207 research outputs found
Investigation of deep flaws in thin walled tanks
Growth of deep surface flaws in thin wall tanks of aluminum and titanium base metal
Vaccine-induced skewing of T cell responses protects against Chikungunya virus disease
Chikungunya virus (CHIKV) infections can cause severe and debilitating joint and muscular pain that can be long lasting. Current CHIKV vaccines under development rely on the generation of neutralizing antibodies for protection; however, the role of T cells in controlling CHIKV infection and disease is still unclear. Using an overlapping peptide library, we identified the CHIKV-specific T cell receptor epitopes recognized in C57BL/6 infected mice at 7 and 14 days post-infection. A fusion protein containing peptides 451, 416, a small region of nsP4, peptide 47, and an HA tag (CHKVf5) was expressed using adenovirus and cytomegalovirus-vectored vaccines. Mice vaccinated with CHKVf5 elicited robust T cell responses to higher levels than normally observed following CHIKV infection, but the vaccine vectors did not elicit neutralizing antibodies. CHKVf5-vaccinated mice had significantly reduced infectious viral load when challenged by intramuscular CHIKV injection. Depletion of both CD
Animal Models of Chikungunya Virus Infection and Disease
Chikungunya virus (CHIKV) is a reemerging alphavirus that causes acute febrile illness and severe joint pain in humans. Although acute symptoms often resolve within a few days, chronic joint and muscle pain can be long lasting. In the last decade, CHIKV has caused widespread outbreaks of unprecedented scale in the Americas, Asia, and the Indian Ocean island regions. Despite these outbreaks and the continued expansion of CHIKV into new areas, mechanisms of chikungunya pathogenesis and disease are not well understood. Experimental animal models are indispensable to the field of CHIKV research. The most commonly used experimental animal models of CHIKV infection are mice and nonhuman primates; each model has its advantages for studying different aspects of CHIKV disease. This review will provide an overview of animal models used to study CHIKV infection and disease and major advances in our understanding of chikungunya obtained from studies performed in these models
The structure of Onsala 1 star forming region
We present new high-sensitivity high-resolution mm-wave observations of the
Onsala 1 ultra-compact HII region that bring to light the internal structure of
this massive star forming cloud. The 1.2 mm continuum map obtained with the
IRAM 30-m radiotelescope (~11" resolution) shows a centrally peaked
condensation of 1' size (~0.5 pc at the assumed distance of 1.8 kpc) which has
been further investigated at higher resolution in the 3 mm continuum and in the
emission lines of H13CO+ J=1--0 and SiO J=2--1 with the IRAM Plateau de Bure
interferometer. The 3 mm data, with a resolution of ~5" X 4", displays a
unresolved continuum source at the peak of the extended 1.2 mm emission and
closely associated with the ultra-compact HII region. The H13CO+ map traces the
central condensation in good agreement with previous NH_3 maps of Zheng et al.
(1985). However, the velocity field of this central condensation, which was
previously thought to arise in a rapidly rotating structure, is better
explained in terms of the dense and compact component of a bipolar outflow.
This interpretation is confirmed by SiO and CO observations of the full region.
In fact, our new SiO data unveils the presence of multiple (at least 4)
outflows in the region. In particular, there is an important center of outflow
activity in the region at about 1' north of the UCHII region. Indeed the
different outflows are related to different members of the Onsala 1 cluster.
The data presented here support a scenario in which the phases of massive star
formation begin much later in the evolution of a cluster and/or UCHII region
last for much longer than 10^5 yrs.Comment: 6 pages and 3 figure
The Pretty Hill Formation as a natural analogue for CO2 storage: an investigation of mineralogical and isotopic changes associated with sandstones exposed to low, intermediate and high CO2 concentrations over geological time
The Pretty Hill Formation of the Otway Basin (Australia) has been studied as a natural analogue for geological storage of anthropogenic CO in order to examine the effects that CO concentration and reservoir heterogeneity have on CO-related reactions. New petrographic data are presented, which validate the use of Hylogger™ as a tool to investigate high-resolution vertical changes in reservoir mineralogy. The integrated data set confirms earlier interpretations, showing that chlorite has been altered to kaolinite and siderite/ankerite in reservoir facies exposed to moderate and high CO concentrations, while chlorite remains the dominant clay mineral in all parts of the formation where CO content is low.Differences have been observed in the degree of CO-related reaction relative to CO concentration and reservoir heterogeneity. Where CO content is very high (c. 98mol%) and associated with high water saturations, both chlorite and detrital feldspars have undergone complete reaction in the reservoir facies, resulting in quartzose sandstones with a kaolinite matrix, and with siderite as the dominant carbonate precipitate. Conversely, where CO content is moderate (c. 29-57mol%) and within the gas leg of the reservoir, chlorite has undergone significant reaction, but much of the original feldspar is preserved, suggesting relatively minor reaction. Carbonate cements from the moderate CO gas-leg comprise calcite, siderite and ankerite, occurring as cemented zones associated with rock heterogeneities and the present-day gas-water contact. Heterogeneities within the gas-leg are likely to have associated pore fluid contacts, whereby relatively high water saturations will be present in the fine-grained baffles and seals. The most advanced feldspar reaction occurs locally at the contact between baffles and reservoir rock, while reactions have been significantly impeded in the finer grained units due to their low permeabilities.Stable isotope data presented for carbonate cements analysed from wells with low and moderate CO levels show no clear distinction. Relatively early formed calcite has δC values that require an organic carbon source, suggesting precipitation unrelated to the reservoir CO in the Otway Basin. In contrast, diagenetically late calcite and siderite samples display two distinct δC groups (dependent on carbonate type), where the calculated fluid carbon isotope compositions are similar to documented magmatic CO reservoired in the nearby Caroline Field. This suggests that magma-derived CO may have been more prevalent through the Pretty Hill Formation than previously thought. Although the CO has not been contained over the long term in the low CO sites, it may have caused the local dissolution of carbonate and laumontite cement, and also contributed a source of carbon for late-stage calcite cements.These studies illustrate the importance of understanding both the reservoir composition and vertical heterogeneity of potential storage systems. Fluid-mineral reactions are likely to be advanced within stacked reservoir facies and impeded within siltstone layers, while the distribution of carbonate cement may increase the reservoir heterogeneity by the formation of cemented siltstone/sandstone layers, thereby creating impermeable barriers or baffles to CO
Studies on Dibenzylamines as Inhibitors of Venezuelan Equine Encephalitis Virus
Alphaviruses are arthropod-transmitted members of the Togaviridae family that can cause severe disease in humans, including debilitating arthralgia and severe neurological complications. Currently, there are no approved vaccines or antiviral therapies directed against the alphaviruses, and care is limited to treating disease symptoms. A phenotypic cell-based high-throughput screen was performed to identify small molecules that inhibit the replication of Venezuelan Equine Encephalitis Virus (VEEV). The compound, 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-(3-fluoro-4-methoxybenzyl)ethan-1-amine (1), was identified as a highly active, potent inhibitor of VEEV with an effective concentration for 90% inhibition of virus (EC90) of 0.89 ÎĽM and 7.49 log reduction in virus titers at 10 ÎĽM concentration. These data suggest that further investigation of compound 1 as an antiviral therapeutic against VEEV, and perhaps other alphaviruses, is warranted. Experiments suggested that the antiviral activity of compound 1 is directed at an early step in the VEEV replication cycle by blocking viral RNA and protein synthesis
GaMin’11 – an International Inter-laboratory Comparison for Geochemical CO2 - Saline Fluid - Mineral Interaction Experiments
Due to the strong interest in geochemical CO2-fluid-rock interaction in the context of geological storage of CO2 a growing number of research groups have used a variety of different experimental ways to identify important geochemical dissolution or precipitation reactions and – if possible – quantify the rates and extent of mineral or rock alteration. In this inter-laboratory comparison the gas-fluid-mineral reactions of three samples of rock-forming minerals have been investigated by 11 experimental labs. The reported results point to robust identification of the major processes in the experiments by most groups. The dissolution rates derived from the changes in composition of the aqueous phase are consistent overall, but the variation could be reduced by using similar corrections for changing parameters in the reaction cells over time. The comparison of experimental setups and procedures as well as of data corrections identified potential improvements for future gas-fluid-rock studies
Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.
BACKGROUND: Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa. METHODS: We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR). RESULTS: We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2). CONCLUSIONS: PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection
To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic
Introduction After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. Material and methods An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses. Results 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers\u2013however, the number of COVID-19 patients and urologists did not reach double digits. Conclusion The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low
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