The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins.

Laminin-111 (Ln-1), an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells (MECs), dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks., thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7 to 1.8, whereas laminin-111 in neutral buffers formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation. These findings support that the microstructure of Ln-1 networks in the basement membrane regulates mammary epithelial cell function.

The causes of spatiotemporal variations in erupted fluxes and compositions along a volcanic arc.

Decades of study on volcanic arcs have provided insight into the overarching processes that control magmatism, and how these processes manifest at individual volcanoes. However, the causes of ubiquitous and dramatic intra-arc variations in volcanic flux and composition remain largely unresolved. Investigating such arc-scale issues requires greater quantitative comparison of geophysical and geochemical data, linked through sets of common intensive variables. To work towards these goals, we use observed lava compositions to estimate the heat budget associated with Quaternary volcanism in the Cascades Arc and compare this to the heat required to produce the observed geophysical properties of the crust. Here we show that along-strike volcanic variability in the Quaternary Cascades Arc is primarily related to variations in the flux of basalt into the crust, rather than variations in their crustal storage history. This approach shows promise for studying other large-scale frontier geologic problems in volcanic arcs.

Phonon Spectroscopy with Chirped Shear and Compressive Acoustic Pulses.

Picosecond duration compressive and shear phonon wave packets injected into (311) GaAs slabs transform after propagation through ∼1 mm into chirped acoustic pulses with a frequency increasing in time due to phonon dispersion. By probing the temporal optical response to coherent phonons in a near surface layer of the GaAs slab, we show that phonon chirping opens a transformational route for high-sensitivity terahertz and subterahertz phonon spectroscopy. Temporal gating of the chirped phonon pulse allows the selection of a narrow band phonon spectrum with a central frequency up to 0.4 THz for longitudinal and 0.2 THz for transverse phonons.

X-ray detection with zinc-blende (cubic) GaN Schottky diodes.

The room temperature X-ray responses as functions of time of two n type cubic GaN Schottky diodes (200 µm and 400 µm diameters) are reported. The current densities as functions of time for both diodes showed fast turn-on transients and increases in current density when illuminated with X-ray photons of energy up to 35 keV. The diodes were also electrically characterized: capacitance, implied depletion width and dark current measurements as functions of applied bias at room temperature are presented. At -5 V reverse bias, the capacitances of the diodes were measured to be (84.05 ± 0.01) pF and (121.67 ± 0.02) pF, respectively. At -5 V reverse bias, the dark current densities of the diodes were measured to be (347.2 ± 0.4) mA cm(-2) and (189.0 ± 0.2) mA cm(-2), respectively. The Schottky barrier heights of the devices (0.52 ± 0.07) eV and (0.63 ± 0.09) eV, respectively, were extracted from the forward dark current characteristics.

Long-term exposure to outdoor air pollution and the incidence of chronic obstructive pulmonary disease in a national English cohort.

OBJECTIVES: The role of outdoor air pollution in the incidence of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated this question using a large, nationally representative cohort based on primary care records linked to hospital admissions. METHODS: A cohort of 812 063 patients aged 40-89 years registered with 205 English general practices in 2002 without a COPD diagnosis was followed from 2003 to 2007. First COPD diagnoses recorded either by a general practitioner (GP) or on admission to hospital were identified. Annual average concentrations in 2002 for particulate matter with an aerodynamic diameter <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), ozone and sulfur dioxide (SO2) at 1 km(2) resolution were estimated from emission-based dispersion models. Hazard ratios (HRs) per interquartile range change were estimated from Cox models adjusting for age, sex, smoking, body mass index and area-level deprivation. RESULTS: 16 034 participants (1.92%) received a COPD diagnosis from their GP and 2910 participants (0.35%) were admitted to hospital for COPD. After adjustment, HRs for GP recorded COPD and PM10, PM2.5 and NO2 were close to unity, positive for SO2 (HR=1.07 (95% CI 1.03 to 1.11) per 2.2 µg/m(3)) and negative for ozone (HR=0.94 (0.89 to 1.00) per 3 µg/m(3)). For admissions HRs for PM2.5 and NO2 remained positive (HRs=1.05 (0.98 to 1.13) and 1.06 (0.98 to 1.15) per 1.9 µg/m(3) and 10.7 µg/m(3), respectively). CONCLUSIONS: This large population-based cohort study found limited, inconclusive evidence for associations between air pollution and COPD incidence. Further work, utilising improved estimates of air pollution over time and enhanced socioeconomic indicators, is required to clarify the association between air pollution and COPD incidence.

High-frequency acousto-optic effects in Bragg reflectors.

Picosecond acoustic interferometry was used to study the acousto-optic properties of a distributed Bragg reflector (DBR) manufactured from two immiscible polymers (cellulose acetate and polyvinylcarbyzole). Picosecond strain pulses were injected into the structure and changes in its reflectance were monitored as a function of time. The reflectance exhibited single-frequency harmonic oscillations as the strain pulse traversed the DBR. A transfer matrix method was used to model the reflectance of the DBR in response to interface modulation and photo-elastic effects. This work shows that photo-elastic effects can account for the acousto-optic response of DBRs with acoustically matched layers.

Dynamics of a vertical cavity quantum cascade phonon laser structure.

Driven primarily by scientific curiosity, but also by the potential applications of intense sources of coherent sound, researchers have targeted the phonon laser (saser) since the invention of the optical laser over 50 years ago. Here we fabricate a vertical cavity structure designed to operate as a saser oscillator device at a frequency of 325 GHz. It is based on a semiconductor superlattice gain medium, inside a multimode cavity between two acoustic Bragg reflectors. We measure the acoustic output of the device as a function of time after applying electrical pumping. The emission builds in intensity reaching a steady state on a timescale of order 0.1 µs. We show that the results are consistent with a model of the dynamics of a saser cavity exactly analogous to the models used for describing laser dynamics. We also obtain estimates for the gain coefficient, steady-state acoustic power output and efficiency of the device.

Subterahertz acoustical pumping of electronic charge in a resonant tunneling device.

We demonstrate that controlled subnanosecond bursts of electronic charge can be transferred through a resonant tunneling diode by successive picosecond acoustic pulses. The effect exploits the nonlinear current-voltage characteristics of the device and its asymmetric response to the compressive and tensile components of the strain pulse. This acoustoelectronic pump opens new possibilities for the control of quantum phenomena in nanostructures.

Participation of patients in the development of advanced therapy medicinal products.

An increasing number of advanced therapy medicinal products (ATMPs) are under development and in clinical trials. Patients are central to this progress. In research, patients have funded, catalysed, coordinated and led projects. In regulation, patient groups have contributed to the creation of the political momentum for regulation of ATMPs, contributed to the debate and now participate in the regulatory process. Once licensed, patients will have a role in the pharmacovigilance, health technology assessment and reimbursement arrangements for these products. Patient groups contribute valuably as equal stakeholders at every step of the development of an ATMP.

The patient with haematemesis and melaena.

Bleeding from the upper gastrointestinal (GI) tract is a common medical emergency, with an incidence of between 50-150 cases per 100,000 per year.1 A recent audit by the British Society of Gastroenterology showed the mortality rate from upper GI bleeds has fallen from 14%2 in 1993 to 10% in 2007.3 However, despite the use of proton pump inhibitors (PPIs), admission rates for peptic ulcer haemorrhage have increased in older age groups,4 probably related to increased use of antiplatelet agents such as aspirin and clopidogrel and anticoagulants in acute coronary syndromes, stroke and atrial fibrillation. The rising age of the population may also have offset further reductions in mortality and morbidity that may have otherwise come about through improved supportive and endoscopic care.

Ultrafast strain-induced current in a GaAs Schottky diode.

Picosecond acoustic pulses generated by femtosecond laser excitation of a metal film induce a transient current with subnanosecond rise time in a GaAs/Au Schottky diode. The signal consists of components due to the strain pulse crossing the edge of the depletion layer in the GaAs and also the GaAs/Au interface. A theoretical model is presented for the former and is shown to be in very good agreement with the experiment.

Coherent terahertz sound amplification and spectral line narrowing in a stark ladder superlattice.

The bias voltage applied to a weakly coupled n-doped GaAs/AlAs superlattice increases the amplitude of the coherent hypersound oscillations generated by a femtosecond optical pulse. This bias-induced amplitude increase and experimentally observed spectral narrowing of the superlattice phonon mode with a frequency 441 GHz provides the evidence for hypersound amplification by stimulated emission of phonons in a system where the inversion of the electron populations for phonon-assisted transitions exists.

The use of symptoms to predict colorectal cancer site. Can we reduce the pressure on our endoscopy services?

OBJECTIVE: Our objective was to determine the value of gastrointestinal symptoms and signs in predicting the site of colorectal cancer (CRC). These symptoms can subsequently be used in determining first-line investigation with either sigmoidoscopy or colonoscopy. METHOD: We interrogated the endoscopic and CRC databases ('Infoflex'), for patients diagnosed with CRC between April 2005 and March 2006 inclusive. These patients were cross-referenced with the pathology database and patient records. Information gathered from these databases include: age, gender, symptoms, site of cancer, histology, Duke's grading, blood parameters, diagnostic tool and treatment. RESULTS: One hundred fifty-three patients were diagnosed with CRC between April 2005 and March 2006. One hundred twenty-six were initially seen in the out-patient department, of whom 38 (29%) were right-sided (proximal to the splenic flexure), and 88 (70%) were left-sided (splenic flexure and beyond). Change in bowel habit (diarrhoea and constipation) and rectal bleeding were significantly associated with left-sided cancers (P < 0.0024 and P < 0.0001, respectively). Haemoglobin (P < 0.0001) and mean corpuscular volume (P < 0.0001) were significantly lower in right-sided cancers. Weight loss, pain and obstruction were not associated with cancer site. C-reactive protein, albumin and carcinoembryonic antigen are not predictive of cancer site, Duke's stage or influenced by patient age or gender. DISCUSSION: Symptoms can accurately predict site of cancer, allowing investigations to be tailored accordingly. We would recommend that patients with altered bowel habit and/or rectal bleeding, and no other symptoms, risk factors or anaemia, can be investigated with a flexible sigmoidoscopy to confirm or refute a diagnosis of colorectal cancer.

Antibiotic-resistant Campylobacter: an increasing problem.

The case is described of a 27-year-old woman who presented with an acute diarrhoeal illness. She was initially poorly responsive to antibiotics and developed lymphocytic ascites. Diagnosis was difficult to establish, and peritoneal tuberculosis was considered to be the most likely cause of her symptoms. Serological tests eventually confirmed Campylobacter jejuni infection. Campylobacter is one of the most common bacterial diarrhoeal infections, and complications, except for colitis, are rare except in specific disease states--for example, patients with cirrhosis or undergoing peritoneal dialysis. Antibiotic resistance is an increasing problem, and this may potentially lead to a greater incidence of complications in the future.

Acoustic phonon emission from a weakly coupled superlattice under vertical electron transport: observation of phonon resonance.

We report measurements of acoustic phonon emission from a weakly coupled AlAs/GaAs superlattice (SL) under vertical electron transport. The phonons were detected using superconducting bolometers. A peak (resonance) was observed in emission parallel to the SL growth axis when the electrical energy drop per SL period matched the energy of the first SL mini-Brillouin zone-center phonon mode. This peak was mirrored by an increase of the differential conductance of the SL. These results are evidence for stimulated emission of terahertz phonons as previously predicted theoretically and suggest that such a SL may form the basis of a SASER (sound amplification by stimulated emission of radiation) device.