Congenital Diaphragmatic hernia – a review

Congenital Diaphragmatic hernia (CDH) is a condition characterized by a defect in the diaphragm leading to protrusion of abdominal contents into the thoracic cavity interfering with normal development of the lungs. The defect may range from a small aperture in the posterior muscle rim to complete absence of diaphragm. The pathophysiology of CDH is a combination of lung hypoplasia and immaturity associated with persistent pulmonary hypertension of newborn (PPHN) and cardiac dysfunction. Prenatal assessment of lung to head ratio (LHR) and position of the liver by ultrasound are used to diagnose and predict outcomes. Delivery of infants with CDH is recommended close to term gestation. Immediate management at birth includes bowel decompression, avoidance of mask ventilation and endotracheal tube placement if required. The main focus of management includes gentle ventilation, hemodynamic monitoring and treatment of pulmonary hypertension followed by surgery. Although inhaled nitric oxide is not approved by FDA for the treatment of PPHN induced by CDH, it is commonly used. Extracorporeal membrane oxygenation (ECMO) is typically considered after failure of conventional medical management for infants ≥ 34 weeks’ gestation or with weight >2 kg with CDH and no associated major lethal anomalies. Multiple factors such as prematurity, associated abnormalities, severity of PPHN, type of repair and need for ECMO can affect the survival of an infant with CDH. With advances in the management of CDH, the overall survival has improved and has been reported to be 70-90% in non-ECMO infants and up to 50% in infants who undergo ECMO

STATUS OF THE VIRGO EXPERIMENT RID B-5375-2009 RID A-1920-2008

The VIRGO experiment was approved in September 1993. The goal of the French-Italian collaboration is to detect gravitational waves using a 3 km arm-length Michelson interferometer. The construction of this detector, which will be installed in Pisa, is under way. The experiment is planned to take data, in a large bandwidth (10 Hz-10 kHz), at the beginning of the year 2000 with nominal sensitivity close to h = 3 X 10-(23)/root Hz. The motivations, detection principle, main sources of noise and status of the experiment are presented

Status of the VIRGO experiment

The Virgo detector will be a 3 km long interferometer antenna with a design sensitivity aiming at the direct observation of gravitational waves. The construction of this detector which will be installed near Pisa is under way. The data taking should start in year 2000 with a design sensitivity dose to (h) over tilde similar or equal to 10(-23) Hz(-1/2). The motivations, detector principle, main sources of noise and status of the experiment are presented

Status of the VIRGO experiment RID B-5375-2009 RID A-1920-2008

The Virgo detector will be a 3 km long interferometer antenna with a design sensitivity aiming at the direct observation of gravitational waves. The construction of this detector which will be installed near Pisa is under way. The data taking should start in year 2000 with a design sensitivity dose to (h) over tilde similar or equal to 10(-23) Hz(-1/2). The motivations, detector principle, main sources of noise and status of the experiment are presented

RasGRP1 opposes proliferative EGFR–SOS1–Ras signals and restricts intestinal epithelial cell growth

The character of EGFR signals can influence cell fate but mechanistic insights into intestinal EGFR-Ras signalling are limited. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of EGFR but act in functional opposition. RasGRP1 is expressed in intestinal crypts where it restricts epithelial growth. High RasGRP1 expression in colorectal cancer (CRC) patient samples correlates with a better clinical outcome. Biochemically, we find that RasGRP1 creates a negative feedback loop that limits proliferative EGFR–SOS1–Ras signals in CRC cells. Genetic Rasgrp1 depletion from mice with either an activating mutation in KRas or with aberrant Wnt signalling due to a mutation in Apc resulted in both cases in exacerbated Ras–ERK signalling and cell proliferation. The unexpected opposing cell biological effects of EGFR–RasGRP1 and EGFR–SOS1 signals in the same cell shed light on the intricacy of EGFR-Ras signalling in normal epithelium and carcinoma