Erythroid anion transporter assembly is mediated by a developmentally regulated recruitment onto a preassembled membrane cytoskeleton

Analysis of the expression and assembly of the anion transporter by metabolic pulse-chase and steady-state protein and RNA measurements reveals that the extent of association of band 3 with the membrane cytoskeleton varies during chicken embryonic development. Pulse-chase studies have indicated that band 3 polypeptides do not associate with the membrane cytoskeleton until they have been transported to the plasma membrane. At this time, band 3 polypeptides are slowly recruited, over a period of hours, onto a preassembled membrane cytoskeletal network and the extent of this cytoskeletal assembly is developmentally regulated. Only 3% of the band 3 polypeptides are cytoskeletal-associated in 4-d erythroid cells vs. 93% in 10-d erythroid cells and 36% in 15-d erythroid cells. This observed variation appears to be regulated primarily at the level of recruitment onto the membrane cytoskeleton rather than by different transport kinetics to the membrane or differential turnover of the soluble and insoluble polypeptides and is not dependent upon the lineage or stage of differentiation of the erythroid cells. Steady-state protein and RNA analyses indicate that the low levels of cytoskeletal band 3 very early in development most likely result from limiting amounts of ankyrin and protein 4.1, the membrane cytoskeletal binding sites for band 3. As embryonic development proceeds, ankyrin and protein 4.1 levels increase with a concurrent rise in the level of cytoskeletal band 3 until, on day 10 of development, virtually all of the band 3 polypeptides are cytoskeletal bound. After day 10, the levels of total and cytoskeletal band 3 decline, whereas ankyrin and protein 4.1 continue to accumulate until day 18, indicating that the cytoskeletal association of band 3 is not regulated solely by the availability of membrane cytoskeletal binding sites at later stages of development. Thus, multiple mechanisms appear to regulate the recruitment of band 3 onto the erythroid membrane cytoskeleton during chicken embryonic development

Immunological investigations and immunotherapy in lung cancer

This thesis examines the value of immunological methods in the treatment, diagnosis and assessment of prognosis of lung cancer.Delayed hypersensitivity skin tests and laboratory tests of immunological function were performed in patients with operable lung cancer who were then randomly allocated to the autograft or non-autograft groups. In a pilot trial in 15 patients, the autograft group received intradermal injections of autologous irradiated tumour cells and BCG. during three weeks after operation. In this trial only, both groups of patients were given radiotherapy to the mediastinum three weeks after operation. In the subsequent main trial in 83 patients, both groups received one pre¬ operative percutaneous injection of BCG.. The autograft group only were given serial injections of autologous irradiated tumour cells and percutaneous BCG. during the three weeks after operation.While the prevalence of positive tuberculin tests among the lung cancer patients before operation was similar to that of controls, sensitisation after challenge by DNCB. was less common in the lung cancer patients, suggesting that there is some impairment of the afferent limb of the immunological response in this condition. Lymphocyte transformation by PPD. but not PHA. or pokeweed mitogen was depressed. Relative depression of certain immunological tests was seen in patients with more advanced disease and a poorer prognosis (total lymphocytes, DNCB.reactivity) and in squamous cell carcinoma (tuberculin test). The main immunological effect of postoperative immunotherapy was a prolonged increase in tuberculin reactivity.By constructing actuarial life table curves for survival and duration of freedom from tumour recurrence and by measuring the median times for these, it was shown that DNCB. positive autograft group patients and those with stage I tumours had better clinical results than non-autograft patients (p = 0.02 to p = 0.09)« Although a higher proportion of stage I patients in the autograft group survived free of tumour recurrence two years after operation, the difference was not statistically significant. Adjuvant specific autologous immunotherapy thus seemed, at best, to have only a weak therapeutic action in operable lung cancer.In a separate study, circulating levels of tumour markers in unselected lung cancer patients were compared with those of control patients with benign pulmonary disease. Elevated levels of carcinoembryonic antigen (CEA.) were found in 17%» of pregnancy-associated a^-glycoprotein (a^-PAG.) in 16%, of casein in 1 b°/o, of human chorionic gonadotrophin in 6°/o and of a-foetoprotein in 1.5%• CEA. levels were higher in patients with extensive disease (23%) • There was discordance between raised levels of CEA. and a^-PAG.. Elevated levels of one or more markers were found in kG'/o of patients in whom four or more markers were measured. In a different series of unselected lung cancer patients, circulating levels of immunoreactive ACTH. were raised in 2k°/o of patients with small cell carcinoma but only in 3°/° of patients with non-small cell carcinoma. Elevated levels were commoner in small cell carcinoma patients with extensive disease.The results showed that when the upper limit of "normal" was that of patients with benign pulmonary disease, the prevalence of elevated levels of tumour markers was much lower than that claimed by other authors. Hence measurement of these markers is of little or no diagnostic value in lung cancer

GEMPAK: An arbitrary aircraft geometry generator

A computer program, GEMPAK, has been developed to aid in the generation of detailed configuration geometry. The program was written to allow the user as much flexibility as possible in his choices of configurations and the detail of description desired and at the same time keep input requirements and program turnaround and cost to a minimum. The program consists of routines that generate fuselage and planar-surface (winglike) geometry and a routine that will determine the true intersection of all components with the fuselage. This paper describes the methods by which the various geometries are generated and provides input description with sample input and output. Also included are descriptions of the primary program variables and functions performed by the various routines. The FORTRAN program GEMPAK has been used extensively in conjunction with interfaces to several aerodynamic and plotting computer programs and has proven to be an effective aid in the preliminary design phase of aircraft configurations

Wall-temperature effects on the aerodynamics of a hydrogen-fueled transport concept in Mach 8 blowdown and shock tunnels

Results are presented from two separate tests on the same blended wing-body hydrogen fueled transport model at a Mach number of about 8 and a range of Reynolds numbers (based on theoretical body length) of 0.597 x 10 to the 6th power to about 156.22 x 10 to the 6th power. Tests were made in conventional hypersonic blowdown tunnel and a hypersonic shock tunnel at angles of attack of -2 deg to about 8 deg, with an extensive study made at a constant angle of attack of 3 deg. The model boundary-layer flow varied from laminar at the lower Reynolds numbers to predominantly turbulent at the higher Reynolds numbers. Model wall temperatures and stream static temperatures varied widely between the two tests, particularly at the lower Reynolds numbers. These temperature differences resulted in marked variations of the axial-force coefficients between the two tests, due in part to the effects of induced pressure and viscous interaction variations. The normal-force coefficient was essentially independent of Reynolds number. Analysis of results utilized current theoretical computer programs and basic boundary-layer theory

The Oyster River Culvert Analysis Project

Studies have already detected intensification of precipitation events consistent with climate change projections. Communities may have a window of opportunity to prepare, but information sufficiently quantified and localized to support adaptation programs is sparse: published literature is typically characterized by general resilience building or regional vulnerability studies. The Fourth Assessment Report of the IPCC observed that adaptation can no longer be postponed pending the effective elimination of uncertainty. Methods must be developed that manage residual uncertainty, providing community leaders with decision-support information sufficient for implementing infrastructure adaptation programs. This study developed a local-scale and actionable protocol for maintaining historical risk levels for communities facing significant impacts from climate change and population growth. For a coastal watershed, the study assessed the capacity of the present stormwater infrastructure capacity for conveying expected peak flow resulting from climate change and population growth. The project transferred coupled-climate model projections to the culvert system, in a form understandable to planners, resource managers and decision-makers; applied standard civil engineering methods to reverse-engineer culverts to determine existing and required capacities; modeled the potential for LID methods to manage peak flow in lieu of, or combination with, drainage system upsizing; and estimated replacement costs using local and national construction cost data. The mid-21st century, most likely 25-year, 24-hour precipitation is estimated to be 35% greater than the TP-40 precipitation for the SRES A1b trajectory, and 64% greater than the TP-40 value for the SRES A1fi trajectory. 5% of culverts are already undersized for the TP-40 event to which they should have been designed. Under the most likely A1b trajectory, an additional 12% of culverts likely will be undersized, while under the most likely A1fi scenario, an additional 19% likely will be undersized. These conditions place people and property at greater risk than that historically acceptable from the TP-4025-year design storm. This risk level may be maintained by a long-term upgrade program, utilizing existing strategies to manage uncertainty and costs. At the upper-95% confidence limit for the A1fi 25-year event, 65% of culverts are adequately sized, and building the remaining 35%, and planned, culverts to thrice the cross-sectional area specified from TP-40 should provide adequate capacity through this event. Realizable LID methods can mitigate significant impacts from climate change and population growth, however effectiveness is limited for the more pessimistic climate change projections. Results indicate that uncertainty in coupled-climate model projections is not an impediment to adaptation. This study makes a significant contribution toward the generation of reliable and specific estimates of impacts from climate change, in support of programs to adapt civil infrastructures. This study promotes a solution to today\u27s arguably most significant challenge in civil infrastructure adaptation: translating the extensive corpus of adaptation theory and regional-scale impacts analyses into localscale action

The Role of Monopoles for Color Confinement

We study the role of the monopole for color confinement by using the monopole current system. For the self-energy of the monopole current less than ln$(2d-1)$, long and complicated monopole world-lines appear and the Wilson loop obeys the area law, and therefore the monopole current system almost reproduces essential features of confinement properties in the long-distance physics. In the short-distance physics, however, the monopole-current theory would become nonlocal due to the monopole size effect. This monopole size would provide a critical scale of QCD in terms of the dual Higgs mechanism.Comment: 3 pages LaTeX, 3 figures, uses espcrc2.sty, Talk presented at lattice97, Edinburgh, Scotland, July. 199

Loop Action for Lattice U(1) Gauge Theory

It is showed that the very recently introduced Lagrangian $loop$ formulation of the lattice Maxwell theory is equivalent to the Villain form in 2+1 dimensions. A transparent description of the classical $loop$ action is given in pure geometrical terms for the $2+1$ and $3+1$ dimensional cases