Geology and geochronology of the mammal-bearing Tertiary of the Valle de Santa María and Río Corral Quemado, Catamarca Province, Argentina / Larry G. Marshall -- , Bryan Patterson -- .

n.s. no.9(1981)

The family Diadectidae and its bearing on the classification of reptiles / Everett Claire Olson --

v.11:no.1(1947)

T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression.

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR.

Modeling of in-situ crystallization processes in the Permian mafic layered intrusion of Mont Collon (Dent Blanche nappe, western Alps)

The Mont Collon mafic complex is one of the best preserved examples of the Early Permian magmatism in the Central Alps, related to the intra-continental collapse of the Variscan belt. It mostly consists (> 95 vol.%) of ol+hy-nonnative plagioclase-wehrlites, olivine- and cpx-gabbros with cumulitic structures, crosscut by acid dikes. Pegmatitic gabbros, troctolites and anorthosites outcrop locally. A well-preserved cumulative, sequence is exposed in the Dents de Bertol area (center of intrusion). PT-calculations indicate that this layered magma chamber emplaced at mid-crustal levels at about 0.5 GPa and 1100 degrees C. The Mont Collon cumulitic rocks record little magmatic differentiation, as illustrated by the restricted range of clinopyroxene mg-number (Mg#(cpx)=83-89). Whole-rock incompatible trace-element contents (e.g. Nb, Zr, Ba) vary largely and without correlation with major-element composition. These features are characteristic of an in-situ crystallization process with variable amounts of interstitial liquid L trapped between the cumulus mineral phases. LA-ICPMS measurements show that trace-element distribution in the latter is homogeneous, pointing to subsolidus re-equilibration between crystals and interstitial melts. A quantitative modeling based on Langmuir's in-situ crystallization equation successfully duplicated the REE concentrations in cumulitic minerals of all rock facies of the intrusion. The calculated amounts of interstitial liquid L vary between 0 and 35% for degrees of differentiation F of 0 to 20%, relative to the least evolved facies of the intrusion. L values are well correlated with the modal proportions of interstitial amphibole and whole-rock incompatible trace-element concentrations (e.g. Zr, Nb) of the tested samples. However, the in-situ crystallization model reaches its limitations with rock containing high modal content of REE-bearing minerals (i.e. zircon), such as pegmatitic gabbros. Dikes of anorthositic composition, locally crosscutting the layered lithologies, evidence that the Mont Collon rocks evolved in open system with mixing of intercumulus liquids of different origins and possibly contrasting compositions. The proposed model is not able to resolve these complex open systems, but migrating liquids could be partly responsible for the observed dispersion of points in some correlation diagrams. Absence of significant differentiation with recurrent lithologies in the cumulitic pile of Dents de Bertol points to an efficiently convective magma chamber, with possible periodic replenishment, (c) 2005 Elsevier B.V. All rights reserved.

Molecular variation at a candidate gene implicated in the regulation of fire ant social behavior

The fire ant Solenopsis invicta and its close relatives display an important social polymorphism involving differences in colony queen number. Colonies are headed by either a single reproductive queen (monogyne form) or multiple queens (polygyne form). This variation in social organization is associated with variation at the gene Gp-9, with monogyne colonies harboring only B-like allelic variants and polygyne colonies always containing b-like variants as well. We describe naturally occurring variation at Gp-9 in fire ants based on 185 full-length sequences, 136 of which were obtained from S. invicta collected over much of its native range. While there is little overall differentiation between most of the numerous alleles observed, a surprising amount is found in the coding regions of the gene, with such substitutions usually causing amino acid replacements. This elevated coding-region variation may result from a lack of negative selection acting to constrain amino acid replacements over much of the protein, different mutation rates or biases in coding and non-coding sequences, negative selection acting with greater strength on non-coding than coding regions, and/or positive selection acting on the protein. Formal selection analyses provide evidence that the latter force played an important role in the basal b-like lineages coincident with the emergence of polygyny. While our data set reveals considerable paraphyly and polyphyly of S. invicta sequences with respect to those of other fire ant species, the b-like alleles of the socially polymorphic species are monophyletic. An expanded analysis of colonies containing alleles of this clade confirmed the invariant link between their presence and expression of polygyny. Finally, our discovery of several unique alleles bearing various combinations of b-like and B-like codons allows us to conclude that no single b-like residue is completely predictive of polygyne behavior and, thus, potentially causally involved in its expression. Rather, all three typical b-like residues appear to be necessary.

Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation.

In neurons, soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins drive the fusion of synaptic vesicles to the plasma membrane through the formation of a four-helix SNARE complex. Members of the Sec1/Munc18 protein family regulate membrane fusion through interactions with the syntaxin family of SNARE proteins. The neuronal protein Munc18a interacts with a closed conformation of the SNARE protein syntaxin1a (Syx1a) and with an assembled SNARE complex containing Syx1a in an open conformation. The N-peptide of Syx1a (amino acids 1-24) has been implicated in the transition of Munc18a-bound Syx1a to Munc18a-bound SNARE complex, but the underlying mechanism is not understood. Here we report the X-ray crystal structures of Munc18a bound to Syx1a with and without its native N-peptide (Syx1aΔN), along with small-angle X-ray scattering (SAXS) data for Munc18a bound to Syx1a, Syx1aΔN, and Syx1a L165A/E166A (LE), a mutation thought to render Syx1a in a constitutively open conformation. We show that all three complexes adopt the same global structure, in which Munc18a binds a closed conformation of Syx1a. We also identify a possible structural connection between the Syx1a N-peptide and SNARE domain that might be important for the transition of closed-to-open Syx1a in SNARE complex assembly. Although the role of the N-peptide in Munc18a-mediated SNARE complex assembly remains unclear, our results demonstrate that the N-peptide and LE mutation have no effect on the global conformation of the Munc18a-Syx1a complex.

Stability analysis of the 2007 Chehalis lake landslide based on long-range terrestrial photogrammetry and airborne LIDAR data

On December 4th 2007, a 3-Mm3 landslide occurred along the northwestern shore of Chehalis Lake. The initiation zone is located at the intersection of the main valley slope and the northern sidewall of a prominent gully. The slope failure caused a displacement wave that ran up to 38 m on the opposite shore of the lake. The landslide is temporally associated with a rain-on-snow meteorological event which is thought to have triggered it. This paper describes the Chehalis Lake landslide and presents a comparison of discontinuity orientation datasets obtained using three techniques: field measurements, terrestrial photogrammetric 3D models and an airborne LiDAR digital elevation model to describe the orientation and characteristics of the five discontinuity sets present. The discontinuity orientation data are used to perform kinematic, surface wedge limit equilibrium and three-dimensional distinct element analyses. The kinematic and surface wedge analyses suggest that the location of the slope failure (intersection of the valley slope and a gully wall) has facilitated the development of the unstable rock mass which initiated as a planar sliding failure. Results from the three-dimensional distinct element analyses suggest that the presence, orientation and high persistence of a discontinuity set dipping obliquely to the slope were critical to the development of the landslide and led to a failure mechanism dominated by planar sliding. The three-dimensional distinct element modelling also suggests that the presence of a steeply dipping discontinuity set striking perpendicular to the slope and associated with a fault exerted a significant control on the volume and extent of the failed rock mass but not on the overall stability of the slope.

L'oficina judicial a Catalunya: mitjà real d'una justícia eficaç pel ciutadà del segle XXI

En aquest estudi es pretenia assolir la pràctica d'un sistema que només s'ha plantejat teòricament, doncs l'experiència acumulada, ja abans de la reforma orgànica de 2003, parteix de la figura dels serveis comuns, amb un criteri d'eficiència, racionalitat i economia per invertir en l'Administració de justícia catalana. Assumir i donar resposta jurídica concreta a tots els reptes tècnics pot fer-se des d'una perspectiva dogmàtica, tot i que el temps transcorregut també permet advertir exigències pràctiques a l'àmbit de la dogmàtica processal, el context socio-cultural i, naturalment, les necessitats laborals. En aquest sentit, els objectius s'introdueixen cap a la garantia d'un apropament material, conceptual i quotidià de l'Administració de justícia al ciutadà, establert com a eix inextricable del sistema, tenint present la de vegades despesa incomprensible en una realitat històricament menystinguda i deficitària, malgrat l'esforç pressupostari fet els darrers anys que, malgrat tot, no ha evitat discordances greus per manca de racionalitat i eficiència en el consum diari dels operadors implicats. Es pretén aconseguir, per mitjà del nou sistema d'oficina judicial estructurat, un avenç efectiu i econòmic a l'estat de la Justícia al país, especialment envers la dilació dels tràmits, a més de reclamar reformes legals, de caire processal especialment, que no es prestin a mers paràmetres d'ajust formal, sinó que incideix substantivament en millores per altre part reclamades fa temps per la doctrina científica. S'han aconseguit les fites definides des del punt de vista teòric, així com s'ha afrontat tots el problemes conceptuals i hipòtesis pràctiques més significatives, establint pautes de resposta sota la prèvia determinació de les qüestions debatudes i els conflictes habituals que correspon enfrontar. D'aquesta manera, s'ha estudiat la normativa en presència i la jurisprudència que hi dona actualitat pràctica, sense oblidar la doctrina d'autors. S'ha repassat el funcionament existent a l'oficina judicial i les previsions de la mateixa en un futur immediat, remarcant les noves tecnologies en ús i projectades, de igual manera que les bondats i crítiques de tots els operador jurídics actuants.

Accessory tendinous slips arising from the extensor carpi ulnaris (ECU) tendon: MRI appearance, prevalence and association with ECU tenosynovitis and tendinopathy

Purpose: To report the MRI features of ECU accessory tendinous slips, assess their observable prevalence and evaluate a potential link between this anatomical variation and ECU tenosynovitis or tendinopathy. Methods and materials: Institutional review board approved this retrospective study, with waiver of patient informed consent. One hundred sixty wrist MRI studies from 158 patients (85 females, 73 males, mean age 45.6 years, range 14-86) performed between March 2008 and February 2009 on a 1.5-T unit were included. MR images were analyzed by two radiologists in consensus. The observable prevalence of ECU accessory tendinous slips was assessed and their origin, diameter and insertion sites were noted. The presence of ECU tenosynovitis and/or tendinopathy was also evaluated. Results: The observable prevalence of ECU accessory tendinous slips was 21.9% (35/160). The origin was always seen: 8 were at the level of, and 27 distal to the ECU subsheath. The slip median diameter was 0.67 mm (range 0.43-0.88). The insertion was seen in 17.1% (6/35): 2 were on the fifth metacarpal bone, 4 on the extensor apparatus of the fifth finger. ECU tenosynovitis (20%), tendinopathy (5.7%) as well as concomitant tenosynovitis and tendinopathy (25.7%) were more frequently encountered in the patients with the anatomical variation than in the control patients group (0.8%, 3.2% and 9.6% respectively). Differences were statistically significant for tenosynovitis (p = 0.0001) and concomitant tenosynovitis and tendinopathy (p = 0.02) of the ECU. Conclusion: ECU accessory tendinous slips are frequent and visible on 1.5-T wrist MRI studies. ECU tenosynovitis and tendinopathy are more frequent in patients bearing this anatomical variation.

Daily physical activity assessment: what is the importance of upper limb movements vs whole body movements?

OBJECTIVE: The movement of the upper limbs (eg fidgeting-like activities) is a meaningful component of nonexercise activity thermogenesis (NEAT). This study examined the relationship between upper limb movements and whole body trunk movements, by simultaneously measuring energy expenditure during the course of the day. DESIGN: A cross-sectional study consisting of 88 subjects with a wide range in body mass index (17.3-32.5 kg/m(2)). The energy expenditure over a 24-h period was measured in a large respiratory chamber. The body movements were assessed by two uniaxial-accelerometers during daytime, one on the waist and the other on the dominant arm. The accelerometry scores from level 0 (=immobile) up to level 9 (=maximal intensity) were recorded. The activities of subjects were classified into eight categories: walking at two speeds on a horizontal treadmill (A & B), ambling (C), self-care tasks (D), desk work (E), meals (F), reading (G), watching TV (H). RESULTS: There was a significant relationship between the accelerometry scores from the waist (ACwaist) and that from the wrist (ACwrist) over the daytime period (R(2)=0.64; P<0.001). The ACwrist was systematically higher than the ACwaist during sedentary activities, whereas it was the reverse for walking activities. ACwrist to ACwaist ratio of activities E-H were above 1.0 and for walking activities (A-C) were below 1.0. A multiple regression analysis for predicting daytime energy expenditure revealed that the explained variance improved by 2% only when the ACwrist was added as a second predictor in addition to the ACwaist. This indicates that the effect of the ACwrist for predicting energy expenditure was of limited importance in our conditions of measurement. CONCLUSIONS: The acceleration of the upper limbs which includes fidgeting is more elevated than that of the whole body for sitting/lying down activities. However, their contribution to energy expenditure is lower than whole body trunk movements, thus indicating that the weight-bearing locomotion activities may be a key component of NEAT. However, its contribution may depend on the total duration of the upper limb movements during the course of the day.

Stratigraphy and palaeoenvironment of Early Jurassic dinosaur-bearing volcaniclastic deposits from Toundoute (Province of Ouarzazate, Haut-Atlas, Morocco)

The Early Jurassic dinosaur site of Toundoute which yielded the basal sauropod Tazoudasaurus naimi is examined in the light of its stratigraphic, sedimentological and palaeoenvironmental context. A thin succession of Early Liassic marine carbonates (probably Hettangian-Sinemurian in age) is continuously overlain by continental beds with dinosaurs. These latter are assumed to be of Middle to Late Liassic age. The continental deposits include a large part of volcanoclastics, different from the Triassic basalts. The Jurassic volcanoclastics originated from an unknown but obviously close eruption centre. The continental sediments (channels and flood plain) were deposited under tropical climate conditions with alternating humid and dry episodes. The bones occur as isolated or partly articulated elements (parts of carcasses). The two bone-beds are related to typical mud-flows. This type of transport protected the bones from erosion, and favoured their burying and fossilization.

Hydrocarbon biomarkers in the Topla-Mezica zinc-lead deposits, northern Karavanke/Drau Range, Slovenia: Paleoenvironment at the site of ore formation

The Mississippi Valley-type zinc and lead deposits at Topla (250,150 metric tons (t) of ore grading 1.0 wt % Zn and 3.3 wt % Pb) and Mezica (19 million metric tons (Mt) of ore grading 5.3 wt % Pb and 2.7 wt % Zn) occur within the Middle to Upper Triassic platform carbonate rocks of the northern Karavanke/Drau Range geotectonic units of the Eastern Alps, Slovenia. The ore and host rocks of these deposits have been investigated by a combination of inorganic and organic geochemical methods to determine major, trace, and rare earth element (REE) concentrations, hydrocarbon distribution, and stable isotope ratios of carbonates, kerogen, extractable organic matter, and individual hydrocarbons. These data combined with sedimentological evidence provide insight into the paleoenvironmental conditions at the site of ore formation. The carbonate isotope composition, the REE patterns, and the distribution of hydrocarbon biomarkers (normal alkanes and steranes) suggest a marine depositional environment. At Topla, a relatively high concentration of redox sensitive trace elements (V, Mo, U) in the host dolostones and REE patterns parallel to that of the North American shale composite suggest that sediments were deposited in a reducing environment. Anoxic conditions enhanced the preservation of organic matter and resulted in relatively higher total organic carbon contents (up to 0.4 wt %). The isotopic composition of the kerogen (delta C-13(kerogon) = -29.4 to -25.0 parts per thousand, delta N-15(kerogen) = -.13.6 to 6.8 parts per thousand) suggests that marine algae and/or bacteria were the main source of organic carbon with a very minor contribution from detrital continental plants and a varying degree of alteration. Extractable organic matter from Topla ore is generally depleted in C-13 compared to the associated kerogen, which is consistent with an indigenous source of the bitumens. The mineralization correlates with delta N-15(kerogen) values around 0 per mil, C-13 depleted kerogen, C-13 enriched n-heptadecane, and relatively high concentrations of bacteria] hydrocarbon biomarkers, indicating a high cyanobacterial biomass at the site of ore formation. Abundant dissimilatory sulfate-reducing bacteria, feeding on the cyanobacterial remains, led to accumulation of biogenic H2S in the pore water of the sediments. This biogenic H2S was mainly incorporated into sedimentary organic matter and diagenetic pyrite. Higher bacterial activity at the ore site also is indicated by specific concentration ratios of hydrocarbons, which are roughly correlated with total Pb plus Zn contents. This correlation is consistent with mixing of hydrothermal metal-rich, fluids and local bacteriogenic sulfide sulfur. The new geochemical data provide supporting evidence that Topla is a low-temperature Mississippi Valley-type deposit formed in an anoxic supratidal saline to hypersaline environment. A laminated cyanobacterial mat, with abundant sulfate-reducing bacteria was the main site of sulfate reduction.