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Brain regions affected by Alzheimer disease (AD) display well-recognized early neuropathologic features in the endolysosomal and autophagy systems of neurons, including enlargement of endosomal compartments, progressive accumulation of autophagic vacuoles, and lysosomal dysfunction. Although the primary causes of these disturbances are still under investigation, a growing body of evidence suggests that the amyloid precursor protein (APP) intracellular C-terminal fragment β (C99), generated by cleavage of APP by β-site APP cleaving enzyme 1 (BACE-1), is the primary cause of the endosome enlargement in AD and the earliest initiator of synaptic plasticity and long-term memory impairment. The aim of the present study was to evaluate the possible relationship between the endolysosomal degradation pathway and autophagy on the proteolytic processing and turnover of C99. We found that pharmacologic treatments that either inhibit autophagosome formation or block the fusion of autophagosomes to endolysosomal compartments caused an increase in C99 levels. We also found that inhibition of autophagosome formation by depletion of Atg5 led to higher levels of C99 and to its massive accumulation in the lumen of enlarged perinuclear, lysosomal-associated membrane protein 1 (LAMP1)-positive organelles. In contrast, activation of autophagosome formation, either by starvation or by inhibition of the mammalian target of rapamycin, enhanced lysosomal clearance of C99. Altogether, our results indicate that autophagosomes are key organelles to help avoid C99 accumulation preventing its deleterious effects.-González, A. E., Muñoz, V. C., Cavieres, V. A., Bustamante, H. A., Cornejo, V.-H., Januário, Y. C., González, I., Hetz, C., daSilva, L. L., Rojas-Fernández, A., Hay, R. T., Mardones, G. A., Burgos, P. V. Autophagosomes cooperate in the degradation of intracellular C-terminal fragments of the amyloid precursor protein

CD4+CD25+ regulatory T cells (Tregs) suppress immune responses to alloantigens. The in vivo circulation and tissue localization of Tregs during an adaptive immune response remain unclear. We noninvasively tracked luciferase-expressing Tregs over time in an allogeneic bone marrow transplant model and demonstrated colocalization with effector T cells and initial expansion in secondary lymphoid organs before migration into inflamed tissues. Inflammation induced by irradiation and the allogeneic setting provided crucial stimuli for early Treg expansion and migration, leading to parallel reduction of effector T-cell proliferation in lymphoid organs and peripheral tissues. Treg transplants conferred long-term protection from systemic inflammatory challenge consistent with Treg in vivo survival. Suppression occurred during multiple phases of inflammation, but is optimal in the initial phase, providing protection from graft-versus-host disease while maintaining the graft-versus-tumor effect even at physiologic doses of Tregs due to their in vivo expansion, hence overcoming a major barrier to potential clinical applications of Tregs given their rarity.

High power lasers are a tool that can be used to determine important parameters in the context of Warm Dense Matter, i.e. at the convergence of low-temperature plasma physics and finite-temperature condensed matter physics. Recent results concerning planet inner core materials such as water and iron are presented. We determined the equation of state, temperature and index of refraction of water for pressures up to 7 Mbar. The release state of iron in a LiF window allowed us to investigate the melting temperature near the inner core boundary conditions. Finally, the first application of proton radiography to the study of shocked material is also discussed.

Objective: To determine whether the two major isoflavones in red clover differ in their effect on low-density lipoprotein cholesterol (LDL-C). Design: A randomised, placebo-controlled, double-blind trial; two parallel groups taking one of the two isoflavones within which treatment and placebo were administered in a crossover design. Setting: Free-living volunteers. Subjects: A total of 46 middle-aged men and 34 postmenopausal women. Interventions: Two mixtures of red clover isoflavones enriched in either biochanin (n=40) or formononetin (n=40) were compared. Placebo and active treatment (40 mg/day) were administered for 6 weeks each in a crossover design within the two parallel groups. Main outcome measures: Plasma lipids were measured twice at the end of each period. Results: Baseline LDL-C concentrations did not differ significantly between men (n=46) and women (n=34), nor between those randomised to biochanin or formononetin. Interaction between time and treatments, biochanin, formononetin and corresponding placebos (two-way ANOVA) on LDL-C showed a significant effect of biochanin treatment alone. The biochanin effect was confined to men; median LDL-C was 3.61 (3.05–4.14) mmol/l with biochanin and 3.99 (3.16–4.29) mmol/l with the corresponding placebo (RM ANOVA with Dunnett's adjustment P

The objective was to compare a pre-synchronization protocol by induction of a dominant follicle using a progesterone intravaginal device before an Ovsynch protocol (Presynch) with Double-Ovsynch in lactating dairy cows. Lactating Bos indicus × Bos taurus crossbred cows (n = 440) were randomly allocated to 1 of 2 treatments (all IM injections): (1) Double-Ov (n = 228): GnRH (Day –17), prostaglandin F2α (PGF2α) 7 days later (Day –10) and gonadotropin-releasing hormone (GnRH) 3 days later (Day –7) followed by an Ovsynch protocol 7 days later (GnRH on Day 0, PGF2α on Day 7, GnRH on Day 9); (2) Presynch (n = 212): insertion of a sustained release progesterone intravaginal device (Day –10), 10 days later (Day 0), an Ovsynch protocol was initiated with progesterone device withdrawal on Day 7. All cows were artificially inseminated 15 to 20 h after the second GnRH injection of the Ovsynch protocol and were pregnancy checked by ultrasonography 30 and 60 days later. On a subsample (n = 102), ultrasonography was performed on Days 0, 7, 9, and 24 of the experimental period. On another subsample (n = 42), blood samples for progesterone analysis were taken on Days 0, 7, and 24. There were no differences between pre-synchronization methods on synchronization parameters [presence of a follicle >12 mm on D0, Double-Ov 94.2% (49/52) and Presynch 92.0% (46/50); P = 0.66], follicular diameter on the 1st GnRH (Double-Ov 17.2 ± 0.7 mm and Presynch 18.6 ± 0.9 mm; P = 0.28), ovulation rate to the 1st GnRH [Double-Ov 86.3% (44/51) and Presynch 81.2% (39/48); P = 0.50], synchronization rate [Double-Ov 84.6% (44/52) and Presynch 86.0% (43/50); P = 0.84], follicular diameter on the 2nd GnRH (Double-Ov 17.5 ± 0.6 mm and Presynch 18.0 ± 0.5 mm; P = 0.48), ovulation rate to the 2nd GnRH [Double-Ov 90.9% (40/44) and Presynch 86.0% (37/43); P = 0.48] and CL diameter on Day 24 (Double-Ov 27.9 ± 0.7 mm and Presynch 29.4 ± 0.9 mm; P = 0.19). Corpus luteum presence on Day 0 was different (P = 0.03) between treatments [Double-Ov 57.7% (30/52) and Presynch 36.0% (18/50)]. Moreover, there was no difference (P = 0.85) between pregnancy rates on Day 30 [Double-Ov 39.0% (89/228) and Presynch 40.1% (85/212)] or Day 60 after AI [Double-Ov 34.8% (79/227) and Presynch 38.7% (82/212); P = 0.41] and gestational loss between 30 and 60 days after AI [Double-Ov 7.9% (7/88) and Presynch 3.5% (3/85); P = 0.13]. Proportion of cows with P4 1 ng mL−1 on Day 7 [Double-Ov 77.3% (17/22) v. Presynch 95.0% (19/20); P = 0.14] and P4 concentration on Day 24 (Double-Ov 4.7 ± 0.6 v. P4-Ov 5.9 ± 0.9; P = 0.84) were similar between treatments. In conclusion, pre-synchronization by induction of follicular persistence using a sustained-release progesterone device before Ovsynch yielded similar results to the Double-Ovsynch protocol on follicular development and regression patterns and on the fertility of lactating dairy cows.

We studied the comparative feeding ecology of three species of colobus (Procolobus badius, Procolobus verus, and Colobus polykomos) on Tiwai Island, Sierra Leone. We collected dietary data on each species by scan-sampling habituated groups. Because these groups were observed in the same study area during overlapping time periods, the confounding effects of temporal and spatial variability in food availability were reduced. Our results show that the annual diets of the two larger species (Procolobus badius and Colobus polykomos) include roughly equal proportions of fruits (including seeds), young leaf parts, and mature leaf parts, although P. badius had a greater intake of floral parts. Procolobus verus consumed almost no mature leaf parts, few fruits and seeds, and many young leaf parts. Colobus polykomos commonly fed from lianas. Seeds were the dominant fruit item eaten by all three colobus, and the fruits they selected were generally dull and non-fleshy, in contrast to the brightly-colored, pulpy fruits eaten by guenons. Leguminous plants contributed substantially to the diets of both the larger species, but comparisons with other African forest sites indicate that colobine biomass is not closely correlated with the abundance of leguminous trees in the forest.

High-resolution seismic reflection profiles and piston cores from bays, fjords, and straits of the inland passage of Chile and the northern Antarctic Peninsula region were used to examine changes in seismic facies along a nearly continuous 24 ° latitudinal transect that encompasses temperate, subpolar, and polar climatic regimes. These climatic regimes are characterized by differences in seismic facies. Eight seismic facies are recognized on the basis of reflection character, intensity of acoustic contrast at bounding surfaces, and external shape of the unit. The northern and central Chilean fjord region is a temperate maritime setting characterized by thick ice-proximal and ice-distal glacial-marine strata and a variety of morainal features. The southern inland passage and the South Shetland Islands of Antarctica represent transitional (sub-polar) glacial-marine settings. These areas are characterized by relict ice-proximal glacialmarine facies and relatively thin ice-distal glacial-marine facies. Morainal ridges occur in bays and fjords of Chile. The northern Antarctic Peninsula is a polar climatic setting. The straits, bays, and fjords of the region have been virtually scraped clean of sediments. A thin, draping glacial-marine unit occurs locally in these areas.

A group of Colobus polykomosat Tiwai, Sierra Leone, demonstrated seasonal flexibility in its diet, with seeds, young leaves, and mature leaves each dominating the diet at different times. Comparison of food consumption with phenological data indicates that seeds are eaten whenever available and are preferred to other foods, while young leaves are preferred to mature leaves. Colobus polykomosalso prefer liane to tree leaves, despite the relatively high quality of mature tree foliage at the Tiwai site. Analysis of protein, fiber, and energy values of foods selected and items available, but not eaten, suggests that preference is related to protein and energy maximization. Leguminous plants, especially Papilionaceae and Mimosaceae, are highlighted as important food sources for C. polykomos;seeds and leaves from these families have a high nitrogen content, and the protein content of leguminous seeds often equals or exceeds that found in leaves. It is predicted, therefore, that colobines living in habitats with a high density of legumes will feed heavily on seeds, subject to constraints such as seasonal availability. Where suitable leguminous species are less common, a mixture of fruits, seeds, and young or mature leaves or both is likely to be selected. The results of this and other recent studies of colobines do not support the notion that colobines are specialist folivores.

Summary Colobine monkeys are widely reported to spend considerable portions of their daily activity budgets resting. To test the hypothesis that resting and associated postures are related to energy conservation and thermoregulation, resting behaviours in Colobus polykomos are examined in relation to vegetation cover, weather conditions and diet. Seasonal differences in hunching are shown to be significantly correlated with cool, wet conditions and low energy intake, while postures associated with heat dissipation are more closely related to hot weather. These results support the hypothesis that C. polykomos are energy limited in wet seasons, and suggest their behaviourial thermoregulation is related not just to climatic conditions, but also to energy content and availability of food. Resume On a rapporte largement que les colobides passent une grande partie de leur temps a se reposer. Pour eprouver l'hypothese selon laquelle le repos et les attitudes qui s'y associent seraient lies a la conservation de l'energie et a la thermoregulation, on examine les comportements de repos chez Colobus polykomos en relation avec le couvert vegetal, les conditions atmospheriques et le regime alimentaire. On montre que les differences saisonnieres de la chasse sont significativement liees a des conditions fraiches et humides et a une faible absorption d'energie alors que les attitudes qui depensent de la chaleur sont plus etroitement liees au temps chaud. Ces resultats supportent l'hypothese que C. polykomos dispose d'une energie limitee en saison des pluies et suggerent que la thermoregulation active n'est pas liee uniquement aux conditions climatiques mais aussi au contenu energetique et a la disponibilite de la nourriture.

The results from a series of experiments that characterize the x-ray flux transmitted through a laser-irradiated Au foil are presented. The purpose of the experiments was to develop a working model for an x-ray source that will create hot, dense plasmas with controllable gradients. These plasmas will be used as a test bed for the study of the complex radiative processes that are intrinsic to the evolution of moderate- and high-[ital Z] matter. The experiments quantitatively measured the time- and frequency-dependent energy transferred to the back of the foil. Angular information and the characterization of the flux as a function of foil thickness are also presented. Tables of the time-dependent flux are given.

To explore sources of variation in tropical forest primate biomass, and, in particular, to test the hypothesis that soil conditions are a major ultimate determinant of the biomass of colobine monkeys and other primates, we compared data on the soils, vegetation, and primate community at a site in West Africa (Tiwai Island, Sierra Leone) with information from other sites, especially two other African sites (Douala-Edea in Cameroon, and Kibale Forest in Uganda). The biomass of eight anthropoid primate species in old secondary high forest on Tiwai was estimated from data on population densities assessed by transect samples combined with data on social group densities and individual body masses. Samples of soil and tree foliage were collected at the same site, and subjected to a variety of chemical and mechanical analyses. Our estimate of anthropoid biomass at Tiwai is 1229-1529 kg/kM2, including 682-889 kg/km2 of colobines. This is one of the highest primate biomasses recorded anywhere. The soils at Tiwai were found to be relatively high in sand content and low in pH, and to have low levels of mineral nutrients. Levels of condensed tannins in the mature foliage of the trees comprising a major part of the forest canopy were higher than at other sites, but the ratio of protein to fiber in this foliage was also higher than at any other site except Kibale. It is argued that a wide range of environmental factors affect primate population densities, and that nutrient-poor soils and high tannin levels in tree foliage do not necessarily produce a low primate (or colobine) biomass, as some earlier studies had suggested. Fur

Shock Hugoniot calculations are carried out for gold using both solid and liquid state theories. The result suggests that shock melting begins to take place at a pressure of 1.2 Mbar. At about 2.1 Mbar, the melting transition is complete. The shock temperature of gold in the liquid phase is substantially lower than that in the corresponding solid phase. The validity of the calculations is tested using equilibrium volume and bulk modulus data, deduced from diamond anvil cell experiments, Hugoniot data and the most recently reported shock temperature data at ∼6 Mbar.

PARALYSIE GENERALE EN MILIEU TROPICAL. ETUDE DE 43 OBSERVATIONS RESUME Description :Les auteurs rapportent une etude de 43 cas de paralysie generale, reveles par un syndrome dementiel et des formes atypiques notamment les troubles confusionnels repetitifs et des crises epileptiformes. Objectif : L'objectif de cette etude est de reevaluer cette pathologie du point de vue clinique et paraclinique en milieu tropical. Methode : Il s'agit d'une etude prospective. Le diagnostic a repose sur la positivite des reactions serologiques ( VDRL-TPHA) dans le sang et le liquide cephalo-rachidien, la presence d'une hypercellularite a predominance lymphocytaire et d'une hyperproteinorachie. Resultats : Les troubles cognitifs et moteurs, les etats confusionnels repetitifs et les crises epileptiques constituent les formes cliniques dominantes de debut. Chez tous les patients, le scanner a mis en evidence une discrete dilatation ventriculaire diffuse et un elargissement des sillons de la convexite. Le trace electroencephalographique etait anormal dans pres de 67% des cas. SUMMARY Description : The authors report a study of 43 cases of general paralysis revealed by some mental disorders and atypical forms notably repeater confessional disorders and some seizure-like attacks. Objective : The goal of this study is to revalue this pathology from the clinical and paraclinic point of view in tropical medium. Method : In this prospective study, the diagnosis was based on the serologic tests (VDRL-TPHA) in the blood and the cerebrospinal fluid (CSF); CSF cell count with lymphocyte predominance ; protein level in the fluid. Result : The diagnosis was based on the serologic tests (VDRL-TPHA) in the blood and the cerebrospinal fluid(CSF); high CSF cell count with lymphocyte predominance; high protein level in the fluid. The cogniture and motor troubles, the repeated confusion status and the epileptic seizures constitute the dominant clinical forms of the onset. In all the patients, the CT-scan revealed discrete diffuse ventricular dilation and widening of the grooves of the convexity. The electroencephalographic traces were abnormal in 67% of the cases. Key Words: Afrique, Guinee, paralysie generale, syphilis nerveuse, Africa, Guinea, general paralysis, neurosyphilis African Journal of Neurological Sciences Vol.23(2) 2004

Various methods are available for measuring the production of reactive oxygen species by phagocytes, but they are limited in their use by the need for their immediate application, cell isolation and of cell-activation by unphysiological stimuli. In addition, after measurement of reactive oxygen metabolites using oxidizing agents, the reduced compounds formed have to be determined during or immediately after their formation. In the present study, an improved cytochrome C assay was investigated which allowed measurements of superoxide anions in whole blood samples following activation of phagocytes by physiological stimuli such as the bacterial tripeptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). The fMLP-stimulated production of superoxide anion (O(2)(-)) showed a sigmoidal-shaped fMLP dose-response curve, and constant O(2)(-) production rates (nmol.1(-1)x10(6) granulocytes) could be determined reliably up to a blood granulocyte concentration of 1 x 10(4) x microl(-1). To allow the determination of reduced cytochrome C later after its formation, the effect of long-term storage at -20 degrees C on the stability of reduced cytochrome C was tested up to 16 weeks. The results obtained show that the determination of reduced cytochrome C in whole blood represents a simple and reliable method. Most importantly, O(2)(-)-reduced cytochrome C can be frozen and stored without any alterations, at least up to 2 weeks. Thus the method seems to be superior to other methods of detection, especially when the experimental conditions do not allow immediate spectrophotometry (e.g. mountain medicine, space medicine). Under such conditions the present assay would allow reliable measurement of reduced cytochrome C, even after weeks of cryopreservation.

An accurate equation of state (EOS) for planetary constituents at extreme conditions is the key to any credible model of planets or low mass stars. However, experimental validation has been carried out on at high pressure (>few Mbar), and then only on the principal Hugoniot. For planetary and stellar interiors, compression occurs from gravitational force so that material states follow a line of isentropic compression (ignoring phase separation) to ultra-high densities. An example of the predicted states for water along the isentrope for Neptune is shown in a figure. The cutaway figure on the left is from Hubbard, and the phase diagram on the right is from Cavazzoni et al. Clearly these states lie at quite a bit lower temperature and higher density than single shock Hugoniot states but they are at higher temperature than can be achieved with accurate diamond anvil experiments. At extreme densities, material states are predicted to have quite unearthly properties such as high temperature superconductivity and low temperature fusion. High density experiments on Earth are achieved with either static compression techniques (i.e.diamond anvil cells) or dynamic compression techniques using large laser facilities, gas guns, or explosives. A major thrust of this work is to develop techniques to create and characterize material states that exists primarily at the core of giant planets and brown dwarf stars. Typically, models used to construct planetary isentropes are constrained by only the planet radius, outer atmospheric spectroscopy, and space probe gravitational moment and magnetic field data. Thus any data, which provide rigid constraints for these models will have a significant impact on a broad community of planetary and condensed matter scientists. Recent laser shock wave experiments have made great strides in recreating material states that exist in the outer 25% (in radius) of the Jovian planets and at the exterior of low-mass stars. Large laser facilities have been used to compressed materials to ultra-high pressures and characterize their thermodynamic and transport properties (plastic Hugoniot to 40 Mbar, deuterium Hugoniot to 3 Mbar, metallization of ''atomic'' deuterium on the Hugoniot). To probe materials properties at these high pressures, several experimental techniques were developed high resolution radiography, optical reflectance, pyrometry, and velocity/displacement sensitive interferometry are some of the diagnostics currently used in laser-generated shock EOS experiments. During our experiments at Vulcan we developed and tested precompressed and multiple shock experimental techniques which allowed us to recreate the extreme core states of giant plants. These experiments compressed water to densities higher than accessible by single shock Hugoniot techniques and showed that the metal-insulator transition of shocked precompressed water is suppressed significantly as compared to uncompressed water. Further, as predicted the temperature of shocked precompressed water is lower than the temperature of uncompressed water enabling us to determine the metallization mechanism for water near the Hugoniot.

Minimally invasive surgery (MIS) is an approach whereby procedures conventionally performed with large and potentially traumatic incisions are replaced by several tiny incisions through which specialized instruments are inserted. Early MIS, often called laparoscopic surgery, used video cameras and laparoscopes to visualize and control the medical devices, which were typically cutting or stapling tools. More recently, catheter-based procedures have become a fast growing sector of all surgeries. In these procedures, small incisions are made into one of the main arteries (e.g. femoral artery in the thigh), and a long thin hollow tube is inserted and positioned near the target area. The key advantage of this technique is that recovery time can be reduced from months to a matter of days. In the United States, over 700,000 catheter procedures are performed annually representing a market of over $350 million. Further growth in this area will require significant improvements in the current catheter technology. In order to effectively navigate a catheter through the tortuous vessels of the body, two capabilities must exist: imaging and positioning. In most cases, catheter procedures rely on radiography for visualization and manual manipulation for positioning of the device. Radiography provides two-dimensional, global images of the vasculature and more » cannot be used continuously due to radiation exposure to both the patient and physician. Intravascular ultrasound devices are available for continuous local imaging at the catheter tip, but these devices cannot be used simultaneously with therapeutic devices. Catheters are highly compliant devices, and manipulating the catheter is similar to pushing on a string. Often, a guide wire is used to help position the catheter, but this procedure has its own set of problems. Three characteristics are used to describe catheter maneuverability: (1) pushability -- the amount of linear displacement of the distal end (inside body) relative to an applied displacement of the proximal end (outside body); (2) torquability -- the amount of rotation of the distal end relative to an applied rotation of the proximal end; and (3) trackability -- the extent to which the catheter tracks along the guide wire without displacing it. « less

Interleukin (IL) 4 is a potent immunomodulatory cytokine secreted by T-helper 2 (Th2) cells and Th2 mast cells that promotes the commitment of cells. However, unregulated production and release of IL-4 can exacerbate allergic reactions and increase susceptibility to infectious organisms and viruses. Here, we present evidence that AG-490, a Janus tyrosine kinase (JAK) 2-JAK3 inhibitor, effectively blocked IL-4 gene expression and secretion in the Th2 cell line D10 that was not occurring after anti-CD3 antibody stimulation, whereas AG-490 had no inhibitory effect on production of other Th2 cytokines or cytokines synthesized by the corresponding Th1 cell line clone 29. AG-490 potently inhibited IL-4-mediated proliferation of both D10 and the IL-4-dependent cell line CT.4S. Moreover, AG-490 markedly inhibited IL-4 activation of JAK3 and blocked the downstream activation of signal transducer and activator of transcription 6, as judged by tyrosine phosphorylation, DNA binding, and transcription assays. In contrast, AG-490 did not affect tumor necrosis factor alpha activation of NF-kappaB at similar concentrations of drug. These data suggest that tyrosine kinase inhibitors that inhibit JAK3 may have previously unrecognized and selective clinical potential as immunotherapeutic drugs to treat Th2-mediated diseases driven by IL-4. (Blood. 2000;95:3816-3822)

T lymphocyte activation is highlighted by the induction of interleukin-2 (IL-2) gene expression, which governs much of the early lymphocyte proliferation responses. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. PPARgamma mRNA expression was found in human peripheral blood T lymphocytes, raising the possibility of PPARgamma involvement in the regulation of T cell function. Here we show that PPARgamma ligands, troglitazone and 15-deoxy-Delta(12,14) prostaglandin J(2), but not PPARalpha agonist Wy14643, inhibited IL-2 production and phytohemagglutinin-inducible proliferation in human peripheral blood T-cells in a dose-dependent manner. This inhibitory effect on IL-2 was restricted to the PPARgamma2-expressing, not the PPARgamma-lacking, subpopulation of transfected Jurkat cells. The activated PPARgamma physically associates with transcriptional factor NFAT regulating the IL-2 promoter, blocking NFAT DNA binding and transcriptional activity. This interaction with T-cell-specific transcription factors indicates an important immunomodulatory role for PPARgamma in T lymphocytes and could suggest a previously unrecognized clinical potential for PPARgamma ligands as immunotherapeutic drugs to treat T-cell-mediated diseases by targeting IL-2 gene expression.

To the Editor, The Montgomery tracheal tube (T-tube) is a surgical device used to maintain a compromised airway following complex tracheal injury. We report an effective and novel use for the endobronchial multiport airway ventilating adapter (Cook , Bloomington, IN, USA) to maintain positive pressure ventilation during difficult Montgomery T-tube placement. A 50-yr-old man with a body mass index of 38 kg m and clinically significant bilateral airspace disease was scheduled for micro-direct laryngoscopy, bronchoscopy, and Montgomery T-tube placement after he had sustained blunt laryngotracheal injuries (thyroid and cricoid cartilage fractures with posterior displacement of anterior cartilage and significant superglottic hematoma). The patient underwent a tracheostomy (size 8.0 cuffed Shilley) to secure his airway. During the Montgomery T-tube placement under general anesthesia, difficulty in ventilation arose while attempting to occlude the upper intralaryngeal section of the T-tube with a Fogarty vascular catheter (Edwards Lifesciences , Irvine, CA, USA) via the extratracheal lumen. This procedure is designed to prevent leaks of volatile anesthetic and fresh gas flows during positive pressure ventilation (as originally described by Montgomery). In discussion with the otorhinolaryngologists, a plan was devised to ventilate the patient’s lungs following re-insertion of the T-tube. A standard endobronchial multiport airway adapter (Cook ) was attached to the extratracheal limb of the Montgomery T-tube via a standard 15 mm endotracheal tube connector (7.5 mm polyvinyl endotracheal tube). The Ttube was re-inserted, and a Fogarty vascular catheter was passed through the 30 angled port of the Cook Multiport Airway Adapter. The catheter was then fed into the upper limb of the T-tube under direct laryngoscopy, and the balloon was inflated to create a tight seal. The right-angled port of the multiport adapter was used for positive pressure ventilation and standard end-tidal carbon dioxide monitoring (Fig. 1). The Montgomery T-tube was secured, and proper positioning of the upper intratracheal stem was confirmed by direct laryngoscopy. Ventilation of the patient’s lungs was maintained through the multiport airway adapter during these critical maneuvers. The Montgomery T-tube can present various challenges to anesthesiologists during its placement, including the potential for acute loss of the airway, inadequate administration of inhalation agents, and inadequacy of controlled mechanical ventilation. Various insertion techniques were developed to overcome some of these difficulties. This case was unique because the patient’s complex laryngotracheal injuries and associated hypopharyngeal and supraglottic lesions precluded the use of the laryngeal mask airwayMontgomery T-tube technique as described by Guha et al. Described, in this case, is a ‘‘combined technique’’ of passing an endotracheal tube through the extratracheal lumen and the intratracheal portion of the T-tube distal to the tracheal lesion. While it can be argued that this ‘‘combined technique’’ may offer the benefit of a secured airway through which positive pressure ventilation can be performed, we would argue that our method is feasible and effective with little interruption to monitoring of ventilation. Placement of the endotracheal tube fed through the extratracheal lumen of the T-tube to the distal trachea may also be complicated by potential kinking and acute loss of the airway. Furthermore, it may not be apparent during this difficult placement whether the kink was due to the endotracheal tube or due to the T-tube. F. Kailash, MD (&) S. L. DaSilva, MD F. E. Block Jr., MD University of Arkansas for Medical Sciences, Little Rock, USA e-mail: kailashkailash@uams.edu

During the Last Glacial Maximum (LGM) ice flowed from the Cordillera Darwin Ice Cap through the study area (Fig. 1) to the Segunda Angostura in the Straits of Magellan [Caldenius,1932; Mercer, 1976; Porter, 1990; Porter, et. al., 1992; Clapperton,1993]. Recent work by Clapperton [1995] indicates that as many as five glacial advances occurred along the Strait of Magellan during the last glacial cycle, with the last advance tentatively occurring between 16,590 – 11,800 14C YBP.

Impaired immune responses are frequently observed in tumor-bearing hosts during progression of tumor growth, but the molecular basis of these functional defects remains unclear. To investigate tumor-induced immunosuppression, we first established that lymphocytes from mice bearing s.c. mammary adenocarcinoma (TS/A) tumors were severely impaired in their ability to generate cellular and humoral Ag-specific responses. Lymphocytes from these mice were then screened for abnormalities in the expression of signal transducing proteins known to be involved in the regulation of cellular immunity. Interestingly, purified T and B cells isolated from immunocompromised tumor-bearing mice displayed a marked decrease in the transcription activators STAT5a and -b at the protein level and to a lesser extent at the mRNA level. By contrast, no change in the expression of STAT1, -3, and -6 or of the TCR itself were detected. The correlation in the loss of T and B cell function with the selective decrease in STAT5a/b expression suggests that regulation of the STAT5 signaling pathway may provide a molecular mechanism for modulating the immune system.

The high pressure equations of state of materials must be accurately known for confident design, simulation, and interpretation of ICF target experiments and for weapons. Here, the authors sketch out a program to perform precise and accurate equation of state (EOS) experiments using large, high-power lasers. The program is divided into three phases: (1) a driver qualification program which will determine the necessary drive and target design parameters; (2) characterization of low and high-Z standard materials; (3) accurate impedance-match experiments to determine equations of state of materials of interest relative to the qualified standards. Novel methods are proposed for the first phase which are an order of magnitude more sensitive than those applied previously. They identify and describe the choices for standards and the samples slated for initial studies. In all cases, their goal is to obtain data that is of sufficiently high quality to serve for design purposes and to validate theories of material response at high pressures of the order of 1--10 TPa. This is particularly important right now, for materials such as CH plastics and hydrogen (DT). In addition, they will suggest a program for EOS measurements for P > 10 TPa, the region of maximum theoretical EOS uncertainty for many materials.

Prolactin (PRL) has recently been demonstrated to induce tyrosine phosphorylation and activation of the cytoplasmic tyrosine kinase JAK2 in PRL-dependent Nb2 lymphoma cells. The present study represents an initial effort to identify cytoplasmic regions of the PRL receptor (PRLR) that are critical to growth signal generation and JAK2 activation. Variably truncated rat PRLRs were stably expressed in the murine 32D cell line. PRL-induced proliferation was mediated by the full-length receptor and the mutant G328, which contains the membrane-proximal Homology Boxes 1 and 2 characteristic of hematopoietin receptors. In contrast, mutant receptors lacking either Box 2 or both Boxes 1 and 2 were not capable of transmitting a growth signal. The mitogenic capacity of the PRLR variants correlated with JAK2 association and activation, as well as with induction of mRNA levels for the growth-related gene ornithine decarboxylase. We conclude that mitogenic competence of rat PRLRs resides within the first 94 amino acids of the cytoplasmic domain. The data suggest that Homology Box 1/Box 2 region is critical to JAK2 phosphorylation and association with the PRLR. These findings will serve as a basis for more detailed molecular characterization of PRLR domains essential for JAK2 interaction and growth signal generation.

Any potential lithography must demonstrate an industrially-compatable reticle pattern repair process before the lithographic process can be seriously considered for production. Repair of clear defects on EUV reticles (i.e., regions on the mask which are reflective and should be non-reflective) requires the deposition of a thin layer of absorbing material. This process has been demonstrated in commercially available tools which were originally developed to repair proximity-print x-ray lithography masks. However, the repair of opaque defects (i.e., the recovery of reflectivity from regions on the reticle covered with an absorber) is more difficult. Opaque defect repair requires the removal of the absorber layer without damaging the underlying multilayer, a process which could degrade the mirror reflectivity. While opaque defect repair processes have been demonstrated in a research environment(1,2), these processes may not be commercially suitable. We are developing reticle repair processes that will be consistent with a commercially available repair tool. In this paper, we report on our first results.

Ultra-short x-ray pulses provide scientists with powerful tools for material diagnostics. Production of coherent, soft-x-ray radiation through the generation of high-order harmonics of (optical) laser radiation has been demonstrated in several laboratories [1]. These high-order harmonics are typically generated using ultra-short laser pulses and are expected to be of short (typically sub-picosecond) temporal duration. While many aspects of harmonic generation have been experimentally investigated, the temporal duration of soft x-rays produced via high-order harmonic generation has not yet been measured. One difficulty is that the temporal resolution achievable with commercial instruments (such as x-ray streak cameras) is limited to approximately 1 ps.

Summary form only given, as follows. Laser-heated foam offers possibility of producing a large plasma with a density much lower than that resulting from laser-heating of a solid. Such plasmas may be of interest as a gain medium in X-ray lasers or as a long-scale-length plasma source for the study of parametric instabilities. Preliminary results of a study exploring the deposition of a 2.3 ns, 0.53 /spl mu/m laser pulse in Agar (CH/sub 2/O) suggest that, for a sufficiently small focal spot, the laser beam propagates into the foam target by strong self-focusing. This yields a plasma filament inside the foam with a diameter less than 50 /spl mu/m and a length exceeding 400 /spl mu/m.

Equine infectious anemia virus (EIAV) encodes a tat gene which is closely related to the trans-activators encoded by the human and simian immunodeficiency viruses. Nucleotide sequence analysis of EIAV cDNA clones revealed that the tat message is composed of three exons; the first two encode tat and the third may encode rev.. Interestingly, EIAV tat translation is initiated at a non-AUG codon in the first exon of the message, perhaps allowing an additional level of gene regulation. The deduced amino acid sequence of EIAV tat, combined with functional analyses of tat cDNAs in transfected cells, have provided some unique insights into the domain structure of this protein. EIAV Tat has a C-terminal basic domain, a highly conserved 16 amino acid core domain, but not the cysteine-rich region, that is present in the primate immunodeficiency virus Tat proteins. Thus EIAV encodes a relatively simple version of this kind of trans-activator.

CD4+CD25+ Regulatory T cells (Treg) reduce the incidence and severity of acute graft-versus-host disease (GvHD) in murine models of allogeneic bone marrow transplantation (BMT) when given at the time of transplantation at a 1:1 ratio with donor effector T cells (Tcon). In our previous study with Treg trafficking, bioluminescene imaging (BLI) indicated a persistence of signal consistent with a prolonged survival of Treg in vivo following allogeneic BMT. In the current study, we evaluated the duration of Treg suppression and the impact of Treg on evolving and established GvHD. Lethally irradiated Balb/c (H2d) hosts received 5x106 T-cell depleted bone marrow (TCD-BM) cells from wild-type FVB mice (H2q) on day 0. On day 2, 3x106 splenocytes, or 1x106 purified CD4+/CD8+ T cells (Tcon) from luciferase+ transgenic mice (FVB) were infused to induce GvHD. Treg, purified from wt-FVB mice, in a 1:1 dose ratio with Tcon, were infused either on day 0, 2, 9, or 23 post-transplantation. Bioluminescence imaging was used to localize and quantitate the proliferation of Tcon in the absence or presence of Treg. Signal intensity, measured by photons/second/mouse, was significantly decreased in animals which received Treg at day 0, 2, or 9 (p-value < 0.05). More importantly, the greatest reduction in signal intensity occurred when Treg were given prior to the induction of GvHD by Tcon. This reduction was associated with a significantly lower clinical score for GvHD. Studies in which Treg are given up to 10 days prior to the addition of Tcon show similar findings. At day 23, when clinical GvHD was fully established in mice which received Tcon, the addition of Treg did not alter the increasing BLI signal level or the clinical course such that all animals died of GvHD (p-value=0.38). Lymphoid reconstitution was not affected by the addition of Treg prior to the induction of GvHD. In dose titration studies whereby Treg are given two days prior to the induction of GvHD, a 10-fold dose reduction in Treg was sufficient to significantly reduce Tcon proliferation and suppress clinical GvHD. We next assessed the duration of Treg suppressive effect by inducing GvHD on day 7, 14, 19 with luc+ Tcon following the infusion of Treg on day 0 of allogeneic BMT. Treg provided protection from the Tcon challenge at all 3 time points, leading to improved survival (p-value < 0.05). We conclude that Treg provide prolonged protection due to their ability to proliferate in vivo in an allogeneic setting. The capacity of Treg to proliferate in vivo permits a significant reduction in the number of Treg needed for adoptive transfer to induce a clinical response, a practical finding given the rarity of Treg. In addition, we conclude that Treg suppress the early proliferation of Tcon, allowing them to prevent and control evolving but not established GvHD.

1. Colobines are widely described as folivorous and a prediction of low basal metabolic rate appears to be supported by low activity levels, but energy budget estimates based on data from a field study of Colobus polykomos question these assumptions. 2. Annual diet and activity budgets are shown to change seasonally: unripe tree seeds are the preferred food type, with increased time spent feeding during the peak of seed production. Time spent resting is highest during wet seasons, when seeds are not available and only leaves are eaten. 3. The high energetic value of seeds compared to fruit flesh, young and mature leaves, is demonstrated. 4. Energy budgets are estimated for adult males and females (non-reproductive, pregnant and lactating), using daily energy expenditure (DEE) as maximum, and average daily metabolic needs (ADMN) as minimum values. 5. A simple model is employed to demonstrate that a diet of 100% seeds supplies sufficient calories for all estimates of energy intake and expenditure, whereas a diet of 100% leaves is unable to meet DEE and only the highest estimates of feeding rate (grams of leaves min-1) approach ADMN. 6. The advantages of detoxification, and the limitations of energy production for small-bodied fore-gut fermenters are outlined. 7. Evidence that C. polykomos is hypometabolic is considered, and it is concluded that the adaptations they show to periodic shortages of high energy foods are behavioural rather than physiological.

We have obtained the first temporally resolved measurement of the entire visible spectrum of shock-induced luminescence from the rear surface of a laser-irradiated aluminum foil. This yielded a detailed time history (200 ps resolution) of the spectral temperature of the target rear surface. The results were consistent with that obtained from brightness temperature measurements. The measured shock-heated temperature also showed good agreement with hydrodynamic simulations addressing the effect of shock-unloading in the target rear side.

The rarefaction of a shock‐heated solid surface into vacuum and the luminous radiation emitted by the surface were studied using a one‐dimensional hydrodynamic code. The temporal evolution of the spectral and brightness temperatures as observed by a remote detector was determined. Moreover, the time‐integrated spectral temperature was computed to simulate the actual experimental measurements. For shock speeds greater than 106 cm/s and for measurement times exceeding a few picoseconds, the code predicted a significiantly lower ‘‘observed’’ temperature, in good agreement with experiments.

We present results of studies on shock-induced shifts in the K photoabsorption edge of aluminum. Time-resolved X-ray spectroscopic measurements indicated maximum red shifts of ∼7 eV for compressions of ∼2.2 times the normal density. The results are interpreted using hydrodynamic simulations which incorporated a new model for calculating the K-edge energy in a dense plasma

We report on the first experimental measurement of principal Hugoniots in aluminum for shock pressures of 0.3-12 Mbar generated by laser-driven ablation. These were derived from independent measurements of the shock speed, shock pressure, and shock-heated target temperature. The results showed excellent agreement with LASNEX simulations and with calculations using SESAME equation-of-state data. More importantly, the results indicated that the shock speed and temperature Hugoniot may provide useful equation-of-state studies in laser-generated shock-wave experiments.