Proton Compton Scattering from Linearly Polarized Gamma Rays.

Differential cross sections for Compton scattering from the proton have been measured at scattering angles of 55°, 90°, and 125° in the laboratory frame using quasimonoenergetic linearly (circularly) polarized photon beams with a weighted mean energy value of 83.4 MeV (81.3 MeV). These measurements were performed at the High Intensity Gamma-Ray Source facility at the Triangle Universities Nuclear Laboratory. The results are compared to previous measurements and are interpreted in the chiral effective field theory framework to extract the electromagnetic dipole polarizabilities of the proton, which gives α_{E1}^{p}=13.8±1.2_{stat}±0.1_{BSR}±0.3_{theo},ß_{M1}^{p}=0.2∓1.2_{stat}±0.1_{BSR}∓0.3_{theo} in units of 10^{-4} fm^{3}.

Thermoacoustic Soret separation.

In a fluid mixture in a channel with an axial time-averaged temperature gradient, high-amplitude oscillating flow can greatly increase the axial flux of thermal diffusion (Soret) separation of the components of the mixture. The enhancement occurs when the oscillating lateral temperature gradient greatly exceeds the axial gradient, causing a large oscillating concentration that can be favorably time-phased with the oscillating flow. This process can occur even with a negligible pressure oscillation or with a negligible temperature response to pressure, as is the case in most liquid solutions. The thermal boundary condition imposed by realistic solids on thermoacoustic liquids is imperfect, adding mathematical complications that are absent for typical gases, for which the solid surface is temporally isothermal. Compared with gas mixtures, the high Lewis number in typical liquid solutions reduces the separation flux associated with the time-averaged temperature gradient, but it also reduces the remixing associated with the time-averaged mole-fraction gradient. For large enough channels, the second-law separation efficiency is only slightly reduced from that of steady liquid Soret separation.

High-purity thermoacoustic isotope enrichment.

In a tube many wavelengths long, thermoacoustic separation of a gas mixture can produce very high purities. A flexible wall allows a spatially continuous supply of acoustic power into such a long tube. Coiling the tube and immersing it in a fluid lets a single-wavelength, circulating, traveling pressure wave in the fluid drive all the wavelengths in the tube wall and gas. Preliminary measurements confirm many aspects of the concept with neon ((20)Ne and (22)Ne) and highlight some challenges of practical implementation.

Negative refraction and the spectral filtering of terahertz radiation by a photonic crystal prism.

We demonstrate how micromachined photonic crystals can be used to negatively refract terahertz frequency light. The photonic crystals, which are constructed from conventional dielectric materials, manipulate the incident beam via interaction with their photonic bands. Consequently, we show that different components of a broadband beam incident on the structure may be positively or negatively refracted, depending upon its frequency and that the structure can be used as an effective spectral filter of THz radiation.

Helping the general physician to improve outcomes after PEG insertion: how we changed our practice.

During their careers, most general physicians are involved in the decision-making process for patients that potentially require percutaneous endoscopic gastrostomy (PEG) insertion. However, poor patient selection and less than favourable outcomes are frequently observed in this group. With the aim of identifying and addressing the underlying issues, the PEG service at University Hospital Llandough was radically changed over an eight-year period. The development of a nurse-led pre-assessment service and design of a specific referral form was successful in reducing the number of PEG referrals and consequently the 30-day mortality rate. Furthermore, the educational and training needs of general physicians of all grades regarding the issues surrounding PEG placement were identified and addressed at formal teaching sessions. A combination of these factors has positively impacted on our service, with more appropriate patient selection and a reduced 30-day mortality rate.

Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice.

Different strains of mice have varying susceptibilities to ultraviolet radiation (UV) of wavelength 280-320 nm (UVB) for 50% suppression of systemic contact hypersensitivity (CHS) responses. Prevalence of histamine-staining dermal mast cells in different strains of mice (C57BL/ 6J, DBA/2, BALB/c) correlated directly with their susceptibility to UVB-induced systemic immunosuppression. BALB/c mice carrying Uvs1, a major locus for susceptibility to UV-induced immunosuppression, contained greater numbers of dermal mast cells than BALB/c mice of the same parental origin. Strains of mice that were differentiated on their susceptibility to UVB-induced downregulation of systemic CHS responses were similar in their susceptibility to histamine-induced immunomodulation. Histamine, but not UVB irradiation, decreased systemic CHS responses in mast cell-depleted mice (W f/W f). Reconstitution of the dorsal skin of W f/W f mice with bone marrow-derived mast cell precursors from nonmutant mice rendered the mice susceptible to UVB irradiation for systemic suppression of CHS responses. UVB irradiation did not suppress delayed type hypersensitivity responses to allogeneic spleen cells in W f/W f mice. In contrast, UV irradiation suppressed CHS responses in W f/W f mice when hapten was applied to the irradiated site. This study demonstrates that dermal mast cells are necessary for the induction of systemic suppression of CHS responses by UVB radiation, and suggests that mast cell- derived histamine is one component of this UVB-induced systemic immunosuppression.

The pulse tube and the pendulum.

An inverted pulse tube in which gravity-driven convection is suppressed by acoustic oscillations is analogous to an inverted pendulum that is stabilized by high-frequency vibration of its pivot point. Gravity acts on the gas density gradient arising from the end-to-end temperature gradient in the pulse tube, exerting a force proportional to that density gradient, tending to cause convection when the pulse tube is inverted. Meanwhile, a nonlinear effect exerts an opposing force proportional to the square of any part of the density gradient that is not parallel to the oscillation direction. Experiments show that convection is suppressed when the pulse-tube convection number N(ptc)=omega(2)a(2)DeltaT/T(avg)/[g(alphaD sin theta-L cos theta)] is greater than 1 in slender tubes, where omega is the radian frequency of the oscillations, a is their amplitude, DeltaT is the end-to-end temperature difference, T(avg) is the average absolute temperature, g is the acceleration of gravity, L is the length of the pulse tube and D is its diameter, alpha is about 1.5, and the tip angle theta ranges from 90 degrees for a horizontal tube to 180 degrees for an inverted tube. Theory suggests that the temperature dependence should be DeltaT/T(avg) instead of DeltaT/T(avg).

Thermoacoustic mixture separation with an axial temperature gradient.

The theory of thermoacoustic mixture separation is extended to include the effect of a nonzero axial temperature gradient. The analysis yields a new term in the second-order mole flux that is proportional to the temperature gradient and to the square of the volumetric velocity and is independent of the phasing of the wave. Because of this new term, thermoacoustic separation stops at a critical temperature gradient and changes direction above that gradient. For a traveling wave, this gradient is somewhat higher than that predicted by a simple four-step model. An experiment tests the theory for temperature gradients from 0 to 416 K/m in 50-50 He-Ar mixtures.

A single element of the elastase I enhancer is sufficient to direct transcription selectively to the pancreas and gut.

The elastase I (EI) gene is expressed at high levels in the exocrine pancreas and at lower levels in other regions of the gut. The transcriptional enhancer of the EI gene, from nucleotides -205 to -72, recapitulates the expression of the endogenous gene in transgenic mice; it directs not only pancreatic acinar cell expression of a human growth hormone (hGH) transgene but also expression to the stomach, duodenum, and colon. This pattern of selective expression limited to the gastroenteropancreatic organ system is specified by the A element, one of three functional elements in the EI enhancer. When multimerized, the A element directed expression of a hGH reporter gene selectively to the pancreas, stomach, and intestine in transgenic mice. Immunofluorescent localization of hGH indicated that the A element multimer transgenes were expressed in the acinar cells of the pancreas as well as in Brunner's gland cells of the duodenum. The A element binds a pancreatic acinar cell-specific factor, PTF1. Our results show that while the A element is responsible for directing tissue and cell type specificity, other elements of the enhancer must be involved in the regulation of the level of gene expression.

Cooperation between elements of an organ-specific transcriptional enhancer in animals.

The elastase I gene enhancer that specifies high levels of pancreatic transcription comprises three functional elements (A, B, and C). When assayed individually in transgenic mice, homomultimers of A are acinar cell specific, those of B are islet specific, and those of C are inactive. To determine how the elements interact in the elastase I enhancer and to investigate further the role of the C element, we have examined the activity of the three possible combinations of synthetic double elements in transgenic animals. Combining the A and B elements reconstitutes the exocrine plus endocrine specificity of the intact enhancer with an increased activity in acinar cells compared with that in the A homomultimer. The B element therefore plays a dual role: in islet cells it is capable of activating transcription, whereas in acinar cells it is inactive alone but greatly augments the activity specified by the A element. The C element augments the activity of either the A or B element without affecting their pancreatic cell type specificity. The roles of each element were verified by examining the effects of mutational inactivation of each element within the context of the elastase I enhancer. These results demonstrated that when tested in animals, the individual enhancer elements can perform discrete, separable functions that combine additively for cell type specificity and cooperatively for the overall strength of a multielement stage- and site-specific transcriptional enhancer.

The rat elastase I regulatory element is an enhancer that directs correct cell specificity and developmental onset of expression in transgenic mice.

A total of 134 base pairs of the 5' flanking sequence of the elastase I gene is sufficient and necessary to direct expression of the passive human growth hormone gene (hGH) to the exocrine pancreas. We demonstrate that this elastase I regulatory region contains a transcriptional enhancer which directs acinar cell-specific expression in transgenic animals. The elastase I enhancer specifies correct expression of the linked hGH gene in an orientation- and position-independent manner and can activate a heterologous promoter. The enhancer also directs the appropriate temporal activation of the hGH gene in the developing pancreas. Transcription is initiated correctly for the elastase I or hGH promoter, and the transcripts are correctly processed regardless of the enhancer position within or outside the fusion gene. The elastase I enhancer generates coincident DNase I-hypersensitive sites in pancreatic chromatin when moved 3 kilobases upstream or within the first intron of the hGH gene and when associated with the hGH promoter.

An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2).

HOX proteins and some orphan homeodomain proteins form complexes with either PBX or MEIS subclasses of homeodomain proteins. This interaction can increase the binding specificity and transcriptional effectiveness of the HOX partner. Here we show that specific members of both PBX and MEIS subclasses form a multimeric complex with the pancreatic homeodomain protein PDX1 and switch the nature of its transcriptional activity. The two activities of PDX1 are exhibited through the 10-bp B element of the transcriptional enhancer of the pancreatic elastase I gene (ELA1). In pancreatic acinar cells the activity of the B element requires other elements of the ELA1 enhancer; in beta-cells the B element can activate a promoter in the absence of other enhancer elements. In acinar cell lines the activity is mediated by a complex comprising PDX1, PBX1b, and MRG1 (MEIS2). In contrast, beta-cell lines are devoid of PBX1b and MRG1, so that a trimeric complex does not form, and the beta-cell-type activity is mediated by PDX1 without PBX1b and MRG1. The presence of specific nuclear isoforms of PBX and MEIS is precisely regulated in a cell-type-specific manner. The beta-cell-type activity can be detected in acinar cells if the B element is altered to retain binding of PDX1 but prevent binding of the PDX1-PBX1b-MRG1 complex. These observations suggest that association with PBX and MEIS partners controls the nature of the transcriptional activity of the organ-specific PDX1 transcription factor in exocrine versus endocrine cells.

Coeliac disease and primary hyperparathyroidism: an association?

Primary hyperparathyroidism may present with non-specific symptoms, and this may be one reason why patients with coeliac disease fail to improve despite compliance with a gluten-free diet. Seven case reports of primary hyperparathyroidism due to sporadic adenoma occurring in a series of 310 patients with coeliac disease are presented, highlighting the importance of looking for this condition in this population group. A prevalence of primary hyperparathyroidism of 2.3% in this series suggests a significant association between hyperparathyroidism and coeliac disease; most studies have indicated a prevalence of 3 in 1000 in the general population, although one study found that it may be as high as 21 in 1000 in women aged 55-75 years. The average age of patients in our series was 59 years and all but one were women. Further studies are needed to establish a possible association between primary hyperparathyroidism and coeliac disease.

Does endoscopy diagnose early gastrointestinal cancer in patients with uncomplicated dyspepsia?

BACKGROUND: Recent guidelines from NICE have proposed that open access gastroscopy is largely limited to patients with "alarm" symptoms. AIMS AND METHODS: This study reviewed the outcome of all our patients with verified oesophageal or gastric carcinoma who presented with uncomplicated dyspepsia to see if endoscopic investigation is warranted in this group. All patients with histologically verified upper gastrointestinal (GI) cancers who presented over a period from 1998 to 2002 were identified. Their presenting symptoms, treatment, and outcome were analysed. RESULTS: 228 upper GI cancers (119 oesophageal, 109 gastric; mean age 72 years (29-99 years); 130 male, 82 female) were identified in 11 145 endoscopies performed. Only 14 patients (6.2%) presented without alarm symptoms; three patients were under 55 years of age and all had gastric carcinoma-one of these had chronic diarrhoea only. Eleven had dyspepsia or reflux symptoms only, and two were under surveillance for Barrett's oesophagus. Only five patients had a curative surgical resection and are still alive two-six years from diagnosis. A sixth patient had a curative operation but died of a cerebrovascular accident one year later. The remaining eight patients unfortunately had either metastatic disease or comorbidity, which precluded surgery. All of these died within two years of diagnosis, mean survival 10 months. CONCLUSION: Only five patients with dyspepsia and no alarm symptoms had resectable upper GI malignancies over a four year period. Limiting open access gastroscopy to those with alarm features only would "miss" a small number of patients who have curable upper GI malignancy.

Biodegradability of polymers in the environment: complexities and significance of definitions and measurements.

There is a world-wide research effort to develop biodegradable polymers as a waste-management option for polymers in the environment. This effort may prove to be fruitless unless we can agree on a definition and test protocols--what do we expect biodegradable polymers to do in the environment and how do we demonstrate that they do what we expect? Establishing a definition and test protocols is not trivial; the task is made complex by the wide range of disciplines involved directly in or interested in the subject, including polymer scientists, biochemists, environmentalists, legislators, and laypeople, all with their own perspectives and expectations. In this paper, I present arguments in favor of biodegradable polymers and indicate what remains to be done to satisfy detractors that they represent a viable option for polymer waste-management.

Analysis of transcriptional regulatory regions in vivo.

Understanding the transcriptional regulation of development and tissue-specific gene expression is a central goal of modern biology. Although the analysis of gene transcription in transfected cultured cells has been essential in establishing many key aspects of this gene control, only analysis in animals can determine developmental timing and cell-specificity of expression within a complex organ and in all the tissues of an animal. The advent of transgenesis made in vivo studies possible. A summary of the in vivo regulatory properties of the pancreas-specific transcriptional enhancer of the rat elastase 1 gene (ELA1) and the role individual elements in this enhancer play in directing high level, cell-specific transcription illustrates the nature, revelations and limitations of transgenic analysis.

Ultraviolet B-induced suppression of immune responses in interleukin-4-/- mice: relationship to dermal mast cells.

Ultraviolet B radiation is immunosuppressive by multiple mechanisms. In interleukin-4-/- mice, ultraviolet B radiation was not able to suppress delayed-type hypersensitivity or contact hypersensitivity responses when the sensitizing antigen was applied to nonirradiated sites. In contrast, ultraviolet B significantly suppressed contact hypersensitivity responses to haptens applied to irradiated sites in interleukin-4-/- mice. In mast cell depleted Wf/Wf mice, ultraviolet B radiation also significantly suppressed contact hypersensitivity responses to sensitizing antigens applied to irradiated but not to unirradiated sites. In both interleukin-4-/- mice and Wf/Wf mice, the mast cell product, histamine, was immunosuppressive implicating mast cells as the dysfunctional cell in interleukin-4-/- mice. The prevalence of dermal mast cells was similar in wild-type and interleukin-4-/- mice. Dermal mast cells of interleukin-4-/- mice, however, express very low levels of c-kit and did not significantly degranulate in response to ultraviolet B. Ultraviolet radiation induced significant and similar levels of serum interleukin-10 in wild-type and interleukin-4-/- mice. We conclude that interleukin-4 indirectly affects ultraviolet B suppression of contact hypersensitivity and delayed-type hypersensitivity responses to sensitizing antigens applied at sites other than those irradiated by providing a critical differentiative signal for dermal mast cells. This study further emphasizes the central role of mast cells in the initial processes by which ultraviolet B radiation is immunomodulatory for immune responses to sensitizing antigens applied to nonirradiated sites.

Survival of rabbit limbal stem cell allografts.

Failure of a specialized population of corneal epithelial stem cells found in the peripheral cornea and limbus results in ocular surface disease, which may be amenable to treatment by transplantation of limbal tissue. This study was designed to investigate donor limbal stem cell allograft survival in rabbits with ocular surface disease. Rabbits underwent corneal epithelial debridement and limbal ablation to induce ocular surface disease and were then treated by limbal stem cell allotransplantation, by allotransplantation plus topical steroid, or by topical steroid only (n = 7 for each group). Donors and recipients were sex mismatched. Recipients were followed for up to 5 months. Outcome was assessed by daily slit-lamp examination, weekly impression cytology and photographic record, end-point sex chromatin and fluorescent cell tracer analyses, histology, and immunohistochemistry. In no case was a completely normal ocular surface regained, but some animals that received grafts plus corticosteroids fared best by all criteria used. In the absence of immunosuppression, graft hemorrhagia (believed to be a manifestation of graft rejection) occurred within the first month, the cornea became resurfaced with conjunctiva-derived cells, and no donor cells survived centrally in the long term. Topical corticosteroids reduced the number and severity of these episodes significantly, and were associated with survival of some donor-derived cells in the central cornea of some grafted animals. Thus, rabbit limbal stem cell allografts appeared to undergo rejection, which could be modified by immunosuppression, but useful regeneration of the ocular surface occurred only where rejection was circumvented.

Assessment of RNA quality by semi-quantitative RT-PCR of multiple regions of a long ubiquitous mRNA.

A simple method to assess the degree of degradation present in a total RNA preparation from cells or tissues is based on the increasing probability of RNA cleavage with increasing length of an RNA molecule. Under ideal conditions, reverse transcription of a particular mRNA species with oligo-dT as the primer generates a population of cDNAs, terminating at the 5' end of the mRNA if all template RNA molecules are intact, or at the first cleavage site 5' to the polyA if some template RNAs are partially degraded. Consequently, for cellular RNA preparations with some degradation, the 5' end of an mRNA is represented in the cDNA population to a lesser extent than the 3' end of the mRNA. We describe a sensitive assay of mRNA quality that compares the relative PCR amplification of 5' and 3' regions of a long and ubiquitous mRNA following oligo-dT-primed reverse transcription.