Recovery Ventilation and Oxygen Debt-A Mathematical Model for the Prediction of Recovery Ventilation

A Mathematical model has been evolved for the estimation of recovery ventilation following an exercise. The model has been used to estimate recovery ventilation in moderate to heavy exercise for a period of 32 minutes. The model gives satisfactory predictions for persons of different age groups and under different environment conditions thus establishing its universal applicability

Biomathematical Study of the Kinetics of Energy Output During Physical Exercise

The kinetics of energy production during different grades of activity has been described in terms of rate constant and workload for submaximal, maximal and supermaximal exercises. Equations have been derived for the aerobic and anaerobic components of energy production for the three cases. The theoretical approach has been validated with the available experimental data

Regression of Body Density on Skinfold Thicknesses in High Altitude Natives: Decline in the Predictive Efficiency on De-Acclimatisation to Low Altitude

Body density, stature, body weight and skinfold thickness at 11 sites were experimentally measured on two groups of high altitude natives (HAN) of Ladakh. Group 1, consisting of 38 similar volunteers was studied after 4-week stay at an altitude of 3658 m and Group 2, consisting of 38 similar volunteers was studied after 4-week stay at Delhi (altitude, 200m). Although, there was a strong relationship between skinfolds, other anthropometric measurements and body density (R=0.898) at high altitude (HA), this relationship was significantly reduced at Delhi (R=0.642). Appropriate regression equations predicting body density from skinfold thicknesses, stature and body weight are given for HAN at both the locations. It is concluded that hyperhydration of the lean body and the adipose tissue may be responsible for the weakening of the multiple Rs on de-acclimatisation to low altitude

Mammary epithelial cell transformation: insights from cell culture and mouse models

Normal human mammary epithelial cells (HMECs) have a finite life span and do not undergo spontaneous immortalization in culture. Critical to oncogenic transformation is the ability of cells to overcome the senescence checkpoints that define their replicative life span and to multiply indefinitely – a phenomenon referred to as immortalization. HMECs can be immortalized by exposing them to chemicals or radiation, or by causing them to overexpress certain cellular genes or viral oncogenes. However, the most efficient and reproducible model of HMEC immortalization remains expression of high-risk human papillomavirus (HPV) oncogenes E6 and E7. Cell culture models have defined the role of tumor suppressor proteins (pRb and p53), inhibitors of cyclin-dependent kinases (p16(INK4a), p21, p27 and p57), p14(ARF), telomerase, and small G proteins Rap, Rho and Ras in immortalization and transformation of HMECs. These cell culture models have also provided evidence that multiple epithelial cell subtypes with distinct patterns of susceptibility to oncogenesis exist in the normal mammary tissue. Coupled with information from distinct molecular portraits of primary breast cancers, these findings suggest that various subtypes of mammary cells may be precursors of different subtypes of breast cancers. Full oncogenic transformation of HMECs in culture requires the expression of multiple gene products, such as SV40 large T and small t, hTERT (catalytic subunit of human telomerase), Raf, phosphatidylinositol 3-kinase, and Ral-GEFs (Ral guanine nucleotide exchange factors). However, when implanted into nude mice these transformed cells typically produce poorly differentiated carcinomas and not adenocarcinomas. On the other hand, transgenic mouse models using ErbB2/neu, Ras, Myc, SV40 T or polyomavirus T develop adenocarcinomas, raising the possibility that the parental normal cell subtype may determine the pathological type of breast tumors. Availability of three-dimensional and mammosphere models has led to the identification of putative stem cells, but more studies are needed to define their biologic role and potential as precursor cells for distinct breast cancers. The combined use of transformation strategies in cell culture and mouse models together with molecular definition of human breast cancer subtypes should help to elucidate the nature of breast cancer diversity and to develop individualized therapies

Ectopic Expression of E2F1 Stimulates β-Cell Proliferation and Function

OBJECTIVE-Generating functional beta-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G(1)- to S-phase transition during the cycling of many cell types and is required for pancreatic beta-cell growth and function. However, the consequences of overexpression of E2F1 in beta-cells are unknown. RESEARCH DESIGN AND METHODS-The effects of E2F1 overexpression on beta-cell proliferation and function were analyzed in isolated rat beta-cells and in transgenic mice. RESULTS-Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat beta-cells 20-fold but also enhanced beta-cell death. Coinfection with adenovirus Ad Akt expressing a constitutively active form of Akt (protein kinase B) suppressed beta-cell death to control levels. At 48 h after infection, the total beta-cell number and insulin content were, respectively, 46 and 79% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase beta-cell mass. Glucose-challenged insulin release was increased, and the mice showed protection against toxin-induced diabetes. CONCLUSIONS-Overexpression of E2F1, either in vitro or in vivo, can stimulate beta-cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult beta-cells, making it a strategic target for therapeutic manipulation of beta-cell function. Diabetes 59:1435-1444, 201

A review of high impact weather for aviation meteorology

This review paper summarizes current knowledge available for aviation operations related to meteorology and provides suggestions for necessary improvements in the measurement and prediction of weather-related parameters, new physical methods for numerical weather predictions (NWP), and next-generation integrated systems. Severe weather can disrupt aviation operations on the ground or in-flight. The most important parameters related to aviation meteorology are wind and turbulence, fog visibility, aerosol/ash loading, ceiling, rain and snow amount and rates, icing, ice microphysical parameters, convection and precipitation intensity, microbursts, hail, and lightning. Measurements of these parameters are functions of sensor response times and measurement thresholds in extreme weather conditions. In addition to these, airport environments can also play an important role leading to intensification of extreme weather conditions or high impact weather events, e.g., anthropogenic ice fog. To observe meteorological parameters, new remote sensing platforms, namely wind LIDAR, sodars, radars, and geostationary satellites, and in situ instruments at the surface and in the atmosphere, as well as aircraft and Unmanned Aerial Vehicles mounted sensors, are becoming more common. At smaller time and space scales (e.g., < 1 km), meteorological forecasts from NWP models need to be continuously improved for accurate physical parameterizations. Aviation weather forecasts also need to be developed to provide detailed information that represents both deterministic and statistical approaches. In this review, we present available resources and issues for aviation meteorology and evaluate them for required improvements related to measurements, nowcasting, forecasting, and climate change, and emphasize future challenges

Altered sirtuin expression is associated with node-positive breast cancer

Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, ‘nonmalignant' breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications

Knockdown of MBP-1 in Human Foreskin Fibroblasts Induces p53-p21 Dependent Senescence

MBP-1 acts as a general transcriptional repressor. Overexpression of MBP-1 induces cell death in a number of cancer cells and regresses tumor growth. However, the function of endogenous MBP-1 in normal cell growth regulation remains unknown. To unravel the role of endogenous MBP-1, we knocked down MBP-1 expression in primary human foreskin fibroblasts (HFF) by RNA interference. Knockdown of MBP-1 in HFF (HFF-MBPsi-4) resulted in an induction of premature senescence, displayed flattened cell morphology, and increased senescence-associated beta-galactosidase activity. FACS analysis of HFF-MBPsi-4 revealed accumulation of a high number of cells in the G1-phase. A significant upregulation of cyclin D1 and reduction of cyclin A was detected in HFF-MBPsi-4 as compared to control HFF. Senescent fibroblasts exhibited enhanced expression of phosphorylated and acetylated p53, and cyclin-dependent kinase inhibitor, p21. Further analysis suggested that promyolocytic leukemia protein (PML) bodies are dramatically increased in HFF-MBPsi-4. Together, these results demonstrated that knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway

The impacts of climate change on the winter water cycle of the western Himalaya

Some 180 million people depend on the Indus River as a key water resource, fed largely by precipitation falling over the western Himalaya. However, the projected response of western Himalayan precipitation to climate change is currently not well constrained: CMIP5 GCMs project a reduced frequency and vorticity of synoptic-scale systems impacting the area, but such systems would exist in a considerably moister atmosphere. In this study, a convection-permitting (4 km horizontal resolution) setup of the Weather Research and Forecasting (WRF) model is used to examine 40 cases of these synoptic-scale systems, known as western disturbances (WDs), as they interact with the western Himalaya. In addition to a present-day control run, three experiments are performed by perturbing the boundary and initial conditions to reflect pre-industrial, RCP4.5 and RCP8.5 background climates respectively. It is found that in spite of the weakening intensity of WDs, net precipitation associated with them in future climate scenarios increases significantly; conversely there is no net change in precipitation between the pre-industrial and control experiments despite a significant conversion of snowfall in the pre-industrial experiment to rainfall in the control experiment, consistent with the changes seen in historical observations. This shift from snowfall to rainfall has profound consequences on water resource management in the Indus Valley, where irrigation is dependent on spring meltwater. Flux decomposition shows that the increase in future precipitation follows directly from the projected moistening of the tropical atmosphere (which increases the moisture flux incident on the western Himalaya by 28%) overpowering the weakened dynamics (which decreases it by 20%). Changes to extreme rainfall events are also examined: it is found that such events may increase significantly in frequency in both future scenarios examined. Two-hour maxima rainfall events that currently occur in 1-in-8 WDs are projected to increase tenfold in frequency in the RCP8.5 scenario; more prolonged (one-week maxima) events are projected to increase fiftyfold

Temozolomide induces senescence but not apoptosis in human melanoma cells

Temozolomide (TMZ), a DNA alkylating agent used in the treatment of melanoma, is believed to mediate its effect by addition of a methyl group to the O6 position of guanine in DNA. Resistance to the agent may be in part due to the activity of O6-methylguanine-DNA methyl transferase (MGMT). In the present study, we show that sensitivity of melanoma cells to TMZ was dependent on their p53 status and levels of MGMT. Analysis of the mechanisms underlying reduced viability showed no evidence for induction of apoptosis even though marked levels of apoptosis was seen in TK6 lymphoma cells. Sensitivity of melanoma cells was associated with p53-dependent G2/M cell cycle arrest and induction of senescence. To verify the role of p53, the assays were repeated in presence of pifithrin-α, an inhibitor of p53. This resulted in increased viability of melanoma cells with wild-type p53 and reversed G2/M cell cycle arrest. Paradoxically, apoptosis was increased in melanoma but decreased as expected in TK6 lymphoma cells. These results are consistent with the view that TMZ is relatively ineffective against melanoma due to defective apoptotic signalling resulting from activation of p53. The nature of the defects in apoptotic signalling remains to be explored