3-D Finite Di erence Modeling for Borehole and Reservoir Applications

ERL's in-house nite difference code (Krasovec et al., 2003) has undergone several upgrades in the past year. Most notably, a stretched grid can now be used to greatly reduce the amount of RAM memory needed by certain types of models. Improvements have been made in the GUI front end, allowing more freedom and ease in building the model, source or source array, and receiver array. The finite difference code has contributed to several different research projects at ERL in the past year. A few of these projects, including borehole seismics, reservoir delineation, and source mechanics, are shown in this report.Massachusetts Institute of Technology. Earth Resources LaboratoryMassachusetts Institute of Technology. Borehole Acoustics and Logging Consortiu

Automatic unpaired shape deformation transfer

Transferring deformation from a source shape to a target shape is a very useful technique in computer graphics. State-of-the-art deformation transfer methods require either point-wise correspondences between source and target shapes, or pairs of deformed source and target shapes with corresponding deformations. However, in most cases, such correspondences are not available and cannot be reliably established using an automatic algorithm. Therefore, substantial user effort is needed to label the correspondences or to obtain and specify such shape sets. In this work, we propose a novel approach to automatic deformation transfer between two unpaired shape sets without correspondences. 3D deformation is represented in a high-dimensional space. To obtain a more compact and effective representation, two convolutional variational autoencoders are learned to encode source and target shapes to their latent spaces. We exploit a Generative Adversarial Network (GAN) to map deformed source shapes to deformed target shapes, both in the latent spaces, which ensures the obtained shapes from the mapping are indistinguishable from the target shapes. This is still an under-constrained problem, so we further utilize a reverse mapping from target shapes to source shapes and incorporate cycle consistency loss, i.e. applying both mappings should reverse to the input shape. This VAE-Cycle GAN (VC-GAN) architecture is used to build a reliable mapping between shape spaces. Finally, a similarity constraint is employed to ensure the mapping is consistent with visual similarity, achieved by learning a similarity neural network that takes the embedding vectors from the source and target latent spaces and predicts the light field distance between the corresponding shapes. Experimental results show that our fully automatic method is able to obtain high-quality deformation transfer results with unpaired data sets, comparable or better than existing methods where strict correspondences are required

EARLY STAGE OF THE CENTRAL ASIAN OROGENIC BELT BUILDING: EVIDENCES FROM THE SOUTHERN SIBERIAN CRATON

The origin of the Central-Asian Orogenic Belt (CAOB), especially of its northern segment nearby the southern margin of the Siberian craton (SC) is directly related to development and closure of the Paleo-Asian Ocean (PAO). Signatures of early stages of the PAO evolution are recorded in the Late Precambrian sedimentary successions of the Sayan-Baikal-Patom Belt (SBPB) on the southern edge of SC. These successions are spread over 2000 km and can be traced along this edge from north-west (Sayan area) to south-east (Baikal area) and further to north-east (Patom area). Here we present the synthesis of all available and reliable LA-ICP-MS U-Pb geochronological studies of detrital zircons from these sedimentary successions.The origin of the Central-Asian Orogenic Belt (CAOB), especially of its northern segment nearby the southern margin of the Siberian craton (SC) is directly related to development and closure of the Paleo-Asian Ocean (PAO). Signatures of early stages of the PAO evolution are recorded in the Late Precambrian sedimentary successions of the Sayan-Baikal-Patom Belt (SBPB) on the southern edge of SC. These successions are spread over 2000 km and can be traced along this edge from north-west (Sayan area) to south-east (Baikal area) and further to north-east (Patom area). Here we present the synthesis of all available and reliable LA-ICP-MS U-Pb geochronological studies of detrital zircons from these sedimentary successions

Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer

The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER+ (estrogen receptor-positive)/PR+ human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observedwith PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PRmodulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER+/PR+ breast cancers should be explored

Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial

Background: The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis. Methods: This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting). Findings: From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57–70]) and every 8 weeks group (159 [64%] of 248 [58–70]) than in the placebo group (81 [33%] of 246 [27–39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22–39] for the every 4 weeks group and 31% [23–40] for the every 8 weeks group; both p<0·0001). Up to week 24, serious adverse events occurred in eight (3%) of 245 patients receiving guselkumab every 4 weeks (three serious infections), three (1%) of 248 receiving guselkumab every 8 weeks (one serious infection), and seven (3%) of 246 receiving placebo (one serious infection). No deaths occurred. Interpretation: Guselkumab, a human monoclonal antibody that specifically inhibits IL-23 by binding the cytokine's p19 subunit, was efficacious and demonstrated an acceptable benefit–risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics. These data support the use of selective inhibition of IL-23 to treat psoriatic arthritis

A Consistently High‐Latitude South China From 820 to 780 Ma: implications for Exclusion From Rodinia and the Feasibility of Large‐Scale True Polar Wander

The Tonian supercontinent Rodinia is hypothesized to have included almost all Proterozoic continental blocks. Competing models variably place South China at the core or periphery of Rodinia or separated from it entirely. Tonian paleogeographic models also vary in whether they incorporate hypothesized large and rapid oscillatory true polar wander associated with the ca. 810–795 Ma Bitter Springs Stage. Here, we present paleomagnetic data paired with U-Pb chemical abrasion isotope dilution thermal ionization mass spectrometry zircon geochronology from the Tonian Xiajiang Group in South China to establish the craton's position and test the Bitter Springs Stage true polar wander hypothesis. Fine-grained siliciclastic sediments and ashes of the Xiajiang Group post-date the Jiangnan Orogeny, which united the Yangtze and Cathaysia blocks. A U-Pb zircon date of 815.73 ± 0.18 Ma from a tuff near the base of the Xiajiang Group constrains the Jiangnan Orogeny to have ended between ca. 830 and 816 Ma. The paleomagnetic and geochronologic data constrain South China to high latitudes ca. 813 Ma and indicate a relatively stable high-latitude position from ca. 821 to 805 Ma. These high-latitude constraints either connect the craton to Rodinia along its periphery or disconnect it from the supercontinent entirely. The difference in pole position between the pre-Bitter Springs Stage Xiajiang Group pole and the syn-Bitter Springs Stage Madiyi Formation pole is significantly less than that predicted for the Bitter Springs Stage true polar wander hypothesis. If this pole difference is interpreted as true polar wander superimposed upon differential plate motion, it requires South China to have been separate from Rodinia

A inovação aberta no processo de internacionalização de empresas: estudo de caso da Brasil Foods

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Sócio-Econômico. Relações Internacionais.A presente monografia tem como objetivo o estudo do papel da inovação aberta no processo de internacionalização de empresas, a partir da revisão teórica dos conceitos na literatura e de um estudo de caso real de uma empresa brasileira de grande porte: a Brasil Foods. A presente pesquisa possui caráter de pesquisa exploratória. Para desenvolver o objetivo principal, o trabalho apresenta três objetivos específicos, que são: primeiro apresentar o conceito de inovação, seus graus de inserção e destacar a sua relevância no setor empresarial; segundo apresentar o conceito de inovação aberta e de inovação fechada e esclarecer a importância da difusão de informações; e, terceiro, apresentar os aspectos históricos da internacionalização de empresas, introduzindo duas teorias do processo: Modelo de Uppsala e Perspectiva de Networks. Assim, pode-se exibir, portanto, um modelo conceitual às relações entre as atividades de inovação aberta e a internacionalização de empresas em redes, levandose em consideração que a gestão de inovação nas empresas, atualmente, transcende a visão de inovação tecnológica, e, as redes internacionais ganham cada vez mais relevância como vantagem competitiva nas empresas ao atuar em mercados exteriores. Como resultado, concluiu-se que as estratégias de internacionalização de empresas em redes e as estratégias de inovação aberta, quando empregadas juntas, aumentam a velocidade de aprendizagem organizacional da Brasil Foods, acelerando os processos de internacionalização, confirmando que a inovação aberta estimula e intensifica a internacionalização de empresas que trabalham em redes

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis

Objectives To evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study. Methods Enthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0–6) and Dactylitis Severity Score (range, 0–60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0–100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test. Results Guselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain (p < 0.001), normalized HAQ-DI (p < 0.001), and PCS response (p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03). Conclusion In biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients

Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

INTRODUCTION Although much effort has been devoted to studying yeast in the past few decades, our understanding of this model organism is still limited. Rapidly developing DNA synthesis techniques have made a “build-to-understand” approach feasible to reengineer on the genome scale. Here, we report on the completion of a 770-kilobase synthetic yeast chromosome II (synII). SynII was characterized using extensive Trans-Omics tests. Despite considerable sequence alterations, synII is virtually indistinguishable from wild type. However, an up-regulation of translational machinery was observed and can be reversed by restoring the transfer RNA (tRNA) gene copy number. RATIONALE Following the “design-build-test-debug” working loop, synII was successfully designed and constructed in vivo. Extensive Trans-Omics tests were conducted, including phenomics, transcriptomics, proteomics, metabolomics, chromosome segregation, and replication analyses. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP -mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium. RESULTS To efficiently construct megabase-long chromosomes, we developed an I- Sce I–mediated strategy, which enables parallel integration of synthetic chromosome arms and reduced the overall integration time by 50% for synII. An I- Sce I site is introduced for generating a double-strand break to promote targeted homologous recombination during mitotic growth. Despite hundreds of modifications introduced, there are still regions sharing substantial sequence similarity that might lead to undesirable meiotic recombinations when intercrossing the two semisynthetic chromosome arm strains. Induction of the I- Sce I–mediated double-strand break is otherwise lethal and thus introduced a strong selective pressure for targeted homologous recombination. Since our strategy is designed to generate a markerless synII and leave the URA3 marker on the wild-type chromosome, we observed a tenfold increase in URA3 -deficient colonies upon I- Sce I induction, meaning that our strategy can greatly bias the crossover events toward the designated regions. By incorporating comprehensive phenotyping approaches at multiple levels, we demonstrated that synII was capable of powering the growth of yeast indistinguishably from wild-type cells (see the figure), showing highly consistent biological processes comparable to the native strain. Meanwhile, we also noticed modest but potentially significant up-regulation of the translational machinery. The main alteration underlying this change in expression is the deletion of 13 tRNA genes. A growth defect was observed in one very specific condition—high temperature (37°C) in medium with glycerol as a carbon source—where colony size was reduced significantly. We targeted and debugged this defect by two distinct approaches. The first approach involved phenotype screening of all intermediate strains followed by a complementation assay with wild-type sequences in the synthetic strain. By doing so, we identified a modification resulting from PCRTag recoding in TSC10 , which is involved in regulation of the yeast high-osmolarity glycerol (HOG) response pathway. After replacement with wild-type TSC10 , the defect was greatly mitigated. The other approach, debugging by SCRaMbLE, showed rearrangements in regions containing HOG regulation genes. Both approaches indicated that the defect is related to HOG response dysregulation. Thus, the phenotypic defect can be pinpointed and debugged through multiple alternative routes in the complex cellular interactome network. CONCLUSION We have demonstrated that synII segregates, replicates, and functions in a highly similar fashion compared with its wild-type counterpart. Furthermore, we believe that the iterative “design-build-test-debug” cycle methodology, established here, will facilitate progression of the Sc2.0 project in the face of the increasing synthetic genome complexity. SynII characterization. ( A ) Cell cycle comparison between synII and BY4741 revealed by the percentage of cells with separated CEN2-GFP dots, metaphase spindles, and anaphase spindles. ( B ) Replication profiling of synII (red) and BY4741 (black) expressed as relative copy number by deep sequencing. ( C ) RNA sequencing analysis revealed that the significant up-regulation of translational machinery in synII is induced by the deletion of tRNA genes in synII. </jats:sec