Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

A Fast Neural Network Approach to Predict Lung Tumor Motion during Respiration for Radiation Therapy Applications

During radiotherapy treatment for thoracic and abdomen cancers, for example, lung cancers, respiratory motion moves the target tumor and thus badly affects the accuracy of radiation dose delivery into the target. A real-time image-guided technique can be used to monitor such lung tumor motion for accurate dose delivery, but the system latency up to several hundred milliseconds for repositioning the radiation beam also affects the accuracy. In order to compensate the latency, neural network prediction technique with real-time retraining can be used. We have investigated real-time prediction of 3D time series of lung tumor motion on a classical linear model, perceptron model, and on a class of higher-order neural network model that has more attractive attributes regarding its optimization convergence and computational efficiency. The implemented static feed-forward neural architectures are compared when using gradient descent adaptation and primarily the Levenberg-Marquardt batch algorithm as the ones of the most common and most comprehensible learning algorithms. The proposed technique resulted in fast real-time retraining, so the total computational time on a PC platform was equal to or even less than the real treatment time. For one-second prediction horizon, the proposed techniques achieved accuracy less than one millimeter of 3D mean absolute error in one hundred seconds of total treatment time

Simulating North American Weather Types With Regional Climate Models

Regional climate models (RCMs) are able to simulate small-scale processes that are missing in their coarser resolution driving data and thereby provide valuable climate information for climate impact assessments. Less attention has been paid to the ability of RCMs to capture large-scale weather types (WTs). An inaccurate representation of WTs can result in biases and uncertainties in current and future climate simulations that cannot be easily detected by standard model evaluation metrics. Here we define 12 hydrologically important WTs in the contiguous United States (CONUS). We test if RCMs from the North American CORDEX (NA-CORDEX) and the Weather Research and Forecasting (WRF) model large physics ensembles (WRF36) can capture those WTs in the current climate and how they simulate changes in the future. Our results show that the NA-CORDEX RCMs are able to simulate WTs more accurately than members of the WRF36 ensemble. The much larger WRF36 domain in combination with not constraining large-scale conditions by spectral nudging results in lower WT skill. The selection of the driving global climate model (GCM) has a large effect on the skill of NA-CORDEX simulations but a smaller impact on the WRF36 runs. The formulation of the RCM is of minor importance except for capturing the variability within WTs. Changing the model physics or increasing the RCM horizontal grid spacing has little effect. These results highlight the importance of selecting GCMs with accurate synoptic-scale variability for downscaling and to find a balance between large domains that can result in biased WT representations and small domains that inhibit the realistic development of mesoscale processes. At the end of the century, monsoonal flow conditions increase systematically by up to 30% and a WT that is a significant source of moisture for the Northern Plains during the growing seasons decreases systematically up to –30%

Seasonality, intensity, and duration of rainfall extremes change in a warmer climate

Precipitation extremes are expected to intensify under climate change with consequent impacts in flooding and ecosystem functioning. Here we use station data and high‐resolution simulations from the WRF convection permitting climate model (∼4 km, 1 h) over the US to assess future changes in hourly precipitation extremes. It is demonstrated that hourly precipitation extremes and storm depths are expected to intensify under climate change and what is now a 20‐year rainfall will become a 7‐year rainfall on average for ∼ 75% of gridpoints over the US. This intensification is mostly expressed as an increase in rainfall tail heaviness. Statistically significant changes in the seasonality and duration of rainfall extremes are also exhibited over ∼ 95% of the domain. Our results suggest more non‐linear future precipitation extremes with shorter spell duration that are distributed more uniformly throughout the year

Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells), placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3) and abnormal (n = 9) pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.</p

A survey on the challenges, limitations, and opportunities of online testing of infants and young children during the COVID-19 pandemic: using our experiences to improve future practices

In developmental psychology, the widespread adoption of new methods for testing children does not typically occur over a matter of months. Yet, the COVID-19 pandemic and its associated social distancing requirements created a sudden need among many research groups to use a new method with which they had little or no experience: online testing. Here, we report results from a survey of 159 researchers detailing their early experiences with online testing. The survey approach allowed us to create a general picture of the challenges, limitations, and opportunities of online research, and it identified aspects of the methods that have the potential to impact interpretations of findings. We use the survey results to present considerations to improve online research practices

Climate change projections of the North American Regional Climate Change Assessment Program (NARCCAP)

We investigate major results of the NARCCAP multiple regional climate model (RCM) experiments driven by multiple global climate models (GCMs) regarding climate change for seasonal temperature and precipitation over North America. We focus on two major questions: How do the RCM simulated climate changes differ from those of the parent GCMs and thus affect our perception of climate change over North America, and how important are the relative contributions of RCMs and GCMs to the uncertainty (variance explained) for different seasons and variables? The RCMs tend to produce stronger climate changes for precipitation: larger increases in the northern part of the domain in winter and greater decreases across a swath of the central part in summer, compared to the four GCMs driving the regional models as well as to the full set of CMIP3 GCM results. We pose some possible process-level mechanisms for the difference in intensity of change, particularly for summer. Detailed process-level studies will be necessary to establish mechanisms and credibility of these results. The GCMs explain more variance for winter temperature and the RCMs for summer temperature. The same is true for precipitation patterns. Thus, we recommend that future RCM-GCM experiments over this region include a balanced number of GCMs and RCMs