Dwell-free input methods for people with motor impairments

Millions of individuals affected by disorders or injuries that cause severe motor impairments have difficulty performing compound manipulations using traditional input devices. This thesis first explores how effective various assistive technologies are for people with motor impairments. The following questions are studied: (1) What activities are performed? (2) What tools are used to support these activities? (3) What are the advantages and limitations of these tools? (4) How do users learn about and choose assistive technologies? (5) Why do users adopt or abandon certain tools? A qualitative study of fifteen people with motor impairments indicates that users have strong needs for efficient text entry and communication tools that are not met by existing technologies. To address these needs, this thesis proposes three dwell-free input methods, designed to improve the efficacy of target selection and text entry based on eye-tracking and head-tracking systems. They yield: (1) the Target Reverse Crossing selection mechanism, (2) the EyeSwipe eye-typing interface, and (3) the HGaze Typing interface. With Target Reverse Crossing, a user moves the cursor into a target and reverses over a goal to select it. This mechanism is significantly more efficient than dwell-time selection. Target Reverse Crossing is then adapted in EyeSwipe to delineate the start and end of a word that is eye-typed with a gaze path connecting the intermediate characters (as with traditional gesture typing). When compared with a dwell-based virtual keyboard, EyeSwipe affords higher text entry rates and a more comfortable interaction. Finally, HGaze Typing adds head gestures to gaze-path-based text entry to enable simple and explicit command activations. Results from a user study demonstrate that HGaze Typing has better performance and user satisfaction than a dwell-time method

Mock X-ray observations of hot gas with L-Galaxies semi-analytic models of galaxy formation

We create mock X-ray observations of hot gas in galaxy clusters with a new extension of L-Galaxies semi-analytic model of galaxy formation, which includes the radial distribution of hot gas in each halo. Based on the model outputs, we first build some mock light cones, then generate mock spectra with SOXS package and derive the mock images in the light cones. Using the mock data, we simulate the mock X-ray spectra for ROSAT all-sky survey, and compare the mock spectra with the observational results. Then, we consider the design parameters of HUBS mission and simulate the observation of the halo hot gas for HUBS as an important application of our mock work. We find: (1) Our mock data match the observations by current X-ray telescopes. (2) The survey of hot baryons in resolved clusters by HUBS is effective below redshift 0.5, and the observations of the emission lines in point-like sources at z>0.5 by HUBS help us understand the hot baryons in the early universe. (3) By taking the advantage of the large simulation box and flexibility in semi-analytic models, our mock X-ray observations provide the opportunity to make target selection and observation strategies for forthcoming X-ray facilities.Comment: 15 pages, 11 figures, comments welcom

Induction of defensive enzymes (isozymes) during defense against two different fungal pathogens in pear calli

Activities of defensive enzymes peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), polyphenol oxidase (PPO) and esterase (EST) and their isozymes in pear calli were studied to reveal their role in the defensive response to different fungal infections and to find some clues to enhance their antimicrobial properties. The results confirm the fact that the activities and isozymes of these five enzymes showed differences in response to different fungal infections. After the inoculation of two different fungi for the same calli, its defensive enzymes’ activities changed relatively when compared with those of the control and in Botryosphaeria berengriana f.sp. piricola (BBP)-infected calli, the enzymes’ activities changed more significantly than those of Monilinia fructigena Honcy (MFH). Meanwhile, more new isozymes were induced by BBP infection. These are in agreement with the fact that the BBP-infected calli decay was slower than that of the MFH. These results suggest that enhancing defensive enzymes’ activities and inducing new isozymes may be related to mitigating pathogen-induced oxidative damage which result in the decrease of calli decay, and this implies that antioxidant defense response may be involved in the mechanisms of plant against fungal pathogen.Keywords: Pear callus, fungi infection, defense enzyme, isozyme, biochemical defense mechanis

G protein-coupled receptor 68 increases the number of B lymphocytes

G protein-coupled receptor 68 (GPR68) is a proton sensor that is activated upon binding to extracellular protons. We have previously found that GPR68 induces a proapoptotic pathway in bone marrow (BM) cells from the patients with myelodysplastic syndromes (MDS) after treated with lenalidomide. However, the function of GPR68 in normal hematopoietic cells remains unclear. With genetic loss of function approach, we found reduced frequency and number of B lymphocytes in the peripheral blood (PB) of whole body Gpr68-/- mice compared to control littermates upon aging. During hematopoietic regeneration, such as in response to fluorouracil (5-FU), we also found reduced frequency and number of B lymphocytes in Gpr68-/- mice compared to wild type mice. Mechanism studies revealed that Gpr68 expression was upregulated in B lymphocytes of BM during aging and in hematopoietic progenitor cells after treatment with 5-FU. In addition, activation of Gpr68 by its activators increased the frequency and number of B lymphocytes. Our studies indicate that Gpr68 expression is upregulated in hematopoietic cells upon aging and during hematopoietic regeneration that ends up with increased number of B lymphocytes

HGaze Typing: head-gesture assisted gaze typing

This paper introduces a bi-modal typing interface, HGaze Typing, which combines the simplicity of head gestures with the speed of gaze inputs to provide efficient and comfortable dwell-free text entry. HGaze Typing uses gaze path information to compute candidate words and allows explicit activation of common text entry commands, such as selection, deletion, and revision, by using head gestures (nodding, shaking, and tilting). By adding a head-based input channel, HGaze Typing reduces the size of the screen regions for cancel/deletion buttons and the word candidate list, which are required by most eye-typing interfaces. A user study finds HGaze Typing outperforms a dwell-time-based keyboard in efficacy and user satisfaction. The results demonstrate that the proposed method of integrating gaze and head-movement inputs can serve as an effective interface for text entry and is robust to unintended selections.https://dl.acm.org/doi/pdf/10.1145/3448017.3457379Published versio

A Comprehensive Analysis of the CaMK2A Gene and Susceptibility to Alzheimer’s Disease in the Han Chinese Population

There is ample evidence suggesting that calcium/calmodulin-dependent protein kinase II alpha (CaMK2A) may play an important role in the pathophysiology of Alzheimer’s disease (AD). This genetic study aimed to investigate whether CaMK2A confers susceptibility to the development of AD in the Han Chinese population. A total of seven single nucleotide polymorphisms (SNPs) within CaMK2A were screened in two independent cohorts from southwestern China (333 AD patients and 334 controls) and eastern China (382 AD patients and 426 controls) to discern the potential association between this gene and AD. In addition, a cross-platform normalized expression resource was used to investigate whether CaMK2A is differentially expressed in the brain between individuals with AD and the controls. In addition, expression quantitative trait loci (eQTL) analysis was used to explore the differences in CaMK2A expression in the brain among different genotypes. The cross-platform normalized data showed significant differences in CaMK2A expression in the hippocampus, entorhinal cortex and temporal cortex between the AD patients and the control subjects (|log FC| > 0.1, P < 0.05); however, only the differences in the hippocampus and temporal cortex remained after the multiple comparisons correction [false discovery rate (FDR)-corrected, P < 0.05]. The frequency of the rs4958445 genotype was significantly different between the AD subjects and the controls from southwestern China (P = 0.013, P = 0.034 after FDR correction). When the two samples were combined, rs4958445 still showed a significant association with AD (P = 0.044). Haplotype analysis indicated that the T-A-C-A-T-C-C and T-G-C-A-T-C-C haplotypes in the southwestern cohort and the T-G-C-G-C-T-C haplotype in the eastern cohort, consisting of rs10051644, rs6869634, rs3797617, rs3756577, rs4958445, rs10515639 and rs6881743, showed a significant association with AD (P = 0.037, P = 0.026 and P = 0.045, respectively). Furthermore, the brain eQTL analysis revealed a significant association between the rs4958445 polymorphism and CaMK2A expression in the inferior olivary nucleus (P = 0.029). Our results suggest an important role for CaMK2A in the pathophysiology of AD in the Han Chinese population, especially the southwestern population

Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1

CRISPR-mediated direct mutation of cancer genes in the mouse liver

The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem (ES) cells1. Here we describe a new method of cancer model generation using the CRISPR/Cas system in vivo in wild-type mice. We have used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs)2–4 to the liver and directly target the tumor suppressor genes Pten5 and p536, alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology7, 8. Simultaneous targeting of Pten and p53 induced liver tumors that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumor tissue revealed insertion or deletion (indel) mutations of the tumor suppressor genes, including bi-allelic mutations of both Pten and p53 in tumors. Furthermore, co-injection of Cas9 plasmids harboring sgRNAs targeting the β-Catenin gene (Ctnnb1) and a single-stranded DNA (ssDNA) oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of β-Catenin. This study demonstrates the feasibility of direct mutation of tumor suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival