Optimal Alignment Sensing of a Readout Mode Cleaner Cavity

Critically coupled resonant optical cavities are often used as mode cleaners in optical systems to improve the signal to noise ratio (SNR) of a signal that is encoded as an amplitude modulation of a laser beam. Achieving the best SNR requires maintaining the alignment of the mode cleaner relative to the laser beam on which the signal is encoded. An automatic alignment system which is primarily sensitive to the carrier field component of the beam will not, in general, provide optimal SNR. We present an approach that modifies traditional dither alignment sensing by applying a large amplitude modulation on the signal field, thereby producing error signals that are sensitive to the signal sideband field alignment. When used in conjunction with alignment actuators, this approach can improve the detected SNR; we demonstrate a factor of 3 improvement in the SNR of a kilometer-scale detector of the Laser Interferometer Gravitational-wave Observatory. This approach can be generalized to other types of alignment sensors

Effects of oncogenic Ras and p38 mitogen-activated protein kinase on the adhesion of normal human cells

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2010.Vita. Cataloged from PDF version of thesis.Includes bibliographical references.Activating mutations in RAS oncogenes commonly arise in human cancers. However, in experimental settings, oncogenic RAS has most often been studied at supraphysiological levels of expression. Importantly, work by others showed that the response of murine cells to expression of oncogenic ras from the endogenous promoter is strikingly different from the response of both human and murine cells to high levels of ectopically expressed oncogenic RAS. Thus, to study the outcome of oncogenic Ras signaling in human cells at a more physiological level, I developed a system in which I could activate oncogenic Ras signaling to either low or high extents in normal human fibroblasts. A low level of oncogenic Ras signaling induced cellular hyperproliferation, whereas a high level of signaling induced cellular senescence. A growing body of literature links loss of p38 mitogen-activated protein kinase (MAPK) activity with the promotion of Ras-induced transformation in murine cells. Accordingly, I examined the effect of inhibiting p38 in normal human cells in which I also activated a low level of oncogenic Ras signaling. Interestingly, the inhibition of p38 cooperated with low activation of oncogenic Ras to alter the morphology and adhesive properties of cells. My results suggest that the inhibition of p38 could predispose human cells to partial transformation by oncogenic Ras through alterations in cellular adhesion.by Lynne K. Waldman.Ph.D

Harvest and habitats of Atlantic sturgeon Acipenser oxyrinchus Mitchill, 1815 in the Hudson River estuary: Lessons for sturgeon conservation

Conservation of the Hudson River population of the sturgeon Acipenser oxyrinchus Mitchill, 1815 has benefitted from the most intensive research programme on any population of the species. We review the history of the fishery for A. oxyrinchus in the Hudson River, and concisely summarise diverse research findings on its life history and habitat use. The fishery for A. oxyrinchus from the Hudson River had one period of very high harvest (pre-1900s), a long period (1900-1979) of minimal harvest and slow population recovery, a period (1980-1992) of restored abundance and high harvest, and finally another decline and suspension of fishing (1996). Sturgeon spawning and early juvenile development occurs in the freshwater portion of the Hudson River, whereas adult and large juvenile sturgeon occupy marine waters, and some of these fish will annually occupy low salinity sites in the Hudson River and other coastal rivers in summer. A. oxyrinchus of the Hudson River are genetically distinct from other populations associated with rivers along the Atlantic coast. Eight different habitats are used during the life cycle of Hudson River A. oxyrinchus, and these are described in physical and temporal terms. The history and biology of the Hudson River A. oxyrinchus suggest three lessons for sturgeon restoration: basic life history knowledge is essential, fishery management is difficult, and regular population monitoring will be needed from the start.La conservación de la población del río Hudson de esturión Acipenser oxyrinchus Mitchill, 1815 se ha beneficiado del programa de investigación más intensivo de los proyectados en la preservación de cualquier otra población de la especie. Se revisa aquí la historia de la pesca de A. oxyrinchus en el río Hudson y se resumen concisamente diversos hallazgos de investigación sobre su historia natural y uso del hábitat. La pesca de A. oxyrinchus en el río Hudson tuvo un periodo de muy alta explotación (antes de 1900), un largo periodo de mínima explotación y lenta recuperación poblacional (1900-1979), un periodo de restauración de abundancia y alta explotación (1980-1992) y, finalmente, otro declive y suspensión de la pesca (1996). La puesta del esturión y el desarrollo temprano de los juveniles tienen lugar en el tramo de agua dulce del río Hudson, mientras los adultos y los juveniles grandes ocupan aguas marinas; algunos de estos peces ocuparán anualmente, en verano, lugares de baja salinidad en el Hudson y en otros ríos costeros. La población de A. oxyrinchus del río Hudson es distinta genéticamente de otras poblaciones asociadas con ríos a lo largo de la costa atlántica. Durante su ciclo vital, el A. oxyrinchus del río Hudson utiliza ocho diferentes hábitats, que son descritos en términos físicos y temporales. La historia y la biología de esta especie del río Hudson sugieren tres lecciones para la restauración de los esturiones: es imprescindible el conocimiento básico de la historia natural, la gestión de la pesca es difícil y el seguimiento regular de la población será necesario desde el principio.Instituto Español de Oceanografí

Carbon-poor stellar cores as supernova progenitors

Exploring stellar models which ignite carbon off-center (in the mass range of about 1.05 - 1.25 Msun, depending on the carbon mass fraction) we find that they may present an interesting SN I progenitor scenario, since whereas in the standard scenario runaway always takes place at the same density of about 2 X 10^9 gr/cm^3, in our case, due to the small amount of carbon ignited, we get a whole range of densities from 1 X 10^9 up to 6 X 10^9 gr/cm^3. These results could contribute in resolving the emerging recognition that at least some diversity among SNe I exists, since runaway at various central densities is expected to yield various outcomes in terms of the velocities and composition of the ejecta, which should be modeled and compared to observations.Comment: 49 pages, 20 figure

Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.

Background: The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8+, but not CD4+, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice. Here, the cancer vaccine Ad5-GUCY2C-PADRE was evaluated in a first-in-man phase I clinical study of patients with early-stage colorectal cancer to assess its safety and immunological efficacy. Methods: Ten patients with surgically-resected stage I or stage II (pN0) colon cancer received a single intramuscular injection of 1011 viral particles (vp) of Ad5-GUCY2C-PADRE. Safety assessment and immunomonitoring were carried out for 6 months following immunization. This trial employed continual monitoring of both efficacy and toxicity of subjects as joint primary outcomes. Results: All patients receiving Ad5-GUCY2C-PADRE completed the study and none developed adverse events greater than grade 1. Antibody responses to GUCY2C were detected in 10% of patients, while 40% exhibited GUCY2C-specific T-cell responses. GUCY2C-specific responses were exclusively CD8+ cytotoxic T cells, mimicking pre-clinical studies in mice in which GUCY2C-specific CD4+ T cells are eliminated by self-tolerance, while CD8+ T cells escape tolerance and mediate antitumor immunity. Moreover, pre-existing neutralizing antibodies (NAbs) to the Ad5 vector were associated with poor vaccine-induced responses, suggesting that Ad5 NAbs oppose GUCY2C immune responses to the vaccine in patients and supported by mouse studies. Conclusions: Split tolerance to GUCY2C in cancer patients can be exploited to safely generate antigen-specific cytotoxic CD8+, but not autoimmune CD4+, T cells by Ad5-GUCY2C-PADRE in the absence of pre-existing NAbs to the viral vector. TRIAL REGISTRATION: This trial (NCT01972737) was registered at ClinicalTrials.gov on October 30th, 2013. https://clinicaltrials.gov/ct2/show/NCT01972737

Future policy implications of tidal energy array interactions

Tidal stream energy technology has progressed to a point where commercial exploitation of this sustainable resource is practical, but tidal physics dictates interactions between tidal farms that raise political, legal and managerial challenges that are yet to be met. Fully optimising the design of a turbine array requires its developer to know about other farms that will be built nearby in the future. Consequently future developments, even those in adjacent channels, have the potential to impact on project efficiency. Here we review the relevant physics, consider the implications for marine policy, and discuss potential solutions. Possible management paths range from minimal regulation to prioritise a free market, to strongly interventionist approaches that prioritise efficient resource use. An attractive exemplar of the latter is unitization, an approach to resource allocation widely used in the oil and gas industry. We argue that an interventionist approach is necessary if the greatest possible energy yield is to be produced for a given level of environmental impact

Longitudinal Profiles of Girls' Irritable, Defiant and Antagonistic Oppositional Symptoms: Evidence for Group Based Differences in Symptom Severity

Three subdimensions of ODD symptoms have been proposed -angry/irritable (IR), argumentative/defiant (DF) and antagonism (AN). This study tested whether longitudinal symptom trajectories could be identified by these subdimensions. Group-based trajectory analysis was used to identify developmental trajectories of IR, DF and AN symptoms. Multi-group trajectory analysis was then used to identify how subdimension trajectories were linked together over time. Data were drawn from the Pittsburgh Girls Study (PGS; N = 2450), an urban community sample of girls between the ages of five--eight at baseline. We included five waves of annual data across ages five-13 to model trajectories. Three trajectories were identified for each ODD subdimension: DF and AN were characterized by high, medium and low severity groups; IR was characterized by low, medium stable, and high increasing groups. Multi-trajectory analysis confirmed these subdimensions were best linked together based on symptom severity. We did not identify girls' trajectory groups that were characterized predominantly by a particular subdimension of ODD symptoms. Membership in more severe symptom groups was significantly associated with worse outcomes five years later. In childhood and early adolescence girls with high levels of ODD symptoms can be identified, and these youth are characterized by a persistently elevated profile of IR, DF and AN symptoms. Further studies in clinical samples are required to examine the ICD-10 proposal that ODD with irritability is a distinct or more severe form of ODD

Endovascular treatment of renal artery thrombosis caused by umbilical artery catheterization

AbstractRenal arterial thrombosis, usually in association with aortic thrombosis, has been reported as a result of prolonged neonatal umbilical artery catheterization. A case of renal artery thrombosis attributable to umbilical artery catheterization, resulting in malignant renovascular hypertension, in a 15-day-old neonate, treated by catheter-directed thrombolysis through the involuting umbilical artery, was studied. Resolution of systemic hypertension and partial return of right renal function followed rapid thrombus dissolution. (J Vasc Surg 1998;28:949-53.