The rockefeller university

The cross sections for the production of t (t) over bar b (b) over bar and t (t) over bar jj events and their ratio sigma(t (t) over bar b (b) over bar)/sigma(t (t) over bar jj) are measured using data corresponding to an integrated luminosity of 2.3 fb(-1) collected in pp collisions at root s = 13 TeV with the CMS detector at the LHC. Events with two leptons (e or mu) and at least four reconstructed jets, including at least two identified as b quark jets, in the final state are selected. In the full phase space, the measured ratio is 0.022 +/- 0.003 (stat) +/- 0.006 (syst), the cross section sigma(t (t) over bar b (b) over bar) bis 4.0 +/- 0.6 (stat)+/- 1.3 (syst) pb and sigma(t (t) over bar jj) is 184 +/- 6 (stat)+/- 33 (syst) pb. The measurements are compared with the standard model expectations obtained from a POWHEG simulation at next-to-leading-order interfaced with PYTHIA. (c) 2017 The Author. Published by Elsevier B.V.

Background and Aims: The aim of this study was to evaluate the feasibility and early safety of catheter-directed irreversible electroporation (IRE) of the normal common bile duct (CBD) in swine. Methods: IRE (2000 V, 90 pulses, 100 mu s pulse) was performed in the CBD of 6 Yorkshire pigs using a catheter electrode under endoscopic guidance. Ductal patency was assessed with immediate retrograde cholangiography and contrast-enhanced CT imaging at 1 or 7 days after treatment. Animals were killed at either 1 day (n = 4, 2 ablations/animal) or 7 days (n = 2, 1 ablation/animal) after treatment. The biliary tract was extracted en bloc and the length of the ablation along the CBD mucosa was measured. The depth of ablation was quantified using cross-sections of the treated CBD wall stained with hematoxylin and eosin. Single-sample hypothesis testing was performed to verify whether the depth of ablation in the CBD was a representative outcome of IRE treatment. Results: IRE of the CBD did not result in perforation or obstruction of the organ at 1 or 7 days after treatment. The length of ablation along the CBD mucosa was 17.27 +/- 5.55 mm on day 1 samples, and transmural ablation of the CBD wall was a representative outcome of the treatment (7/8 samples, P < .05). Day 1 samples demonstrated loss of epithelium, transmural necrosis, with preservation of lumen integrity. Day 7 samples demonstrated reepithelialization, with diffuse transmural fibrosis of the CBD wall. These findings were absent from sham tissue samples. Conclusions: Intraluminal catheter-directed IRE is feasible and safe for full-thickness ablation of the normal porcine CBD without affecting lumen patency up to 1 week after treatment.

Apolipoprotein CI (ApoCI) belongs to the Apolipoprotein superfamily, members of which are involved in lipid transport, uptake and homeostasis. Excessive ApoCI has been implicated in atherosclerosis and Alzheimer's disease in humans. In this study we report the isolation of Xenopus laevis apoCI and describe the expression pattern of this gene during early development, using reverse transcription polymerase chain reaction and whole mount in situ hybridization. Xenopus apoCI is enriched in the dorsal ectoderm during gastrulation, and is subsequently expressed in sensory placodes, neural tube and cranial neural crest. These data suggest as yet uncharacterized roles for ApoCI during early vertebrate embryogenesis.

Stem cells of the small and large intestine are marked by expression of the Wnt target gene LGR5, a leucine-rich-repeat-containing G protein-coupled receptor. Previous studies reported increased expression of LGR5 in human colorectal cancer (CRC) compared to normal tissue either by immunohistochemistry or in situ hybridization (ISH). However, as these studies were semi-quantitative they did not provide a numerical estimate of the magnitude of this effect. While we confirm that LGR5(+) cells are exclusively located at the base of normal human small and large intestinal crypts, representing approximately 6% of total crypt cells, we show this cell population is 10-fold expanded in all grades of CRC, representing as much as 70% of the cells of tumor crypt-like structures. This expansion of the LGR5 compartment coincides with maintenance of crypt-like glandular structure (adenomas, and well and moderately differentiated adenocarcinomas), and is reduced in poorly differentiated CRC, where crypt-like glandular architecture is lost, accompanied by reduced epithelial terminal differentiation. Altogether these results indicate that LGR5(+) cell expansion is a hallmark of CRC tumorigenesis occurring during progression to adenoma, supporting CRC as a stem cell disease with implications for CRC therapy.

The mammalian brain is a densely interconnected network that consists of millions to billions of neurons. Decoding how information is represented and processed by this neural circuitry requires the ability to capture and manipulate the dynamics of large populations at high speed and high resolution over a large area of the brain. Although the use of optical approaches by the neuroscience community has rapidly increased over the past two decades, most microscopy approaches are unable to record the activity of all neurons comprising a functional network across the mammalian brain at relevant temporal and spatial resolutions. In this review, we survey the recent development in optical technologies for Ca2+ imaging in this regard and provide an overview of the strengths and limitations of each modality and its potential for scalability. We provide guidance from the perspective of a biological user driven by the typical biological applications and sample conditions. We also discuss the potential for future advances and synergies that could be obtained through hybrid approaches or other modalities.

Neurons in Caenorhabditis elegans and other nematodes have been thought to lack classical action potentials. Unexpectedly, we observe membrane potential spikes with defining characteristics of action potentials in C. elegans AWA olfactory neurons recorded under current-clamp conditions. Ion substitution experiments, mutant analysis, pharmacology, and modeling indicate thatAWA fires calcium spikes, which are initiated by EGL-19 voltage-gated CaV1 calcium channels and terminated by SHK-1 Shaker-type potassium channels. AWA action potentials result in characteristic signals in calcium imaging experiments. These calcium signals are also observed when intact animals are exposed to odors, suggesting that natural odor stimuli induce AWA spiking. The stimuli that elicit action potentials match AWA's specialized function in climbing odor gradients. Our results provide evidence that C. elegans neurons can encode information through regenerative all-or-none action potentials, expand the computational repertoire of its nervous system, and inform future modeling of its neural coding and network dynamics.

Cancer immunotherapy represents a promising treatment approach for malignant gliomas but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified cluster of differentiation (CD)70 as a novel immunosuppressive ligand and glioma target. Normal tissues derived from 52 different organs and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression. The association between CD70 and patients' overall survival and its impact on T-cell death was also evaluated. Human and mouse CD70-specific chimeric antigen receptors (CARs) were tested respectively against human primary GBMs and murine glioma lines. The antitumor efficacies of these CARs were also examined in orthotopic xenograft and syngeneic models. CD70 was not detected in peripheral and brain normal tissues but was constitutively overexpressed by isocitrate dehydrogenase (IDH) wild-type primary LGGs and GBMs in the mesenchymal subgroup and recurrent tumors. CD70 was also associated with poor survival in these subgroups, which may link to its direct involvement in glioma chemokine productions and selective induction of CD8+ T-cell death. To explore the potential for therapeutic targeting of this newly identified immunosuppressive axis in GBM tumors, we demonstrate that both human and mouse CD70-specific CAR T cells recognize primary CD70+ GBM tumors in vitro and mediate the regression of established GBM in xenograft and syngeneic models without illicit effect. These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.

Although the surge in research into the neuroscience of resilience is relatively new, it has been able to elucidate the brain structures that underlie resilience and identify strategies for supporting brain health and mental health across the lifespan. Despite advances, neuroscientists need the input of social work clinicians and clinical researchers to continue to move the field forward. This article provides a narrative review of the recent literature on the neuroscience of resilience with the goal of informing social workers and social work researchers about the state of knowledge in this field. We restricted our review to research in the past 20 years on resilience to stress and trauma, including only those papers that relate to neuroscience or mental functioning. We summarize recent developments in the neuroscience of resiliencenotably the neural circuitry and physiology that underlie resilience in humans and animals. We go on to identify a number of interventions likely to promote resilience and resilient brain function, including parenting and community-based interventions for children and adolescents, hardiness training, meditation and mindfulness approaches, and aerobic exercise. Recommendations are made for future cross-disciplinary work.

The prevalence of affective disorders such as depression and anxiety is particularly high in patients with autoimmune diseases, including inflammatory skin diseases such as psoriasis, atopic dermatitis, and hidradenitis suppurativa. A dys-regulated immune response has been linked to the precipitation of depression in many patient populations. However, studies examining the extent to which the underlying skin disease inflammatory processes contribute to depression and a subsequent decline in quality of life are limited. The published literature over the past 5 years was reviewed for evidence of a relationship between depression and inflammatory processes in the context of skin pathology. The findings, particularly the evidence from interventional clinical trials of targeted anti-cytokine therapies, suggest that pro-inflammatory cytokines associated with several skin diseases may be causally linked with the coexistent depressive symptomology. (C) 2018 S. Karger AG, Basel

Hidradenitis Suppurativa (HS) is a chronic debilitating skin condition that impairs the productivity and the quality of patients` lives. HS has recently drawn lots of attention among scholars to further expand their knowledge but it still loads with uncertainties and gaps to be explored. This publication addresses these uncertainties, and provides a road-map for researchers, scholars and clinicians from different disciplines for their future studies about HS. This is a proceeding report of the first Symposium on Hidradenitis Suppurativa Advances (SHSA), and it reviews the scientific sessions about the epidemiology, pathophysiology, presentations, and management of HS. This symposium was a great opportunity for experts in the HS field to exchange their knowledge, and improve their mutual understanding of this disease.