2,239 research outputs found

    The Uniformity Factor-a Proposed Method for Expressing Variations in Specific Gravity

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    Existing measures of uniformity of specific gravity, as obtained by X-ray densitometry, are examined in light of how well they fulfill the requirements thought to be necessary for a uniformity indicator. Based upon an examination of mass and volume specific gravity distributions, a new indicator is proposed. This indicator, the uniformity factor, relates the volume distribution of specific gravity within an increment of wood to a selected reference base. The suitability of the uniformity factor for estimating wood uniformity is shown using data from two species of different uniformities. This approach appears to have potential as a new tool in predicting wood quality

    Preclinical Analysis of JAA-F11, a Specific Anti-Thomsen-Friedenreich Antibody via Immunohistochemistry and In Vivo Imaging.

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    The tumor specificity of JAA-F11, a novel monoclonal antibody specific for the Thomsen-Friedenreich cancer antigen (TF-Ag-alpha linked), has been comprehensively studied by in vitro immunohistochemical (IHC) staining of human tumor and normal tissue microarrays and in vivo biodistribution and imaging by micro-positron emission tomography imaging in breast and lung tumor models in mice. The IHC analysis detailed herein is the comprehensive biological analysis of the tumor specificity of JAA-F11 antibody performed as JAA-F11 is progressing towards preclinical safety testing and clinical trials. Wide tumor reactivity of JAA-F11, relative to the matched mouse IgG3 (control), was observed in 85% of 1269 cases of breast, lung, prostate, colon, bladder, and ovarian cancer. Staining on tissues from breast cancer cases was similar regardless of hormonal or Her2 status, and this is particularly important in finding a target on the currently untargetable triple-negative breast cancer subtype. Humanization of JAA-F11 was recently carried out as explained in a companion paper "Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis" (Neoplasia 19: 716-733, 2017), and it was confirmed that humanization did not affect chemical specificity. IHC studies with humanized JAA-F11 showed similar binding to human breast tumor tissues. In vivo imaging and biodistribution studies in a mouse syngeneic breast cancer model and in a mouse-human xenograft lung cancer model with humanized 124I- JAA-F11 construct confirmed in vitro tumor reactivity and specificity. In conclusion, the tumor reactivity of JAA-F11 supports the continued development of JAA-F11 as a targeted cancer therapeutic for multiple cancers, including those with unmet need

    Forming Student Online Teams For Maximum Performance

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    What is the best way to assign graduate business students to online team-based projects?  Team assignments are frequently made on the basis of alphabet, time zones or previous performance.  This study reviews personality as an indicator of student online team performance.  The personality assessment IDE (Insights Discovery Evaluator) was administered to 450 students in the first six-week course of a proprietary online university MBA program. The IDE was utilized for the study because the university had selected the IDE as a part of its business curriculum. In the second week, students were randomly placed on 138 virtual teams and quantitative data collected from an assignment where students self-reported their IDE type. A qualitative method was used to determine subject IDE type in those cases where subjects did not clearly identify their type. Performance was measured using three instructor- graded assignments completed during the course. Student virtual teams were categorized as random, variable and dominant, contingent upon the composition of team personality types. This study found no statistically significant relationship between IDE’s personality types or the cognitive trait variables of attitude (extroversion and introversion) or trait function (thinking and feeling) on team performance.  Personality trait did not appear to be a variable with the intentional formation of higher performing online student teams. All personality traits performed equally as well. Personality Bias (IDE type homogeneity) was the closest to being statistically significant as a factor in virtual team performance. A model is presented describing the relationship between personality and performance

    Recoiling from a kick in the head-on collision of spinning black holes

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    Recoil ``kicks'' induced by gravitational radiation are expected in the inspiral and merger of black holes. Recently the numerical relativity community has begun to measure the significant kicks found when both unequal masses and spins are considered. Because understanding the cause and magnitude of each component of this kick may be complicated in inspiral simulations, we consider these effects in the context of a simple test problem. We study recoils from collisions of binaries with initially head-on trajectories, starting with the simplest case of equal masses with no spin and then adding spin and varying the mass ratio, both separately and jointly. We find spin-induced recoils to be significant relative to unequal-mass recoils even in head-on configurations. Additionally, it appears that the scaling of transverse kicks with spins is consistent with post-Newtonian theory, even though the kick is generated in the nonlinear merger interaction, where post-Newtonian theory should not apply. This suggests that a simple heuristic description might be effective in the estimation of spin-kicks.Comment: 12 pages, 10 figures. Replaced with published version, including more discussion of convergence and properties of final hol

    Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: A systematic review and meta-analysis

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    BACKGROUND: The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i\u27s) and lower extremity amputation is unclear. PURPOSE: To systematically review randomized control trials (RCTs) and observational studies quantifying risk of lower extremity amputations associated with SGLT2i use. DATA SOURCES AND STUDY SELECTION: We searched PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from January 2011 to February 2020 for RCTs and observational studies including lower extremity amputation outcomes for individuals with type 2 diabetes mellitus treated with SGLT2i\u27s vs. alternative treatments or placebo. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data. MAIN OUTCOMES AND MEASURES: Our primary outcome was risk of lower limb amputation. Secondary outcomes included peripheral arterial disease, peripheral vascular disease, venous ulcerations, and diabetic foot infections. We also evaluated the risk of bias. We conducted random and fixed effects relative risk meta-analysis of RCTs. RESULTS: After screening 2,006 studies, 12 RCTs and 18 observational studies were included, of which 7 RCTs and 18 observational studies had at least one event. The random effects meta-analysis of 7 RCTs suggested the absence of a statistically significant association between SGLT2i exposure with evidence of substantial statistical heterogeneity (n = 424/23,716 vs n = 267/18,737 in controls; RR 1.28, CI\u27s 0.93-1.76; I2 = 62.0%; p = 0.12) whereas fixed effects analysis showed an increased risk with statistical heterogeneity (RR 1.27, 1.09-1.48; I2 = 62%; p = 0.003). Subgroup analysis of canagliflozin vs placebo showed a statistically significantly increased risk in a fixed effects meta-analysis (n = 2 RCTs, RR 1.59, 1.26-2.01; I2 = 88%; p = 0.0001) whereas the meta-analysis of dapagliflozin or empagliflozin (n = 2 RCTs each) and a single RCT for ertugliflozin did not show a significantly increased risk. The findings from observational studies were too heterogeneous to be pooled in a meta-analysis and draw meaningful conclusions. Both randomized and observational studies were of generally good methodological quality. CONCLUSIONS: Overall, there was no consistent evidence of SGLT2i exposure and increased risk of amputation. The increased risk of amputation seen in the large, long-term Canagliflozin Cardiovascular Assessment Study (CANVAS) trial for canagliflozin, and select observational studies, merits continued exploration

    Transfer of memory retrieval cues attenuates the context specificity of latent inhibition

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    Previous studies have demonstrated that the transfer of retrieval cues for original acquisition memories, old \u27reactivated‘ memories, and extinction memories attenuated the context shift effect. This study examined whether latent inhibition (CS preexposure) cues would also transfer, thus alleviating the context specificity. Rats preexposed to a particular context were immediately exposed to a different, novel context. When these rats were trained and tested in the shifted context following preexposure/exposure they showed the latent inhibition effect, i.e., retarded learning in the context that differed from preexposure. That the rats treated the shifted context as the preexposure context demonstrates that the preexposure retrieval cues transferred. These results are consistent with other findings that a novel context can serve as retrieval cues for an event learned in a different setting

    Uncovering the In Vivo Proxisome Using Proximity‐Tagging Methods

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    International audienceThe development of new approaches is critical to gain further insights into biological processes that cannot be obtained by existing methods or technologies. The detection of protein–protein interaction is often challenging, especially for weak and transient interactions or for membrane proteins. Over the last decade, several proximity‐tagging methodologies have been developed to explore protein interactions in living cells. Among those, the most efficient are based on protein partner modification, such as biotinylation or pupylation. Such technologies are based on engineered variants of enzymes like peroxidases or ligases that release reactive molecules, in the presence of specific substrates, that bind surrounding proteins. Fusing a protein of interest (POI) to these enzymes allows the definition of an unbiased “proxisome,” that is, all of the proteins in interaction or in close vicinity of the POI. Here, the different proximity‐labeling tools available are described and comprehensive comparison to discuss advantages and limitations is provided

    Fe−3s core-level splitting and local magnetism in Fe2VAl

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    X-ray and soft x-ray photoelectron spectra were taken on Fe2VAl samples. The Fe−3s spectra show a shoulder on the higher binding energy side of the main peak, split by ≈4.7 eV. Based on current understanding of core-level multiplet splitting in transition-metal compounds, we believe this is direct evidence of a local moment in Fe2VAl

    Chapare Virus, a Newly Discovered Arenavirus Isolated from a Fatal Hemorrhagic Fever Case in Bolivia

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    A small focus of hemorrhagic fever (HF) cases occurred near Cochabamba, Bolivia, in December 2003 and January 2004. Specimens were available from only one fatal case, which had a clinical course that included fever, headache, arthralgia, myalgia, and vomiting with subsequent deterioration and multiple hemorrhagic signs. A non-cytopathic virus was isolated from two of the patient serum samples, and identified as an arenavirus by IFA staining with a rabbit polyvalent antiserum raised against South American arenaviruses known to be associated with HF (Guanarito, Machupo, and Sabiá). RT-PCR analysis and subsequent analysis of the complete virus S and L RNA segment sequences identified the virus as a member of the New World Clade B arenaviruses, which includes all the pathogenic South American arenaviruses. The virus was shown to be most closely related to Sabiá virus, but with 26% and 30% nucleotide difference in the S and L segments, and 26%, 28%, 15% and 22% amino acid differences for the L, Z, N, and GP proteins, respectively, indicating the virus represents a newly discovered arenavirus, for which we propose the name Chapare virus. In conclusion, two different arenaviruses, Machupo and Chapare, can be associated with severe HF cases in Bolivia

    The Arabidopsis translocator protein (AtTSPO) is regulated at multiple levels in response to salt stress and perturbations in tetrapyrrole metabolism

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    <p>Abstract</p> <p>Background</p> <p>The translocator protein 18 kDa (TSPO), previously known as the peripheral-type benzodiazepine receptor (PBR), is important for many cellular functions in mammals and bacteria, such as steroid biosynthesis, cellular respiration, cell proliferation, apoptosis, immunomodulation, transport of porphyrins and anions. <it>Arabidopsis thaliana </it>contains a single <it>TSPO/PBR</it>-related gene with a 40 amino acid N-terminal extension compared to its homologs in bacteria or mammals suggesting it might be chloroplast or mitochondrial localized.</p> <p>Results</p> <p>To test if the TSPO N-terminal extension targets it to organelles, we fused three potential translational start sites in the <it>TSPO </it>cDNA to the N-terminus of GFP (<it>At</it>TSPO:eGFP). The location of the <it>At</it>TSPO:eGFP fusion protein was found to depend on the translational start position and the conditions under which plants were grown. Full-length <it>At</it>TSPO:eGFP fusion protein was found in the endoplasmic reticulum and in vesicles of unknown identity when plants were grown in standard conditions. However, full length <it>At</it>TSPO:eGFP localized to chloroplasts when grown in the presence of 150 mM NaCl, conditions of salt stress. In contrast, when <it>At</it>TSPO:eGFP was truncated to the second or third start codon at amino acid position 21 or 42, the fusion protein co-localized with a mitochondrial marker in standard conditions. Using promoter <it>GUS </it>fusions, qRT-PCR, fluorescent protein tagging, and chloroplast fractionation approaches, we demonstrate that <it>At</it>TSPO levels are regulated at the transcriptional, post-transcriptional and post-translational levels in response to abiotic stress conditions. Salt-responsive genes are increased in a <it>tspo-1 knock-down </it>mutant compared to wild type under conditions of salt stress, while they are decreased when <it>At</it>TSPO is overexpressed. Mutations in tetrapyrrole biosynthesis genes and the application of chlorophyll or carotenoid biosynthesis inhibitors also affect <it>AtTSPO </it>expression.</p> <p>Conclusion</p> <p>Our data suggest that AtTSPO plays a role in the response of <it>Arabidopsis </it>to high salt stress. Salt stress leads to re-localization of the AtTSPO from the ER to chloroplasts through its N-terminal extension. In addition, our results show that <it>AtTSPO </it>is regulated at the transcriptional level in tetrapyrrole biosynthetic mutants. Thus, we propose that <it>At</it>TSPO may play a role in transporting tetrapyrrole intermediates during salt stress and other conditions in which tetrapyrrole metabolism is compromised.</p
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