chemokine receptors, tumor necrosis factor (TNF) family members, and soluble factors. (Auto-) antigens and/or autonomous mechanisms activate the B-cell receptor (BCR) and its downstream signaling cascade in secondary lymphatic tissues, playing a central pathogenetic role in CLL. Novel small molecule inhibitors, including the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib and the phosphoinositide-3-kinase delta (PI3Kδ) inhibitor idelalisib, target BCR signaling and have become the most successful new therapeutics in this disease. We here review the cellular and molecular characteristics of CLL cells, and discuss the cellular components and key pathways involved in the cross-talk with their microenvironment. We also highlight the relevant novel treatment strategies, focusing on immunomodulatory agents and BCR signaling inhibitors and how these treatments disrupt CLL-microenvironment interactions. PMID:26193078

The effects of Vibro-medical insole on vibrotactile sensation in diabetic patients with mild-to-moderate peripheral neuropathy.

PubMed

Bagherzadeh Cham, Masumeh; Mohseni-Bandpei, Mohammad Ali; Bahramizadeh, Mahmood; Kalbasi, Saeed; Biglarian, Akbar

2018-06-01

Peripheral sensory neuropathy seems to be the main risk factor for diabetic foot ulceration. Previous studies demonstrated that stochastic resonance can improve the vibrotactile sensation of diabetic patients. The aim of this study was to evaluate the effects of Vibro-medical insole on pressure and vibration sensation in diabetic patients with mild-to-moderate peripheral neuropathy. A total of 20 patients with mild-to-moderate diabetic neuropathy were included in the pre-test and post-test clinical trial study. Vibro-medical insole consists of medical insole and vibratory system. Medical insole was made independently for each participant and vibratory system was inserted in it. Pressure and vibration sensation were evaluated before and after 30-min walking with Vibro-medical insole. Semmes-Weinstein monofilaments and tuning fork were used to evaluate pressure and vibration sensation, respectively. Pressure sensation showed significantly improvement using Vibro-medical insole at the heel, first and fifth metatarsophalangeal heads, and hallux of both feet in all participants (p < 0.001). Vibration sensation also improved at the big toe of both feet with 256 Hz tuning fork (p < 0.05) but no statistically significant effect was found with 128 Hz tuning fork (p > 0.05). Vibro-medical insole significantly improved pressure and vibration sensation of the foot in diabetic patients with mild-to-moderate peripheral neuropathy. The results suggest that Vibro-medical insole can be used for daily living activities to overcome sensory loss in diabetic neuropathy patients.

Influence of foot orthosis customisation on perceived comfort during running.

PubMed

Lucas-Cuevas, A G; Pérez-Soriano, P; Priego-Quesada, J I; Llana-Belloch, S

2014-01-01

Although running is associated with many health benefits, it also exposes the body to greater risk of injury. Foot orthoses are an effective strategy to prevent such injuries. Comfort is an essential element in orthosis design since any discomfort alters the runner's biomechanics, compromising performance and increasing the risk of injury. The present study analyses the perceived comfort of three types of orthoses: custom-made, prefabricated and original running shoe insoles. Nine comfort variables for each insole were assessed in a sample of 40 runners. Custom-made and prefabricated insoles were both perceived as significantly more comfortable than the original insoles. The differences were clinically relevant and were potentially causes of modifications in running gait. Although the prefabricated insoles were rated slightly higher than the custom-made insoles, the differences were not statistically significant. This study shows that prefabricated insoles constitute a reasonable alternative to custom-made insoles in terms of comfort. The perceived level of comfort of footwear is considered to be a protective measure of the potential risk of running injuries. We here compared runners' perception of comfort of custom-made and prefabricated orthoses while running. We found that even though custom-made orthoses are closely matched to each individual's foot, such customisation does not necessarily imply greater comfort.

Immunological dysregulation in multiple myeloma microenvironment.

PubMed

Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

2014-01-01

Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

PubMed Central

Justus, Calvin R.; Sanderlin, Edward J.; Yang, Li V.

2015-01-01

Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention. PMID:25988385

Use of a Textured Insole to Improve the Association Between Postural Balance and Ankle Discrimination in Young Male and Female Dancers.

PubMed

Steinberg, Nili; Waddington, Gordon; Adams, Roger; Karin, Janet; Tirosh, Oren

2015-12-01

Ballet dancers require a high level of postural balance (PB) and proprioception ability during performance. As textured insoles inserted into ballet shoes were found to improve proprioception ability, and better proprioceptive acuity was associated with better PB, the aim of the present study was to investigate whether the association between ankle inversion movement discrimination (AIMD) and PB changed following wearing textured insoles in young male and female dancers. Forty-four dancers from the Australian Ballet School, ages 14-19 yrs, were tested for static and dynamic PB and AIMD under two conditions: in ballet shoes, and in ballet shoes with textured insoles inserted. Female dancers demonstrated a significant inverse relationship between AIMD and static PB in the medio-lateral direction when wearing ballet shoes, but not when wearing textured insoles. Male dancers showed a non-monotonic relationship when tested with ballet shoes only, but a significant inverse relationship between AIMD and dynamic PB in the vertical direction and with the waist/head cross-correlation acceleration in the three movement directions when they were tested with textured insoles. Male dancers demonstrated an improved association between dynamic PB and proprioception ability when using textured insoles, suggesting that the increased afferent information from the plantar surface had a beneficial effect on proprioception feedback about their PB. Conversely, for female dancers, that association was present when wearing ballet shoes, but not when using textured insoles, suggesting that the increased afferent information for female dancers who already had high proprioception ability was "overloaded" by wearing the textured insoles.

A method for subject-specific modelling and optimisation of the cushioning properties of insole materials used in diabetic footwear.

PubMed

Chatzistergos, Panagiotis E; Naemi, Roozbeh; Chockalingam, Nachiappan

2015-06-01

This study aims to develop a numerical method that can be used to investigate the cushioning properties of different insole materials on a subject-specific basis. Diabetic footwear and orthotic insoles play an important role for the reduction of plantar pressure in people with diabetes (type-2). Despite that, little information exists about their optimum cushioning properties. A new in-vivo measurement based computational procedure was developed which entails the generation of 2D subject-specific finite element models of the heel pad based on ultrasound indentation. These models are used to inverse engineer the material properties of the heel pad and simulate the contact between plantar soft tissue and a flat insole. After its validation this modelling procedure was utilised to investigate the importance of plantar soft tissue stiffness, thickness and loading for the correct selection of insole material. The results indicated that heel pad stiffness and thickness influence plantar pressure but not the optimum insole properties. On the other hand loading appears to significantly influence the optimum insole material properties. These results indicate that parameters that affect the loading of the plantar soft tissues such as body mass or a person's level of physical activity should be carefully considered during insole material selection. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Nonlinear response of summer temperature to Holocene insolation forcing in Alaska.

PubMed

Clegg, Benjamin F; Kelly, Ryan; Clarke, Gina H; Walker, Ian R; Hu, Feng Sheng

2011-11-29

Regional climate responses to large-scale forcings, such as precessional changes in solar irradiation and increases in anthropogenic greenhouse gases, may be nonlinear as a result of complex interactions among earth system components. Such nonlinear behaviors constitute a major source of climate "surprises" with important socioeconomic and ecological implications. Paleorecords are key for elucidating patterns and mechanisms of nonlinear responses to radiative forcing, but their utility has been greatly limited by the paucity of quantitative temperature reconstructions. Here we present Holocene July temperature reconstructions on the basis of midge analysis of sediment cores from three Alaskan lakes. Results show that summer temperatures during 10,000-5,500 calibrated years (cal) B.P. were generally lower than modern and that peak summer temperatures around 5,000 were followed by a decreasing trend toward the present. These patterns stand in stark contrast with the trend of precessional insolation, which decreased by ∼10% from 10,000 y ago to the present. Cool summers before 5,500 cal B.P. coincided with extensive summer ice cover in the western Arctic Ocean, persistence of a positive phase of the Arctic Oscillation, predominantly La Niña-like conditions, and variation in the position of the Alaskan treeline. These results illustrate nonlinear responses of summer temperatures to Holocene insolation radiative forcing in the Alaskan sub-Arctic, possibly because of state changes in the Arctic Oscillation and El Niño-Southern Oscillation and associated land-atmosphere-ocean feedbacks.

Nonlinear response of summer temperature to Holocene insolation forcing in Alaska

PubMed Central

Clegg, Benjamin F.; Kelly, Ryan; Clarke, Gina H.; Walker, Ian R.; Hu, Feng Sheng

2011-01-01

Regional climate responses to large-scale forcings, such as precessional changes in solar irradiation and increases in anthropogenic greenhouse gases, may be nonlinear as a result of complex interactions among earth system components. Such nonlinear behaviors constitute a major source of climate “surprises” with important socioeconomic and ecological implications. Paleorecords are key for elucidating patterns and mechanisms of nonlinear responses to radiative forcing, but their utility has been greatly limited by the paucity of quantitative temperature reconstructions. Here we present Holocene July temperature reconstructions on the basis of midge analysis of sediment cores from three Alaskan lakes. Results show that summer temperatures during 10,000–5,500 calibrated years (cal) B.P. were generally lower than modern and that peak summer temperatures around 5,000 were followed by a decreasing trend toward the present. These patterns stand in stark contrast with the trend of precessional insolation, which decreased by ∼10% from 10,000 y ago to the present. Cool summers before 5,500 cal B.P. coincided with extensive summer ice cover in the western Arctic Ocean, persistence of a positive phase of the Arctic Oscillation, predominantly La Niña-like conditions, and variation in the position of the Alaskan treeline. These results illustrate nonlinear responses of summer temperatures to Holocene insolation radiative forcing in the Alaskan sub-Arctic, possibly because of state changes in the Arctic Oscillation and El Niño-Southern Oscillation and associated land–atmosphere–ocean feedbacks. PMID:22084085

Effect of Laterally Wedged Insoles on the External Knee Adduction Moment across Different Reference Frames.

PubMed

Yamaguchi, Satoshi; Kitamura, Masako; Ushikubo, Tomohiro; Murata, Atsushi; Akagi, Ryuichiro; Sasho, Takahisa

2015-01-01

Biomechanical effects of laterally wedged insoles are assessed by reduction in the knee adduction moment. However, the degree of reduction may vary depending on the reference frame with which it is calculated. The purpose of this study was to clarify the effect of reference frame on the reduction in the knee adduction moment by laterally wedged insoles. Twenty-nine healthy participants performed gait trials with a laterally wedged insole and with a flat insole as a control. The knee adduction moment, including the first and second peaks and the angular impulse, were calculated using four different reference frames: the femoral frame, tibial frame, laboratory frame and the Joint Coordinate System. There were significant effects of reference frame on the knee adduction moment first and second peaks (P < 0.001 for both variables), while the effect was not significant for the angular impulse (P = 0.84). No significant interaction between the gait condition and reference frame was found in either of the knee adduction moment variables (P = 0.99 for all variables), indicating that the effects of laterally wedged insole on the knee adduction moments were similar across the four reference frames. On the other hand, the average percent changes ranged from 9% to 16% for the first peak, from 16% to 18% for the second peak and from 17% to 21% for the angular impulse when using the different reference frames. The effects of laterally wedged insole on the reduction in the knee adduction moment were similar across the reference frames. On the other hand, Researchers need to recognize that when the percent change was used as the parameter of the efficacy of laterally wedged insole, the choice of reference frame may influence the interpretation of how laterally wedged insoles affect the knee adduction moment.

A study on the decontamination of insoles colonized by Trichophyton rubrum: effect of terbinafine spray powder 1% and terbinafine spray solution 1%.

PubMed

Feuilhade de Chauvin, M

2012-07-01

Shoes worn with bare feet function as a fungal reservoir and lead to persistent dermatophytosis. This study was designed to evaluate two formulations of terbinafine (1% spray powder or solution) to treat the insoles of shoes colonized by skin scales infected with Trichophyton rubrum and to determine the contact time necessary to achieve decontamination. Infected skin scales weighing 0.5 g, taken from the feet of patients with confirmed T. rubrum infection, was dispersed onto insoles pre-moistened with sterile saline solution (to mimic perspiration). Three types of insole were tested (felt, latex, leather). After inoculation, insoles were placed separately in new cardboard boxes at ambient temperature, and re-humidified with sterile normal saline solution for 48 h before being treated; untreated insoles served as controls. Scales were scraped off at 48 h or 96 h, and dropped into tubes of Sabouraud agar, incubated at 27°C and examined at 3 and 6 weeks. Cultures from all control insoles showed numerous T. rubrum colonies. In contrast, cultures from all insoles treated with a single application of terbinafine 1% spray solution or powder, and taken after 48 h or 96 h contact with the product, remained sterile at 3 weeks and 6 weeks. This study demonstrated the successful treatment of insoles colonized by T. rubrum-infected skin scales. Terbinafine 1% spray solution and powder showed good efficacy; the dermatophyte could no longer be cultured 48 h after a single application of terbinafine. © 2011 The Author. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Hybrid insolation forcing of Pliocene monsoon dynamics in West Africa

NASA Astrophysics Data System (ADS)

Kuechler, Rony R.; Dupont, Lydie M.; Schefuß, Enno

2018-01-01

The Pliocene is regarded as a potential analogue for future climate with conditions generally warmer-than-today and higher-than-preindustrial atmospheric CO2 levels. Here we present the first orbitally resolved records of continental hydrology and vegetation changes from West Africa for two Pliocene time intervals (5.0-4.6 Ma, 3.6-3.0 Ma), which we compare with records from the last glacial cycle (Kuechler et al., 2013). Our results indicate that changes in local insolation alone are insufficient to explain the full degree of hydrologic variations. Generally two modes of interacting insolation forcings are observed: during eccentricity maxima, when precession was strong, the West African monsoon was driven by summer insolation; during eccentricity minima, when precession-driven variations in local insolation were minimal, obliquity-driven changes in the summer latitudinal insolation gradient became dominant. This hybrid monsoonal forcing concept explains orbitally controlled tropical climate changes, incorporating the forcing mechanism of latitudinal gradients for the Pliocene, which probably increased in importance during subsequent Northern Hemisphere glaciations.

Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1

PubMed Central

Catena, Raúl; Bhattacharya, Nandita; Rayes, Tina El; Wang, Suming; Choi, Hyejin; Gao, Dingcheng; Ryu, Seongho; Joshi, Natasha; Bielenberg, Diane; Lee, Sharrell B.; Haukaas, Svein A.; Gravdal, Karsten; Halvorsen, Ole J.; Akslen, Lars A.; Watnick, Randolph S.; Mittal, Vivek

2013-01-01

Metastatic tumors have been shown to establish permissive microenvironments for metastases via recruitment of bone marrow (BM)- derived cells. Here, we show that metastasis-incompetent tumors are also capable of generating such microenvironments. However, in these situations the otherwise pro-metastatic Gr1+ myeloid cells create a metastasis-refractory microenvironment via the induction of thrombospondin-1 (Tsp-1) by tumor-secreted prosaposin. (BM)-specific genetic deletion of Tsp-1 abolished the inhibition of metastasis, which was restored by BM transplant from Tsp-1+ donors. We also developed a 5-amino acid peptide from prosaposin as a pharmacological inducer of Tsp-1 in Gr1+ BM cells, which dramatically suppresses metastasis. These results provide mechanistic insights into why certain tumors are deficient in metastatic potential and implicate recruited Gr1+ myeloid cells as the main source of Tsp-1. The results underscore the plasticity of Gr1+ cells, which, depending on the context, promote or inhibit metastasis, and suggest that the peptide could be a potential therapeutic agent against metastatic cancer. PMID:23633432

Associations of blood pressure, sunlight, and vitamin D in community-dwelling adults.

PubMed

Rostand, Stephen G; McClure, Leslie A; Kent, Shia T; Judd, Suzanne E; Gutiérrez, Orlando M

2016-09-01

Vitamin D deficiency/insufficiency is associated with hypertension. Blood pressure (BP) and circulating vitamin D concentrations vary with the seasons and distance from the equator suggesting BP varies inversely with the sunshine available (insolation) for cutaneous vitamin D photosynthesis. To determine if the association between insolation and BP is partly explained by vitamin D, we evaluated 1104 participants in the Reasons for Racial and Geographic Differences in Stroke study whose BP and plasma 25-hydroxyvitamin D [25(OH)D] concentrations were measured. We found a significant inverse association between SBP and 25(OH)D concentration and an inverse association between insolation and BP in unadjusted analyses. After adjusting for other confounding variables, the association of solar insolation and BP was augmented, -0.3.5 ± SEM 0.01 mmHg/1 SD higher solar insolation, P = 0.01. The greatest of effects of insolation on SBP were observed in whites (-5.2 ± SEM 0.92 mmHg/1 SD higher solar insolation, P = 0.005) and in women (-3.8 ± SEM 1.7 mmHg, P = 0.024). We found that adjusting for 25(OH)D had no effect on the association of solar insolation with SBP. We conclude that although 25(OH)D concentration is inversely associated with SBP, it did not explain the association of greater sunlight exposure with lower BP.

The effect of removing plugs and adding arch support to foam based insoles on plantar pressures in people with diabetic peripheral neuropathy.

PubMed

Lin, Tung-Liang; Sheen, Huey-Min; Chung, Chin-Teng; Yang, Sai-Wei; Lin, Shih-Yi; Luo, Hong-Ji; Chen, Chung-Yu; Chan, I-Cheng; Shih, Hsu-Sheng; Sheu, Wayne Huey-Herng

2013-07-29

Removable plug insoles appear to be beneficial for patients with diabetic neuropathic feet to offload local plantar pressure. However, quantitative evidence of pressure reduction by means of plug removal is limited. The value of additional insole accessories, such as arch additions, has not been tested. The purpose of this study was to evaluate the effect of removing plugs from foam based insoles, and subsequently adding extra arch support, on plantar pressures. In-shoe plantar pressure measurements were performed on 26 patients with diabetic neuropathic feet at a baseline condition, in order to identify the forefoot region with the highest mean peak pressure (MPP). This was defined as the region of interest (ROI) for plug removal.The primary outcome was measurement of MPP using the pedar® system in the baseline and another three insole conditions (pre-plug removal, post-plug removal, and post-plug removal plus arch support). Among the 26 ROIs, a significant reduction in MPP (32.3%, P<0.001) was found after removing the insole plugs. With an arch support added, the pressure was further reduced (9.5%, P<0.001). There were no significant differences in MPP at non-ROIs between pre- and post-plug removal conditions. These findings suggest that forefoot plantar pressure can be reduced by removing plugs and adding arch support to foam-based insoles. This style of insole may therefore be clinically useful in managing patients with diabetic peripheral neuropathy.

Effect of Full-Length Carbon Fiber Insoles on Lower Limb Kinetics in Patients With Midfoot Osteoarthritis: A Pilot Study.

PubMed

Yi, Taeim; Kim, Jung Hyun; Oh-Park, Mooyeon; Hwang, Ji Hye

2018-03-01

We investigated the effects of full-length carbon fiber (FCF) insoles on gait, muscle activity, kinetics, and pain in patients with midfoot osteoarthritis (OA). We enrolled 13 patients with unilateral midfoot OA (mild: Visual Analog Scale [VAS] range, 1-3; moderate, VAS range, 4-7) and healthy controls. All participants were asked to walk under two conditions: with and without FCF insole. The outcome measures were ground reaction force, quantitative gait parameters, electromyography activities and pain severity (VAS). In the patients with moderate midfoot OA, significantly longer gait cycle and higher muscle activity of lower limb during loading-response phase were observed while walking without FCF insoles. In the mild midfoot OA group, there was no significant difference in VAS score (without, 2.0 ± 1.0 vs. with, 2.0 ± 0.5) with FCF insole use. However, significantly reduced VAS score (without, 5.5 ± 1.4 vs. with, 2.0 ± 0.5) and muscle activity of the tibialis anterior and increased muscle activity of gastrocnemius were observed in the moderate midfoot OA group by using an FCF insole (P < 0.05). Full-length carbon fiber insoles can improve pain in individuals with moderate midfoot OA, which might be associated with changes in the kinetics and muscle activities of the lower limb. Taken together, the results of the present study suggest that FCF insoles may be used as a helpful option for midfoot OA.

Plantar pressure relief under the metatarsal heads: therapeutic insole design using three-dimensional finite element model of the foot.

PubMed

Chen, Wen-Ming; Lee, Sung-Jae; Lee, Peter Vee Sin

2015-02-26

Therapeutic footwear with specially-made insoles is often used in people with diabetes and rheumatoid arthritis to relieve ulcer risks and pain due to high pressures from areas beneath bony prominences of the foot, in particular to the metatarsal heads (MTHs). In a three-dimensional finite element study of the foot and footwear with sensitivity analysis, effects of geometrical variations of a therapeutic insole, in terms of insole thicknesses and metatarsal pad (MP) placements, on local peak plantar pressure under MTHs and stress/strain states within various forefoot tissues, were determined. A validated musculoskeletal finite element model of the human foot was employed. Analyses were performed in a simulated muscle-demanding instant in gait. For many design combinations, increasing insole thicknesses consistently reduce peak pressures and internal tissue strain under MTHs, but the effects reach a plateau when insole becomes very thick (e.g., a value of 12.7mm or greater). Altering MP placements, however, showed a proximally- and a distally-placed MP could result in reverse effects on MTH pressure-relief. The unsuccessful outcome due to a distally-placed MP may attribute to the way it interacts with plantar tissue (e.g., plantar fascia) adjacent to the MTH. A uniform pattern of tissue compression under metatarsal shaft is necessary for a most favorable pressure-relief under MTHs. The designated functions of an insole design can best be achieved when the insole is very thick, and when the MP can achieve a uniform tissue compression pattern adjacent to the MTH. Copyright © 2015 Elsevier Ltd. All rights reserved.

Football boot insoles and sensitivity to extent of ankle inversion movement.

PubMed

Waddington, G; Adams, R

2003-04-01

The capacity of the plantar sole of the foot to convey information about foot position is reduced by conventional smooth boot insoles, compared with barefoot surface contact. To test the hypothesis that movement discrimination may be restored by inserting textured replacement insoles, achieved by changing footwear conditions and measuring the accuracy of judgments of the extent of ankle inversion movement. An automated testing device, the ankle movement extent discrimination apparatus (AMEDA), developed to assess active ankle function in weight bearing without a balance demand, was used to test the effects of sole inserts in soccer boots. Seventeen elite soccer players, the members of the 2000 Australian Women's soccer squad (34 ankles), took part in the study. Subjects were randomly allocated to start testing in: bare feet, their own football boots, own football boot and replacement insole, and on the left or right side. Subjects underwent six 50 trial blocks, in which they completed all footwear conditions. The sole inserts were cut to size for each foot from textured rubber "finger profile" sheeting. Movement discrimination scores were significantly worse when subjects wore their football boots and socks, compared with barefoot data collected at the same time. The substitution of textured insoles for conventional smooth insoles in the football boots was found to restore movement discrimination to barefoot levels. The lower active movement discrimination scores of athletes when wearing football boots with smooth insoles suggest that the insole is one aspect of football boot and sport shoe design that could be modified to provide the sensory feedback needed for accurate foot positioning.

Dynamic Reciprocity in the Wound Microenvironment

PubMed Central

Schultz, Gregory S.; Davidson, Jeffrey M.; Kirsner, Robert S.; Bornstein, Paul; Herman, Ira M.

2011-01-01

Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction amongst cells and their surrounding microenvironment. In the review, we posit that DR is especially meaningful during wound healing as the DR-driven biochemical, biophysical and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell-extracellular matrix interactions not only guide and regulate cellular morphology, but cellular differentiation, migration, proliferation, and survival during tissue development, including e.g. embryogenesis, angiogenesis, as well as during pathologic processes including cancer diabetes, hypertension and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology, which may be understood within the DR framework. The implications of applying the principles of dynamic reciprocity to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered. PMID:21362080

Correlation of LEND and Diviner Data

NASA Technical Reports Server (NTRS)

McClanahan, Tim; Boynton, William; Mitrofanov, Igor; Sagdeev, Raold; Bennet, Kristen; Starr, Richard; Evans, Larry; Paige, Dave; Sanin, Anton; Litvak, Max;

Reduction of plantar pressures in leprosy patients by using custom made shoes and total contact insoles.

PubMed

Tang, Simon Fuk-Tan; Chen, Carl P C; Lin, Shih-Cherng; Wu, Chih-Kuan; Chen, Chih-Kuang; Cheng, Shun-Ping

2015-02-01

The purpose of this study was to observe whether our custom made shoes and total contact insoles can effectively increase the plantar contact areas and reduce peak pressures in patients with leprosy. In the rehabilitation laboratory of a tertiary medical center. Six male and two female leprosy patients were recruited in this study. In this study, parameters related to foot pressures were compared between these patients wearing commercial available soft-lining kung-fu shoes and our custom made shoes with total contact insoles. The custom made shoes were made with larger toe box and were able to accommodate both the foot and the insoles. Custom made total contact insoles were made with the subtalar joints under neutral and non-weight-bearing positions. The insole force measurement system of Novel Pedar-X (Novel, Munich, Germany) was used to measure the plantar forces. The parameters of contact area (cm(2)), peak plantar pressures (kPa), contact time (s), and pressure time integral (kPa s) were measured. There were significant contact area increases in the right and left foot heel areas, left medial arch, and second to fifth toes after wearing the custom made shoes and insoles. There were significant decreases in peak plantar pressures in bilateral heels, left lateral midfoot, bilateral second to fourth metatarsal areas, and left fifth metatarsal head after wearing the custom made shoes and insoles (p<0.05). Plantar ulceration is a common serious disability in leprosy patients. As a result, footwear and measures able to reduce plantar pressures may be beneficial in preventing plantar ulcers from occurring in these patients. Our custom made shoes and total contact insoles were proven to be effective in increasing contact areas and decreasing peak pressures in plantar surfaces, and may therefore be a feasible treatment option in preventing leprosy patients from developing plantar ulcers. © 2015 Elsevier B.V. All rights reserved.

Parametric study of orthopedic insole of valgus foot on partial foot amputation.

PubMed

Guo, Jun-Chao; Wang, Li-Zhen; Chen, Wei; Du, Cheng-Fei; Mo, Zhong-Jun; Fan, Yu-Bo

2016-01-01

Orthopedic insole was important for partial foot amputation (PFA) to achieve foot balance and avoid foot deformity. The inapposite insole orthosis was thought to be one of the risk factors of reamputation for foot valgus patient, but biomechanical effects of internal tissues on valgus foot had not been clearly addressed. In this study, plantar pressure on heel and metatarsal regions of PFA was measured using F-Scan. The three-dimensional finite element (FE) model of partial foot evaluated different medial wedge angles (MWAs) (0.0°-10.0°) of orthopedic insole on valgus foot. The effect of orthopedic insole on the internal bone stress, the medial ligament tension of ankle, plantar fascia tension, and plantar pressure was investigated. Plantar pressure on medial heel region was about 2.5 times higher than that of lateral region based on the F-Scan measurements. FE-predicted results showed that the tension of medial ankle ligaments was the lowest, and the plantar pressure was redistributed around the heel, the first metatarsal, and the lateral longitudinal arch regions when MWA of orthopedic insole ranged from 7.5° to 8.0°. The plantar fascias maintained about 3.5% of the total load bearing on foot. However, the internal stresses from foot bones increased. The simulation in this study would provide the suggestion of guiding optimal design of orthopedic insole and therapeutic planning to pedorthist.

A Simple Modeling Tool and Exercises for Incoming Solar Radiation Demonstrations

ERIC Educational Resources Information Center

Werts, Scott; Hinnov, Linda

2011-01-01

We present a MATLAB script INSOLATE.m that calculates insolation at the top of the atmosphere and the total amount of daylight during the year (and other quantities) with respect to geographic latitude and Earth's obliquity (axial tilt). The script output displays insolation values for an entire year on a three-dimensional graph. This tool…

3D microvascular model recapitulates the diffuse large B-cell lymphoma tumor microenvironment in vitro.

PubMed

Mannino, Robert G; Santiago-Miranda, Adriana N; Pradhan, Pallab; Qiu, Yongzhi; Mejias, Joscelyn C; Neelapu, Sattva S; Roy, Krishnendu; Lam, Wilbur A

2017-01-31

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that affects ∼22 000 people in the United States yearly. Understanding the complex cellular interactions of the tumor microenvironment is critical to the success and development of DLBCL treatment strategies. In vitro platforms that successfully model the complex tumor microenvironment without introducing the variability of in vivo systems are vital for understanding these interactions. To date, no such in vitro model exists that can accurately recapitulate the interactions that occur between immune cells, cancer cells, and endothelial cells in the tumor microenvironment of DLBCL. To that end, we developed a lymphoma-on-chip model consisting of a hydrogel based tumor model traversed by a vascularized, perfusable, round microchannel that successfully recapitulates key complexities and interactions of the in vivo tumor microenvironment in vitro. We have shown that the perfusion capabilities of this technique allow us to study targeted treatment strategies, as well as to model the diffusion of infused reagents spatiotemporally. Furthermore, this model employs a novel fabrication technique that utilizes common laboratory materials, and allows for the microfabrication of multiplex microvascular environments without the need for advanced microfabrication facilities. Through our facile microfabrication process, we are able to achieve micro vessels within a tumor model that are highly reliable and precise over the length of the vessel. Overall, we have developed a tool that enables researchers from many diverse disciplines to study previously inaccessible aspects of the DLBCL tumor microenvironment, with profound implications for drug delivery and design.

3D microvascular model recapitulates the diffuse large B-cell lymphoma tumor microenvironment in vitro

PubMed Central

Mannino, Robert G.; Santiago-Miranda, Adriana N.; Pradhan, Pallab; Qiu, Yongzhi; Mejias, Joscelyn C.; Neelapu, Sattva S.; Roy, Krishnendu; Lam, Wilbur A.

2017-01-01

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that affects ~22,000 people in the United States yearly. Understanding the complex cellular interactions of the tumor microenvironment is critical to the success and development of DLBCL treatment strategies. In vitro platforms that successfully model the complex tumor microenvironment without introducing the variability of in vivo systems are vital for understanding these interactions. To date, no such in vitro model exists that can accurately recapitulate the interactions that occur between immune cells, cancer cells, and endothelial cells in the tumor microenvironment of DLBCL. To that end, we developed a lymphoma-on-chip model consisting of a hydrogel based tumor model traversed by a vascularized, perfusable, round microchannel that successfully recapitulates key complexities and interactions of the in vivo tumor microenvironment in vitro. We have shown that the perfusion capabilities of this technique allow us to study targeted treatment strategies, as well as to model the diffusion of infused reagents spatiotemporally. Furthermore, this model employs a novel fabrication technique that utilizes common laboratory materials, and allows for the microfabrication of multiplex microvascular environments without the need for advanced microfabrication facilities. Through our facile microfabrication process, we are able to achieve micro vessels within a tumor model that are highly reliable and precise over the length of the vessel. Overall, we have developed a tool that enables researchers from many diverse disciplines to study previously inaccessible aspects of the DLBCL tumor microenvironment, with profound implications for drug delivery and design. PMID:28054086

Effects of long-term stimulation of textured insoles on postural control in health elderly.

PubMed

Annino, Giuseppe; Palazzo, Francesco; Alwardat, Mohammad S; Manzi, Vincenzo; Lebone, Pietro; Tancredi, Virginia; Sinibaldi Salimei, Paola; Caronti, Alfio; Panzarino, Michele; Padua, Elvira

2018-04-01

The aim of this study was to confirm the effects of long term (chronic) stimulating surface (textured insole) on body balance of elderly people. Twenty-four healthy elderly individuals were randomly distributed in two groups: control and experimental (67.75±6.04 years, 74.55±12.14 kg, 163.7±8.55 cm, 27.75±3.04 kg/m2). Over one month, control group (CG) used smooth insoles and the experimental group (ExG) used textured insoles every day. Velocity net (Vnet), anteroposterior (VA/P), mediolateral (VM/L) and sway path of CoP were assessed in different eye conditions before and after the experimental procedure. A mixed between-within subject ANOVA was conducted to assess the impact of soft and textured insoles and two visual conditions (vision vs. no vision) across two time periods (α≤0.05). The results showed any statistical difference between groups in each parameter assessed in this study. CoP, Vnet and VM/L in the experimental group showed a statistically significant effect of textured insoles only without vision (CoP: P=0.002; η2=0.35), Vnet P=0.02; η2=0.24, VM/L P=0.04; η2=0.177) whereas VA/P showed no statistically significant effect in the same group and condition. There was no significant effect in Vnet, VA/P, VM/L and COP in control group that used smooth insole for both eye conditions. The results confirm that postural stability improved in healthy elderly individuals, increasing somatosensory information's from feet plantar mechanoreceptors. Long term stimulation with textured insoles decreased CoP, Vnet and VM/L with eyes closed.

Kinetic factors of vertical jumping for heading a ball in flexible flatfooted amateur soccer players with and without insole adoption.

PubMed

Arastoo, Ali Asghar; Aghdam, Esmaeil Moharrami; Habibi, Abdoul Hamid; Zahednejad, Shahla

2014-06-01

According to literature, little is known regarding the effects of orthotic management of flatfoot on kinetics of vertical jump. To compare the kinetic and temporal events of two-legged vertical jumping take-off from a force plate for heading a ball in normal and flexible flatfoot subjects with and without insole. A functional based interventional controlled study. Random sampling method was employed to draw a control group of 15 normal foot subjects to a group of 15 flatfoot subjects. A force platform was used to record kinetics of two-legged vertical jump shots. Results indicate that insole did not lead to a significant effect on kinetics regarding anterior-posterior and mediolateral directions (p > 0.05). Results of kinetics related to vertical direction for maximum force due to take-off and stance duration revealed significant differences between the normal and flexible flatfoot subjects without insole (p < 0.05) and no significant differences between the normal foot and flexible flatfoot subjects with insole adoption (p > 0.05). These results suggest that the use of an insole in the flexible flatfoot subjects led to improved stance time and decrease of magnitude of kinetics regarding vertical direction at take-off as the main feature of two-legged vertical jumping function. Adoption of the insole improved the design of the shoe-foot interface support for the flexible flatfoot athletes, enabling them to develop more effective take-off kinetics for vertical jumping in terms of ground reaction force and stance duration similar to that of normal foot subjects without insole. © The International Society for Prosthetics and Orthotics 2013.

Special Pyrheliometer Shroud Development

NASA Technical Reports Server (NTRS)

Dennison, E. W.

1984-01-01

To insure that the insolation values accurately represent the input power to a power conversion unit the field of view (FOV) of the concentrator aperture and the insolation radiometer must be the same. The calculations, implementation, and results of this approach are covered. Three instruments were used to measure the insolation: an Eppley Normal Incidence Radiometer (NIP) and two versions of the kendall cavity radiometer. The shrouds used to limit the FOV of the radiometers were designed to simulate the FOV of the PDC-1 concentrater with the cold water cavity calorimeter. This technique of matching the FOV of an insolation radiometer to the FOV of a specific concentrater and receiver aperture appears to be both practical and effective. The efficiency of a power conversion unit will be too low if the insolation is measured with a radiometer which has a FOV which is larger than the FOV of the concentrator.

Analysis of walking improvement with dynamic shoe insoles, using two accelerometers

NASA Astrophysics Data System (ADS)

Tsuruoka, Yuriko; Tamura, Yoshiyasu; Shibasaki, Ryosuke; Tsuruoka, Masako

2005-07-01

The orthopedics at the rehabilitation hospital found that disorders caused by sports injuries to the feet or caused by lower-back are improved by wearing dynamic shoe insoles, these improve walking balance and stability. However, the relationship of the lower-back and knees and the rate of increase in stability were not quantitatively analyzed. In this study, using two accelerometers, we quantitatively analyzed the reciprocal spatiotemporal contributions between the lower-back and knee of patients with left lower-back pain by means of Relative Power Contribution Analysis. When the insoles were worn, the contribution of the left and right knee relative to the left lower-back pain was up to 26% ( p<0.05) greater than without the insoles. Comparing patients with and without insoles, we found that the variance in the step response analysis of the left and right knee decreased by up to 67% ( p<0.05). This shows an increase in stability.

Local effects of partly-cloudy skies on solar and emitted radiations

NASA Technical Reports Server (NTRS)

Whitney, D. A.; Griffin, T. J.

1983-01-01

Atmospheric aerosol and turbidity measurements were analyzed and the results are presented. The correlation of global insolation with cloud cover fractions for the first complete year's data set was completed. A theoretical model was developed to parameterize the effects of local aerosols upon insolation received at the ground using satellite radiometric data and insolation measurements under clear sky conditions. A February data set, composed of one minute integrated global insolation and direct solar irradiances, cloud cover fractions, meteorological data from nearby weather stations, and GOES East satellite radiometric data was collected to test the model and used to calculate the effects of local aerosols.

The specification of personalised insoles using additive manufacturing.

PubMed

Salles, André S; Gyi, Diane E

2012-01-01

Research has been conducted to explore a process that delivers insoles for personalised footwear for the high street using additive manufacturing (AM) and to evaluate the use of such insoles in terms of discomfort. Therefore, the footwear personalisation process was first identified: (1) foot capture; (2) anthropometric measurements; (3) insole design; and (4) additive manufacturing. In order to explore and evaluate this process, recreational runners were recruited. They had both feet scanned and 15 anthropometric measurements taken. Personalised insoles were designed from the scans and manufactured using AM. Participants were fitted with footwear under two experimental conditions: personalised and control, which were compared in terms of discomfort. The mean ratings for discomfort variables were generally low for both conditions and no significant differences were detected between conditions. In general, the personalisation process showed promise in terms of the scan data, although the foot capture position may not be considered 'gold standard'. Polyamide, the material used for the insoles, demonstrated positive attributes: visual inspection revealed no signs of breaking. The footwear personalisation process described and explored in this study shows potential and can be considered a good starting point for designer and researchers.

Testing competing forms of the Milankovitch hypothesis: A multivariate approach

NASA Astrophysics Data System (ADS)

Kaufmann, Robert K.; Juselius, Katarina

2016-02-01

We test competing forms of the Milankovitch hypothesis by estimating the coefficients and diagnostic statistics for a cointegrated vector autoregressive model that includes 10 climate variables and four exogenous variables for solar insolation. The estimates are consistent with the physical mechanisms postulated to drive glacial cycles. They show that the climate variables are driven partly by solar insolation, determining the timing and magnitude of glaciations and terminations, and partly by internal feedback dynamics, pushing the climate variables away from equilibrium. We argue that the latter is consistent with a weak form of the Milankovitch hypothesis and that it should be restated as follows: internal climate dynamics impose perturbations on glacial cycles that are driven by solar insolation. Our results show that these perturbations are likely caused by slow adjustment between land ice volume and solar insolation. The estimated adjustment dynamics show that solar insolation affects an array of climate variables other than ice volume, each at a unique rate. This implies that previous efforts to test the strong form of the Milankovitch hypothesis by examining the relationship between solar insolation and a single climate variable are likely to suffer from omitted variable bias.

Changes in organisation of instep kicking as a function of wearing compression and textured materials.

PubMed

Hasan, Hosni; Davids, Keith; Chow, Jia Yi; Kerr, Graham

2017-04-01

This study investigated effects of wearing compression garments and textured insoles on modes of movement organisation emerging during performance of lower limb interceptive actions in association football. Participants were six skilled (age = 15.67 ± 0.74 years) and six less-skilled (age = 15.17 ± 1.1 years) football players. All participants performed 20 instep kicks with maximum velocity in four randomly organised insoles and socks conditions, (a) Smooth Socks with Smooth Insoles (SSSI); (b) Smooth Socks with Textured Insoles (SSTI); (c) Compression Socks with Smooth Insoles (CSSI); and (d), Compression Socks with Textured Insoles (CSTI). Results showed that, when wearing textured and compression materials (CSSI condition), less-skilled participants displayed significantly greater hip extension and flexion towards the ball contact phase, indicating larger ranges of motion in the kicking limb than in other conditions. Less-skilled participants also demonstrated greater variability in knee-ankle intralimb (angle-angle plots) coordination modes in the CSTI condition. Findings suggested that use of textured and compression materials increased attunement to somatosensory information from lower limb movement, to regulate performance of dynamic interceptive actions like kicking, especially in less-skilled individuals.

Intratumoral heterogeneity and clonal evolution in blood malignancies and solid tumors.

PubMed

Varela, Ignacio; Menendez, Pablo; Sanjuan-Pla, Alejandra

2017-09-12

This meeting held at the University of Barcelona in March 2017, brought together scientists and clinicians worldwide to discuss current and future clinico-biological implications of intratumoral heterogeneity (ITH) and subclonal evolution in cancer diagnosis, patient stratification, and treatment resistance in diagnosis, treatment and follow-up. There was consensus that both longitudinal and tumor multi-region studies in matched samples are needed to better understand the dynamics of ITH. The contribution of the epigenome and microenvironment to ITH and subclone evolution remains understudied. It was recommended to combine computational, pathology and imaging tools to study the role of the microenvironment in subclone selection/evolution.

Immediate effects of foot orthoses on pain during functional tasks in people with patellofemoral osteoarthritis: A cross-over, proof-of-concept study.

PubMed

Collins, Natalie J; Hinman, Rana S; Menz, Hylton B; Crossley, Kay M

2017-01-01

The purpose of the study was to determine whether prefabricated foot orthoses immediately reduce pain during functional tasks in people with patellofemoral osteoarthritis, compared to flat insoles and shoes alone. Eighteen people with predominant lateral patellofemoral osteoarthritis (nine women; mean [SD] age 59 [10]years; body mass index 27.9 [3.2]kg/m 2 ) performed functional tasks wearing running sandals, and then wearing foot orthoses and flat insoles (random order). Participants rated knee pain during each task (11-point numerical rating scales), ease of performance and knee stability (five-point Likert scales), and comfort (100mm visual analogue scales). Compared to shoes alone, foot orthoses (p=0.002; median difference 1.5 [IQR 3]) and flat insoles (p<0.001; 2 [3]) significantly reduced pain during step-downs; foot orthoses reduced pain during walking (p=0.008; 1 [1.25]); and flat insoles reduced pain during stair ambulation (p=0.001; 1 [1.75]). No significant differences between foot orthoses and flat insoles were observed for pain severity, ease of performance or knee stability. Foot orthoses were less comfortable than flat insoles and shoes alone (p<0.05). In people with patellofemoral osteoarthritis, immediate pain-relieving effects of prefabricated, contoured foot orthoses are equivalent to flat insoles. Further studies should investigate whether similar outcomes occur with longer-term wear or different orthosis designs. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation on penetration rate of cloud for incoming solar radiation using geostationary satellite data

NASA Astrophysics Data System (ADS)

Yeom, Jong-Min; Han, Kyung-Soo; Kim, Jae-Jin

2012-05-01

Solar surface insolation (SSI) represents how much solar radiance reaches the Earth's surface in a specified area and is an important parameter in various fields such as surface energy research, meteorology, and climate change. This study calculates insolation using Multi-functional Transport Satellite (MTSAT-1R) data with a simplified cloud factor over Northeast Asia. For SSI retrieval from the geostationary satellite data, the physical model of Kawamura is modified to improve insolation estimation by considering various atmospheric constituents, such as Rayleigh scattering, water vapor, ozone, aerosols, and clouds. For more accurate atmospheric parameterization, satellite-based atmospheric constituents are used instead of constant values when estimating insolation. Cloud effects are a key problem in insolation estimation because of their complicated optical characteristics and high temporal and spatial variation. The accuracy of insolation data from satellites depends on how well cloud attenuation as a function of geostationary channels and angle can be inferred. This study uses a simplified cloud factor that depends on the reflectance and solar zenith angle. Empirical criteria to select reference data for fitting to the ground station data are applied to suggest simplified cloud factor methods. Insolation estimated using the cloud factor is compared with results of the unmodified physical model and with observations by ground-based pyranometers located in the Korean peninsula. The modified model results show far better agreement with ground truth data compared to estimates using the conventional method under overcast conditions.

Redistribution of knee stress using laterally wedged insole intervention: Finite element analysis of knee-ankle-foot complex.

PubMed

Liu, Xuan; Zhang, Ming

2013-01-01

Laterally wedged insoles are widely applied in the conservative treatment for medial knee osteoarthritis. Experimental studies have been conducted to understand the effectiveness of such an orthotic intervention. However, the information was limited to the joint external loading such as knee adduction moment. The internal stress distribution is difficult to be obtained from in vivo experiment alone. Thus, a three-dimensional finite element model of the human knee-ankle-foot complex, together with orthosis, was developed in this study and used to investigate the redistribution of knee stress using laterally wedged insole intervention. Laterally wedged insoles with wedge angles of 0, 5, and 10° were fabricated for intervention. The subject-specific geometry of the lower extremity with details was characterized in the reconstruction of MR images. Motion analysis data and muscle forces were input to drive the model. The established finite element model was employed to investigate the loading responses of tibiofemoral articulation in three wedge angle conditions during simulated walking stance phase. With either of the 5° or 10° laterally wedged insole, significant decreases in von Mises stress and contact force at the medial femur cartilage region and the medial meniscus were predicted comparing with the 0° insole. The diminished stress and contact force at the medial compartment of the knee joint demonstrate the immediate effect of the laterally wedged insoles. The intervention may contribute to medial knee osteoarthritis rehabilitation. Copyright © 2012 Elsevier Ltd. All rights reserved.

A 3D Visualization and Analysis Model of the Earth Orbit, Milankovitch Cycles and Insolation.

NASA Astrophysics Data System (ADS)

Kostadinov, Tihomir; Gilb, Roy

2013-04-01

Milankovitch theory postulates that periodic variability of Earth's orbital elements is a major climate forcing mechanism. Although controversies remain, ample geologic evidence supports the major role of the Milankovitch cycles in climate, e.g. glacial-interglacial cycles. There are three Milankovitch orbital parameters: orbital eccentricity (main periodicities of ~100,000 and ~400,000 years), precession (quantified as the longitude of perihelion, main periodicities 19,000-24,000 years) and obliquity of the ecliptic (Earth's axial tilt, main periodicity 41,000 years). The combination of these parameters controls the spatio-temporal patterns of incoming solar radiation (insolation) and the timing of the seasons with respect to perihelion, as well as season duration. The complex interplay of the Milankovitch orbital parameters on various time scales makes assessment and visualization of Earth's orbit and insolation variability challenging. It is difficult to appreciate the pivotal importance of Kepler's laws of planetary motion in controlling the effects of Milankovitch cycles on insolation patterns. These factors also make Earth-Sun geometry and Milankovitch theory difficult to teach effectively. Here, an astronomically precise and accurate Earth orbit visualization model is presented. The model offers 3D visualizations of Earth's orbital geometry, Milankovitch parameters and the ensuing insolation forcings. Both research and educational uses are envisioned for the model, which is developed in Matlab® as a user-friendly graphical user interface (GUI). We present the user with a choice between the Berger et al. (1978) and Laskar et al. (2004) astronomical solutions for eccentricity, obliquity and precession. A "demo" mode is also available, which allows the three Milankovitch parameters to be varied independently of each other (and over much larger ranges than the naturally occurring ones), so the user can isolate the effects of each parameter on orbital geometry, the seasons, and insolation. Users select a calendar date and the Earth is placed in its orbit using Kepler's laws; the calendar can be started on either vernal equinox (March 20) or perihelion (Jan. 3). Global insolation is computed as a function of latitude and day of year, using the chosen Milankovitch parameters. 3D surface plots of insolation and insolation anomalies (with respect to J2000) are then produced. Insolation computations use the model's own orbital geometry with no additional a-priori input other than the Milankovitch parameter solutions. Insolation computations are successfully validated against Laskar et al. (2004) values. The model outputs other relevant parameters as well, e.g. Earth's radius-vector length, solar declination and day length for the chosen date and latitude. Time-series plots of the Milankovitch parameters and EPICA ice core CO2 and temperature data can be produced. Envisioned future developments include computational efficiency improvements, more options for insolation plots on user-chosen spatio-temporal scales, and overlaying additional paleoclimatological proxy data.

Inorganic Arsenic–Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell–Conditioned Media Model

PubMed Central

Shearer, Joseph J.; Wold, Eric A.; Umbaugh, Charles S.; Lichti, Cheryl F.; Nilsson, Carol L.; Figueiredo, Marxa L.

2015-01-01

Background: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal–epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer. Objective: The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate molecular mechanisms of iAs-induced changes to stromal signaling by an enriched prostate tumor microenvironment cell population, adipose-derived mesenchymal stem/stromal cells (ASCs). Results: ASC-conditioned media (CM) collected after 1 week of iAs exposure increased prostate cancer cell viability, whereas CM from ASCs that received no iAs exposure decreased cell viability. Cytokine array analysis suggested changes to cytokine signaling associated with iAs exposure. Subsequent proteomic analysis suggested a concentration-dependent alteration to the HMOX1/THBS1/TGFβ signaling pathway by iAs. These results were validated by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blotting, confirming a concentration-dependent increase in HMOX1 and a decrease in THBS1 expression in ASC following iAs exposure. Subsequently, we used a TGFβ pathway reporter construct to confirm a decrease in stromal TGFβ signaling in ASC following iAs exposure. Conclusions: Our results suggest a concentration-dependent alteration of stromal signaling: specifically, attenuation of stromal-mediated TGFβ signaling following exposure to iAs. Our results indicate iAs may enhance prostate cancer cell viability through a previously unreported stromal-based mechanism. These findings indicate that the stroma may mediate the effects of iAs in tumor progression, which may have future therapeutic implications. Citation: Shearer JJ, Wold EA, Umbaugh CS, Lichti CF, Nilsson CL, Figueiredo ML. 2016. Inorganic arsenic–related changes in the stromal tumor microenvironment in a prostate cancer cell–conditioned media model. Environ Health Perspect 124:1009–1015; http://dx.doi.org/10.1289/ehp.1510090 PMID:26588813

Targeting the Neural Microenvironment in Prostate Cancer

DTIC Science & Technology

2016-10-01

neurotrophic factor (GDNF), which is expressed by peripheral nerves. GDNF binds to RET, a receptor tyrosine kinase, in conjunction with its co-receptor...kinase, in conjunction with its co- receptor GFRα1 and activates cellular signaling. Studies in pancreatic cancer strongly implicate RET signaling as

The clinical implications of immunogenomics in colorectal cancer: A path for precision medicine.

PubMed

Riley, Jenny M; Cross, Ashley W; Paulos, Chrystal M; Rubinstein, Mark P; Wrangle, John; Camp, E Ramsay

2018-04-15

Colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths in the United States. Large multi-omic databases, such as The Cancer Genome Atlas and the International Colorectal Cancer Subtyping Consortium, have identified distinct molecular subtypes related to anatomy. The identification of genomic alterations in CRC is now critical because of the recent success and US Food and Drug Administration approval of pembrolizumab and nivolumab for microsatellite-instable tumors. In parallel, landmark studies have established the prognostic significance of the CRC tumor-infiltrating lymphocyte and the clinical impact of the tumor immune microenvironment. As a result, there is a growing appreciation for immunogenomics, the interconnected relation between tumor genomics and the immune microenvironment. The clinical implications of CRC immunogenomics continue to expand, and it will likely serve as a guide for next-generation immunotherapy strategies for improving outcomes for this disease. Cancer 2018;124:1650-9. © 2018 American Cancer Society. © 2018 American Cancer Society.

Estimation of clear-sky insolation using satellite and ground meteorological data

NASA Technical Reports Server (NTRS)

Staylor, W. F.; Darnell, W. L.; Gupta, S. K.

1983-01-01

Ground based pyranometer measurements were combined with meteorological data from the Tiros N satellite in order to estimate clear-sky insolations at five U.S. sites for five weeks during the spring of 1979. The estimates were used to develop a semi-empirical model of clear-sky insolation for the interpretation of input data from the Tiros Operational Vertical Sounder (TOVS). Using only satellite data, the estimated standard errors in the model were about 2 percent. The introduction of ground based data reduced errors to around 1 percent. It is shown that although the errors in the model were reduced by only 1 percent, TOVS data products are still adequate for estimating clear-sky insolation.

Solar microclimatology. [tables (data) on insolation for application to solar energy conversion by electric power plants

NASA Technical Reports Server (NTRS)

Mckenney, D. B.; Beauchamp, W. T.

1975-01-01

It has become apparent in recent years that solar energy can be used for electric power production by several methods. Because of the diffuse nature of the solar insolation, the area involved in any central power plant design can encompass several square miles. A detailed design of these large area collection systems will require precise knowledge of the local solar insolation. Detailed information will also be needed concerning the temporal nature of the insolation and the local spatial distribution. Therefore, insolation data was collected and analyzed for a network of sensors distributed over an area of several square kilometers in Arizona. The analyses of this data yielded probability distributions of cloud size, velocity, and direction of motion which were compared with data obtained from the National Weather Service. Microclimatological analyses were also performed for suitable modeling parameters pertinent to large scale electric power plant design. Instrumentation used to collect the data is described.

Development of inexpensive prosthetic feet for high-heeled shoes using simple shoe insole model.

PubMed

Meier, Margrit R; Tucker, Kerice A; Hansen, Andrew H

2014-01-01

The large majority of prosthetic feet are aimed at low-heeled shoes, with a few models allowing a heel height of up to 5 cm. However, a survey by the American Podiatric Medical Association indicates that most women wear heels over 5 cm; thus, current prosthetic feet limit most female prosthesis users in their choice. Some prosthetic foot components are heel-height adjustable; however, their plantar surface shapes do not change to match the insole shapes of the shoes with different heel heights. The aims of the study were therefore (1) to develop a model that allows prediction of insole shape for various heel height shoes in combination with different shoe sizes and (2) to develop and field-test low-cost prototypes of prosthetic feet whose insole shapes were based on the new model. An equation was developed to calculate insole shapes independent of shoe size. Field testing of prototype prosthetic feet fabricated based on the equation was successful and demonstrated the utility of the equation.

Bulk Insolation Models as Predictors for Locations for High Lunar Hydrogen Concentrations

NASA Technical Reports Server (NTRS)

Mcclanahan, T. P.; Mitrofanov, I.G.; Boynton, W. V.; Chin, G.; Starr, R. D.; Evans, L. G.; Sanin, A.; Livengood, T.; Sagdeev, R.; Milikh, G.

2013-01-01

In this study we consider the bulk effects of surface illumination on topography (insolation) and the possible thermodynamic effects on the Moon's hydrogen budget. Insolation is important as one of the dominant loss processes governing distributions of hydrogen volatiles on the Earth, Mars and most recently Mercury. We evaluated three types of high latitude > 65 deg., illumination models that were derived from the Lunar Observing Laser Altimetry (LOLA) digital elevation models (DEM)'s. These models reflect varying accounts of solar flux interactions with the Moon's near-surface. We correlate these models with orbital collimated epithermal neutron measurements made by the Lunar Exploration Neutron Detector (LEND). LEND's measurements derive the Moon's spatial distributions of hydrogen concentration. To perform this analysis we transformed the topographic model into an insolation model described by two variables as each pixels 1) slope and 2) slope angular orientation with respect to the pole. We then decomposed the illumination models and epithermal maps as a function of the insolation model and correlate the datasets.

A calibrated, high-resolution goes satellite solar insolation product for a climatology of Florida evapotranspiration

USGS Publications Warehouse

Paech, S.J.; Mecikalski, J.R.; Sumner, D.M.; Pathak, C.S.; Wu, Q.; Islam, S.; Sangoyomi, T.

2009-01-01

Estimates of incoming solar radiation (insolation) from Geostationary Operational Environmental Satellite observations have been produced for the state of Florida over a 10-year period (1995-2004). These insolation estimates were developed into well-calibrated half-hourly and daily integrated solar insolation fields over the state at 2 km resolution, in addition to a 2-week running minimum surface albedo product. Model results of the daily integrated insolation were compared with ground-based pyranometers, and as a result, the entire dataset was calibrated. This calibration was accomplished through a three-step process: (1) comparison with ground-based pyranometer measurements on clear (noncloudy) reference days, (2) correcting for a bias related to cloudiness, and (3) deriving a monthly bias correction factor. Precalibration results indicated good model performance, with a station-averaged model error of 2.2 MJ m-2/day (13%). Calibration reduced errors to 1.7 MJ m -2/day (10%), and also removed temporal-related, seasonal-related, and satellite sensor-related biases. The calibrated insolation dataset will subsequently be used by state of Florida Water Management Districts to produce statewide, 2-km resolution maps of estimated daily reference and potential evapotranspiration for water management-related activities. ?? 2009 American Water Resources Association.

Effects of experimental insoles on body posture, mandibular kinematics and masticatory muscles activity. A pilot study in healthy volunteers.

PubMed

Marini, Ida; Alessandri Bonetti, Giulio; Bortolotti, Francesco; Bartolucci, Maria Lavinia; Gatto, Maria Rosaria; Michelotti, Ambra

2015-06-01

It has been hypothesized that different plantar sensory inputs could influence the whole body posture and dental occlusion but there is a lack of evidence on this possible association. To investigate the effects of experimental insoles redistributing plantar pressure on body posture, mandibular kinematics and electromyographic (EMG) activity of masticatory muscles on healthy subjects. A pilot study was conducted on 19 healthy volunteers that wore custom-made insoles normalizing the plantar pressure distribution for 2 weeks. Body posture parameters were measured by means of an optoelectronic stereophotogrammetric analysis; mandibular kinematics was analyzed by means of gothic arch tracings; superficial EMG activity of head and neck muscles was performed. Measurements were carried out 10 days before the insertion of the insoles, immediately before the insertion, the day after, 7 and 14 days after, in four different exteroceptive conditions. The outcomes of the present study show that insoles do not modify significantly over time the parameters of body posture, SEMG activity of head and neck muscles and mandibular kinematics. In this pilot study the experimental insoles did not significantly influence the body posture, the mandibular kinematics and the activity of masticatory muscles during a 14-day follow up period. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution and morphology of microenvironment-enhanced malignancy of three-dimensional invasive solid tumors

NASA Astrophysics Data System (ADS)

Jiao, Yang; Torquato, Salvatore

2013-05-01

The emergence of invasive and metastatic behavior in malignant tumors can often lead to fatal outcomes for patients. The collective malignant tumor behavior resulting from the complex tumor-host interactions and the interactions between the tumor cells is currently poorly understood. In this paper, we employ a cellular automaton (CA) model to investigate microenvironment-enhanced malignant behaviors and morphologies of in vitro avascular invasive solid tumors in three dimensions. Our CA model incorporates a variety of microscopic-scale tumor-host interactions, including the degradation of the extracellular matrix by the malignant cells, nutrient-driven cell migration, pressure buildup due to the deformation of the microenvironment by the growing tumor, and its effect on the local tumor-host interface stability. Moreover, the effects of cell-cell adhesion on tumor growth are explicitly taken into account. Specifically, we find that while strong cell-cell adhesion can suppress the invasive behavior of the tumors growing in soft microenvironments, cancer malignancy can be significantly enhanced by harsh microenvironmental conditions, such as exposure to high pressure levels. We infer from the simulation results a qualitative phase diagram that characterizes the expected malignant behavior of invasive solid tumors in terms of two competing malignancy effects: the rigidity of the microenvironment and cell-cell adhesion. This diagram exhibits phase transitions between noninvasive and invasive behaviors. We also discuss the implications of our results for the diagnosis, prognosis, and treatment of malignant tumors.

Effects of orthopedic insoles on static balance of older adults wearing thick socks.

PubMed

Ma, Christina Zong-Hao; Wong, Duo Wai-Chi; Wan, Anson Hong-Ping; Lee, Winson Chiu-Chun

2018-06-01

The wearing of socks and insoles may affect the ability of the foot to detect tactile input influencing postural balance. The aim of this study was to investigate whether (1) thick socks adversely affected the elderly postural balance and (2) orthopedic insoles could improve the elderly postural balance while wearing thick socks. Repeated-measures study design. In total, 14 healthy older adults were recruited. A monofilament test was conducted to evaluate foot plantar sensation with and without thick socks. Subjects then performed the Romberg tests under three conditions: (1) barefoot, (2) with socks only, and (3) with both socks and insoles. Postural balance was assessed by measuring the center of pressure movement during standing in each experimental condition. Thick socks significantly decreased the monofilament score ( p < 0.001), suggesting reduction in ability to detect external forces. All center of pressure parameters increased significantly while wearing thick socks ( p < 0.017), implying reduction of postural stability. They then decreased significantly with the additional use of insoles ( p < 0.017). Previous studies have documented the changes in plantar pressure distribution with the use of orthopedic insoles. This study further suggests that such changes in contact mechanics could produce some balance-improving effects, which appears not to have been reported earlier. Clinical relevance Wearing thick socks reduces plantar pressure sensitivity and increases postural sway which may increase risk of falls. Orthopedic insoles and footwear with similar design could potentially be a cost-effective method in maintaining postural balance when wearing thick socks.

Lateral Wedge Insoles for Reducing Biomechanical Risk Factors for Medial Knee Osteoarthritis Progression: A Systematic Review and Meta-Analysis.

PubMed

Arnold, John B; Wong, Daniel X; Jones, Richard K; Hill, Catherine L; Thewlis, Dominic

2016-07-01

Lateral wedge insoles are intended to reduce biomechanical risk factors of medial knee osteoarthritis (OA) progression, such as increased knee joint load; however, there has been no definitive consensus on this topic. The aim of this systematic review and meta-analysis was to establish the within-subject effects of lateral wedge insoles on knee joint load in people with medial knee OA during walking. Six databases were searched from inception until February 13, 2015. Included studies reported on the immediate biomechanical effects of lateral wedge insoles during walking in people with medial knee OA. Primary outcomes of interest relating to the biomechanical risk of disease progression were the first and second peak external knee adduction moment (EKAM) and knee adduction angular impulse (KAAI). Eligible studies were pooled using random-effects meta-analysis. Eighteen studies were included with a total of 534 participants. Lateral wedge insoles resulted in a small but statistically significant reduction in the first peak EKAM (standardized mean difference [SMD] -0.19; 95% confidence interval [95% CI] -0.23, -0.15) and second peak EKAM (SMD -0.25; 95% CI -0.32, -0.19) with a low level of heterogeneity (I(2)  = 5% and 30%, respectively). There was a favorable but small reduction in the KAAI with lateral wedge insoles (SMD -0.14; 95% CI -0.21, -0.07, I(2)  = 31%). Risk of methodologic bias scores (quality index) ranged from 8 to 13 out of 16. Lateral wedge insoles cause small reductions in the EKAM and KAAI during walking in people with medial knee OA. Current evidence demonstrates that lateral wedge insoles appear ineffective at attenuating structural changes in people with medial knee OA as a whole and may be better suited to targeted use in biomechanical phenotypes associated with larger reductions in knee load. © 2016, American College of Rheumatology.

Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

NASA Astrophysics Data System (ADS)

Cruz, Nelly M.; Song, Xuewen; Czerniecki, Stefan M.; Gulieva, Ramila E.; Churchill, Angela J.; Kim, Yong Kyun; Winston, Kosuke; Tran, Linh M.; Diaz, Marco A.; Fu, Hongxia; Finn, Laura S.; Pei, York; Himmelfarb, Jonathan; Freedman, Benjamin S.

2017-11-01

Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

ASHMET: A computer code for estimating insolation incident on tilted surfaces

NASA Technical Reports Server (NTRS)

Elkin, R. F.; Toelle, R. G.

1980-01-01

A computer code, ASHMET, was developed by MSFC to estimate the amount of solar insolation incident on the surfaces of solar collectors. Both tracking and fixed-position collectors were included. Climatological data for 248 U. S. locations are built into the code. The basic methodology used by ASHMET is the ASHRAE clear-day insolation relationships modified by a clearness index derived from SOLMET-measured solar radiation data to a horizontal surface.

Novel methodology to obtain salient biomechanical characteristics of insole materials.

PubMed

Lavery, L A; Vela, S A; Ashry, H R; Lanctot, D R; Athanasiou, K A

1997-06-01

Viscoelastic inserts are commonly used as artificial shock absorbers to prevent neuropathic foot ulcerations by decreasing pressure on the sole of the foot. Unfortunately, there is little scientific information available to guide physicians in the selection of appropriate insole materials. Therefore, a novel methodology was developed to form a rational platform for biomechanical characterizations of insole material durability, which consisted of in vivo gait analysis and in vitro bioengineering measurements. Results show significant differences in the compressive stiffness of the tested insoles and the rate of change over time in both compressive stiffness and peak pressures measured. Good correlations were found between pressure-time integral and Young's modulus (r2 = 0.93), and total energy applied and Young's modulus (r2 = 0.87).

Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

PubMed

Allison, Katrina E; Coomber, Brenda L; Bridle, Byram W

2017-10-01

Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed. © 2017 John Wiley & Sons Ltd.

Compartmentalized and systemic control of tissue immunity by commensals

PubMed Central

Belkaid, Yasmine; Naik, Shruti

2013-01-01

The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology. PMID:23778791

Single-Cell RNA-Sequencing in Glioma.

PubMed

Johnson, Eli; Dickerson, Katherine L; Connolly, Ian D; Hayden Gephart, Melanie

2018-04-10

In this review, we seek to summarize the literature concerning the use of single-cell RNA-sequencing for CNS gliomas. Single-cell analysis has revealed complex tumor heterogeneity, subpopulations of proliferating stem-like cells and expanded our view of tumor microenvironment influence in the disease process. Although bulk RNA-sequencing has guided our initial understanding of glioma genetics, this method does not accurately define the heterogeneous subpopulations found within these tumors. Single-cell techniques have appealing applications in cancer research, as diverse cell types and the tumor microenvironment have important implications in therapy. High cost and difficult protocols prevent widespread use of single-cell RNA-sequencing; however, continued innovation will improve accessibility and expand our of knowledge gliomas.

Finite Element Study into the effect of footwear temperature on the Forces transmitted to the foot during quasi- static compression loading

NASA Astrophysics Data System (ADS)

Shariatmadari, M. R.; English, R.; Rothwell, G.

2010-06-01

The determination of plantar stresses using computational footwear models which include temperature effects are crucial to predict foam performance in service and to aid material development and product design. Finite Element Method (FEM) provides an efficient computational framework to investigate the foot-footwear interaction. The aim of this research is to use FEM to investigate the effect of varying footwear temperature on plantar stresses. The results obtained will provide data which can be used to help optimise shoe design in terms of minimising damaging stresses in the foot particularly for individuals with diabetes who are susceptible to lower extremity complications. The FE simulation results showed significant reductions in foot stresses with the modifications from FE model (1) without footwear to model (2) with midsole only and to model (3) with midsole and insole. In summary, insole and midsole layers made from various foam materials aim to reduce the Ground Reaction Forces (GRF's) and foot stresses considerably and temperature variation can affect their cushioning and consequently the shock attenuation properties. The loss of footwear cushioning effect can have important clinical implications for those individuals with a history of lower limb overuse injuries or diabetes.

SOLINS- SOLAR INSOLATION MODEL FOR COMPUTING AVAILABLE SOLAR ENERGY TO A SURFACE OF ARBITRARY ORIENTATION

NASA Technical Reports Server (NTRS)

Smith, J. H.

1994-01-01

This computer program, SOLINS, was developed to aid engineers and solar system designers in the accurate modeling of the average hourly solar insolation on a surface of arbitrary orientation. The program can be used to study insolation problems specific to residential and commercial applications where the amount of space available for solar collectors is limited by shadowing problems, energy output requirements, and costs. For tandem rack arrays, SOLINS will accommodate the use of augmentation reflectors built into the support structure to increase insolation values at the collector surface. As the use of flat plate solar collectors becomes more prevalent in the building industry, the engineer and designer must have the capability to conduct extensive sensitivity analyses on the orientation and location of solar collectors. SOLINS should prove to be a valuable aid in this area of engineering. SOLINS uses a modified version of the National Bureau of Standards model to calculate the direct, diffuse, and reflected components of total insolation on a tilted surface with a given azimuthal orientation. The model is based on the work of Liu and Jordan with corrections by Kusuda and Ishii to account for early morning and late afternoon errors. The model uses a parametric description of the average day solar climate to generate monthly average day profiles by hour of the insolation level on the collector surface. The model includes accommodation of user specified ground and landscape reflectivities at the collector site. For roof or ground mounted, tilted arrays, SOLINS will calculate insolation including the effects of shadowing and augmentation reflectors. The user provides SOLINS with data describing the array design, array orientation, the month, the solar climate parameter, the ground reflectance, and printout control specifications. For the specified array and environmental conditions, SOLINS outputs the hourly insolation the array will receive during an average day during the month specified, along with the total insolation the collector surface will receive over an average 24-hour period. This program is written in FORTRAN IV for batch execution and has been implemented on an IBM 370 computer with a central memory requirement of approximately 46K of 8 bit bytes. The SOLINS routines were developed in 1979.

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

PubMed Central

Bennell, Kim; Bowles, Kelly-Ann; Payne, Craig; Cicuttini, Flavia; Osborne, Richard; Harris, Anthony; Hinman, Rana

2007-01-01

Background Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA. Methods/Design Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA. Trial registration ACTR12605000503628; NCT00415259. PMID:17892539

Assessment of the global monthly mean surface insolation estimated from satellite measurements using global energy balance archive data

NASA Technical Reports Server (NTRS)

Li, Zhanqing; Whitlock, Charles H.; Charlock, Thomas P.

1995-01-01

Global sets of surface radiation budget (SRB) have been obtained from satellite programs. These satellite-based estimates need validation with ground-truth observations. This study validates the estimates of monthly mean surface insolation contained in two satellite-based SRB datasets with the surface measurements made at worldwide radiation stations from the Global Energy Balance Archive (GEBA). One dataset was developed from the Earth Radiation Budget Experiment (ERBE) using the algorithm of Li et al. (ERBE/SRB), and the other from the International Satellite Cloud Climatology Project (ISCCP) using the algorithm of Pinker and Laszlo and that of Staylor (GEWEX/SRB). Since the ERBE/SRB data contain the surface net solar radiation only, the values of surface insolation were derived by making use of the surface albedo data contained GEWEX/SRB product. The resulting surface insolation has a bias error near zero and a root-mean-square error (RMSE) between 8 and 28 W/sq m. The RMSE is mainly associated with poor representation of surface observations within a grid cell. When the number of surface observations are sufficient, the random error is estimated to be about 5 W/sq m with present satellite-based estimates. In addition to demonstrating the strength of the retrieving method, the small random error demonstrates how well the ERBE derives from the monthly mean fluxes at the top of the atmosphere (TOA). A larger scatter is found for the comparison of transmissivity than for that of insolation. Month to month comparison of insolation reveals a weak seasonal trend in bias error with an amplitude of about 3 W/sq m. As for the insolation data from the GEWEX/SRB, larger bias errors of 5-10 W/sq m are evident with stronger seasonal trends and almost identical RMSEs.

Full-length silicone insoles versus ultrasound-guided corticosteroid injection in the management of plantar fasciitis: a randomized clinical trial.

PubMed

Yucel, Ufuk; Kucuksen, Sami; Cingoz, Havva T; Anliacik, Emel; Ozbek, Orhan; Salli, Ali; Ugurlu, Hatice

2013-12-01

Plantar fasciitis often leads to disability. Optimal treatment for this clinical condition is still unknown. To compare the effectiveness of wearing a full-length silicone insole with ultrasound-guided corticosteroid injection in the management of plantar fasciitis. Randomized clinical trial. Forty-two patients with chronic unilateral plantar fasciitis were allocated randomly to have an ultrasound-guided corticosteroid injection or wear a full-length silicone insole. Data were collected before the procedure and 1 month after. The primary outcome measures included first-step heel pain via Visual Analogue Scale and Heel Tenderness Index. Other outcome measures were the Foot and Ankle Outcome Score and ultrasonographic thickness of the plantar fascia. After 1 month, a significant improvement was shown in Visual Analogue Scale, Heel Tenderness Index, Foot and Ankle Outcome Score, and ultrasonographic thickness of plantar fascia in both groups. Visual Analogue Scale scores, Foot and Ankle Outcome Score pain, Foot and Ankle Outcome Score for activities of daily living, Foot and Ankle Outcome Score for sport and recreation function, and plantar fascia thickness were better in injection group than in insole group (p < 0.05). Although both ultrasound-guided corticosteroid injection and wearing a full-length silicone insole were effective in the conservative treatment of plantar fasciitis, we recommend the use of silicone insoles as a first line of treatment for persons with plantar fasciitis.

Does Wearing Textured Insoles during Non-class Time Improve Proprioception in Professional Dancers?

PubMed

Steinberg, N; Tirosh, O; Adams, R; Karin, J; Waddington, G

2015-11-01

This study sought to determine whether textured insoles inserted in the sports shoes of young dancers improved their inversion and eversion ankle movement discrimination. 26 ballet dancers (14 female, 12 male) from the Australian Ballet School, ages 14-19 years, were divided into 2 groups according to sex and class levels. During the first 4 weeks, the first intervention group (GRP1) was asked to wear textured insoles in their sports shoes during non-class periods, and the second intervention group (GRP2) followed standard practice. In the next 4 weeks, GRP2 was asked to wear the textured insoles and GRP1 did not wear the textured insoles. Participants were tested pre-intervention, after 4 weeks, and at 8 weeks for both inversion and eversion ankle discrimination. In both inversion and eversion testing positions, interaction was found between the 2 groups and the 3 testing times (p<0.001), with significant differences between the first testing and the second testing (p=0.038 and p=0.019, respectively), and between the third testing and the second testing (p=0.003 and p=0.029, respectively). In conclusion, the stimulation to the proprioceptive system arising from textured insoles worn for 4 weeks was sufficient to improve the ankle proprioception of ballet dancers, in both inversion and eversion movements. © Georg Thieme Verlag KG Stuttgart · New York.

Designing an Orthotic Insole by Using Kinect® XBOX Gaming Sensor Scanner and Computer Aided Engineering Software

NASA Astrophysics Data System (ADS)

Hafiz Burhan, Mohd; Nor, Nik Hisyamudin Muhd; Yarwindran, Mogan; Ibrahim, Mustaffa; Fahrul Hassan, Mohd; Azwir Azlan, Mohd; Turan, Faiz Mohd; Johan, Kartina

2017-08-01

Healthcare and medical is one of the most expensive field in the modern world. In order to fulfil medical requirement, this study aimed to design an orthotic insole by using Kinect Xbox Gaming Sensor Scanner and CAE softwares. The accuracy of the Kinect® XBOX 360 gaming sensor is capable of producing 3D reconstructed geometry with the maximum and minimum error of 3.78% (2.78mm) and 1.74% (0.46mm) respectively. The orthotic insole design process had been done by using Autodesk Meshmixer 2.6 and Solidworks 2014 software. Functionality of the orthotic insole designed was capable of reducing foot pressure especially in the metatarsal area. Overall, the proposed method was proved to be highly potential in the design of the insole where it promises low cost, less time consuming, and efficiency in regards that the Kinect® XBOX 360 device promised low price compared to other digital 3D scanner since the software needed to run the device can be downloaded for free.

Observational Evidence of Changes in Water Vapor, Clouds, and Radiation at the ARM SGP Site

NASA Technical Reports Server (NTRS)

Dong, Xiquan; Xi, Baike; Minnus, Patrick

2006-01-01

Characterizing water vapor and cloud effects on the surface radiation budget is critical for understanding the current climate because water vapor is the most important greenhouse gas in the atmosphere and clouds are one of the largest sources of uncertainty in predicting potential future climate change. Several studies have shown that insolation over land declined until 1990 then increased until the present. Using 8 years of surface data, we observed the increasing trend of insolation from 1997 to 2000, but detected a significant decrease from 2001 to 2004. The variation of cloud fraction mirrors that of insolation with an overall increase of 1 percent per year. Under clear-sky conditions, water vapor changes have a greater impact on longwave flux than on insolation.

Influence of a Viscoelastic Insole on Foot, Knee and Back Pain among Members of the United States Army Band

DTIC Science & Technology

2010-07-13

band members by providing them shoes with some favorable properties such as outsoles with built in compression pads in the heel and forefoot as well...compared to a no insole condition49 and that peak pressure generated at the forefoot and heel have been reduced by 24 percent and 37 percent...Attenuation of spinal transients at heel strike using viscoelastic heel insoles: an in vivo study. Preventive Medicine. 2004;39:351-354. 30

Effects of low-energy laser insolation upon the development of postradiation syndrome

NASA Astrophysics Data System (ADS)

Pavlova, Rimma N.; Gomberg, Vladimir G.; Boiko, Vladimir A.; Pupkova, Ludmila S.; Reznikov, Leonid L.; Dadali, V. A.

1996-04-01

Basic pathogenic research as well as the studies of clinical therapeutic aspects dealing with the long-term gamma radiation effects are of utmost significance nowadays. The main goal of the present study was to establish the capability of low-energy laser insolation to oppose the free radical oxidative chain reactions inherent to the effects of radiation. Adequate doses of low- energy laser insolation were shown to produce positive effects upon the metabolism similar to those of pharmacologic radioprotectors.

Solar energy microclimate as determined from satellite observations

NASA Technical Reports Server (NTRS)

Vonder Haar, T. H.; Ellis, J. S.

1975-01-01

A method is presented for determining solar insolation at the earth's surface using satellite broadband visible radiance and cloud imagery data, along with conventional in situ measurements. Conventional measurements are used to both tune satellite measurements and to develop empirical relationships between satellite observations and surface solar insolation. Cloudiness is the primary modulator of sunshine. The satellite measurements as applied in this method consider cloudiness both explicitly and implicitly in determining surface solar insolation at space scales smaller than the conventional pyranometer network.

ODP Sites 967 and 968 (eastern Mediterranean) revisited and implications for the global oxygen stable isotope chronology of the late Pleistocene

NASA Astrophysics Data System (ADS)

Konijnendijk, Tiuri; Lourens, Lucas; Ziegler, Martin

2013-04-01

ODP Sites 967 and 968 (eastern Mediterranean) revisited and implications for the global oxygen stable isotope chronology of the late Pleistocene ODP Sites 967 and 968, located in the Eastern Mediterranean at the Eratosthenes Seamount, are ideally situated to study both regional and global climate signals. Evidently, changes in the titanium to aluminum ratio of the bulk sediment reflect variations in North African aridity, and hence North African monsoon strength: increased levels of titanium are associated with enhanced windblown dust input from the Sahara and increased levels of aluminum with enhanced runoff from the river Nile. In addition, changes in the benthic foraminiferal stable isotope composition reflect primarily changes in global ice volume and deep sea temperature (Lourens et al., 2010; Ziegler et al., 2010). Here we completed and spliced the Ti/Al and benthic d18O data sets of ODP Site 968 and 967 for the past one million years at approximately 200-400 year resolution. The Ti/Al ratio reflect dominantly precession-controlled African monsoon intensity changes and was used to build an astronomically tuned age model for the composite record. This approach enabled us in first instance to establish an alternative and highly accurate chronology for sapropels in the Eastern Mediterranean, and lead to revisions of existing age models, especially around MIS 11 and 19, when the 405-kyr eccentricity cycle is at a minimum. Color reflectance, typically indicative of sapropels, appears incongruent with insolation forcing during these episodes. Secondly our Ti/Al-based chronology provides an independent age model for the benthic d18O record, which may shed new light upon the relationship between insolation and global climate (e.g. ice volume) changes. Our research indicates negligible differences between our record and the global benthic stack of Lisiecki and Raymo (LR04) between the present and MIS 11. However, there are significant discrepancies in the timing of terminations and onset of glaciation for several isotope stages prior to MIS 11 of up to 10,000 years. The direct comparison of our stable isotope record to insolation appears to suggest a dominant role of obliquity forcing in ice volume behavior for much further into the Pleistocene than generally assumed. References Lourens, L.J., J. Becker, R. Bintanja et al. (2010), Linear and non-linear response of late Neogene glacial cycles to obliquity forcing and implications for the Milankovitch theory. Quaternary Science Reviews 29(1-2), pp.352-365. Ziegler, M., E. Tuenter & L.J. Lourens. (2010), The precession phase of the boreal summer monsoon as viewed from the eastern Mediterranean (ODP Site 968). Quaternary Science Reviews 29(11-12), pp.1481-1490.

Insolation-driven 100 kyr glacial cycles and millennial climate change

NASA Astrophysics Data System (ADS)

Abe-Ouchi, A.; Saito, F.; Kawamura, K.; Raymo, M. E.; Okuno, J.; Takahashi, K.; Blatter, H.

2013-12-01

The waxing and waning of Northern Hemisphere ice sheets over the past one million years is dominated by an approximately 100-kyr periodicity and a sawtooth pattern (gradual growth and fast termination). Milankovitch theory proposes that summer insolation at high northern latitudes drives the glacial cycles, and statistical tests demonstrated that the glacial cycles are indeed linked to eccentricity, obliquity and precession cycles. However, insolation alone cannot explain the strong 100 kyr cycle which presumably arises through internal climatic feedbacks. Prior work with conceptual models, for example, showed that glacial terminations are associated with the build-up of Northern Hemisphere 'excess ice', but the physical mechanisms of 100-kyr cycle at work remain unclear. Here, using comprehensive climate and ice sheet models, we show that the ~100-kyr periodicity is explained by insolation and internal feedback amongst the climate, ice sheet and lithosphere/asthenosphere system (reference). We found that equilibrium states of ice sheets exhibit hysteresis responses to summer insolation, and that the shape and position of the hysteresis loop play a key role in determining the periodicities of glacial cycles. The hysteresis loop of the North American ice sheet is such that, after its inception, the ice sheet mass balance remains mostly positive or neutral through several precession cycles whose amplitude decreases towards an eccentricity minimum. The larger the ice sheet grows and extends towards lower latitudes, the smaller is the insolation required to turn the mass balance to negative. Therefore, once the large ice sheet is established, only a moderate increase in insolation can trigger a negative mass balance, leading to a complete retreat within several thousand years, due to the delayed isostatic rebound. The effect of ocean circulation and millennial scale climate change are not playing the dominant role for determing the 100kyr cycle, but are effective for modifying the speed and geographical pattern of the waxing and waning of the Northern Hemisphere ice sheets and their melt water. (reference of the basic results: Abe-Ouchi et al, 2013, Insolation-driven 100,000 year glacial cycles and hysteresis of ice-sheet volume, Nature, 500, 190-193.)

Solar Radiation on Mars: Tracking Photovoltaic Array

NASA Technical Reports Server (NTRS)

Appelbaum, Joseph; Flood, Dennis J.; Crutchik, Marcos

1994-01-01

A photovoltaic power source for surface-based operation on Mars can offer many advantages. Detailed information on solar radiation characteristics on Mars and the insolation on various types of collector surfaces are necessary for effective design of future planned photovoltaic systems. In this article we have presented analytical expressions for solar radiation calculation and solar radiation data for single axis (of various types) and two axis tracking surfaces and compared the insulation to horizontal and inclined surfaces. For clear skies (low atmospheric dust load) tracking surfaces resulted in higher insolation than stationary surfaces, whereas for highly dusty atmospheres, the difference is small. The insolation on the different types of stationary and tracking surfaces depend on latitude, season and optical depth of the atmosphere, and the duration of system operation. These insolations have to be compared for each mission.

Biomechanics of stair walking and jumping.

PubMed

Loy, D J; Voloshin, A S

1991-01-01

Physical activities such as stair walking and jumping result in increased dynamic loading on the human musculoskeletal system. Use of light weight, externally attached accelerometers allows for in-vivo monitoring of the shock waves invading the human musculoskeletal system during those activities. Shock waves were measured in four subjects performing stair walking up and down, jumping in place and jumping off a fixed elevation. The results obtained show that walking down a staircase induced shock waves with amplitude of 130% of that observed in walking up stairs and 250% of the shock waves experienced in level gait. The jumping test revealed levels of the shock waves nearly eight times higher than that in level walking. It was also shown that the shock waves invading the human musculoskeletal system may be generated not only by the heel strike, but also by the metatarsal strike. To moderate the risk of degenerative joint disorders four types of viscoelastic insoles were utilized to reduce the impact generated shock waves. The insoles investigated were able to reduce the amplitude of the shock wave by between 9% and 41% depending on the insole type and particular physical activity. The insoles were more effective in the reduction of the heel strike impacts than in the reduction of the metatarsal strike impacts. In all instances, the shock attenuation capacities of the insoles tested were greater in the jumping trials than in the stair walking studies. The insoles were ranked in three groups on the basis of their shock absorbing capacity.

A Study of a Two Stage Maximum Power Point Tracking Control of a Photovoltaic System under Partially Shaded Insolation Conditions

NASA Astrophysics Data System (ADS)

Kobayashi, Kenji; Takano, Ichiro; Sawada, Yoshio

A photovoltaic array shows relatively low output power density, and has a greatly drooping Current-Voltage (I-V) characteristic. Therefore, Maximum Power Point Tracking (MPPT) control is used to maximize the output power of the array. Many papers have been reported in relation to MPPT. However, the Current-Power (I-P) curve sometimes shows multi-local maximum points mode under non-uniform insolation conditions. The operating point of the PV system tends to converge to a local maximum output point which is not the real maximal output point on the I-P curve. Some papers have been also reported, trying to avoid this difficulty. However most of those control systems become rather complicated. Then, the two stage MPPT control method is proposed in this paper to realize a relatively simple control system which can track the real maximum power point even under non-uniform insolation conditions. The feasibility of this control concept is confirmed for steady insolation as well as for rapidly changing insolation by simulation study using software PSIM and LabVIEW. In addition, simulated experiment confirms fundament al operation of the two stage MPPT control.

A proposed adaptive step size perturbation and observation maximum power point tracking algorithm based on photovoltaic system modeling

NASA Astrophysics Data System (ADS)

Huang, Yu

Solar energy becomes one of the major alternative renewable energy options for its huge abundance and accessibility. Due to the intermittent nature, the high demand of Maximum Power Point Tracking (MPPT) techniques exists when a Photovoltaic (PV) system is used to extract energy from the sunlight. This thesis proposed an advanced Perturbation and Observation (P&O) algorithm aiming for relatively practical circumstances. Firstly, a practical PV system model is studied with determining the series and shunt resistances which are neglected in some research. Moreover, in this proposed algorithm, the duty ratio of a boost DC-DC converter is the object of the perturbation deploying input impedance conversion to achieve working voltage adjustment. Based on the control strategy, the adaptive duty ratio step size P&O algorithm is proposed with major modifications made for sharp insolation change as well as low insolation scenarios. Matlab/Simulink simulation for PV model, boost converter control strategy and various MPPT process is conducted step by step. The proposed adaptive P&O algorithm is validated by the simulation results and detail analysis of sharp insolation changes, low insolation condition and continuous insolation variation.

Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis

PubMed Central

Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony

2011-01-01

In 1889, Dr. Stephen Paget proposed the “seed and soil” hypothesis, which states that cancer cells (the seeds) need the proper microenvironment (the soil) for them to grow, spread and metastasize systemically. In this hypothesis, Dr. Paget rightfully recognized that the tumor microenvironment has an important role to play in cancer progression and metastasis. In this regard, a series of recent studies have elegantly shown that the production of hydrogen peroxide, by both cancer cells and cancer-associated fibroblasts, may provide the necessary “fertilizer,” by driving accelerated aging, DNA damage, inflammation and cancer metabolism, in the tumor microenvironment. By secreting hydrogen peroxide, cancer cells and fibroblasts are mimicking the behavior of immune cells (macrophages/neutrophils), driving local and systemic inflammation, via the innate immune response (NFκB). Thus, we should consider using various therapeutic strategies (such as catalase and/or other antioxidants) to neutralize the production of cancer-associated hydrogen peroxide, thereby preventing tumor-stroma co-evolution and metastasis. The implications of these findings for overcoming chemo-resistance in cancer cells are also discussed in the context of hydrogen peroxide production and cancer metabolism. PMID:21734470

Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment.

PubMed

Guzman-Rojas, Liliana; Rangel, Roberto; Salameh, Ahmad; Edwards, Julianna K; Dondossola, Eleonora; Kim, Yun-Gon; Saghatelian, Alan; Giordano, Ricardo J; Kolonin, Mikhail G; Staquicini, Fernanda I; Koivunen, Erkki; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2012-01-31

Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APN-null mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.

Air content and O2/N2 tuned chronologies on local insolation signatures in the Vostok ice core are similar

NASA Astrophysics Data System (ADS)

Lipenkov, V.; Raynaud, D.; Loutre, M.-F.; Duval, P.; Lemieux-Dudon, B.

2009-04-01

An accurate chronology of ice cores is needed for interpreting the paleoclimatic record and understanding the relation between insolation and climate. A new domain of research in this area has been initially stimulated by the work of M. Bender (2002) linking the record of O2/N2 ratio in the air trapped in the Vostok ice with the local insolation. More recently, it has been proposed that the long-term changes in air content, V, recorded in ice from the high Antarctic plateau is also dominantly imprinted by the local summer insolation (Raynaud et al., 2007). The present paper presents a new V record from Vostok, which is compared with the published Vostok O2/N2 record for the same period of time (150-400 ka BP) by using the same spectral analysis methods. The spectral differences between the two properties and the possible mechanisms linking them with insolation through the surface snow structure and the close-off processes are discussed. The main result of our study is that the two experimentally independent local insolation proxies lead to absolute (orbital) time scales, which agree together within a standard deviation of 0.6 ka. This result strongly adds credibility to the air content of ice and the O2 to N2 ratio of the air trapped in ice as equally reliable and complementary tools for accurate dating of existing and future deep ice cores. References: M. Bender, Orbital tuning chronology for the Vostok climate record supported by trapped gas composition, Earth and Planetary Science Letters 204(2002) 275-289. D. Raynaud, V. Lipenkov, B. Lemieux-Dudon, P. Duval, M.F. Loutre, N. Lhomme, The local insolation signature of air content in Antarctic ice: a new step toward an absolute dating of ice records, Earth and Planetary Science Letters 261(2007) 337-349.

Reduced knee joint loading with lateral and medial wedge insoles for management of knee osteoarthritis: a protocol for a randomized controlled trial.

PubMed

Lewinson, Ryan T; Collins, Kelsey H; Vallerand, Isabelle A; Wiley, J Preston; Woodhouse, Linda J; Reimer, Raylene A; Worobets, Jay T; Herzog, Walter; Stefanyshyn, Darren J

2014-12-03

Knee osteoarthritis (OA) progression has been linked to increased peak external knee adduction moments (KAMs). Although some trials have attempted to reduce pain and improve function in OA by reducing KAMs with a wedged footwear insole intervention, KAM reduction has not been specifically controlled for in trial designs, potentially explaining the mixed results seen in the literature. Therefore, the primary purpose of this trial is to identify the effects of reduced KAMs on knee OA pain and function. Forty-six patients with radiographically confirmed diagnosis medial knee OA will be recruited for this 3 month randomized controlled trial. Recruitment will be from Alberta and surrounding areas. Eligibility criteria include being between the ages of 40 and 85 years, have knee OA primarily localized to the medial tibiofemoral compartment, based on the American College of Rheumatology diagnostic criteria and be classified as having a Kellgren-Lawrence grade of 1 to 3. Patients will visit the laboratory at baseline for testing that includes dual x-ray absorptiometry, biomechanical testing, and surveys (KOOS, PASE activity scale, UCLA activity scale, comfort visual analog scale). At baseline, patients will be randomized to either a wedged insole group to reduce KAMs, or a waitlist control group where no intervention is provided. The survey tests will be repeated at 3 months, and response to wedged insoles over 3 months will be evaluated. This study represents the first step in systematically evaluating the effects of reduced KAMs on knee OA management by using a patient-specific wedged insole prescription procedure rather than providing the same insole to all patients. The results of this trial will provide indications as to whether reduced KAMs are an effective strategy for knee OA management, and whether a personalized approach to footwear insole prescription is warranted. NCT02067208.

The timing of Mediterranean sapropel deposition relative to insolation, sea-level and African monsoon changes

NASA Astrophysics Data System (ADS)

Grant, Katharine; Grimm, Rosina; Mikolajewicz, Uwe; Marino, Gianluca; Rohling, Eelco

2016-04-01

The periodic deposition of organic rich layers or 'sapropels' in eastern Mediterranean sediments can be linked to orbital-driven changes in the strength and location of (east) African monsoon precipitation. Sapropels are therefore an extremely useful tool for establishing orbital chronologies, and for providing insights about African monsoon variability on long timescales. However, the link between sapropel formation, insolation variations, and African monsoon 'maxima' is not straightforward because other processes (notably, sea-level rise) may have contributed to their deposition, and because there are uncertainties about monsoon-sapropel phase relationships. For example, different phasings are observed between Holocene and early Pleistocene sapropels, and between proxy records and model simulations. To address these issues, we have established geochemical and ice-volume-corrected planktonic foraminiferal stable isotope records for sapropels S1, S3, S4, and S5 in core LC21 from the southern Aegean Sea. The records have a radiometrically constrained chronology that has already been synchronised with the Red Sea relative sea-level record, and this allows us to examine in detail the timing of sapropel deposition relative to insolation, sea-level, and African monsoon changes. Our records suggest that the onset of sapropel deposition and monsoon run-off was near synchronous, yet insolation-sapropel/monsoon phasings varied, whereby monsoon/sapropel onset was relatively delayed (with respect to insolation maxima) after glacial terminations. We suggest that large meltwater discharges into the North Atlantic modified the timing of sapropel deposition by delaying the timing of peak African monsoon run-off. Hence, the previous assumption of a systematic 3-kyr lag between insolation maxima and sapropel midpoints may lead to overestimated insolation-sapropel phasings. We also surmise that both monsoon run-off and sea-level rise were important buoyancy-forcing mechanisms for the studied sapropels, and their relative influences differed per sapropel case. For instance, sea-level rise was clearly important for sapropel S1, whereas monsoon forcing was likely more important for sapropel S5.

Insolation-driven 100,000-year glacial cycles and hysteresis of ice-sheet volume.

PubMed

Abe-Ouchi, Ayako; Saito, Fuyuki; Kawamura, Kenji; Raymo, Maureen E; Okuno, Jun'ichi; Takahashi, Kunio; Blatter, Heinz

2013-08-08

The growth and reduction of Northern Hemisphere ice sheets over the past million years is dominated by an approximately 100,000-year periodicity and a sawtooth pattern (gradual growth and fast termination). Milankovitch theory proposes that summer insolation at high northern latitudes drives the glacial cycles, and statistical tests have demonstrated that the glacial cycles are indeed linked to eccentricity, obliquity and precession cycles. Yet insolation alone cannot explain the strong 100,000-year cycle, suggesting that internal climatic feedbacks may also be at work. Earlier conceptual models, for example, showed that glacial terminations are associated with the build-up of Northern Hemisphere 'excess ice', but the physical mechanisms underpinning the 100,000-year cycle remain unclear. Here we show, using comprehensive climate and ice-sheet models, that insolation and internal feedbacks between the climate, the ice sheets and the lithosphere-asthenosphere system explain the 100,000-year periodicity. The responses of equilibrium states of ice sheets to summer insolation show hysteresis, with the shape and position of the hysteresis loop playing a key part in determining the periodicities of glacial cycles. The hysteresis loop of the North American ice sheet is such that after inception of the ice sheet, its mass balance remains mostly positive through several precession cycles, whose amplitudes decrease towards an eccentricity minimum. The larger the ice sheet grows and extends towards lower latitudes, the smaller is the insolation required to make the mass balance negative. Therefore, once a large ice sheet is established, a moderate increase in insolation is sufficient to trigger a negative mass balance, leading to an almost complete retreat of the ice sheet within several thousand years. This fast retreat is governed mainly by rapid ablation due to the lowered surface elevation resulting from delayed isostatic rebound, which is the lithosphere-asthenosphere response. Carbon dioxide is involved, but is not determinative, in the evolution of the 100,000-year glacial cycles.

Measurement of pressure walking in footwear used in leprosy.

PubMed

Birke, J A; Foto, J G; Deepak, S; Watson, J

1994-09-01

Pressure measurements were made on 10 leprosy patients while walking barefoot and while using 6 sample shoes. The sample shoes, which represented footwear currently used worldwide in leprosy programmes, included: 1, a USA extradepth shoe without insole; 2, a USA extradepth shoe with insole; 3, a Chinese tennis shoe; 4, a Mozambique sandal; 5, a Bombay sandal; 6, a Bombay sandal with rigid sole; and 7, the patients' prescribed footwear. Peak pressure was significantly lower while walking in all footwear, except with the extradepth shoe without an insole, when compared to barefoot walking. Peak pressure was significantly lower walking in the Bombay sandals, the Chinese tennis shoe, the extradepth shoe with an insert and the patients' prescribed shoe when compared to the extradepth shoe without an insert. Regression analysis showed a significant inverse relationship between pressure and insole thickness (P < 0.001, R2 = 0.17).

Urban air pollution and solar energy

NASA Technical Reports Server (NTRS)

Gammon, R. B.; Huning, J. R.; Reid, M. S.; Smith, J. H.

1981-01-01

The design and performance of solar energy systems for many potential applications (industrial/residential heat, electricity generation by solar concentration and photovoltaics) will be critically affected by local insolation conditions. The effects of urban air pollution are considered and reviewed. A study of insolation data for Alhambra, California (9 km south of Pasadena) shows that, during a recent second-stage photochemical smog alert (greater than or equal to 0.35 ppm ozone), the direct-beam insolation at solar noon was reduced by 40%, and the total global by 15%, from clean air values. Similar effects have been observed in Pasadena, and are attributable primarily to air pollution. Effects due to advecting smog have been detected 200 km away, in the Mojave Desert. Preliminary performance and economic simulations of solar thermal and photovoltaic power systems indicate increasing nonlinear sensitivity of life cycle plant cost to reductions in insolation levels due to pollution.

Impact of sunlight on the age of onset of bipolar disorder

PubMed Central

Bauer, Michael; Glenn, Tasha; Alda, Martin; Andreassen, Ole A; Ardau, Raffaella; Bellivier, Frank; Berk, Michael; Bjella, Thomas D; Bossini, Letizia; Zompo, Maria Del; Dodd, Seetal; Fagiolini, Andrea; Frye, Mark A; Gonzalez-Pinto, Ana; Henry, Chantal; Kapczinski, Flávio; Kliwicki, Sebastian; König, Barbara; Kunz, Mauricio; Lafer, Beny; Lopez-Jaramillo, Carlos; Manchia, Mirko; Marsh, Wendy; Martinez-Cengotitabengoa, Mónica; Melle, Ingrid; Morken, Gunnar; Munoz, Rodrigo; Nery, Fabiano G; O’Donovan, Claire; Pfennig, Andrea; Quiroz, Danilo; Rasgon, Natalie; Reif, Andreas; Rybakowski, Janusz; Sagduyu, Kemal; Simhandl, Christian; Torrent, Carla; Vieta, Eduard; Zetin, Mark; Whybrow, Peter C

2012-01-01

Objective Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= −4.724, 95% CI: −8.124 to −1.323, p = 0.006), controlling for each country’s median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder. PMID:22612720

Evidence for insolation and Pacific forcing of late glacial through Holocene climate in the Central Mojave Desert (Silver Lake, CA)

NASA Astrophysics Data System (ADS)

Kirby, Matthew E.; Knell, Edward J.; Anderson, William T.; Lachniet, Matthew S.; Palermo, Jennifer; Eeg, Holly; Lucero, Ricardo; Murrieta, Rosa; Arevalo, Andrea; Silveira, Emily; Hiner, Christine A.

2015-09-01

Silver Lake is the modern terminal playa of the Mojave River in southern California (USA). As a result, it is well located to record both influences from the winter precipitation dominated San Bernardino Mountains - the source of the Mojave River - and from the late summer to early fall North American monsoon at Silver Lake. Here, we present various physical, chemical and biological data from a new radiocarbon-dated, 8.2 m sediment core taken from Silver Lake that spans modern through 14.8 cal ka BP. Texturally, the core varies between sandy clay, clayey sand, and sand-silt-clay, often with abrupt sedimentological transitions. These grain-size changes are used to divide the core into six lake status intervals over the past 14.8 cal ka BP. Notable intervals include a dry Younger Dryas chronozone, a wet early Holocene terminating 7.8 - 7.4 cal ka BP, a distinct mid-Holocene arid interval, and a late Holocene return to ephemeral lake conditions. A comparison to potential climatic forcings implicates a combination of changing summer - winter insolation and tropical and N Pacific sea-surface temperature dynamics as the primary drivers of Holocene climate in the central Mojave Desert.

Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a "Watch-and-Wait" Approach to Cancer.

PubMed

Li, Shengwen Calvin; Vu, Long T; Luo, Jane Jianying; Zhong, Jiang F; Li, Zhongjun; Dethlefs, Brent A; Loudon, William G; Kabeer, Mustafa H

2017-01-01

Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific manner. Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a "watchand- wait" approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology - a balance that needs to be maintained for the "watch-and-wait" approach to cancer. This review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a “Watch-and-Wait” Approach to Cancer

PubMed Central

Li, Shengwen Calvin; Vu, Long T.; Luo, Jane Jianying; Zhong, Jiang F.; Li, Zhongjun; Dethlefs, Brent A; Loudon, William G.; Kabeer, Mustafa H.

2017-01-01

Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open up new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME-driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cell-specific manner. Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a “watch-and-wait” approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology – a balance that needs to be maintained for the “watch-and-wait” approach to cancer. Thus, this review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application. PMID:28270089

The effects of prolonged wear of textured shoe insoles on gait, foot sensation and proprioception in people with multiple sclerosis: study protocol for a randomised controlled trial.

PubMed

Hatton, Anna L; Dixon, John; Rome, Keith; Brauer, Sandra G; Williams, Katrina; Kerr, Graham

2016-04-21

Many people with multiple sclerosis experience problems with walking, which can make daily activities difficult and often leads to falls. Foot sensation plays an important role in keeping the body balanced whilst walking; however, people with multiple sclerosis often have poor sensation on the soles of their feet. Wearing a specially designed shoe insole, which enhances plantar sensory information, could help people with multiple sclerosis to walk better. This study will explore whether long-term wear of a textured insole can improve walking in people with multiple sclerosis. A prospective randomised controlled trial with two parallel groups will be conducted aiming to recruit 176 people with multiple sclerosis living in the community (Brisbane, Australia). Adults with a clinical diagnosis of multiple sclerosis, Disease Steps score 1-4, who are ambulant over 100 m and who meet specific inclusion criteria will be recruited. Participants will be randomised to a smooth control insole (n = 88) or textured insole (n = 88) group. The allocated insole will be worn for 12-weeks within participants' own footwear, with self-report wear diaries and falls calendars being completed over this period. Blinded assessors will conduct two baseline assessments and one post-intervention assessment. Gait tasks will be completed barefoot, wearing standardised footwear only, and wearing standardised footwear with smooth and textured insoles. The primary outcome measure will be mediolateral base of support when walking over even and uneven surfaces. Secondary measures include spatiotemporal gait parameters (stride length, stride time variability, double-limb support time, velocity), gait kinematics (hip, knee, and ankle joint angles, toe clearance, trunk inclination, arm swing, mediolateral pelvis/head displacement), foot sensation (light touch-pressure, vibration, two-point discrimination) and proprioception (ankle joint position sense). Group allocation will be concealed and all analyses will be based on an intention-to-treat principle. This study will explore the effects of wearing textured insoles over 12-weeks on gait, foot sensation and proprioception in people with multiple sclerosis. The study has the potential to identify a new, evidence-based footwear intervention which has the capacity to enhance mobility and independent living in people with multiple sclerosis. Australian New Zealand Clinical Trials Registry ACTRN12615000421538 . Registered 4 May 2015.

Solar insolation in springtime influences age of onset of bipolar I disorder.

PubMed

Bauer, M; Glenn, T; Alda, M; Aleksandrovich, M A; Andreassen, O A; Angelopoulos, E; Ardau, R; Ayhan, Y; Baethge, C; Bharathram, S R; Bauer, R; Baune, B T; Becerra-Palars, C; Bellivier, F; Belmaker, R H; Berk, M; Bersudsky, Y; Bicakci, Ş; Birabwa-Oketcho, H; Bjella, T D; Bossini, L; Cabrera, J; Cheung, E Y W; Del Zompo, M; Dodd, S; Donix, M; Etain, B; Fagiolini, A; Fountoulakis, K N; Frye, M A; Gonzalez-Pinto, A; Gottlieb, J F; Grof, P; Harima, H; Henry, C; Isometsä, E T; Janno, S; Kapczinski, F; Kardell, M; Khaldi, S; Kliwicki, S; König, B; Kot, T L; Krogh, R; Kunz, M; Lafer, B; Landén, M; Larsen, E R; Lewitzka, U; Licht, R W; Lopez-Jaramillo, C; MacQueen, G; Manchia, M; Marsh, W; Martinez-Cengotitabengoa, M; Melle, I; Meza-Urzúa, F; Yee Ming, M; Monteith, S; Morken, G; Mosca, E; Munoz, R; Mythri, S V; Nacef, F; Nadella, R K; Nery, F G; Nielsen, R E; O'Donovan, C; Omrani, A; Osher, Y; Østermark Sørensen, H; Ouali, U; Pica Ruiz, Y; Pilhatsch, M; Pinna, M; da Ponte, F D R; Quiroz, D; Ramesar, R; Rasgon, N; Reddy, M S; Reif, A; Ritter, P; Rybakowski, J K; Sagduyu, K; Scippa, Â M; Severus, E; Simhandl, C; Stein, D J; Strejilevich, S; Subramaniam, M; Sulaiman, A H; Suominen, K; Tagata, H; Tatebayashi, Y; Tondo, L; Torrent, C; Vaaler, A E; Veeh, J; Vieta, E; Viswanath, B; Yoldi-Negrete, M; Zetin, M; Zgueb, Y; Whybrow, P C

2017-12-01

To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of proprioceptive insoles on spinal curvature in patients with slight idiopathic scoliosis.

PubMed

Noll, Christine; Steitz, Vanessa; Daentzer, Dorothea

2017-01-01

Proprioceptive insoles are known to influence the functions of posture and gait by modulations of the sensory structures at the sole of the foot. Literature has shown that they could improve the position of the upper-body in patients with postural complaints of the musculoskeletal system. The aim of this study was to evaluate the influence of proprioceptive insoles on the spinal curvature in patients with slight idiopathic scoliosis. Eighteen patients were included in this prospective, single-centre, randomized study. All patients needed to have a relevant growth potential and suffered from a slight idiopathic scoliosis. Two groups were used, where group 1 performed physiotherapy twice a week, whereas group 2 was additionally supplied with proprioceptive insoles. Patients underwent three-dimensional rasterstereography for back-shape analysis. Furthermore, a conventional x-ray imaging of the spine was performed at the beginning and 1 year later to document the curvatures. There was no statistical difference in the Cobb angles, and in almost all parameters of the rasterstereography, there was no statistically significant change between and within both groups. According to the results of this study, there was no evidence of any statistical significant effect of proprioceptive insoles on spinal curvature in patients with slight idiopathic scoliosis.

Shoe-Insole Technology for Injury Prevention in Walking

PubMed Central

Nagano, Hanatsu

2018-01-01

Impaired walking increases injury risk during locomotion, including falls-related acute injuries and overuse damage to lower limb joints. Gait impairments seriously restrict voluntary, habitual engagement in injury prevention activities, such as recreational walking and exercise. There is, therefore, an urgent need for technology-based interventions for gait disorders that are cost effective, willingly taken-up, and provide immediate positive effects on walking. Gait control using shoe-insoles has potential as an effective population-based intervention, and new sensor technologies will enhance the effectiveness of these devices. Shoe-insole modifications include: (i) ankle joint support for falls prevention; (ii) shock absorption by utilising lower-resilience materials at the heel; (iii) improving reaction speed by stimulating cutaneous receptors; and (iv) preserving dynamic balance via foot centre of pressure control. Using sensor technology, such as in-shoe pressure measurement and motion capture systems, gait can be precisely monitored, allowing us to visualise how shoe-insoles change walking patterns. In addition, in-shoe systems, such as pressure monitoring and inertial sensors, can be incorporated into the insole to monitor gait in real-time. Inertial sensors coupled with in-shoe foot pressure sensors and global positioning systems (GPS) could be used to monitor spatiotemporal parameters in real-time. Real-time, online data management will enable ‘big-data’ applications to everyday gait control characteristics. PMID:29738486

Shock-absorbing insoles reduce the incidence of lower limb overuse injuries sustained during Royal Marine training.

PubMed

House, Carol; Reece, Allyson; Roiz de Sa, Dan

2013-06-01

This study was undertaken to determine whether the incidence of lower limb overuse injuries (LLOIs) sustained during Royal Marine training could be reduced by issuing the recruits with shock-absorbing insoles (SAIs) to wear in their military boots. This was a retrospective longitudinal trial conducted in two phases. Injury data from 1,416 recruits issued with standard Saran insoles and 1,338 recruits issued with SAI were compared. The recruits in the two groups were of similar height, body mass, and aerobic fitness and followed the same training course. The incidence of LLOI sustained by the recruits was lower (p < 0.05) in the SAI Group (19.0%) compared to the Saran Insole Group (31.7%). The incidences of lower limb stress fractures, tibial periostitis, tenosynovitis of foot, achilles tendonopathy, other tendonopathy and anterior knee pain were lower (p < 0.05) in the SAI Group. Tibial stress fracture incidence was lower (p < 0.05) in the SAI Group but metatarsal and femoral stress fracture incidences were the same for the two insole groups. Thus, issuing SAIs to military recruits undertaking a sustained, arduous physical training program with a high incidence of LLOI would provide a beneficial reduction in the incidence of LLOI. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

How to Make Eccentricity Cycles in Stratigraphy: the Role of Compaction

NASA Astrophysics Data System (ADS)

Liu, W.; Hinnov, L.; Wu, H.; Pas, D.

2017-12-01

Milankovitch cycles from astronomically driven climate variations have been demonstrated as preserved in cyclostratigraphy throughout geologic time. These stratigraphic cycles have been identified in many types of proxies, e.g., gamma ray, magnetic susceptibility, oxygen isotopes, carbonate content, grayscale, etc. However, the commonly prominent spectral power of orbital eccentricity cycles in stratigraphy is paradoxical to insolation, which is dominated by precession index power. How is the spectral power transferred from precession to eccentricity in stratigraphy? Nonlinear sedimentation and bioturbation have long been identified as players in this transference. Here, we propose that in the absence of bioturbation differential compaction can generate the transference. Using insolation time series, we trace the steps by which insolation is transformed into stratigraphy, and how differential compaction of lithology acts to transfer spectral power from precession to eccentricity. Differential compaction is applied to unique values of insolation, which is assumed to control the type of deposited sediment. High compaction is applied to muds, and progressively lower compaction is applied to silts and sands, or carbonate. Linear differential compaction promotes eccentricity spectral power, but nonlinear differential compaction elevates eccentricity spectral power to dominance and precession spectral power to near collapse as is often observed in real stratigraphy. Keywords: differential compaction, cyclostratigraphy, insolation, eccentricity

Replicating the Ice-Volume Signal of the Early Pleistocene with a Complex Earth System Model

NASA Astrophysics Data System (ADS)

Tabor, C. R.; Poulsen, C. J.; Pollard, D.

2013-12-01

Milankovitch theory proposes high-latitude summer insolation intensity paces the ice ages by controlling perennial snow cover amounts (Milankovitch, 1941). According to theory, the ~21 kyr cycle of precession should dominate the ice-volume records since it has the greatest influence on high-latitude summer insolation. Modeling experiments frequently support Milankovitch theory by attributing the majority of Northern Hemisphere high-latitude summer snowmelt to changes in the cycle of precession (e.g. Jackson and Broccoli, 2003). However, ice-volume proxy records, especially those of the Early Pleistocene (2.6-0.8 Ma), display variability with a period of ~41 kyr (Raymo and Lisiecki, 2005), indicative of insolation forcing from obliquity, which has a much smaller influence on summer insolation intensity than precession. Several hypotheses attempt to explain the discrepancies between Milkankovitch theory and the proxy records by invoking phenomena such as insolation gradients (Raymo and Nisancioglu, 2003), hemispheric offset (Raymo et al., 2006; Lee and Poulsen, 2009), and integrated summer energy (Huybers, 2006); however, all of these hypotheses contain caveats (Ruddiman, 2006) and have yet to be supported by modeling studies that use a complex GCM. To explore potential solutions to this '41 kyr problem,' we use an Earth system model composed of the GENESIS GCM and Land Surface model, the BIOME4 vegetation model, and the Pennsylvania State ice-sheet model. Using an asynchronous coupling technique, we run four idealized transient combinations of obliquity and precession, representing the orbital extremes of the Pleistocene (Berger and Loutre, 1991). Each experiment is run through several complete orbital cycles with a dynamic ice domain spanning North America and Greenland, and fixed preindustrial greenhouse-gas concentrations. For all orbital configurations, model results produce greater ice-volume spectral power at the frequency of obliquity despite significantly greater summer insolation variability from the cycle of precession. We find obliquity enhances the climate sensitivity to direct insolation forcing through positive high-latitude surface feedbacks between vegetation, sea-ice, and mean-annual insolation while the seasonal dichotomy of precessional forcing leads to climate counterbalancing that dampens the annual ice-volume response. Longer cycle duration further amplifies the ice-volume response to obliquity. Our results help remedy the discrepancies between Milankovitch theory and the ice-volume proxy records. However, summer insolation intensity remains the most important factor for determining ice-volume rate-of-change in our experiments. Consequently, we still find a significant ice-volume response to precession, which is inconsistent with the Early Pleistocene records. The disconnect is likely attributable to climate phenomena not accounted for in the model or our choice of initial conditions, which are poorly constrained for the Early Pleistocene and ice-sheet modeling in general. Future work will examine the importance of initial climate conditions on ice-volume response.

Biological and Clinical Implications of Clonal Heterogeneity and Clonal Evolution in Multiple Myeloma.

PubMed

Bianchi, Giada; Ghobrial, Irene M

Clonal heterogeneity and clonal evolution have emerged as critical concepts in the field of oncology over the past four decades, largely thanks to the implementation of novel technologies such as comparative genomic hybridization, whole genome/exome sequencing and epigenetic analysis. Along with the identification of cancer stem cells in the majority of neoplasia, the recognition of intertumor and intratumor variability has provided a novel perspective to understand the mechanisms behind tumor evolution and its implication in terms of treatment failure and cancer relapse or recurrence. First hypothesized over two decades ago, clonal heterogeneity and clonal evolution have been confirmed in multiple myeloma (MM), an incurable cancer of plasma cells, almost universally preceded by a pre-malignant conditioned named monoclonal gammopathy of undetermined significance (MGUS). The genetic events and molecular mechanisms underlying such evolution have been difficult to dissect. Moreover, while a role for the bone marrow microenvironment in supporting MM cell survival, proliferation and drug-resistance has been well established, whether it is directly involved in driving evolution from MGUS to MM is at present unclear. We present in this review a historical excursus on the concepts of clonal heterogeneity and clonal evolution in MM with a special emphasis on their role in the progression from MGUS to MM; the contribution of the microenvironment; and the clinical implications in terms of resistance to treatment and disease relapse/recurrence.

Biological and Clinical Implications of Clonal Heterogeneity and Clonal Evolution in Multiple Myeloma

PubMed Central

Bianchi, Giada; Ghobrial, Irene M.

2015-01-01

Clonal heterogeneity and clonal evolution have emerged as critical concepts in the field of oncology over the past four decades, largely thanks to the implementation of novel technologies such as comparative genomic hybridization, whole genome/exome sequencing and epigenetic analysis. Along with the identification of cancer stem cells in the majority of neoplasia, the recognition of intertumor and intratumor variability has provided a novel perspective to understand the mechanisms behind tumor evolution and its implication in terms of treatment failure and cancer relapse or recurrence. First hypothesized over two decades ago, clonal heterogeneity and clonal evolution have been confirmed in multiple myeloma (MM), an incurable cancer of plasma cells, almost universally preceded by a pre-malignant conditioned named monoclonal gammopathy of undetermined significance (MGUS). The genetic events and molecular mechanisms underlying such evolution have been difficult to dissect. Moreover, while a role for the bone marrow microenvironment in supporting MM cell survival, proliferation and drug-resistance has been well established, whether it is directly involved in driving evolution from MGUS to MM is at present unclear. We present in this review a historical excursus on the concepts of clonal heterogeneity and clonal evolution in MM with a special emphasis on their role in the progression from MGUS to MM; the contribution of the microenvironment; and the clinical implications in terms of resistance to treatment and disease relapse/recurrence. PMID:25705146

Ozone changes under solar geoengineering: implications for UV exposure and air quality

NASA Astrophysics Data System (ADS)

Nowack, P. J.; Abraham, N. L.; Braesicke, P.; Pyle, J. A.

2015-11-01

Various forms of geoengineering have been proposed to counter anthropogenic climate change. Methods which aim to modify the Earth's energy balance by reducing insolation are often subsumed under the term Solar Radiation Management (SRM). Here, we present results of a standard SRM modelling experiment in which the incoming solar irradiance is reduced to offset the global mean warming induced by a quadrupling of atmospheric carbon dioxide. For the first time in an atmosphere-ocean coupled climate model, we include atmospheric composition feedbacks such as ozone changes under this scenario. Including the composition changes, we find large reductions in surface UV-B irradiance, with implications for vitamin D production, and increases in surface ozone concentrations, both of which could be important for human health. We highlight that both tropospheric and stratospheric ozone changes should be considered in the assessment of any SRM scheme, due to their important roles in regulating UV exposure and air quality.

In the hot seat : Insolation and ENSO controls on vegetation productivity in tropical Africa inferred from NDVI

NASA Astrophysics Data System (ADS)

Ivory, S.; Russell, J. L.; Cohen, A. S.

2010-12-01

Threats to tropical biodiversity with serious and costly implications for both ecosystems and human well-being in Africa have led the IPCC to classify this region as vulnerable to negative impacts from climate change. Yet little is known about how vegetation communities respond to altered patterns of rainfall and evaporation. Paleoclimate records within the tropics can help answer questions about how vegetation response to climate forcing changes over time. However, sparse spatial extent of records and uncertainty surrounding the climate-vegetation relationship complicate these insights. Understanding the climatic mechanisms involved in landscape change at all temporal scales creates the need for quantitative constraints of the modern relationship between climatic controls, hydrology, and vegetation. Though modern observational data can help elucidate this relationship, low resolution and complicated rainfall/vegetation associations make them less than ideal. Satellite data of vegetation productivity (NDVI) with continuous high-resolution spatial coverage provides a robust and elegant tool for identifying the link between global and regional controls and vegetation. We use regression analyses of variables either previously proposed or potentially important in regulating Afro-tropical vegetation (insolation, out-going long-wave radiation, geopotential height, Southern Oscillation Index, Indian Ocean Dipole, Indian Monsoon precipitation, sea-level pressure, surface wind, sea-surface temperature) on continuous, time-varying spatial fields of 8km NDVI for sub-Saharan Africa. These analyses show the importance of global atmospheric controls in producing regional intra-annual and inter-annual vegetation variability. Dipole patterns emerge primarily correlated with both the seasonal and inter-annual extent of the Intertropical Convergence Zone (ITCZ). Inter-annual ITCZ variability drives patterns in African vegetation resulting from the effect of insolation anomalies and ENSO events on atmospheric circulation rather than sea surface temperatures or teleconnections to mid/high latitudes. Global controls on tropical atmospheric circulation regulate vegetation throughout sub-Saharan Africa on many time scales through alteration of dry season length and moisture convergence, rather than precipitation amount.

Textured insoles reduce vertical loading rate and increase subjective plantar sensation in overground running.

PubMed

Wilkinson, Michael; Ewen, Alistair; Caplan, Nicholas; O'leary, David; Smith, Neil; Stoneham, Richard; Saxby, Lee

2018-05-01

The effect of textured insoles on kinetics and kinematics of overground running was assessed. 16 male injury-free-recreational runners attended a single visit (age 23 ± 5 yrs; stature 1.78 ± 0.06 m; mass 72.6 ± 9.2 kg). Overground 15-m runs were completed in flat, canvas plimsolls both with and without textured insoles at self-selected velocity on an indoor track in an order that was balanced among participants. Average vertical loading rate and peak vertical force (F peak ) were captured by force platforms. Video footage was digitised for sagittal plane hip, knee and ankle angles at foot strike and mid stance. Velocity, stride rate and length and contact and flight time were determined. Subjectively rated plantar sensation was recorded by visual scale. 95% confidence intervals estimated mean differences. Smallest worthwhile change in loading rate was defined as standardised reduction of 0.54 from a previous comparison of injured versus non-injured runners. Loading rate decreased (-25 to -9.3 BW s -1 ; 60% likely beneficial reduction) and plantar sensation was increased (46-58 mm) with the insole. F peak (-0.1 to 0.14 BW) and velocity (-0.02 to 0.06 m s -1 ) were similar. Stride length, flight and contact time were lower (-0.13 to -0.01 m; -0.02 to-0.01 s; -0.016 to -0.006 s) and stride rate was higher (0.01-0.07 steps s -1 ) with insoles. Textured insoles elicited an acute, meaningful decrease in vertical loading rate in short distance, overground running and were associated with subjectively increased plantar sensation. Reduced vertical loading rate could be explained by altered stride characteristics.

Prevention of lower extremity stress fractures: a controlled trial of a shock absorbent insole.

PubMed Central

Gardner, L I; Dziados, J E; Jones, B H; Brundage, J F; Harris, J M; Sullivan, R; Gill, P

1988-01-01

A prospective controlled trial was carried out to determine the usefulness of a viscoelastic polymer insole in prevention of stress fractures and stress reactions of the lower extremities. The subjects were 3,025 US Marine recruits who were followed for 12 weeks of training at Parris Island, South Carolina. Polymer and standard mesh insoles were systematically distributed in boots that were issued to members of odd and even numbered platoons. The most important finding was that an elastic polymer insole with good shock absorbency properties did not prevent stress reactions of bone during a 12-week period of vigorous physical training. To control for the confounding effects of running in running shoes, which occurred for about one and one-half hours per week for the first five weeks, we also examined the association of age of shoes and cost of shoes with injury incidence. A slight trend of increasing stress injuries by increasing age of shoes was observed. However, this trend did not account for the similarity of rates in the two insole groups. In addition, we observed a strong trend of decreasing stress injury rate by history of increasing physical activity, as well as a higher stress injury rate in White compared to Black recruits. The results of the trial were not altered after controlling for these factors. This prospective study confirms previous clinical reports of the association of stress fractures with physical activity history. The clinical application of a shock absorbing insole as a preventive for lower extremity stress reactions is not supported in these uniformly trained recruits. The findings are relevant to civilian populations. PMID:3056045

Quantifying stair gait stability in young and older adults, with modifications to insole hardness.

PubMed

Antonio, Patrick J; Perry, Stephen D

2014-07-01

Stair gait falls are prevalent in older adults aged 65 years and older. Extrinsic variables such as changes to insole hardness are important factors that can compromise the balance control system and increase the incidence of falls, especially since age-related decline in the cutaneous sensation is common. Balance measurements such as the minimum center of mass/base of support (COM-BOS, termed 'stability margin') and COM-BOS medial/lateral range provide information about stability during stair gait. This study was conducted to investigate stair gait stability of young and older adults, with modifications to insole hardness. Twenty healthy adults (10 young adults, 10 older adults) were recruited (mean age = 23.1, SD 2.1; mean age = 73.2, SD 5.5) and instructed to descend a 4 step staircase, for a total of 40 trials. All participants wore similar canvas shoes of varying sizes, and corresponding insole hardnesses (barefoot, soft, medium, hard). Kinematic equipment utilized 12 infrared markers anteriorly placed on the individual to record COM motion and BOS location. The findings from the study demonstrated that older adults were less stable during stair descent. Consequently, insole conditions revealed that the barefoot condition may increase the likelihood of falls, as opposed to the other insole hardnesses (soft, medium and hard). These results suggest that older adults while barefoot are putting themselves at a great risk of falling during stair descent. Since age-related changes are inevitable and the preferred footwear of choice inside the home is bare feet, this is a crucial issue that should be addressed. Copyright © 2014 Elsevier B.V. All rights reserved.

Reduced knee adduction moments for management of knee osteoarthritis:: A three month phase I/II randomized controlled trial.

PubMed

Lewinson, Ryan T; Vallerand, Isabelle A; Collins, Kelsey H; Wiley, J Preston; Lun, Victor M Y; Patel, Chirag; Woodhouse, Linda J; Reimer, Raylene A; Worobets, Jay T; Herzog, Walter; Stefanyshyn, Darren J

2016-10-01

Wedged insoles are believed to be of clinical benefit to individuals with knee osteoarthritis by reducing the knee adduction moment (KAM) during gait. However, previous clinical trials have not specifically controlled for KAM reduction at baseline, thus it is unknown if reduced KAMs actually confer a clinical benefit. Forty-eight participants with medial knee osteoarthritis were randomly assigned to either a control group where no footwear intervention was given, or a wedged insole group where KAM reduction was confirmed at baseline. KAMs, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Physical Activity Scale for the Elderly (PASE) scores were measured at baseline. KOOS and PASE surveys were re-administered at three months follow-up. The wedged insole group did not experience a statistically significant or clinically meaningful change in KOOS pain over three months (p=0.173). Furthermore, there was no association between change in KAM magnitude and change in KOOS pain over three months within the wedged insole group (R 2 =0.02, p=0.595). Improvement in KOOS pain for the wedged insole group was associated with worse baseline pain, and a change in PASE score over the three month study (R 2 =0.57, p=0.007). As an exploratory comparison, there was no significant difference in change in KOOS pain (p=0.49) between the insole and control group over three months. These results suggest that reduced KAMs do not appear to provide any clinical benefit compared to no intervention over a follow-up period of three months. ClinicalTrials.gov ID Number: NCT02067208. Copyright © 2016 Elsevier B.V. All rights reserved.

10 CFR 71.71 - Normal conditions of transport.

Code of Federal Regulations, 2014 CFR

2014-01-01

... NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Package... each package design under normal conditions of transport must include a determination of the effect on... following table: Insolation Data Form and location of surface Total insolation for a 12-hour period(g cal...

10 CFR 71.71 - Normal conditions of transport.

Code of Federal Regulations, 2012 CFR

2012-01-01

... NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Package... each package design under normal conditions of transport must include a determination of the effect on... following table: Insolation Data Form and location of surface Total insolation for a 12-hour period(g cal...

10 CFR 71.71 - Normal conditions of transport.

Code of Federal Regulations, 2011 CFR

2011-01-01

... NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Package... each package design under normal conditions of transport must include a determination of the effect on... following table: Insolation Data Form and location of surface Total insolation for a 12-hour period(g cal...

10 CFR 71.71 - Normal conditions of transport.

Code of Federal Regulations, 2010 CFR

2010-01-01

... NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Package... each package design under normal conditions of transport must include a determination of the effect on... following table: Insolation Data Form and location of surface Total insolation for a 12-hour period(g cal...

10 CFR 71.71 - Normal conditions of transport.

Code of Federal Regulations, 2013 CFR

2013-01-01

... NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Package... each package design under normal conditions of transport must include a determination of the effect on... following table: Insolation Data Form and location of surface Total insolation for a 12-hour period(g cal...

Observational Evidence of Changes in Water Vapor, Clouds, and Radiation at the ARM SGP Site

NASA Technical Reports Server (NTRS)

Dong, Xiquan; Xi, Baike; Minnis, Patrick

2006-01-01

Characterizing water vapor and cloud effects on the surface radiation budget is critical for understanding the current climate because water vapor is the most important greenhouse gas in the atmosphere and clouds are one of the largest sources of uncertainty in predicting potential future climate change. Several studies have shown that insolation over land declined until 1990 then increased until the present. Using 8 years of data collected at the ARM Southern Great Plains (SGP) surface site, we found that the insolation increased from 1997 to 2000, but significantly decreased from 2001 to 2004, changes that exactly mirror the variation in the second-order fit of cloud fraction. Under clear-sky conditions, the rates of water vapor, insolation and downwelling longwave (LW) flux are -0.166 cm/yr, 0.48 Wm(exp -2)/yr, and -1.16 Wm(exp -2)/yr, respectively, indicating that water vapor changes are more important for LW flux than for insolation.

A preliminary objective evaluation of leprosy footwear using in-shoe pressure measurement.

PubMed

Linge, K

1996-01-01

The primary function of leprosy shoes, insoles and podiatric orthoses is to provide an underfoot environment capable of distributing the inevitable vertical forces, so reducing areas of peak pressure and ideally the period through which they are applied. Many patients with Hansen's disease have both skeletal deformity and anesthetised feet and the presence of high plantar pressures is the key reason for foot ulceration. This objective investigation using in-shoe dynamic pressure measurements showed that the addition of a shank to control insole rigidity reduced the overall peak pressures under the foot. When a deep canvas shoe was used to test single- and double-thickness insoles of two different types of material it was found in each case that the double-thickness mode was advantageous overall. Microcellular rubber insoles in two types of leprosy shoe were replaced by the polymer Poron. The Poron proved to be superior to both microcellular rubbers. The peak pressure and pressure-time integral should be considered as complimentary variables when determining the efficacy of footwear.

Effect of magnetic therapy on selected physical performances.

PubMed

Schall, David M; Ishee, Jimmy H; Titlow, Larry W

2003-05-01

The purpose of this study was to investigate the effects of magnetic therapy in the form of shoe insoles on vertical jump, bench squat, 40-yd dash, and a soccer-specific fitness test performance. Subjects were 14 collegiate male soccer players who were pretested, retested 3 weeks later, and then placed into a double-blind control or treatment group using a matching procedure. The control group received magnetic shoe insoles with a rating of 125 gauss, and the treatment group received insoles with a rating of 600 gauss. Subjects wore the insoles during practice and games for 7 weeks and were then retested. Results indicated significant differences among test scores during the 3 time periods but not between the treatment and control groups. There was a decline in 40-yd dash performance from the initial evaluation (5.10 seconds) to the final evaluation (5.08 seconds). There were no other significant differences. Within the limitations of the study, magnetic therapy did not improve physical performance.

Model Errors in Simulating Precipitation and Radiation fields in the NARCCAP Hindcast Experiment

NASA Astrophysics Data System (ADS)

Kim, J.; Waliser, D. E.; Mearns, L. O.; Mattmann, C. A.; McGinnis, S. A.; Goodale, C. E.; Hart, A. F.; Crichton, D. J.

2012-12-01

The relationship between the model errors in simulating precipitation and radiation fields including the surface insolation and OLR, is examined from the multi-RCM NARCCAP hindcast experiment for the conterminous U.S. region. Findings in this study suggest that the RCM biases in simulating precipitation are related with those in simulating radiation fields. For a majority of RCMs participated in the NARCCAP hindcast experiment as well as their ensemble, the spatial pattern of the insolation bias is negatively correlated with that of the precipitation bias, suggesting that the biases in precipitation and surface insolation are systematically related, most likely via the cloud fields. The relationship varies according to seasons as well with stronger relationship between the simulated precipitation and surface insolation during winter. This suggests that the RCM biases in precipitation and radiation are related via cloud fields. Additional analysis on the RCM errors in OLR is underway to examine more details of this relationship.

View-limiting shrouds for insolation radiometers

NASA Technical Reports Server (NTRS)

Dennison, E. W.; Trentelman, G. F.

1985-01-01

Insolation radiometers (normal incidence pyrheliometers) are used to measure the solar radiation incident on solar concentrators for calibrating thermal power generation measurements. The measured insolation value is dependent on the atmospheric transparency, solar elevation angle, circumsolar radiation, and radiometer field of view. The radiant energy entering the thermal receiver is dependent on the same factors. The insolation value and the receiver input will be proportional if the concentrator and the radiometer have similar fields of view. This report describes one practical method for matching the field of view of a radiometer to that of a solar concentrator. The concentrator field of view can be calculated by optical ray tracing methods and the field of view of a radiometer with a simple shroud can be calculated by using geometric equations. The parameters for the shroud can be adjusted to provide an acceptable match between the respective fields of view. Concentrator fields of view have been calculated for a family of paraboloidal concentrators and receiver apertures. The corresponding shroud parameters have also been determined.

Global and Arctic climate engineering: numerical model studies.

PubMed

Caldeira, Ken; Wood, Lowell

2008-11-13

We perform numerical simulations of the atmosphere, sea ice and upper ocean to examine possible effects of diminishing incoming solar radiation, insolation, on the climate system. We simulate both global and Arctic climate engineering in idealized scenarios in which insolation is diminished above the top of the atmosphere. We consider the Arctic scenarios because climate change is manifesting most strongly there. Our results indicate that, while such simple insolation modulation is unlikely to perfectly reverse the effects of greenhouse gas warming, over a broad range of measures considering both temperature and water, an engineered high CO2 climate can be made much more similar to the low CO2 climate than would be a high CO2 climate in the absence of such engineering. At high latitudes, there is less sunlight deflected per unit albedo change but climate system feedbacks operate more powerfully there. These two effects largely cancel each other, making the global mean temperature response per unit top-of-atmosphere albedo change relatively insensitive to latitude. Implementing insolation modulation appears to be feasible.

Solar Insolation Effect on the Local Distribution of Lunar Hydroxyl

NASA Astrophysics Data System (ADS)

Kim, Suyeon; Yi, Yu; Hong, Ik-Seon; Sohn, Jongdae

2018-03-01

Moon mineralogy mapper (M3)'s work proved that the moon is not completely dry but has some hydroxyl/water. M3's data confirmed that the amount of hydroxyl on the lunar surface is inversely related to the measured signal brightness, suggesting the lunar surface is sensitive to temperature by solar insolation. We tested the effect of solar insolation on the local distribution of hydroxyl by using M3 data, and we found that most craters had more hydroxyl in shade areas than in sunlit areas. This means that the local distribution of hydroxyl is absolutely influenced by the amount of sunshine. We investigated the factors affecting differences in hydroxyl; we found that the higher the latitude, the larger the difference during daytime. We also measured the pyroxene content and found that pyroxene affects the amount of hydroxyl, but it does not affect the difference in hydroxyl between sunlit and shaded areas. Therefore, we confirmed that solar insolation plays a significant role in the local distribution of hydroxyl, regardless of surface composition.

Fundamentals of microfluidic cell culture in controlled microenvironments†

PubMed Central

Young, Edmond W. K.; Beebe, David J.

2010-01-01

Microfluidics has the potential to revolutionize the way we approach cell biology research. The dimensions of microfluidic channels are well suited to the physical scale of biological cells, and the many advantages of microfluidics make it an attractive platform for new techniques in biology. One of the key benefits of microfluidics for basic biology is the ability to control parameters of the cell microenvironment at relevant length and time scales. Considerable progress has been made in the design and use of novel microfluidic devices for culturing cells and for subsequent treatment and analysis. With the recent pace of scientific discovery, it is becoming increasingly important to evaluate existing tools and techniques, and to synthesize fundamental concepts that would further improve the efficiency of biological research at the microscale. This tutorial review integrates fundamental principles from cell biology and local microenvironments with cell culture techniques and concepts in microfluidics. Culturing cells in microscale environments requires knowledge of multiple disciplines including physics, biochemistry, and engineering. We discuss basic concepts related to the physical and biochemical microenvironments of the cell, physicochemical properties of that microenvironment, cell culture techniques, and practical knowledge of microfluidic device design and operation. We also discuss the most recent advances in microfluidic cell culture and their implications on the future of the field. The goal is to guide new and interested researchers to the important areas and challenges facing the scientific community as we strive toward full integration of microfluidics with biology. PMID:20179823

Heparanase Mechanisms in Melanoma Brain Metastasis

DTIC Science & Technology

2015-10-01

and ultimately affecting the modulation of BMM. 4 2. KEYWORDS: Brain-metastatic melanoma (BMM), Heparanase (HPSE), Exosomes , proteomic profiling...levels of exosomes , microvescicles that were found to be significantly implicated in the metastatic cancer events, notably to brain (6). Exosomes ...microenvironment. Thus, exosomes isolated from our melanoma/BMM cell models were interrogated for HPSE, MicroRNAs, and for protein expression contents by

Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms

PubMed Central

Hoermann, Gregor; Greiner, Georg; Valent, Peter

2015-01-01

The term myeloproliferative neoplasms (MPN) refers to a heterogeneous group of diseases including not only polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), but also chronic myeloid leukemia (CML), and systemic mastocytosis (SM). Despite the clinical and biological differences between these diseases, common pathophysiological mechanisms have been identified in MPN. First, aberrant tyrosine kinase signaling due to somatic mutations in certain driver genes is common to these MPN. Second, alterations of the bone marrow microenvironment are found in all MPN types and have been implicated in the pathogenesis of the diseases. Finally, elevated levels of proinflammatory and microenvironment-regulating cytokines are commonly found in all MPN-variants. In this paper, we review the effects of MPN-related oncogenes on cytokine expression and release and describe common as well as distinct pathogenetic mechanisms underlying microenvironmental changes in various MPN. Furthermore, targeting of the microenvironment in MPN is discussed. Such novel therapies may enhance the efficacy and may overcome resistance to established tyrosine kinase inhibitor treatment in these patients. Nevertheless, additional basic studies on the complex interplay of neoplastic and stromal cells are required in order to optimize targeting strategies and to translate these concepts into clinical application. PMID:26543328

Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy

PubMed Central

Duffield, Amy S.; Ascierto, Maria Libera; Anders, Robert A.; Taube, Janis M.; Meeker, Alan K.; Chen, Shuming; McMiller, Tracee L.; Phillips, Neil A.; Xu, Haiying; Ogurtsova, Aleksandra; Berger, Alan E.; Pardoll, Drew M.; Ambinder, Richard F.

2017-01-01

Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1. In addition, because the Epstein-Barr virus (EBV) residing in some CHL tumors is strongly immunogenic, we hypothesized that characteristics of the tumor immune microenvironment in EBV+ CHL would be distinct from EBV− CHL, with specific implications for designing combination treatment regimens. Employing immunohistochemistry for immune cell subsets and checkpoint molecules, as well as gene expression profiling, we characterized 32 CHLs from the Johns Hopkins archives, including 12 EBV+ and 20 EBV− tumors. Our results revealed a dichotomous cellular and cytokine immune milieu in EBV+ vs EBV− CHL. EBV+ tumors displayed a T helper 1 (Th1) profile typical of effective antitumor immunity, with increased infiltration of CD8+ T cells and coordinate expression of the canonical Th1 transcription factor Tbet (TBX21), interferon-γ (IFNG), and the IFN-γ–inducible immunosuppressive enzyme indoleamine 2,3-dioxygenase. In contrast, EBV− tumors manifested a pathogenic Th17 profile and ongoing engagement of the interleukin-23 (IL-23)/IL-17 axis, with heightened phosphorylated signal transducer and activator of transcription 3 expression in infiltrating lymphocytes. These findings suggest that drugs blocking the IL-23/IL-17 axis, which are already in the clinic for treating certain autoimmune disorders, may enhance the therapeutic impact of anti-PD-1 therapy in EBV− CHL. PMID:29296775

Changes during the holocene in the size of white-tailed deer ( Odocoileus virginianus) from central Illinois

NASA Astrophysics Data System (ADS)

Purdue, James R.

1989-11-01

White-tailed deer ( Odocoileus virginianus) from central Illinois varied in size during the Holocene. The record, which extends back to 8450 yr B.P., indicates small deer through the mid-Holocene until 3650 yr B.P., after which size increases. Although influences of winter climate, seasonality, anthropogenic effects, and other ecological factors should not be discounted, an intriguing possible cause of the deer size shifts is insolation-driven summer climate and its influence on food resources. In the Holocene, small deer size is correlated with high summer insolation and with low winter insolation. Climatic models indicate that in spite of changes in insolation, Holocene winters did not vary greatly through time, especially in contrast to summers, which were dynamic. Physiological constraints peculiar to O. virginianus make critical the quality of summer forage for determining final adult size. Summer temperature averaged 2°C warmer than present during the middle Holocene, which increased evaporation and probably reduced the period of availability of high-quality forage low in fiber and high in protein. Consequently, less fuel for growth was consumed by mid-Holocene deer and only small body size was achieved. Other possible causes (e.g., Bergmann's rule, seasonality) of clinal variation are considered with reference to central Illinois deer, but at present the most parsimonious explanation appears to be the summer insolation hypothesis.

CD4+ T-cells Contribute to the Remodeling of the Microenvironment Required for Sustained Tumor Regression upon Oncogene Inactivation

PubMed Central

Rakhra, Kavya; Bachireddy, Pavan; Zabuawala, Tahera; Zeiser, Robert; Xu, Liwen; Kopelman, Andrew; Fan, Alice C.; Yang, Qiwei; Braunstein, Lior; Crosby, Erika; Ryeom, Sandra; Felsher, Dean W.

2010-01-01

Summary Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the induction and restraint of tumorigenesis, but their role in oncogene inactivation mediated tumor regression is unclear. Here, we show that an intact immune system, specifically CD4+ T-cells, is required for the induction of cellular senescence, shut down of angiogenesis and chemokine expression resulting in sustained tumor regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T-cell acute lymphoblastic lymphoma and pro-B-cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained tumor regression. Hence, CD4+ T-cells are required for the remodeling of the tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction. PMID:21035406

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response.

PubMed

Eng, Jason W-L; Kokolus, Kathleen M; Reed, Chelsey B; Hylander, Bonnie L; Ma, Wen W; Repasky, Elizabeth A

2014-11-01

Long conserved mechanisms maintain homeostasis in living creatures in response to a variety of stresses. However, continuous exposure to stress can result in unabated production of stress hormones, especially catecholamines, which can have detrimental health effects. While the long-term effects of chronic stress have well-known physiological consequences, recent discoveries have revealed that stress may affect therapeutic efficacy in cancer. Growing epidemiological evidence reveals strong correlations between progression-free and long-term survival and β-blocker usage in cancer patients. In this review, we summarize the current understanding of how the catecholamines, epinephrine and norepinephrine, affect cancer cell survival and tumor progression. We also highlight new data exploring the potential contributions of stress to immunosuppression in the tumor microenvironment and the implications of these findings for the efficacy of immunotherapies.

The effects of regional insolation differences upon advanced solar thermal electric power plant performance and energy costs

NASA Technical Reports Server (NTRS)

Latta, A. F.; Bowyer, J. M.; Fujita, T.

1979-01-01

This paper presents the performance and cost of four 10-MWe advanced solar thermal electric power plants sited in various regions of the continental United States. Each region has different insolation characteristics which result in varying collector field areas, plant performance, capital costs, and energy costs. The paraboloidal dish, central receiver, cylindrical parabolic trough, and compound parabolic concentrator (CPC) comprise the advanced concepts studied. This paper contains a discussion of the regional insolation data base, a description of the solar systems' performances and costs, and a presentation of a range for the forecast cost of conventional electricity by region and nationally over the next several decades.

Bone Marrow Stem Cells in Response to Intervertebral Disc-Like Matrix Acidity and Oxygen Concentration: Implications for Cell-based Regenerative Therapy.

PubMed

Naqvi, Syeda M; Buckley, Conor T

2016-05-01

In vitro culture of porcine bone marrow stem cells (BMSCs) in varying pH microenvironments in a three-dimensional hydrogel system. To characterize the response of BMSCs to varying pH environments (blood [pH 7.4], healthy intervertebral disc (IVD) (pH 7.1), mildly degenerated IVD (pH 6.8), and severely degenerated IVD (pH 6.5) in three-dimensional culture under normoxic (20%) and hypoxic (5%) conditions. The IVD is an avascular organ relying on diffusion of essential nutrients through the cartilaginous endplates (CEPs) thereby creating a challenging microenvironment. Within a degenerated IVD, oxygen and glucose concentrations decrease further (<5% oxygen, <5 mmol/L glucose) and matrix acidity (

Development of a surface isolation estimation technique suitable for application of polar orbiting satellite data

NASA Technical Reports Server (NTRS)

Davis, P. A.; Penn, L. M. (Principal Investigator)

1981-01-01

A technique is developed for the estimation of total daily insolation on the basis of data derivable from operational polar-orbiting satellites. Although surface insolation and meteorological observations are used in the development, the algorithm is constrained in application by the infrequent daytime polar-orbiter coverage.

Handbook of solar energy data for south-facing surfaces in the United States. Volume 1: An insolation, array shadowing, and reflector augmentation model

NASA Technical Reports Server (NTRS)

Smith, J. H.

1980-01-01

A quick reference for obtaining estimates of available solar insolation for numerous locations and array angles is presented. A model and a computer program are provided which considered the effects of array shadowing reflector augmentation as design variables.

Data challenges in estimating the capacity value of solar photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gami, Dhruv; Sioshansi, Ramteen; Denholm, Paul

We examine the robustness of solar capacity-value estimates to three important data issues. The first is the sensitivity to using hourly averaged as opposed to subhourly solar-insolation data. The second is the sensitivity to errors in recording and interpreting load data. The third is the sensitivity to using modeled as opposed to measured solar-insolation data. We demonstrate that capacity-value estimates of solar are sensitive to all three of these factors, with potentially large errors in the capacity-value estimate in a particular year. If multiple years of data are available, the biases introduced by using hourly averaged solar-insolation can be smoothedmore » out. Multiple years of data will not necessarily address the other data-related issues that we examine. Our analysis calls into question the accuracy of a number of solar capacity-value estimates relying exclusively on modeled solar-insolation data that are reported in the literature (including our own previous works). Lastly, our analysis also suggests that multiple years’ historical data should be used for remunerating solar generators for their capacity value in organized wholesale electricity markets.« less

Data Challenges in Estimating the Capacity Value of Solar Photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gami, Dhruv; Sioshansi, Ramteen; Denholm, Paul

We examine the robustness of solar capacity-value estimates to three important data issues. The first is the sensitivity to using hourly averaged as opposed to subhourly solar-insolation data. The second is the sensitivity to errors in recording and interpreting load data. The third is the sensitivity to using modeled as opposed to measured solar-insolation data. We demonstrate that capacity-value estimates of solar are sensitive to all three of these factors, with potentially large errors in the capacity-value estimate in a particular year. If multiple years of data are available, the biases introduced by using hourly averaged solar-insolation can be smoothedmore » out. Multiple years of data will not necessarily address the other data-related issues that we examine. Our analysis calls into question the accuracy of a number of solar capacity-value estimates relying exclusively on modeled solar-insolation data that are reported in the literature (including our own previous works). Our analysis also suggests that multiple years' historical data should be used for remunerating solar generators for their capacity value in organized wholesale electricity markets.« less

Data challenges in estimating the capacity value of solar photovoltaics

DOE PAGES

Gami, Dhruv; Sioshansi, Ramteen; Denholm, Paul

2017-04-30

We examine the robustness of solar capacity-value estimates to three important data issues. The first is the sensitivity to using hourly averaged as opposed to subhourly solar-insolation data. The second is the sensitivity to errors in recording and interpreting load data. The third is the sensitivity to using modeled as opposed to measured solar-insolation data. We demonstrate that capacity-value estimates of solar are sensitive to all three of these factors, with potentially large errors in the capacity-value estimate in a particular year. If multiple years of data are available, the biases introduced by using hourly averaged solar-insolation can be smoothedmore » out. Multiple years of data will not necessarily address the other data-related issues that we examine. Our analysis calls into question the accuracy of a number of solar capacity-value estimates relying exclusively on modeled solar-insolation data that are reported in the literature (including our own previous works). Lastly, our analysis also suggests that multiple years’ historical data should be used for remunerating solar generators for their capacity value in organized wholesale electricity markets.« less

Lunar fingerprints in the modulated incoming solar radiation: In situ insolation and latitudinal insolation gradients as two important interpretative metrics for paleoclimatic data records and theoretical climate modeling

NASA Astrophysics Data System (ADS)

Cionco, Rodolfo Gustavo; Valentini, José Ernesto; Quaranta, Nancy Esther; Soon, Willie W.-H.

2018-01-01

We present a new set of solar radiation forcing that now incorporated not only the gravitational perturbation of the Sun-Earth-Moon geometrical orbits but also the intrinsic solar magnetic modulation of the total solar irradiance (TSI). This new dataset, covering the past 2000 years as well as a forward projection for about 100 years based on recent result by Velasco-Herrera et al. (2015), should provide a realistic basis to examine and evaluate the role of external solar forcing on Earth climate on decadal, multidecadal to multicentennial timescales. A second goal of this paper is to propose both in situ insolation forcing variable and the latitudinal insolation gradients (LIG) as two key metrics that are subjected to a deterministic modulation by lunar nodal cycle which are often confused with tidal forcing impacts as assumed and interpreted in previous studies of instrumental and paleoclimatic records. Our new results and datasets are made publicly available for all at PANGAEA site.

Power Flow Simulations of a More Renewable California Grid Utilizing Wind and Solar Insolation Forecasting

NASA Astrophysics Data System (ADS)

Hart, E. K.; Jacobson, M. Z.; Dvorak, M. J.

2008-12-01

Time series power flow analyses of the California electricity grid are performed with extensive addition of intermittent renewable power. The study focuses on the effects of replacing non-renewable and imported (out-of-state) electricity with wind and solar power on the reliability of the transmission grid. Simulations are performed for specific days chosen throughout the year to capture seasonal fluctuations in load, wind, and insolation. Wind farm expansions and new wind farms are proposed based on regional wind resources and time-dependent wind power output is calculated using a meteorological model and the power curves of specific wind turbines. Solar power is incorporated both as centralized and distributed generation. Concentrating solar thermal plants are modeled using local insolation data and the efficiencies of pre-existing plants. Distributed generation from rooftop PV systems is included using regional insolation data, efficiencies of common PV systems, and census data. The additional power output of these technologies offsets power from large natural gas plants and is balanced for the purposes of load matching largely with hydroelectric power and by curtailment when necessary. A quantitative analysis of the effects of this significant shift in the electricity portfolio of the state of California on power availability and transmission line congestion, using a transmission load-flow model, is presented. A sensitivity analysis is also performed to determine the effects of forecasting errors in wind and insolation on load-matching and transmission line congestion.

On the Departure from Isothermality of Pluto's Volatile Ice due to Local Insolation and Topography

NASA Astrophysics Data System (ADS)

Trafton, Laurence M.; Stansberry, John A.

2015-11-01

Pluto’s atmosphere is known to be supported by the vapor pressure of ices that are volatile at low temperature, primarily N2 and secondarily CH4 and CO. The atmospheric bulk is regulated by the globally average temperature of the ice, which is determined by a radiative balance between the diurnally average insolation absorbed globally by the volatile ice and the global volatile ice thermal radiation. This bulk is sufficient that Pluto’s atmosphere is close to hydrostatic equilibrium, though this may not remain so as Pluto continues to move towards aphelion. With the weight of the atmosphere currently distributed evenly around the body, the ice temperature is expected to be globally isothermal in absence of topographic variations, due to the transport of latent heat from regions of high insolation to low insolation through sublimation and condensation. Images returned from the New Horizons spacecraft show topographical features, including mountain ranges that extend above 3.5 km, with albedo variations that suggest a topographical dimension or dependence of the volatile ice deposits. In general, the conditions often applied to a volatile atmosphere of hydrostatic equilibrium and vapor-solid phase equilibrium are approximations that may not always both be appropriate. This is particularly the case in the presence of topography when the atmospheric lapse rate differs from the wet adiabat. We present our results of an investigation of the effect of variable insolation and topography on Pluto’s local ice temperature assuming an atmosphere close to hydrostatic equilibrium.

Comparison of Two Types of Insoles on Musculoskeletal Symptoms and Plantar Pressure Distribution in a Work Environment: A Randomized Clinical Trial.

PubMed

Almeida, Josiane S; Vanderlei, Franciele M; Pastre, Eliane C; Martins, Rodrigo A D M; Padovani, Carlos R; Filho, Guaracy C

2016-06-01

The aim of the present study was to assess plantar pressure distribution and musculoskeletal symptoms following the use of customized insoles among female assembly line workers. The study included 29 female assembly line workers (age, 29.76 ± 5.79 years; weight, 63.79 ± 12.11 kg) with musculoskeletal symptoms who work predominantly while standing. The Nordic Musculoskeletal Questionnaire was administered to the study population. Plantar pressure was determined using a computerized plantar pressure feedback system. A control group (n=13) used ethylvinylacetate insoles (Podaly®) that were individually heat molded and heat glued. The intervention group (n=14) also used the insoles and a strip of the same material was added to the site of greatest plantar pressure as determined by the electronic feedback device. After five weeks, the plantar pressure data were collected again and the questionnaire was administered a second time. There was no significant difference between groups with regard to pain in any anatomic site. However, within each group the lumbar region exhibited a reduction in symptoms in the intervention group (P<0.05), and the feet exhibited a reduction in symptoms in both groups (P<0.05). Mean plantar pressure increased and plantar surface decreased in the intervention group (P<0.05). Insoles increased foot comfort in both groups. However, the added strip did not significantly modify either plantar pressure or other symptoms in female workers. © 2016 Marshfield Clinic.

Influence of topographic complexity on solar insolation estimates for the Colorado River, Grand Canyon, AZ

USGS Publications Warehouse

Yard, M.D.; Bennett, G.E.; Mietz, S.N.; Coggins, L.G.; Stevens, L.E.; Hueftle, S.; Blinn, D.W.

2005-01-01

Rugged topography along the Colorado River in Glen and Grand Canyons, exemplifies features common to canyon-bound streams and rivers of the arid southwest. Physical relief influences regulated river systems, especially those that are altered, and have become partially reliant on aquatic primary production. We measured and modeled instantaneous solar flux in a topographically complex environment to determine where differences in daily, seasonal and annual solar insolation occurred in this river system. At a system-wide scale, topographic complexity generates a spatial and temporal mosaic of varying solar insolation. This solar variation is a predictable consequence of channel orientation, geomorphology, elevation angles and viewshed. Modeled estimates for clear conditions corresponded closely with observed measurements for both instantaneous photosynthetic photon flux density (PPFD: ??mol m-2 s-1) and daily insolation levels (relative error 2.3%, CI ??0.45, S.D. 0.3, n = 29,813). Mean annual daily insolation levels system-wide were estimated to be 36 mol m-2 d -1 (17.5 S.D.), and seasonally varied on average from 13.4-57.4 mol m-2 d-1, for winter and summer, respectively. In comparison to identical areas lacking topographic effect (idealized plane), mean daily insolation levels were reduced by 22% during summer, and as much as 53% during winter. Depending on outlying topography, canyon bound regions having east-west (EW) orientations had higher seasonal variation, averaging from 8.1 to 61.4 mol m-2 d-1, for winter and summer, respectively. For EW orientations, 70% of mid-channel sites were obscured from direct incidence during part of the year; and of these sites, average diffuse light conditions persisted for 19.3% of the year (70.5 days), and extended upwards to 194 days. This predictive model has provided an initial quantitative step to estimate and determine the importance of autotrophic production for this ecosystem, as well as a broader application for other canyon systems. ?? 2004 Published by Elsevier B.V.

The timing of Mediterranean sapropel deposition relative to insolation, sea-level and African monsoon changes

NASA Astrophysics Data System (ADS)

Grant, K. M.; Grimm, R.; Mikolajewicz, U.; Marino, G.; Ziegler, M.; Rohling, E. J.

2016-05-01

The Mediterranean basin is sensitive to global sea-level changes and African monsoon variability on orbital timescales. Both of these processes are thought to be important to the deposition of organic-rich sediment layers or 'sapropels' throughout the eastern Mediterranean, yet their relative influences remain ambiguous. A related issue is that an assumed 3-kyr lag between boreal insolation maxima and sapropel mid-points remains to be tested. Here we present new geochemical and ice-volume-corrected planktonic foraminiferal stable isotope records for sapropels S1 (Holocene), S3, S4, and S5 (Marine Isotope Stage 5) in core LC21 from the southern Aegean Sea. The records have a radiometrically constrained chronology that has already been synchronised with the Red Sea relative sea-level record, and this allows detailed examination of the timing of sapropel deposition relative to insolation, sea-level, and African monsoon changes. We find that sapropel onset was near-synchronous with monsoon run-off into the eastern Mediterranean, but that insolation-sapropel/monsoon phasings were not systematic through the last glacial cycle. These latter phasings instead appear to relate to sea-level changes. We propose that persistent meltwater discharges into the North Atlantic (e.g., at glacial terminations) modified the timing of sapropel deposition by delaying the timing of peak African monsoon run-off. These observations may reconcile apparent model-data offsets with respect to the orbital pacing of the African monsoon. Our observations also imply that the previous assumption of a systematic 3-kyr lag between insolation maxima and sapropel midpoints may lead to overestimated insolation-sapropel phasings. Finally, we surmise that both sea-level rise and monsoon run-off contributed to surface-water buoyancy changes at times of sapropel deposition, and their relative influences differed per sapropel case, depending on their magnitudes. Sea-level rise was clearly important for sapropel S1, whereas monsoon forcing was more important for sapropels S3, S4, and S5.

Short-term effects of customized arch support insoles on symptomatic flexible flatfoot in children: A randomized controlled trial.

PubMed

Hsieh, Ru-Lan; Peng, Hui-Ling; Lee, Wen-Chung

2018-05-01

Limited evidence is available regarding the effects of insoles on pediatric flexible flatfoot because of the heterogeneity and low methodological quality of previous studies. The purpose of this prospective trial is to examine the short-term effects of customized arch support insoles on symptomatic flexible flatfoot in children by using the International Classification of Functioning, randomized controlled Disability, and Health (ICF) framework. This study was conducted in a rehabilitation outpatient clinic of a teaching hospital. Fifty-two children with symptomatic flexible flatfoot were included. The children in the treatment group wore customized arch support insoles for 12 weeks, whereas those in the control group did not wear the insoles. Both clinical and radiographic measurements, including the navicular drop, foot posture index, Beighton hypermobility score, talonavicular coverage angle, calcaneal inclination angle, and calcaneal-first metatarsal angle, were used for diagnosing flexible flatfoot. Physical activity (10-m normal and fast walking, stair ascent, stair descent, and chair rising), physical function, and psychometric properties (Pediatric Outcome Data Collection Instrument and Pediatric Quality of Life Inventory) were evaluated at the baseline and 12 weeks after the intervention. Compared with the control group, the treatment group exhibited significant improvement in pain/comfort (P = .048), physical health (P = .035), stair ascent time (P = .015), upper extremity and physical function (P = .016), and transfer and basic mobility (P = .042) during the intervention period. Children with flexible flatfoot who wore customized arch support insoles for 12 weeks exhibited significantly improved pain/comfort, physical health, stair ascent time, upper extremity and physical function, and transfer and basic mobility. These variables belong to the domains of body functions and structures and activity and participation in the ICF framework. However, because the groups were not comparable, additional studies with larger sample sizes should be conducted.

The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5.

PubMed

Guaita-Esteruelas, S; Gumà, J; Masana, L; Borràs, J

2018-02-15

The adipose tissue microenvironment plays a key role in tumour initiation and progression because it provides fatty acids and adipokines to tumour cells. The fatty acid-binding protein (FABP) family is a group of small proteins that act as intracellular fatty acid transporters. Adipose-derived FABPs include FABP4 and FABP5. Both have an important role in lipid-related metabolic processes and overexpressed in many cancers, such as breast, prostate, colorectal and ovarian. Moreover, their expression in peritumoural adipose tissue is deregulated, and their circulating levels are upregulated in some tumours. In this review, we discuss the role of the peritumoural adipose tissue and the related adipokines FABP4 and FABP5 in cancer initiation and progression and the possible pathways implicated in these processes. Copyright © 2017 Elsevier B.V. All rights reserved.

The Architectural Organization of Human Stem Cell Cycle Regulatory Machinery

PubMed Central

Stein, Gary S.; Stein, Janet L.; Wijnen, Andre van J; Lian, Jane B.; Montecino, Martin; Medina, Ricardo; Kapinas, Kristie; Ghule, Prachi; Grandy, Rodrigo; Zaidi, Sayyed K.; Becker, Klaus A.

2013-01-01

Two striking features of human embryonic stem cells that support biological activity are an abbreviated cell cycle and reduced complexity to nuclear organization. The potential implications for rapid proliferation of human embryonic stem cells within the context of sustaining pluripotency, suppressing phenotypic gene expression and linkage to simplicity in the architectural compartmentalization of regulatory machinery in nuclear microenvironments is explored. Characterization of the molecular and architectural commitment steps that license human embryonic stem cells to initiate histone gene expression is providing understanding of the principal regulatory mechanisms that control the G1/S phase transition in primitive pluripotent cells. From both fundamental regulatory and clinical perspectives, further understanding of the pluripotent cell cycle in relation to compartmentalization of regulatory machinery in nuclear microenvironments is relevant to applications of stem cells for regenerative medicine and new dimensions to therapy where traditional drug discovery strategies have been minimally effective. PMID:22394165

MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells.

PubMed

Soley, Luna; Falank, Carolyne; Reagan, Michaela R

2017-06-01

Multiple myeloma remains an incurable disease, largely due to the tumor-supportive role of the bone marrow microenvironment. Bone marrow adipose tissue (BMAT) is one component of the fertile microenvironment which is believed to contribute to myeloma progression and drug resistance, as well as participate in a vicious cycle of osteolysis and tumor growth. MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular processes that enable the development and dissemination of cancer. This review highlights the intersection between two emerging research fields and pursues the scientific and clinical implications of miRNA transfer between BMAT and myeloma cells. This review provides a concise and provocative summary of the evidence to support exosome-mediated transfer of tumor-supportive miRNAs. The work may prompt researchers to better elucidate the mechanisms by which this novel means of genetic communication between tumor cells and their environment could someday yield targeted therapeutics.

Handbook of solar energy data for south-facing surfaces in the United States. Volume 2: Average hourly and total daily insolation data for 235 localities. Alaska - Montana

NASA Technical Reports Server (NTRS)

Smith, J. H.

1980-01-01

Average hourly and daily total insolation estimates for 235 United States locations are presented. Values are presented for a selected number of array tilt angles on a monthly basis. All units are in kilowatt hours per square meter.

Foot model for tracking temperature of safety boot insoles: application to different insole materials in firefighter boots.

PubMed

García-Hernández, César; Sánchez-Álvarez, Eduardo J; Huertas-Talón, José-Luis

2016-01-01

This research is based on the development of a human foot model to study the temperature conditions of a foot bottom surface under extreme external conditions. This foot model is made by combining different manufacturing techniques to enable the simulation of bones and tissues, allowing the placement of sensors on its surface to track the temperature values of different points inside a shoe. These sensors let researchers capture valuable data during a defined period of time, making it possible to compare the features of different safety boots, socks or soles, among others. In this case, it has been applied to compare different plantar insole materials, placed into safety boots on a high-temperature surface.

Strategies of Echinococcus species responses to immune attacks: implications for therapeutic tool development.

PubMed

Zheng, Yadong

2013-11-01

Echinococcus species have been studied as a model to investigate parasite-host interactions. Echinococcus spp. can actively communicate dynamically with a host to facilitate infection, growth and proliferation partially via secretion of molecules, especially in terms of harmonization of host immune attacks. This review systematically outlines our current knowledge of how the Echinococcus species have evolved to adapt to their host's microenvironment. This understanding of parasite-host interplay has implications in profound appreciation of parasite plasticity and is informative in designing novel and effective tools including vaccines and drugs for the treatment of echinococcosis and other diseases. © 2013.

The Role of Hypoxia in the Tumor Microenvironment: Implications for Ovarian Cancer Therapy

DTIC Science & Technology

2017-07-01

microenvironmental factor promoting metastatic progression. A critical step in metastatic tumor progression is the ability of tumor cells to evade immune attack...Tumor cells utilize a complex set of mechanisms that prevent the immune system from mounting effective anti-tumor responses. Moreover, the hypoxic...promote the immunosuppressive phenotypes of both tumor cells as well as infiltrating immune cells . However, the mechanisms by which hypoxia promotes

Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments.

PubMed

Horne, Gillian A; Copland, Mhairi

2017-05-01

Self-renewal is considered a defining property of stem cells. Self-renewal is essential in embryogenesis and normal tissue repair and homeostasis. However, in cancer, self-renewal pathways, e.g. WNT, NOTCH, Hedgehog and BMP, frequently become de-regulated in stem cells, or more mature progenitor cells acquire self-renewal properties, resulting in abnormal tissue growth and tumorigenesis. Areas covered: This review considers the conserved embryonic self-renewal pathways, including WNT, NOTCH, Hedgehog and BMP. The article describes recent advances in our understanding of these pathways in leukemia and, more specifically, leukemia stem cells (LSC), how these pathways cross-talk and interact with the LSC microenvironment, and discusses the clinical implications and potential therapeutic strategies, both in preclinical and in clinical trials for hematological malignancies. Expert opinion: The conserved embryonic self-renewal pathways are frequently de-regulated in cancer stem cells (CSC), including LSCs. There is significant cross-talk between self-renewal pathways, and their downstream targets, and the microenvironment. Effective targeting of these pathways is challenging due to cross-talk, and importantly, because these pathways are important for normal stem cells as well as CSC, adverse effects on normal tissues may mean a therapeutic window cannot be identified. Nonetheless, several agents targeting these pathways are currently in clinical trials in hematological malignancies.

Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.

PubMed

Asma, Gati; Amal, Gorrab; Raja, Marrakchi; Amine, Derouiche; Mohammed, Chebil; Amel, Ben Ammar Elgaaied

2015-05-01

The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

Tone-Inhibiting Insoles Enhance the Reciprocal Inhibition of Ankle Plantarflexors of Subjects With Hemiparesis After Stroke: An Electromyographic Study.

PubMed

Takahashi, Nobushige; Takahashi, Hidetoshi; Takahashi, Osamu; Ushijima, Ryosuke; Umebayashi, Rie; Nishikawa, Junji; Okajima, Yasutomo

2018-02-01

Spasticity is a common sequela of upper motor neuron pathology, such as cerebrovascular diseases and cerebral palsy. Intervention for spasticity of the ankle plantarflexors in physical therapy may include tone-inhibiting casting and/or orthoses for the ankle and foot. However, the physiological mechanism of tone reduction by such orthoses remains unclarified. To investigate the electrophysiologic effects of tone-inhibiting insoles in stroke subjects with hemiparesis by measuring changes in reciprocal Ia inhibition (RI) in the ankle plantarflexor. An interventional before-after study. Acute stroke unit or ambulatory rehabilitation clinic of a university hospital in Japan. Ten subjects (47-84 years) with hemiparesis and 10 healthy male control subjects (31-59 years) were recruited. RI of the spastic soleus in response to the electrical stimulation of the deep peroneal nerve was evaluated by stimulus-locked averaging of rectified electromyography (EMG) of the soleus while subjects were standing. The magnitude of RI, defined as the ratio of the lowest to the baseline amplitude of the rectified EMG at approximately 40 milliseconds after stimulation, was measured while subjects were standing with and without the tone-inhibiting insole on the hemiparesis side. Enhancement of EMG reduction with the tone-inhibiting insole was significant (P < .05) in the subjects with hemiparesis, whereas no significant changes were found in controls. Tone-inhibiting insoles enhanced RI of the soleus in subjects after stroke, which might enhance standing stability by reducing unfavorable ankle plantarflexion tone. III. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Control conditions for footwear insole and orthotic research.

PubMed

Lewinson, Ryan T; Worobets, Jay T; Stefanyshyn, Darren J

2016-07-01

Footwear insoles/orthotics alter variables associated with musculoskeletal injury; however, their clinical effectiveness is inconclusive. One explanation for this is the possibility that control conditions may actually produce biomechanical changes that induce clinical responses. The purpose of this study was to compare insole/orthotic control conditions to identify if variables at the ground, ankle and knee that are associated with injury are altered relative to what participants would normally experience in their own shoes. Gait analysis was performed on 15 participants during walking and running while wearing (1) their own shoes, (2) #1 with a 3mm flat insole, (3) a standardized shoe, and (4) #3 with a 3mm flat insole, where external knee adduction moments, external knee adduction angular impulses, internal ankle inversion moments, and vertical ground reaction force loading rates were determined. Conditions 2-4 were expressed as percent changes relative to condition 1, and tests of proportions assessed if there were a significant number of individuals experiencing a biomechanically relevant change for each variable. Repeated-measures ANOVAs were used to identify group differences between conditions. The majority of movement-footwear-variable combinations contained a proportion of individuals experiencing biomechanically relevant changes compared to condition 1 that was significantly greater than the expected proportion of 20%. No systematic differences were found between conditions. This suggests that conditions 2-4 may alter biomechanics relative to baseline for many participants, but not in a consistent way across participants. It is recommended that participant's own footwear be used as control conditions in future trials where biomechanics are primary variables of interest. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of bacterial DNA profiles of footwear insoles and soles of feet for the forensic discrimination of footwear owners.

PubMed

Goga, Haruhisa

2012-09-01

It is crucial to identify the owner of unattended footwear left at a crime scene. However, retrieving enough DNA for DNA profiling from the owner's foot skin (plantar skin) cells from inside the footwear is often unsuccessful. This is sometimes because footwear that is used on a daily basis contains an abundance of bacteria that degrade DNA. Further, numerous other factors related to the inside of the shoe, such as high humidity and temperature, can encourage bacterial growth inside the footwear and enhance DNA degradation. This project sought to determine if bacteria from inside footwear could be used for footwear trace evidence. The plantar skins and insoles of shoes of volunteers were swabbed for bacteria, and their bacterial community profiles were compared using bacterial 16S rRNA terminal restriction fragment length polymorphism analysis. Sufficient bacteria were recovered from both footwear insoles and the plantar skins of the volunteers. The profiling identified that each volunteer's plantar skins harbored unique bacterial communities, as did the individuals' footwear insoles. In most cases, a significant similarity in the bacterial community was identified for the matched foot/insole swabs from each volunteer, as compared with those profiles from different volunteers. These observations indicate the probability to discriminate the owner of footwear by comparing the microbial DNA fingerprint from inside footwear with that of the skin from the soles of the feet of the suspected owner. This novel strategy will offer auxiliary forensic footwear evidence for human DNA identification, although further investigations into this technique are required.

The effects of regional insolation differences upon advanced solar thermal electric power plant performance and energy costs

NASA Technical Reports Server (NTRS)

Latta, A. F.; Bowyer, J. M.; Fujita, T.; Richter, P. H.

1979-01-01

The performance and cost of the 10 MWe advanced solar thermal electric power plants sited in various regions of the continental United States were determined. The regional insolation data base is discussed. A range for the forecast cost of conventional electricity by region and nationally over the next several cades are presented.

Topographic and Other Influences on Pluto's Volatile Ices

NASA Astrophysics Data System (ADS)

Lewis, Briley Lynn; Stansberry, John; Grundy, William M.; Schmitt, Bernard; Protopapa, Silvia; Trafton, Laurence M.; Holler, Bryan J.; McKinnon, William B.; Schenk, Paul M.; Stern, S. Alan; Young, Leslie; Weaver, Harold A.; Olkin, Catherine; Ennico, Kimberly; New Horizons Science Team, The New Horizons Composition Team

2018-01-01

Pluto’s surface is known to consist of various volatile ices, mostly N2, CH4, and CO, which sublimate and condense on varying timescales, generally moving from points of high insolation to those of low insolation. The New Horizons Pluto encounter data provide multiple lenses through which to view Pluto’s detailed surface topography and composition and to investigate the distribution of volatiles on its surface, including albedo and elevation maps from the imaging instruments and composition maps from the LEISA spectral imager. The volatile surface ice is expected to be generally isothermal, due to the fact that their vapor pressures are in equilibrium with the atmosphere. Although secular topographic transport mechanisms suggest that points at low elevation should slowly fill with volatile ices (Trafton 2015 DPS abstract, Bertrand and Forget 2017), there are counter-examples of this across the surface, implying that energy discrepancies caused by insolation differences, albedo variations, local slopes, and other effects may take precedence at shorter timescales. Using data from the 2015 New Horizons flyby, we present our results of this investigation into the effects of variations in insolation, albedo, and topography on the presence of the different volatile ices across the surface of Pluto.

The response of East Asian monsoon to the precessional cycle

NASA Astrophysics Data System (ADS)

Lee, J. E.

2017-12-01

The oxygen isotopic composition of cave speleothems exhibits a large amplitude change following the insolation, particularly the precessional cycle. Whether speleothem d18O reflects local precipitation amount, however, has been questioned by alternative hypotheses: (1) d18O reflects upstream Indian monsoon precipitation, which influences the isotopic composition of the input vapor to East Asia, and (2) the isotopic composition of pre-monsoon and monsoon exhibits a large difference, and the seasonality of precipitation may have shifted in response to insolation. Motivated the fact that the magnitude of Asian monsoon d18O was not reproduced by most climate models, here I show new results, using the fully coupled GFDL model, that precipitation increases when the northern hemisphere receives more summer insolation, similar to the original claim. I argue that previous models do not produce enough rainfall during the monsoon season, possibly because the westerly jet is located too north in relation to the Tibetan Plateau during the monsoon season. I conclude that Asian monsoon intensity probably increases with increasing insolation there, given a large change in speleothem d18O. My next step will be testing this hypothesis after incorporating isotopes into the GFDL model.

Topographic and Other Influences on Pluto's Volatile Ices

NASA Astrophysics Data System (ADS)

Lewis, Briley Lynn; Stansberry, John; Grundy, William M.; Schmitt, Bernard; Protopapa, Silvia; Trafton, Laurence M.; Holler, Bryan J.; McKinnon, William B.; Schenk, Paul M.; Stern, S. Alan; Young, Leslie; Weaver, Harold A.; Olkin, Catherine; Ennico, Kimberly; New Horizons Science Team

2017-10-01

Pluto’s surface is known to consist of various volatile ices, mostly N2, CH4, and CO, which sublimate and condense on varying timescales, generally moving from points of high insolation to those of low insolation. The New Horizons Pluto encounter data provide multiple lenses through which to view Pluto’s detailed surface topography and composition and to investigate the distribution of volatiles on its surface, including albedo and elevation maps from the imaging instruments and composition maps from the LEISA spectral imager. The volatile surface ice is expected to be generally isothermal, due to the fact that their vapor pressures are in equilibrium with the atmosphere. Although secular topographic transport mechanisms suggest that points at low elevation should slowly fill with volatile ices (Trafton 2015 DPS abstract, Bertrand and Forget 2017), there are counter-examples of this across the surface, implying that energy discrepancies caused by insolation differences, albedo variations, local slopes, and other effects may take precedence at shorter timescales. Using data from the 2015 New Horizons flyby, we present our results of this investigation into the effects of variations in insolation, albedo, and topography on the presence of the different volatile ices across the surface of Pluto.

Energy sources for triton's geyser-like plumes

USGS Publications Warehouse

Brown, R.H.; Kirk, R.L.; Johnson, T.V.; Soderblom, L.A.

1990-01-01

Four geyser-like plumes were discovered near Triton's south pole in areas now in permanent sunlight. Because Triton's southern hemisphere is nearing a maximum summer solstice, insolation as a driver or a trigger for Triton's geyser-like plumes is an attractive hypothesis. Trapping of solar radiation in a translucent, low-conductivity surface layer (in a solid-state greenhouse), which is subsequently released in the form of latent heat of sublimation, could provide the required energy. Both the classical solid-state greenhouse consisting of exponentially absorbed insolation in a gray, translucent layer of solid nitrogen, and the "super" greenhouse consisting of a relatively transparent solid-nitrogen layer over an opaque, absorbing layer are plausible candidates. Geothermal heat may also play a part if assisted by the added energy input of seasonal cycles of insolation.

The effects of regional insolation differences upon advanced solar thermal electric power plant performance and energy costs

NASA Technical Reports Server (NTRS)

Latta, A. F.; Bowyer, J. M.; Fujita, T.; Richter, P. H.

1980-01-01

The performance and cost of four 10 MWe advanced solar thermal electric power plants sited in various regions of the continental United States was studied. Each region has different insolation characteristics which result in varying collector field areas, plant performance, capital costs and energy costs. The regional variation in solar plant performance was assessed in relation to the expected rise in the future cost of residential and commercial electricity supplied by conventional utility power systems in the same regions. A discussion of the regional insolation data base is presented along with a description of the solar systems performance and costs. A range for the forecast cost of conventional electricity by region and nationally over the next several decades is given.

Space reflector technology and its system implications

NASA Technical Reports Server (NTRS)

Billman, K. W.; Gilbreath, W. P.; Bowen, S. W.

1979-01-01

The technical feasibility of providing nearly continuous solar energy to a world-distributed set of conversion sites by means of a system of orbiting, large-area, low-areal-density reflecting structures is examined. Requisite mirror area to provide a chosen, year-averaged site intensity is shown. A modeled reflector structure, with suitable planarity and ability to meet operational torques and loads, is discussed. Typical spatial and temporal insolation profiles are presented. These determine the sizing of components and the output electric power from a baselined photovoltaic conversion system. Technical and economic challenges which, if met, would allow the system to provide a large fraction of future world energy needs at costs competitive to circa-1995 fossil and nuclear sources are discussed.

Microsensor studies on Padina from a natural CO2 seep: implications of morphology on acclimation to low pH.

PubMed

Hofmann, Laurie C; Fink, Artur; Bischof, Kai; de Beer, Dirk

2015-12-01

Low seawater pH can be harmful to many calcifying marine organisms, but the calcifying macroalgae Padina spp. flourish at natural submarine carbon dioxide seeps where seawater pH is low. We show that the microenvironment created by the rolled thallus margin of Padina australis facilitates supersaturation of CaCO3 and calcifi-cation via photosynthesis-induced elevated pH. Using microsensors to investigate oxygen and pH dynamics in the microenvironment of P. australis at a shallow CO2 seep, we found that, under saturating light, the pH inside the microenvironment (pHME ) was higher than the external seawater (pHSW ) at all pHSW levels investigated, and the difference (i.e., pHME - pHSW ) increased with decreasing pHSW (0.9 units at pHSW 7.0). Gross photosynthesis (Pg ) inside the microenvironment increased with decreasing pHSW , but algae from the control site reached a threshold at pH 6.5. Seep algae showed no pH threshold with respect to Pg within the pHSW range investigated. The external carbonic anhydrase (CA) inhibitor, acetazolamide, strongly inhibited Pg of P. australis at pHSW 8.2, but the effect was diminished under low pHSW (6.4-7.5), suggesting a greater dependence on membrane-bound CA for the dehydration of HCO3 (-) ions during dissolved inorganic carbon uptake at the higher pHSW . In comparison, a calcifying green alga, Halimeda cuneata f. digitata, was not inhibited by AZ, suggesting efficient bicarbonate transport. The ability of P. australis to elevate pHME at the site of calcification and its strong dependence on CA may explain why it can thrive at low pHSW . © 2015 Phycological Society of America.

Pattern response of dendritic cells in the tumor microenvironment and breast cancer

PubMed Central

da Cunha, Alessandra; Michelin, Marcia A; Murta, Eddie FC

2014-01-01

Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development, including malignancy grade and patient prognosis, is influenced by various mutations that occur in the tumor cell and by the immune system’s status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Among the immune response cells, dendritic cells (DCs) play a key role in the induction and maintenance of anti-tumor responses owing to their unique abilities for antigen cross-presentation and promotion of the activation of specific lymphocytes that target neoplasic cells. However, the tumor microenvironment can polarize DCs, transforming them into immunosuppressive regulatory DCs, a tolerogenic phenotype which limits the activity of effector T cells and supports tumor growth and progression. Various factors and signaling pathways have been implicated in the immunosuppressive functioning of DCs in cancer, and researchers are working on resolving processes that can circumvent tumor escape and developing viable therapeutic interventions to prevent or reverse the expression of immunosuppressive DCs in the tumor microenvironment. A better understanding of the pattern of DC response in patients with BC is fundamental to the development of specific therapeutic approaches to enable DCs to function properly. Various studies examining DCs immunotherapy have demonstrated its great potential for inducing immune responses to specific antigens and thereby reversing immunosuppression and related to clinical response in patients with BC. DC-based immunotherapy research has led to immense scientific advances, both in our understanding of the anti-tumor immune response and for the treatment of these patients. PMID:25114862

Comparison of speleothem δ 18O records from eastern China with solar insolation, ice core and marine records: Similarities and discrepancies on different time scales

NASA Astrophysics Data System (ADS)

Wan, Naijung; Chung, Weiling; Li, Hong-Chun; Lin, Huilin; Ku, Teh-Lung; Shen, Chuan-Chou; Yuan, Daoxian; Zhang, Meiliang; Lin, Yushi

2011-04-01

Four 230Th-dated δ 18O records in three stalagmites: one from Dragon Spring (stalagmite L12) and two from Golden Lion Caves (stalagmites JSD-01 and JSD-02) located in Libo County, southeast Guizhou, China, are presented. These records cover age ranges of 0.75-2 ka (late Holocene), 9-9.6 ka (early Holocene), 87.9-88.2 ka and 93.8-95.2 ka (late Pleistocene). They fit well with the published Dongge Cave record from the same area, where the climate has been much influenced by the East Asian Monsoon. The agreement reinforces the role of stalagmite δ 18O as a proxy for regional precipitation or monsoon strength. On millennial or longer time scales, the δ 18O record of Dongge Cave resembles those of Sanbao Cave in Hubei and Hulu Cave in Jiangsu of China. The matching of these records with the northern hemisphere solar-insolation variations points to the importance of insolation in affecting the East Asian Summer Monsoon strength on 10 3-10 4-yr scales. While the monsoon variations as depicted by these Chinese speleothem δ 18O records show a strong coupling to insolation's precession component (23-kyr period), other climate records of global significance extracted from oceanic and terrestrial deposits (e.g., deep-sea sediments, polar ice cores, cave deposits from non-monsoonal regions) do not. Although the latter records were thought to be also influenced by the large changes in global ice volume, they show variations modulated chiefly by insolation due to earth's eccentricity change (100-kyr period). It is hypothesized that precession variations control the distribution of solar insolation between the northern and southern hemispheres, the ITCZ position and the modulation of low-latitude summer monsoon variability. Increasing rainfall and/or summer/winter precipitation ratio brought about by strong summer monsoons leads to δ 18O depletion in stalagmites grown in monsoonal regions. One should use caution to compare speleothem δ 18O records with other paleoclimate records reflecting Pleistocene ice ages on 10 4-10 5-yr timescales.

Insolation-induced mid-Brunhes transition in Southern Ocean ventilation and deep-ocean temperature.

PubMed

Yin, Qiuzhen

2013-02-14

Glacial-interglacial cycles characterized by long cold periods interrupted by short periods of warmth are the dominant feature of Pleistocene climate, with the relative intensity and duration of past and future interglacials being of particular interest for civilization. The interglacials after 430,000 years ago were characterized by warmer climates and higher atmospheric concentrations of carbon dioxide than the interglacials before, but the cause of this climatic transition (the so-called mid-Brunhes event (MBE)) is unknown. Here I show, on the basis of model simulations, that in response to insolation changes only, feedbacks between sea ice, temperature, evaporation and salinity caused vigorous pre-MBE Antarctic bottom water formation and Southern Ocean ventilation. My results also show that strong westerlies increased the pre-MBE overturning in the Southern Ocean via an increased latitudinal insolation gradient created by changes in eccentricity during austral winter and by changes in obliquity during austral summer. The stronger bottom water formation led to a cooler deep ocean during the older interglacials. These insolation-induced differences in the deep-sea temperature and in the Southern Ocean ventilation between the more recent interglacials and the older ones were not expected, because there is no straightforward systematic difference in the astronomical parameters between the interglacials before and after 430,000 years ago. Rather than being a real 'event', the apparent MBE seems to have resulted from a series of individual interglacial responses--including notable exceptions to the general pattern--to various combinations of insolation conditions. Consequently, assuming no anthropogenic interference, future interglacials may have pre- or post-MBE characteristics without there being a systematic change in forcings. These findings are a first step towards understanding the magnitude change of the interglacial carbon dioxide concentration around 430,000 years ago.

How and when to terminate the Pleistocene ice ages?

NASA Astrophysics Data System (ADS)

Abe-Ouchi, A.; Saito, F.; Kawamura, K.; Takahashi, K.; Raymo, M. E.; Okuno, J.; Blatter, H.

2015-12-01

Climate change with wax and wane of large Northern Hemisphere ice sheet occurred in the past 800 thousand years characterized by 100 thousand year cycle with a large amplitude of sawtooth pattern, following a transition from a period of 40 thousand years cycle with small amplitude of ice sheet change at about 1 million years ago. Although the importance of insolation as the ultimate driver is now appreciated, the mechanism what determines timing and strength of terminations are far from clearly understood. Here we show, using comprehensive climate and ice-sheet models, that insolation and internal feedbacks between the climate, the ice sheets and the lithosphere-asthenosphere system explain the 100,000-year periodicity. The responses of equilibrium states of ice sheets to summer insolation show hysteresis, with the shape and position of the hysteresis loop playing a key part in determining the periodicities of glacial cycles. The hysteresis loop of the North American ice sheet is such that after inception of the ice sheet, its mass balance remains mostly positive through several precession cycles, whose amplitudes decrease towards an eccentricity minimum. The larger the ice sheet grows and extends towards lower latitudes, the smaller is the insolation required to make the mass balance negative. Therefore, once a large ice sheet is established, a moderate increase in insolation is sufficient to trigger a negative mass balance, leading to an almost complete retreat of the ice sheet within several thousand years. We discuss further the mechanism which determine the timing of ice age terminations by examining the role of astronomical forcing and change of atmospheric carbon dioxide contents through sensitivity experiments and comparison of several ice age cycles with different settings of astronomical forcings.

Insights into changes in precipitation patterns in Brazil from oxygen isotope ratios on speleothems

NASA Astrophysics Data System (ADS)

Cruz, F.; Mathias, V.; Stephen, B. J.; Wang, X.; Cheng, H.; Werner, M.; Edwards, R. L.; Karmann, I.; Auler, A. S.

2008-12-01

Variations in tropical precipitation on millennial and orbital time scales can reflect a Hadley-cell-related anti- phasing between the Northern and Southern hemispheres due to the influence of insolation on the global summer monsoons. A new δ18O speleothem record from northeastern Brazil shows that insolation- driven changes in monsoon intensity are capable of producing a similar, zonally oriented anti-phasing within the same hemisphere. Comparison of our speleothem record with other precipitation-sensitive proxies from the central Andes and southeastern Brazil shows that precipitation in Northeastern Brazil has been out of phase with insolation and rainfall in the rest of tropical South America south of the equator since the Last Glacial Maximum. Northeastern Brazil experienced humid conditions when summer insolation was reduced and arid conditions when insolation was high. While previous interpretations of past climate change in NE South America have commonly invoked meridional displacements in ITCZ location as the main mechanism for changes in precipitation on millennial time scales, our results suggest that remote monsoon forcing is responsible for much of the observed precipitation changes on orbital time scales during the Holocene. These results demonstrate that orbitally driven out-of-phase relationships in precipitation are not limited to interhemispheric anti-phasing as demonstrated previously, but may well occur within the same hemisphere. Speleothem records also indicate contrasting climatic conditions around the Last Glacial Maximum in Brazil, characterized by marked dry and wet climates in the Nordeste and in southeastern Brazil, respectively. It is likely, however, that these regional differences primarily reflect more distant extratropical teleconnections from the Atlantic Ocean and high northern latitude changes during glacial conditions.

The dynamics of the Snowball Earth Hadley circulation for off-equatorial and seasonally varying insolation

NASA Astrophysics Data System (ADS)

Voigt, A.

2013-11-01

I study the Hadley circulation of a completely ice-covered Snowball Earth through simulations with a comprehensive atmosphere general circulation model. Because the Snowball Earth atmosphere is an example of a dry atmosphere, these simulations allow me to test to what extent dry theories and idealized models capture the dynamics of realistic dry Hadley circulations. Perpetual off-equatorial as well as seasonally varying insolation is used, extending a previous study for perpetual on-equatorial (equinox) insolation. Vertical diffusion of momentum, representing the momentum transport of dry convection, is fundamental to the momentum budgets of both the winter and summer cells. In the zonal budget, it is the primary process balancing the Coriolis force. In the meridional budget, it mixes meridional momentum between the upper and the lower branch and thereby decelerates the circulation. Because of the latter, the circulation intensifies by a factor of three when vertical diffusion of momentum is suppressed. For seasonally varying insolation, the circulation undergoes rapid transitions from the weak summer into the strong winter regime. Consistent with previous studies in idealized models, these transitions result from a mean-flow feedback, because of which they are insensitive to the treatment of vertical diffusion of momentum. Overall, the results corroborate previous findings for perpetual on-equatorial insolation. They demonstrate that descriptions of realistic dry Hadley circulations, in particular their strength, need to incorporate the vertical momentum transport by dry convection, a process that is neglected in most dry theories and idealized models. An improved estimate of the strength of the Snowball Earth Hadley circulation will also help to better constrain the climate of a possible Neoproterozoic Snowball Earth and its deglaciation threshold.

The dynamics of the Snowball Earth Hadley circulation for off-equatorial and seasonally-varying insolation

NASA Astrophysics Data System (ADS)

Voigt, A.

2013-08-01

I study the Hadley circulation of a completely ice-covered Snowball Earth through simulations with a comprehensive atmosphere general circulation model. Because the Snowball Earth atmosphere is an example of a dry atmosphere, these simulations allow me to test to what extent dry theories and idealized models capture the dynamics of dry Hadley circulations. Perpetual off-equatorial as well as seasonally-varying insolation is used, extending a previous study for perpetual on-equatorial (equinox) insolation. Vertical diffusion of momentum, representing the momentum transport of dry convection, is fundamental to the momentum budgets of both the winter and summer cells. In the zonal budget, it is the primary process balancing the Coriolis force. In the meridional budget, it mixes meridional momentum between the upper and the lower branch and thereby decelerates the circulation. Because of the latter, the circulation intensifies by a factor of three when vertical diffusion of momentum is suppressed. For seasonally-varying insolation, the circulation undergoes rapid transitions from the weak summer into the strong winter regime. Consistent with previous studies in idealized models, these transitions result from a mean-flow feedback, because of which they are insensitive to the treatment of vertical diffusion of momentum. Overall, the results corroborate previous findings for perpetual on-equatorial insolation. They demonstrate that an appropriate description of dry Hadley circulations, in particular their strength, needs to incorporate the vertical momentum transport by dry convection, a process that is neglected in most dry theories and idealized models. An improved estimate of the strength of the Snowball Earth Hadley circulation will also help to better constrain the climate of a possible Neoproterozoic Snowball Earth and its deglaciation threshold.

Effects of medially posted insoles on foot and lower limb mechanics across walking and running in overpronating men.

PubMed

Kosonen, Jukka; Kulmala, Juha-Pekka; Müller, Erich; Avela, Janne

2017-03-21

Anti-pronation orthoses, like medially posted insoles (MPI), have traditionally been used to treat various of lower limb problems. Yet, we know surprisingly little about their effects on overall foot motion and lower limb mechanics across walking and running, which represent highly different loading conditions. To address this issue, multi-segment foot and lower limb mechanics was examined among 11 overpronating men with normal (NORM) and MPI insoles during walking (self-selected speed 1.70±0.19m/s vs 1.72±0.20m/s, respectively) and running (4.04±0.17m/s vs 4.10±0.13m/s, respectively). The kinematic results showed that MPI reduced the peak forefoot eversion movement in respect to both hindfoot and tibia across walking and running when compared to NORM (p<0.05-0.01). No differences were found in hindfoot eversion between conditions. The kinetic results showed no insole effects in walking, but during running MPI shifted center of pressure medially under the foot (p<0.01) leading to an increase in frontal plane moments at the hip (p<0.05) and knee (p<0.05) joints and a reduction at the ankle joint (p<0.05). These findings indicate that MPI primarily controlled the forefoot motion across walking and running. While kinetic response to MPI was more pronounced in running than walking, kinematic effects were essentially similar across both modes. This suggests that despite higher loads placed upon lower limb during running, there is no need to have a stiffer insoles to achieve similar reduction in the forefoot motion than in walking. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insolation-oriented model of photovoltaic module using Matlab/Simulink

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, Huan-Liang

2010-07-15

This paper presents a novel model of photovoltaic (PV) module which is implemented and analyzed using Matlab/Simulink software package. Taking the effect of sunlight irradiance on the cell temperature, the proposed model takes ambient temperature as reference input and uses the solar insolation as a unique varying parameter. The cell temperature is then explicitly affected by the sunlight intensity. The output current and power characteristics are simulated and analyzed using the proposed PV model. The model verification has been confirmed through an experimental measurement. The impact of solar irradiation on cell temperature makes the output characteristic more practical. In addition,more » the insolation-oriented PV model enables the dynamics of PV power system to be analyzed and optimized more easily by applying the environmental parameters of ambient temperature and solar irradiance. (author)« less

A new approach to implement a customized anatomic insole in orthopaedic footwear of lower limb orthosis

NASA Astrophysics Data System (ADS)

Peixoto, J.; Flores, P.; Souto, A. P.

2017-10-01

This paper concerns the development of a new approach for orthopaedic footwear to apply in KAFO orthosis (acronym for Knee Ankle Foot Orthosis). This procedure starts with full characterization of the problem with the purpose to characterize a plantar of a patient’s foot with polio. A 3D Scanner was used to collect their feet’s data to produce an anatomic insole. After this step, the patient performs a study of his gait using a static and dynamic study with the aim of characterizing the parameters to improve quality in the footwear. The insole was produced using a 3D printing technology. It was essential to optimize manufacturing processes and it was developed a footwear prototype with innovative characteristics, which is 25% lighter, allowing the user to consume less energy in daily routines.

Parametric design of pressure-relieving foot orthosis using statistics-based finite element method.

PubMed

Cheung, Jason Tak-Man; Zhang, Ming

2008-04-01

Custom-molded foot orthoses are frequently prescribed in routine clinical practice to prevent or treat plantar ulcers in diabetes by reducing the peak plantar pressure. However, the design and fabrication of foot orthosis vary among clinical practitioners and manufacturers. Moreover, little information about the parametric effect of different combinations of design factors is available. As an alternative to the experimental approach, therefore, computational models of the foot and footwear can provide efficient evaluations of different combinations of structural and material design factors on plantar pressure distribution. In this study, a combined finite element and Taguchi method was used to identify the sensitivity of five design factors (arch type, insole and midsole thickness, insole and midsole stiffness) of foot orthosis on peak plantar pressure relief. From the FE predictions, the custom-molded shape was found to be the most important design factor in reducing peak plantar pressure. Besides the use of an arch-conforming foot orthosis, the insole stiffness was found to be the second most important factor for peak pressure reduction. Other design factors, such as insole thickness, midsole stiffness and midsole thickness, contributed to less important roles in peak pressure reduction in the given order. The statistics-based FE method was found to be an effective approach in evaluating and optimizing the design of foot orthosis.

Anti-angiogenic and anti-metastatic activity of JAK inhibitor AZD1480

PubMed Central

Xin, Hong; Herrmann, Andreas; Reckamp, Karen; Zhang, Wang; Pal, Sumanta; Hedvat, Michael; Zhang, Chunyan; Liang, Wei; Scuto, Anna; Weng, Shaobu; Morosini, Deborah; Cao, Zhu A.; Zinda, Michael; Figlin, Robert; Huszar, Dennis; Jove, Richard; Yu, Hua

2011-01-01

STAT3 has important functions in both tumor cells and the tumor microenvironment to facilitate cancer progression. The STAT regulatory kinase JAK has been strongly implicated in promoting oncogenesis of various solid tumors, including through the use of JAK kinase inhibitors such as AZD1480. However, direct evidence that JAK drives STAT3 function and cancer pathogenesis at the level of the tumor microenvironment has yet to be established clearly. In this study, we show that AZD1480 inhibits STAT3 in tumor-associated myeloid cells, reducing their number and inhibiting tumor metastasis. Myeloid cell-mediated angiogenesis was also diminished by AZD1480, with additional direct inhibition of endothelial cell function in vitro and in vivo. AZD1480 blocked lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduced angiogenesis and metastasis in a human xenograft tumor model. Although the effects of AZD1480 on the tumor microenvironment were important for the observed anti-angiogenic activity, constitutive activation of STAT3 in tumor cells themselves could block these anti-angiogenic effects demonstrating the complexity of the JAK/STAT signaling network in tumor progression. Together, our results indicated that AZD1480 can effectively inhibit tumor angiogenesis and metastasis mediated by STAT3 in stromal cells as well as tumor cells. PMID:21920898

mTOR and MEK1/2 inhibition differentially modulate tumor growth and the immune microenvironment in syngeneic models of oral cavity cancer

PubMed Central

Cash, Harrison; Shah, Sujay; Moore, Ellen; Caruso, Andria; Uppaluri, Ravindra; Van Waes, Carter; Allen, Clint

2015-01-01

We investigated the effects of mTOR and MEK1/2 inhibition on tumor growth and the tumor microenvironment in immunogenic and poorly immunogenic models of murine oral cancer. In vitro, rapamycin and PD901 inhibited signaling through expected downstream targets, but only PD901 reduced viability and altered function of MOC cells. Following transplantation of MOC cells into immune-competent mice, effects on both cancer and infiltrating immune cells were characterized following rapamycin and/or PD901 treatment for 21 days. In vivo, both rapamycin and PD901 inhibition reduced primary growth of established MOC tumors on treatment. Following withdrawal of PD901, rapid rebound of tumor growth limited survival, whereas durable tumor control was observed following rapamycin treatment in immunogenic MOC1 tumors despite more robust inhibition of oncogenic signaling by PD901. Characterization of the immune microenvironment revealed diminished infiltration and activation of antigen-specific CD8+ T-cells and other immune cells following PD901 but not rapamycin in immunogenic tumors. Subsequent in vitro T-cell assays validated robust inhibition of T-cell expansion and activation following MEK inhibition compared to mTOR inhibition. CD8 cell depletion abrogated rapamycin-induced primary tumor growth inhibition in MOC1 mice. These data have critical implications in the design of combination targeted and immune therapies in oral cancer. PMID:26506415

Altering micro-environments to change population health behaviour: towards an evidence base for choice architecture interventions.

PubMed

Hollands, Gareth J; Shemilt, Ian; Marteau, Theresa M; Jebb, Susan A; Kelly, Michael P; Nakamura, Ryota; Suhrcke, Marc; Ogilvie, David

2013-12-21

The idea that behaviour can be influenced at population level by altering the environments within which people make choices (choice architecture) has gained traction in policy circles. However, empirical evidence to support this idea is limited, especially its application to changing health behaviour. We propose an evidence-based definition and typology of choice architecture interventions that have been implemented within small-scale micro-environments and evaluated for their effects on four key sets of health behaviours: diet, physical activity, alcohol and tobacco use. We argue that the limitations of the evidence base are due not simply to an absence of evidence, but also to a prior lack of definitional and conceptual clarity concerning applications of choice architecture to public health intervention. This has hampered the potential for systematic assessment of existing evidence. By seeking to address this issue, we demonstrate how our definition and typology have enabled systematic identification and preliminary mapping of a large body of available evidence for the effects of choice architecture interventions. We discuss key implications for further primary research, evidence synthesis and conceptual development to support the design and evaluation of such interventions. This conceptual groundwork provides a foundation for future research to investigate the effectiveness of choice architecture interventions within micro-environments for changing health behaviour. The approach we used may also serve as a template for mapping other under-explored fields of enquiry.

Differential effects of the extracellular microenvironment on human embryonic stem cell differentiation into keratinocytes and their subsequent replicative life span.

PubMed

Movahednia, Mohammad Mehdi; Kidwai, Fahad Karim; Zou, Yu; Tong, Huei Jinn; Liu, Xiaochen; Islam, Intekhab; Toh, Wei Seong; Raghunath, Michael; Cao, Tong

2015-04-01

Culture microenvironment plays a critical role in the propagation and differentiation of human embryonic stem cells (hESCs) and their differentiated progenies. Although high efficiency of hESC differentiation to keratinocytes (hESC-Kert) has been achieved, little is known regarding the effects of early culture microenvironment and pertinent extracellular matrix (ECM) interactions during epidermal commitment on subsequent proliferative capacity of hESC-Kert. The aim of this study is to evaluate the effects of the different ECM microenvironments during hESC differentiation on subsequent replicative life span of hESC-Kert. In doing so, H1-hESCs were differentiated to keratinocytes (H1-Kert) in two differentiation systems. The first system employed autologous fibroblast feeder support, in which keratinocytes (H1-Kert(ACC)) were derived by coculture of hESCs with hESC-derived fibroblasts (H1-ebFs). The second system employed a novel decellularized matrix from H1-ebFs to create a dermoepidermal junction-like (DEJ) matrix. H1-Kert(AFF) were derived by differentiation of hESCs on the feeder-free system employing the DEJ matrix. Our study indicated that the feeder-free system with the use of DEJ matrix was more efficient in differentiation of hESCs toward epidermal progenitors. However, the feeder-free system was not sufficient to support the subsequent replicative capacity of differentiated keratinocytes. Of note, H1-Kert(AFF) showed limited replicative capacity with reduced telomere length and early cellular senescence. We further showed that the lack of cell-cell interactions during epidermal commitment led to heightened production of TGF-β1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system. This study highlights for the first time the importance of the culture microenvironment and cell-ECM interactions during differentiation of hESCs on subsequent replicative life span and cellular senescence of the differentiated keratinocytes, with implications for use of these cells for applications in tissue engineering and regenerative medicine.

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

PubMed Central

Garcia-Gomez, Antonio; Las Rivas, Javier De; Ocio, Enrique M.; Díaz-Rodríguez, Elena; Montero, Juan C.; Martín, Montserrat; Blanco, Juan F.; Sanchez-Guijo, Fermín M.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

2014-01-01

Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease. PMID:25268740

Hypoxia enhances innate immune activation to Aspergillus fumigates through cell wall modulation

PubMed Central

Shepardson, Kelly M.; Ngo, Lisa Y.; Aimanianda, Vishukumar; Latge, Jean-Paul; Barker, Bridget M.; Blosser, Sara J.; Iwakura, Yoichiro; Hohl, Tobias M.; Cramer, Robert A.

2013-01-01

Infection by the human fungal pathogen Aspergillus fumigatus induces hypoxic microenvironments within the lung that can alter the course of fungal pathogenesis. How hypoxic microenvironments shape the composition and immune activating potential of the fungal cell wall remains undefined. Herein we demonstrate that hypoxic conditions increase the hyphal cell wall thickness and alter its composition particularly by augmenting total and surface-exposed β-glucan content. In addition, hypoxia-induced cell wall alterations increase macrophage and neutrophil responsiveness and antifungal activity as judged by inflammatory cytokine production and ability to induce hyphal damage. We observe that these effects are largely dependent on the mammalian β-glucan receptor dectin-1. In a corticosteroid model of invasive pulmonary aspergillosis, A. fumigatus β-glucan exposure correlates with the presence of hypoxia in situ. Our data suggest that hypoxia-induced fungal cell wall changes influence the activation of innate effector cells at sites of hyphal tissue invasion, which has potential implications for therapeutic outcomes of invasive pulmonary aspergillosis. PMID:23220005

The Chemo-Biological Outreach of Nano-Biomaterials: Implications for Tissue Engineering and Regenerative Medicine.

PubMed

Kumar, Pradeep; Choonara, Yahya E; Khan, Riaz A; Pillay, Viness

2017-01-01

Nanobiomaterials can be defined as materials interacting with and influencing the biological microenvironment at a nanointerface. Recently the basic as well as applied research related to nanobiomaterials - a conjugation of nano-, material- and life-sciences - has immensely evolved for therapeutics and related biotechnology areas. The current overview focused on the potential of nanobiomaterial-based substrates towards the generation of biocompatible surfaces, tissue engineering architectures, and regenerative medicine. Emphasis was given to chemomolecular functionalization of nanobiomaterials, nanobiomaterial composites, and morphomechanically modified nanoarchetypes and their inherent chemo-biological interaction with the biological microenvironment. Additionally, recent developments in nanobiomaterial substrate design and structure, chemo-biological interface related bio-systems uses and further evolving applications in health care, therapeutics and nanomedicine were discussed herein. Furthermore, a special emphasis was placed on the nano-chemo-biological interactions inherent to various nanobiomaterial substrates in close vicinity with biological systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

MicroRNA Transfer between Bone Marrow Adipose and Multiple Myeloma Cells

PubMed Central

Soley, Luna; Falank, Carolyne; Reagan, Michaela R.

2017-01-01

Purpose of Review Multiple myeloma remains an incurable disease, largely due to the tumor-supportive role of the bone marrow microenvironment. Bone marrow adipose tissue (BMAT) is one component of the fertile microenvironment which is believed to contribute to myeloma progression and drug resistance, as well as participate in a vicious cycle of osteolysis and tumor growth. Recent Findings MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular processes that enable the development and dissemination of cancer. This review highlights the intersection between two emerging research fields and pursues the scientific and clinical implications of miRNA transfer between BMAT and myeloma cells. Summary This review provides a concise and provocative summary of the evidence to support exosome-mediated transfer of tumor-supportive miRNAs. The work may prompt researchers to better elucidate the mechanisms by which this novel means of genetic communication between tumor cells and their environment could someday yield targeted therapeutics. PMID:28432594

Determination of the cumulus size distribution from LANDSAT pictures

NASA Technical Reports Server (NTRS)

Karg, E.; Mueller, H.; Quenzel, H.

1983-01-01

Varying insolation causes undesirable thermic stress to the receiver of a solar power plant. The rapid change of insolation depends on the size distribution of the clouds; in order to measure these changes, it is suitable to determine typical cumulus size distributions. For this purpose, LANDSAT-images are adequate. Several examples of cumulus size distributions will be presented and their effects on the operation of a solar power plant are discussed.

Intermediate photovoltaic system application experiment operational performance report. Volume 6: Beverly High School, Beverly, Mass.

NASA Astrophysics Data System (ADS)

1982-03-01

Performance data are given for the month of February, 1982 for a photovoltaic power supply at a Massachusetts high school. Data given include: monthly and daily electrical energy yield; monthly and daily insolation; monthly and daily array efficiency; energy production as a function of power level, voltage, cell temperature, and hour of day; insolation as a function of hour of the day; input, output and efficiency for each of two power conditioning units and for the total power conditioning system; energy supplied to the load by the photovoltaic system and by the grid; photovoltaic system efficiency; dollar value of the energy supplied by the photovoltaic system; capacity factor; daily photovoltaic energy to load; daily system availability and hours of daylight; heating and cooling degree days; hourly cell temperature, ambient temperature, wind speed, and insolation; average monthly wind speed; wind direction distribution; and daily data acquisition mode and recording interval plot.

Estimating Photosynthetically Available Radiation (PAR) at the Earth's surface from satellite observations

NASA Technical Reports Server (NTRS)

Frouin, Robert

1993-01-01

Current satellite algorithms to estimate photosynthetically available radiation (PAR) at the earth' s surface are reviewed. PAR is deduced either from an insolation estimate or obtained directly from top-of-atmosphere solar radiances. The characteristics of both approaches are contrasted and typical results are presented. The inaccuracies reported, about 10 percent and 6 percent on daily and monthly time scales, respectively, are useful to model oceanic and terrestrial primary productivity. At those time scales variability due to clouds in the ratio of PAR and insolation is reduced, making it possible to deduce PAR directly from insolation climatologies (satellite or other) that are currently available or being produced. Improvements, however, are needed in conditions of broken cloudiness and over ice/snow. If not addressed properly, calibration/validation issues may prevent quantitative use of the PAR estimates in studies of climatic change. The prospects are good for an accurate, long-term climatology of PAR over the globe.

GRAVITY-DARKENED SEASONS: INSOLATION AROUND RAPID ROTATORS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahlers, John P.

2016-11-20

I model the effect of rapid stellar rotation on a planet’s insolation. Fast-rotating stars have induced pole-to-equator temperature gradients (known as gravity darkening) of up to several thousand Kelvin that affect the star’s luminosity and peak emission wavelength as a function of latitude. When orbiting such a star, a planet’s annual insolation can strongly vary depending on its orbital inclination. Specifically, inclined orbits result in temporary exposure to the star’s hotter poles. I find that gravity darkening can drive changes in a planet’s equilibrium temperature of up to ∼15% due to increased irradiance near the stellar poles. This effect canmore » also vary a planet’s exposure to UV radiation by up to ∼80% throughout its orbit as it is exposed to an irradiance spectrum corresponding to different stellar effective temperatures over time.« less

Simulating 3-D radiative transfer effects over the Sierra Nevada Mountains using WRF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, Y.; Liou, K. N.; Lee, W. -L.

2012-01-01

A surface solar radiation parameterization based on deviations between 3-D and conventional plane-parallel radiative transfer models has been incorporated into the Weather Research and Forecasting (WRF) model to understand the solar insolation over mountain/snow areas and to investigate the impact of the spatial and temporal distribution and variation of surface solar fluxes on land-surface processes. Using the Sierra-Nevada in the western United States as a testbed, we show that mountain effect could produce up to -50 to + 50 W m -2 deviations in the surface solar fluxes over the mountain areas, resulting in a temperature increase of up tomore » 1 °C on the sunny side. Upward surface sensible and latent heat fluxes are modulated accordingly to compensate for the change in surface solar fluxes. Snow water equivalent and surface albedo both show decreases on the sunny side of the mountains, indicating more snowmelt and hence reduced snow albedo associated with more solar insolation due to mountain effect. Soil moisture increases on the sunny side of the mountains due to enhanced snowmelt, while decreases on the shaded side. Substantial differences are found in the morning hours from 8–10 a.m. and in the afternoon around 3–5 p.m., while differences around noon and in the early morning and late afternoon are comparatively smaller. Variation in the surface energy balance can also affect atmospheric processes, such as cloud fields, through the modulation of vertical thermal structure. Negative changes of up to -40 g m -2 are found in the cloud water path, associated with reductions in the surface insolation over the cloud region. The day-averaged deviations in the surface solar flux are positive over the mountain areas and negative in the valleys, with a range between -12~12 W m -2. Changes in sensible and latent heat fluxes and surface skin temperature follow the solar insolation pattern. Differences in the domain-averaged diurnal variation over the Sierras show that the mountain area receives more solar insolation during early morning and late afternoon, resulting in enhanced upward sensible heat and latent heat fluxes from the surface and a corresponding increase in surface skin temperature. During the middle of the day, however, the surface insolation and heat fluxes show negative changes, indicating a cooling effect. Hence overall, the diurnal variations of surface temperature and surface fluxes in the Sierra-Nevada are reduced through the interactions of radiative transfer and mountains. Finally, the hourly differences of the surface solar insolation in higher elevated regions, however, show smaller magnitude in negative changes during the middle of the day and possibly more solar fluxes received during the whole day.« less

Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

PubMed

Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

2017-06-01

The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

High Northern Latitude Insolation Forcing of Tropical Monsoons or Monsoon Forcing of High Northern Latitude Ice Volume?

NASA Astrophysics Data System (ADS)

Beck, W.; Zhou, W.; Cheng, L.; Wu, Z.; Xian, F.; Kong, X.; Cottam, T.; An, Z.; White, L.

2017-12-01

We show that atmospheric 10Be flux is a quantitative proxy for rainfall, and use it to derive a 530Ka-long record of East Asian summer monsoon rainfall from Chinese Loess. Our record strongly resembles the Red Sea paleosea level and LR04 benthic foram δ18O records, with 53% & 45% of its variance reflected in each of these two global ice volume proxies. This suggests EASM intensity is closely coupled to ice volume by some mechanism. At first glance, this seems to support the claim based on strongly correlated Chinese cave δ18O and 65°N summer solar insolation that Asian monsoon intensity is controlled by high northern latitude insolation. Nevertheless, our 10Be-proxy has only 17% common variance with cave δ18O. Furthermore, Chinese cave δ18O records are very poorly correlated with sea-level/global ice volume, conflicting with both our proxy and Milankovitch theory, if interpreted as a monsoon intensity proxy. We argue that cave δ18O is instead a mixing proxy for monsoon moisture derived from (δ18O depleted) Indian vs Pacific monsoon sectors. We suggest both this mixing ratio and EASM intensity are not governed by high northern latitude insolation, but rather by orbital forcing of the low latitude interhemispheric insolation gradient, which mimics the 65°N insolation pattern. We show this gradient regulates the ratio of Asian monsoon outflow to the Indian vs. North Pacific subtropical highs, providing a coupling to both Hadley and Walker circulations. When outflow strengthens in one of these sectors it weakens in the other, regulating the relative strength of the Trade and Westerly winds in each sector. Trade wind coupling to monsoon strength in each sector controls the ISM/Pacific monsoon moisture mixing ratio and EASM intensity, although intensity is also influenced by other factors. This model provides mechanisms by which the monsoons may influence ice volume. Westerlies strength adjacent to the North Pacific Subtropical High strongly regulates transient eddy energy transport to the north polar region. Likewise, the Trades and Westerlies in the Indian Ocean both influence AMOC strength by regulating Agulhas leakage into the Atlantic, or can influence air/sea CO2 fluxes. These mechanisms may all strongly influence northern hemisphere ice volume, begging the question: Where does global climate control originate?

200,000 years of monsoonal history recorded on the lower Bengal Fan - strong response to insolation forcing

NASA Astrophysics Data System (ADS)

Weber, Michael E.; Lantzsch, Hendrik; Dekens, Petra; Das, Supriyo K.; Reilly, Brendan T.; Martos, Yasmina M.; Meyer-Jacob, Carsten; Agrahari, Sandip; Ekblad, Alf; Titschack, Jürgen; Holmes, Beth; Wolfgramm, Philipp

2018-07-01

We conducted a multidisciplinary study to provide the stratigraphic and palaeoclimatic context of monsoonal rainfall dynamics and their responses to orbital forcing for the Bay of Bengal. Using sediment lightness we established an age model at orbital resolution for International Ocean Discovery Programme (IODP) Core U1452C-1H that covers the last 200 ka in the lower Bengal Fan. The low-resolution δ18O of G. sacculifer is consistent with global δ18O records, at least for major glacial-to-interglacial transitions. The variability of total organic carbon, total nitrogen, and the δ13C composition of organic matter indicate the marine origin of organic matter. Marine primary productivity likely increased during insolation minima, indicative for an enhanced NE monsoon during glacials and stadials. Pristine insolation forcing is also documented for wet-bulk density, red-green color variability, and grain-size variations, indicating that darker and coarser-grained material deposited at higher sedimentation rates during insolation minima. Stronger NE monsoon likely amplified ocean-atmosphere interactions over the Indian Ocean, leading to stronger upwelling through shoaling the thermocline, and higher delivery of sediment to the Bay of Bengal due to higher soil erosion on land. In addition, lower glacial and stadial sea levels as well as stronger westward surface circulation favored delivery of coarser-grained fluvial material to the lower Bengal Fan. At the same time the stronger NE monsoon might have increased the aeolian supply. Total inorganic carbon, the Ca/Ti ratio, and biogenic silica vary dominantly on obliquity frequencies, suggesting mobilization and transport of lithogenic material primarily during lowered sea levels and/or higher influence of the Northern Hemisphere westerlies on the dust transport from the Tibetan Plateau. The close resemblance of sediment lightness and the climate record of Antarctic ice cores over multiple glacial cycles indicate close relationship between high southern latitude and tropical Asian climate through shifts in position of the Intertropical Convergence Zone. The Bengal Fan monsoonal record shows very clear and strict responses to insolation forcing in the lower part from 200 ka to the Younger Toba Tuff during Marine Isotope Stage (MIS) 7 - 5, and less distinct response patterns after deposition of the ash during MIS 4 - 2, consistent with low-amplitude changes in insolation.

Lightweight Phase-Change Material For Solar Power

NASA Technical Reports Server (NTRS)

Stark, Philip

1993-01-01

Lightweight panels containing phase-change materials developed for use as heat-storage elements of compact, lightweight, advanced solar dynamic power system. During high insolation, heat stored in panels via latent heat of fusion of phase-change material; during low insolation, heat withdrawn from panels. Storage elements consist mainly of porous carbon-fiber structures imbued with germanium. Developed for use aboard space station in orbit around Earth, also adapted to lightweight, compact, portable solar-power systems for use on Earth.

FreeWalker: a smart insole for longitudinal gait analysis.

PubMed

Wang, Baitong; Rajput, Kuldeep Singh; Tam, Wing-Kin; Tung, Anthony K H; Yang, Zhi

2015-08-01

Gait analysis is an important diagnostic measure to investigate the pattern of walking. Traditional gait analysis is generally carried out in a gait lab, with equipped force and body tracking sensors, which needs a trained medical professional to interpret the results. This procedure is tedious, expensive, and unreliable and makes it difficult to track the progress across multiple visits. In this paper, we present a smart insole called FreeWalker, which provides quantitative gait analysis outside the confinement of traditional lab, at low- cost. The insole consists of eight pressure sensors and two motion tracking sensors, i.e. 3-axis accelerometer and 3-axis gyroscope. This enables measurement of under-foot pressure distribution and motion sequences in real-time. The insole is enabled with onboard SD card as well as wireless data transmission, which help in continuous gait-cycle analysis. The data is then sent to a gateway, for analysis and interpretation of data, using a user interface where gait features are graphically displayed. We also present validation result of a subject's left foot, who was asked to perform a specific task. Experiment results show that we could achieve a data-sampling rate of over 1 KHz, transmitting data up to a distance of 20 meter and maintain a battery life of around 24 hours. Taking advantage of these features, FreeWalker can be used in various applications, like medical diagnosis, rehabilitation, sports and entertainment.

Footwear affects the behavior of low back muscles when jogging.

PubMed

Ogon, M; Aleksiev, A R; Spratt, K F; Pope, M H; Saltzman, C L

2001-08-01

Use of modified shoes and insole materials has been widely advocated to treat low back symptoms from running impacts, although considerable uncertainty remains regarding the effects of these devices on the rate of shock transmission to the spine. This study investigated the effects of shoes and insole materials on a) the rate of shock transmission to the spine, b) the temporal response of spinal musculature to impact loading, and c) the time interval between peak lumbar acceleration and peak lumbar muscle response. It was hypothesised that shoes and inserts a) decrease the rate of shock transmission, b) decrease the low back muscle response time, and c) shorten the time interval between peak lumbar acceleration and peak lumbar muscle response. Twelve healthy subjects were tested while jogging barefoot (unshod) or wearing identical athletic shoes (shod). Either no material, semi-rigid (34 Shore A), or soft (9.5 Shore A) insole material covered the force plate in the barefoot conditions and was placed as insole when running shod. Ground reaction forces, acceleration at the third lumbar level, and erector spinae myoelectric activity were recorded simultaneously. The rate of shock transmission to the spine was greater (p < 0.0003) unshod (acceleration rate: Means +/- SD 127.35 +/- 87.23 g/s) than shod (49.84 +/- 33.98 g/s). The temporal response of spinal musculature following heel strike was significantly shorter (p < 0.023) unshod (0.038 +/- 0.021 s) than shod (0.047 +/- 0.036 s). The latency between acceleration peak (maximal external force) and muscle response peak (maximal internal force) was significantly (p < 0.021) longer unshod (0.0137 +/- 0.022s) than shod (0.004 +/- 0.040 s). These results suggest that one of the benefits of running shoes and insoles is improved temporal synchronization between potentially destabilizing external forces and stabilizing internal forces around the lumbar spine.

[Therapeutic effect of extracorporeal shock wave combined with orthopaedic insole on plantar fasciitis].

PubMed

Yan, Wenguang; Sun, Shaodan; Li, Xuhong

2014-12-01

To observe the therapeutic effect of extracorporeal shock wave combined with orthopaedic insole on plantar fasciitis. A total of 153 plantar with plantar fasciitis were randomly divided into a combined group (n=51), an extracorporeal shock wave group (n=53) and an orthopaedic group (n=49). The combined group received treatment of both extracorporeal shock wave and orthopaedic insole while the extracorporeal shock wave or the orthopaedic group only received the treatment of extracorporeal shock wave or orthopaedic insole. The therapeutic parameters such as visual analogue scale (VAS) scores, continued walking time and thickness of the plantar fascia were monitored before and aft er the treatment for 2 weeks, 1 month and 3 months, respectively. The VAS scores in the 3 groups were all reduced after the treatment compared with the corresponding scores before the therapy (P< 0.05). The VAS score in the extracorporeal shock wave group was greater than that in the orthopedic group after the treatment for 2 weeks. The VAS score in the combined group was smaller than that in the orthopedic group after the treatment for 2 weeks and 3 months (P< 0.05). The VAS scores in the orthopedic group and the combined group were smaller than those in the extracorporeal shock wave group after the treatment for 1 month or 3 months (P< 0.05). The continued walking time and thickness of the plantar fascia was improved after the treatment (P< 0.05). The cure rate and total effective rate in the combination group were obviously greater than those in the two other groups. The cure rate in the orthopedic group was greater than that in the extracorporeal shock wave group (P< 0.05). Extracorporeal shock wave combined with orthopaedic insole therapy is an effective method to treat plantar fasciitis. It is recommended to spread in clinic.

Indian monsoon variations during three contrasting climatic periods: The Holocene, Heinrich Stadial 2 and the last interglacial-glacial transition

NASA Astrophysics Data System (ADS)

Zorzi, Coralie; Sanchez Goñi, Maria Fernanda; Anupama, Krishnamurthy; Prasad, Srinivasan; Hanquiez, Vincent; Johnson, Joel; Giosan, Liviu

2015-10-01

In contrast to the East Asian and African monsoons the Indian monsoon is still poorly documented throughout the last climatic cycle (last 135,000 years). Pollen analysis from two marine sediment cores (NGHP-01-16A and NGHP-01-19B) collected from the offshore Godavari and Mahanadi basins, both located in the Core Monsoon Zone (CMZ) reveals changes in Indian summer monsoon variability and intensity during three contrasting climatic periods: the Holocene, the Heinrich Stadial (HS) 2 and the Marine Isotopic Stage (MIS) 5/4 during the ice sheet growth transition. During the first part of the Holocene between 11,300 and 4200 cal years BP, characterized by high insolation (minimum precession, maximum obliquity), the maximum extension of the coastal forest and mangrove reflects high monsoon rainfall. This climatic regime contrasts with that of the second phase of the Holocene, from 4200 cal years BP to the present, marked by the development of drier vegetation in a context of low insolation (maximum precession, minimum obliquity). The historical period in India is characterized by an alternation of strong and weak monsoon centennial phases that may reflect the Medieval Climate Anomaly and the Little Ice Age, respectively. During the HS 2, a period of low insolation and extensive iceberg discharge in the North Atlantic Ocean, vegetation was dominated by grassland and dry flora indicating pronounced aridity as the result of a weak Indian summer monsoon. The MIS 5/4 glaciation, also associated with low insolation but moderate freshwater fluxes, was characterized by a weaker reduction of the Indian summer monsoon and a decrease of seasonal contrast as recorded by the expansion of dry vegetation and the development of Artemisia, respectively. Our results support model predictions suggesting that insolation changes control the long term trend of the Indian monsoon precipitation, but its millennial scale variability and intensity are instead modulated by atmospheric teleconnections to remote phenomena in the North Atlantic, Eurasia or the Indian Ocean.

Response of the Asian summer monsoons to idealized precession and obliquity forcing in a set of GCMs

NASA Astrophysics Data System (ADS)

Bosmans, J. H. C.; Erb, M. P.; Dolan, A. M.; Drijfhout, S. S.; Tuenter, E.; Hilgen, F. J.; Edge, D.; Pope, J. O.; Lourens, L. J.

2018-05-01

We examine the response of the Indian and East Asian summer monsoons to separate precession and obliquity forcing, using a set of fully coupled high-resolution models for the first time: EC-Earth, GFDL CM2.1, CESM and HadCM3. We focus on the effect of insolation changes on monsoon precipitation and underlying circulation changes, and find strong model agreement despite a range of model physics, parameterization, and resolution. Our results show increased summer monsoon precipitation at times of increased summer insolation, i.e. minimum precession and maximum obliquity, accompanied by a redistribution of precipitation and convection from ocean to land. Southerly monsoon winds over East Asia are strengthened as a consequence of an intensified land-sea pressure gradient. The response of the Indian summer monsoon is less straightforward. Over south-east Asia low surface pressure is less pronounced and winds over the northern Indian Ocean are directed more westward. An Indian Ocean Dipole pattern emerges, with increased precipitation and convection over the western Indian Ocean. Increased temperatures occur during minimum precession over the Indian Ocean, but not during maximum obliquity when insolation is reduced over the tropics and southern hemisphere during northern hemisphere summer. Evaporation is reduced over the northern Indian Ocean, which together with increased precipitation over the western Indian Ocean dampens the increase of monsoonal precipitation over the continent. The southern tropical Indian Ocean as well as the western tropical Pacific (for precession) act as a moisture source for enhanced monsoonal precipitation. The models are in closest agreement for precession-induced changes, with more model spread for obliquity-induced changes, possibly related to a smaller insolation forcing. Our results indicate that a direct response of the Indian and East Asian summer monsoons to insolation forcing is possible, in line with speleothem records but in contrast to what most marine proxy climate records suggest.

Microprocessor-controlled step-down maximum-power-point tracker for photovoltaic systems

NASA Astrophysics Data System (ADS)

Mazmuder, R. K.; Haidar, S.

1992-12-01

An efficient maximum power point tracker (MPPT) has been developed and can be used with a photovoltaic (PV) array and a load which requires lower voltage than the PV array voltage to be operated. The MPPT makes the PV array to operate at maximum power point (MPP) under all insolation and temperature, which ensures the maximum amount of available PV power to be delivered to the load. The performance of the MPPT has been studied under different insolation levels.

A probabilistic approach to photovoltaic generator performance prediction

NASA Astrophysics Data System (ADS)

Khallat, M. A.; Rahman, S.

1986-09-01

A method for predicting the performance of a photovoltaic (PV) generator based on long term climatological data and expected cell performance is described. The equations for cell model formulation are provided. Use of the statistical model for characterizing the insolation level is discussed. The insolation data is fitted to appropriate probability distribution functions (Weibull, beta, normal). The probability distribution functions are utilized to evaluate the capacity factors of PV panels or arrays. An example is presented revealing the applicability of the procedure.

Development of a quantitative in-shoe measurement system for assessing balance: sixteen-sensor insoles.

PubMed

Bamberg, Stacy M; Lastayo, Paul; Dibble, Lee; Musselman, Josh; Raghavendra, Swarna Kiran Dasa

2006-01-01

This work presents the first phase in the development of an in-shoe sensor system designed to evaluate balance. Sixteen force-sensitive resistors were strategically mounted to a removable insole, and the bilateral outputs were recorded. The initial results indicate that these sensors are capable of detecting subtle changes in weight distribution, corresponding to the subject's ability to balance. Preliminary analysis of this data found a clear correlation between the ability to balance and the state of health of the subject.

The role of Sema4D/CD100 as a therapeutic target for tumor microenvironments and for autoimmune, neuroimmune and bone diseases.

PubMed

Wu, Mingfu; Li, Jing; Gao, Qinglei; Ye, Fei

2016-07-01

Semaphorin 4D (Sema4D), also known as CD100, has been implicated in physiologic roles in the immune and nervous systems. However, the interaction of Sema4D with its high affinity receptor, Plexin-B1, reveals a novel role for Sema4D produced by the tumor microenvironment in tumor angiogenesis and metastasis. The ligation of Sema4D/CD100 with CD72 on immune and inflammatory cells is known to stimulate immune responses and regulation. Because CD100 and CD72 are expressed on lung immune and nonimmune cells, as well as on mast cells, the CD100/CD72 interaction plays another important role in allergic airway inflammation and mast cell functions. A better understanding of Sema4D-mediated cell signaling in physiological and pathological processes may be crucial for crafting new Sema4D-based therapeutics for human disease and tumor microenvironments. Strategies to achieve effective management through treatment with Sema4D include special siRNAs, neutralizing antibodies and knockdown. This review focuses on the links between Sema4D and human diseases such as cancer, bone metabolism, immune responses and organ development. The current knowledge regarding the expression of Sema4D and its receptors and its functional roles is systemically reviewed to explore Sema4D as both a target and a therapeutic in human diseases.

Complement anaphylatoxins as immune regulators in cancer.

PubMed

Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

2014-08-01

The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediated suppression of immune effector cells responsible for immunosurveillance within the tumor microenvironment. This paradigm accords with models of immune dysregulation, such as autoimmunity and infectious disease, which have defined a pathophysiological role for abnormal complement signaling. Several types of immune cells express the cognate receptors for the complement anaphylatoxins, C3aR and C5aR, and demonstrate functional modulation in response to complement stimulation. In turn, impairment of antitumor immunity has been intimately tied to tumor progression in animal models of cancer. In this article, the literature was systematically reviewed to identify studies that have characterized the effects of the complement anaphylatoxins on the composition and function of immune cells within the tumor microenvironment. The search identified six studies based upon models of lymphoma and ovarian, cervical, lung, breast, and mammary cancer, which collectively support the paradigm of complement as an immune regulator in the tumor microenvironment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Altering micro-environments to change population health behaviour: towards an evidence base for choice architecture interventions

PubMed Central

2013-01-01

Background The idea that behaviour can be influenced at population level by altering the environments within which people make choices (choice architecture) has gained traction in policy circles. However, empirical evidence to support this idea is limited, especially its application to changing health behaviour. We propose an evidence-based definition and typology of choice architecture interventions that have been implemented within small-scale micro-environments and evaluated for their effects on four key sets of health behaviours: diet, physical activity, alcohol and tobacco use. Discussion We argue that the limitations of the evidence base are due not simply to an absence of evidence, but also to a prior lack of definitional and conceptual clarity concerning applications of choice architecture to public health intervention. This has hampered the potential for systematic assessment of existing evidence. By seeking to address this issue, we demonstrate how our definition and typology have enabled systematic identification and preliminary mapping of a large body of available evidence for the effects of choice architecture interventions. We discuss key implications for further primary research, evidence synthesis and conceptual development to support the design and evaluation of such interventions. Summary This conceptual groundwork provides a foundation for future research to investigate the effectiveness of choice architecture interventions within micro-environments for changing health behaviour. The approach we used may also serve as a template for mapping other under-explored fields of enquiry. PMID:24359583

Making microenvironments: A look into incorporating macromolecular crowding into in vitro experiments, to generate biomimetic microenvironments which are capable of directing cell function for tissue engineering applications.

PubMed

Benny, Paula; Raghunath, Michael

2017-01-01

Biomimetic microenvironments are key components to successful cell culture and tissue engineering in vitro. One of the most accurate biomimetic microenvironments is that made by the cells themselves. Cell-made microenvironments are most similar to the in vivo state as they are cell-specific and produced by the actual cells which reside in that specific microenvironment. However, cell-made microenvironments have been challenging to re-create in vitro due to the lack of extracellular matrix composition, volume and complexity which are required. By applying macromolecular crowding to current cell culture protocols, cell-made microenvironments, or cell-derived matrices, can be generated at significant rates in vitro. In this review, we will examine the causes and effects of macromolecular crowding and how it has been applied in several in vitro systems including tissue engineering.

Noise in pressure transducer readings produced by variations in solar radiation

USGS Publications Warehouse

Cain, S. F.; Davis, G.A.; Loheide, Steven P.; Butler, J.J.

2004-01-01

Variations in solar radiation can produce noise in readings from gauge pressure transducers when the transducer cable is exposed to direct sunlight. This noise is a result of insolation-induced heating and cooling of the air column in the vent tube of the transducer cable. A controlled experiment was performed to assess the impact of variations in solar radiation on transducer readings. This experiment demonstrated that insolation-induced fluctuations in apparent pressure head can be as large as 0.03 m. The magnitude of these fluctuations is dependent on cable color, the diameter of the vent tube, and the length of the transducer cable. The most effective means of minimizing insolation-induced noise is to use integrated transducer-data logger units that fit within a well. Failure to address this source of noise can introduce considerable uncertainty into analyses of hydraulic tests when the head change is relatively small, as is often the case for tests in highly permeable aquifers or for tests using distant observation wells.

Airborne Measurement of Insolation Impact on the Atmospheric Surface Boundary Layer

NASA Astrophysics Data System (ADS)

Jacob, Jamey; Chilson, Phil; Houston, Adam; Detweiler, Carrick; Bailey, Sean; Cloud-Map Team

2017-11-01

Atmospheric surface boundary layer measurements of wind and thermodynamic parameters are conducted during variable insolation conditions, including the 2017 eclipse, using an unmanned aircraft system. It is well known that the air temperatures can drop significantly during a total solar eclipse as has been previously observed. In past eclipses, these observations have primarily been made on the ground. We present results from airborne measurements of the near surface boundary layer using a small unmanned aircraft with high temporal resolution wind and thermodynamic observations. Questions that motivate the study include: How does the temperature within the lower atmospheric boundary vary during an eclipse? What impact does the immediate removal of radiative heating on the ground have on the lower ABL? Do local wind patterns change during an eclipse event and if so why? Will there be a manifestation of the nocturnal boundary layer wind maximum? Comparisons are made with the DOE ARM SGP site that experiences a lower but still significant insolation. Supported by the National Science Foundation under Award Number 1539070.

Climate drivers of the Amazon forest greening.

PubMed

Wagner, Fabien Hubert; Hérault, Bruno; Rossi, Vivien; Hilker, Thomas; Maeda, Eduardo Eiji; Sanchez, Alber; Lyapustin, Alexei I; Galvão, Lênio Soares; Wang, Yujie; Aragão, Luiz E O C

2017-01-01

Our limited understanding of the climate controls on tropical forest seasonality is one of the biggest sources of uncertainty in modeling climate change impacts on terrestrial ecosystems. Combining leaf production, litterfall and climate observations from satellite and ground data in the Amazon forest, we show that seasonal variation in leaf production is largely triggered by climate signals, specifically, insolation increase (70.4% of the total area) and precipitation increase (29.6%). Increase of insolation drives leaf growth in the absence of water limitation. For these non-water-limited forests, the simultaneous leaf flush occurs in a sufficient proportion of the trees to be observed from space. While tropical cycles are generally defined in terms of dry or wet season, we show that for a large part of Amazonia the increase in insolation triggers the visible progress of leaf growth, just like during spring in temperate forests. The dependence of leaf growth initiation on climate seasonality may result in a higher sensitivity of these ecosystems to changes in climate than previously thought.

The Mars climate for a photovoltaic system operation

NASA Technical Reports Server (NTRS)

Appelbaum, Joseph; Flood, Dennis J.

1989-01-01

Detailed information on the climatic conditions on Mars are very desirable for the design of photovoltaic systems for establishing outposts on the Martian surface. The distribution of solar insolation (global, direct and diffuse) and ambient temperature is addressed. This data are given at the Viking lander's locations and can also be used, to a first approximation, for other latitudes. The insolation data is based on measured optical depth of the Martian atmosphere derived from images taken of the sun with a special diode on the Viking cameras; and computation based on multiple wavelength and multiple scattering of the solar radiation. The ambient temperature (diurnal and yearly distribution) is based on direct measurements with a thermocouple at 1.6 m above the ground at the Viking lander locations. The insolation and ambient temperature information are short term data. New information about Mars may be forthcoming in the future from new analysis of previously collected data or from future flight missions. The Mars climate data for photovoltaic system operation will thus be updated accordingly.

High-Rise Construction in Densely Dwelled Cities: Requirements for Premises Insolation and Consequences of their Violation in Russian Law and Jurisprudence

NASA Astrophysics Data System (ADS)

Gongalo, Boris; Gudovicheva, Lubov; Gubareva, Anna; Dobrynina, Larisa

2018-03-01

The issues of constructing high-rise, primarily residential, buildings have a great social significance. Not every plot of land, acquired in the Russian Federation is suitable for high-rise construction. Therefore, every construction company that plans to erect a multi-apartment building, a high-rise office building, or a skyscraper must take into account not only technical norms but as well sanitary legislation regulations that set obligatory requirements about insolation of apartments. The article includes a short study of several norms in the Russian legislation regarding insolation of dwellings; analises the problems of judicial interpretation of the statutory limitations. In this aspect it researches the debatable questions arising in practice of state arbitration courts dealing with the lawsuits on allocation of land-plots by the local administration. The analysis of the judicial practice is followed by description of the difficulties facing the developers of land-plots, concerning the project and territorial planning documentation.

Radiation modelling and performance evaluations of fixed, single- and double-axis tracking surfaces: a case study for Dhahran city, Saudi Arabia

NASA Astrophysics Data System (ADS)

Abdulsalam, Alrowashed; Idris, Azni Bin; Ahmad, Thamer; Ahsan, Amimul

2017-01-01

This work overviews the solar radiation basics and insolation of different surfaces is presented. A complete solar radiation modelling and investigation on the effect of horizontal plate, yearly tilt, monthly tilt, and single-axis and double-axis tracking surface on the insolation are carried out to conduct performance evaluation using the case study in Dhahran city of Saudi Arabia. The increments received by insolation for the yearly tilt, monthly tilt, and single-axis and dual-axis tracking surface with respect to traditional flat-plate collector is estimated. The results show that the yearly optimal tilt angle due to the south is close to the 0.913 time latitude of Dhahran. It is found that the yearly irradiation gains using yearly and monthly optimal tilts relative to flat panel installation are 7% and 14%, respectively. The yearly insulation gains made by single-axis and dual-axis continuous tracking surfaces are 33% and 48%, respectively.

Variation of solar cell sensitivity and solar radiation on tilted surfaces

NASA Technical Reports Server (NTRS)

Klucher, T. M.

1978-01-01

An empirical study was performed (1) to evaluate the validity of various insolation models used to compute solar radiation incident on tilted surfaces from global data measured on horizontal surfaces and (2) to determine the variation of solar cell sensitivity to solar radiation over a wide range of atmospheric condition. Evaluation of the insolation data indicates that the isotropic sky model of Liu and Jordan underestimates the amount of solar radiation falling on tilted surfaces by as much as 10%. An anisotropic-clear-sky model proposed by Temps and Coulson was also evaluated and found to be deficient under cloudy conditions. A new model, formulated herein, reduced the deviations between measured and predicted insolation to less than 3%. Evaluation of solar cell sensitivity data indicates small change (2-3%) in sensitivity from winter to summer for tilted cells. The feasibility of using such global data as a means for calibrating terrestrial solar cells as done by Treble is discussed.

Noise in pressure transducer readings produced by variations in solar radiation.

PubMed

Cain, Samuel F; Davis, Gregory A; Loheide, Steven P; Butler, James J

2004-01-01

Variations in solar radiation can produce noise in readings from gauge pressure transducers when the transducer cable is exposed to direct sunlight. This noise is a result of insolation-induced heating and cooling of the air column in the vent tube of the transducer cable. A controlled experiment was performed to assess the impact of variations in solar radiation on transducer readings. This experiment demonstrated that insolation-induced fluctuations in apparent pressure head can be as large as 0.03 m. The magnitude of these fluctuations is dependent on cable color, the diameter of the vent tube, and the length of the transducer cable. The most effective means of minimizing insolation-induced noise is to use integrated transducer-data logger units that fit within a well. Failure to address this source of noise can introduce considerable uncertainty into analyses of hydraulic tests when the head change is relatively small, as is often the case for tests in highly permeable aquifers or for tests using distant observation wells.

Response of rainy season duration over Asian monsoon region to astronomical forcing under glacial and interglacial conditions

NASA Astrophysics Data System (ADS)

Shi, Z.

2017-12-01

The responses of Asian summer monsoon and associated precipitation to astronomical forcing have beenintensively explored during the past decades, but debate still exists regarding whether or not the Asianmonsoon is controlled by northern or southern summer insolation. Various modeling studies have been conducted that support the potential roles played by the insolation in bothhemispheres. Among these previous studies, however, the main emphasis has been on the Asianmonsoon intensity, with the response of monsoon duration having received little consideration. In thepresent study, the response of the rainy season duration over different monsoon areas to astronomical forcingand its contribution to total annual precipitation are evaluated using an atmospheric general circulationmodel. The results show that the durations of the rainy seasons, especially their withdrawal, in northernEast Asia and the India-Bay of Bengal region, are sensitive to precession change under interglacial-likeconditions. Compared to those during stronger boreal summer insolation, the Asian monsoon associatedrainy seasons at weaker insolation last longer, although the peak intensity is smaller. Thislonger duration of rainfall, which results from the change in land-ocean thermal contrast associated withatmospheric diabatic heating, can counterbalance the weakened intensity in certain places and induce anopposite response of total annual precipitation. However, the duration effect of Asian monsoon is limitedunder glacial-like conditions. Nevertheless, monsoon duration is a factor that can dominate the astronomical-scalevariability of Asian monsoon, alongside the intensity, and it should therefore receive greaterattention when attempting to explain astronomical-scale monsoon change.

Tumor microenvironment: Sanctuary of the devil.

PubMed

Hui, Lanlan; Chen, Ye

2015-11-01

Tumor cells constantly interact with the surrounding microenvironment. Increasing evidence indicates that targeting the tumor microenvironment could complement traditional treatment and improve therapeutic outcomes for these malignancies. In this paper, we review new insights into the tumor microenvironment, and summarize selected examples of the cross-talk between tumor cells and their microenvironment, which have enhanced our understanding of pathophysiology of the microenvironment. We believe that this rapidly moving field promises many more to come, and they will guide the rational design of combinational therapies for success in cancer eradication. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The measurement of ultraviolet radiation and sunburn time over southern Ontario

NASA Technical Reports Server (NTRS)

Evans, W. F. J.

1994-01-01

Studies of the depletion of ozone which have been conducted from the TOMS instrument on the NIMBUS 7 satellite indicate that total ozone has declined by 5 percent over the last 12 years at most mid-latitudes in the Northern Hemisphere typical of southern Ontario. The measurement of the actual resultant increases in UVB is now important. A monitoring program of UVB (biologically active solar ultraviolet radiation) has been conducted for the last 24 months at a site near Bolton, Ontario. The sunburn time varies from less than 17 minutes in late July, to over 4 hours in December on clear days. The levels depend on solar insolation and total ozone column. The ultraviolet levels are strongly affected by cloud and sky conditions. The implications of present and future depletion on the sunburn time are discussed.

Reading the climate record of the martian polar layered deposits

USGS Publications Warehouse

Hvidberg, C.S.; Fishbaugh, K.E.; Winstrup, M.; Svensson, A.; Byrne, S.; Herkenhoff, K. E.

2012-01-01

The martian polar regions have layered deposits of ice and dust. The stratigraphy of these deposits is exposed within scarps and trough walls and is thought to have formed due to climate variations in the past. Insolation has varied significantly over time and caused dramatic changes in climate, but it has remained unclear whether insolation variations could be linked to the stratigraphic record. We present a model of layer formation based on physical processes that expresses polar deposition rates of ice and dust in terms of insolation. In this model, layer formation is controlled by the insolation record, and dust-rich layers form by two mechanisms: (1) increased summer sublimation during high obliquity, and (2) variations in the polar deposition of dust modulated by obliquity variations. The model is simple, yet physically plausible, and allows for investigations of the climate control of the polar layered deposits (PLD). We compare the model to a stratigraphic column obtained from the north polar layered deposits (NPLD) (Fishbaugh, K.E., Hvidberg, C.S., Byrne, S., Russel, P.S., Herkenhoff, K.E., Winstrup, M., Kirk, R. [2010a]. Geophys. Res. Lett., 37, L07201) and show that the model can be tuned to reproduce complex layer sequences. The comparison with observations cannot uniquely constrain the PLD chronology, and it is limited by our interpretation of the observed stratigraphic column as a proxy for NPLD composition. We identified, however, a set of parameters that provides a chronology of the NPLD tied to the insolation record and consistently explains layer formation in accordance with observations of NPLD stratigraphy. This model dates the top 500 m of the NPLD back to ∼1 million years with an average net deposition rate of ice and dust of 0.55 mm a−1. The model stratigraphy contains a quasi-periodic ∼30 m cycle, similar to a previously suggested cycle in brightness profiles from the NPLD (Laskar, J., Levrard, B., Mustard, F. [2002]. Nature, 419, 375–377; Milkovich, S., Head, J.W. [2005]. J. Geophys. Res. 110), but here related to half of the obliquity cycles of 120 and 99 kyr and resulting from a combination of the two layer formation mechanisms. Further investigations of the non-linear insolation control of PLD formation should consider data from other geographical locations and include radar data and other stratigraphic datasets that can constrain the composition and stratigraphy of the NPLD layers.

The immunological contribution of NF-κB within the tumor microenvironment: A potential protective role of zinc as an anti-tumor agent

PubMed Central

Bao, Bin; Thakur, Archana; Li, Yiwei; Ahmad, Aamir; Azmi, Asfar S.; Banerjee, Sanjeev; Kong, Dejuan; Ali, Shadan; Lum, Lawrence G.; Sarkar, Fazlul H.

2013-01-01

Over decades, cancer treatment has been mainly focused on targeting cancer cells and not much attention to host tumor microenvironment. Recent advances suggest that the tumor microenvironment requires in-depth investigation for understanding the interactions between tumor cell biology and immunobiology in order to optimize therapeutic approaches. Tumor microenvironment consists of cancer cells and tumor associated reactive fibroblasts, infiltrating non-cancer cells, secreted soluble factors or molecules, and non-cellular support materials. Tumor associated host immune cells such as Th1, Th2, Th17, regulatory cells, dendritic cells, macrophages, and myeloid-derived suppressor cells are major components of the tumor microenvironment. Accumulating evidence suggests that these tumor associated immune cells may play important roles in cancer development and progression. However, the exact functions of these cells in the tumor microenvironment are poorly understood. In the tumor microenvironment, NF-κB plays an important role in cancer development and progression because this is a major transcription factor which regulates immune functions within the tumor microenvironment. In this review, we will focus our discussion on the immunological contribution of NF-κB in tumor associated host immune cells within the tumor microenvironment. We will also discuss the potential protective role of zinc, a well-known immune response mediator, in the regulation of these immune cells and cancer cells in the tumor microenvironment especially because zinc could be useful for conditioning the tumor microenvironment toward innovative cancer therapy. PMID:22155217

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

PubMed Central

Senthebane, Dimakatso Alice; Rowe, Arielle; Shipanga, Hendrina; Munro, Daniella; Al Mazeedi, Mohammad A. M.; Almazyadi, Hashim A. M.; Kallmeyer, Karlien

2017-01-01

Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially ‘omics’ technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously ‘unsupportive’ microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix. PMID:28754000

TNF-α signaling in Fanconi anemia

PubMed Central

Du, Wei; Erden, Ozlem; Pang, Qishen

2013-01-01

Tumor necrosis factor-alpha (TNF-α is a major pro-inflammatory cytokine involved in systemic inflammation and the acute phase reaction. Dysregulation of TNF production has been implicated in a variety of human diseases including Fanconi anemia (FA). FA is a genomic instability syndrome characterized by progressive bone marrow failure and cancer susceptibility. The patients with FA are often found overproducing TNF-α, which may directly affect hematopoietic stem cell (HSC) function by impairing HSC survival, homing and proliferation, or indirectly change the bone marrow microenvironment critical for HSC homeostasis and function, therefore contribute to disease progression in FA. In this brief review, we discuss the link between TNF-α signaling and FA pathway with emphasis on the implication of inflammation in the pathophysiology and abnormal hematopoiesis in FA. PMID:23890415

TNF-α signaling in Fanconi anemia.

PubMed

Du, Wei; Erden, Ozlem; Pang, Qishen

2014-01-01

Tumor necrosis factor-alpha (TNF-α) is a major pro-inflammatory cytokine involved in systemic inflammation and the acute phase reaction. Dysregulation of TNF production has been implicated in a variety of human diseases including Fanconi anemia (FA). FA is a genomic instability syndrome characterized by progressive bone marrow failure and cancer susceptibility. The patients with FA are often found overproducing TNF-α, which may directly affect hematopoietic stem cell (HSC) function by impairing HSC survival, homing and proliferation, or indirectly change the bone marrow microenvironment critical for HSC homeostasis and function, therefore contributing to disease progression in FA. In this brief review, we discuss the link between TNF-α signaling and FA pathway with emphasis on the implication of inflammation in the pathophysiology and abnormal hematopoiesis in FA. © 2013.

Implications of immune dysfunction on endometriosis associated infertility

PubMed Central

Miller, Jessica E.; Ahn, Soo Hyun; Monsanto, Stephany P.; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

2017-01-01

Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure. PMID:27740937

Implications of immune dysfunction on endometriosis associated infertility.

PubMed

Miller, Jessica E; Ahn, Soo Hyun; Monsanto, Stephany P; Khalaj, Kasra; Koti, Madhuri; Tayade, Chandrakant

2017-01-24

Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.

Microenvironmental independence associated with tumor progression.

PubMed

Anderson, Alexander R A; Hassanein, Mohamed; Branch, Kevin M; Lu, Jenny; Lobdell, Nichole A; Maier, Julie; Basanta, David; Weidow, Brandy; Narasanna, Archana; Arteaga, Carlos L; Reynolds, Albert B; Quaranta, Vito; Estrada, Lourdes; Weaver, Alissa M

2009-11-15

Tumor-microenvironment interactions are increasingly recognized to influence tumor progression. To understand the competitive dynamics of tumor cells in diverse microenvironments, we experimentally parameterized a hybrid discrete-continuum mathematical model with phenotypic trait data from a set of related mammary cell lines with normal, transformed, or tumorigenic properties. Surprisingly, in a resource-rich microenvironment, with few limitations on proliferation or migration, transformed (but not tumorigenic) cells were most successful and outcompeted other cell types in heterogeneous tumor simulations. Conversely, constrained microenvironments with limitations on space and/or growth factors gave a selective advantage to phenotypes derived from tumorigenic cell lines. Analysis of the relative performance of each phenotype in constrained versus unconstrained microenvironments revealed that, although all cell types grew more slowly in resource-constrained microenvironments, the most aggressive cells were least affected by microenvironmental constraints. A game theory model testing the relationship between microenvironment resource availability and competitive cellular dynamics supports the concept that microenvironmental independence is an advantageous cellular trait in resource-limited microenvironments.

Tumor Microenvironment Modulation via Gold Nanoparticles Targeting Malicious Exosomes: Implications for Cancer Diagnostics and Therapy

PubMed Central

Roma-Rodrigues, Catarina; Raposo, Luís R.; Cabral, Rita; Paradinha, Fabiana; Baptista, Pedro V.; Fernandes, Alexandra R.

2017-01-01

Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes’ release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs’ properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs’ role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression. PMID:28098821

Crossroads of integrins and cadherins in epithelia and stroma remodeling

PubMed Central

Epifano, Carolina; Perez-Moreno, Mirna

2012-01-01

Adhesion events mediated by cadherin and integrin adhesion receptors have fundamental roles in the maintenance of the physiological balance of epithelial tissues, and it is well established that perturbations in their normal functional activity and/or changes in their expression are associated with tumorigenesis. Over the last decades, increasing evidence of a dynamic collaborative interaction between these complexes through their shared interactions with cytoskeletal proteins and common signaling pathways has emerged not only as an important regulator of several aspects of epithelial cell behavior, but also as a coordinated adhesion module that senses and transmits signals from and to the epithelia surrounding microenvironment. The tight regulation of their crosstalk is particularly important during epithelial remodeling events that normally take place during morphogenesis and tissue repair, and when defective it leads to cell transformation and aggravated responses of the tumor microenvironment that contribute to tumorigenesis. In this review we highlight some of the interactions that regulate their crosstalk and how this could be implicated in regulating signals across epithelial tissues to sustain homeostasis. PMID:22568988

Activation of blood coagulation in cancer: implications for tumour progression

PubMed Central

Lima, Luize G.; Monteiro, Robson Q.

2013-01-01

Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies. PMID:23889169

Dynamic Interactions Between Cancer Stem Cells And Their Stromal Partners.

PubMed

Park, Tea Soon; Donnenberg, Vera S; Donnenberg, Albert D; Zambidis, Elias T; Zimmerlin, Ludovic

2014-03-01

The cancer stem cell (CSC) paradigm presumes the existence of self-renewing cancer cells capable of regenerating all tumor compartments and exhibiting stem cell-associated phenotypes. Recent interpretations of the CSC hypothesis envision stemness as a dynamic trait of tumor-initiating cells rather than a defined and unique cell type. Bidirectional crosstalk between the tumor microenvironment and the cancer bulk is well described in the literature and the tumor-associated stroma, vasculature and immune infiltrate have all been implicated as direct contributors to tumor development. These non-neoplastic cell types have also been shown to organize specific niches within the tumor bulk where they can control the intra-tumor CSC content and alter the fate of CSCs and tumor progenitors during tumorigenesis to acquire phenotypic features for invasion, metastasis and dormancy. Despite the complexity of the tumor-stroma interactome, novel therapeutic approaches envision combining tumor-ablative treatment with manipulation of the tumor microenvironment. We will review the currently available literature that provides clues about the complex cellular network that regulate the CSC phenotype and its niches during tumor progression.

Tumor Microenvironment Modulation via Gold Nanoparticles Targeting Malicious Exosomes: Implications for Cancer Diagnostics and Therapy.

PubMed

Roma-Rodrigues, Catarina; Raposo, Luís R; Cabral, Rita; Paradinha, Fabiana; Baptista, Pedro V; Fernandes, Alexandra R

2017-01-14

Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs' properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs' role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.

Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma

PubMed Central

2017-01-01

The tumor microenvironment is implicated in orchestrating cancer cell transformation and metastasis. However, specific cell–ligand interactions between cancer cells and the extracellular matrix are difficult to decipher due to a dynamic and multivariate presentation of many signaling molecules. Here we report a versatile peptide microarray platform that is capable of screening for cancer cell phenotypic changes in response to ligand–receptor interactions. Using a screen of 78 peptide combinations derived from proteins present in the melanoma microenvironment, we identify a proteoglycan binding and bone morphogenic protein 7 (BMP7) derived sequence that selectively promotes the expression of several putative melanoma initiating cell markers. We characterize signaling associated with each of these peptides in the activation of melanoma pro-tumorigenic signaling and reveal a role for proteoglycan mediated adhesion and signaling through Smad 2/3. A defined substratum that controls the state of malignant melanoma may prove useful in spatially normalizing a heterogeneous population of tumor cells for discovery of therapeutics that target a specific state and for identifying new drug targets and reagents for intervention. PMID:28573199

Acid-Sensitive Sheddable PEGylated, Mannose-Modified Nanoparticles Increase the Delivery of Betamethasone to Chronic Inflammation Sites in a Mouse Model.

PubMed

O'Mary, Hannah L; Aldayel, Abdulaziz M; Valdes, Solange A; Naguib, Youssef W; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-06-05

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions.

Intravital imaging of multicolor-labeled tumor immune microenvironment through skin-fold window chamber

NASA Astrophysics Data System (ADS)

Qi, Shuhong; Zhang, Zhihong

2015-03-01

Tumor immune microenvironment became very important for the tumor immunotherapy. There were several kinds of immune cells in tumor stromal, and they played very different roles in tumor growth. In order to observe the behaviors of multiple immune cells in tumor microenvironment and the interaction between immune cells and tumor cells at the same time, we generated a multicolor-labeled tumor immune microenvironment model. The tumor cells and immune cells were labeled by different fluorescent proteins. By using of skin-fold window chamber implanted into mice and intravital imaging technology, we could dynamically observe the different immune cells in tumor microenvironment. After data analysis from the video, we could know the behavior of TILs, DCs and Tregs in tumor immune microenvironment; furthermore, we could know these immune cells play different roles in the tumor microenvironment.

Pharmacological targets of breast cancer stem cells: a review.

PubMed

Pindiprolu, Sai Kiran S S; Krishnamurthy, Praveen T; Chintamaneni, Pavan Kumar

2018-05-01

Breast cancers contain small population of tumor-initiating cells called breast cancer stem cells (BCSCs), which are spared even after chemotherapy. Recently, BCSCs are implicated to be a cause of metastasis, tumor relapse, and therapy resistance in breast cancer. BCSCs have unique molecular mechanisms, which can be targeted to eliminate them. These include surface biomarkers, proteins involved in self-renewal pathways, drug efflux transporters, apoptotic/antiapoptotic proteins, autophagy, metabolism, and microenvironment regulation. The complex molecular mechanisms behind the survival of BCSCs and pharmacological targets for elimination of BCSCs are described in this review.

A Smart Insole to Promote Healthy Aging for Frail Elderly Individuals: Specifications, Design, and Preliminary Results.

PubMed

Piau, Antoine; Charlon, Yoann; Campo, Eric; Vellas, Bruno; Nourhashemi, Fati

2015-05-25

Older individuals frequently experience reversible "frailty syndrome,", increasing incidence of disability. Although physical exercise interventions may delay functional decline, there are difficulties in implementing them and performing seamless follow-up at home. Very few technological solutions attempt to address this challenge and improve individual participation. Our objectives are to (1) develop a technological solution designed to support active aging of frail older persons, (2) conduct a first laboratory evaluation of the device, and (3) design a multidimensional clinical trial to validate our solution. We conducted a first phase of multidisciplinary meetings to identify real end users and health professional's unmet needs, and to produce specifications for the architecture of the solution. In a second phase, we performed laboratory tests of the first proposed prototype (a smart insole) with 3 healthy volunteers. We then designed an ongoing clinical trial to finalize the multidimensional evaluation and improvement of the solution. To respond to the needs expressed by the stakeholders (frailty monitoring and adherence improvement), we developed a prototype of smart shoe insole to monitor key parameters of frailty during daily life and promote walking. It is a noninvasive wireless insole, which automatically measures gait parameters and transmits information to a remote terminal via a secure Internet connection. To ensure the solution's autonomy and transparency, we developed an original energy harvesting system, which transforms mechanical energy produced by the user's walking movement into electrical energy. The first laboratory tests of this technological solution showed good reliability measures and also a good acceptability for the users. We have planned an original iterative medical research protocol to validate our solution in real life. Our smart insole could support preventive strategies against disability in primary care by empowering the older patients without increasing the busy health professional's workload. Clinicaltrials.gov NCT02316600; https://clinicaltrials.gov/ct2/results?term=NCT02316600&Search=Search. Accessed: 2015-05-13 . (Archived by WebCite at http://www.webcitation.org/6YUTkObrQ). ©Antoine Piau, Yoann Charlon, Eric Campo, Bruno Vellas, Fati Nourhashemi. Originally published in JMIR Rehabilitation and Assistive Technology (http://rehab.jmir.org), 25.05.2015.

Indian monsoon variations during three contrasting climatic periods: the Holocene, Heinrich Stadial 2 and the last interglacial-glacial transition

NASA Astrophysics Data System (ADS)

Zorzi, Coralie; Fernanda Sanchez Goñi, Maria; Anupama, Krishnamurthy; Prasad, Srinivasan; Hanquiez, Vincent; Johnson, Joel; Giosan, Liviu

2016-04-01

In contrast to the East Asian and African monsoons the Indian monsoon is still poorly documented throughout the last climatic cycle (last 135,000 years). Pollen analysis from two marine sediment cores (NGHP-01-16A and NGHP-01-19B) collected from the offshore Godavari and Mahanadi basins, both located in the Core Monsoon Zone (CMZ) reveals changes in Indian summer monsoon variability and intensity during three contrasting climatic periods: the Holocene, the Heinrich Stadial (HS) 2 and the Marine Isotopic Stage (MIS) 5/4 during the ice sheet growth transition. During the first part of the Holocene between 11,300 and 4,200 cal years BP, characterized by high insolation (minimum precession, maximum obliquity), the maximum extension of the coastal forest and mangrove reflects high monsoon rainfall. This climatic regime contrasts with that of the second phase of the Holocene, from 4,200 cal years BP to the present, marked by the development of drier vegetation in a context of low insolation (maximum precession, minimum obliquity). The historical period in India is characterized by an alternation of strong and weak monsoon centennial phases that may reflect the Medieval Climate Anomaly and the Little Ice Age, respectively. During the HS 2, a period of low insolation and extensive iceberg discharge in the North Atlantic Ocean, vegetation was dominated by grassland and dry flora indicating pronounced aridity as the result of a weak Indian summer monsoon. The MIS 5/4 glaciation, also associated with low insolation but moderate freshwater fluxes, was characterized by a weaker reduction of the Indian summer monsoon and a decrease of seasonal contrast as recorded by the expansion of dry vegetation and the development of Artemisia, respectively. Our results support model predictions suggesting that insolation changes control the long term trend of the Indian monsoon precipitation, but its millennial scale variability and intensity are instead modulated by atmospheric teleconnections to remote phenomena in the North Atlantic, Eurasia or the Indian Ocean.

Seychelles coral record of changes in sea surface temperature bimodality in the western Indian Ocean from the Mid-Holocene to the present

NASA Astrophysics Data System (ADS)

Zinke, J.; Pfeiffer, M.; Park, W.; Schneider, B.; Reuning, L.; Dullo, W.-Chr.; Camoin, G. F.; Mangini, A.; Schroeder-Ritzrau, A.; Garbe-Schönberg, D.; Davies, G. R.

2014-08-01

We report fossil coral records from the Seychelles comprising individual time slices of 14-20 sclerochronological years between 2 and 6.2 kyr BP to reconstruct changes in the seasonal cycle of western Indian Ocean sea surface temperature (SST) compared to the present (1990-2003). These reconstructions allowed us to link changes in the SST bimodality to orbital changes, which were causing a reorganization of the seasonal insolation pattern. Our results reveal the lowest seasonal SST range in the Mid-Holocene (6.2-5.2 kyr BP) and around 2 kyr BP, while the highest range is observed around 4.6 kyr BP and between 1990 and 2003. The season of maximum temperature shifts from austral spring (September to November) to austral autumn (March to May), following changes in seasonal insolation over the past 6 kyr. However, the changes in SST bimodality do not linearly follow the insolation seasonality. For example, the 5.2 and 6.2 kyr BP corals show only subtle SST differences in austral spring and autumn. We use paleoclimate simulations of a fully coupled atmosphere-ocean general circulation model to compare with proxy data for the Mid-Holocene around 6 kyr BP. The model results show that in the Mid-Holocene the austral winter and spring seasons in the western Indian Ocean were warmer while austral summer was cooler. This is qualitatively consistent with the coral data from 6.2 to 5.2 kyr BP, which shows a similar reduction in the seasonal amplitude compared to the present day. However, the pattern of the seasonal SST cycle in the model appears to follow the changes in insolation more directly than indicated by the corals. Our results highlight the importance of ocean-atmosphere interactions for Indian Ocean SST seasonality throughout the Holocene. In order to understand Holocene climate variability in the countries surrounding the Indian Ocean, we need a much more comprehensive analysis of seasonally resolved archives from the tropical Indian Ocean. Insolation data alone only provides an incomplete picture.

Review of microfluidic cell culture devices for the control of gaseous microenvironments in vitro

NASA Astrophysics Data System (ADS)

Wu, H.-M.; Lee, T.-A.; Ko, P.-L.; Chiang, H.-J.; Peng, C.-C.; Tung, Y.-C.

2018-04-01

Gaseous microenvironments play important roles in various biological activities in vivo. However, it is challenging to precisely control gaseous microenvironments in vitro for cell culture due to the high diffusivity nature of gases. In recent years, microfluidics has paved the way for the development of new types of cell culture devices capable of manipulating cellular microenvironments, and provides a powerful tool for in vitro cell studies. This paper reviews recent developments of microfluidic cell culture devices for the control of gaseous microenvironments, and discusses the advantages and limitations of current devices. We conclude with suggestions for the future development of microfluidic cell culture devices for the control of gaseous microenvironments.

Should Ballet Dancers Vary Postures and Underfoot Surfaces When Practicing Postural Balance?

PubMed

Steinberg, Nili; Waddington, Gordon; Adams, Roger; Karin, Janet; Tirosh, Oren

2018-01-01

Postural balance (PB) is an important component skill for professional dancers. However, the effects of different types of postures and different underfoot surfaces on PB have not adequately been addressed. The main aim of this study was to investigate the effect of different conditions of footwear, surfaces, and standing positions on static and dynamic PB ability of young ballet dancers. A total of 36 male and female young professional ballet dancers (aged 14-19 years) completed static and dynamic balance testing, measured by head and lumbar accelerometers, while standing on one leg in the turnout position, under six different conditions: (1) "relaxed" posture; (2) "ballet" posture; (3) barefoot; (4) ballet shoes with textured insoles; (5) barefoot on a textured mat; and (6) barefoot on a spiky mat. A condition effect was found for static and dynamic PB. Static PB was reduced when dancers stood in the ballet posture compared with standing in the relaxed posture and when standing on a textured mat and on a spiky mat (p < .05), and static PB in the relaxed posture was significantly better than PB in all the other five conditions tested. Dynamic PB was significantly better while standing in ballet shoes with textured insoles and when standing on a spiky mat compared with all other conditions (p < .05). The practical implications derived from this study are that both male and female dancers should try to be relaxed in their postural muscles when practicing a ballet aligned position, including dance practice on different types of floors and on different types of textured/spiky materials may result in skill transfer to practice on normal floor surfaces, and both static and dynamic PB exercises should be assessed and generalized into practical dance routines.

Optical imaging of tumor microenvironment

PubMed Central

Wu, Yihan; Zhang, Wenjie; Li, Jinbo; Zhang, Yan

2013-01-01

Tumor microenvironment plays important roles in tumor development and metastasis. Features of the tumor microenvironment that are significantly different from normal tissues include acidity, hypoxia, overexpressed proteases and so on. Therefore, these features can serve as not only biomarkers for tumor diagnosis but also theraputic targets for tumor treatment. Imaging modalities such as optical, positron emission tomography (PET) and magnetic resonance imaging (MRI) have been intensively applied to investigate tumor microenvironment. Various imaging probes targeting pH, hypoxia and proteases in tumor microenvironment were thus well developed. In this review, we will focus on recent examples on fluorescent probes for optical imaging of tumor microenvironment. Construction of these fluorescent probes were based on characteristic feature of pH, hypoxia and proteases in tumor microenvironment. Strategies for development of these fluorescent probes and applications of these probes in optical imaging of tumor cells or tissues will be discussed in this review paper. PMID:23342297

Concurrent validation of an index to estimate fall risk in community dwelling seniors through a wireless sensor insole system: A pilot study.

PubMed

Di Rosa, Mirko; Hausdorff, Jeff M; Stara, Vera; Rossi, Lorena; Glynn, Liam; Casey, Monica; Burkard, Stefan; Cherubini, Antonio

2017-06-01

Falls are a major health problem for older adults with immediate effects, such as fractures and head injuries, and longer term effects including fear of falling, loss of independence, and disability. The goals of the WIISEL project were to develop an unobtrusive, self-learning and wearable system aimed at assessing gait impairments and fall risk of older adults in the home setting; assessing activity and mobility in daily living conditions; identifying decline in mobility performance and detecting falls in the home setting. The WIISEL system was based on a pair of electronic insoles, able to transfer data to a commercially available smartphone, which was used to wirelessly collect data in real time from the insoles and transfer it to a backend computer server via mobile internet connection and then onwards to a gait analysis tool. Risk of falls was calculated by the system using a novel Fall Risk Index (FRI) based on multiple gait parameters and gait pattern recognition. The system was tested by twenty-nine older users and data collected by the insoles were compared with standardized functional tests with a concurrent validity approach. The results showed that the FRI captures the risk of falls with accuracy that is similar to that of conventional performance-based tests of fall risk. These preliminary findings support the idea that theWIISEL system can be a useful research tool and may have clinical utility for long-term monitoring of fall risk at home and in the community setting. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

PubMed

Bauer, Michael; Glenn, Tasha; Alda, Martin; Andreassen, Ole A; Angelopoulos, Elias; Ardau, Raffaella; Baethge, Christopher; Bauer, Rita; Bellivier, Frank; Belmaker, Robert H; Berk, Michael; Bjella, Thomas D; Bossini, Letizia; Bersudsky, Yuly; Cheung, Eric Yat Wo; Conell, Jörn; Del Zompo, Maria; Dodd, Seetal; Etain, Bruno; Fagiolini, Andrea; Frye, Mark A; Fountoulakis, Kostas N; Garneau-Fournier, Jade; González-Pinto, Ana; Harima, Hirohiko; Hassel, Stefanie; Henry, Chantal; Iacovides, Apostolos; Isometsä, Erkki T; Kapczinski, Flávio; Kliwicki, Sebastian; König, Barbara; Krogh, Rikke; Kunz, Mauricio; Lafer, Beny; Larsen, Erik R; Lewitzka, Ute; Lopez-Jaramillo, Carlos; MacQueen, Glenda; Manchia, Mirko; Marsh, Wendy; Martinez-Cengotitabengoa, Mónica; Melle, Ingrid; Monteith, Scott; Morken, Gunnar; Munoz, Rodrigo; Nery, Fabiano G; O'Donovan, Claire; Osher, Yamima; Pfennig, Andrea; Quiroz, Danilo; Ramesar, Raj; Rasgon, Natalie; Reif, Andreas; Ritter, Philipp; Rybakowski, Janusz K; Sagduyu, Kemal; Scippa, Ângela M; Severus, Emanuel; Simhandl, Christian; Stein, Dan J; Strejilevich, Sergio; Sulaiman, Ahmad Hatim; Suominen, Kirsi; Tagata, Hiromi; Tatebayashi, Yoshitaka; Torrent, Carla; Vieta, Eduard; Viswanath, Biju; Wanchoo, Mihir J; Zetin, Mark; Whybrow, Peter C

2014-01-01

The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. Recall bias for onset and family history data. A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Volatile Transport Implications from the New Horizons Flyby of Pluto

NASA Astrophysics Data System (ADS)

Young, Leslie; Grundy, William M.; Binzel, RIchard P.; Earle, Alissa M.; Linscott, Ivan R.; Hinson, David P.; Zangari, Amanda M.; McKinnon, William B.; Stern, S. Alan; Weaver, Harold A.; Olkin, Catherine B.; Ennico, Kimberly; Gladstone, G. Randall; Summers, Michael E.; Moore, Jeffrey M.; Spencer, John R.

2015-11-01

The New Horizons flyby of Pluto has revealed a striking range of terrains, from the very bright region informally named Sputnik Planum, to very dark regions such as the informally named Cthulhu Regio. Such a variety was beyond the scope of recent models of Pluto's seasonal volatile cycle (Young 2013, ApJL 766, L22; Hansen, Paige and Young 2015, Icarus 246, 183), which assumed globally uniform substrate albedos. The "Exchange with Pressure Plateau (EPP)" class of models in Young (2013) and the favored runs from Hansen et al (2015) had long periods of exchange of volatiles between northern and southern hemispheres. In these models, the equators were largely devoid of volatiles; even though the equatorial latitudes received less insolation than the poles over a Pluto year, they were never the coldest place on the icy world. New models that include a variety of substrate albedos can investigate questions such as whether Sputnik Planum has an albedo that is high enough to act as a local cold trap for much of Pluto's year. We will present the implications of this and other assumption-busting revelations from the New Horizons flyby. This work was supported by NASA’s New Horizons project.

Implication of mountain shading and topographic scaling on energy for snowmelt

NASA Astrophysics Data System (ADS)

Marsh, C.; Pomeroy, J. W.; Spiteri, R.

2011-12-01

In many parts of the world, snowmelt energetics are dominated by incoming solar radiation. This is the case in the Canadian Rockies, where sunny winters result in high insolation. Solar irradiance on the snow surface is affected by the atmosphere, the slope and aspect of the immediate topography, and shading from surrounding terrain. Errors in estimating solar irradiation are cumulative over a season and can lead to large errors in snowmelt predictions. Adaptive triangular meshes, a type of unstructured triangular mesh that can adapt to fine-scale processes during model runtime, are more efficient in their use of DEM data than fixed grids when producing solar irradiance maps. An experimental design to calculate the effect of changes in DEM resolution on adaptive mesh irradiation calculations and implication for snowmelt is presented. As part of this experiment, the accuracy of these techniques is compared to measurements of mountain shadows and solar irradiance collected in Marmot Creek Research Basin, Alberta. Time-lapse digital cameras and networks of radiometers provide datasets for diagnosis of model accuracy. Further improvements in computational efficiency are achieved by taking advantage of parallel processing using graphical processing units (GPUs) is also discussed.

The Asian monsoon over the past 640,000 years and ice age terminations.

PubMed

Cheng, Hai; Edwards, R Lawrence; Sinha, Ashish; Spötl, Christoph; Yi, Liang; Chen, Shitao; Kelly, Megan; Kathayat, Gayatri; Wang, Xianfeng; Li, Xianglei; Kong, Xinggong; Wang, Yongjin; Ning, Youfeng; Zhang, Haiwei

2016-06-30

Oxygen isotope records from Chinese caves characterize changes in both the Asian monsoon and global climate. Here, using our new speleothem data, we extend the Chinese record to cover the full uranium/thorium dating range, that is, the past 640,000 years. The record's length and temporal precision allow us to test the idea that insolation changes caused by the Earth's precession drove the terminations of each of the last seven ice ages as well as the millennia-long intervals of reduced monsoon rainfall associated with each of the terminations. On the basis of our record's timing, the terminations are separated by four or five precession cycles, supporting the idea that the '100,000-year' ice age cycle is an average of discrete numbers of precession cycles. Furthermore, the suborbital component of monsoon rainfall variability exhibits power in both the precession and obliquity bands, and is nearly in anti-phase with summer boreal insolation. These observations indicate that insolation, in part, sets the pace of the occurrence of millennial-scale events, including those associated with terminations and 'unfinished terminations'.

A Novel Detection Model and Its Optimal Features to Classify Falls from Low- and High-Acceleration Activities of Daily Life Using an Insole Sensor System

PubMed Central

Cates, Benjamin; Sim, Taeyong; Heo, Hyun Mu; Kim, Bori; Kim, Hyunggun; Mun, Joung Hwan

2018-01-01

In order to overcome the current limitations in current threshold-based and machine learning-based fall detectors, an insole system and novel fall classification model were created. Because high-acceleration activities have a high risk for falls, and because of the potential damage that is associated with falls during high-acceleration activities, four low-acceleration activities, four high-acceleration activities, and eight types of high-acceleration falls were performed by twenty young male subjects. Encompassing a total of 800 falls and 320 min of activities of daily life (ADLs), the created Support Vector Machine model’s Leave-One-Out cross-validation provides a fall detection sensitivity (0.996), specificity (1.000), and accuracy (0.999). These classification results are similar or superior to other fall detection models in the literature, while also including high-acceleration ADLs to challenge the classification model, and simultaneously reducing the burden that is associated with wearable sensors and increasing user comfort by inserting the insole system into the shoe. PMID:29673165

Insole-pressure distribution for normal children in different age groups.

PubMed

Liu, Xue-Cheng; Lyon, Roger; Thometz, John G; Curtin, Brian; Tarima, Serge; Tassone, Channing

2011-09-01

In measuring plantar pressures during gait, earlier methods have used a platform system that does not take into account the interactions feet have with orthotics and shoe wearing. The purpose of the study was to provide normal insole plantar pressure parameter data during stance phase using the Pedar pressure insole system. Twenty-nine normal children, age 6 to 16 years, were recruited and walked along the 25 m walkway at self-selected speeds. Patients were divided into 2 separate groups for statistical analysis--juniors (< 12 y old) and teenagers (> 13 y old). The pressure map was divided into 8 regions (masks) determined by anatomic landmarks and a total of 7 pressure parameters were analyzed of each mask. We did not detect significant differences in foot pressures between juniors and teenagers when regarding sex, or left and right feet for 7 parameters measured. This normative data will provide a basis with which to more accurately assess pediatric pathologic foot deformities and to distinguish dynamic foot deformities from anatomic foot deformities. THE LEVEL OF EVIDENCE: Level II.

GRP78 is implicated in the modulation of tumor aerobic glycolysis by promoting autophagic degradation of IKKβ.

PubMed

Li, Zongwei; Wang, Yingying; Newton, Ian P; Zhang, Lichao; Ji, Pengyu; Li, Zhuoyu

2015-06-01

Compared with normal differentiated cells, cancer cells take up much more glucose and metabolize it mainly via aerobic glycolysis. This metabolic phenotype is characterized with high expression of glucose transporters (Gluts) and pyruvate kinase M2 (PKM2). Glucose regulated protein 78 (GRP78) is a glucose-sensing protein and frequently up-regulated in cancer cells, however, whether it is directly implicated in glucose metabolism remains to be elucidated. Here we report that upon glucose deficiency, the induction of GRP78 resulted in enhanced HIF-1α transcription, accompanied by a transient increased expression of Glut-1. In addition, GRP78 was likely to facilitate the membrane translocation of Glut-1 via protein-protein interaction. Glucose starvation-stimulated GRP78 also impaired the expression of PKM2 but promoted the expression of mitochondrial pyruvate dehydrogenase A (PDHA) and B (PDHB), resulting in the metabolic shift from glycolysis to the TCA cycle. Interestingly, the inhibition of PKM2 by GRP78 was abrogated when glucose supply was restored, suggesting that GRP78 and PKM2 expressions are adaptable to the nutritional levels in the microenvironment. Further mechanistic study indicated that GRP78 overexpression activated the Class III PI3K-mediated autophagy pathway and induced autophagic degradation of IKKβ, which caused inactivation of NF-κB pathway and subsequently altered the expression of PKM2 and HIF-1α. Our study establishes GRP78 and PKM2 as the crucial molecular links between cancer cell glucose metabolism and tumor microenvironment alterations. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology.

PubMed

Tilan, Jason; Kitlinska, Joanna

2016-02-01

Neuropeptide Y (NPY) is a sympathetic neurotransmitter with pleiotropic actions, many of which are highly relevant to tumor biology. Consequently, the peptide has been implicated as a factor regulating the growth of a variety of tumors. Among them, two pediatric malignancies with high endogenous NPY synthesis and release - neuroblastoma and Ewing sarcoma - became excellent models to investigate the role of NPY in tumor growth and progression. The stimulatory effect on tumor cell proliferation, survival, and migration, as well as angiogenesis in these tumors, is mediated by two NPY receptors, Y2R and Y5R, which are expressed in either a constitutive or inducible manner. Of particular importance are interactions of the NPY system with the tumor microenvironment, as hypoxic conditions commonly occurring in solid tumors strongly activate the NPY/Y2R/Y5R axis. This activation is triggered by hypoxia-induced up-regulation of Y2R/Y5R expression and stimulation of dipeptidyl peptidase IV (DPPIV), which converts NPY to a selective Y2R/Y5R agonist, NPY(3-36). While previous studies focused mainly on the effects of NPY on tumor growth and vascularization, they also provided insight into the potential role of the peptide in tumor progression into a metastatic and chemoresistant phenotype. This review summarizes our current knowledge of the role of NPY in neuroblastoma and Ewing sarcoma and its interactions with the tumor microenvironment in the context of findings in other malignancies, as well as discusses future directions and potential clinical implications of these discoveries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Properties of shoe insert materials related to shock wave transmission during gait.

PubMed

Forner, A; García, A C; Alcántara, E; Ramiro, J; Hoyos, J V; Vera, P

1995-12-01

The influence of the mechanical characteristics of certain insole materials in the generation and transmission of heel strike impacts while walking was studied. Three insole materials were selected according to their mechanical characteristics under heel strike impacts. The selection of materials has made it possible to distinguish the effect of rigidity and loss tangent in the transmission of heel strike impacts. A lower rigidity and a high loss tangent have been shown to reduce the transmission of impacts to the tibia. A low rigidity was seen to significantly increase the transmission of impacts from tibia to forehead.

Plantar pressure cartography reconstruction from 3 sensors.

PubMed

Abou Ghaida, Hussein; Mottet, Serge; Goujon, Jean-Marc

2014-01-01

Foot problem diagnosis is often made by using pressure mapping systems, unfortunately located and used in the laboratories. In the context of e-health and telemedicine for home monitoring of patients having foot problems, our focus is to present an acceptable system for daily use. We developed an ambulatory instrumented insole using 3 pressures sensors to visualize plantar pressure cartographies. We show that a standard insole with fixed sensor position could be used for different foot sizes. The results show an average error measured at each pixel of 0.01 daN, with a standard deviation of 0.005 daN.

Hydrodynamic control of microphytoplankton bloom in a coastal sea

NASA Astrophysics Data System (ADS)

Murty, K. Narasimha; Sarma, Nittala S.; Pandi, Sudarsana Rao; Chiranjeevulu, Gundala; Kiran, Rayaprolu; Muralikrishna, R.

2017-08-01

The influence of hydrodynamics on phytoplankton bloom occurrence/formation has not been adequately reported. Here, we document diurnal observations in the tropical Bay of Bengal's mid-western shelf region which reveal microphytoplankton cell density maxima in association with neap tide many times more than what could be accounted for by solar insolation and nutrient levels. When in summer, phytoplankton cells were abundant and the cell density of Guinardia delicatula reached critical value by tide caused zonation, aggregation happened to an intense bloom. Mucilaginous exudates from the alga due to heat and silicate stress likely promoted and stable water column and weak winds left undisturbed, the transient bloom. The phytoplankton aggregates have implication as food resource in the benthic region implying higher fishery potential, in carbon dioxide sequestration (carbon burial) and in efforts towards improving remote sensing algorithms for chlorophyll in the coastal region.

Ceres: predictions for near-surface water ice stability and implications for plume generating processes

USGS Publications Warehouse

Titus, Timothy N.

2015-01-01

This paper will constrain the possible sources and processes for the formation of recently observed H2O vapor plumes above the surface of the dwarf planet Ceres. Two hypotheses have been proposed: (1) cryovolcanism where the water source is the mantle and the heating source is still unknown or (2) comet-like sublimation where near-surface water ice is vaporized by seasonally increasing solar insolation. We test hypothesis #2, comet-like near-surface sublimation, by using a thermal model to examine the stability of water-ice in the near surface. For a reasonable range of physical parameters (thermal inertia, surface roughness, slopes), we find that water ice is only stable at latitudes higher than ~40-60 degrees. These results indicate that either (a) the physical properties of Ceres are unlike our expectations or (b) an alternative to comet-like sublimation, such as the cryovolcanism hypothesis, must be invoked.

Regional comparisons of on-site solar potential in the residential and industrial sectors

NASA Astrophysics Data System (ADS)

Gatzke, A. E.; Skewes-Cox, A. O.

1980-10-01

Regional and subregional differences in the potential development of decentralized solar technologies are studied. Two sectors of the economy were selected for intensive analysis: the residential and industrial sectors. The sequence of analysis follows the same general steps: (1) selection of appropriate prototypes within each land use sector disaggregated by census region; (2) characterization of the end-use energy demand of each prototype in order to match an appropriate decentralized solar technology to the energy demand; (3) assessment of the energy conservation potential within each prototype limited by land use patterns, technology efficiency, and variation in solar insolation; and (4) evaluation of the regional and subregional differences in the land use implications of decentralized energy supply technologies that result from the combination of energy demand, energy supply potential, and the subsequent addition of increasingly more restrictive policies to increase the percent contribution of on-site solar energy.

Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics

PubMed Central

LaBarge, Mark A; Parvin, Bahram; Lorens, James B

2014-01-01

The field of bioengineering has pioneered the application of new precision fabrication technologies to model the different geometric, physical or molecular components of tissue microenvironments on solid-state substrata. Tissue engineering approaches building on these advances are used to assemble multicellular mimetic-tissues where cells reside within defined spatial contexts. The functional responses of cells in fabricated microenvironments has revealed a rich interplay between the genome and extracellular effectors in determining cellular phenotypes, and in a number of cases has revealed the dominance of microenvironment over genotype. Precision bioengineered substrata are limited to a few aspects, whereas cell/tissue-derived microenvironments have many undefined components. Thus introducing a computational module may serve to integrate these types of platforms to create reasonable models of drug responses in human tissues. This review discusses how combinatorial microenvironment microarrays and other biomimetic microenvironments have revealed emergent properties of cells in particular microenvironmental contexts, the platforms that can measure phenotypic changes within those contexts, and the computational tools that can unify the microenvironment-imposed functional phenotypes with underlying constellations of proteins and genes. Ultimately we propose that a merger of these technologies will enable more accurate pre-clinical drug discovery. PMID:24582543

Suppression of insolation heating induced by electromagnetic scatteringdue to fine spheres

NASA Astrophysics Data System (ADS)

Horie, J.; Mikada, H.; Goto, T.; Takekawa, J.; Manaka, Y.; Taniguchi, K.; Ashida, Y.

2013-12-01

The 2011 off the Pacific coast of Tohoku Earthquake, i.e., the greatest earthquake in the Japanese history, and the successive disaster at the Fukushima Daiichi Nuclear Power Plant have caused a fatal electric power shortage problem in summer in 2011. It is of key importance to reduce electricity demand and to save the energy. About one third of the total electricity demand at the peak consumption in summer is for the air-conditioning in the household and office sectors in Japan. It is, therefore, necessary to think deliberately of the reduction of electric power demand for air-conditioning. In fact, the temperature of materials rises when they are exposed to the sunlight (insolation heating) in particular in summer and the air-conditioning would become necessary for restoring the comfort in insolated housings. The energy for the air-conditioning is spent to pump out the heat changed in the materials of the insolated housings and would be proportional to the temperature to lower down. It is, therefore, clear that the reduction of the energy for the air-conditioning would strongly depend on relaxation of temperature rise or the insulation of insolated materials. Insolation heating could be suppressed when the materials are coated with paint admixed with fine silica spheres (insulating paint). By coating buildings' walls and roofs with such paint, the temperature of interior rooms could be kept lower without air-conditioning. These insulation effects are well known and have been utilized in the past, but have hardly been analyzed theoretically yet. Theoretical analysis would greatly enhance the effects of the suppression of insolation heating. In preceding studies, Ohkawa et al.(2009; 2011) and Mikada et al.(2011) focused on the electromagnetic wave scattering induced by fine spheres and developed the analytical method using superposition of scattered waves from each sphere (the first Born approximation), and indicated that the size of the spheres is one of the parameters affecting the light intensity transmitted through the paint. However, the rigorous results, not using such approximation or considering other parameters than the size of spheres, are still unknown. Such rigorous solution is necessary to find the best structure of the paint for insulating phenomena. In this study, we consider fine spheres randomly distributed in a paint layer coating a material, and analyze its scattering characteristics using the Monte Carlo ray tracing method based on the Mie theory. Three layers (air, paint and iron) are first assumed and a number of photons incident on the paint layer. The optical paths of photons are successively traced. We use their ratio between the number of reflected and transmitted photons and their phases in order toestimate the intensity of near-infrared sunlight that reaches the material (transmission intensity). As a result, it is found that the sphere radius should be less than 0.5 μm and the refractive index of sphere is less than 1.45 if we want to decrease the transmission intensity to less than about 0.1. We conclude that the introduction of the Monte Carlo simulation has led us to a quantitative analysis of the insulation effects caused by electromagnetic scattering and to find the optimum size and material of spheres to be admixed with paint.

Sensory enhancing insoles improve athletic performance during a hexagonal agility task.

PubMed

Miranda, Daniel L; Hsu, Wen-Hao; Gravelle, Denise C; Petersen, Kelsey; Ryzman, Rachael; Niemi, James; Lesniewski-Laas, Nicholas

2016-05-03

Athletes incorporate afferent signals from the mechanoreceptors of their plantar feet to provide information about posture, stability, and joint position. Sub-threshold stochastic resonance (SR) sensory enhancing insoles have been shown to improve balance and proprioception in young and elderly participant populations. Balance and proprioception are correlated with improved athletic performance, such as agility. Agility is defined as the ability to quickly change direction. An athlete's agility is commonly evaluated during athletic performance testing to assess their ability to participate in a competitive sporting event. Therefore, the purpose of this study was to examine the effects of SR insoles during a hexagonal agility task routinely used by coaches and sports scientists. Twenty recreational athletes were recruited to participate in this study. Each athlete was asked to perform a set of hexagonal agility trials while SR stimulation was either on or off. Vicon motion capture was used to measure feet position during six successful trials for each stimulation condition. Stimulation condition was randomized in a pairwise fashion. The study outcome measures were the task completion time and the positional accuracy of footfalls. Pairwise comparisons revealed a 0.12s decrease in task completion time (p=0.02) with no change in hopping accuracy (p=0.99) when SR stimulation was on. This is the first study to show athletic performance benefits while wearing proprioception and balance improving equipment on healthy participants. With further development, a self-contained sensory enhancing insole device could be used by recreational and professional athletes to improve movements that require rapid changes in direction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Critical insolation-CO2 relation for diagnosing past and future glacial inception.

PubMed

Ganopolski, A; Winkelmann, R; Schellnhuber, H J

2016-01-14

The past rapid growth of Northern Hemisphere continental ice sheets, which terminated warm and stable climate periods, is generally attributed to reduced summer insolation in boreal latitudes. Yet such summer insolation is near to its minimum at present, and there are no signs of a new ice age. This challenges our understanding of the mechanisms driving glacial cycles and our ability to predict the next glacial inception. Here we propose a critical functional relationship between boreal summer insolation and global carbon dioxide (CO2) concentration, which explains the beginning of the past eight glacial cycles and might anticipate future periods of glacial inception. Using an ensemble of simulations generated by an Earth system model of intermediate complexity constrained by palaeoclimatic data, we suggest that glacial inception was narrowly missed before the beginning of the Industrial Revolution. The missed inception can be accounted for by the combined effect of relatively high late-Holocene CO2 concentrations and the low orbital eccentricity of the Earth. Additionally, our analysis suggests that even in the absence of human perturbations no substantial build-up of ice sheets would occur within the next several thousand years and that the current interglacial would probably last for another 50,000 years. However, moderate anthropogenic cumulative CO2 emissions of 1,000 to 1,500 gigatonnes of carbon will postpone the next glacial inception by at least 100,000 years. Our simulations demonstrate that under natural conditions alone the Earth system would be expected to remain in the present delicately balanced interglacial climate state, steering clear of both large-scale glaciation of the Northern Hemisphere and its complete deglaciation, for an unusually long time.

Weight-bearing recommendations after operative fracture treatment-fact or fiction? Gait results with and feasibility of a dynamic, continuous pedobarography insole.

PubMed

Braun, Benedikt J; Veith, Nils T; Rollmann, Mika; Orth, Marcel; Fritz, Tobias; Herath, Steven C; Holstein, Jörg H; Pohlemann, Tim

2017-08-01

Rehabilitation after lower-extremity fractures is based on the physicians' recommendation for non-, partial-, or full weight-bearing. Clinical studies rely on this assumption, but continuous compliance or objective loading rates are unknown. The purpose of this study was to determine the compliance to weight-bearing recommendations by introducing a novel, pedobarography system continuously registering postoperative ground forces into ankle, tibial shaft and proximal femur fracture aftercare and test its feasibility for this purpose. In this prospective, observational study, a continuously measuring pedobarography insole was placed in the patients shoe during the immediate post-operative aftercare after ankle, tibial shaft and intertrochanteric femur fractures. Weight-bearing was ordered as per the institutional standard and controlled by physical therapy. The insole was retrieved after a maximum of six weeks (28 days [range 5-42 days]). Non-compliance was defined as a failure to maintain, or reach the ordered weight-bearing within 30%. Overall 30 patients were included in the study. Fourteen (47%) of the patients were compliant to the weight-bearing recommendations. Within two weeks after surgery patients deviated from the recommendation by over 50%. Sex, age and weight did not influence the performance (p > 0.05). Ankle fracture patients (partial weight-bearing) showed a significantly increased deviation from the recommendation (p = 0.01). Our study results show that, despite physical therapy training, weight-bearing compliance to recommended limits was low. Adherence to the partial weight-bearing task was further decreased over time. Uncontrolled weight-bearing recommendations should thus be viewed with caution and carefully considered as fiction. The presented insole is feasible to determine weight bearing continuously, could immediately help define real-time patient behaviour and establish realistic, individual weight-bearing recommendations.

Estimation of Foot Plantar Center of Pressure Trajectories with Low-Cost Instrumented Insoles Using an Individual-Specific Nonlinear Model.

PubMed

Hu, Xinyao; Zhao, Jun; Peng, Dongsheng; Sun, Zhenglong; Qu, Xingda

2018-02-01

Postural control is a complex skill based on the interaction of dynamic sensorimotor processes, and can be challenging for people with deficits in sensory functions. The foot plantar center of pressure (COP) has often been used for quantitative assessment of postural control. Previously, the foot plantar COP was mainly measured by force plates or complicated and expensive insole-based measurement systems. Although some low-cost instrumented insoles have been developed, their ability to accurately estimate the foot plantar COP trajectory was not robust. In this study, a novel individual-specific nonlinear model was proposed to estimate the foot plantar COP trajectories with an instrumented insole based on low-cost force sensitive resistors (FSRs). The model coefficients were determined by a least square error approximation algorithm. Model validation was carried out by comparing the estimated COP data with the reference data in a variety of postural control assessment tasks. We also compared our data with the COP trajectories estimated by the previously well accepted weighted mean approach. Comparing with the reference measurements, the average root mean square errors of the COP trajectories of both feet were 2.23 mm (±0.64) (left foot) and 2.72 mm (±0.83) (right foot) along the medial-lateral direction, and 9.17 mm (±1.98) (left foot) and 11.19 mm (±2.98) (right foot) along the anterior-posterior direction. The results are superior to those reported in previous relevant studies, and demonstrate that our proposed approach can be used for accurate foot plantar COP trajectory estimation. This study could provide an inexpensive solution to fall risk assessment in home settings or community healthcare center for the elderly. It has the potential to help prevent future falls in the elderly.

Feasibility of solar power for Mars

NASA Technical Reports Server (NTRS)

Appelbaum, Joseph; Landis, Geoffrey A.

1991-01-01

NASA, through Project Pathfinder, has put in place an advanced technology program to address future needs of manned space exploration. Included in the missions under study is the establishment of outposts on the surface of Mars. The Surface Power program in Pathfinder is aimed at providing photovoltaic array technology for such an application (as well as for the lunar surface). Another important application is for unmanned precursor missions, such as the photovoltaic-power aircraft, which will scout landing sites and investigate Mars geology for a 1 to 2 year mission without landing on the surface. Effective design and utilization of solar energy depend to a large extent on adequate knowledge of solar radiation characteristics in the region of solar energy system operation. The two major climatic components needed for photovoltaic system designs are the distributions of solar insolation and ambient temperature. These distributions for the Martian climate are given at the two Viking lander locations but can also be used, to the first approximation, for other latitudes. One of the most important results is that there is a large diffuse component of the insolation, even at high optical depth, so that solar energy system operation is still possible. If the power system is to continue to generate power even on high optical opacity days, it is thus important that the photovoltaic system be designed to collect diffuse irradiance as well as direct. In absence of long term insolation and temperature data for Mars, the data presented can be used until updated data are available. The ambient temperature data are given as measured directly by the temperature sensor; the insolation data are calculated from optical depth measurements of the atmosphere.

Effects of foot orthoses with medial arch support and lateral wedge on knee adduction moment in patients with medial knee osteoarthritis.

PubMed

Dessery, Yoann; Belzile, Étienne; Turmel, Sylvie; Corbeil, Philippe

2017-08-01

There is contradictory evidence regarding whether the addition of medial arch supports to laterally wedged insoles reduces knee adduction moment, improves comfort, and reduces knee pain during the late stance phase of gait. To verify if such effects occur in participants with medial knee osteoarthritis. Randomized single-blinded study. Gait analysis was performed on 18 patients affected by medial knee osteoarthritis. Pain and comfort scores, frontal plane kinematics and kinetics of ankle, knee, and hip were compared in four conditions: without foot orthosis, with foot orthoses, with medial arch support, and with foot orthoses with medial arch support and lateral wedge insoles with 6° and 10° inclination. Lower-extremity gait kinetics were characterized by a significant decrease, greater than 6%, in second peak knee adduction moment in laterally wedged insole conditions compared to the other conditions ( p < 0.001; effect size = 0.6). No significant difference in knee adduction moment was observed between laterally wedged insole conditions. In contrast, a significant increase of 7% in knee adduction moment during the loading response was observed in the customized foot orthoses without lateral inclination condition ( p < 0.001; effect size = 0.3). No difference was found in comfort or pain ratings between conditions. Our study suggests that customized foot orthoses with a medial arch support may only be suitable for the management of medial knee osteoarthritis when a lateral wedge is included. Clinical relevance Our data suggest that customized foot orthoses with medial arch support and a lateral wedge reduce knee loading in patients with medial knee osteoarthritis (KOA). We also found evidence that medial arch support may increase knee loading, which could potentially be detrimental in KOA patients.

Accuracy and precision of loadsol® insole force-sensors for the quantification of ground reaction force-based biomechanical running parameters.

PubMed

Seiberl, Wolfgang; Jensen, Elisabeth; Merker, Josephine; Leitel, Marco; Schwirtz, Ansgar

2018-05-29

Force plates represent the "gold standard" in measuring running kinetics to predict performance or to identify the sources of running-related injuries. As these measurements are generally limited to laboratory analyses, wireless high-quality sensors for measuring in the field are needed. This work analysed the accuracy and precision of a new wireless insole forcesensor for quantifying running-related kinetic parameters. Vertical ground reaction force (GRF) was simultaneously measured with pit-mounted force plates (1 kHz) and loadsol ® sensors (100 Hz) under unshod forefoot and rearfoot running-step conditions. GRF data collections were repeated four times, each separated by 30 min treadmill running, to test influence of extended use. A repeated-measures ANOVA was used to identify differences between measurement devices. Additionally, mean bias and Bland-Altman limits of agreement (LoA) were calculated. We found a significant difference (p < .05) in ground contact time, peak force, and force rate, while there was no difference in parameters impulse, time to peak, and negative force rate. There was no influence of time point of measurement. The mean bias of ground contact time, impulse, peak force, and time to peak ranged between 0.6% and 3.4%, demonstrating high accuracy of loadsol ® devices for these parameters. For these same parameters, the LoA analysis showed that 95% of all measurement differences between insole and force plate measurements were less than 12%, demonstrating high precision of the sensors. However, highly dynamic behaviour of GRF, such as force rate, is not yet sufficiently resolved by the insole devices, which is likely explained by the low sampling rate.

Estimation of Foot Plantar Center of Pressure Trajectories with Low-Cost Instrumented Insoles Using an Individual-Specific Nonlinear Model

PubMed Central

Hu, Xinyao; Zhao, Jun; Peng, Dongsheng

2018-01-01

Postural control is a complex skill based on the interaction of dynamic sensorimotor processes, and can be challenging for people with deficits in sensory functions. The foot plantar center of pressure (COP) has often been used for quantitative assessment of postural control. Previously, the foot plantar COP was mainly measured by force plates or complicated and expensive insole-based measurement systems. Although some low-cost instrumented insoles have been developed, their ability to accurately estimate the foot plantar COP trajectory was not robust. In this study, a novel individual-specific nonlinear model was proposed to estimate the foot plantar COP trajectories with an instrumented insole based on low-cost force sensitive resistors (FSRs). The model coefficients were determined by a least square error approximation algorithm. Model validation was carried out by comparing the estimated COP data with the reference data in a variety of postural control assessment tasks. We also compared our data with the COP trajectories estimated by the previously well accepted weighted mean approach. Comparing with the reference measurements, the average root mean square errors of the COP trajectories of both feet were 2.23 mm (±0.64) (left foot) and 2.72 mm (±0.83) (right foot) along the medial–lateral direction, and 9.17 mm (±1.98) (left foot) and 11.19 mm (±2.98) (right foot) along the anterior–posterior direction. The results are superior to those reported in previous relevant studies, and demonstrate that our proposed approach can be used for accurate foot plantar COP trajectory estimation. This study could provide an inexpensive solution to fall risk assessment in home settings or community healthcare center for the elderly. It has the potential to help prevent future falls in the elderly. PMID:29389857

Influence of the Solar Luminosity on the Glaciations, sea Level Changes and Resulting Earthquakes.

NASA Astrophysics Data System (ADS)

Shopov, Y. Y.; Stoykova, D. A.; Tsankov, L. T.; Sanabria, M. E.; Georgieva, D. I.; Ford, D. C.; Georgiev, L. N.

2002-12-01

Glaciations were attributed to variations of the Earth's orbit (Milankovitch cycles). But the best ever dated paleoclimatic record (from Devils Hole, Nevada) demonstrated that the end of the last glacial period (termination II) happened 10 000 years before the one suggested by the orbital variations, i.e. the result appeared before the reason. This fact suggests that there is something wrong in the theory. Calcite speleothems luminescence of organics depends exponentially upon soil temperatures that are determined primarily by the solar radiation. So the microzonality of luminescence of speleothems may be used as an indirect Solar Insolation (radiation) proxy index. We obtained luminescence solar insolation proxy records in speleothems (from Jewel Cave, South Dakota, US and Duhlata cave, Bulgaria). These records exhibit very rapid increasing of the solar insolation at 139 kyrs BP responsible for the termination II (the end of the last glaciation) and demonstrate that solar luminosity variations contribute to Earth's heating almost as much as the orbital variations of the Earth's orbit (Milankovitch cycles). The most powerful cycle of the solar luminosity (11500 yrs) is responsible for almost 1/2 of the variations in solar insolation experimental records. Changes in the speed of Earth's rotation during glacial- interglacial transitions produce fracturing of the Earth's crust and major earthquakes along the fractures. The intensity of this process is as higher as faster is the change of the sea level and as higher is its amplitude. Glaciations and deglaciations drive changes of the sea level. Much higher dimensions of this process should be caused by eruptive increasing of solar luminosity, which may be caused only by collision of large asteroids with the Sun. We demonstrate that such collision may cause "Bible Deluge" type of event.

Northern Hemisphere forcing of Southern Hemisphere climate during the last deglaciation.

PubMed

He, Feng; Shakun, Jeremy D; Clark, Peter U; Carlson, Anders E; Liu, Zhengyu; Otto-Bliesner, Bette L; Kutzbach, John E

2013-02-07

According to the Milankovitch theory, changes in summer insolation in the high-latitude Northern Hemisphere caused glacial cycles through their impact on ice-sheet mass balance. Statistical analyses of long climate records supported this theory, but they also posed a substantial challenge by showing that changes in Southern Hemisphere climate were in phase with or led those in the north. Although an orbitally forced Northern Hemisphere signal may have been transmitted to the Southern Hemisphere, insolation forcing can also directly influence local Southern Hemisphere climate, potentially intensified by sea-ice feedback, suggesting that the hemispheres may have responded independently to different aspects of orbital forcing. Signal processing of climate records cannot distinguish between these conditions, however, because the proposed insolation forcings share essentially identical variability. Here we use transient simulations with a coupled atmosphere-ocean general circulation model to identify the impacts of forcing from changes in orbits, atmospheric CO(2) concentration, ice sheets and the Atlantic meridional overturning circulation (AMOC) on hemispheric temperatures during the first half of the last deglaciation (22-14.3 kyr BP). Although based on a single model, our transient simulation with only orbital changes supports the Milankovitch theory in showing that the last deglaciation was initiated by rising insolation during spring and summer in the mid-latitude to high-latitude Northern Hemisphere and by terrestrial snow-albedo feedback. The simulation with all forcings best reproduces the timing and magnitude of surface temperature evolution in the Southern Hemisphere in deglacial proxy records. AMOC changes associated with an orbitally induced retreat of Northern Hemisphere ice sheets is the most plausible explanation for the early Southern Hemisphere deglacial warming and its lead over Northern Hemisphere temperature; the ensuing rise in atmospheric CO(2) concentration provided the critical feedback on global deglaciation.

Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo.

PubMed

Haider, Marie-Therese; Hunter, Keith D; Robinson, Simon P; Graham, Timothy J; Corey, Eva; Dear, T Neil; Hughes, Russell; Brown, Nicola J; Holen, Ingunn

2015-12-01

Bone metastasis remains incurable with treatment restricted to palliative care. Cabozantinib (CBZ) is targeted against multiple receptor tyrosine kinases involved in tumour pathobiology, including hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR-2). CBZ has demonstrated clinical activity in advanced prostate cancer with resolution of lesions visible on bone scans, implicating a potential role of the bone microenvironment as a mediator of CBZ effects. We characterised the effects of short-term administration of CBZ on bone in a range of in vivo models to determine how CBZ affects bone in the absence of tumour. Studies were performed in a variety of in vivo models including male and female BALB/c nude mice (age 6-17-weeks). Animals received CBZ (30 mg/kg, 5× weekly) or sterile H2O control for 5 or 10 days. Effects on bone integrity (μCT), bone cell activity (PINP, TRAP ELISA), osteoblast and osteoclast number/mm trabecular bone surface, area of epiphyseal growth plate cartilage, megakaryocyte numbers and bone marrow composition were assessed. Effects of longer-term treatment (15-day & 6-week administration) were assessed in male NOD/SCID and beige SCID mice. CBZ treatment had significant effects on the bone microenvironment, including reduced osteoclast and increased osteoblast numbers compared to control. Trabecular bone structure was altered after 8 administrations. A significant elongation of the epiphyseal growth plate, in particular the hypertrophic chondrocyte zone, was observed in all CBZ treated animals irrespective of administration schedule. Both male and female BALB/c nude mice had increased megakaryocyte numbers/mm(2) tissue after 10-day CBZ treatment, in addition to vascular ectasia, reduced bone marrow cellularity and extravasation of red blood cells into the extra-vascular bone marrow. All CBZ-induced effects were transient and rapidly lost following cessation of treatment. Short-term administration of CBZ induces rapid, reversible effects on the bone microenvironment in vivo highlighting a potential role in mediating treatment responses. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

LDEF materials data analysis: Representative examples

NASA Technical Reports Server (NTRS)

Pippin, H. Gary; Crutcher, E. R.

1992-01-01

Results of measurements on silverized teflon, heat shrink tubing and nylon tie downs on the wire harness clamps, silvered hex nuts, and contamination deposits are presented. We interpret the results in terms of our microenvironments exposure model and locations on the Long Duration Exposure Facility (LDEF). Distinct changes in the surface properties of FEP were observed as a function of UV exposure. Significant differences in outgassing characteristics were detected for hardware on the interior row 3 relative to identical hardware on the interior row 3 relative to identical hardware on nearby rows. The implications for in service performance are reviewed.

Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics.

PubMed

Labarge, Mark A; Parvin, Bahram; Lorens, James B

2014-04-01

The field of bioengineering has pioneered the application of new precision fabrication technologies to model the different geometric, physical or molecular components of tissue microenvironments on solid-state substrata. Tissue engineering approaches building on these advances are used to assemble multicellular mimetic-tissues where cells reside within defined spatial contexts. The functional responses of cells in fabricated microenvironments have revealed a rich interplay between the genome and extracellular effectors in determining cellular phenotypes and in a number of cases have revealed the dominance of microenvironment over genotype. Precision bioengineered substrata are limited to a few aspects, whereas cell/tissue-derived microenvironments have many undefined components. Thus, introducing a computational module may serve to integrate these types of platforms to create reasonable models of drug responses in human tissues. This review discusses how combinatorial microenvironment microarrays and other biomimetic microenvironments have revealed emergent properties of cells in particular microenvironmental contexts, the platforms that can measure phenotypic changes within those contexts, and the computational tools that can unify the microenvironment-imposed functional phenotypes with underlying constellations of proteins and genes. Ultimately we propose that a merger of these technologies will enable more accurate pre-clinical drug discovery. Copyright © 2014 Elsevier B.V. All rights reserved.

Acid-sensitive sheddable PEGylated, mannose-modified nanoparticles increase the delivery of betamethasone to chronic inflammation sites in a mouse model

PubMed Central

O’Mary, Hannah L.; Aldayel, Abdulaziz M.; Valdes, Solange A.; Naguib, Youssef W.; Li, Xu; Salvady, Karun; Cui, Zhengrong

2017-01-01

Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions. PMID:28463518

Targeting complement-mediated immunoregulation for cancer immunotherapy.

PubMed

Kolev, Martin; Markiewski, Maciej M

2018-06-01

Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response. The discovery of functional intracellular complement and its roles in cellular metabolism opened novel avenues for research and potential therapeutic implications. The recent studies demonstrating immunoregulatory functions of complement in the tumor microenvironment and the premetastatic niche shifted the paradigm on our understanding of functions of the complement system in regulating immunity. Several complement proteins, through their interaction with cells in the tumor microenvironment and in metastasis-targeted organs, contribute to modulating tumor growth, antitumor immunity, angiogenesis, and therefore, the overall progression of malignancy and, perhaps, responsiveness of cancer to different therapies. Here, we focus on recent progress in our understanding of immunostimulatory vs. immunoregulatory functions of complement and potential applications of these findings to the design of novel therapies for cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

PubMed Central

Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

2009-01-01

Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

Mechanoregulatory tumor-stroma crosstalk in pancreatic cancer: Measurements of the effects of extracellular matrix mechanics on tumor growth behavior, and vice-versa, to inform therapeutics

NASA Astrophysics Data System (ADS)

Celli, Jonathan; Jones, Dustin; El-Hamidi, Hamid; Cramer, Gwendolyn; Hanna, William; Caide, Andrew; Jafari, Seyedehrojin

The rheological properties of the extracellular matrix (ECM) have been shown to play key roles in regulating tumor growth behavior through mechanotranduction pathways. The role of the mechanical microenvironment may be particularly important tumors of the pancreas, noted for an abundance of rigid fibrotic stroma, implicated in therapeutic resistance. At the same time, cancer cells and their stromal partners (e.g. tumor associated fibroblasts) continually alter the mechanical microenvironment in response to extracellular physical and biochemical cues as part of a two-way mechanoregulatory dialog. Here, we describe experimental studies using 3D pancreatic cell cultures with customized mechanical properties, combined with optical microrheology to provide insight into tumor-driven matrix remodeling. Quantitative microscopy provides measurements of phenotypic changes accompanying systematic variation of ECM composition in collagen and laminin-rich basement membrane admixtures, while analysis of the trajectories of passive tracer particles embedded in ECM report dynamic changes in heterogeneity, microstructure and local shear modulus accompanying both ECM stiffening (fibrosis) processes, and ECM degradation near invading cells. We gratefully acknowledge funding from the National Cancer Institute, R00CA155045 (PI: Celli).

Interaction between tumor cell surface receptor RAGE and proteinase 3 mediates prostate cancer metastasis to bone

PubMed Central

Kolonin, Mikhail G.; Sergeeva, Anna; Staquicini, Daniela I.; Smith, Tracey L.; Tarleton, Christy A.; Molldrem, Jeffrey J.; Sidman, Richard L.; Marchiò, Serena; Pasqualini, Renata; Arap, Wadih

2017-01-01

Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a non-proteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short time frame. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. PMID:28428279

Tumor Macroenvironment and Metabolism

PubMed Central

Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

2014-01-01

In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%–20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient’s outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. PMID:24787299

Tumor macroenvironment and metabolism.

PubMed

Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

2014-04-01

In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

On-tissue Direct Monitoring of Global Hydrogen/Deuterium Exchange by MALDI Mass Spectrometry: Tissue Deuterium Exchange Mass Spectrometry (TDXMS)*

PubMed Central

Quanico, Jusal; Franck, Julien

2016-01-01

Hydrogen/deuterium exchange mass spectrometric (H/DXMS) methods for protein structural analysis are conventionally performed in solution. We present Tissue Deuterium Exchange Mass Spectrometry (TDXMS), a method to directly monitor deuterium uptake on tissue, as a means to better approximate the deuterium exchange behavior of proteins in their native microenvironment. Using this method, a difference in deuterium uptake behavior was observed when the same proteins were monitored in solution and on tissue. The higher maximum deuterium uptake at equilibrium for all proteins analyzed in solution suggests a more open conformation in the absence of interacting partners normally observed on tissue. We also demonstrate a difference in the deuterium uptake behavior of a few proteins across different morphological regions of the same tissue section. Modifications of the total number of hydrogens exchanged, as well as the kinetics of exchange, were both observed. These results provide information on the implication of protein interactions with partners as well as on the conformational changes related to these interactions, and illustrate the importance of examining protein deuterium exchange behavior in the presence of its specific microenvironment directly at the level of tissues. PMID:27512083

Investigation of the turbulent wind field below 500 feet altitude at the Eastern Test Range, Florida

NASA Technical Reports Server (NTRS)

Blackadar, A. K.; Panofsky, H. A.; Fiedler, F.

1974-01-01

A detailed analysis of wind profiles and turbulence at the 150 m Cape Kennedy Meteorological Tower is presented. Various methods are explored for the estimation of wind profiles, wind variances, high-frequency spectra, and coherences between various levels, given roughness length and either low-level wind and temperature data, or geostrophic wind and insolation. The relationship between planetary Richardson number, insolation, and geostrophic wind is explored empirically. Techniques were devised which resulted in surface stresses reasonably well correlated with the surface stresses obtained from low-level data. Finally, practical methods are suggested for the estimation of wind profiles and wind statistics.

A real time study of the human equilibrium using an instrumented insole with 3 pressure sensors.

PubMed

Abou Ghaida, Hussein; Mottet, Serge; Goujon, Jean-Marc

2014-01-01

The present work deals with the study of the human equilibrium using an ambulatory e-health system. One of the point on which we focus is the fall risk, when losing equilibrium control. A specific postural learning model is presented, and an ambulatory instrumented insole is developed using 3 pressures sensors per foot, in order to determine the real-time displacement and the velocity of the centre of pressure (CoP). The increase of these parameters signals a loss of physiological sensation, usually of vision or of the inner ear. The results are compared to those obtained from classical more complex systems.

The climatic and hydrologic history of southern Nevada during the late Quaternary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forester, R.M.; Bradbury, J.P.; Carter, C.

Understanding climate change during the expected life span of a potential high-level nuclear-waste repository at Yucca Mountain, Nevada, requires estimates of future climate boundary conditions. These climate boundary conditions are governed by changes in the Earth's orbital properties (eccentricity, obliquity, precession) that determine insolation. Subcycles of the 400,000 year insolation-controlled climate cycles last approximately 100,000 years. This report describes the changes which have occurred in the climatic history of Southern Nevada during the past 400,000 years. These changes provide a basis for understanding the changes which may occur during the long-term future in this area.

Variation of solar cell sensitivity and solar radiation on tilted surfaces

NASA Technical Reports Server (NTRS)

Klucher, T. M.

1978-01-01

The validity is studied that one of various insolation models used to compute solar radiation incident on tilted surfaces from global data measured on horizontal surfaces. The variation of solar cell sensitivity to solar radiation is determined over a wide range of atmospheric condition. A new model was formulated that reduced the deviations between measured and predicted insolation to less than 3 percent. Evaluation of solar cell sensitivity data indicates small change (2-3 percent) in sensitivity from winter to summer for tilted cells. The feasibility of using such global data as a means for calibrating terrestrial solar cells is discussed.

Smoothing PV System’s Output by Tuning MPPT Control

NASA Astrophysics Data System (ADS)

Ina, Nobuhiko; Yanagawa, Shigeyuki; Kato, Takeyoshi; Suzuoki, Yasuo

A PV system’s output is not stable and fluctuates depending on a weather condition. Using a battery is one of the feasible ways to stabilize a PV system’s output, although it requires an additional cost and provides an additional waste of the used battery. In this paper, we propose tuning a characteristic of Maxiumum Power Point Tracking (MPPT) control for smoothing a short term change of PV system’s output during a sharp insolation fluctuation, as an approach without additional equipments. In our proposed method, when an insolation increases rapidly, the operation point of MPPT control changes to the new point where the maximum power is not generated with present insolation, so that the speed of PV system’s output increase is limited to a certain value, i. e. 1%/min. In order to evaluate the effect of our proposed method in terms of reducing the additional operation task of the electric power system, we evaluated the additional LFC capacity for a large-scale installation of PV systems. As a result, it was revealed that the additional LFC capacity is not required even if a PV system is installed by 5% of utility system, when our proposed method is applied to all PV systems.

Synchronous flowering of the rubber tree (Hevea brasiliensis) induced by high solar radiation intensity.

PubMed

Yeang, Hoong-Yeet

2007-01-01

How tropical trees flower synchronously near the equator in the absence of significant day length variation or other meteorological cues has long been a puzzle. The rubber tree (Hevea brasiliensis) is used as a model to investigate this phenomenon. The annual cycle of solar radiation intensity is shown to correspond closely with the flowering of the rubber tree planted near the equator and in the subtropics. Unlike in temperate regions, where incoming solar radiation (insolation) is dependent on both day length and radiation intensity, insolation at the equator is due entirely to the latter. Insolation at the upper atmosphere peaks twice a year during the spring and autumn equinoxes, but the actual solar radiation that reaches the ground is attenuated to varying extents in different localities. The rubber tree shows one or two flowering seasons a year (with major and minor seasons in the latter) in accordance with the solar radiation intensity received. High solar radiation intensity, and in particular bright sunshine (as distinct from prolonged diffuse radiation), induces synchronous anthesis and blooming in Hevea around the time of the equinoxes. The same mechanism may be operational in other tropical tree species.

Development of a real time activity monitoring Android application utilizing SmartStep.

PubMed

Hegde, Nagaraj; Melanson, Edward; Sazonov, Edward

2016-08-01

Footwear based activity monitoring systems are becoming popular in academic research as well as consumer industry segments. In our previous work, we had presented developmental aspects of an insole based activity and gait monitoring system-SmartStep, which is a socially acceptable, fully wireless and versatile insole. The present work describes the development of an Android application that captures the SmartStep data wirelessly over Bluetooth Low energy (BLE), computes features on the received data, runs activity classification algorithms and provides real time feedback. The development of activity classification methods was based on the the data from a human study involving 4 participants. Participants were asked to perform activities of sitting, standing, walking, and cycling while they wore SmartStep insole system. Multinomial Logistic Discrimination (MLD) was utilized in the development of machine learning model for activity prediction. The resulting classification model was implemented in an Android Smartphone. The Android application was benchmarked for power consumption and CPU loading. Leave one out cross validation resulted in average accuracy of 96.9% during model training phase. The Android application for real time activity classification was tested on a human subject wearing SmartStep resulting in testing accuracy of 95.4%.

Towards Greenland Glaciation: Cumulative or Abrupt Transition?

NASA Astrophysics Data System (ADS)

Tan, N.; Ramstein, G.; Contoux, C.; Ladant, J. B.; Dumas, C.; Donnadieu, Y.

2014-12-01

The insolation evolution [Laskar 2004] from 4 to 2.5 Ma depicts a series of three summer solstice insolation minima between 2.7 and 2.6 Ma, but there are other more important summer solstice minima notably around 3.82 and 3.05 Ma. On such a time span of more than 1 Ma, data shows that there are variations in the evolution of atmospheric CO2 concentration with a local maximum around 3 Ma [Seki et al.2010; Bartoli et al. 2011], before a decrease between 3 and 2.6 Ma. The latter, suggesting an abrupt ice sheet inception around 2.7 Ma, has been shown to be a major culprit for the full Greenland Glaciation [Lunt et al. 2008]. However, a recent study [Contoux et al. 2014, in review] suggests that a lowering of CO2 is not sufficient to initiate a glaciation on Greenland and must be combined to low summer insolation, with surviving ice during insolation maximum, suggesting a cumulative process in the first place, which could further lead to full glaciation at 2.7 Ma. Through a new tri-dimensional interpolation method implemented within the asynchronous coupling between an atmosphere ocean general circulation model (IPSL-CM5A) and an ice sheet model (GRISLI), we investigate the transient evolution of Greenland ice sheet during the Pliocene to diagnose whether the ice sheet inception is an abrupt event or rather a cumulative process, involving waxing and waning of the ice sheet during several orbital cycles. ReferencesBartoli, G., Hönisch, B., & Zeebe, R. E. (2011). Atmospheric CO2 decline during the Pliocene intensification of Northern Hemisphere glaciations. Paleoceanography, 26(4). Contoux C, Dumas C, Ramstein G, Jost A, Dolan A. M. (2014) Modelling Greenland Ice sheet inception and sustainability during the late Pliocene. (in review for Earth and Planetary Science Letters.).Laskar, J., Robutel, P., Joutel, F., Gastineau, M., Correia, A. C. M., & Levrard, B. (2004). A long-term numerical solution for the insolation quantities of the Earth. Astronomy & Astrophysics, 428(1), 261-285. Lunt, D. J., Foster, G. L., Haywood, A. M., & Stone, E. J. (2008). Late Pliocene Greenland glaciation controlled by a decline in atmospheric CO2 levels. Nature, 454(7208), 1102-1105. Seki, O., Foster, G. L., Schmidt, D. N., Mackensen et al. (2010). Alkenone and boron-based Pliocene pCO 2 records. Earth and Planetary Science Letters, 292(1), 201-211.

A systematic review and meta-analysis into the effect of lateral wedge arch support insoles for reducing knee joint load in patients with medial knee osteoarthritis.

PubMed

Xing, Fei; Lu, Bin; Kuang, Ming-Jie; Wang, Ying; Zhao, Yun-Long; Zhao, Jie; Sun, Lei; Wang, Yan; Ma, Jian-Xiong; Ma, Xin-Long

2017-06-01

The aim of this study was to evaluate the immediate effects of lateral wedge arch support insoles (LWAS) on reducing the knee joint load in patients with medial knee osteoarthritis (OA) compared with an appropriate control. Databases including Medline, EMBASE, Web of Science, Wiley Online Library, Cochrane library, and Google Scholar were searched with no limits on study date or language, from the earliest available date to October 31, 2016. The included studies had to have the aim of reducing knee load and have an appropriate control. The main measured values were the first and second peak external knee adduction moments (EKAM) and the knee adduction angular impulse (KAAI). The random-effects model was used for analyzing the eligible studies. Nine studies met the inclusion criteria with a total of 356 participants of whom 337 received LWAS treatment. The risk of methodological bias scores (quality index) ranged from 21 to 27 of 32. Treatment with LWAS resulted in statistically significant reductions in the first peak EKAM (P = .005), the second peak EKAM (P = .01), and the KAAI (P = .03). However, among trials in which the control treatment was control shoes, the LWAS showed no associations on the first peak EKAM (P = .10) or the KAAI (P =  .06); among trials in which the control treatment was neutral insoles, the LWAS showed no associations on the second peak EKAM (P = .21) or the KAAI (P = .23). At the same time, the LWAS showed no statistically significant reduction on the first peak EKAM (P = .39) when compared with flat insoles. Although meta-analysis outcomes of all studies indicated statistically significant associations between LWAS and reductions of the first peak EKAM, second peak EKAM and KAAI in people with medial knee OA while walking, different results existed in subgroups using various control conditions for comparison. These findings do not support the use of LWAS insoles for reducing knee load. An optimal LWAS treatment should provide the appropriate height of arch support and amount of lateral wedging. Further research should investigate the best combination of these 2 parameters to achieve efficacy without altered comfort.

A systematic review and meta-analysis into the effect of lateral wedge arch support insoles for reducing knee joint load in patients with medial knee osteoarthritis

PubMed Central

Xing, Fei; Lu, Bin; Kuang, Ming-jie; Wang, Ying; Zhao, Yun-long; Zhao, Jie; Sun, Lei; Wang, Yan; Ma, Jian-xiong; Ma, Xin-long

2017-01-01

Abstract Objective: The aim of this study was to evaluate the immediate effects of lateral wedge arch support insoles (LWAS) on reducing the knee joint load in patients with medial knee osteoarthritis (OA) compared with an appropriate control. Methods: Databases including Medline, EMBASE, Web of Science, Wiley Online Library, Cochrane library, and Google Scholar were searched with no limits on study date or language, from the earliest available date to October 31, 2016. The included studies had to have the aim of reducing knee load and have an appropriate control. The main measured values were the first and second peak external knee adduction moments (EKAM) and the knee adduction angular impulse (KAAI). The random-effects model was used for analyzing the eligible studies. Results: Nine studies met the inclusion criteria with a total of 356 participants of whom 337 received LWAS treatment. The risk of methodological bias scores (quality index) ranged from 21 to 27 of 32. Treatment with LWAS resulted in statistically significant reductions in the first peak EKAM (P = .005), the second peak EKAM (P = .01), and the KAAI (P = .03). However, among trials in which the control treatment was control shoes, the LWAS showed no associations on the first peak EKAM (P = .10) or the KAAI (P =  .06); among trials in which the control treatment was neutral insoles, the LWAS showed no associations on the second peak EKAM (P = .21) or the KAAI (P = .23). At the same time, the LWAS showed no statistically significant reduction on the first peak EKAM (P = .39) when compared with flat insoles. Conclusion: Although meta-analysis outcomes of all studies indicated statistically significant associations between LWAS and reductions of the first peak EKAM, second peak EKAM and KAAI in people with medial knee OA while walking, different results existed in subgroups using various control conditions for comparison. These findings do not support the use of LWAS insoles for reducing knee load. An optimal LWAS treatment should provide the appropriate height of arch support and amount of lateral wedging. Further research should investigate the best combination of these 2 parameters to achieve efficacy without altered comfort. PMID:28614253

The STAP-study: The (cost) effectiveness of custom made orthotic insoles in the treatment for plantar fasciopathy in general practice and sports medicine: design of a randomized controlled trial.

PubMed

Rasenberg, N; Fuit, L; Poppe, E; Kruijsen-Terpstra, A J A; Gorter, K J; Rathleff, M S; van Veldhoven, P L J; Bindels, P J; Bierma-Zeinstra, S M; van Middelkoop, M

2016-01-16

Plantar fasciopathy is a common cause of foot pain, accounting for 11 to 15% of all foot symptoms requiring professional care in adults. Although many patients have complete resolution of symptoms within 12 months, many patients wish to reduce this period as much as possible. Orthotic devices are a frequently applied option of treatment in daily practice, despite a lack of evidence on the effectiveness. Therefore, the objective is to study the (cost)-effectiveness of custom made insoles by a podiatrist, compared to placebo insoles and usual care in patients with plantar fasciopathy in general practice and sports medicine clinics. This study is a multi-center three-armed participant and assessor-blinded randomized controlled trial with 6-months follow-up. Patients with plantar fasciopathy, with a minimum duration of complaints of 2 weeks and aged between 18 and 65, who visit their general practitioner or sport physician are eligible for inclusion. A total of 185 patients will be randomized into three parallel groups. One group will receive usual care by the general practitioner or sports physician alone, one group will be referred to a podiatrist and will receive a custom made insole, and one group will be referred to a podiatrist and will receive a placebo insole. The primary outcome will be the change from baseline to 12 weeks follow-up in pain severity at rest and during activity on a 0-10 numerical rating scale (NRS). Secondary outcomes include foot function (according to the Foot Function Index) at 6, 12 and 26 weeks, recovery (7-point Likert) at 6, 12 and 26 weeks, pain at rest and during activity (NRS) at 6 and 26 weeks and cost-effectiveness of the intervention at 26-weeks. Measurements will take place at baseline and at, 2, 4, 6, 12 and 26 weeks of follow-up. The treatment of plantar fasciopathy is a challenge for health care professionals. Orthotic devices are frequently applied, despite a lack of evidence of the effectiveness on patient reported outcome. The results of this randomized controlled trial will improve the evidence base for treating this troublesome condition in daily practice. Dutch Trial Registration: NTR5346 . Date of registration: August 5(th) 2015.

CLL Exosomes Modulate the Transcriptome and Behaviour of Recipient Stromal Cells and Are Selectively Enriched in miR-202-3p

PubMed Central

Farahani, Mosavar; Rubbi, Carlos; Liu, Luning; Slupsky, Joseph R.; Kalakonda, Nagesh

2015-01-01

Bi-directional communication with the microenvironment is essential for homing and survival of cancer cells with implications for disease biology and behaviour. In chronic lymphocytic leukemia (CLL), the role of the microenvironment on malignant cell behaviour is well described. However, how CLL cells engage and recruit nurturing cells is poorly characterised. Here we demonstrate that CLL cells secrete exosomes that are nanovesicles originating from the fusion of multivesicular bodies with the plasma membrane, to shuttle proteins, lipids, microRNAs (miR) and mRNAs to recipient cells. We characterise and confirm the size (50–100 nm) and identity of the CLL-derived exosomes by Electron microscopy (EM), Atomic force microscopy (AFM), flow cytometry and western blotting using both exosome- and CLL-specific markers. Incubation of CLL-exosomes, derived either from cell culture supernatants or from patient plasma, with human stromal cells shows that they are readily taken up into endosomes, and induce expression of genes such as c-fos and ATM as well as enhance proliferation of recipient HS-5 cells. Furthermore, we show that CLL exosomes encapsulate abundant small RNAs and are enriched in certain miRs and specifically hsa-miR-202-3p. We suggest that such specific packaging of miR-202-3p into exosomes results in enhanced expression of ‘suppressor of fused’ (Sufu), a Hedgehog (Hh) signalling intermediate, in the parental CLL cells. Thus, our data show that CLL cells secrete exosomes that alter the transcriptome and behaviour of recipient cells. Such communication with microenvironment is likely to have an important role in CLL disease biology. PMID:26509439

Immunological network analysis in HPV associated head and neck squamous cancer and implications for disease prognosis.

PubMed

Chen, Xiaohang; Yan, Bingqing; Lou, Huihuang; Shen, Zhenji; Tong, Fangjia; Zhai, Aixia; Wei, Lanlan; Zhang, Fengmin

2018-04-01

Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV-) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV- HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV- HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

PubMed

Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

2003-10-01

Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, whichmore » is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment. • DCA augments BMC cellularity, differentiation and repolarization of macrophages.« less

Histone Deacetylase Inhibitors Target the Leukemic Microenvironment by Enhancing a Nherf1-Protein Phosphatase 1α-TAZ Signaling Pathway in Osteoblasts*

PubMed Central

Kremer, Kimberly N.; Dudakovic, Amel; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; van Wijnen, Andre J.; Hedin, Karen E.

2015-01-01

Disrupting the protective signals provided by the bone marrow microenvironment will be critical for more effective combination drug therapies for acute myeloid leukemia (AML). Cells of the osteoblast lineage that reside in the endosteal niche have been implicated in promoting survival of AML cells. Here, we investigated how to prevent this protective interaction. We previously showed that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis of AML cells, unless the leukemic cells receive protective signals provided by differentiating osteoblasts (8, 10). We now identify a novel signaling pathway in differentiating osteoblasts that can be manipulated to disrupt the osteoblast-mediated protection of AML cells. Treating differentiating osteoblasts with histone deacetylase inhibitors (HDACi) abrogated their ability to protect co-cultured AML cells from SDF-1-induced apoptosis. HDACi prominently up-regulated expression of the Nherf1 scaffold protein, which played a major role in preventing osteoblast-mediated protection of AML cells. Protein phosphatase-1α (PP1α) was identified as a novel Nherf1 interacting protein that acts as the downstream mediator of this response by promoting nuclear localization of the TAZ transcriptional modulator. Moreover, independent activation of either PP1α or TAZ was sufficient to prevent osteoblast-mediated protection of AML cells even in the absence of HDACi. Together, these results indicate that HDACi target the AML microenvironment by enhancing activation of the Nherf1-PP1α-TAZ pathway in osteoblasts. Selective drug targeting of this osteoblast signaling pathway may improve treatments of AML by rendering leukemic cells in the bone marrow more susceptible to apoptosis. PMID:26491017

No pain, no gain: lack of exercise obstructs neurogenesis.

PubMed

Watson, Nate; Ji, Xunming; Yasuhara, Takao; Date, Isao; Kaneko, Yuji; Tajiri, Naoki; Borlongan, Cesar V

2015-01-01

Bedridden patients develop atrophied muscles, their daily activities greatly reduced, and some display a depressive mood. Patients who are able to receive physical rehabilitation sometimes show surprising clinical improvements, including reduced depression and attenuation of other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for CNS disorders, namely, transplantation of exogenous stem cells and amplification of endogenous neurogenesis. The latter strategy embraces a natural way of reinnervating the damaged brain and correcting the neurological impairments. In this study, we discussed how immobilization-induced disuse atrophy, using the hindlimb suspension model, affects neurogenesis in rats. The overarching hypothesis is that immobilization suppresses neurogenesis by reducing the circulating growth or trophic factors, such as vascular endothelial growth factor or brain-derived neurotrophic factor. That immobilization alters neurogenesis and stem cell differentiation in the CNS requires characterization of the stem cell microenvironment by examining the trophic and growth factors, as well as stress-related proteins that have been implicated in exercise-induced neurogenesis. Although accumulating evidence has revealed the contribution of "increased" exercise on neurogenesis, the reverse paradigm involving "lack of exercise," which mimics pathological states (e.g., stroke patients are often immobile), remains underexplored. This novel paradigm will enable us to examine the effects on neurogenesis by a nonpermissive stem cell microenvironment likely produced by lack of exercise. BrdU labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and brain levels of trophic factors, growth factors, and stress-related proteins are proposed as indices of neurogenesis, while quantitative measurements of spontaneous movements will reveal psychomotor components of immobilization. Studies designed to reveal how in vivo stimulation, or lack thereof, alters the stem cell microenvironment are needed to begin to develop treatment strategies for enhancing neurogenesis in bedridden patients.

Contribution of Persistent Organic Pollutant Exposure to the Adipose Tissue Oxidative Microenvironment in an Adult Cohort: A Multipollutant Approach.

PubMed

Artacho-Cordón, Francisco; León, Josefa; Sáenz, José M; Fernández, Mariana F; Martin-Olmedo, Piedad; Olea, Nicolás; Arrebola, Juan P

2016-12-20

Despite growing in vitro and in vivo evidence of the putative role of persistent organic pollutants (POPs) in the induction of oxidative damage in cell structures, this issue has been poorly addressed from an epidemiologic perspective. The aim of this study was to explore associations between adipose tissue POP concentrations and the in situ oxidative microenvironment. A cross-sectional study was conducted in a subsample (n = 271) of a previously established cohort, quantifying levels of eight POPs and four groups of oxidative stress biomarkers in adipose tissue. Associations were explored using multivariate linear regression analyses adjusted for potential confounders. We assessed the combined effect of POPs on oxidative stress/glutathione system biomarkers using weighted quantile sum regression (WQS). Increased concentrations of p,p'-DDE, HCB, β-HCH, dicofol, and PCBs (congeners -138, -153, and -180) were predominantly associated with higher lipid peroxidation (TBARS) [exp(β) = 1.09-1.78, p < 0.01-0.04)] and SOD activity [exp(β) = 1.13-1.48, p < 0.01-0.05)] levels. However, only a few associations were observed with glutathione system biomarkers, e.g., PCB-180 with total glutathione [exp(β) = 1.98, p = 0.03]. The WQS index was found to be positively associated with SOD activity, and PCB-138, PCB-180, and β-HCH were the main contributors to the index. Likewise, the WQS index was positively associated with TBARS levels, with the three PCBs acting as the main contributors. This is the first epidemiological evidence of the putative disruption by POPs of the adipose tissue oxidative microenvironment. Our results indicate that POP exposure may enhance alternative pathways to the glutathione detoxification route, which might result in tissue damage. Further research is warranted to fully elucidate the potential health implications.

Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

PubMed

Rayes, Roni F; Milette, Simon; Fernandez, Maria Celia; Ham, Boram; Wang, Ni; Bourdeau, France; Perrino, Stephanie; Yakar, Shoshana; Brodt, Pnina

2018-03-20

The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls. However, unlike controls, these neutrophils did not acquire the (anti-inflammatory) tumor-promoting phenotype, as evidenced by retention of high ICAM-1 expression and nitric oxide production and low CXCR4, CCL5, and VEGF expression and arginase production, all characteristic of the (pro-inflammatory) phenotype. This coincided with an increase in apoptotic tumor cells and reduced metastasis. Neutrophils isolated from these mice also had reduced IGF-IR expression levels. These changes were not observed in iLID mice with a short-term (2 days) IGF-I depletion, despite a 70% reduction in their circulating IGF-I levels, indicating that a sustained IGF-I deficiency was necessary to alter the neutrophil phenotype. Similar results were obtained with the highly metastatic Lewis lung carcinoma subline H-59 cells and in mice injected with an IGF-Trap that blocks IGF-IR signaling by reducing ligand bioavailability. Our results implicate the IGF axis in neutrophil polarization and the induction of a pro-metastatic microenvironment in the liver.

The epididymal microenvironment: a site of attack for a male contraceptive?

PubMed

Hinton, B T

1980-07-01

During their development, spermatozoa are continually bathed in fluid provided by epithelial secretions of the seminiferous tubule and the epididymal duct. This fluid or microenvironment is probably very important for spermatozoal maturation and survival. Micropuncture and microanalytic studies have revealed the occurrence of several biochemical changes of this specialized microenvironment along the epididymal duct; these changes seem to be linked to sperm maturation. The interactions between maturing spermatozoa and their microenvironment must be understood before interference in sperm maturation through intervention of the formation of the microenvironment is possible. Several compounds have been shown to interfere in spermatozoal maturation in the epididymis although their use as male contraceptives requires further investigation.

The influence of the microenvironment on the malignant phenotype

NASA Technical Reports Server (NTRS)

Park, C. C.; Bissell, M. J.; Barcellos-Hoff, M. H.

2000-01-01

Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. As tissue becomes cancerous, there are reciprocal interactions between neoplastic cells, adjacent normal cells such as stroma and endothelium, and their microenvironments. The current dominant paradigm wherein multiple genetic lesions provide both the impetus for, and the Achilles heel of, cancer might be inadequate to understand cancer as a disease process. In the following brief review, we will use selected examples to illustrate the influence of the microenvironment in the evolution of the malignant phenotype. We will also discuss recent studies that suggest novel therapeutic interventions might be derived from focusing on microenvironment and tumor cells interactions.

Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

PubMed

Celià-Terrassa, Toni

2018-05-04

Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

Exosome-derived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy.

PubMed

Tomasetti, Marco; Lee, Wan; Santarelli, Lory; Neuzil, Jiri

2017-01-20

Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape. Altered cell metabolism is one of the hallmarks of cancer. A number of different types of tumor rely on mitochondrial metabolism by triggering adaptive mechanisms to optimize their oxidative phosphorylation in relation to their substrate supply and energy demands. Exogenous exosomes can induce metabolic reprogramming by restoring the respiration of cancer cells and supress tumor growth. The exosomal miRs involved in the modulation of cancer metabolism may be potentially utilized for better diagnostics and therapy.

Senescence in chronic liver disease: Is the future in aging?

PubMed

Aravinthan, Aloysious D; Alexander, Graeme J M

2016-10-01

Cellular senescence is a fundamental, complex mechanism with an important protective role present from embryogenesis to late life across all species. It limits the proliferative potential of damaged cells thus protecting against malignant change, but at the expense of substantial alterations to the microenvironment and tissue homeostasis, driving inflammation, fibrosis and paradoxically, malignant disease if the process is sustained. Cellular senescence has attracted considerable recent interest with recognition of pathways linking aging, malignancy and insulin resistance and the current focus on therapeutic interventions to extend health-span. There are major implications for hepatology in the field of fibrosis and cancer, where cellular senescence of hepatocytes, cholangiocytes, stellate cells and immune cells has been implicated in chronic liver disease progression. This review focuses on cellular senescence in chronic liver disease and explores therapeutic opportunities. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The biology, function and clinical implications of exosomes in lung cancer.

PubMed

Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

2017-10-28

Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

[Prostate cancer microenvironment: Its structure, functions and therapeutic applications].

PubMed

Lorion, R; Bladou, F; Spatz, A; van Kempen, L; Irani, J

2016-06-01

In the field of prostate cancer there is a growing tendency for more and more studies to emphasise the predominant role of the zone situated between the tumour and the host: the tumour microenvironment. The aim of this article is to describe the structure and the functions of the prostate cancer microenvironment as well as the principal treatments that are being applied to it. PubMed and ScienceDirect databases have been interrogated using the association of keywords "tumour microenvironment" and "neoplasm therapy" along with "microenvironnement tumoral" and "traitements". Of the 593 articles initially found, 50 were finally included. The tumour microenvironment principally includes host elements that are diverted from their primary functions and encourage the development of the tumour. In it we find immunity cells, support tissue as well as vascular and lymphatic neovascularization. Highlighting the major role played by this microenvironment has led to the development of specific treatments, notably antiangiogenic therapy and immunotherapy. The tumour microenvironment, the tumour and the host influence themselves mutually and create a variable situation over time. Improvement of the knowledge of the prostate cancer microenvironment gradually enables us to pass from an approach centred on the tumour to a broader approach to the whole tumoral ecosystem. This enabled the emergence of new treatments whose place in the therapeutic arsenal still need to be found. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Development and characterization of a microfluidic model of the tumour microenvironment.

PubMed

Ayuso, Jose M; Virumbrales-Muñoz, María; Lacueva, Alodia; Lanuza, Pilar M; Checa-Chavarria, Elisa; Botella, Pablo; Fernández, Eduardo; Doblare, Manuel; Allison, Simon J; Phillips, Roger M; Pardo, Julián; Fernandez, Luis J; Ochoa, Ignacio

2016-10-31

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live 'window' into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device's potential to enable more physiological in vitro drug screening.

On the microenvironment of polymers in solution. Pt. 2. Polarity of the polymer microenvironment in binary solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strop, P.; Mikes, F.; Kalal, J.

1976-03-25

In Pt. 1 of this work, solvatochromic compounds embedded in polymer chains were used for measuring the polarity of their microenvironment. The semiempirical expression of the polarity of solvents by means of the energy of the charge-transfer (C-T) absorption band of 1-ethyl-4-carbomethylpyridinium iodide, as proposed by Kosower, was shown to be applicable in principle for measuring the polarity of the polymer microenvironment. In this present work, this approach was employed to measure the polarity of microenvironments of the synthetic polymers polymethacrylamide (PMA), poly(2-hydroxethyl methacrylate) (PHEMA), poly(2-vinylpyridine) (P-2VP), poly(4-vinylpyridine) (P-4VP), poly(methyl methacrylate) (PMMA), poly(butyl methacrylate) (PBMA), and polystyrene (PS) in binarymore » solvents and to compare them with the polarities of these solvents. It is concluded that comparisons with a solution with the same polarity expressed by the semi-empirical scale represents only the first approximation for characterizing the polymer microenvironment. (12 refs.)« less

Microenvironmental regulation of the progression of oral potentially malignant disorders towards malignancy

PubMed Central

Ai, Ruixue; Tao, Yan; Hao, Yilong; Jiang, Lu; Dan, Hongxia; Ji, Ning; Zeng, Xin; Zhou, Yu; Chen, Qianming

2017-01-01

Oral potentially malignant disorders (OPMD) develop in a complex tissue microenvironment where they grow sustainably, acquiring oral squamous cell carcinoma (OSCC) characteristics. The malignant tumor depends on interactions with the surrounding microenvironment to achieve loco-regional invasion and distant metastases. Unlike abnormal cells, the multiple cell types in the tissue microenvironment are relatively stable at the genomic level and, thus, become therapeutic targets with lower risk of resistance, decreasing the risk of OPMD acquiring cancer characteristics and carcinoma recurrence. However, deciding how to disrupt the OPMD and OSCC microenvironments is itself a daunting challenge, since their microenvironments present opposite capacities, resulting in diverse consequences. Furthermore, recent studies revealed that tumor-associated immune cells also participate in the process of differentiation from OPMD to OSCC, suggesting that reeducating stromal cells may be a new strategy to prevent OPMD from acquiring OSCC characteristics and to treat OSCC. In this review, we discuss the characteristics of the microenvironment of OPMD and OSCC as well as new therapeutic strategies. PMID:29113419

Stratospheric ozone changes under solar geoengineering: implications for UV exposure and air quality

NASA Astrophysics Data System (ADS)

Nowack, Peer Johannes; Abraham, Nathan Luke; Braesicke, Peter; Pyle, John Adrian

2016-03-01

Various forms of geoengineering have been proposed to counter anthropogenic climate change. Methods which aim to modify the Earth's energy balance by reducing insolation are often subsumed under the term solar radiation management (SRM). Here, we present results of a standard SRM modelling experiment in which the incoming solar irradiance is reduced to offset the global mean warming induced by a quadrupling of atmospheric carbon dioxide. For the first time in an atmosphere-ocean coupled climate model, we include atmospheric composition feedbacks for this experiment. While the SRM scheme considered here could offset greenhouse gas induced global mean surface warming, it leads to important changes in atmospheric composition. We find large stratospheric ozone increases that induce significant reductions in surface UV-B irradiance, which would have implications for vitamin D production. In addition, the higher stratospheric ozone levels lead to decreased ozone photolysis in the troposphere. In combination with lower atmospheric specific humidity under SRM, this results in overall surface ozone concentration increases in the idealized G1 experiment. Both UV-B and surface ozone changes are important for human health. We therefore highlight that both stratospheric and tropospheric ozone changes must be considered in the assessment of any SRM scheme, due to their important roles in regulating UV exposure and air quality.

Enhanced solar energy options using earth-orbiting mirrors

NASA Technical Reports Server (NTRS)

Gilbreath, W. P.; Billman, K. W.; Bowen, S. W.

1978-01-01

A system of orbiting space reflectors is described, analyzed, and shown to economically provide nearly continuous insolation to preselected ground sites, producing benefits hitherto lacking in conventional solar farms and leading to large reductions in energy costs for such installations. Free-flying planar mirrors of about 1 sq km are shown to be optimum and can be made at under 10 g/sq m of surface, thus minimizing material needs and space transportation costs. Models are developed for both the design of such mirrors and for the analysis of expected ground insolation as a function of orbital parameters, time, and site location. Various applications (agricultural, solar-electric production, weather enhancement, etc.) are described.

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment.

PubMed

Huang, Guoyou; Li, Fei; Zhao, Xin; Ma, Yufei; Li, Yuhui; Lin, Min; Jin, Guorui; Lu, Tian Jian; Genin, Guy M; Xu, Feng

2017-10-25

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

PubMed Central

Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul

2014-01-01

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future. PMID:25143954

Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances.

PubMed

Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul; Vrana, Nihal Engin

2014-01-01

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

Development and characterization of a microfluidic model of the tumour microenvironment

PubMed Central

Ayuso, Jose M.; Virumbrales-Muñoz, María; Lacueva, Alodia; Lanuza, Pilar M.; Checa-Chavarria, Elisa; Botella, Pablo; Fernández, Eduardo; Doblare, Manuel; Allison, Simon J.; Phillips, Roger M.; Pardo, Julián; Fernandez, Luis J.; Ochoa, Ignacio

2016-01-01

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live ‘window’ into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device’s potential to enable more physiological in vitro drug screening. PMID:27796335

One size fits all electronics for insole-based activity monitoring.

PubMed

Hegde, Nagaraj; Bries, Matthew; Melanson, Edward; Sazonov, Edward

2017-07-01

Footwear based wearable sensors are becoming prominent in many areas of monitoring health and wellness, such as gait and activity monitoring. In our previous research we introduced an insole based wearable system SmartStep, which is completely integrated in a socially acceptable package. From a manufacturing perspective, SmartStep's electronics had to be custom made for each shoe size, greatly complicating the manufacturing process. In this work we explore the possibility of making a universal electronics platform for SmartStep - SmartStep 3.0, which can be used in the most common insole sizes without modifications. A pilot human subject experiments were run to compare the accuracy between the one-size fits all (SmartStep 3.0) and custom size SmartStep 2.0. A total of ~10 hours of data was collected in the pilot study involving three participants performing different activities of daily living while wearing SmartStep 2.0 and SmartStep 3.0. Leave one out cross validation resulted in a 98.5% average accuracy from SmartStep 2.0, while SmartStep 3.0 resulted in 98.3% accuracy, suggesting that the SmartStep 3.0 can be as accurate as SmartStep 2.0, while fitting most common shoe sizes.

Global correlation between surface heat fluxes and insolation in the 11-year solar cycle: The latitudinal effect

NASA Astrophysics Data System (ADS)

Volobuev, D. M.; Makarenko, N. G.

2014-12-01

Because of the small amplitude of insolation variations (1365.2-1366.6 W m-2 or 0.1%) from the 11-year solar cycle minimum to the cycle maximum and the structural complexity of the climatic dynamics, it is difficult to directly observe a solar signal in the surface temperature. The main difficulty is reduced to two factors: (1) a delay in the temperature response to external action due to thermal inertia, and (2) powerful internal fluctuations of the climatic dynamics suppressing the solar-driven component. In this work we take into account the first factor, solving the inverse problem of thermal conductivity in order to calculate the vertical heat flux from the measured temperature near the Earth's surface. The main model parameter—apparent thermal inertia—is calculated from the local seasonal extremums of temperature and albedo. We level the second factor by averaging mean annual heat fluxes in a latitudinal belt. The obtained mean heat fluxes significantly correlate with a difference between the insolation and optical depth of volcanic aerosol in the atmosphere, converted into a hindered heat flux. The calculated correlation smoothly increases with increasing latitude to 0.4-0.6, and the revealed latitudinal dependence is explained by the known effect of polar amplification.

Preliminary evaluation of prototype footwear and insoles to optimise balance and gait in older people.

PubMed

Menz, Hylton B; Auhl, Maria; Munteanu, Shannon E

2017-09-11

Footwear has the potential to influence balance in either a detrimental or beneficial manner, and is therefore an important consideration in relation to falls prevention. The objective of this study was to evaluate balance ability and gait patterns in older women while wearing prototype footwear and insoles designed to improve balance. Older women (n = 30) aged 65 - 83 years (mean 74.4, SD 5.6) performed a series of laboratory tests of balance ability (postural sway on a foam rubber mat, limits of stability and tandem walking, measured with the Neurocom® Balance Master) and gait patterns (walking speed, cadence, step length and step width at preferred speed, measured with the GAITRite® walkway) while wearing (i) flexible footwear (Dunlop Volley™), (ii) their own footwear, and (iii) prototype footwear and insoles designed to improve dynamic balance. Perceptions of the footwear were also documented using a structured questionnaire. There was no difference in postural sway, limits of stability or gait patterns between the footwear conditions. However, when performing the tandem walking test, there was a significant reduction in step width and end sway when wearing the prototype footwear compared to both the flexible footwear and participants' own footwear. Participants perceived their own footwear to be more attractive, comfortable, well-fitted and easier to put on and off compared to the prototype footwear. Despite this, most participants (n = 18, 60%) reported that they would consider wearing the prototype footwear to reduce their risk of falling. The prototype footwear and insoles used in this study improve balance when performing a tandem walk test, as evidenced by a narrower step width and decreased sway at completion of the task. However, further development of the design is required to make the footwear acceptable to older women from the perspective of aesthetics and comfort. Australian New Zealand Clinical Trials Registry. ACTRN12617001128381 , 01/08/2017 (retrospectively registered).

Variability of East Asian summer monsoon precipitation during the Holocene and possible forcing mechanisms

NASA Astrophysics Data System (ADS)

Lu, Fuzhi; Ma, Chunmei; Zhu, Cheng; Lu, Huayu; Zhang, Xiaojian; Huang, Kangyou; Guo, Tianhong; Li, Kaifeng; Li, Lan; Li, Bing; Zhang, Wenqing

2018-03-01

Projecting how the East Asian summer monsoon (EASM) rainfall will change with global warming is essential for human sustainability. Reconstructing Holocene climate can provide critical insight into its forcing and future variability. However, quantitative reconstructions of Holocene summer precipitation are lacking for tropical and subtropical China, which is the core region of the EASM influence. Here we present high-resolution annual and summer rainfall reconstructions covering the whole Holocene based on the pollen record at Xinjie site from the lower Yangtze region. Summer rainfall was less seasonal and 30% higher than modern values at 10-6 cal kyr BP and gradually declined thereafter, which broadly followed the Northern Hemisphere summer insolation. Over the last two millennia, however, the summer rainfall has deviated from the downward trend of summer insolation. We argue that greenhouse gas forcing might have offset summer insolation forcing and contributed to the late Holocene rainfall anomaly, which is supported by the TraCE-21 ka transient simulation. Besides, tropical sea-surface temperatures could modulate summer rainfall by affecting evaporation of seawater. The rainfall pattern concurs with stalagmite and other proxy records from southern China but differs from mid-Holocene rainfall maximum recorded in arid/semiarid northern China. Summer rainfall in northern China was strongly suppressed by high-northern-latitude ice volume forcing during the early Holocene in spite of high summer insolation. In addition, the El Niño/Southern Oscillation might be responsible for droughts of northern China and floods of southern China during the late Holocene. Furthermore, quantitative rainfall reconstructions indicate that the Paleoclimate Modeling Intercomparison Project (PMIP) simulations underestimate the magnitude of Holocene precipitation changes. Our results highlight the spatial and temporal variability of the Holocene EASM precipitation and potential forcing mechanisms, which are very helpful for calibration of paleoclimate models and prediction of future precipitation changes in East Asia in the scenario of global warming.

Upper ocean climate of the Eastern Mediterranean Sea during the Holocene Insolation Maximum - a model study

NASA Astrophysics Data System (ADS)

Adloff, F.; Mikolajewicz, U.; Kučera, M.; Grimm, R.; Maier-Reimer, E.; Schmiedl, G.; Emeis, K.-C.

2011-10-01

Nine thousand years ago (9 ka BP), the Northern Hemisphere experienced enhanced seasonality caused by an orbital configuration close to the minimum of the precession index. To assess the impact of this "Holocene Insolation Maximum" (HIM) on the Mediterranean Sea, we use a regional ocean general circulation model forced by atmospheric input derived from global simulations. A stronger seasonal cycle is simulated by the model, which shows a relatively homogeneous winter cooling and a summer warming with well-defined spatial patterns, in particular, a subsurface warming in the Cretan and western Levantine areas. The comparison between the SST simulated for the HIM and a reconstruction from planktonic foraminifera transfer functions shows a poor agreement, especially for summer, when the vertical temperature gradient is strong. As a novel approach, we propose a reinterpretation of the reconstruction, to consider the conditions throughout the upper water column rather than at a single depth. We claim that such a depth-integrated approach is more adequate for surface temperature comparison purposes in a situation where the upper ocean structure in the past was different from the present-day. In this case, the depth-integrated interpretation of the proxy data strongly improves the agreement between modelled and reconstructed temperature signal with the subsurface summer warming being recorded by both model and proxies, with a small shift to the south in the model results. The mechanisms responsible for the peculiar subsurface pattern are found to be a combination of enhanced downwelling and wind mixing due to strengthened Etesian winds, and enhanced thermal forcing due to the stronger summer insolation in the Northern Hemisphere. Together, these processes induce a stronger heat transfer from the surface to the subsurface during late summer in the western Levantine; this leads to an enhanced heat piracy in this region, a process never identified before, but potentially characteristic of time slices with enhanced insolation.

Corrigendum to "Upper ocean climate of the Eastern Mediterranean Sea during the Holocene Insolation Maximum - a model study" published in Clim. Past, 7, 1103-1122, 2011

NASA Astrophysics Data System (ADS)

Adloff, F.; Mikolajewicz, U.; Kučera, M.; Grimm, R.; Maier-Reimer, E.; Schmiedl, G.; Emeis, K.-C.

2011-11-01

Nine thousand years ago (9 ka BP), the Northern Hemisphere experienced enhanced seasonality caused by an orbital configuration close to the minimum of the precession index. To assess the impact of this "Holocene Insolation Maximum" (HIM) on the Mediterranean Sea, we use a regional ocean general circulation model forced by atmospheric input derived from global simulations. A stronger seasonal cycle is simulated by the model, which shows a relatively homogeneous winter cooling and a summer warming with well-defined spatial patterns, in particular, a subsurface warming in the Cretan and western Levantine areas. The comparison between the SST simulated for the HIM and a reconstruction from planktonic foraminifera transfer functions shows a poor agreement, especially for summer, when the vertical temperature gradient is strong. As a novel approach, we propose a reinterpretation of the reconstruction, to consider the conditions throughout the upper water column rather than at a single depth. We claim that such a depth-integrated approach is more adequate for surface temperature comparison purposes in a situation where the upper ocean structure in the past was different from the present-day. In this case, the depth-integrated interpretation of the proxy data strongly improves the agreement between modelled and reconstructed temperature signal with the subsurface summer warming being recorded by both model and proxies, with a small shift to the south in the model results. The mechanisms responsible for the peculiar subsurface pattern are found to be a combination of enhanced downwelling and wind mixing due to strengthened Etesian winds, and enhanced thermal forcing due to the stronger summer insolation in the Northern Hemisphere. Together, these processes induce a stronger heat transfer from the surface to the subsurface during late summer in the western Levantine; this leads to an enhanced heat piracy in this region, a process never identified before, but potentially characteristic of time slices with enhanced insolation.

Topographic, latitudinal and climatic distribution of Pinus coulteri: geographic range limits are not at the edge of the climate envelope

USGS Publications Warehouse

Chardon, Nathalie I.; Cornwell, William K.; Flint, Lorraine E.; Flint, Alan L.; Ackerly, David D.

2015-01-01

With changing climate, many species are projected to move poleward or to higher elevations to track suitable climates. The prediction that species will move poleward assumes that geographically marginal populations are at the edge of the species' climatic range. We studied Pinus coulteri from the center to the northern (poleward) edge of its range, and examined three scenarios regarding the relationship between the geographic and climatic margins of a species' range. We used herbarium and iNaturalist.org records to identify P. coulteri sites, generated a species distribution model based on temperature, precipitation, climatic water deficit, and actual evapotranspiration, and projected suitability under future climate scenarios. In fourteen populations from the central to northern portions of the range, we conducted field studies and recorded elevation, slope and aspect (to estimate solar insolation) to examine relationships between local and regional distributions. We found that northern populations of P. coulteri do not occupy the cold or wet edge of the species' climatic range; mid-latitude, high elevation populations occupy the cold margin. Aspect and insolation of P. coulteri populations changed significantly across latitudes and elevations. Unexpectedly, northern, low-elevation stands occupy north-facing aspects and receive low insolation, while central, high-elevation stands grow on more south-facing aspects that receive higher insolation. Modeled future climate suitability is projected to be highest in the central, high elevation portion of the species range, and in low-lying coastal regions under some scenarios, with declining suitability in northern areas under most future scenarios. For P. coulteri, the lack of high elevation habitat combined with a major dispersal barrier may limit northward movement in response to a warming climate. Our analyses demonstrate the importance of distinguishing geographically vs. climatically marginal populations, and the importance of quantitative analysis of the realized climate space to understand species range limits.

Obliquity (41kyr) Paced SE Asian Monsoon Variability Following the Miocene Climate Transition

NASA Astrophysics Data System (ADS)

Heitmann, E. O.; Breecker, D.; Ji, S.; Nie, J.

2016-12-01

We investigated Asian monsoon variability during the Miocene, which may provide a good analog for the future given the lack of northern hemisphere ice sheets. In the Miocene Yanwan Section (Tianshui Basin, China) 25cm thick CaCO3-cemented horizons overprint siltstones every 1m. We suggest this rhythmic layering records variations in water availability influenced by the Asian monsoon. We interpret the siltstones as stacked soils that formed in a seasonal climate with a fluctuating water table, evidenced by roots, clay films, mottling, presence of CaCO3 nodules, and stacked carbonate nodule δ13C and δ18O profiles that mimic modern soils. We interpret the CaCO3-cemented horizons as capillary-fringe carbonates that formed in an arid climate with a steady water table and high potential evapotranspiration (PET), evidenced by sharp upper and basal contacts, micrite, sparite, and root-pore cements. The magnetostratigraphy-based age model indicates obliquity-pacing of the CaCO3-cemented horizons suggesting an orbital control on water availability, for which we propose two mechanisms: 1) summer monsoon strength, moderated by the control of obliquity on the cross-equatorial pressure gradient, and 2) PET, moderated by the control of precession on 35oN summer insolation. We use orbital configurations to predict lithology. Coincidence of obliquity minima and insolation maxima drives strong summer monsoons, seasonal variations in water table depth and soil formation. Coincidence of obliquity maxima and insolation minima drives weak summer monsoons, high PET, and carbonate accumulation above a deepened, stable water table. Coincidence of obliquity and insolation minima drives strong monsoons, low PET, and a high water table, explaining the evidence for aquatic plants previously observed in this section. Southern hemisphere control of summer monsoon variability in the Miocene may thus have resulted in large water availability variations in central China.

Effect of Footwear on Joint Pain and Function in Older Adults With Lower Extremity Osteoarthritis.

PubMed

Wagner, Amy; Luna, Sarah

Lower extremity osteoarthritis (OA) is a common condition among older adults; given the risks of surgical and pharmaceutical interventions, conservative, lower-cost management options such as footwear warrant further investigation. This systematic review investigated the effects of footwear, including shoe inserts, in reducing lower extremity joint pain and improving gait, mobility, and quality of life in older adults with OA. The CINAHL, SPORTDiscus, PubMed, RECAL, and Web of Knowledge databases were searched for publications from January 1990 to September 2014, using the terms "footwear," "shoes," "gait," "pain," and "older adult." Participants who were 50 years or older and those who had OA in at least one lower extremity joint narrowed the results. Outcomes of interest included measures of pain, comfort, function, gait, or quality of life. Exclusion criteria applied to participants with rheumatoid arthritis, amputation, diabetes, multiple sclerosis, use of modified footwear or custom orthotics, purely biomechanical studies, and outcomes of balance or falls only. Single-case studies, qualitative narrative descriptions, and expert opinions were also excluded. The initial search resulted in a total of 417 citations. Eleven articles met inclusion criteria. Two randomized controlled trials and 3 quasiexperimental studies reported lateral wedge insoles may have at least some pain-relieving effects and improved functional mobility in older adults at 4 weeks to 2 years' follow-up, particularly when used with subtalar and ankle strapping. Three randomized controlled trials with large sample sizes reported that lateral wedges provided no knee pain relief compared with flat insoles. Hardness of shoe soles did not significantly affect joint comfort in the foot in a quasiexperimental study. A quasiexperimental designed study investigating shock-absorbing insoles showed reduction in knee joint pain with 1 month of wear. Finally, a cross-sectional prognostic study indicated poor footwear at early ages exhibits an association with hindfoot pain later in life. Because of the limited number of randomized control trials, it is not possible to make a definitive conclusion about the long-term effects of footwear on lower extremity joint pain caused by OA. There is mounting evidence that shock-absorbing insoles, subtalar strapping, and avoidance of high heels and sandals early in life may prevent lower extremity joint pain in older adults, but no conclusive evidence exists to show that lateral wedge insoles will provide long-term relief from knee joint pain and improved mobility in older adults with OA. More high-quality randomized control trials are needed to study the effectiveness of footwear and shoe inserts on joint pain and function in older adults with OA.

The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints

PubMed Central

Llosa, Nicolas J.; Cruise, Michael; Tam, Ada; Wick, Elizabeth C.; Hechenbleikner, Elizabeth M.; Taube, Janis M.; Blosser, Lee; Fan, Hongni; Wang, Hao; Luber, Brandon; Zhang, Ming; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Sears, Cynthia L.; Anders, Robert A.; Pardoll, Drew M.; Housseau, Franck

2014-01-01

We examined the immune microenvironment of primary colorectal cancer (CRC) using immunohistochemistry, laser capture microdissection/qRT-PCR, flow cytometry and functional analysis of tumor infiltrating lymphocytes. A subset of CRC displayed high infiltration with activated CD8+ CTL as well as activated Th1 cells characterized by IFN-γ production and the Th1 transcription factor Tbet. Parallel analysis of tumor genotypes revealed that virtually all of the tumors with this active Th1/CTL microenvironment had defects in mismatch repair, as evidenced by microsatellite instability (MSI). Counterbalancing this active Th1/CTL microenvironment, MSI tumors selectively demonstrated highly up-regulated expression of multiple immune checkpoints, including five – PD-1, PD-L1, CTLA-4, LAG-3 and IDO – currently being targeted clinically with inhibitors. These findings link tumor genotype with the immune microenvironment, and explain why MSI tumors are not naturally eliminated despite a hostile Th1/CTL microenvironment. They further suggest that blockade of specific checkpoints may be selectively efficacious in the MSI subset of CRC. PMID:25358689

Key Features of the Intragraft Microenvironment that Determine Long-Term Survival Following Transplantation

PubMed Central

Bruneau, Sarah; Woda, Craig Bryan; Daly, Kevin Patrick; Boneschansker, Leonard; Jain, Namrata Gargee; Kochupurakkal, Nora; Contreras, Alan Gabriel; Seto, Tatsuichiro; Briscoe, David Michael

2012-01-01

In this review, we discuss how changes in the intragraft microenvironment serve to promote or sustain the development of chronic allograft rejection. We propose two key elements within the microenvironment that contribute to the rejection process. The first is endothelial cell proliferation and angiogenesis that serve to create abnormal microvascular blood flow patterns as well as local tissue hypoxia, and precedes endothelial-to-mesenchymal transition. The second is the overexpression of local cytokines and growth factors that serve to sustain inflammation and, in turn, function to promote a leukocyte-induced angiogenesis reaction. Central to both events is overexpression of vascular endothelial growth factor (VEGF), which is both pro-inflammatory and pro-angiogenic, and thus drives progression of the chronic rejection microenvironment. In our discussion, we focus on how inflammation results in angiogenesis and how leukocyte-induced angiogenesis is pathological. We also discuss how VEGF is a master control factor that fosters the development of the chronic rejection microenvironment. Overall, this review provides insight into the intragraft microenvironment as an important paradigm for future direction in the field. PMID:22566935

Lateral Wedge Insoles as a Conservative Treatment for Pain in Patients With Medial Knee Osteoarthritis

PubMed Central

Parkes, Matthew J.; Maricar, Nasimah; Lunt, Mark; LaValley, Michael P.; Jones, Richard K.; Segal, Neil A.; Takahashi-Narita, Kayoko; Felson, David T.

2015-01-01

IMPORTANCE There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis. OBJECTIVE To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control. DATA SOURCES Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language. The metaRegister of Controlled Trials and the NHS Evidence website were also searched. STUDY SELECTION Included were randomized trials comparing shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition in patients with painful medial knee osteoarthritis. Studies must have included patient-reported pain as an outcome. DATA EXTRACTION AND SYNTHESIS Trial data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed using the Cochrane Risk of Bias tool by 2 observers. Eligible studies were pooled using a random-effects approach. MAIN OUTCOME AND MEASURES Change in self-reported knee pain at follow-up. RESULTS Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment. The pooled standardized mean difference (SMD) suggested a favorable association with lateral wedges compared with control (SMD, −0.47; 95% CI, −0.80 to −0.14); however, substantial heterogeneity was present (I2 = 82.7%). This effect size represents an effect of −2.12 points on the 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. Larger trials with a lower risk of bias suggested a null association. Meta-regression analyses showed that higher effect sizes (unstandardized β, 1.07 [95% CI, 0.28 to 1.87] for trials using a no treatment control) were seen in trials using a no wedge treatment control group (n = 4 trials; SMD, −1.20 [95% CI, −2.09 to −0.30]) and lower effect sizes (unstandardized β, 0.26 [95% CI, 0.002 to 0.52] for each bias category deemed low risk) when the study method was deemed at low risk of bias. Among trials in which the control treatment was a neutral insole (n = 7), lateral wedges showed no association (SMD, −0.03 [95% CI, −0.18 to 0.12] on WOMAC; this represents an effect of −0.12 points), and results showed little heterogeneity (I2 = 7.1%). CONCLUSIONS AND RELEVANCE Although meta-analytic pooling of all studies showed a statistically significant association between use of lateral wedges and lower pain in medial knee osteoarthritis, restriction of studies to those using a neutral insole comparator did not show a significant or clinically important association. These findings do not support the use of lateral wedges for this indication. PMID:23989797

A Geographic Mosaic of Climate Change Impacts on Terrestrial Vegetation: Which Areas Are Most at Risk?

PubMed Central

Ackerly, David D.; Cornwell, William K.; Weiss, Stuart B.; Flint, Lorraine E.; Flint, Alan L.

2015-01-01

Changes in climate projected for the 21st century are expected to trigger widespread and pervasive biotic impacts. Forecasting these changes and their implications for ecosystem services is a major research goal. Much of the research on biotic responses to climate change has focused on either projected shifts in individual species distributions or broad-scale changes in biome distributions. Here, we introduce a novel application of multinomial logistic regression as a powerful approach to model vegetation distributions and potential responses to 21st century climate change. We modeled the distribution of 22 major vegetation types, most defined by a single dominant woody species, across the San Francisco Bay Area. Predictor variables included climate and topographic variables. The novel aspect of our model is the output: a vector of relative probabilities for each vegetation type in each location within the study domain. The model was then projected for 54 future climate scenarios, spanning a representative range of temperature and precipitation projections from the CMIP3 and CMIP5 ensembles. We found that sensitivity of vegetation to climate change is highly heterogeneous across the region. Surprisingly, sensitivity to climate change is higher closer to the coast, on lower insolation, north-facing slopes and in areas of higher precipitation. While such sites may provide refugia for mesic and cool-adapted vegetation in the face of a warming climate, the model suggests they will still be highly dynamic and relatively sensitive to climate-driven vegetation transitions. The greater sensitivity of moist and low insolation sites is an unexpected outcome that challenges views on the location and stability of climate refugia. Projections provide a foundation for conservation planning and land management, and highlight the need for a greater understanding of the mechanisms and time scales of potential climate-driven vegetation transitions. PMID:26115485

Precise time-window for the onset of glacial termination found

NASA Astrophysics Data System (ADS)

Lai, C.-C.; Tseng, Y.-H.; Dietrich, D. E.

2009-04-01

Following a set of three simple rules, we have found a precise time-window (TW) for each onset of a glacial termination (GT) appeared during the last million years. The onset of GT (OGT) is defined as the year when the following two conditions are met: (1) the benthic delta 18-O is a maximum and greater than 4.5‰ and (2) its value continually drops 1‰ within 5 Ky. We developed the rules based on three hypotheses. We hypothesize that: (H1) The Earth's three orbital parameters (eccentricity, obliquity and precession of equinox) determine the insolation which is the key force to the climate system. (H2) However, only a small fraction of insolation is converted into sensible heat (SH) and chemical energy through photosynthesis (CETP) as influxes to the climate system's main heat capacitors (HCs), namely the world oceans. When insolation increases, both the SH flux and CETP increase. The downward SH flux will only increase the stability of the seawater. Nonetheless, the CETP gets accumulated faster than average. The CETP cascades through the marine food web and bacterial degradation. Finally, it is stored in the simple gas molecules (such as CH4) that form methane hydrate (MH) and other hydrates such as hydrogen sulfide hydrate (HSH) in deep sea sediments after a long time. While hydrates deposit accumulates with time, it also breaks off from the sediments from time to time. Since the density of MH is slightly smaller than average seawater, the MH ascends slowly from deep sea into upper part of ocean. But, HSH is slightly denser than the warm seawater in the upper part of ocean. Over the portion of glacial cycle when insolation is strong, the existence of a residual SH prevents the ascension of hydrates. (H3) Internal forcing - An internal energy converter or a heat generator exists in the oceans. Lai (2007) has found the link between the observed seawater warming at intermediate depth (400 - 750 m) (Barnett et al. 2001) and the dissociation of floating microscopic MH and subsequent methane oxidation via bacteria. We postulate that the cooling of deep seawater when the insolation is weak leads to more hydrates ascending through seawater to the level for dissociation (which is a process depending on seawater temperature and pressure). The oxidation of CH4 and H2S after hydrate-dissociation is a multi-step process/phenomenon that we refer to as ocean slow-burn (OSB). It generates the maximum heat per mole of atom-C among all carbon-containing compounds, including sugars. Through oxidation, the CETP is now released as heat that is transferred via biomass, eventually being deposited into the seawater. Since the heat generated in the OSB is greater than that required to dissociate hydrates, they become self-sustained and run-away as long as all players (MH, bacteria, and methane ice worms (Fisher et al. 2000)) are present. So, the glacial termination is a process to release the stored CETP instead of trapping more insolation energy. (H4) Having accumulated enough energy sources, the OGT will happen when the joint effect of the three parameters triggers the discharge of the HCs. The trigger is an abrupt reduction in insolation over the Southern Oceans, especially South Atlantic under which lies the active Mid-Atlantic Ridge. The three rules were found through following steps: (1) finding a wide time-window (WTW) within which the energy (stored in hydrates) required to sustain a GT can be accumulated. (2) Then, we find a narrow time-window (NTW) (within that WTW) when the HC is abruptly cooled down due to a quick reduction in insolation. That NTW shall be the ideal time for the OGT. The variation of eccentricity is the factor controlling the annual global integral of insolation (AGII). The bigger the eccentricity the greater the AGII is. The greater the AGII the more the global CETP capture is. Presume that eccentricity varies like a sinusoidal function of time with a single period of 95 Ky. Then, the CETP being stored into the HCs varies in the same cycle, too. On the other hand, the hydrates are being consumed by OSB process at a rate, (namely r(OSB)), that is not directly controlled by the eccentricity. Assume that during the glacial period r(OSB) is significant but smaller than the accumulation rate of CETP (namely, r(CETP)). This leads us to think that during the phase -90o to 90o (valley to peak) half cycle is a better WTW to accumulate hydrates than the 90o to 270o (peak to valley) half cycle. This is Rule 1. The NTW is regulated by Rules 2 and 3. Rule 2 is that the obliquity must be increasing. Rule 3 is that precession must be near 180o phase angle. The reasons for these two rules will be explained. The NTW will be shown to match every OGT appeared in last one million years.

Effects of surface characteristics on the plantar shape of feet and subjects' perceived sensations.

PubMed

Witana, Channa P; Goonetilleke, Ravindra S; Xiong, Shuping; Au, Emily Y L

2009-03-01

Orthotics and other types of shoe inserts are primarily designed to reduce injury and improve comfort. The interaction between the plantar surface of the foot and the load-bearing surface contributes to foot and surface deformations and hence to perceived comfort, discomfort or pain. The plantar shapes of 16 participants' feet were captured when standing on three support surfaces that had different cushioning properties in the mid-foot region. Foot shape deformations were quantified using 3D laser scans. A questionnaire was used to evaluate the participant's perceptions of perceived shape and perceived feeling. The results showed that the structure in the mid-foot could change shape, independent of the rear-foot and forefoot regions. Participants were capable of identifying the shape changes with distinct preferences towards certain shapes. The cushioning properties of the mid-foot materials also have a direct influence on perceived feelings. This research has strong implications for the design and material selection of orthotics, insoles and footwear.

Insolation Effects on Lunar Hydrogen: Observation from the LRO LEND and LOLA Instruments

NASA Technical Reports Server (NTRS)

McClanahan, T. P.; Mitrofanov, I. G.; Boynton, W. V.; Chin, G.; Droege, G.; Evans, L. G.; Garvin, J.; Harshman, K.; Livak, M. M.; Malakhov, A.;

Lunar and Planetary Science XXXV: Special Session: Mars Climate Change

NASA Technical Reports Server (NTRS)

2004-01-01

The session "Mars Climate Change" contained the following reports:Geological Evidence for Climate Change on Mars; A New Astronomical Solution for the Long Term Evolution of the Insolation Quantities of Mars; Interpreting Martian Paleoclimate with a Mars General Circulation Model; History and Progress of GCM Simulations on Recent Mars Climate Change; Northern and Southern Permafrost Regions on Mars with High Content of Water Ice: Similarities and Differences; Periods of Active Permafrost Layer Formation in the Recent Geological History of Mars; Microclimate Zones in the Dry Valleys of Antarctica: Implications for Landscape; Evolution and Climate Change on Mars; Geomorphic Evidence for Martian Ground Ice and Climate Change; Explaining the Mid-Latitude Ice Deposits with a General Circulation Model; Tharsis Montes Cold-based Glaciers: Observations and Constraints for Modeling and Preliminary Results; Ice Sheet Modeling: Terrestrial Background and Application to Arsia Mons Lobate Deposit, Mars; Enhanced Water-Equivalent Hydrogen on the Western Flanks of the Tharsis Montes and Olympus Mons: Remnant Subsurface Ice or Hydrate Minerals?; and New Age Mars.

Lunar and Planetary Science XXXV: Special Session: Mars Climate Change

NASA Technical Reports Server (NTRS)

2004-01-01

The session "Mars Climate Change" included the following topics:Geological Evidence for Climate Change on Mars; A New Astronomical Solution for the Long Term Evolution of the Insolation Quantities of Mars; Interpreting Martian Paleoclimate with a Mars General Circulation Model; History and Progress of GCM Simulations on Recent Mars Climate Change; Northern and Southern Permafrost Regions on Mars with High Content of Water Ice: Similarities and Differences; Periods of Active Permafrost Layer Formation in the Recent Geological History of Mars; Microclimate Zones in the Dry Valleys of Antarctica: Implications for Landscape Evolution and Climate Change on Mars; Geomorphic Evidence for Martian Ground Ice and Climate Change; Explaining the Mid-Latitude Ice Deposits with a General Circulation Model; Tharsis Montes Cold-based Glaciers: Observations and Constraints for Modeling and Preliminary Results; Ice Sheet Modeling: Terrestrial Background and Application to Arsia Mons Lobate Deposit, Mars; Enhanced Water-Equivalent Hydrogen on the Western Flanks of the Tharsis Montes and Olympus Mons: Remnant Subsurface Ice or Hydrate Minerals?; and New Age Mars.

Integrating the glioblastoma microenvironment into engineered experimental models

PubMed Central

Xiao, Weikun; Sohrabi, Alireza; Seidlits, Stephanie K

2017-01-01

Glioblastoma (GBM) is the most lethal cancer originating in the brain. Its high mortality rate has been attributed to therapeutic resistance and rapid, diffuse invasion – both of which are strongly influenced by the unique microenvironment. Thus, there is a need to develop new models that mimic individual microenvironmental features and are able to provide clinically relevant data. Current understanding of the effects of the microenvironment on GBM progression, established experimental models of GBM and recent developments using bioengineered microenvironments as ex vivo experimental platforms that mimic the biochemical and physical properties of GBM tumors are discussed. PMID:28883992

Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression

PubMed Central

Mondello, Patrizia; Cuzzocrea, Salvatore; Navarra, Michele; Mian, Michael

2017-01-01

Despite the advent of many therapeutic agents, such as bortezomib and lenalidomide that have significantly improved the overall survival, multiple myeloma remains an incurable disease. Failure to cure is multifactorial and can be attributed to the underlying genetic heterogeneity of the cancer and to the surrounding micro-environment. Understanding the mutual interaction between myeloma cells and micro-environment may lead to the development of novel treatment strategies able to eradicate this disease. In this review we discuss the principal molecules involved in the micro-environment network in multiple myeloma and the currently available therapies targeting them. PMID:28099912

Microenvironment-Mediated Mechanisms of Resistance to HER2 Inhibitors Differ between HER2+ Breast Cancer Subtypes.

PubMed

Watson, Spencer S; Dane, Mark; Chin, Koei; Tatarova, Zuzana; Liu, Moqing; Liby, Tiera; Thompson, Wallace; Smith, Rebecca; Nederlof, Michel; Bucher, Elmar; Kilburn, David; Whitman, Matthew; Sudar, Damir; Mills, Gordon B; Heiser, Laura M; Jonas, Oliver; Gray, Joe W; Korkola, James E

2018-03-28

Extrinsic signals are implicated in breast cancer resistance to HER2-targeted tyrosine kinase inhibitors (TKIs). To examine how microenvironmental signals influence resistance, we monitored TKI-treated breast cancer cell lines grown on microenvironment microarrays composed of printed extracellular matrix proteins supplemented with soluble proteins. We tested ∼2,500 combinations of 56 soluble and 46 matrix microenvironmental proteins on basal-like HER2+ (HER2E) or luminal-like HER2+ (L-HER2+) cells treated with the TKIs lapatinib or neratinib. In HER2E cells, hepatocyte growth factor, a ligand for MET, induced resistance that could be reversed with crizotinib, an inhibitor of MET. In L-HER2+ cells, neuregulin1-β1 (NRG1β), a ligand for HER3, induced resistance that could be reversed with pertuzumab, an inhibitor of HER2-HER3 heterodimerization. The subtype-specific responses were also observed in 3D cultures and murine xenografts. These results, along with bioinformatic pathway analysis and siRNA knockdown experiments, suggest different mechanisms of resistance specific to each HER2+ subtype: MET signaling for HER2E and HER2-HER3 heterodimerization for L-HER2+ cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Leucine Rich α-2 Glycoprotein: A Novel Neutrophil Granule Protein and Modulator of Myelopoiesis

PubMed Central

Druhan, Lawrence J.; Lance, Amanda; Li, Shimena; Price, Andrea E.; Emerson, Jacob T.; Baxter, Sarah A.; Gerber, Jonathan M.; Avalos, Belinda R.

2017-01-01

Leucine-rich α2 glycoprotein (LRG1), a serum protein produced by hepatocytes, has been implicated in angiogenesis and tumor promotion. Our laboratory previously reported the expression of LRG1 in murine myeloid cell lines undergoing neutrophilic granulocyte differentiation. However, the presence of LRG1 in primary human neutrophils and a role for LRG1 in regulation of hematopoiesis have not been previously described. Here we show that LRG1 is packaged into the granule compartment of human neutrophils and secreted upon neutrophil activation to modulate the microenvironment. Using immunofluorescence microscopy and direct biochemical measurements, we demonstrate that LRG1 is present in the peroxidase-negative granules of human neutrophils. Exocytosis assays indicate that LRG1 is differentially glycosylated in neutrophils, and co-released with the secondary granule protein lactoferrin. Like LRG1 purified from human serum, LRG1 secreted from activated neutrophils also binds cytochrome c. We also show that LRG1 antagonizes the inhibitory effects of TGFβ1 on colony growth of human CD34+ cells and myeloid progenitors. Collectively, these data invoke an additional role for neutrophils in innate immunity that has not previously been reported, and suggest a novel mechanism whereby neutrophils may modulate the microenvironment via extracellular release of LRG1. PMID:28081565

Role of Modulator of Inflammation Cyclooxygenase-2 in Gammaherpesvirus Mediated Tumorigenesis

PubMed Central

Gandhi, Jaya; Khera, Lohit; Gaur, Nivedita; Paul, Catherine; Kaul, Rajeev

2017-01-01

Chronic inflammation is recognized as a threat factor for cancer progression. Release of inflammatory molecules generates microenvironment which is highly favorable for development of tumor, cancer progression and metastasis. In cases of latent viral infections, generation of such a microenvironment is one of the major predisposing factors related to virus mediated tumorigenesis. Among various inflammatory mediators implicated in pathological process associated with cancer, the cyclooxygenase (COX) and its downstream effector molecules are of greater significance. Though the role of infectious agents in causing inflammation leading to transformation of cells has been more or less well established, however, the mechanism by which inflammation in itself modulates the events in life cycle of infectious agent is not very much clear. This is specifically important for gammaherpesviruses infections where viral life cycle is characterized by prolonged periods of latency when the virus remains hidden, immunologically undetectable and expresses only a very limited set of genes. Therefore, it is important to understand the mechanisms for role of inflammation in virus life cycle and tumorigenesis. This review is an attempt to summarize the latest findings highlighting the significance of COX-2 and its downstream signaling effectors role in life cycle events of gammaherpesviruses leading to progression of cancer. PMID:28400769

Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

PubMed Central

Bovenzi, Cory D.; Hamilton, James; Tassone, Patrick; Johnson, Jennifer; Cognetti, David M.; Luginbuhl, Adam; Keane, William M.; Zhan, Tingting; Tuluc, Madalina; Bar-Ad, Voichita; Martinez-Outschoorn, Ubaldo; Curry, Joseph M.

2015-01-01

Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations. PMID:26779534

Porcine spermatogonial stem cells self-renew effectively in a three dimensional culture microenvironment.

PubMed

Park, Ji Eun; Park, Min Hee; Kim, Min Seong; Park, Yeo Reum; Yun, Jung Im; Cheong, Hee Tae; Kim, Minseok; Choi, Jung Hoon; Lee, Eunsong; Lee, Seung Tae

2017-12-01

Generally, self-renewal of spermatogonial stem cells (SSCs) is maintained in vivo in a three-dimensional (3D) microenvironment consisting of the seminiferous tubule basement membrane, indicating the importance of the 3D microenvironment for in vitro culture of SSCs. Here, we report a 3D culture microenvironment that effectively maintains porcine SSC self-renewal during culture. Porcine SSCs were cultured in an agarose-based 3D hydrogel and in 2D culture plates either with or without feeder cells. Subsequently, the effects of 3D culture on the maintenance of undifferentiated SSCs were identified by analyzing cell colony formation and morphology, AP activity, and transcriptional and translational regulation of self-renewal-related genes and the effects on proliferation by analyzing cell viability and single cell-derived colony number. The 3D culture microenvironment constructed using a 0.2% (w/v) agarose-based 3D hydrogel showed the strongest maintenance of porcine SSC self-renewal and induced significant improvements in proliferation compared with 2D culture microenvironments. These results demonstrate that self-renewal of porcine SSCs can be maintained more effectively in a 3D than in a 2D culture microenvironment. Moreover, this will play a significant role in developing novel culture systems for SSCs derived from diverse species in the future, which will contribute to SSC-related research. © 2017 International Federation for Cell Biology.

Results of heating mode performance tests of a solar-assisted heat pump

NASA Technical Reports Server (NTRS)

Jones, C. B.; Smetana, F. O.

1979-01-01

The performance of a heat pump, utilizing 8.16 square meters of low-cost solar collectors as the evaporator in a Freon-114 refrigeration cycle, was determined under actual insolation conditions during the summer and fall of 1976. C.O.P.'s (coefficient of performance) greater than 3 were obtained with condensing temperatures around 78 C and evaporating temperatures around 27 C. Ambient temperatures were about 3 C above evaporating temperatures. Similar performance levels were obtained at other insolation and temperature conditions. Experience with the system has identified some component and system changes which should increase the obtainable C.O.P. to about 4.0. These are described along with the system's design rationale. The accumulated data are presented as an appendix.

The ice age cycle and the deglaciations: an application of nonlinear regression modelling

NASA Astrophysics Data System (ADS)

Dalgleish, A. N.; Boulton, G. S.; Renshaw, E.

2000-03-01

We have applied the nonlinear regression technique known as additivity and variance stabilisation (AVAS) to time series which reflect Earth's climate over the last 600 ka. AVAS estimates a smooth, nonlinear transform for each variable, under the assumption of an additive model. The Earth's orbital parameters and insolation variations have been used as regression variables. Analysis of the contribution of each variable shows that the deglaciations are characterised by periods of increasing obliquity and perihelion approaching the vernal equinox, but not by any systematic change in eccentricity. The magnitude of insolation changes also plays no role. By approximating the transforms we can obtain a future prediction, with a glacial maximum at 60 ka AP, and a subsequent obliquity and precession forced deglaciation.

Orbital Noise in the Earth System is a Common Cause of Climate and Greenhouse-Gas Fluctuation

NASA Technical Reports Server (NTRS)

Liu, H. S.; Kolenkiewicz, R.; Wade, C., Jr.; Smith, David E. (Technical Monitor)

2002-01-01

The mismatch between fossil isotopic data and climate models known as the cool-tropic paradox implies that either the data are flawed or we understand very little about the climate models of greenhouse warming. Here we question the validity of the climate models on the scientific background of orbital noise in the Earth system. Our study shows that the insolation pulsation induced by orbital noise is the common cause of climate change and atmospheric concentrations of carbon dioxide and methane. In addition, we find that the intensity of the insolation pulses is dependent on the latitude of the Earth. Thus, orbital noise is the key to understanding the troubling paradox in climate models.

Studies of humid continental haze during SPACE

NASA Technical Reports Server (NTRS)

Bowdle, D. A.; Greene, W. A.

1985-01-01

A concept for a solar radiometer network to provide supporting data during the Satellite Preciptiation and Cloud Experiment (SPACE) was developed. Each of the 9 prime and 10 supplementary SPACE ground sites will be equipped with an upward pointing global solar pyranometer. About half of the sites will also be equipped with upward pointing diffuse (shade ring) solar pyranometers, and a downward pointing global albedo pyranometer. These radiometers will be used to monitor the spatial and temporal variability of solar insolation and haze optical depth. The insolation data will ultimately be input to numerical models of the pre-storm and near-storm boundary layer. The optical depth data will be compared with simultaneous measurements from airborne and satellite-based passive visible radiometers and airborne lidars.

Solar panel parallel mounting configuration

NASA Technical Reports Server (NTRS)

Mutschler, Jr., Edward Charles (Inventor)

1998-01-01

A spacecraft includes a plurality of solar panels interconnected with a power coupler and an electrically operated device to provide power to the device when the solar cells are insolated. The solar panels are subject to bending distortion when entering or leaving eclipse. Spacecraft attitude disturbances are reduced by mounting each of the solar panels to an elongated boom made from a material with a low coefficient of thermal expansion, so that the bending of one panel is not communicated to the next. The boom may be insulated to reduce its bending during changes in insolation. A particularly advantageous embodiment mounts each panel to the boom with a single mounting, which may be a hinge. The single mounting prevents transfer of bending moments from the panel to the boom.

Areas of Anomalous Surface Temperature in Archuleta County, Colorado, as Identified from ASTER Thermal Data

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains areas of anomalous surface temperature in Archuleta County identified from ASTER thermal data and spatial based insolation model. The temperature is calculated using the Emissivity Normalization Algorithm that separate temperature from emissivity. The incoming solar radiation was calculated using spatial based insolation model developed by Fu and Rich (1999). Then the temperature due to solar radiation was calculated using emissivity derived from ASTER data. The residual temperature, i.e. temperature due to solar radiation subtracted from ASTER temperature was used to identify thermally anomalous areas. Areas that had temperature greater than 2o were considered ASTER modeled very warm surface exposures (thermal anomalies). Note: 'o' is used in this description to represent lowercase sigma

Areas of Anomalous Surface Temperature in Dolores County, Colorado, as Identified from ASTER Thermal Data

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains areas of anomalous surface temperature in Dolores County identified from ASTER thermal data and spatial based insolation model. The temperature is calculated using the Emissivity Normalization Algorithm that separate temperature from emissivity. The incoming solar radiation was calculated using spatial based insolation model developed by Fu and Rich (1999). Then the temperature due to solar radiation was calculated using emissivity derived from ASTER data. The residual temperature, i.e. temperature due to solar radiation subtracted from ASTER temperature was used to identify thermally anomalous areas. Areas that had temperature greater than 2o were considered ASTER modeled very warm surface exposures (thermal anomalies). Note: 'o' is used in this description to represent lowercase sigma

Areas of Anomalous Surface Temperature in Chaffee County, Colorado, as Identified from ASTER Thermal Data

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains areas of anomalous surface temperature in Chaffee County identified from ASTER thermal data and spatial based insolation model. The temperature is calculated using the Emissivity Normalization Algorithm that separate temperature from emissivity. The incoming solar radiation was calculated using spatial based insolation model developed by Fu and Rich (1999). Then the temperature due to solar radiation was calculated using emissivity derived from ASTER data. The residual temperature, i.e. temperature due to solar radiation subtracted from ASTER temperature was used to identify thermally anomalous areas. Areas that had temperature greater than 2o were considered ASTER modeled very warm surface exposures (thermal anomalies). Note: 'o' is used in this description to represent lowercase sigma

Areas of Anomalous Surface Temperature in Garfield County, Colorado, as Identified from ASTER Thermal Data

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains areas of anomalous surface temperature in Garfield County identified from ASTER thermal data and spatial based insolation model. The temperature is calculated using the Emissivity Normalization Algorithm that separate temperature from emissivity. The incoming solar radiation was calculated using spatial based insolation model developed by Fu and Rich (1999). Then the temperature due to solar radiation was calculated using emissivity derived from ASTER data. The residual temperature, i.e. temperature due to solar radiation subtracted from ASTER temperature was used to identify thermally anomalous areas. Areas that had temperature greater than 2o were considered ASTER modeled very warm surface exposures (thermal anomalies). Note: 'o' is used in this description to represent lowercase sigma.

Areas of Anomalous Surface Temperature in Routt County, Colorado, as Identified from ASTER Thermal Data

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains areas of anomalous surface temperature in Routt County identified from ASTER thermal data and spatial based insolation model. The temperature is calculated using the Emissivity Normalization Algorithm that separate temperature from emissivity. The incoming solar radiation was calculated using spatial based insolation model developed by Fu and Rich (1999). Then the temperature due to solar radiation was calculated using emissivity derived from ASTER data. The residual temperature, i.e. temperature due to solar radiation subtracted from ASTER temperature was used to identify thermally anomalous areas. Areas that had temperature greater than 2o were considered ASTER modeled very warm surface exposures (thermal anomalies). Note: 'o' is used in this description to represent lowercase sigma.

Sensitivity of the Oceanic Turbulent Boundary Layer to Cyclic Insolation Change with Response Periods of 23 to 2.5 Ky: an Equatorial Atlantic Record for the Last 200 Ka

NASA Technical Reports Server (NTRS)

Mcintyre, Andrew

1990-01-01

Time series of sea-surface temperature in cores sited beneath the region of maximum divergence centered on 10 degrees W are characterized by two sets of periodic signals. The dominant signal is centered on a period of 23 Ky and is coherent with and lags, approx. 2.5 Ky, the precessional component of orbitally controlled insolation. The subdominant periods occur between 4.0 and 2.5 Ky. Both sets of signals record variation in the seasonal intensity of oceanic divergence modulated by variation in tropical easterly intensity. The longer periods are a response to precessional forcing. The forcing responsible for the shorter periods is unknown.

Measuring personal exposure from 900MHz mobile phone base stations in Australia and Belgium using a novel personal distributed exposimeter.

PubMed

Bhatt, Chhavi Raj; Thielens, Arno; Redmayne, Mary; Abramson, Michael J; Billah, Baki; Sim, Malcolm R; Vermeulen, Roel; Martens, Luc; Joseph, Wout; Benke, Geza

2016-01-01

The aims of this study were to: i) measure personal exposure in the Global System for Mobile communications (GSM) 900MHz downlink (DL) frequency band with two systems of exposimeters, a personal distributed exposimeter (PDE) and a pair of ExpoM-RFs, ii) compare the GSM 900MHz DL exposures across various microenvironments in Australia and Belgium, and iii) evaluate the correlation between the PDE and ExpoM-RFs measurements. Personal exposure data were collected using the PDE and two ExpoM-RFs simultaneously across 34 microenvironments (17 each in Australia and Belgium) located in urban, suburban and rural areas. Summary statistics of the electric field strengths (V/m) were computed and compared across similar microenvironments in Australia and Belgium. The personal exposures across urban microenvironments were higher than those in the rural or suburban microenvironments. Likewise, the exposure levels across the outdoor were higher than those for indoor microenvironments. The five highest median exposure levels were: city centre (0.248V/m), bus (0.124V/m), railway station (0.105V/m), mountain/forest (rural) (0.057V/m), and train (0.055V/m) [Australia]; and bicycle (urban) (0.238V/m), tram station (0.238V/m), city centre (0.156V/m), residential outdoor (urban) (0.139V/m) and park (0.124V/m) [Belgium]. Exposures in the GSM900 MHz frequency band across most of the microenvironments in Australia were significantly lower than the exposures across the microenvironments in Belgium. Overall correlations between the PDE and the ExpoM-RFs measurements were high. The measured exposure levels were far below the general public reference levels recommended in the guidelines of the ICNIRP and the ARPANSA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Critical assessment of day time traffic noise level at curbside open-air microenvironment of Kolkata City, India.

PubMed

Kundu Chowdhury, Anirban; Debsarkar, Anupam; Chakrabarty, Shibnath

2015-01-01

The objective of the research work is to assess day time traffic noise level at curbside open-air microenvironment of Kolkata city, India under heterogeneous environmental conditions. Prevailing traffic noise level in terms of A-weighted equivalent noise level (Leq) at the microenvironment was in excess of 12.6 ± 2.1 dB(A) from the day time standard of 65 dB(A) for commercial area recommended by the Central Pollution Control Board (CPCB) of India. Noise Climate and Traffic Noise Index of the microenvironment were accounted for 13 ± 1.8 dB(A) and 88.8 ± 6.1 dB(A) respectively. A correlation analysis explored that prevailing traffic noise level of the microenvironment had weak negative (-0.21; p < 0.01) and very weak positive (0.19; p < 0.01) correlation with air temperature and relative humidity. A Varimax rotated principal component analysis explored that motorized traffic volume had moderate positive loading with background noise component (L90, L95, L99) and prevailing traffic noise level had very strong positive loading with peak noise component (L1, L5, L10). Background and peak noise component cumulatively explained 80.98 % of variance in the data set. Traffic noise level at curbside open-air microenvironment of Kolkata City was higher than the standard recommended by CPCB of India. It was highly annoying also. Air temperature and relative humidity had little influence and the peak noise component had the most significant influence on the prevailing traffic noise level at curbside open-air microenvironment. Therefore, traffic noise level at the microenvironment of the city can be reduced with careful honking and driving.

Tumor microenvironment indoctrination: an emerging hallmark of cancer.

PubMed

Goetz, Jacky G

2012-01-01

Nastiness of cancer does not only reside in the corruption of cancer cells by genetic aberrations that drive their sustained proliferative power--the roots of malignancy--but also in its aptitude to reciprocally sculpt its surrounding environment and cellular stromal ecosystem, in such a way that the corrupted tumor microenvironment becomes a full pro-tumorigenic entity. Such a contribution had been appreciated three decades ago already, with the discovery of tumor angiogenesis and extracellular matrix remodeling. Nevertheless, the recent emergence of the tumor microenvironment as the critical determinant in cancer biology is paralleled by the promising therapeutic potential it carries, opening alternate routes to fight cancer. The study of the tumor microenvironment recruited numerous lead-scientists over the years, with distinct perspectives, and some of them have kindly accepted to contribute to the elaboration of this special issue entitled Tumor microenvironment indoctrination: An emerging hallmark of cancer.

Tumor microenvironment indoctrination

PubMed Central

2012-01-01

Nastiness of cancer does not only reside in the corruption of cancer cells by genetic aberrations that drive their sustained proliferative power—the roots of malignancy—but also in its aptitude to reciprocally sculpt its surrounding environment and cellular stromal ecosystem, in such a way that the corrupted tumor microenvironment becomes a full pro-tumorigenic entity. Such a contribution had been appreciated three decades ago already, with the discovery of tumor angiogenesis and extracellular matrix remodeling. Nevertheless, the recent emergence of the tumor microenvironment as the critical determinant in cancer biology is paralleled by the promising therapeutic potential it carries, opening alternate routes to fight cancer. The study of the tumor microenvironment recruited numerous lead-scientists over the years, with distinct perspectives, and some of them have kindly accepted to contribute to the elaboration of this special issue entitled Tumor microenvironment indoctrination: An emerging hallmark of cancer. PMID:22863738

Dry Eye Management: Targeting the Ocular Surface Microenvironment.

PubMed

Zhang, Xiaobo; M, Vimalin Jeyalatha; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo; Li, Wei

2017-06-29

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment.

Dry Eye Management: Targeting the Ocular Surface Microenvironment

PubMed Central

Zhang, Xiaobo; Jeyalatha M, Vimalin; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo

2017-01-01

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment. PMID:28661456

Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency

PubMed Central

Kong, Miao; Tang, Jiamin; Qiao, Qi; Wu, Tingting; Qi, Yan; Tan, Songwei; Gao, Xueqin; Zhang, Zhiping

2017-01-01

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect. PMID:28900509

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments.

PubMed

Kwakwa, Kristin A; Vanderburgh, Joseph P; Guelcher, Scott A; Sterling, Julie A

2017-08-01

Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes.

Enduring epigenetic landmarks define the cancer microenvironment

PubMed Central

Pidsley, Ruth; Lawrence, Mitchell G.; Zotenko, Elena; Niranjan, Birunthi; Statham, Aaron; Song, Jenny; Chabanon, Roman M.; Qu, Wenjia; Wang, Hong; Richards, Michelle; Nair, Shalima S.; Armstrong, Nicola J.; Nim, Hieu T.; Papargiris, Melissa; Balanathan, Preetika; French, Hugh; Peters, Timothy; Norden, Sam; Ryan, Andrew; Pedersen, John; Kench, James; Daly, Roger J.; Horvath, Lisa G.; Stricker, Phillip; Frydenberg, Mark; Taylor, Renea A.; Stirzaker, Clare; Risbridger, Gail P.; Clark, Susan J.

2018-01-01

The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic samples. PMID:29650553

Commensal bacteria modulate the tumor microenvironment.

PubMed

Poutahidis, Theofilos; Erdman, Susan E

2016-09-28

It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The intestinal microenvironment in sepsis.

PubMed

Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

2017-10-01

The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

Modeling the Spatiotemporal Evolution of the Melanoma Tumor Microenvironment

NASA Astrophysics Data System (ADS)

Signoriello, Alexandra; Bosenberg, Marcus; Shattuck, Mark; O'Hern, Corey

The tumor microenvironment, which includes tumor cells, tumor-associated macrophages (TAM), cancer-associated fibroblasts, and endothelial cells, drives the formation and progression of melanoma tumors. Using quantitative analysis of in vivo confocal images of melanoma tumors in three spatial dimensions, we examine the physical properties of the melanoma tumor microenvironment, including the numbers of different cells types, cell size, and morphology. We also compute the nearest neighbor statistics and measure intermediate range spatial correlations between different cell types. We also calculate the step size distribution, mean-square displacement, and non-Gaussian parameter from the spatial trajectories of different cell types in the tumor microenvironment.

Recapitulation of complex transport and action of drugs at tumor microenvironment using tumor-microenvironment-on-chip

PubMed Central

Han, Bumsoo; Qu, Chunjing; Park, Kinam; Konieczny, Stephen F.; Korc, Murray

2016-01-01

Targeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicines. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed. PMID:26688098

One microenvironment does not fit all: heterogeneity beyond cancer cells.

PubMed

Kim, Ik Sun; Zhang, Xiang H-F

2016-12-01

Human cancers exhibit formidable molecular heterogeneity, to a large extent accounting for the incomplete and transitory efficacy of current anti-cancer therapies. However, neoplastic cells alone do not manifest the disease, but conscript a battery of non-tumor cells to enable and sustain hallmark capabilities of cancer. Escaping immunosurveillance is one of such capabilities. Tumors evolve immunosuppressive microenvironment to subvert anti-tumor immunity. In this review, we will focus on tumor-associated myeloid cells, which constitute an essential part of the immune microenvironment and reciprocally interact with cancer cells to establish malignancy toward metastasis. The diversity and plasticity of these cells constitute another layer of heterogeneity, beyond the heterogeneity of cancer cells themselves. We envision that immune microenvironment co-evolves with the genetic heterogeneity of tumor. Addressing the question of how genetically distinct tumors shape and are shaped by unique immune microenvironment will provide an attractive rationale to develop novel immunotherapeutic modalities. Here, we discuss the complex nature of tumor microenvironment, with an emphasis on the cellular and functional heterogeneity among tumor-associated myeloid cells as well as immune environment heterogeneity in the context of a full spectrum of human breast cancers.

Engineering cancer microenvironments for in vitro 3-D tumor models

PubMed Central

Asghar, Waseem; El Assal, Rami; Shafiee, Hadi; Pitteri, Sharon; Paulmurugan, Ramasamy; Demirci, Utkan

2017-01-01

The natural microenvironment of tumors is composed of extracellular matrix (ECM), blood vasculature, and supporting stromal cells. The physical characteristics of ECM as well as the cellular components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, and differentiation. To mimic the tumor microenvironment outside the human body for drug testing, two-dimensional (2-D) and murine tumor models are routinely used. Although these conventional approaches are employed in preclinical studies, they still present challenges. For example, murine tumor models are expensive and difficult to adopt for routine drug screening. On the other hand, 2-D in vitro models are simple to perform, but they do not recapitulate natural tumor microenvironment, because they do not capture important three-dimensional (3-D) cell–cell, cell–matrix signaling pathways, and multi-cellular heterogeneous components of the tumor microenvironment such as stromal and immune cells. The three-dimensional (3-D) in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening. Herein, we review recent advances in 3-D tumor model generation and highlight directions for future applications in drug testing. PMID:28458612

Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen

PubMed Central

Spurgeon, Megan E.; den Boon, Johan A.; Horswill, Mark; Barthakur, Sonalee; Forouzan, Omid; Rader, Janet S.; Beebe, David J.; Roopra, Avtar; Ahlquist, Paul; Lambert, Paul F.

2017-01-01

High-risk human papillomaviruses (HPVs) infect epithelial cells and are causally associated with cervical cancer, but HPV infection is not sufficient for carcinogenesis. Previously, we reported that estrogen signaling in the stromal tumor microenvironment is associated with cervical cancer maintenance and progression. We have now determined how HPV oncogenes and estrogen treatment affect genome-wide host gene expression in laser-captured regions of the cervical epithelium and stroma of untreated or estrogen-treated nontransgenic and HPV-transgenic mice. HPV oncogene expression in the cervical epithelium elicited significant gene-expression changes in the proximal stromal compartment, and estrogen treatment uniquely affected gene expression in the cervical microenvironment of HPV-transgenic mice compared with nontransgenic mice. Several potential estrogen-induced paracrine-acting factors were identified in the expression profile of the cervical tumor microenvironment. The microenvironment of estrogen-treated HPV-transgenic mice was significantly enriched for chemokine/cytokine activity and inflammatory and immune functions associated with carcinogenesis. This inflammatory signature included several proangiogenic CXCR2 receptor ligands. A subset of the same CXCR2 ligands was likewise increased in cocultures of early-passage cells from human cervical samples, with levels highest in cocultures of cervical fibroblasts and cancer-derived epithelial cells. Our studies demonstrate that high-risk HPV oncogenes profoundly reprogram the tumor microenvironment independently of and synergistically with estrogen. These observations illuminate important means by which HPVs can cause cancer through alterations in the tumor microenvironment. PMID:29073104

MEMS-based sensing and algorithm development for fall detection and gait analysis

NASA Astrophysics Data System (ADS)

Gupta, Piyush; Ramirez, Gabriel; Lie, Donald Y. C.; Dallas, Tim; Banister, Ron E.; Dentino, Andrew

2010-02-01

Falls by the elderly are highly detrimental to health, frequently resulting in injury, high medical costs, and even death. Using a MEMS-based sensing system, algorithms are being developed for detecting falls and monitoring the gait of elderly and disabled persons. In this study, wireless sensors utilize Zigbee protocols were incorporated into planar shoe insoles and a waist mounted device. The insole contains four sensors to measure pressure applied by the foot. A MEMS based tri-axial accelerometer is embedded in the insert and a second one is utilized by the waist mounted device. The primary fall detection algorithm is derived from the waist accelerometer. The differential acceleration is calculated from samples received in 1.5s time intervals. This differential acceleration provides the quantification via an energy index. From this index one may ascertain different gait and identify fall events. Once a pre-determined index threshold is exceeded, the algorithm will classify an event as a fall or a stumble. The secondary algorithm is derived from frequency analysis techniques. The analysis consists of wavelet transforms conducted on the waist accelerometer data. The insole pressure data is then used to underline discrepancies in the transforms, providing more accurate data for classifying gait and/or detecting falls. The range of the transform amplitude in the fourth iteration of a Daubechies-6 transform was found sufficient to detect and classify fall events.

The temperature dependance of photoinhibition in the tropical basidiomycete lichen Cora pavonia E. Fries.

PubMed

Coxson, D S

1987-09-01

The response of net photosynthesis (NP) and dark respiration to periods of high insolation exposure was examined in the tropical basidiomycete lichen Cora pavonia. Photoinhibition of NP proved quite dependant on temperature. Rates of light saturated NP were severely impaired immediately after pretreatment high light exposure at temperatures of 10, 20 and 40°C, while similar exposure at 30°C resulted in only minimal photoinhibition. Apparent quantum yield proved an even more sensitive indicator of photoinhibition, reduced in all temperature treatments, although inhibition was again greatest at low and high temperatures. Concurrent exposure to reduced O 2 tensions during high light exposure mitigated some of the deleterious effects of high light exposure at 10 and 20°C, suggesting an interaction of O 2 with the inactivation of photosynthetic function. This represents the first reported instance of light dependant chilling stress in lichens, and may be an important limitation on the distribution of this and other tropical lichen species. This narrow range of temperatures within which thalli of C. pavonia can withstand periods of high insolation exposure coincides with that faced by hydrated thalli during rare periods of high insolation exposure within the cloud/shroud zone on La Soufrière, and points to the necessity of considering periods of atypical or unusual climatic events when interpreting patterns of net photosynthetic response, both in tropical and in north temperate lichen species.

Onset of deglacial warming in West Antarctica driven by local orbital forcing.

PubMed

2013-08-22

The cause of warming in the Southern Hemisphere during the most recent deglaciation remains a matter of debate. Hypotheses for a Northern Hemisphere trigger, through oceanic redistributions of heat, are based in part on the abrupt onset of warming seen in East Antarctic ice cores and dated to 18,000 years ago, which is several thousand years after high-latitude Northern Hemisphere summer insolation intensity began increasing from its minimum, approximately 24,000 years ago. An alternative explanation is that local solar insolation changes cause the Southern Hemisphere to warm independently. Here we present results from a new, annually resolved ice-core record from West Antarctica that reconciles these two views. The records show that 18,000 years ago snow accumulation in West Antarctica began increasing, coincident with increasing carbon dioxide concentrations, warming in East Antarctica and cooling in the Northern Hemisphere associated with an abrupt decrease in Atlantic meridional overturning circulation. However, significant warming in West Antarctica began at least 2,000 years earlier. Circum-Antarctic sea-ice decline, driven by increasing local insolation, is the likely cause of this warming. The marine-influenced West Antarctic records suggest a more active role for the Southern Ocean in the onset of deglaciation than is inferred from ice cores in the East Antarctic interior, which are largely isolated from sea-ice changes.

Onset of deglacial warming in West Antarctica driven by local orbital forcing

USGS Publications Warehouse

WAIS Divide Project Members,; Fudge, T. J.; Steig, Eric J.; Markle, Bradley R.; Schoenemann, Spruce W.; Ding, Qinghua; Taylor, Kendrick C.; McConnell, Joseph R.; Brook, Edward J.; Sowers, Todd; White, James W. C.; Alley, Richard B.; Cheng, Hai; Clow, Gary D.; Cole-Dai, Jihong; Conway, Howard; Cuffey, Kurt M.; Edwards, Jon S.; Edwards, R. Lawrence; Edwards, Ross; Fegyveresi, John M.; Ferris, David; Fitzpatrick, Joan J.; Johnson, Jay; Hargreaves, Geoffrey; Lee, James E.; Maselli, Olivia J.; Mason, William; McGwire, Kenneth C.; Mitchell, Logan E.; Mortensen, Nicolai B.; Neff, Peter; Orsi, Anais J.; Popp, Trevor J.; Schauer, Andrew J.; Severinghaus, Jeffrey P.; Sigl, Michael; Spencer, Matthew K.; Vaughn, Bruce H.; Voigt, Donald E.; Waddington, Edwin D.; Wang, Xianfeng; Wong, Gifford J.

2013-01-01

The cause of warming in the Southern Hemisphere during the most recent deglaciation remains a matter of debate. Hypotheses for a Northern Hemisphere trigger, through oceanic redistributions of heat, are based in part on the abrupt onset of warming seen in East Antarctic ice cores and dated to 18,000 years ago, which is several thousand years after high-latitude Northern Hemisphere summer insolation intensity began increasing from its minimum, approximately 24,000 years ago. An alternative explanation is that local solar insolation changes cause the Southern Hemisphere to warm independently. Here we present results from a new, annually resolved ice-core record from West Antarctica that reconciles these two views. The records show that 18,000 years ago snow accumulation in West Antarctica began increasing, coincident with increasing carbon dioxide concentrations, warming in East Antarctica and cooling in the Northern Hemisphere associated with an abrupt decrease in Atlantic meridional overturning circulation. However, significant warming in West Antarctica began at least 2,000 years earlier. Circum-Antarctic sea-ice decline, driven by increasing local insolation, is the likely cause of this warming. The marine-influenced West Antarctic records suggest a more active role for the Southern Ocean in the onset of deglaciation than is inferred from ice cores in the East Antarctic interior, which are largely isolated from sea-ice changes.

Assessing Walking Strategies Using Insole Pressure Sensors for Stroke Survivors.

PubMed

Munoz-Organero, Mario; Parker, Jack; Powell, Lauren; Mawson, Susan

2016-10-01

Insole pressure sensors capture the different forces exercised over the different parts of the sole when performing tasks standing up such as walking. Using data analysis and machine learning techniques, common patterns and strategies from different users to achieve different tasks can be automatically extracted. In this paper, we present the results obtained for the automatic detection of different strategies used by stroke survivors when walking as integrated into an Information Communication Technology (ICT) enhanced Personalised Self-Management Rehabilitation System (PSMrS) for stroke rehabilitation. Fourteen stroke survivors and 10 healthy controls have participated in the experiment by walking six times a distance from chair to chair of approximately 10 m long. The Rivermead Mobility Index was used to assess the functional ability of each individual in the stroke survivor group. Several walking strategies are studied based on data gathered from insole pressure sensors and patterns found in stroke survivor patients are compared with average patterns found in healthy control users. A mechanism to automatically estimate a mobility index based on the similarity of the pressure patterns to a stereotyped stride is also used. Both data gathered from stroke survivors and healthy controls are used to evaluate the proposed mechanisms. The output of trained algorithms is applied to the PSMrS system to provide feedback on gait quality enabling stroke survivors to self-manage their rehabilitation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rose, Brian E. J.; Cronin, Timothy W.; Bitz, Cecilia M., E-mail: brose@albany.edu

Planetary obliquity determines the meridional distribution of the annual mean insolation. For obliquity exceeding 55°, the weakest insolation occurs at the equator. Stable partial snow and ice cover on such a planet would be in the form of a belt about the equator rather than polar caps. An analytical model of planetary climate is used to investigate the stability of ice caps and ice belts over the widest possible range of parameters. The model is a non-dimensional diffusive Energy Balance Model, representing insolation, heat transport, and ice−albedo feedback on a spherical planet. A complete analytical solution for any obliquity ismore » given and validated against numerical solutions of a seasonal model in the “deep-water” regime of weak seasonal ice line migration. Multiple equilibria and unstable transitions between climate states (ice-free, Snowball, or ice cap/belt) are found over wide swaths of parameter space, including a “Large Ice-Belt Instability” and “Small Ice-Belt Instability” at high obliquity. The Snowball catastrophe is avoided at weak radiative forcing in two different scenarios: weak albedo feedback and inefficient heat transport (favoring stable partial ice cover), or efficient transport at high obliquity (favoring ice-free conditions). From speculative assumptions about distributions of planetary parameters, three-fourths to four-fifths of all planets with stable partial ice cover should be in the form of Earth-like polar caps.« less

MAGNETIC SCALING LAWS FOR THE ATMOSPHERES OF HOT GIANT EXOPLANETS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menou, Kristen

2012-02-01

We present scaling laws for advection, radiation, magnetic drag, and ohmic dissipation in the atmospheres of hot giant exoplanets. In the limit of weak thermal ionization, ohmic dissipation increases with the planetary equilibrium temperature (T{sub eq} {approx}> 1000 K) faster than the insolation power does, eventually reaching values {approx}> 1% of the insolation power, which may be sufficient to inflate the radii of hot Jupiters. At higher T{sub eq} values still magnetic drag rapidly brakes the atmospheric winds, which reduces the associated ohmic dissipation power. For example, for a planetary field strength B = 10 G, the fiducial scaling lawsmore » indicate that ohmic dissipation exceeds 1% of the insolation power over the equilibrium temperature range T{sub eq} {approx} 1300-2000 K, with a peak contribution at T{sub eq} {approx} 1600 K. Evidence for magnetically dragged winds at the planetary thermal photosphere could emerge in the form of reduced longitudinal offsets for the dayside infrared hotspot. This suggests the possibility of an anticorrelation between the amount of hotspot offset and the degree of radius inflation, linking the atmospheric and interior properties of hot giant exoplanets in an observationally testable way. While providing a useful framework to explore the magnetic scenario, the scaling laws also reveal strong parameter dependencies, in particular with respect to the unknown planetary magnetic field strength.« less

The role of shoe design on the prediction of free torque at the shoe-surface interface using pressure insole technology.

PubMed

Weaver, Brian Thomas; Fitzsimons, Kathleen; Braman, Jerrod; Haut, Roger

2016-09-01

The goal of the current study was to expand on previous work to validate the use of pressure insole technology in conjunction with linear regression models to predict the free torque at the shoe-surface interface that is generated while wearing different athletic shoes. Three distinctly different shoe designs were utilised. The stiffness of each shoe was determined with a material's testing machine. Six participants wore each shoe that was fitted with an insole pressure measurement device and performed rotation trials on an embedded force plate. A pressure sensor mask was constructed from those sensors having a high linear correlation with free torque values. Linear regression models were developed to predict free torques from these pressure sensor data. The models were able to accurately predict their own free torque well (RMS error 3.72 ± 0.74 Nm), but not that of the other shoes (RMS error 10.43 ± 3.79 Nm). Models performing self-prediction were also able to measure differences in shoe stiffness. The results of the current study showed the need for participant-shoe specific linear regression models to insure high prediction accuracy of free torques from pressure sensor data during isolated internal and external rotations of the body with respect to a planted foot.

Validation of Moticon’s OpenGo sensor insoles during gait, jumps, balance and cross-country skiing specific imitation movements

PubMed Central

Stöggl, Thomas; Martiner, Alex

2017-01-01

ABSTRACT The purpose of this study was the experimental validation of the OpenGo sensor insole system compared to PedarX sensor insole and AMTI force-plate systems. Sixteen healthy participants performed trials in walking, running, jumping (drop and counter movement jumps), imitation drills and balance, with simultaneous measures of all three systems. Detected ground contact and flight times with OpenGo during walking, running and jumping were similar to those of AMTI. Force–time curves revealed comparable shapes between all three systems. Force impulses were 13–34% lower with OpenGo when compared to AMTI. Despite differences in mean values in some exercise modes, correlations towards AMTI were between r = 0.8 and r = 1.0 in most situations. During fast motions, with high force and impact, OpenGo provided lower force and latency in force kinetics. During balance tasks, discrepancy in the centre of pressure was found medio-lateral, while anterio–posterior direction was closer to AMTI. With awareness of these limitations, OpenGo can be applied in both clinical and research settings to evaluate temporal, force and balance parameters during different types of motion. The fully mobile OpenGo system allows for the easy and quick system application, analysis and feedback under complex field conditions, as well. PMID:27010531

Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

PubMed Central

Mavroudi, Irene; Papadaki, Helen A.

2012-01-01

Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA) molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients. PMID:22956967

The greenhouse effect in a gray planetary atmosphere.

NASA Technical Reports Server (NTRS)

Wildt, R.

1966-01-01

Hopf analytical solution for values of ratio of gray absorption coefficients for insolating and escaping radiation /greenhouse parameter/ assumed constant at all depths, presenting temperature distribution graphs

NFAT Signaling and the Tumorigenic Microenvironment of the Prostate

DTIC Science & Technology

2017-12-01

ABSTRACT Although the importance of microenvironment in prostate cancer is widely recognized, the molecular and cellular processes leading from genetic ...non-invasive clinical tests. Second, the illustration of the main cellular and molecular components in the tumorigenic microenvironment provides new...potential of NFATc1 as a novel biomarker for prostate cancer diagnosis/prognosis. We will take advantage of the cellular precision, genetic manipulability

Glutamine Metabolism in Cancer: Understanding the Heterogeneity

PubMed Central

Cluntun, Ahmad A; Lukey, Michael J; Cerione, Richard A; Locasale, Jason W

2017-01-01

Reliance on glutamine has long been considered a hallmark of cancer cell metabolism. However, some recent studies have challenged this notion in vivo, prompting a need for further clarifications on the role of glutamine metabolism in cancer. We find that there is ample evidence of an essential role for glutamine in tumors and that a variety of factors, including tissue type, the underlying cancer genetics, the tumor microenvironment and other variables such as diet and host physiology collectively influence the role of glutamine in cancer. Thus the requirements for glutamine in cancer are overall highly heterogeneous. In this review, we discuss the implications both for basic science and for targeting glutamine metabolism in cancer therapy. PMID:28393116

Substantial Differentiation of Human Neural Stem Cells Into Motor Neurons on a Biomimetic Polyureaa

PubMed Central

Yun, Donghwa; Lee, Young M.; Laughter, Melissa R.; Freed, Curt R.

2015-01-01

To find the first restorative treatment for spinal cord injury (SCI), researchers have focused on stem cell therapies. However, one obstacle is the lack of an implantable cell scaffold that can support efficient motor neuron (MN) differentiation and proliferation. We aimed to overcome this through the use of an RGD functionalized novel biomimetic polyurea, optimized to encourage efficient differentiation of MNs. Images taken after 14-days showed increased differentiation (~40%) of hNSCs into MNs as well as increased cell count on the biomimetic polymer compared to PDL-Laminin coating, indicating that the RGD-polyurea provides a favorable microenvironment for hNSC survival, having promising implications for future SCI therapies. PMID:26033933

Differentiated State of Initiating Tumor Cells Is Key to Distinctive Immune Responses Seen in H-RasG12V-Induced Squamous Tumors.

PubMed

Podolsky, Michael A; Bailey, Jacob T; Gunderson, Andrew J; Oakes, Carrie J; Breech, Kyle; Glick, Adam B

2017-03-01

Heterogeneity in tumor immune responses is a poorly understood yet critical parameter for successful immunotherapy. In two doxycycline-inducible models where oncogenic H-Ras G12V is targeted either to the epidermal basal/stem cell layer with a Keratin14-rtTA transgene (K14Ras), or committed progenitor/suprabasal cells with an Involucrin-tTA transgene (InvRas), we observed strikingly distinct tumor immune responses. On threshold doxycycline levels yielding similar Ras expression, tumor latency, and numbers, tumors from K14Ras mice had an immunosuppressed microenvironment, whereas InvRas tumors had a proinflammatory microenvironment. On a Rag1 -/- background, InvRas mice developed fewer and smaller tumors that regressed over time, whereas K14Ras mice developed more tumors with shorter latency than Rag1 +/+ controls. Adoptive transfer and depletion studies revealed that B-cell and CD4 T-cell cooperation was critical for tumor yield, lymphocyte polarization, and tumor immune phenotype in Rag1 +/+ mice of both models. Coculture of tumor-conditioned B cells with CD4 T cells implicated direct contact for Th1 and regulatory T cell (Treg) polarization, and CD40-CD40L for Th1, Th2, and Treg generation, a response not observed from splenic B cells. Anti-CD40L caused regression of InvRas tumors but enhanced growth in K14Ras, whereas a CD40 agonist mAb had opposite effects in each tumor model. These data show that position of tumor-initiating cells within a stratified squamous epithelial tissue provokes distinct B- and CD4 T-cell interactions, which establish unique tumor microenvironments that regulate tumor development and response to immunotherapy. Cancer Immunol Res; 5(3); 198-210. ©2017 AACR . ©2017 American Association for Cancer Research.

Spatial variability of soil and vegetation characteristics in an urban park in Tel-Aviv

NASA Astrophysics Data System (ADS)

Sarah, Pariente; Zhevelev, Helena M.; Oz, Atar

2010-05-01

Mosaic-like spatial patterns, consisting of divers soil microenvironments, characterize the landscapes of many urban parks. These microenvironments may differ in their pedological, hydrological and floral characteristics, and they play important roles in urban ecogeomorphic system functioning. In and around a park covering 50 ha in Tel Aviv, Israel, soil properties and herbaceous vegetation were measured in eight types of microenvironments. Six microenvironments were within the park: area under Ceratonia siliqua (Cs-U), area under Ficus sycomorus (Fi-U), a rest area under F. sycomorus (Re-U), an open area with bare soil (Oa-S), an open area with biological crusts (Oa-C), and an open area with herbaceous vegetation (Oa-V). Outside the park were two control microenvironments, located, respectively, on a flat area (Co-P) and an inclined open area (Co-S). The soil was sampled from two depths (0-2 and 5-10 cm), during the peak of the growing season (March). For each soil sample, moisture content, organic matter content, CaCO3 content, texture, pH, electrical conductivity, and soluble ions contents were determined in 1:1 water extraction. In addition, prior to the soil sampling, vegetation cover, number of species, and species diversity of herbaceous vegetation were measured. The barbecue fires and visitors in each of the microenvironments were counted. Whereas the soil organic matter and vegetation in Fi-U differed from those in the control(Co-P, Co-S), those in Oa-V were similar to those in the control. Fi-U was characterized by higher values of soil moisture, organic matter, penetration depth, and vegetation cover than Cs-U. Open microenvironments within the park (Oa-S, Oa-C, Oa-V) showed lower values of soil penetration than the control microenvironments. In Oa-V unique types of plants such as Capsella bursa-pastoris and Anagallis arvensis, which did not appear in the control microenvironments, were found. This was true also for Fi-U, in which species like Oxalis pes-caprae were found. Significant differences in soil and vegetation properties were found between Re-U and the rest of microenvironments. Differences in levels of human activities, in addition to differences in vegetation types, increased the spatial heterogeneity of soil properties. The rest microenvironment (Re-U) exhibited degraded soil conditions and can be regarded as forming the fragile areas of the park. An urban park offers potential for presence and growth of natural vegetation and, therefore, also for preservation of biodiversity. Natural vegetation, in its role as a part of the urban park, enriches the landscape diversity and thereby may contribute to the enjoyment of the visitors in the park.

Areas of Anomalous Surface Temperature in Alamosa and Saguache Counties, Colorado, as Identified from ASTER Thermal Data

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains areas of anomalous surface temperature in Alamosa and Saguache Counties identified from ASTER thermal data and spatial based insolation model. The temperature is calculated using the Emissivity Normalization Algorithm that separate temperature from emissivity. The incoming solar radiation was calculated using spatial based insolation model developed by Fu and Rich (1999). Then the temperature due to solar radiation was calculated using emissivity derived from ASTER data. The residual temperature, i.e. temperature due to solar radiation subtracted from ASTER temperature was used to identify thermally anomalous areas. Areas that had temperature greater than 2o were considered ASTER modeled very warm surface exposures (thermal anomalies) Note: 'o' is used in this description to represent lowercase sigma.

Nineteenth century Mexican statures in the United States and their relationship with insolation and vitamin D.

PubMed

Carson, Scott Alan

2010-01-01

The use of height data to measure living standards is now a well-established method in economics. However, there are still some populations, places and times for which the comparison across groups remains unclear. One example is 19th century Mexicans in the US. This study demonstrates that after comparing the statures of Mexicans born in Mexico and the US the primary source of the stature difference between the two groups was birth year, and the stature gap increased as the US economy developed while the Mexican economy stagnated. Moreover, the stature growth of Mexicans born in the US was related to vitamin D, and the Mexican relationship between stature and insolation was more like that of Europeans than Africans.

Astronomical forcing, insolation and millennial-scale climate variability: evidence from the North Atlantic Ocean (IODP Expedition 306, Site U1313) during the Early-Middle Pleistocene

NASA Astrophysics Data System (ADS)

Ferretti, Patrizia; Crowhurst, Simon; Naafs, David; Barbante, Carlo

2015-04-01

Since the seminal work by Hays, Imbrie and Shackleton (1976), a plethora of studies mostly based on marine sediments collected during DSDP-ODP-IODP Expeditions has demonstrated a correlation between orbital variations and climatic change. However, information on how changes in orbital boundary conditions affected the frequency and amplitude of millennial-scale climate variability is still fragmentary. Here we examine the record of climatic conditions from MIS 23 to 17 (c. 920-670 ka) using high-resolution stable isotope records from benthic and planktonic foraminifera from a sedimentary sequence in the North Atlantic (Integrated Ocean Drilling Program Expedition 306, Site U1313) in order to evaluate the climate system's response in the millennial band to known orbitally induced insolation changes. Special emphasis is placed on Marine Isotope Stage (MIS) 19, an interglacial centred at around 785 ka during which the insolation appears comparable to the current orbital geometry: MIS 19 is characterised by a minimum of the 400-kyr eccentricity cycle, subdued amplitude of precessional changes, and small amplitude variations in insolation making this marine isotopic stage a potential astronomical analogue for the Holocene and its future evolution, if this remains governed by natural forcing (Loutre and Berger 2000). Benthic and planktonic foraminiferal oxygen isotope values indicate relatively stable conditions during the peak warmth of MIS 19, but sea-surface and deep-water reconstructions start diverging during the transition towards the glacial MIS 18, when large, cold excursions disrupt the surface waters whereas low amplitude millennial scale fluctuations persist in the deep waters as recorded by the oxygen isotope signal (Ferretti et al., 2015). The glacial inception occurred at ˜779 ka, in agreement with an increased abundance of tetra-unsaturated alkenones, reflecting the influence of icebergs and associated meltwater pulses and high-latitude waters at the study site. Using a variety of time series analysis techniques, we evaluate the evolution of millennial climate variability in response to changing orbital boundary conditions during the early-middle Pleistocene. Suborbital variability in both surface- and deep-water records is mainly concentrated at a period of ˜11 kyr and, additionally, at ˜5.8 and ˜3.9 kyr in the deep ocean; these periods are equal to harmonics of precession band oscillations. The fact that the response at the 11 kyr period increased over the same interval during which the amplitude of the response to the precessional cycle increased supports the notion that most of the variance in the 11 kyr band in the sedimentary record is nonlinearly transferred from precession band oscillations. Considering that these periodicities are important features in the equatorial and intertropical insolation, these observations are in line with the view that the low-latitude regions play an important role in the response of the climate system to the astronomical forcing. We conclude that the effect of the orbitally induced insolation is of fundamental importance in regulating the timing and amplitude of millennial scale climate variability. Ferretti P., Crowhurst S.J., Naafs B.D.A., Barbante C., 2015. Quaternary Science Reviews 108, 95-110. Hays J.D., Imbrie J., Shackleton N.J., 1976. Science 194, 1121-1132. Loutre M.F., Berger A., 2000. Climatic Change 46, 61-90.

Brucite microbialites in living coral skeletons: Indicators of extreme microenvironments in shallow-marine settings

USGS Publications Warehouse

Nothdurft, L.D.; Webb, G.E.; Buster, N.A.; Holmes, C.W.; Sorauf, J.E.; Kloprogge, J.T.

2005-01-01

Brucite [Mg(OH)2] microbialites occur in vacated interseptal spaces of living scleractinian coral colonies (Acropora, Pocillopora, Porites) from subtidal and intertidal settings in the Great Barrier Reef, Australia, and subtidal Montastraea from the Florida Keys, United States. Brucite encrusts microbial filaments of endobionts (i.e., fungi, green algae, cyanobacteria) growing under organic biofilms; the brucite distribution is patchy both within interseptal spaces and within coralla. Although brucite is undersaturated in seawater, its precipitation was apparently induced in the corals by lowered pCO 2 and increased pH within microenvironments protected by microbial biofilms. The occurrence of brucite in shallow-marine settings highlights the importance of microenvironments in the formation and early diagenesis of marine carbonates. Significantly, the brucite precipitates discovered in microenvironments in these corals show that early diagenetic products do not necessarily reflect ambient seawater chemistry. Errors in environmental interpretation may arise where unidentified precipitates occur in microenvironments in skeletal carbonates that are subsequently utilized as geochemical seawater proxies. ?? 2005 Geological Society of America.

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

PubMed Central

Kwakwa, Kristin A.; Vanderburgh, Joseph P.; Guelcher, Scott A.

2018-01-01

Purpose of Review Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. Recent Findings 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. Summary 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes. PMID:28646444

Microscale screening systems for 3D cellular microenvironments: platforms, advances, and challenges

PubMed Central

Montanez-Sauri, Sara I.; Beebe, David J.; Sung, Kyung Eun

2015-01-01

The increasing interest in studying cells using more in vivo-like three-dimensional (3D) microenvironments has created a need for advanced 3D screening platforms with enhanced functionalities and increased throughput. 3D screening platforms that better mimic in vivo microenvironments with enhanced throughput would provide more in-depth understanding of the complexity and heterogeneity of microenvironments. The platforms would also better predict the toxicity and efficacy of potential drugs in physiologically relevant conditions. Traditional 3D culture models (e.g. spinner flasks, gyratory rotation devices, non-adhesive surfaces, polymers) were developed to create 3D multicellular structures. However, these traditional systems require large volumes of reagents and cells, and are not compatible with high throughput screening (HTS) systems. Microscale technology offers the miniaturization of 3D cultures and allows efficient screening of various conditions. This review will discuss the development, most influential works, and current advantages and challenges of microscale culture systems for screening cells in 3D microenvironments. PMID:25274061

Modeling North American Ice Sheet Response to Changes in Precession and Obliquity

NASA Astrophysics Data System (ADS)

Tabor, C.; Poulsen, C. J.; Pollard, D.

2012-12-01

Milankovitch theory proposes that changes in insolation due to orbital perturbations dictate the waxing and waning of the ice sheets (Hays et al., 1976). However, variations in solar forcing alone are insufficient to produce the glacial oscillations observed in the climate record. Non-linear feedbacks in the Earth system likely work in concert with the orbital cycles to produce a modified signal (e.g. Berger and Loutre, 1996), but the nature of these feedbacks remain poorly understood. To gain a better understand of the ice dynamics and climate feedbacks associated with changes in orbital configuration, we use a complex Earth system model consisting of the GENESIS GCM and land surface model (Pollard and Thompson, 1997), the Pennsylvania State University ice sheet model (Pollard and DeConto, 2009), and the BIOME vegetation model (Kaplan et al., 2001). We began this study by investigating ice sheet sensitivity to a range of commonly used ice sheet model parameters, including mass balance and albedo, to optimize simulations for Pleistocene orbital cycles. Our tests indicate that choice of mass balance and albedo parameterizations can lead to significant differences in ice sheet behavior and volume. For instance, use of an insolation-temperature mass balance scheme (van den Berg, 2008) allows for a larger ice sheet response to orbital changes than the commonly employed positive degree-day method. Inclusion of a large temperature dependent ice albedo, representing phenomena such as melt ponds and dirty ice, also enhances ice sheet sensitivity. Careful tuning of mass balance and albedo parameterizations can help alleviate the problem of insufficient ice sheet retreat during periods of high summer insolation (Horton and Poulsen, 2007) while still accurately replicating the modern climate. Using our optimized configuration, we conducted a series of experiments with idealized transient orbits in an asynchronous coupling scheme to investigate the influence of obliquity and precession on the Laurentide and Cordillera ice sheets of North America. Preliminary model results show that the ice sheet response to changes in obliquity are larger than for precession despite providing a smaller direct insolation variation in the Northern Hemisphere high latitudes. A combination of enhanced Northern Hemisphere mid-latitude temperature gradient and longer cycle duration allow for a larger ice sheet response to obliquity than would be expected from insolation forcing alone. Conversely, a shorter duration dampens the ice sheet response to precession. Nevertheless, the precession cycle does cause significant changes in ice volume, a feature not observed in the Early Pleistocene δ18O records (Raymo and Nisancioglu, 2003). Future work will examine the climate response to an idealized transient orbit that includes concurrent variations in obliquity, precession, and eccentricity.

Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer: Normalization, Not Destruction.

PubMed

Whatcott, Clifford J; Han, Haiyong; Von Hoff, Daniel D

2015-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the "perfect storms" that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects.

Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

PubMed

Hoarau-Véchot, Jessica; Rafii, Arash; Touboul, Cyril; Pasquier, Jennifer

2018-01-18

An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

Cabozantinib Affects Osteosarcoma Growth Through A Direct Effect On Tumor Cells and Modifications In Bone Microenvironment.

PubMed

Fioramonti, M; Fausti, V; Pantano, F; Iuliani, M; Ribelli, G; Lotti, F; Pignochino, Y; Grignani, G; Santini, D; Tonini, G; Vincenzi, B

2018-03-08

Osteosarcoma (OS) is the most common primary malignant tumor of the bone. Due to its high heterogeneity and to survival signals from bone microenvironment, OS can resist to standard treatments, therefore novel therapies are needed. c-MET oncogene, a tyrosine-kinase receptor, plays a crucial role in OS initiation and progression. The present study aimed to evaluate the effect of c-MET inhibitor cabozantinib (CBZ) on OS both directly and through its action on bone microenvironment. We tested different doses of CBZ in in vitro models of OS alone or in co-culture with bone cells in order to reproduce OS-tumor microenvironment interactions. CBZ is able to decrease proliferation and migration of OS cells, inhibiting ERK and AKT signaling pathways. Furthermore, CBZ leads to the inhibition of the proliferation of OS cells expressing receptor activator of nuclear factor κB (RANK), due to its effect on bone microenvironment, where it causes an overproduction of osteoprotegerin and a decrease of production of RANK ligand by osteoblasts. Overall, our data demonstrate that CBZ might represent a new potential treatment against OS, affecting both OS cells and their microenvironment. In this scenario, RANK expression in OS cells could represent a predictive factor of better response to CBZ treatment.

Invasion emerges from cancer cell adaptation to competitive microenvironments: Quantitative predictions from multiscale mathematical models

PubMed Central

Rejniak, Katarzyna A.; Gerlee, Philip

2013-01-01

Summary In this review we summarize our recent efforts using mathematical modeling and computation to simulate cancer invasion, with a special emphasis on the tumor microenvironment. We consider cancer progression as a complex multiscale process and approach it with three single-cell based mathematical models that examine the interactions between tumor microenvironment and cancer cells at several scales. The models exploit distinct mathematical and computational techniques, yet they share core elements and can be compared and/or related to each other. The overall aim of using mathematical models is to uncover the fundamental mechanisms that lend cancer progression its direction towards invasion and metastasis. The models effectively simulate various modes of cancer cell adaptation to the microenvironment in a growing tumor. All three point to a general mechanism underlying cancer invasion: competition for adaptation between distinct cancer cell phenotypes, driven by a tumor microenvironment with scarce resources. These theoretical predictions pose an intriguing experimental challenge: test the hypothesis that invasion is an emergent property of cancer cell populations adapting to selective microenvironment pressure, rather than culmination of cancer progression producing cells with the “invasive phenotype”. In broader terms, we propose that fundamental insights into cancer can be achieved by experimentation interacting with theoretical frameworks provided by computational and mathematical modeling. PMID:18524624

Engineering Breast Cancer Microenvironments and 3D Bioprinting

PubMed Central

Belgodere, Jorge A.; King, Connor T.; Bursavich, Jacob B.; Burow, Matthew E.; Martin, Elizabeth C.; Jung, Jangwook P.

2018-01-01

The extracellular matrix (ECM) is a critical cue to direct tumorigenesis and metastasis. Although two-dimensional (2D) culture models have been widely employed to understand breast cancer microenvironments over the past several decades, the 2D models still exhibit limited success. Overwhelming evidence supports that three dimensional (3D), physiologically relevant culture models are required to better understand cancer progression and develop more effective treatment. Such platforms should include cancer-specific architectures, relevant physicochemical signals, stromal–cancer cell interactions, immune components, vascular components, and cell-ECM interactions found in patient tumors. This review briefly summarizes how cancer microenvironments (stromal component, cell-ECM interactions, and molecular modulators) are defined and what emerging technologies (perfusable scaffold, tumor stiffness, supporting cells within tumors and complex patterning) can be utilized to better mimic native-like breast cancer microenvironments. Furthermore, this review emphasizes biophysical properties that differ between primary tumor ECM and tissue sites of metastatic lesions with a focus on matrix modulation of cancer stem cells, providing a rationale for investigation of underexplored ECM proteins that could alter patient prognosis. To engineer breast cancer microenvironments, we categorized technologies into two groups: (1) biochemical factors modulating breast cancer cell-ECM interactions and (2) 3D bioprinting methods and its applications to model breast cancer microenvironments. Biochemical factors include matrix-associated proteins, soluble factors, ECMs, and synthetic biomaterials. For the application of 3D bioprinting, we discuss the transition of 2D patterning to 3D scaffolding with various bioprinting technologies to implement biophysical cues to model breast cancer microenvironments. PMID:29881724

Half-precessional climate forcing of Indian Ocean monsoon dynamics on the East African equator

NASA Astrophysics Data System (ADS)

Verschuren, D.; Sinninghe Damste, J. S.; Moernaut, J.; Kristen, I.; Fagot, M.; Blaauw, M.; Haug, G. H.; Project Members, C.

2008-12-01

The EuroCLIMATE project CHALLACEA produced a detailed multi-proxy reconstruction of the climate history of equatorial East Africa, based on the sediment record of Lake Challa, a 4.2 km2, 92-m deep crater lake on the lower East slope of Mt. Kilimanjaro (Kenya/Tanzania). Relatively stable sedimentation dynamics over the past 25,000 years resulted in a unique combination of high temporal resolution, excellent radiometric (210Pb, 14C) age control, and confidence that recording parameters of the climatic proxy signals extracted from the sediment have remained constant through time. The equatorial (3 deg. S) location of our study site in East Africa, where seasonal migration of convective activity spans the widest latitude range worldwide, produced unique information on how varying rainfall contributions from the northeasterly and southeasterly Indian Ocean monsoons shaped regional climate history. The Challa proxy records for temperature (TEX86) and moisture balance (reflection-seismic stratigraphy and the BIT index of soil bacterial input) uniquely weave together tropical climate variability at orbital and shorter time scales. The temporal pattern of reconstructed moisture balance bears the clear signature of half- precessional insolation forcing of Indian Ocean monsoon dynamics, modified by northern-latitude influence on moisture-balance variation at millennial and century time scales. During peak glacial time (but not immediately before) and the Younger Dryas, NH ice sheet influences overrode local insolation influence on monsoon intensity. After the NH ice sheets had melted and a relatively stable interglacial temperature regime developed, precession-driven summer insolation became the dominant determinant of regional moisture balance, with anti-phased patterns of Holocene hydrological change in the northern and southern (sub)tropics, and a uniquely hybrid pattern on the East African equator. In the last 2-3000 years a series of multi-century droughts with links to high latitude climate variability exerted widespread influence across the African continent. In northern and western tropical Africa these drought episodes accentuated the late- Holocene drying trend; in southern tropical Africa they mitigated or aborted the trend to increasing monsoon rainfall prescribed by SH insolation forcing.

Analysis of Global Horizontal Irradiance in Version 3 of the National Solar Radiation Database.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, Clifford; Martin, Curtis E.; Guay, Nathan Gene

We report an analysis that compares global horizontal irradiance (GHI) estimates from version 3 of the National Solar Radiation Database (NSRDB v3) with surface measurements of GHI at a wide variety of locations over the period spanning from 2005 to 2012. The NSRDB v3 estimate of GHI are derived from the Physical Solar Model (PSM) which employs physics-based models to estimate GHI from measurements of reflected visible and infrared irradiance collected by Geostationary Operational Environment Satellites (GOES) and several other data sources. Because the ground measurements themselves are uncertain our analysis does not establish the absolute accuracy for PSM GHI.more » However by examining the comparison for trends and for consistency across a large number of sites, we may establish a level of confidence in PSM GHI and identify conditions which indicate opportunities to improve PSM. We focus our evaluation on annual and monthly insolation because these quantities directly relate to prediction of energy production from solar power systems. We find that generally, PSM GHI exhibits a bias towards overestimating insolation, on the order of 5% when all sky conditions are considered, and somewhat less (-3%) when only clear sky conditions are considered. The biases persist across multiple years and are evident at many locations. In our opinion the bias originates with PSM and we view as less credible that the bias stems from calibration drift or soiling of ground instruments. We observe that PSM GHI may significantly underestimate monthly insolation in locations subject to broad snow cover. We found examples of days where PSM GHI apparently misidentified snow cover as clouds, resulting in significant underestimates of GHI during these days and hence leading to substantial understatement of monthly insolation. Analysis of PSM GHI in adjacent pixels shows that the level of agreement between PSM GHI and ground data can vary substantially over distances on the order of 2 km. We conclude that the variance most likely originates from dramatic contrasts in the ground's appearance over these distances.« less

Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

DTIC Science & Technology

2016-09-01

regulators of branching morphogenesis during mammary gland development 17,18, arguing that normal mammary epithelial cells cooperate with these innate ...CD45+CD11b+F4/80+ cells lacking lymphoid and granulocytic markers (Supplementary Fig.3B). viSNE plots 30 of myelo- monocytic cells (Fig.5A) showed that...cancer cells and how the microenvironment in these primary sites named P-TMEM (Primary Tumor Microenvironment of Metastases) contribute to early

Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy

PubMed Central

Nagarsheth, Nisha; Wicha, Max S.; Zou, Weiping

2017-01-01

The tumour microenvironment is the primary location in which tumour cells and the host immune system interact. Different immune cell subsets are recruited into the tumour microenvironment via interactions between chemokines and chemokine receptors, and these populations have distinct effects on tumour progression and therapeutic outcomes. In this Review, we focus on the main chemokines that are found in the human tumour microenvironment; we elaborate on their patterns of expression, their regulation and their roles in immune cell recruitment and in cancer and stromal cell biology, and we consider how they affect cancer immunity and tumorigenesis. We also discuss the potential of targeting chemokine networks, in combination with other immunotherapies, for the treatment of cancer. PMID:28555670

[Advances in nanoparticle-targeting tumor associated macrophages for cancer imaging and therapy].

PubMed

Fengliang, Guo; Guping, Tang; Qinglian, H U

2017-03-25

Tumor tissues are composed of tumor cells and complicate microenvironment. Tumor associated macrophages (TAMs) as an important component in tumor microenvironment, play fundamental roles in tumor progression, metastasis and microenvironment regulation. Recently, studies have found that nanotechnology, as an emerging platform, provides unique potential for cancer imaging and therapy. With the nanotechnology, TAMs imaging presents direct evidence for cancer development, progression, and the effectiveness of cancer treatments; it also can regulate the immunosuppression of tumor microenvironment and improve therapeutic efficiency through TAMs targeted killing or phenotypic transformation. In this article, we illustrate the function of TAMs and review the latest development in nano-carriers and their applications in tumor associated macrophage targeting cancer imaging and therapy.

Noncoding RNAs and immune checkpoints-clinical implications as cancer therapeutics.

PubMed

Smolle, Maria A; Calin, Horatiu N; Pichler, Martin; Calin, George A

2017-07-01

A major mechanism of tumor development and progression is silencing of the patient's immune response to cancer-specific antigens. Defects in the so-called cancer immunity cycle may occur at any stage of tumor development. Within the tumor microenvironment, aberrant expression of immune checkpoint molecules with activating or inhibitory effects on T lymphocytes induces immune tolerance and cellular immune escape. Targeting immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and its ligand PD-L1 with specific antibodies has proven to be a major advance in the treatment of several types of cancer. Another way to therapeutically influence the tumor microenvironment is by modulating the levels of microRNAs (miRNAs), small noncoding RNAs that shuttle bidirectionally between malignant and tumor microenvironmental cells. These small RNA transcripts have two features: (a) their expression is quite specific to distinct tumors, and (b) they are involved in early regulation of immune responses. Consequently, miRNAs may be ideal molecules for use in cancer therapy. Many miRNAs are aberrantly expressed in human cancer cells, opening new opportunities for cancer therapy, but the exact functions of these miRNAs and their interactions with immune checkpoint molecules have yet to be investigated. This review summarizes recently reported findings about miRNAs as modulators of immune checkpoint molecules and their potential application as cancer therapeutics in clinical practice. © 2017 Federation of European Biochemical Societies.

The Microenvironment of Lung Cancer and Therapeutic Implications.

PubMed

Mittal, Vivek; El Rayes, Tina; Narula, Navneet; McGraw, Timothy E; Altorki, Nasser K; Barcellos-Hoff, Mary Helen

2016-01-01

The tumor microenvironment (TME) represents a milieu that enables tumor cells to acquire the hallmarks of cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. Concerted interactions between genetically altered tumor cells and genetically stable intratumoral stromal cells result in an "activated/reprogramed" stroma that promotes carcinogenesis by contributing to inflammation, immune suppression, therapeutic resistance, and generating premetastatic niches that support the initiation and establishment of distant metastasis. The lungs present a unique milieu in which tumors progress in collusion with the TME, as evidenced by regions of aberrant angiogenesis, acidosis and hypoxia. Inflammation plays an important role in the pathogenesis of lung cancer, and pulmonary disorders in lung cancer patients such as chronic obstructive pulmonary disease (COPD) and emphysema, constitute comorbid conditions and are independent risk factors for lung cancer. The TME also contributes to immune suppression, induces epithelial-to-mesenchymal transition (EMT) and diminishes efficacy of chemotherapies. Thus, the TME has begun to emerge as the "Achilles heel" of the disease, and constitutes an attractive target for anti-cancer therapy. Drugs targeting the components of the TME are making their way into clinical trials. Here, we will focus on recent advances and emerging concepts regarding the intriguing role of the TME in lung cancer progression, and discuss future directions in the context of novel diagnostic and therapeutic opportunities.

A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion.

PubMed

Bidarra, S J; Oliveira, P; Rocha, S; Saraiva, D P; Oliveira, C; Barrias, C C

2016-06-03

Epithelial-to-mesenchymal transitions (EMT) are strongly implicated in cancer dissemination. Intermediate states, arising from inter-conversion between epithelial (E) and mesenchymal (M) states, are characterized by phenotypic heterogeneity combining E and M features and increased plasticity. Hybrid EMT states are highly relevant in metastatic contexts, but have been largely neglected, partially due to the lack of physiologically-relevant 3D platforms to study them. Here we propose a new in vitro model, combining mammary E cells with a bioengineered 3D matrix, to explore phenotypic and functional properties of cells in transition between E and M states. Optimized alginate-based 3D matrices provided adequate 3D microenvironments, where normal epithelial morphogenesis was recapitulated, with formation of acini-like structures, similar to those found in native mammary tissue. TGFβ1-driven EMT in 3D could be successfully promoted, generating M-like cells. TGFβ1 removal resulted in phenotypic switching to an intermediate state (RE cells), a hybrid cell population expressing both E and M markers at gene/protein levels. RE cells exhibited increased proliferative/clonogenic activity, as compared to M cells, being able to form large colonies containing cells with front-back polarity, suggesting a more aggressive phenotype. Our 3D model provides a powerful tool to investigate the role of the microenvironment on metastable EMT stages.

Rapid dissolution of ZnO nanocrystals in acidic cancer microenvironment leading to preferential apoptosis

NASA Astrophysics Data System (ADS)

Sasidharan, Abhilash; Chandran, Parwathy; Menon, Deepthy; Raman, Sreerekha; Nair, Shantikumar; Koyakutty, Manzoor

2011-09-01

The microenvironment of cancer plays a very critical role in the survival, proliferation and drug resistance of solid tumors. Here, we report an interesting, acidic cancer microenvironment-mediated dissolution-induced preferential toxicity of ZnO nanocrystals (NCs) against cancer cells while leaving primary cells unaffected. Irrespective of the size-scale (5 and 200 nm) and surface chemistry differences (silica, starch or polyethylene glycol coating), ZnO NCs exhibited multiple stress mechanisms against cancer cell lines (IC50 ~150 μM) while normal human primary cells (human dermal fibroblast, lymphocytes, human umbilical vein endothelial cells) remain less affected. Flow cytometry and confocal microscopy studies revealed that ZnO NCs undergo rapid preferential dissolution in acidic (pH ~5-6) cancer microenvironment causing elevated ROS stress, mitochondrial superoxide formation, depolarization of mitochondrial membrane, and cell cycle arrest at S/G2 phase leading to apoptosis. In effect, by elucidating the unique toxicity mechanism of ZnO NCs, we show that ZnO NCs can destabilize cancer cells by utilizing its own hostile acidic microenvironment, which is otherwise critical for its survival.The microenvironment of cancer plays a very critical role in the survival, proliferation and drug resistance of solid tumors. Here, we report an interesting, acidic cancer microenvironment-mediated dissolution-induced preferential toxicity of ZnO nanocrystals (NCs) against cancer cells while leaving primary cells unaffected. Irrespective of the size-scale (5 and 200 nm) and surface chemistry differences (silica, starch or polyethylene glycol coating), ZnO NCs exhibited multiple stress mechanisms against cancer cell lines (IC50 ~150 μM) while normal human primary cells (human dermal fibroblast, lymphocytes, human umbilical vein endothelial cells) remain less affected. Flow cytometry and confocal microscopy studies revealed that ZnO NCs undergo rapid preferential dissolution in acidic (pH ~5-6) cancer microenvironment causing elevated ROS stress, mitochondrial superoxide formation, depolarization of mitochondrial membrane, and cell cycle arrest at S/G2 phase leading to apoptosis. In effect, by elucidating the unique toxicity mechanism of ZnO NCs, we show that ZnO NCs can destabilize cancer cells by utilizing its own hostile acidic microenvironment, which is otherwise critical for its survival. Electronic supplementary information (ESI) available: FTIR data, MTT assay and zinc ion release. See DOI: 10.1039/c1nr10272a

High arch

MedlinePlus

... and improve walking. This includes changes to the shoes, such as an arch insert and a support insole. Surgery to flatten the foot is sometimes needed in severe cases. Any nerve problems that exist must be treated by specialists.

A method to integrate patterned electrospun fibers with microfluidic systems to generate complex microenvironments for cell culture applications

PubMed Central

Wallin, Patric; Zandén, Carl; Carlberg, Björn; Hellström Erkenstam, Nina; Liu, Johan; Gold, Julie

2012-01-01

The properties of a cell’s microenvironment are one of the main driving forces in cellular fate processes and phenotype expression invivo. The ability to create controlled cell microenvironments invitro becomes increasingly important for studying or controlling phenotype expression in tissue engineering and drug discovery applications. This includes the capability to modify material surface properties within well-defined liquid environments in cell culture systems. One successful approach to mimic extra cellular matrix is with porous electrospun polymer fiber scaffolds, while microfluidic networks have been shown to efficiently generate spatially and temporally defined liquid microenvironments. Here, a method to integrate electrospun fibers with microfluidic networks was developed in order to form complex cell microenvironments with the capability to vary relevant parameters. Spatially defined regions of electrospun fibers of both aligned and random orientation were patterned on glass substrates that were irreversibly bonded to microfluidic networks produced in poly-dimethyl-siloxane. Concentration gradients obtained in the fiber containing channels were characterized experimentally and compared with values obtained by computational fluid dynamic simulations. Velocity and shear stress profiles, as well as vortex formation, were calculated to evaluate the influence of fiber pads on fluidic properties. The suitability of the system to support cell attachment and growth was demonstrated with a fibroblast cell line. The potential of the platform was further verified by a functional investigation of neural stem cell alignment in response to orientation of electrospun fibers versus a microfluidic generated chemoattractant gradient of stromal cell-derived factor 1 alpha. The described method is a competitive strategy to create complex microenvironments invitro that allow detailed studies on the interplay of topography, substrate surface properties, and soluble microenvironment on cellular fate processes. PMID:23781291

Differential vitamin D 24-hydroxylase/CYP24A1 gene promoter methylation in endothelium from benign and malignant human prostate

PubMed Central

Karpf, Adam R; Omilian, Angela R; Bshara, Wiam; Tian, Lili; Tangrea, Michael A; Morrison, Carl D; Johnson, Candace S

2011-01-01

Epigenetic alterations occur in tumor-associated vessels in the tumor microenvironment. Methylation of the CYP24A1 gene promoter differs in endothelial cells isolated from tumors and non-tumor microenvironments in mice. The epigenetic makeup of endothelial cells of human tumor-associated vasculature is unknown due to difficulty of isolating endothelial cells populations from a heterogeneous tissue microenvironment. To ascertain CYP24A1 promoter methylation in tumor-associated endothelium, we utilized laser microdissection guided by CD31 immunohistochemistry to procure endothelial cells from human prostate tumor specimens. Prostate tissues were obtained following robotic radical prostatectomy from men with clinically localized prostate cancer. Adjacent histologically benign prostate tissues were used to compare endothelium from benign versus tumor microenvironments. Sodium bisulfite sequencing of CYP24A1 promoter region showed that the average CYP24A1 promoter methylation in the endothelium was 20% from the tumor microenvironment compared with 8.2% in the benign microenvironment (p < 0.05). A 2-fold to 17-fold increase in CYP24A1 promoter methylation was observed in the prostate tumor endothelium compared with the matched benign prostate endothelium in four patient samples, while CYP24A1 promoter methylation remained unchanged in two patient samples. In addition, there is no correlation of the level of CYP24A1 promoter methylation in prostate tumor-associated endothelium with that of epithelium/stroma. This study demonstrates that the CYP24A1 promoter is methylated in tumor-associated endothelium, indicating that epigenetic alterations in CYP24A1 may play a role in determining the phenotype of tumor-associated vasculature in the prostate tumor microenvironment. PMID:21725204

Air Force Logistics Command (AFLC) solar thermal plant

NASA Technical Reports Server (NTRS)

1983-01-01

The plant proved its capability to deliver the desired energy product in a USAF industrial environment. The collector proved capable of energy conversion at insolation levels up to 25% below design minimum. The plant and the project were negatively affected by severe winter weather, with total insolation during the test period 60 percent less than the expected value. Environmental effects reduced plant availability to 55 percent. Only five, minimally good operating days were experienced during the test period. The subsequent lack of performance data prohibits the drawing of general conclusions regarding system performance. System operability was rated generally high. The only inhibiting factor was the difficulty in procuring replacement parts for rapid repair under USAF stockage and procurement policies. No inherently serious system failures were recorded, although a thermostatic valve malfunction in the freeze protection system ultimately took 30 days to repair.

The capacity credit of grid-connected photovoltaic systems

NASA Astrophysics Data System (ADS)

Alsema, E. A.; van Wijk, A. J. M.; Turkenburg, W. C.

The capacity credit due photovoltaic (PV) power plants if integrated into the Netherlands grid was investigated, together with an estimate of the total allowable penetration. An hourly simulation was performed based on meteorological data from five stations and considering tilted surfaces, the current grid load pattern, and the load pattern after PV-power augmentation. The reliability of the grid was assessed in terms of a loss of load probability analysis, assuming power drops were limited to 1 GW. A projected tolerance for 2.5 GW of PV power was calculated. Peak demands were determined to be highest in winter, contrary to highest insolation levels; however, daily insolation levels coincided with daily peak demands. Combining the PV input with an equal amount of wind turbine power production was found to augment the capacity credit for both at aggregate outputs of 2-4 GW.

Pyranometer station for the assessment of solar energy influx in eastern New Mexico. Final report, December 12, 1976-June 1, 1978

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sittler, O.D.; Agogino, M.M.

1979-05-01

This project was undertaken to improve the data base for estimating solar energy influx in eastern New Mexico. A precision pyranometer station has been established at Eastern New Mexico University in Portales. A program of careful calibration and data management procedures is conducted to maintain high standards of precision and accuracy. Data from the first year of operation were used to upgrade insolation data of moderate accuracy which had been obtained at this site with an inexpensive pyranograph. Although not as accurate as the data expected from future years of operation of this station, these upgraded pyranograph measurements show thatmore » eastern New Mexico receives somewhat less solar energy than would be expected from published data. A detailed summary of these upgraded insolation data is included.« less

Climate variations on Earth-like circumbinary planets

PubMed Central

Popp, Max; Eggl, Siegfried

2017-01-01

The discovery of planets orbiting double stars at close distances has sparked increasing scientific interest in determining whether Earth-analogues can remain habitable in such environments and how their atmospheric dynamics is influenced by the rapidly changing insolation. In this work we present results of the first three-dimensional numerical experiments of a water-rich planet orbiting a double star. We find that the periodic forcing of the atmosphere has a noticeable impact on the planet's climate. Signatures of the forcing frequencies related to the planet's as well as to the binary's orbital periods are present in a variety of climate indicators such as temperature and precipitation, making the interpretation of potential observables challenging. However, for Earth-like greenhouse gas concentrations, the variable forcing does not change the range of insolation values allowing for habitable climates substantially. PMID:28382929

Satellite estimation of incident photosynthetically active radiation using ultraviolet reflectance

NASA Technical Reports Server (NTRS)

Eck, Thomas F.; Dye, Dennis G.

1991-01-01

A new satellite remote sensing method for estimating the amount of photosynthetically active radiation (PAR, 400-700 nm) incident at the earth's surface is described and tested. Potential incident PAR for clear sky conditions is computed from an existing spectral model. A major advantage of the UV approach over existing visible band approaches to estimating insolation is the improved ability to discriminate clouds from high-albedo background surfaces. UV spectral reflectance data from the Total Ozone Mapping Spectrometer (TOMS) were used to test the approach for three climatically distinct, midlatitude locations. Estimates of monthly total incident PAR from the satellite technique differed from values computed from ground-based pyranometer measurements by less than 6 percent. This UV remote sensing method can be applied to estimate PAR insolation over ocean and land surfaces which are free of ice and snow.

Local effects of partly-cloudy skies on solar and emitted radiation

NASA Technical Reports Server (NTRS)

Whitney, D. A.; Venable, D. D.

1982-01-01

A computer automated data acquisition system for atmospheric emittance, and global solar, downwelled diffuse solar, and direct solar irradiances is discussed. Hourly-integrated global solar and atmospheric emitted radiances were measured continuously from February 1981 and hourly-integrated diffuse solar and direct solar irradiances were measured continuously from October 1981. One-minute integrated data are available for each of these components from February 1982. The results of the correlation of global insolation with fractional cloud cover for the first year's data set. A February data set, composed of one-minute integrated global insolation and direct solar irradiance, cloud cover fractions, meteorological data from nearby weather stations, and GOES East satellite radiometric data, was collected to test the theoretical model of satellite radiometric data correlation and develop the cloud dependence for the local measurement site.

YORP torque as the function of shape harmonics

NASA Astrophysics Data System (ADS)

Breiter, Sławomir; Michalska, Hanna

2008-08-01

The second-order analytical approximation of the mean Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) torque components is given as an explicit function of the shape spherical harmonics coefficients for a sufficiently regular minor body. The results are based upon a new expression for the insolation function, significantly simpler than in previous works. Linearized plane-parallel model of the temperature distribution derived from the insolation function allows us to take into account a non-zero conductivity. Final expressions for the three average components of the YORP torque related with rotation period, obliquity and precession are given in a form of the Legendre series of the cosine of obliquity. The series have good numerical properties and can be easily truncated according to the degree of the Legendre polynomials or associated functions, with first two terms playing the principal role.

Determination of the Solar Energy Microclimate of the United States Using Satellite Data

NASA Technical Reports Server (NTRS)

Vonderharr, T. H.; Ellis, J. S.

1978-01-01

The determination of total solar energy reaching the ground over the United States using measurements from meteorological satellites as the basic data set is examined. The methods of satellite data processing are described. Uncertainty analysis and comparison of results with well calibrated surface pyranometers are used to estimate the probable error in the satellite-based determination of ground insolation. It is 10 to 15 percent for daily information, and about 5 percent for monthly values. However, the natural space and time variability of insolation is much greater than the uncertainty in the method. The most important aspect of the satellite-based technique is the ability to determine the solar energy reaching the ground over small areas where no other measurements are available. Thus, it complements the widely spaced solar radiation measurement network of ground stations.

An Ambulatory System for Gait Monitoring Based on Wireless Sensorized Insoles.

PubMed

González, Iván; Fontecha, Jesús; Hervás, Ramón; Bravo, José

2015-07-09

A new gait phase detection system for continuous monitoring based on wireless sensorized insoles is presented. The system can be used in gait analysis mobile applications, and it is designed for real-time demarcation of gait phases. The system employs pressure sensors to assess the force exerted by each foot during walking. A fuzzy rule-based inference algorithm is implemented on a smartphone and used to detect each of the gait phases based on the sensor signals. Additionally, to provide a solution that is insensitive to perturbations caused by non-walking activities, a probabilistic classifier is employed to discriminate walking forward from other low-level activities, such as turning, walking backwards, lateral walking, etc. The combination of these two algorithms constitutes the first approach towards a continuous gait assessment system, by means of the avoidance of non-walking influences.

Surface modified and medicated polyurethane materials capable of controlling microorganisms causing foot skin infection in athletes.

PubMed

Gnanasundaram, Saraswathy; Ranganathan, Mohan; Das, Bhabendra Nath; Mandal, Asit Baran

2013-02-01

Foot odor and foot infection are major problems of athletes and persons with hyperhidrosis. Many shoes especially sports shoes have removable cushion insoles/foot beds for foot comfort. Polyurethane (PU) foam and elastomer have been used as cushion insole in shoes. In the present work, new insole materials based on porous viscoelastic PU sheets having hydrophilic property and antimicrobial drug coating to control foot infection and odor were developed. Bacteria and fungus that are causing infection and bad odor of the foot of athletes were isolated by microbial cell culturing of foot sweat. The surface of porous viscoelastic PU sheets was modified using hydrophilic polymers and coated with antimicrobial agent, silver sulfadiazine (SS). The surface modified PU sheets were characterized using ATR-FTIR, TGA, DSC, SEM, contact angle measurement and water absorption study. Results had shown that modified PU sheets have hydrophilicity greater than that of original PU sheet. FTIR spectra and SEM pictures confirmed modification of PU surface with hydrophilic polymers and coating with SS. Minimum inhibitory concentration studies indicated that SS has activity on all isolated bacteria of athletic foot sweat. The maximum inhibition was found for Pseudomonas (20mm) followed by Micrococci (17 mm), Diphtheroids (16 mm) and Staphylococci (12 mm). During perspiration of foot the hydrophilic polymers on PU surface will swell and release SS. Future work will confirm the application of these materials as inserts in athletic shoes. Copyright © 2012 Elsevier B.V. All rights reserved.

Ocean-atmosphere forcing of South American tropical paleoclimate, LGM to present

NASA Astrophysics Data System (ADS)

Baker, P. A.; Fritz, S. C.; Dwyer, G. S.; Rigsby, C. A.; Silva, C. G.; Burns, S. J.

2012-12-01

Because of many recent terrestrial paleoclimatic and marine paleoceanographic records, late Quaternary South American tropical paleoclimate is as well understood as that anywhere in the world. While lessons learned from the recent instrumental record of climate are informative, this record is too short to capture much of the lower frequency variability encountered in the paleoclimate records and much of the observed paleoclimate is without modern analogue. This paleoclimate is known to be regionally variable with significant differences both north and south of the equator and between the western high Andes and eastern lowlands of the Amazon and Nordeste Brazil. Various extrinsic forcing mechanisms affected climate throughout the period, including global concentrations of GHGs, Northern Hemisphere ice sheet forcing, seasonal insolation forcing of the South American summer monsoon (SASM), millennial-scale Atlantic forcing, and Pacific forcing of the large-scale Walker circulation. The magnitude of the climate response to these forcings varied temporally, largely because of the varying amplitude of the forcing itself. For example, during the last glacial, large-amplitude north Atlantic forcing during Heinrich 1 and the LGM itself, led to wet (dry) conditions south (north) of the equator. During the Holocene, Atlantic forcing was lower amplitude, thus seasonal insolation forcing generally predominated with a weaker-than-normal SASM during the early Holocene resulting in dry conditions in the south-western tropics and wet conditions in the eastern lowlands and Nordeste; in the late Holocene seasonal insolation reached a maximum in the southern tropics and climate conditions reversed.

Effect of an ankle-foot orthosis on knee joint mechanics: a novel conservative treatment for knee osteoarthritis.

PubMed

Fantini Pagani, Cynthia H; Willwacher, Steffen; Benker, Rita; Brüggemann, Gert-Peter

2014-12-01

Several conservative treatments for medial knee osteoarthritis such as knee orthosis and laterally wedged insoles have been shown to reduce the load in the medial knee compartment. However, those treatments also present limitations such as patient compliance and inconsistent results regarding the treatment success. To analyze the effect of an ankle-foot orthosis on the knee adduction moment and knee joint alignment in the frontal plane in subjects with knee varus alignment. Controlled laboratory study, repeated measurements. In total, 14 healthy subjects with knee varus alignment were analyzed in five different conditions: without orthotic, with laterally wedged insoles, and with an ankle-foot orthosis in three different adjustments. Three-dimensional kinetic and kinematic data were collected during gait analysis. Significant decreases in knee adduction moment, knee lever arm, and joint alignment in the frontal plane were observed with the ankle-foot orthosis in all three different adjustments. No significant differences could be found in any parameter while using the laterally wedged insoles. The ankle-foot orthosis was effective in reducing the knee adduction moment. The decreases in this parameter seem to be achieved by changing the knee joint alignment and thereby reducing the knee lever arm in the frontal plane. This study presents a novel approach for reducing the load in the medial knee compartment, which could be developed as a new treatment option for patients with medial knee osteoarthritis. © The International Society for Prosthetics and Orthotics 2013.

Rocky Mountain hydroclimate: Holocene variability and the role of insolation, ENSO, and the North American Monsoon

USGS Publications Warehouse

Anderson, Lesleigh

2012-01-01

Over the period of instrumental records, precipitation maximum in the headwaters of the Colorado Rocky Mountains has been dominated by winter snow, with a substantial degree of interannual variability linked to Pacific ocean–atmosphere dynamics. High-elevation snowpack is an important water storage that is carefully observed in order to meet increasing water demands in the greater semi-arid region. The purpose here is to consider Rocky Mountain water trends during the Holocene when known changes in earth's energy balance were caused by precession-driven insolation variability. Changes in solar insolation are thought to have influenced the variability and intensity of the El Niño Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and North American Monsoon and the seasonal precipitation balance between rain and snow at upper elevations. Holocene records are presented from two high elevation lakes located in northwest Colorado that document decade-to-century scale precipitation seasonality for the past ~ 7000 years. Comparisons with sub-tropical records of ENSO indicate that the snowfall-dominated precipitation maxima developed ~ 3000 and 4000 years ago, coincident with evidence for enhanced ENSO/PDO dynamics. During the early-to-mid Holocene the records suggest a more monsoon affected precipitation regime with reduced snowpack, more rainfall, and net moisture deficits that were more severe than recent droughts. The Holocene perspective of precipitation indicates a far broader range of variability than that of the past century and highlights the non-linear character of hydroclimate in the U.S. west.

Assembly of hydrogel units for 3D microenvironment in a poly(dimethylsiloxane) channel

NASA Astrophysics Data System (ADS)

Cho, Chang Hyun; Kwon, Seyong; Park, Je-Kyun

2017-12-01

Construction of three-dimensional (3D) microenvironment become an important issue in recent biological studies due to their biological relevance compared to conventional two-dimensional (2D) microenvironment. Various fabrication techniques have been employed to construct a 3D microenvironment, however, it is difficult to fully satisfy the biological and mechanical properties required for the 3D cell culture system, such as heterogeneous tissue structures generated from the functional differences or diseases. We propose here an assembly method for facile construction of 3D microenvironment in a poly(dimethylsiloxane) (PDMS) channel using hydrogel units. The high-aspect-ratio of hydrogel units was achieved by fabricating these units using a 2D mold. With this approach, 3D heterogeneous hydrogel units were produced and assembled in a PDMS channel by structural hookup. In vivo-like 3D heterogeneous microenvironment in a precisely controllable fluidic system was also demonstrated using a controlled assembly of different types of hydrogel units, which was difficult to obtain from previous methods. By regulating the flow condition, the mechanical stability of the assembled hydrogel units was verified by the flow-induced deformation of hydrogel units. In addition, in vivo-like cell culture environment was demonstrated using an assembly of cell-coated hydrogel units in the fluidic channel. Based on these features, our method expects to provide a beneficial tool for the 3D cell culture module and biomimetic engineering.

High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease.

PubMed

Palacios, Florencia; Moreno, Pilar; Morande, Pablo; Abreu, Cecilia; Correa, Agustín; Porro, Valentina; Landoni, Ana Ines; Gabus, Raul; Giordano, Mirta; Dighiero, Guillermo; Pritsch, Otto; Oppezzo, Pablo

2010-06-03

Interaction of chronic lymphocytic leukemia (CLL) B cells with tissue microenvironment has been suggested to favor disease progression by promoting malignant B-cell growth. Previous work has shown expression in peripheral blood (PB) of CLL B cells of activation-induced cytidine deaminase (AID) among CLL patients with an unmutated (UM) profile of immunoglobulin genes and with ongoing class switch recombination (CSR) process. Because AID expression results from interaction with activated tissue microenvironment, we speculated whether the small subset with ongoing CSR is responsible for high levels of AID expression and could be derived from this particular microenvironment. In this work, we quantified AID expression and ongoing CSR in PB of 50 CLL patients and characterized the expression of different molecules related to microenvironment interaction. Our results show that among UM patients (1) high AID expression is restricted to the subpopulation of tumoral cells ongoing CSR; (2) this small subset expresses high levels of proliferation, antiapoptotic and progression markers (Ki-67, c-myc, Bcl-2, CD49d, and CCL3/4 chemokines). Overall, this work outlines the importance of a cellular subset in PB of UM CLL patients with a poor clinical outcome, high AID levels, and ongoing CSR, whose presence might be a hallmark of a recent contact with the microenvironment.

Volatile organic compounds in a multi-storey shopping mall in guangzhou, South China

NASA Astrophysics Data System (ADS)

Tang, Jianhui; Chan, C. Y.; Wang, Xinming; Chan, L. Y.; Sheng, Guoying; Fu, Jiamo

Volatile organic compounds (VOCs) specified in the USEPA TO-14 list were analysed in microenvironments of a multi-storey shopping mall in Guangzhou city, South China. The microenvironments studied include both indoor (department store, supermarket, fast-food court, electronic games room, children's playground, gallery and book store) and outdoor ones (rooftop and ground level entrance). The characteristics and concentration of VOCs varied widely in differing microenvironments. The average concentrations of the total VOCs in the indoor microenvironments ranged from 178.5 to 457.7 μg m -3 with a maximum of 596.8 μg m -3. The fast-food court and a leather products department store had the highest concentrations of benzene, toluene, ethylbenzene, xylenes and chlorinated hydrocarbons. A high level of 1,4-dichlorobenzene was found in all indoor microenvironments with an average of 12.3 μg m -3 and a maximum of 44.3 μg m -3. The ratios of average indoor to outdoor concentrations (I/O ratio) in all indoor microenvironments fell between 1 and 3, except an average of 24.6 and a maximum of 77.8 in the fashion department store for 1,4-dichlorobenzene. Indoor emission sources of monocyclic aromatic hydrocarbons in the shopping mall might include cooking stoves, leather products and building materials. Chlorinated hydrocarbons, however, were possibly connected with their use as cleaning agents or deodorizers.

Fetal Membranes-Derived Stem Cells Microenvironment.

PubMed

Favaron, Phelipe Oliveira; Miglino, Maria Angelica

2017-01-01

Recently, the regenerative medicine has been trying to congregate different areas such as tissue engineering and cellular therapy, in order to offer effective treatments to overcome several human and veterinary medical problems. In this regard, fetal membranes have been proposed as a powerful source for obtainment of multipotent stem cells with low immunogenicity, anti-inflammatory properties and nontumorigenicity properties for the treatment of several diseases, including replacing cells lost due to tissue injuries or degenerative diseases. Morpho-physiological data have shown that fetal membranes, especially the yolk sac and amnion play different functions according to the gestational period, which are direct related to the features of the microenvironment that their cells are subject. The characteristics of the microenvironment affect or controls important cellular events involved with proliferation, division and maintenance of the undifferentiated stage or differentiation, especially acting on the extracellular matrix components. Considering the importance of the microenvironment and the diversity of embryonic and fetal membrane-derived stem cells, this chapter will addressed advances in the isolation, phenotyping, characteristics of the microenvironment, and applications of yolk sac and amniotic membrane-derived stem cells for human and veterinary regenerative medicine.

Dynamic Microenvironment Induces Phenotypic Plasticity of Esophageal Cancer Cells Under Flow

NASA Astrophysics Data System (ADS)

Calibasi Kocal, Gizem; Güven, Sinan; Foygel, Kira; Goldman, Aaron; Chen, Pu; Sengupta, Shiladitya; Paulmurugan, Ramasamy; Baskin, Yasemin; Demirci, Utkan

2016-12-01

Cancer microenvironment is a remarkably heterogeneous composition of cellular and non-cellular components, regulated by both external and intrinsic physical and chemical stimuli. Physical alterations driven by increased proliferation of neoplastic cells and angiogenesis in the cancer microenvironment result in the exposure of the cancer cells to elevated levels of flow-based shear stress. We developed a dynamic microfluidic cell culture platform utilizing eshopagael cancer cells as model cells to investigate the phenotypic changes of cancer cells upon exposure to fluid shear stress. We report the epithelial to hybrid epithelial/mesenchymal transition as a result of decreasing E-Cadherin and increasing N-Cadherin and vimentin expressions, higher clonogenicity and ALDH positive expression of cancer cells cultured in a dynamic microfluidic chip under laminar flow compared to the static culture condition. We also sought regulation of chemotherapeutics in cancer microenvironment towards phenotypic control of cancer cells. Such in vitro microfluidic system could potentially be used to monitor how the interstitial fluid dynamics affect cancer microenvironment and plasticity on a simple, highly controllable and inexpensive bioengineered platform.

Pirfenidone normalizes the tumor microenvironment to improve chemotherapy

PubMed Central

Papageorgis, Panagiotis; Voutouri, Chrysovalantis; Stylianopoulos, Triantafyllos

2017-01-01

Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization. Using two orthotopic mammary tumor models we demonstrate that Pirfenidone reduces collagen and hyaluronan levels and, as a result, significantly increases blood vessel functionality and perfusion and improves the anti-tumor efficacy of doxorubicin. Reduction of extracellular matrix components were mediated via TGFβ signaling pathway inhibition due to downregulation of TGFβ1, COL1A1, COL3A1, HAS2, HAS3 expression levels. Our findings provide evidence that repurposing Pirfenidone could be used as a promising strategy to enhance drug delivery to solid tumors by normalizing the tumor microenvironment. PMID:28445938

Cancer prevention and therapy through the modulation of the tumor microenvironment

PubMed Central

Casey, Stephanie C.; Amedei, Amedeo; Aquilano, Katia; Benencia, Fabian; Bhakta, Dipita; Boosani, Chandra S.; Chen, Sophie; Ciriolo, Maria Rosa; Crawford, Sarah; Fujii, Hiromasa; Georgakilas, Alexandros G.; Guha, Gunjan; Halicka, Dorota; Helferich, William G.; Heneberg, Petr; Honoki, Kanya; Kerkar, Sid P.; Mohammed, Sulma I.; Niccolai, Elena; Nowsheen, Somaira; Rupasinghe, H. P. Vasantha; Samadi, Abbas; Singh, Neetu; Talib, Wamidh H.; Venkateswaran, Vasundara; Whelan, Richard; Yang, Xujuan; Felsher, Dean W.

2015-01-01

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adapative immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2, 3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer. PMID:25865775

Influence of aerobic and anoxic microenvironments on polyhydroxyalkanoates (PHA) production from food waste and acidogenic effluents using aerobic consortia.

PubMed

Reddy, M Venkateswar; Mohan, S Venkata

2012-01-01

The functional role of aerobic and anoxic microenvironments on polyhydroxyalkanoates (PHA) production using food waste (UFW) and effluents from acidogenic biohydrogen production process (FFW) were studied employing aerobic mixed culture as biocatalyst. Anoxic microenvironment documented higher PHA production, while aerobic microenvironment showed higher substrate degradation. FFW showed higher PHA accumulation (39.6%) than UFW (35.6%) due to ready availability of precursors (fatty acids). Higher fraction of poly-3-hydroxy butyrate (PHB) was observed compared to poly-3-hydroxy valerate (PHV) in the accumulated PHA in the form of co-polymer [P3(HB-co-HV)]. Dehydrogenase, phosphatase and protease enzymatic activities were monitored during process operation. Integration with fermentative biohydrogen production yielded additional substrate degradation under both aerobic (78%) and anoxic (72%) microenvironments apart from PHA production. Microbial community analysis documented the presence of aerobic and facultative organisms capable of producing PHA. Integration strategy showed feasibility of producing hydrogen along with PHA by consuming fatty acids generated during acidogenic process in association with increased treatment efficiency. Copyright © 2011 Elsevier Ltd. All rights reserved.

Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells

PubMed Central

Yoo, Ki-Chun; Lee, Ji-Hyun; Kim, In-Gyu; Kim, Min-Jung; Chang, Jong Hee; Kang, Seok-Gu; Lee, Su-Jae

2017-01-01

Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GBM) cells. However, the cellular mechanism underlying HA-rich microenvironment in GBM remains unexplored. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) contribute to abundance of hyaluronic acid (HA) in tumor microenvironment through HA synthase-2 (HAS2) induction, and thereby enhances invasiveness of GBM cells. In an autocrine manner, C5a secreted by tMSLCs activated ERK MAPK for HAS2 induction in tMSLCs. Importantly, HA acted as a signaling ligand of its cognate receptor RHAMM for intracellular signaling activation underlying invasiveness of GBM cells. Taken together, our study suggests that tMSLCs contribute to HA-rich proinvasive ECM microenvironment in GBM. PMID:27903965

Validation of a device for the active manipulation of the tumor microenvironment during intravital imaging

PubMed Central

Williams, James K.; Entenberg, David; Wang, Yarong; Avivar-Valderas, Alvaro; Padgen, Michael; Clark, Ashley; Aguirre-Ghiso, Julio A.; Castracane, James; Condeelis, John S.

2016-01-01

ABSTRACT The tumor microenvironment is recognized as playing a significant role in the behavior of tumor cells and their progression to metastasis. However, tools to manipulate the tumor microenvironment directly, and image the consequences of this manipulation with single cell resolution in real time in vivo, are lacking. We describe here a method for the direct, local manipulation of microenvironmental parameters through the use of an implantable Induction Nano Intravital Device (iNANIVID) and simultaneous in vivo visualization of the results at single-cell resolution. As a proof of concept, we deliver both a sustained dose of EGF to tumor cells while intravital imaging their chemotactic response as well as locally induce hypoxia in defined microenvironments in solid tumors. PMID:27790386

Changing paradigms in radiobiology.

PubMed

Mothersill, Carmel; Seymour, Colin

2012-01-01

The last 25 years have seen a major shift in emphasis in the field of radiobiology from a DNA-centric view of how radiation damage occurs to a much more biological view that appreciates the importance of macro-and micro-environments, hierarchical organization, underlying genetics, evolution, adaptation and signaling at all levels from atoms to ecosystems. The new view incorporates concepts of hormesis, nonlinear systems, bioenergy field theory, uncertainty and homeodynamics. While the mechanisms underlying these effects and responses are still far from clear, it is very apparent that their implications are much wider than the field of radiobiology. This reflection discusses the changing views and considers how they are influencing thought in environmental and medical science and systems biology. Copyright © 2012 Elsevier B.V. All rights reserved.

Potential role of the glycolytic oscillator in acute hypoxia in tumors

NASA Astrophysics Data System (ADS)

Che Fru, Leonard; Adamson, Erin B.; Campos, David D.; Fain, Sean B.; Jacques, Steven L.; van der Kogel, Albert J.; Nickel, Kwang P.; Song, Chihwa; Kimple, Randall J.; Kissick, Michael W.

2015-12-01

Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

Micropost microenvironments for studying luminal-basal lineage commitment of breast cancer cells

NASA Astrophysics Data System (ADS)

Kesavaraju, Anand; Qing, Bo; Jabart, Eric; Labarge, Mark; Sohn, Lydia

2013-03-01

MCF-7 breast cancer cells were plated onto polydimethylsiloxane (PDMS) microposts in order to examine the effects of the microenvironment on cell lineage. Different stiffnesses and sizes of the microposts are postulated to impact cell surface marker expression levels. We will provide preliminary results analyzing CD271 and focal adhesion markers such as vinculin. 3D shear flow will also be applied to the microposts to study how external mechanical stimuli affect cancer cells within their microenvironment.

Dynamic microenvironments: the fourth dimension.

PubMed

Tibbitt, Mark W; Anseth, Kristi S

2012-11-14

The extracellular space, or cell microenvironment, choreographs cell behavior through myriad controlled signals, and aberrant cues can result in dysfunction and disease. For functional studies of human cell biology or expansion and delivery of cells for therapeutic purposes, scientists must decipher this intricate map of microenvironment biology and develop ways to mimic these functions in vitro. In this Perspective, we describe technologies for four-dimensional (4D) biology: cell-laden matrices engineered to recapitulate tissue and organ function in 3D space and over time.

Simple device measures solar radiation

NASA Technical Reports Server (NTRS)

Humphries, W. R.

1977-01-01

Simple inexpensive thermometer, insolated from surroundings by transparent glass or plastic encasement, measures intensities of solar radiation, or radiation from other sources such as furnaces or ovens. Unit can be further modified to accomplish readings from remote locations.

The effect of commuting microenvironment on commuter exposures to vehicular emission in Hong Kong

NASA Astrophysics Data System (ADS)

Chan, L. Y.; Chan, C. Y.; Qin, Y.

Vehicular exhaust emission has gradually become the major air pollution source in modern cities and traffic related exposure is found to contribute significantly to total human exposure level. A comprehensive survey was conducted from November 1995 to July 1996 in Hong Kong to assess the effect of traffic-induced air pollution inside different commuting microenvironments on commuter exposure. Microenvironmental monitoring is performed for six major public commuting modes (bus, light bus, MTR, railway, tram, ferry), plus private car and roadside pavement. Traffic-related pollutants, CO, NO x, THC and O 3 were selected as the target pollutants. The results indicate that commuter exposure is highly influenced by the choice of commuting microenvironment. In general, the exposure level in decreasing order of measured pollutant level for respective commuting microenvironments are: private car, the group consisting light bus, bus, tram and pavement, MTR and train, and finally ferry. In private car, the CO level is several times higher than that in the other microenvironments with a trip averaged of 10.1 ppm and a maximum of 24.9 ppm. Factors such as the body position of the vehicle, intake point of the ventilation system, fuel used, ventilation, transport mode, road and driving conditions were used in the analysis. Inter-microenvironment, intra-microenvironment and temporal variation of CO concentrations were used as the major indicator. The low body position and low intake point of the ventilation system of the private car are believed to be the cause of higher intake of exhaust of other vehicles and thus result in high pollution level in this microenvironment. Compared with other metropolis around the world and the Hong Kong Air Quality Objectives (HKAQO), exposure levels of commuter to traffic-related air pollution in Hong Kong are relatively low for most pollutants measured. Only several cases of exceedence of HKAQO by NO 2 were recorded. The strong prevailing wind plus the channeling effect created by the harbor, the fuel used, the relative abundance of new cars and the successful implementation of the vehicle emission control program are factors that compensate the effect of the emission source strength and thus lead to low exposure levels.

A 27,000 year record of Red Sea Outflow: Implication for timing of post-glacial monsoon intensification

NASA Astrophysics Data System (ADS)

Naqvi, Wajih A.; Fairbanks, Richard G.

We reconstruct here the history of the Red Sea Outflow (RSO) over the past 27,000 years from an AMS 14C-dated high-resolution δ13C record of benthic foraminifera from the inner Gulf of Aden assuming the dominance of circulation over productivity in regulating benthic δ13C. The results reveal that, following a period of suppressed RSO due to shallow sill 24,000-18,000 yr BP, the Red Sea was vigorously flushed for ˜2,000 years before a major monsoon intensification caused the cessation of deep water formation from 15,500 to 7,300 yr BP. It appears that the monsoon intensification did lag behind insolation until 15,500 yr BP. Between 15,500 and the present, however, there was no lag in conflict with the previous reports, implying a negligible dampening effect of continental albedo during this period. However, since our analysis is confined to a single depth horizon and our record is sensitive to sea level, it has some limitations as an indicator of monsoon intensity.

Quantum Tunnelling to the Origin and Evolution of Life

PubMed Central

Trixler, Frank

2013-01-01

Quantum tunnelling is a phenomenon which becomes relevant at the nanoscale and below. It is a paradox from the classical point of view as it enables elementary particles and atoms to permeate an energetic barrier without the need for sufficient energy to overcome it. Tunnelling might seem to be an exotic process only important for special physical effects and applications such as the Tunnel Diode, Scanning Tunnelling Microscopy (electron tunnelling) or Near-field Optical Microscopy operating in photon tunnelling mode. However, this review demonstrates that tunnelling can do far more, being of vital importance for life: physical and chemical processes which are crucial in theories about the origin and evolution of life can be traced directly back to the effects of quantum tunnelling. These processes include the chemical evolution in stellar interiors and within the cold interstellar medium, prebiotic chemistry in the atmosphere and subsurface of planetary bodies, planetary habitability via insolation and geothermal heat as well as the function of biomolecular nanomachines. This review shows that quantum tunnelling has many highly important implications to the field of molecular and biological evolution, prebiotic chemistry and astrobiology. PMID:24039543

Experimental investigation of insolation-driven dust ejection from Mars' CO2 ice caps

NASA Astrophysics Data System (ADS)

Kaufmann, E.; Hagermann, A.

2017-01-01

Mars' polar caps are - depending on hemisphere and season - partially or totally covered with CO2 ice. Icy surfaces such as the polar caps of Mars behave differently from surfaces covered with rock and soil when they are irradiated by solar light. The latter absorb and reflect incoming solar radiation within a thin layer beneath the surface. In contrast, ices are partially transparent in the visible spectral range and opaque in the infrared. Due to this fact, the solar radiation can penetrate to a certain depth and raise the temperature of the ice or dust below the surface. This may play an important role in the energy balance of icy surfaces in the solar system, as already noted in previous investigations. We investigated the temperature profiles inside CO2 ice samples including a dust layer under Martian conditions. We have been able to trigger dust eruptions, but also demonstrated that these require a very narrow range of temperature and ambient pressure. We discuss possible implications for the understanding of phenomena such as arachneiform patterns or fan shaped deposits as observed in Mars' southern polar region.

Implications for Nucleus Heterogeneity from the Comparison of Pre- and Post-Equinox Neutral ROSINA Observations Inbound and Outbound Beyond 3 AU

NASA Astrophysics Data System (ADS)

Luspay-Kuti, A.; Altwegg, K.; Berthelier, J. J.; Beth, A.; Dhooghe, F.; Fiethe, B.; Fuselier, S. A.; Gombosi, T. I.; Hansen, K. C.; Hässig, M.; Mall, U.; Mandt, K.; Mousis, O.; Steven, P. M.; Rubin, M.; Trattner, K. J.; Tzou, C. Y.; Wurz, P.

2017-12-01

Pre-equinox ROSINA/DFMS measurements revealed a strongly heterogeneous coma. The concentrations of major and various minor volatile species were found to depend on the latitude and longitude of the nadir point of the spacecraft. The observed time variability of coma species remained consistent for about three months up to equinox. The chemical variability could be generally interpreted in terms of temperature and seasonal effects superposed on some kind of nucleus heterogeneity. We compare here pre-equinox (inbound) ROSINA/DFMS measurements from 2014 to measurements taken after the outbound equinox in 2016, both at heliocentric distances larger than 3 AU. For a direct comparison we limit our observations to the southern, poorly illuminated hemisphere only. We report the similarities and differences in the concentrations and time variability of neutral species under similar insolation conditions (heliocentric distance, season) pre- and post-equinox, and interpret them in light of the pre-equinox observations. Such direct comparison of the neutral behavior is important to better understand the evolution of cometary outgassing.

A New ɛNd Record Covering Termination II

NASA Astrophysics Data System (ADS)

Deaney, E. L.; Thornalley, D. J.; van de Flierdt, T.; Kreissig, K.; Barker, S.

2014-12-01

The 143Nd/144Nd ratio (ɛNd) of seawater is used as a quasi-conservative tracer to examine past changes in water mass composition of the deep ocean. Records of ɛNd across the last deglaciation (Termination 1, T1) provide valuable information about water mass mixing that has improved our understanding of the ocean dynamics relevant to the process of deglaciation. However, questions remain concerning end-member source characteristics and regional hydrographic processes. Here we present a high resolution record of ɛNd derived from fish debris from ODP site 1063 across Termination 2. The different external and internal forcing (e.g. insolation versus freshwater) applicable to T2 make this a useful comparator for studies focused on T1. Accordingly we find large (up to 4 ɛNd units) fluctuations across T2 that can be related to high latitude climate changes as recorded by ice cores and other high resolution climate archives. We also identify periods of extremely negative values that require new explanations for changing end-member compositions. Our results have important implications for understanding North Atlantic deep water formation processes during critical climate transitions.

Tumor Biology and Microenvironment Research

Cancer.gov

Part of NCI's Division of Cancer Biology's research portfolio, research in this area seeks to understand the role of tumor cells and the tumor microenvironment (TME) in driving cancer initiation, progression, maintenance and recurrence.

Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury

PubMed Central

Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A; Graf, Rudolf; Strong, Anthony John

2011-01-01

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves. PMID:21045864

On the relationship between cardboard burning in a sunshine recorder and the direct solar irradiance.

NASA Astrophysics Data System (ADS)

Sanchez, A.; Calbó, J.; González, J. A.

2012-04-01

Since the end of XIX century, the Campbell-Stokes recorder (CSR) has been the instrument used to measure the insolation (hours of sunshine during per day). Due to the large number of records that exist worldwide (some of them extending over more than 100 years), valuable climatic information can be extracted from them. There are various articles that relate the insolation with the cloudiness and the global solar irradiation (Angstrom-Prescott type formulas). Theoretically, the insolation is defined as the number of hours that direct solar irradiance (DSI) exceeds 120 W/m2, thus corresponding to the total length of the burning in the bands. The width of the burn has not been well studied, so the aim of this research is to relate this width, first with the DSI and then, with other variables. The research was carried out in Girona (NE Spain) for a period extending since February 2011. A CSR from Thies Clima and a pyrheliometer from Kipp&Zonen were used to measure insolation and the direct solar irradiance. Other meteorological variables were also stored for the study. For each band, we made two independent measurements of the width of the burn every 10 minutes: first, we measured directly the width of the perforated portion of the burn; second, we measured the width of the burn after applying a digital image process that increases the contrast of the burn. The burn in a band has a direct relationship with the DSI. Specifically, correlation coefficients of the perforation width and the burning width with DSI were 0.838 and 0.864 respectively. However, we found that there are times when despite of DSI is as high as 400 W/m2 (i.e. much greater than 120 W/m2), there is no burn in the band. Contrarily, sometimes a burn occurs with almost no DSI. Furthermore, a higher DSI does not always correspond to a wider burn of the band. Because of this, we consider that characteristics of band burns must also depend on other meteorological variables (temperature, humidity...). The physical characteristics of the heliograph and of the cardboard from which the bands are made may also have an important role in this relationship. The method was applied to a limited series of bands so the results and conclusions are preliminary. The first conclusion is the lack of accuracy that has the threshold value of 120 W/m2 and the difficulty of giving a single value of this threshold. The sudden changes and intermittent weather conditions, combined with the poor temporal resolution of the measure of the burn width, reduce the correlation between burn and DSI. For further research aimed at the study of the behavior of the insolation due to the changing concentration of aerosols in the atmosphere, we need to increase the number of burned sunshine bands and to describe with more accuracy the limitations of heliographs.

The Tumor Microenvironment: A Pitch for Multiple Players

PubMed Central

Schiavoni, Giovanna; Gabriele, Lucia; Mattei, Fabrizio

2013-01-01

The cancer microenvironment may be conceptually regarded as a pitch where the main players are resident and non-resident cellular components, each covering a defined role and interconnected by a complex network of soluble mediators. The crosstalk between these cells and the tumor cells within this environment crucially determines the fate of tumor progression. Immune cells that infiltrate the tumor bed are transported there by blood circulation and exert a variety of effects, either counteracting or favoring tumor outgrowth. Here, we review and discuss the multiple populations composing the tumor bed, with special focus on immune cells subsets that positively or negatively dictate neoplastic progression. In this scenario, the contribution of cancer stem cells within the tumor microenvironment will also be discussed. Finally, we illustrate recent advances on new integrated approaches to investigate the tumor microenvironment in vitro. PMID:23616948

The potential influence of radiation-induced microenvironments in neoplastic progression

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1998-01-01

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Lung microenvironment promotes the metastasis of human hepatocellular carcinoma cells to the lungs.

PubMed

Jin, Yun; Ai, Junhua; Shi, Jun

2015-01-01

Cancer metastasis is a highly tissue-specific and organ-selective process. It has been shown that the affected tissues and/or organs play a major role in this complex process. The lung is the most common target organ of extrahepatic hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism underlying this organ-specific metastasis remains unclear. We hypothesized that lung microenvironment was able to promote the metastasis of HCC cells to the lungs leading to distant metastases. In support of our hypothesis, we provided evidence from targeted metastasis in various types of cancer and contributing factors in the microenvironment of targeted tissues/organs. A better understanding of the steps involved in the interplay between HCC cells and lung microenvironment may offer new perspectives for the medical management of lung metastases of HCC.

[Design of an anesthesia and micro-environment information management system in mobile operating room].

PubMed

Wang, Xianwen; Liu, Zhiguo; Zhang, Wenchang; Wu, Qingfu; Tan, Shulin

2013-08-01

We have designed a mobile operating room information management system. The system is composed of a client and a server. A client, consisting of a PC, medical equipments, PLC and sensors, provides the acquisition and processing of anesthesia and micro-environment data. A server is a powerful computer that stores the data of the system. The client gathers the medical device data by using the C/S mode, and analyzes the obtained HL7 messages through the class library call. The client collects the micro-environment information with PLC, and finishes the data reading with the OPC technology. Experiment results showed that the designed system could manage the patient anesthesia and micro-environment information well, and improve the efficiency of the doctors' works and the digital level of the mobile operating room.

Neutrophils and the Inflammatory Tissue Microenvironment in the Mucosa

PubMed Central

Campbell, Eric L.; Kao, Daniel J.; Colgan, Sean P.

2016-01-01

The interaction of neutrophils (PMNs) and epithelial cells are requisite lines of communication during mucosal inflammatory responses. Consequences of such interactions often determine endpoint organ function, and for this reason, much interest has developed around defining the constituents of the tissue microenvironment of inflammatory lesions. Physiologic in vitro and in vivo models have aided in discovery of components that define the basic inflammatory machinery that mold the inflammatory tissue microenvironment. Here, we will review the recent literature related to the contribution of PMNs to molding of the tissue microenvironment, with an emphasis on the gastrointestinal (GI) tract. We focus on endogenous pathways for promoting tissue homeostasis and the molecular determinants of neutrophil-epithelial cell interactions during ongoing inflammation. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation. PMID:27558331

Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.

2016-03-01

Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

Expanding Applications of the Nano Intravital Device as a Platform for Exploring Tumor Microenvironments

NASA Astrophysics Data System (ADS)

Padgen, Michael R.

The tumor microenvironment has been demonstrated to be a key determinant in the progression of cancer. Unfortunately, the mechanisms behind the different microenvironments (cytokine gradients, hypoxia, hypoglycemia, etc) have not been fully elucidated. Identifying these mechanisms can lead to targeted, individualized therapy to prevent metastasis. The Nano Intravital Device (NANIVID) is a microfabricated, implantable device designed to initiate specific microenvironments in vivo so that the time course of the effects can be observed. With both spatial and temporal control over the induced environments, the affected regions of the tumor can be compared to the rest of the tumor. The NANIVID was first used to establish cytokine gradients to monitor the migration of invasive cancer cells. The three projects that comprise this work expand the applications of the NANIVID to establish the device as a robust platform for investigating tumor microenvironment interactions. The first project released chemical mimics from the device to induce the cellular hypoxic response in tumors to determine how hypoxia affects the fate of disseminated tumor cells. The second project used the NANIVID in combination with an atomic force microscope to investigate the altered mechanics of migrating invasive cancer cells. The final project was to develop a cell counter to monitor the isolation of the invasive subpopulation of cells that were drawn into the device using a chemoattractant. These three projects demonstrate the potential of the NANIVID as a platform for investigating the tumor microenvironment.

Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment

PubMed Central

Kim, Yong Sook; Jeong, Hye-yun; Kim, Ah Ra; Kim, Woong-Hee; Cho, Haaglim; Um, JungIn; Seo, Youngha; Kang, Wan Seok; Jin, Suk-Won; Kim, Min Chul; Kim, Yong-Chul; Jung, Da-Woon; Williams, Darren R.; Ahn, Youngkeun

2016-01-01

The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI. PMID:27510556

Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment.

PubMed

Pink, Ryan Charles; Elmusrati, Areeg A; Lambert, Daniel; Carter, David Raul Francisco

2018-01-05

Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meeting to explore the roles of EVs in the tumour microenvironment. This cross-disciplinary meeting explored examples of how aberrant crosstalk between tumour and stromal cells can promote cancer progression, and how such signalling can be targeted for diagnostic, prognostic and therapeutic benefit. In this review, and the special edition of Philosophical Transactions of the Royal Society B that follows, we will provide an overview of the content and outcomes of this exciting meeting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Author(s).

Copper speciation in the gill microenvironment of carp (Cyprinus carpio) at various levels of pH.

PubMed

Tao, Shu; Long, Aimin; Xu, Fuliu; Dawson, R W

2002-07-01

The fish gill microenvironment of Cyprinus carpio under stress of copper exposure was investigated. pH and other parameters including free copper activity, alkalinity, and inorganic and organic carbons in the surrounding water (inspired water) and in the gill microenvironment (expired water) were measured or calculated at various levels of pH and varying total copper concentrations. The chemical equilibrium calculation (from MINEQA2) and complexation modeling (mucus-copper) were coupled to calculate both species distribution. The results indicate that the pH in the fish gill microenvironment was different from that in the surrounding water with a balance point around 6.9. The secretion of both CO(2) and mucus was affected in both linear and nonlinear ways when the fish were exposed to elevated concentrations of copper. The complexation capacity of the gill mucus was characterized by a conditional stability constant (logk(Cu-mucus)) of 5.37 along with a complexation equivalent concentration (L(Cu-mucus)) of 0.96 mmol Cu/mg C. For both the fish microenvironment and the surrounding water, the dominant copper species shifted from Cu(2+) to CuCO(3)(0) and to Cu(OH)(2)(0) when the pH of the surrounding water changed from 6.12 to 8.11. The change in copper speciation in the gill microenvironment is smaller than that in the surrounding water due to the pH buffering capacity of the fish gills.

Accelerated thermokarst formation in the McMurdo Dry Valleys, Antarctica.

PubMed

Levy, Joseph S; Fountain, Andrew G; Dickson, James L; Head, James W; Okal, Marianne; Marchant, David R; Watters, Jaclyn

2013-01-01

Thermokarst is a land surface lowered and disrupted by melting ground ice. Thermokarst is a major driver of landscape change in the Arctic, but has been considered to be a minor process in Antarctica. Here, we use ground-based and airborne LiDAR coupled with timelapse imaging and meteorological data to show that 1) thermokarst formation has accelerated in Garwood Valley, Antarctica; 2) the rate of thermokarst erosion is presently ~ 10 times the average Holocene rate; and 3) the increased rate of thermokarst formation is driven most strongly by increasing insolation and sediment/albedo feedbacks. This suggests that sediment enhancement of insolation-driven melting may act similarly to expected increases in Antarctic air temperature (presently occurring along the Antarctic Peninsula), and may serve as a leading indicator of imminent landscape change in Antarctica that will generate thermokarst landforms similar to those in Arctic periglacial terrains.

Late Pleistocene variations in Antarctica sea ice. I - Effect of orbital isolation changes. II - Effect of interhemispheric deep-ocean heat exchange

NASA Technical Reports Server (NTRS)

Crowley, Thomas J.; Parkinson, Claire L.

1988-01-01

A dynamic-thermodynamic sea-ice model is presently used to ascertain the effects of orbitally-induced insolation changes on Antarctic sea-ice cover; the results thus obtained are compared with modified CLIMAP reconstructions of sea-ice 18,000 years ago. The minor influence exerted by insolation on Pleistocene sea-ice distributions is attributable to a number of factors. In the second part of this investigation, variations in the production of warm North Atlantic Deep Water are proposed as a mechanism constituting the linkage between climate fluctuations in the Northern and Southern hemispheres during the Pleistocene; this hypothesis is tested by examining the sensitivity of the dynamic-thermodynamic model for Antarctic sea-ice changes in vertical ocean heat flux, and comparing the simulations with modified CLIMAP sea-ice maps for 18,000 years ago.

A comparative study of satellite estimation for solar insolation in Albania with ground measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitrushi, Driada, E-mail: driadamitrushi@yahoo.com; Berberi, Pëllumb, E-mail: pellumb.berberi@gmail.com; Muda, Valbona, E-mail: vmuda@hotmail.com

The main objective of this study is to compare data provided by Database of NASA with available ground data for regions covered by national meteorological net NASA estimates that their measurements of average daily solar radiation have a root-mean-square deviation RMSD error of 35 W/m{sup 2} (roughly 20% inaccuracy). Unfortunately valid data from meteorological stations for regions of interest are quite rare in Albania. In these cases, use of Solar Radiation Database of NASA would be a satisfactory solution for different case studies. Using a statistical method allows to determine most probable margins between to sources of data. Comparison of meanmore » insulation data provided by NASA with ground data of mean insulation provided by meteorological stations show that ground data for mean insolation results, in all cases, to be underestimated compared with data provided by Database of NASA. Converting factor is 1.149.« less

An Ambulatory System for Gait Monitoring Based on Wireless Sensorized Insoles

PubMed Central

González, Iván; Fontecha, Jesús; Hervás, Ramón; Bravo, José

2015-01-01

A new gait phase detection system for continuous monitoring based on wireless sensorized insoles is presented. The system can be used in gait analysis mobile applications, and it is designed for real-time demarcation of gait phases. The system employs pressure sensors to assess the force exerted by each foot during walking. A fuzzy rule-based inference algorithm is implemented on a smartphone and used to detect each of the gait phases based on the sensor signals. Additionally, to provide a solution that is insensitive to perturbations caused by non-walking activities, a probabilistic classifier is employed to discriminate walking forward from other low-level activities, such as turning, walking backwards, lateral walking, etc. The combination of these two algorithms constitutes the first approach towards a continuous gait assessment system, by means of the avoidance of non-walking influences. PMID:26184199

Accelerated thermokarst formation in the McMurdo Dry Valleys, Antarctica

PubMed Central

Levy, Joseph S.; Fountain, Andrew G.; Dickson, James L.; Head, James W.; Okal, Marianne; Marchant, David R.; Watters, Jaclyn

2013-01-01

Thermokarst is a land surface lowered and disrupted by melting ground ice. Thermokarst is a major driver of landscape change in the Arctic, but has been considered to be a minor process in Antarctica. Here, we use ground-based and airborne LiDAR coupled with timelapse imaging and meteorological data to show that 1) thermokarst formation has accelerated in Garwood Valley, Antarctica; 2) the rate of thermokarst erosion is presently ~ 10 times the average Holocene rate; and 3) the increased rate of thermokarst formation is driven most strongly by increasing insolation and sediment/albedo feedbacks. This suggests that sediment enhancement of insolation-driven melting may act similarly to expected increases in Antarctic air temperature (presently occurring along the Antarctic Peninsula), and may serve as a leading indicator of imminent landscape change in Antarctica that will generate thermokarst landforms similar to those in Arctic periglacial terrains. PMID:23881292

Greening of the Sahara suppressed ENSO activity during the mid-Holocene

PubMed Central

Pausata, Francesco S. R.; Zhang, Qiong; Muschitiello, Francesco; Lu, Zhengyao; Chafik, Léon; Niedermeyer, Eva M.; Stager, J. Curt; Cobb, Kim M.; Liu, Zhengyu

2017-01-01

The evolution of the El Niño-Southern Oscillation (ENSO) during the Holocene remains uncertain. In particular, a host of new paleoclimate records suggest that ENSO internal variability or other external forcings may have dwarfed the fairly modest ENSO response to precessional insolation changes simulated in climate models. Here, using fully coupled ocean-atmosphere model simulations, we show that accounting for a vegetated and less dusty Sahara during the mid-Holocene relative to preindustrial climate can reduce ENSO variability by 25%, more than twice the decrease obtained using orbital forcing alone. We identify changes in tropical Atlantic mean state and variability caused by the momentous strengthening of the West Africa Monsoon (WAM) as critical factors in amplifying ENSO’s response to insolation forcing through changes in the Walker circulation. Our results thus suggest that potential changes in the WAM due to anthropogenic warming may influence ENSO variability in the future as well. PMID:28685758

Greening of the Sahara suppressed ENSO activity during the mid-Holocene.

PubMed

Pausata, Francesco S R; Zhang, Qiong; Muschitiello, Francesco; Lu, Zhengyao; Chafik, Léon; Niedermeyer, Eva M; Stager, J Curt; Cobb, Kim M; Liu, Zhengyu

2017-07-07

The evolution of the El Niño-Southern Oscillation (ENSO) during the Holocene remains uncertain. In particular, a host of new paleoclimate records suggest that ENSO internal variability or other external forcings may have dwarfed the fairly modest ENSO response to precessional insolation changes simulated in climate models. Here, using fully coupled ocean-atmosphere model simulations, we show that accounting for a vegetated and less dusty Sahara during the mid-Holocene relative to preindustrial climate can reduce ENSO variability by 25%, more than twice the decrease obtained using orbital forcing alone. We identify changes in tropical Atlantic mean state and variability caused by the momentous strengthening of the West Africa Monsoon (WAM) as critical factors in amplifying ENSO's response to insolation forcing through changes in the Walker circulation. Our results thus suggest that potential changes in the WAM due to anthropogenic warming may influence ENSO variability in the future as well.

The best way to reduce reulcerations: if you understand biomechanics of the diabetic foot, you can do it.

PubMed

Lázaro-Martínez, José Luis; Aragón-Sánchez, Javier; Alvaro-Afonso, Francisco Javier; García-Morales, Esther; García-Álvarez, Yolanda; Molines-Barroso, Raúl Juan

2014-12-01

Foot ulcer recurrence is still an unresolved issue. Although several therapies have been described for preventing foot ulcers, the rates of reulcerations are very high. Footwear and insoles have been recommended as effective therapies that prevent the development of new ulcers; however, the majority of studies have analyzed their effects in terms of reducing peak plantar pressure rather than ulcer relapse. Knowledge of biomechanical considerations is low, in general, in the team approach to diabetic foot because heterogeneous professionals having competence in recurrence prevention are involved. Assessment of biomechanical alterations define a foot type position; examining foot structure and recording plantar pressure could help in appropriate insole and footwear prescription and design. Patient education and compliance should be taken into consideration for better therapy success. When patients suffer from rigid deformities or have undergone an amputation, surgical offloading should be considered as an alternative. © The Author(s) 2014.