Enhancing Security with Superlens-Enabled Laser Direct Marking of Anti-counterfeiting DotCode

We report a novel anti-counterfeiting laser marking technology based on superlens- assisted nanoscale marking of 2D Dotcodes, which replaces conventional TEXT or other 2D code schemes for enhanced security

Paper Session II-A - SIRTF: The Fourth Great Observatory

The Space Infrared Telescope Facility (SIRTF), the fourth of the Great Observatories, will look through a new window on the universe. Using SIRTF, the astronomical community will be able to explore the infrared universe with a depth and precision complementary to that achieved by NASA’s other Great Observatories-the Hubble Space Telescope (HST), the Advanced X-ray Astrophysics Facility (AXAF), and the Compton Gamma Ray Observatory (GRO). SIRTF will achieve unprecedented infrared sensitivity by fully utilizing a new generation of infrared detector arrays. The new detectors, combined with an 85-cm cryogenic telescope, will allow SIRTF to provide scientific capabilities so impressive that SIRTF was designated the highest priority major new mission for all US astronomy in the 1990s. This paper will provide a review of the SIRTF program—the science, mission design, facility, and the instruments. Emphasis will be placed on those features of the program which will allow us to realize the great scientific potential of the Observatory in a resource-constrained environment

An Extension Study: fMRI use to Distinguish Between Deception andGeneral Memory

The purpose of this study is to expand upon the findings published by Junhong Yu, Qian Tao,Ruibin Zhang, Chetwyn C.H. Chan, and Tatia M.C. Lee in their paper, “Can fMRI discriminatebetween deception and false memory? A meta-analytic comparison between deception and falsememory studies” by conducting a meta-analysis to compare brain activation between deceptionand general memory1 recollection (Yu et al., 2019). Meta-analyses compile fMRI results frommany individual studies with regard to a specific cognitive task into one, cumulative dataset. Themeta-analyses for this extension were compiled by Neurosynth using FMRIB Software Library(FSL) to measure the amount of brain activation corresponding to areas involved in bothdeception and memory in general (“Nipype: Neuroimaging in Python,” 2020). The purpose ofthis extension is to understand how general memory recollection might compare to deception.The prediction of this study is that by broadening the memory dataset to include data from falseand true memory, activation will be reported in more areas than those reported in Yu and hiscolleagues separate analysis of each kind of memory. This, in turn, should make it more difficultto differentiate deception from memory recollection when it is not known to be true or false.While Yu et al. 2019 concluded that areas associated with truthful memory and false memorywere both separately distinguishable from deception, the results found in this study indicate thatactivation involved with general memory was distinguishable from deception only in theprecuneus and cingulate gyrus

Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers

Major histocompatibility complex (MHC) class II tetramers allow the direct visualization of antigen specific CD4+ T cells by flow cytometry. This method relies on the highly specific interaction between peptide loaded MHC and the corresponding T-cell receptor. While the affinity of a single MHC/peptide molecule is low, cross-linking MHC/peptide complexes with streptavidin increases the avidity of the interaction, enabling their use as staining reagents. Because of the relatively low frequencies of CD4+ T cells (~1 in 300,000 for a single specificity) this assay utilizes an in vitro amplification step to increase its threshold of detection. Mononuclear cells are purified from peripheral blood by Ficoll underlay. CD4+ cells are then separated by negative selection using biotinylated antibody cocktail and anti-biotin labeled magnetic beads. Using adherent cells from the CD4- cell fraction as antigen presenting cells, CD4+ T cells are expanded in media by adding an antigenic peptide and IL-2. The expanded cells are stained with the corresponding class II tetramer by incubating at 37 C for one hour and subsequently stained using surface antibodies such as anti-CD4, anti-CD3, and anti-CD25. After labeling, the cells can be directly analyzed by flow cytometry. The tetramer positive cells typically form a distinct population among the expanded CD4+ cells. Tetramer positive cells are usually CD25+ and often CD4 high. Because the level of background tetramer staining can vary, positive staining results should always be compared to the staining of the same cells with an irrelevant tetramer. Multiple variations of this basic assay are possible. Tetramer positive cells may be sorted for further phenotypic analysis, inclusion in ELISPOT or proliferation assays, or other secondary assays. Several groups have also demonstrated co-staining using tetramers and either anti-cytokine or anti-FoxP3 antibodies

RMRP Is a Non-Coding RNA Essential for Early Murine Development

RMRP is a non-coding RNA that is ubiquitously expressed in both humans and mice. RMRP mutations that lead to decreased RMRP levels are found in the pleiotropic syndrome Cartilage Hair Hypoplasia. To assess the effects of deleting RMRP, we engineered a targeting vector that contains loxP sequences flanking RMRP and created hemizygous mice harboring this engineered allele (RMRP conditional). We found that insertion of this cassette suppressed RMRP expression, and we failed to obtain viable mice homozygous for the RMRP conditional allele. Furthermore, we were unable to obtain viable homozygous RMRP null mice, indicating that RMRP is essential for early embryonic development

Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide

An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)–DR4 molecule, and T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A (OspA163–175). We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and correlated these frequencies with in vitro binding of the OspA163–175 peptide to 14 DRB molecules. Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes were similar to those in control subjects. However, when stratified by antibiotic response, the frequencies of DRB1 alleles in the 71 patients with antibiotic-refractory arthritis differed significantly from those in the 50 antibiotic-responsive patients (log likelihood test, P = 0.006; exact test, P = 0.008; effect size, Wn = 0.38). 7 of the 14 DRB molecules (DRB1*0401, 0101, 0404, 0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA163–175, whereas the other seven showed negligible or no binding of the peptide. Altogether, 79% of the antibiotic-refractory patients had at least one of the seven known OspA peptide–binding DR molecules compared with 46% of the antibiotic-responsive patients (odds ratio = 4.4; P < 0.001). We conclude that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic-refractory Lyme arthritis and might play a role in the pathogenesis of the disease

TOHAN: A One-step Approach towards Few-shot Hypothesis Adaptation

In few-shot domain adaptation (FDA), classifiers for the target domain are trained with accessible labeled data in the source domain (SD) and few labeled data in the target domain (TD). However, data usually contain private information in the current era, e.g., data distributed on personal phones. Thus, the private information will be leaked if we directly access data in SD to train a target-domain classifier (required by FDA methods). In this paper, to thoroughly prevent the privacy leakage in SD, we consider a very challenging problem setting, where the classifier for the TD has to be trained using few labeled target data and a well-trained SD classifier, named few-shot hypothesis adaptation (FHA). In FHA, we cannot access data in SD, as a result, the private information in SD will be protected well. To this end, we propose a target orientated hypothesis adaptation network (TOHAN) to solve the FHA problem, where we generate highly-compatible unlabeled data (i.e., an intermediate domain) to help train a target-domain classifier. TOHAN maintains two deep networks simultaneously, where one focuses on learning an intermediate domain and the other takes care of the intermediate-to-target distributional adaptation and the target-risk minimization. Experimental results show that TOHAN outperforms competitive baselines significantly

Pifithrin-alpha inhibits p53 signaling after interaction of the tumor suppressor protein with hsp90 and its nuclear translocation

Pifithrin-alpha (PFTalpha) was originally thought to be a specific inhibitor of signaling by the tumor suppressor protein p53. However, the laboratory that discovered pifithrin recently reported that the compound also inhibits heat shock and glucocorticoid receptor (GR) signaling, and they suggested that PFTalpha targets a factor common to all three signal transduction pathways, such as the hsp90/hsp70-based chaperone machinery (Komarova, E. A., Neznanov, N., Komarov, P. G., Chernov, M. V., Wang, K., and Gudkov, A. V. (2003) J. Biol. Chem. 278, 15465-15468). Because it is important for the mechanistic study of this machinery to identify unique inhibitors of chaperone action, we have examined the effect of PFTalpha on transcriptional activation, the hsp90 heterocomplex assembly, and hsp90-dependent nuclear translocation for both p53 and the GR. At concentrations where PFTalpha blocks p53-mediated induction of p21/Waf-1 in human embryonic kidney cells, we observed no inhibition of GR-mediated induction of a chloramphenicol acetyl transferase reporter in LMCAT cells. PFTalpha did, however, cause a left shift in the dexamethasone dose response curve by increasing intracellular dexamethasone concentration, apparently by competing for dexamethasone efflux from the cell. The assembly of p53 or GR heterocomplexes with hsp90 and immunophilins was not affected by PFTalpha either in vivo or in vitro and did not affect the nuclear translocation of either transcription factor. Thus, we conclude that PFTalpha does not inhibit GR-mediated induction or the function of the chaperone machinery, and, as originally thought, it may specifically inhibit p53 signaling by acting at a stage after p53 translocation to the nucleus.Fil: Murphy, Patrick J.. University of Michigan; Estados UnidosFil: Galigniana, Mario Daniel. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morishima, Yoshihiro. University of Michigan; Estados UnidosFil: Harrell, Jennifer M.. University of Michigan; Estados UnidosFil: Kwok, Roland P.. University of Michigan; Estados UnidosFil: Ljungman, Mats. University of Michigan; Estados UnidosFil: Pratt, William B.. University of Michigan; Estados Unido

Etiology and Pathogenesis of Epithelial Ovarian Cancer

Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established