Experimental observation of the optical spin-orbit torque

Spin polarized carriers electrically injected into a magnet from an external polarizer can exert a spin transfer torque (STT) on the magnetization. The phe- nomenon belongs to the area of spintronics research focusing on manipulating magnetic moments by electric fields and is the basis of the emerging technologies for scalable magnetoresistive random access memories. In our previous work we have reported experimental observation of the optical counterpart of STT in which a circularly polarized pump laser pulse acts as the external polarizer, allowing to study and utilize the phenomenon on several orders of magnitude shorter timescales than in the electric current induced STT. Recently it has been theoretically proposed and experimentally demonstrated that in the absence of an external polarizer, carriers in a magnet under applied electric field can develop a non-equilibrium spin polarization due to the relativistic spin-orbit coupling, resulting in a current induced spin-orbit torque (SOT) acting on the magnetization. In this paper we report the observation of the optical counterpart of SOT. At picosecond time-scales, we detect excitations of magnetization of a ferromagnetic semiconductor (Ga,Mn)As which are independent of the polarization of the pump laser pulses and are induced by non-equilibrium spin-orbit coupled photo-holes.Comment: 4 figure, supplementary information. arXiv admin note: text overlap with arXiv:1101.104

Generation of Human CEACAM1 Transgenic Mice and Binding of Neisseria Opa Protein to Their Neutrophils

Human CEACAM1 is a cell-cell adhesion molecule with multiple functions including insulin clearance in the liver, vasculogenesis in endothelial cells, lumen formation in the mammary gland, and binding of certain human pathogens.Three genomic BAC clones containing the human CEACAM1 gene were microinjected into pronuclei of fertilized FVB mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by PCR for the presence of the human CEACAM1 gene. Feces of the PCR positive offspring screened for expression of human CEACAM1. Using this assay, one out of five PCR positive lines was positive for human CEACAM1 expression and showed stable transmission to the F1 generation with the expected transmission frequency (0.5) for heterozygotes. Liver, lung, intestine, kidney, mammary gland, and prostate were strongly positive for the dual expression of both murine and human CEACAM1 and mimic that seen in human tissue. Peripheral blood and bone marrow granulocytes stained strongly for human CEACAM1 and bound Neisseria Opa proteins similar to that in human neutrophils.These transgenic animals may serve as a model for the binding of human pathogens to human CEACAM1

The CEACAM1 expression is decreased in the liver of severely obese patients with or without diabetes

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes is mainly caused by insulin resistance. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an important candidate for causing insulin resistance.</p> <p>Methods</p> <p>The CEACAM1 expression was evaluated immunohistochemically in the liver tissues of 99 severely obese or non-obese subjects with or without diabetes. The CEACAM1 expression was classified into two categories: a normal expression or a decreased expression.</p> <p>Results</p> <p>The CEACAM1 expression was markedly decreased in the hepatocytes with macrovesicular steatosis. A decreased CEACAM1 expression was noted in 29 (29%) of 99 cases. The incidence of a decreased CEACAM1 expression was significantly higher in high grade fatty liver as well as severe obesity with or without diabetes (p < 0.05). The incidence of a decreased CEACAM1 expression was not different between the diabetic and non-diabetic groups.</p> <p>Conclusions</p> <p>This data supports that a decreased CEACAM1 expression is related to obesity and a fatty liver.</p

Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells

Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs

Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models. METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(-/-) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(-/-) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/-) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/-) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(-/-) vs. control T cells. CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation

Imaging of Disease Dynamics during Meningococcal Sepsis

Neisseria meningitidis is a human pathogen that causes septicemia and meningitis with high mortality. The disease progression is rapid and much remains unknown about the disease process. The understanding of disease development is crucial for development of novel therapeutic strategies and vaccines against meningococcal disease. The use of bioluminescent imaging combined with a mouse disease model allowed us to investigate the progression of meningococcal sepsis over time. Injection of bacteria in blood demonstrated waves of bacterial clearance and growth, which selected for Opa-expressing bacteria, indicating the importance of this bacterial protein. Further, N. meningitidis accumulated in the thyroid gland, while thyroid hormone T4 levels decreased. Bacteria reached the mucosal surfaces of the upper respiratory tract, which required expression of the meningococcal PilC1 adhesin. Surprisingly, PilC1 was dispensable for meningococcal growth in blood and for crossing of the blood-brain barrier, indicating that the major role of PilC1 is to interact with mucosal surfaces. This in vivo study reveals disease dynamics and organ targeting during meningococcal disease and presents a potent tool for further investigations of meningococcal pathogenesis and vaccines in vivo. This might lead to development of new strategies to improve the outcome of meningococcal disease in human patients

A Novel Anti-CEACAM5 Monoclonal Antibody, CC4, Suppresses Colorectal Tumor Growth and Enhances NK Cells-Mediated Tumor Immunity

Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be associated with various types of cancers, particularly colorectal carcinoma, and developed to be a molecular target for cancer diagnosis and therapy. In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical studies found that mAb CC4 specifically and strongly binds to tumor tissues, especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is specifically accumulated in tumor site and remarkably represses colorectal tumor growth. In vitro functional analysis showed that mAb CC4 significantly suppresses cell proliferation, migration and aggregation of colorectal cancer cells and also raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a novel tumor-targeting carrier and cancer therapeutic

Variations in corticosteroid/anesthetic injections for painful shoulder conditions: comparisons among orthopaedic surgeons, rheumatologists, and physical medicine and primary-care physicians

<p>Abstract</p> <p>Background</p> <p>Variations in corticosteroid/anesthetic doses for injecting shoulder conditions were examined among orthopaedic surgeons, rheumatologists, and primary-care sports medicine (PCSMs) and physical medicine and rehabilitation (PMRs) physicians to provide data needed for documenting inter-group differences for establishing uniform injection guidelines.</p> <p>Methods</p> <p>264 surveys, sent to these physicians in our tri-state area of the western United States, addressed corticosteroid/anesthetic doses and types used for subacromial impingement, degenerative glenohumeral and acromioclavicular arthritis, biceps tendinitis, and peri-scapular trigger points. They were asked about preferences regarding: 1) fluorinated vs. non-fluorinated corticosteroids, 2) acetate vs. phosphate types, 3) patient age, and 4) adjustments for special considerations including young athletes and diabetics.</p> <p>Results</p> <p>169 (64% response rate, RR) surveys were returned: 105/163 orthopaedic surgeons (64%RR), 44/77 PCSMs/PMRs (57%RR), 20/24 rheumatologists (83%RR). Although corticosteroid doses do not differ significantly between specialties (p > 0.3), anesthetic volumes show broad variations, with surgeons using larger volumes. Although 29% of PCSMs/PMRs, 44% rheumatologists, and 41% surgeons exceed "recommended" doses for the acromioclavicular joint, >98% were within recommendations for the subacromial bursa and glenohumeral joint. Depo-Medrol^®(methylprednisolone acetate) and Kenalog^®(triamcinolone acetonide) are most commonly used. More rheumatologists (80%) were aware that there are acetate and phosphate types of corticosteroids as compared to PCSMs/PMRs (76%) and orthopaedists (60%). However, relatively fewer rheumatologists (25%) than PCSMs/PMRs (32%) or orthopaedists (32%) knew that phosphate types are more soluble. Fluorinated corticosteroids, which can be deleterious to soft tissues, were used with these frequencies for the biceps sheath: 17% rheumatologists, 8% PCSMs/PMRs, 37% orthopaedists. Nearly 85% use the same non-fluorinated corticosteroid for all injections; <10% make adjustments for diabetic patients.</p> <p>Conclusion</p> <p>Variations between specialists in anesthetic doses suggest that surgeons (who use significantly larger volumes) emphasize determining the percentage of pain attributable to the injected region. Alternatively, this might reflect a more profound knowledge that non-surgeons specialists have of the potentially adverse cardiovascular effects of these agents. Variations between these specialists in corticosteroid/anesthetic doses and/or types, and their use in some special situations (e.g., diabetics), bespeak the need for additional investigations aimed at establishing uniform injection guidelines, and for identifying knowledge deficiencies that warrant advanced education.</p

CEACAM1 Negatively Regulates IL-1β Production in LPS Activated Neutrophils by Recruiting SHP-1 to a SYK-TLR4-CEACAM1 Complex

LPS-activated neutrophils secrete IL-1β by activation of TLR-4. Based on studies in macrophages, it is likely that ROS and lysosomal destabilization regulated by Syk activation may also be involved. Since neutrophils have abundant expression of the ITIM-containing co-receptor CEACAM1 and Gram-negative bacteria such as Neisseria utilize CEACAM1 as a receptor that inhibits inflammation, we hypothesized that the overall production of IL-1β in LPS treated neutrophils may be negatively regulated by CEACAM1. We found that LPS treated neutrophils induced phosphorylation of Syk resulting in the formation of a complex including TLR4, p-Syk, and p-CEACAM1, which in turn, recruited the inhibitory phosphatase SHP-1. LPS treatment leads to ROS production, lysosomal damage, caspase-1 activation and IL-1β secretion in neutrophils. The absence of this regulation in Ceacam1−/− neutrophils led to hyper production of IL-1β in response to LPS. The hyper production of IL-1β was abrogated by in vivo reconstitution of wild type but not ITIM-mutated CEACAM1 bone marrow stem cells. Blocking Syk activation by kinase inhibitors or RNAi reduced Syk phosphorylation, lysosomal destabilization, ROS production, and caspase-1 activation in Ceacam1−/− neutrophils. We conclude that LPS treatment of neutrophils triggers formation of a complex of TLR4 with pSyk and pCEACAM1, which upon recruitment of SHP-1 to the ITIMs of pCEACAM1, inhibits IL-1β production by the inflammasome. Thus, CEACAM1 fine-tunes IL-1β production in LPS treated neutrophils, explaining why the additional utilization of CEACAM1 as a pathogen receptor would further inhibit inflammation

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente