In the
very special relativity
(VSR) proposal by Cohen and Glashow, it was pointed out that invariance under
HOM
(2) is both necessary and sufficient to explain the null result of the ...Michelson-Morely experiment. It is the quantum field theoretic demand of locality, or the requirement of
P, T, CP
, or
CT
invariance, that makes invariance under the Lorentz group a necessity. Originally it was conjectured that VSR operates at the Planck scale; we propose that the natural arena for VSR is at energies similar to the standard model, but in the dark sector. To this end we provide an
ab initio
spinor representation invariant under the
SIM
(2) avatar of VSR and construct a mass dimension one fermionic quantum field of spin one half. This field turns out to be a very close sibling of Elko and it exhibits the same striking property of intrinsic darkness with respect to the standard model fields. In the new construct, the tension between Elko and Lorentz symmetries is fully resolved. We thus entertain the possibility that the symmetries underlying the standard model matter and gauge fields are those of Lorentz, while the event space underlying the dark matter and the dark gauge fields supports the algebraic structure underlying VSR.
Glioblastoma is the most common primary malignant brain tumor of adults and one of the most lethal of all cancers. Patients with this disease have a median survival of 15 months from the time of ...diagnosis despite surgery, radiation, and chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit from molecularly targeted therapies. Here, we address the compelling need for identification of new molecular targets. Leveraging global gene expression data from two independent sets of clinical tumor samples (n = 55 and n = 65), we identify a gene coexpression module in glioblastoma that is also present in breast cancer and significantly overlaps with the "metasignature" for undifferentiated cancer. Studies in an isogenic model system demonstrate that this module is downstream of the mutant epidermal growth factor receptor, EGFRvIII, and that it can be inhibited by the epidermal growth factor receptor tyrosine kinase inhibitor Erlotinib. We identify ASPM (abnormal spindle-like microcephaly associated) as a key gene within this module and demonstrate its overexpression in glioblastoma relative to normal brain (or body tissues). Finally, we show that ASPM inhibition by siRNA-mediated knockdown inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM as a potential molecular target in glioblastoma. Our weighted gene coexpression network analysis provides a blueprint for leveraging genomic data to identify key control networks and molecular targets for glioblastoma, and the principle eluted from our work can be applied to other cancers.
Ultracold atomic gases have realized numerous paradigms of condensed matter physics, where control over interactions has crucially been afforded by tunable Feshbach resonances. So far, the ...characterization of these Feshbach resonances has almost exclusively relied on experiments in the threshold regime near zero energy. Here, we use a laser-based collider to probe a narrow magnetic Feshbach resonance of rubidium above threshold. By measuring the overall atomic loss from colliding clouds as a function of magnetic field, we track the energy-dependent resonance position. At higher energy, our collider scheme broadens the loss feature, making the identification of the narrow resonance challenging. However, we observe that the collisions give rise to shifts in the center-of-mass positions of outgoing clouds. The shifts cross zero at the resonance and this allows us to accurately determine its location well above threshold. Our inferred resonance positions are in excellent agreement with theory.Studies on energy-dependent scattering of ultracold atoms were previously carried out near zero collision energies. Here, the authors observe a magnetic Feshbach resonance in ultracold Rb collisions for above-threshold energies and their method can also be used to detect higher partial wave resonances.
PTEN is an important tumor-suppressor gene associated with many cancers. Through expression profiling of glioblastoma tissue samples and prostate cancer xenografts, we identified a molecular ...signature for loss of the PTEN tumor suppressor in glioblastoma and prostate tumors. The PTEN signature consists of a minimum of nine genes, several of which are involved in various pathways already implicated in tumor formation. Among these signature genes, the most significant was an increase in insulin growth factor-binding protein 2 (IGFBP-2) mRNA. Up-regulation of IGFBP-2 was confirmed at the protein level by Western blot analysis and validated in samples not included in the microarray analysis. The link between IGFBP-2 and PTEN was of particular interest because elevated serum IGFBP-2 levels have been reported in patients with prostate and brain tumors. To further investigate this link, we determined that IGFBP-2 expression is negatively regulated by PTEN and positively regulated by phosphatidylinositol 3-kinase (PI3K) and Akt activation. In addition, Akt-driven transformation is impaired in IGFBP2⁻/⁻ mouse embryo fibroblasts, implicating a functional role for IGFBP-2 in PTEN signaling. Collectively, these studies establish that PTEN and IGFBP-2 expression are inversely correlated in human brain and prostate cancers and implicate serum IGFBP-2 levels as a potential serum biomarker of PTEN status and PI3K Akt pathway activation in cancer patients.
Zeeman spectroscopy is used to demonstrate that phenomenological crystal-field parameters determined for the two
C
1
point-group symmetry sites in Er
3+
:Y
2
SiO
5
may be transferred to other ions. ...The two crystallographic six-and seven-coordinate substitutional sites may be distinguished by comparing the spectra with crystal-field calculations.
There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection ...(ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi‐array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one‐by‐one analysis strategy to model the real clinical application of this test. Multiple three‐way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction.
This study of kidney transplantation describes a three‐way classifier based on global gene expression profiling of peripheral blood and the blood signatures of patients with excellent functioning grafts that can be used in the setting of acute kidney transplant dysfunction to accurately distinguish between biopsy‐proven acute rejection and acute dysfunction with no rejection.
Gamma-aminobutyric acid (GABA)-ergic disturbances are hallmark features of schizophrenia and other neuropsychiatric disorders and encompass multiple interneuronal cell types. Using bacterial ...artificial chromosome-driven, miRNA silencing technology we generated transgenic mouse lines that suppress glutamic acid decarboxylase 1 (GAD1) in either cholecystokinin (CCK)- or neuropeptide Y (NPY)-expressing interneurons. In situ lipidomic and proteomic analyses on brain tissue sections revealed distinct, brain region-specific profiles in each transgenic line. Behavioral analyses revealed that suppression of GAD1 in CCK+ interneurons resulted in locomotor and olfactory sensory changes, whereas suppression in NPY+ interneurons affected anxiety-related behaviors and social interaction. Both transgenic mouse lines had altered sensitivity to amphetamine albeit in opposite directions. Together, these data argue that reduced GAD1 expression leads to altered molecular and behavioral profiles in a cell type-dependent manner, and that these subpopulations of interneurons are strong and opposing modulators of dopamine system function. Furthermore, our findings also support the hypothesis that neuronal networks are differentially controlled by diverse inhibitory subnetworks.
Aim To determine the influence of solvents on gutta‐percha and sealer remaining on root canal walls and in dentinal tubules.
Methodology The root canals of 70 teeth were prepared chemomechanically ...to apical size 40. In group 1 (n = 10; control group), the canals remained unfilled. In groups 2–4 (n = 20 each), the canals were filled using lateral compaction with gutta‐percha and sealer. Removal of root fillings was undertaken after 2 weeks using Gates Glidden burs and hand files without solvent (group 2), with eucalyptol (60 μL; group 3) and with chloroform (60 μL; group 4) to size 50. After further irrigation using sodium hypochlorite and ethylenediaminetetraacetic acid, the roots were split, photographed and scanning electron microscopy (SEM) was performed. The number of filled dentinal tubules (SEM) and the surface covered by root filling remnants (photographs) were evaluated for the coronal, middle and apical third of each root half. Statistical analysis was performed via mixed model for clustered data followed by Tukey’s test.
Results After pooling the results of all thirds of the canal, open tubules were more prevalent in the control group, followed by the nonsolvent group, the eucalyptol group and the chloroform group (P < 0.05 between all groups). Less surface was covered by root filling remnants in the nonsolvent group than in the eucalyptol group and the chloroform group (P < 0.05); again, fewer remnants were found in the control group than in all other groups (P < 0.05).
Conclusions Solvents led to more gutta‐percha and sealer remnants on root canal walls and inside dentinal tubules.
Early hepatic allograft dysfunction (EAD) manifests posttransplantation with high serum transaminases, persistent cholestasis, and coagulopathy. The biological mechanisms are poorly understood. This ...study investigates the molecular mechanisms involved in EAD and defines a gene expression signature revealing different biological pathways in subjects with EAD from those without EAD, a potential first step in developing a molecular classifier as a potential clinical diagnostic. Global gene expression profiles of 30 liver transplant recipients of deceased donor grafts with EAD and 26 recipients without graft dysfunction were investigated using microarrays of liver biopsies performed at the end of cold storage and after graft reperfusion prior to closure. Results reveal a shift in inflammatory and metabolic responses between the two time points and differences between EAD and non‐EAD. We identified relevant pathways (PPARα and NF‐κB) and targets (such as CXCL1, IL1, TRAF6, TIPARP, and TNFRSF1B) associated with the phenotype of EAD. Preliminary proof of concept gene expression classifiers that distinguish EAD from non‐EAD patients, with Area Under the Curve (AUC) >0.80 were also identified. This data may have mechanistic and diagnostic implications for EAD.
This global gene expression profiling study of liver transplant biopsies from patients with early allograft dysfunction demonstrates a shift in specific inflammatory and metabolic responses and suggests an associated genomic signature.
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