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The biological effects of near infrared radiation (850 nm) modulated by an acoustic frequency of 101 Hz were studied. The study was conducted on rats; the effect was registered by succinate dehydrogenase activity in lymphocytes in blood smears after the administration of an activating dose of adrenaline, which simulates the state of the organism at early stages of a pathogenic action (stress). A pronounced regulating effect of infrared radiation on the activity of succinate dehydrogenase in animals that were activated by adrenaline was shown. Infrared radiation has a normalizing effect via the reduction of the degree of inhibition or activation of the enzyme induced by adrenaline and has no effect on the control animals. Thus, by modulation of the activity of succinate dehydrogenase, infrared radiation regulates energy production in mitochondria that is provided by the most potent oxidation substrate, viz., succinic acid; the effect is especially pronounced under stress. [ABSTRACT FROM AUTHOR]

Susceptibility to most common cancers is likely to involve interaction between multiple low risk genetic variants. Although there has been great progress in identifying such variants, their effect on phenotype and the mechanisms by which they contribute to disease remain largely unknown. We have developed a mouse melanoma model harboring two mutant oncogenes implicated in human melanoma, CDK4R24C and NRASQ61K. In these mice, tumors arise from benign precursor lesions that are a recognized strong risk factor for this neoplasm in humans. To define molecular events involved in the pathway to melanoma, we have for the first time applied the Collaborative Cross (CC) to cancer research. The CC is a powerful resource designed to expedite discovery of genes for complex traits. We characterized melanoma genesis in more than 50 CC strains and observed tremendous variation in all traits, including nevus and melanoma age of onset and multiplicity, anatomical site predilection, time for conversion of nevi to melanoma and metastases. Intriguingly, neonatal ultraviolet radiation exposure exacerbated nevus and melanoma formation in most, but not all CC strain backgrounds, suggesting that genetic variation within the CC will help explain individual sensitivity to sun exposure, the major environmental skin carcinogen. As genetic variation brings about dramatic phenotypic diversity in a single mouse model, melanoma-related endophenotype comparisons provide us with information about mechanisms of carcinogenesis, such as whether melanoma incidence is dependent upon the density of pre-existing nevus cells. Mouse models have been used to examine the functional role of gene mutations in tumorigenesis. This work represents their next phase of development to study how biological variation greatly influences lesion onset and aggressiveness even in the setting of known somatic driver mutations. [ABSTRACT FROM AUTHOR]

Ultraviolet B (UVB) irradiation of the skin has the benefit of causing the local production of previtamin D3 but also results in cutaneous DNA damage and suppression of the skin immune system (SIS). Strains of mice differ in their ability to be suppressed by UVB irradiation: BALB/c mice are considered “resistant” and C57BL/6 “sensitive”. This study evaluated whether vitamin D-replete (D+) and deficient (D−) BALB/c and C57BL/6 mice differed in their cutaneous response to UVB irradiation. Immunosuppression was assessed by measuring the contact hypersensitivity (CHS) response, DNA damage and repair determined by counting thymine dimer positive keratinocyte nuclei, and cutaneous inflammation and epidermal hyperplasia evaluated by light microscopy. The suppression in the CHS response induced by the UVB irradiation was reduced in the D+ C57BL/6 mice compared with the D− C57BL/6 mice. Similarly there was a reduction in DNA damage and promotion of its repair in the D+ C57BL/6 mice compared with the D− C57BL/6 mice. A reduction in inflammation in female D+ C57BL/6 mice compared with D− C57BL/6 females also occurred. In contrast, the suppression in the CHS response, DNA damage and its repair, and inflammation induced by UVB irradiation were similar in the D+ and D− BALB/c mice. These results indicate that dietary vitamin D3 can reduce UVB-induced suppression of the CHS response depending on the genetic background of the mice, an effect that may relate to the reduction in DNA damage and an increase in its rate of repair. [ABSTRACT FROM AUTHOR]

Over the past thirty years, extensive studies of strong-field photoionization of atoms have revealed both quantum and classical aspects including above-threshold ionization, electron wave-packet drift, quiver and rescattering motions. Increasingly sophisticated spectroscopic techniques and sculpted laser pulses coupled with theoretical advances have led to a seemingly complete picture of this fundamental laser–atom interaction. Here, we describe an effect that seems to have escaped observation: the photoelectron energy distribution manifests an unexpected characteristic spike-like structure at low energy, which becomes prominent using mid-infrared laser wavelengths (λ>1.0 μm). The low-energy structure is observed in all atoms and molecules investigated and thus seems to be universal. The structure is qualitatively reproduced by numerical solutions of the time-dependent Schrödinger equation but its physical origin is not yet identified. [ABSTRACT FROM AUTHOR]

In 1964 Keldysh helped lay the foundations of strong-field physics by introducing a theoretical framework that characterized atomic ionization as a process that evolves with the intensity and wavelength of the fundamental field. Within this context, experiments have examined the intensity-dependent ionization but, except for a few cases, technological limitations have confined the majority to wavelengths below 1 μm. The development of intense, ultrafast laser sources in the mid-infrared (1 μm<λ<5 μm) region enables exploration of the wavelength scaling of the Keldysh picture while enabling new opportunities in strong-field physics, control of electronic motion and attosecond science. Here we report a systematic experimental investigation of the wavelength scaling in this region by concurrently analysing the production of energetic electrons and photons emitted by argon atoms interacting with few-cycle, mid-infrared fields. The results support the implicit predictions contained in Keldysh’s work, and pave the way to the realization of brighter and shorter attosecond pulsed light sources using longer-wavelength driving fields. [ABSTRACT FROM AUTHOR]

One of the most remarkable aspects of Devil Facial Tumour Disease (DFTD) is its infectious nature, and for successful transmission it must avoid detection by the devil’s immune system. For this to occur, the devil either is severely immunosuppressed or factors produced by the tumor contribute to its avoidance of immune detection. An analysis of the devil’s immune system revealed the presence of normal-looking lymphoid organs and lymphoid cells. At a functional level the lymphocytes proliferated in response to mitogen stimulation. Subcutaneous injection of a cellular antigen produced a strong antibody response, providing compelling evidence that the devil has a competent immune system. Tumor cell analysis demonstrated that the tumor expresses the genes of the major histocompatibility complex; however, there was a limited diversity. Therefore, the most likely explanation for devil-to-devil transmission of DFTD is that the tumor is not recognized by the devil as “non-self” because of the limited genetic diversity. With its consistent morphology and relatively stable genome, this tumor would provide a reasonable target for a vaccine approach, provided the immune system can be coaxed into recognizing the tumor as “non-self.” [ABSTRACT FROM AUTHOR]

To identify possible genetic interactions between the mechanisms of tumor suppression of menin and pRb, we intercrossed mice with targeted deletions of Men1 and Rb1, and compared tumor development in cohorts of animals carrying single or dual mutations of these tumor-suppressor genes. In mice lacking one copy of Men1, pancreatic islet and anterior pituitary adenomas are common. In animals lacking one copy of Rb1, intermediate pituitary and thyroid tumors occur at high frequency, with less frequent development of pancreatic islet hyperplasia and parathyroid lesions. In mice heterozygous for both Men1 and Rb1, pancreatic hyperplasia and tumors of the intermediate pituitary and thyroid occurred at high frequency. Serum measurements of calcium and glucose did not vary significantly between genotypic groups. Loss of heterozygosity at the Rb1 locus was common in pituitary and thyroid tumors, whereas loss of menin was observed in pancreatic and parathyroid lesions. The tumor spectrum in the double heterozygotes was a combination of pathologies seen in each of the individual heterozygotes, without decrease in age of onset, indicating independent, non-additive effects of the two mutations. Together with the lack of increased tumor spectrum, this suggests that menin and pRb function in a common pathway of tumor suppression.Oncogene (2007) 26, 4009–4017. doi:10.1038/sj.onc.1210163; published online 18 December 2006 [ABSTRACT FROM AUTHOR]

Atoms exposed to intense light lose one or more electrons and become ions. In strong fields, the process is predicted to occur via tunnelling through the binding potential that is suppressed by the light field near the peaks of its oscillations. Here we report the real-time observation of this most elementary step in strong-field interactions: light-induced electron tunnelling. The process is found to deplete atomic bound states in sharp steps lasting several hundred attoseconds. This suggests a new technique, attosecond tunnelling, for probing short-lived, transient states of atoms or molecules with high temporal resolution. The utility of attosecond tunnelling is demonstrated by capturing multi-electron excitation (shake-up) and relaxation (cascaded Auger decay) processes with subfemtosecond resolution. [ABSTRACT FROM AUTHOR]

Solar radiation in the UVB range is absorbed primarily by the epidermal DNA where characteristic photodamage results in altered immune responses and mutagenic lesions. UVB exposure of the skin results in a profound upregulation of the anti-inflammatory cytokine, IL-10 and suppression of contact hypersensitivity (CHS). Given that IL-10 is produced after UVB exposure, and that antibodies against IL-10 have been shown to reverse UVB-induced immune suppression, we hypothesized that IL-10 transgenic mice would show an enhanced immune suppression in response to UVB. Using an IL-10 transgenic mouse model (IL-10tg), we examined the CHS response in unexposed animals and those exposed to UVB. Unexposed IL-10tg animals showed a diminished CHS response compared to wild-type. Surprisingly, however, when IL-10tg animals were exposed to UVB, the CHS response was not further suppressed, but rather was restored to the level observed in unexposed wild-type animals. [ABSTRACT FROM AUTHOR]

The resistance of Eucalyptus to browsing mammals has been related to the level and type of formylated phloroglucinol compounds (FPCs) present in the leaf. The antifeedant activity of FPCs appears to depend on their aldehyde groups, but little else is known of their mode of action. We have sought to elucidate this further by examining the biological reactivity and disposition of jensenone, a model FPC. Neither jensenone nor any metabolites were detected in urine or feces of marsupial brushtail or ringtail possums that had ingested up to 725 mg·kg-0.75. When jensenone was incubated in rat gastrointestinal segments in vitro, it rapidly disappeared. Jensenone also reacted rapidly with glutathione, cysteine, glycine, ethanolamine, and trypsin, and more slowly with acetylcysteine and albumin. Sideroxylonal, a more complex FPC, exhibited the same reactivity. Torquatone, a related compound that lacks both aldehyde groups and antifeedant activity, was unreactive. Mass spectroscopic analysis indicated that the adducts were Schiff bases formed between the aldehyde groups of FPCs and amine groups of the conjugating molecules. Successive adducts were formed with the two aldehyde groups of jensenone, and the four groups of sideroxylonal. The jensenone bis-glutathione adduct appeared to cyclize to the disulfide form. These findings suggest that the antifeedant effects of FPCs are due to their facile binding to amine groups on critical molecules in the gastrointestinal tract, leading to a loss of metabolic function. The consequent toxic reaction, probably involving chemical mediators such as 5-hydroxytryptamine (5HT), may cause colic, nausea, and a general malaise, resulting in anorexia. [ABSTRACT FROM AUTHOR]

Web caches are traditionally organised in a simple tree like hierarchy. In this paper, a new architecture is proposed, where federations of caches are distributed globally, caching data partially. The advantages of the proposed system are that contention on global caches is reduced, while at the same time improving the scalability of the system since extra cache resources can be added on the fly. Among other topics discussed in this papers, is the scalability of the proposed system, the algorithms used to control the federation of Web caches and the approach used to identify the potential Web cache partners. In order to obtain a successful collaborative Web caching system, the formation of federations must be controlled by an algorithm that takes the dynamics of the Internet traffic into consideration. We use the history of Web cache access in order to determine how federations should be formed. Initial performance results of a simulation of a number of nodes are promising. [ABSTRACT FROM AUTHOR]

Focuses on the use of optical amplifiers, semiconductor lasers and optical fibers lasers in the realization of high performance laser Doppler anemometer systems. Application of laser sources with high output powers; Importance of photodetectors to detect the velocity of the measured flow component; Use of optical fiber amplifiers as booster amplifier.

To assess the role of the p53 tumor suppressor gene in skin carcinogenesis by UV radiation, mice constitutively lacking one or both copies of the functional p53 gene were compared to wild-type mice for their susceptibility to UV carcinogenesis. Heterozygous mice showed greatly increased susceptibility to skin cancer induction, and homozygous p53 knockout mice were even more susceptible. Accelerated tumor development in the heterozygotes was not associated with loss of the remaining wild-type allele of p53, as reported for tumors induced by other carcinogens, but in many cases was associated with UV-induced mutations in p53. Tumors arose on the ears and dorsal skin of mice of all three genotypes, and homozygous knockout mice also developed ocular tumors, mainly melanomas. Skin tumors in the p53 knockout mice were predominately squamous cell carcinomas and were associated with premalignant lesions resembling actinic keratoses, whereas those in the heterozygous and wild-type mice were mainly sarcomas. These results demonstrate the importance of p53 in protecting against UV-induced cancers, particularly in the eye and epidermis. [ABSTRACT FROM AUTHOR]

In five out of 51 adult, male patients with acute non-lymphocytic leukemia, Klinefelter's syndrome was demonstrated karyotypically. The incidence of this syndrome in our material is very much increased in comparison with the frequency at birth. In this article the medical histories of the patients are given and the possible connection between the constitutional chromosome abnormality and acute non-lymphocytic leukemia is discussed. Immunological or hormonal abnormalities or an increased virus susceptibility might be predisposing factors. [ABSTRACT FROM AUTHOR]

The chemical carcinogen 7, 12-dimethylbenz(a)anthracene (DMBA) depletes Langerhans cells from murine epidermis. Application of contact sensitizers to DMBA-treated skin induces specific immunological tolerance due to a DMBA-resistant epidermal antigen presenting cell (APC) migrating to local lymph nodes where it presents antigen in a way which activates suppressor cells. As alterations in local lymph node lymphocytes may enhance the ability of the DMBA-resistant APC to activate suppressor cells, these cells were examined in DMBA-treated mice. Lymph nodes in DMBA-treated mice had normal morphology but were larger and contained increased numbers of lymphocytes. Cell cycle analysis revealed that these lymphocytes did not arise from division within the lymph node, suggesting alterations in homing properties of lymphocytes. Contact sensitizer applied to DMBA-treated skin did not increase lymphocyte division, possibly due to suppressor cell inhibition of the development of effector lymphocytes. DMBA treatment had no effect on B cells or Ia expression, but decreased levels of the T lymphocyte cell surface molecule Thy-1, and increased L3T4 and Lyt-2 as quantitated by flow cytofluorimetry. These changes could influence the development of immune responses as these T cell molecules are receptors involved in lymphocyte interactions. [ABSTRACT FROM AUTHOR]

The distribution and number of Peyer's patches (5) in two species of marsupial mice, Antechinus swainsonii and Antechinus stuartii was found to he the same even though the length of the intestine in the latter species was half that of the former. Both species lack a caecum and appendix. The position of the Peyer's patches is unusual in that the first three Peyer's patches are on the right side of the small intestine whereas the penultimate and ultimate Peyers patches are large, contain many lymphoid follicles and are in an anti-mesenteric position in the small intestine and sometimes in the large intestine (ultimate Peyer's patch). The number of Peyer's patches in eutherian mice of similar size, and intestinal length is greater (13) although the number of Peyer's patch lymphoid follicles per centimetre intestine is less (1.8) than in A. swainsonii (4) and A. stuartii (4.4). Marsupial mice have most of their lymphoid follicles confined to a few large Peyer's patches, whereas eutherian mice have fewer lymphoid follicles per unit intestinal length, more Peyer's patches (with fewer lymphoid follicles) evenly distributed along the intestine and more single lymphoid follicles interspersed between them. [ABSTRACT FROM AUTHOR]

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The basic food science course at Leeds University takes four years and leads to the degree of B.Sc. Since entrants have variable mathematical ability the food rheology course is divided into a basic non-mathematical course for all students in the second year and a mathematical component for selected students only, in the fourth. Courses are kept up to date by a study of the literature, and the circulation of questionnaires to the British Food Industry. [ABSTRACT FROM AUTHOR]