95 research outputs found

    How Japan’s Cultural Norms Affect Policing: A Side-By-Side Comparison with the United States

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    The ways of policing have been critiqued throughout the years—some have advocated for a direct approach while others value diplomatic techniques. Consideration is emphasized by how culture affects policing in the United States and Japan. In the United States, the customs of policing involve violence, individualism, pragmatism, social mobility, and low power distance, whereas Japan encourages non-violence, face-saving, conservatism, and high power distance. The difference in these cultural norms reflects how policing is conducted in these two countries. To understand how policing in these two countries are different, this paper examines the difference of cultural norms and its impact on both police and community

    An AAPI Haven: A Virtual Sanctuary and Brand Empowerment Initiative

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    The project focuses on creating a brand identity for the Asian American and Pacific Islander (AAPI) community of San Luis Obispo (SLO). The branding begins with research and analysis of the target audience and the organization\u27s mission statement and values. This information is used to develop a brand strategy that aligns with the organization\u27s goals and resonates with the AAPI community. The brand identity, including the logo, colors, and visual elements, is then created to reflect the organization\u27s brand strategy and appeal to the target audience (Tarver, 2023). The brand guidelines ensure consistency in all marketing and communication materials. Overall, creating a strong and cohesive brand for the AAPI SLO organization is crucial for building trust and engagement with the community and achieving the organization\u27s goals of unity and visibility. The second component of the proposed project aims to create a safe space for Asian American individuals to anonymously report hate incidents they have experienced. The primarily virtual platform will provide a safe space for AAPI folks in the community to submit details of the incident, including the type of incident, location, and any other relevant information. Focusing on designing with the environment in mind, the AAPI brand and space will be welcoming and safe, reflecting the purpose that the organization and platform are created to serve. The submissions will be stored safely with the AAPI SLO organization and resources for support will be provided. Additionally, the platform will feature resources for Asian American individuals, including information on legal rights and mental health support. This project aims to address the rising incidence of hate crimes against Asian Americans and empower individuals to speak out against discrimination in a county where they may not feel empowered to

    Robustness of Image-Based Malware Analysis

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    In previous work, “gist descriptor” features extracted from images have been used in malware classification problems and have shown promising results. In this research, we determine whether gist descriptors are robust with respect to malware obfuscation techniques, as compared to Convolutional Neural Networks (CNN) trained directly on malware images. Using the Python Image Library (PIL), we create images from malware executables and from malware that we obfuscate. We conduct experiments to compare classifying these images with a CNN as opposed to extracting the gist descriptor features from these images to use in classification. For the gist descriptors, we consider a variety of classification algorithms including k-nearest neighbors, random forest, support vector machine, and multi-layer perceptron. We find that gist descriptors are more robust than CNNs, with respect to the obfuscation techniques that we consider

    Long-Term Estrogen Therapy Improves Vascular Function in Male to Female Transsexuals

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    AbstractObjectives. This study sought to examine the effects of long-term estrogen therapy on vascular function in male to female transsexuals and to compare the findings with those observed in men and premenopausal women.Background. Gender differences in coronary artery disease have largely been attributed to the beneficial effects of estrogen on vascular function and plasma lipids in women. However, the effects of estrogen on the male vasculature have not been widely studied.Methods. We compared the effects of estrogen on vascular function in 14 male to female transsexuals, 14 age-matched men and 15 premenopausal women. Flow-mediated vasodilation and response to nitroglycerin were assessed in the brachial artery using noninvasive ultrasound.Results. Flow-mediated vasodilation was similar in transsexuals and women but greater than that in men ([mean ± SE] 11.5 ± 1.3% and 9.4 ± 1.1% vs. 5.2 ± 1.0% respectively, p < 0.005). Responses to nitroglycerin were also greater in transsexuals and women than in men (21.6 ± 1.7% and 21.0 ± 0.9% vs. 14.5 ± 1.2%, respectively, p = 0.0005). These differences persisted even after adjusting for vessel size. Despite similar total cholesterol levels, transsexuals had high density lipoprotein cholesterol levels similar to those in women and greater than those observed in men (1.76 ± 0.12 and 1.82 ± 0.11 mmol/liter vs. 1.35 ± 0.07 mmol/liter, respectively, p < 0.005). Moreover, triglyceride levels were greater in transsexuals than in men and women, and low density lipoprotein cholesterol (LDL-C) particle size was smaller (25.7 ± 0.2 nm vs. 26.2 ± 0.1 and 26.6 ± 0.1 nm, respectively, p = 0.0001). Serum testosterone (an index of estrogen therapy in transsexuals) was markedly suppressed in transsexuals and similar to that in women. Univariate analysis revealed that there was a strong inverse correlation between serum testosterone and flow-mediated vasodilation (rs= −0.48, p < 0.005). Multivariate analysis revealed that the best combination of predictors of flow-mediated vasodilation was serum testosterone, vessel size and LDL-C (R2= 0.3, p < 0.005).Conclusions. Long-term estrogen therapy appears to improve vascular function in male to female transsexuals and occurs despite higher triglyceride levels and the presence of small, dense LDL-C. The beneficial effects of estrogen are not gender specific or solely mediated through endothelium-derived nitric oxide.(J Am Coll Cardiol 1997;29:1437–44

    Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

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    CONTEXT: The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. OBJECTIVE: To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. DESIGN: A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. RESULTS: Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. CONCLUSION: Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition

    Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.

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    Background: Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults and children presenting to health care facilities in low resource settings such as the South Asia.  A 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime, or azithromycin is commonly used for its treatment. Increasing antimicrobial resistance threatens the effectiveness of these treatment choices. We hypothesize that combined treatment with azithromycin (active mainly intracellularly) and cefixime (active mainly extracellularly) will be a better option for the treatment of clinically suspected and culture-confirmed typhoid fever in South Asia. Methods: This is a phase IV, international multi-center, multi-country, comparative participant-and observer-blind, 1:1 randomised clinical trial. Patients with suspected uncomplicated typhoid fever will be randomized to one of the two interventions: Arm A: azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) and cefixime 20mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days, Arm B: azithromycin 20mg/kg/day oral dose once daily (max 1gm/day) for 7 days AND cefixime-matched placebo for 7 days. We will recruit 1500 patients across sites in Bangladesh, India, Nepal, and Pakistan. We will assess whether treatment outcomes are better with the combination after one week of treatment and at one- and three-months follow-up. Discussion: Combined treatment may limit the emergence of resistance if one of the components is active against resistant sub-populations not covered by the other antimicrobial activity. If the combined treatment is better than the single antimicrobial treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. Clinicaltrials.gov registration: NCT04349826 (16/04/2020)

    Early Treatment with Fumagillin, an Inhibitor of Methionine Aminopeptidase-2, Prevents Pulmonary Hypertension in Monocrotaline-Injured Rats

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    Pulmonary Hypertension (PH) is a pathophysiologic condition characterized by hypoxemia and right ventricular strain. Proliferation of fibroblasts, smooth muscle cells, and endothelial cells is central to the pathology of PH in animal models and in humans. Methionine aminopeptidase-2 (MetAP2) regulates proliferation in a variety of cell types including endothelial cells, smooth muscle cells, and fibroblasts. MetAP2 is inhibited irreversibly by the angiogenesis inhibitor fumagillin. We have previously found that inhibition of MetAP2 with fumagillin in bleomycin-injured mice decreased pulmonary fibrosis by selectively decreasing the proliferation of lung myofibroblasts. In this study, we investigated the role of fumagillin as a potential therapy in experimental PH. In vivo, treatment of rats with fumagillin early after monocrotaline injury prevented PH and right ventricular remodeling by decreasing the thickness of the medial layer of the pulmonary arteries. Treatment with fumagillin beginning two weeks after monocrotaline injury did not prevent PH but was associated with decreased right ventricular mass and decreased cardiomyocyte hypertrophy, suggesting a direct effect of fumagillin on right ventricular remodeling. Incubation of rat pulmonary artery smooth muscle cells (RPASMC) with fumagillin and MetAP2-targeting siRNA inhibited proliferation of RPASMC in vitro. Platelet-derived growth factor, a growth factor that is important in the pathogenesis of PH and stimulates proliferation of fibroblasts and smooth muscle cells, strongly increased expression of MetP2. By immunohistochemistry, we found that MetAP2 was expressed in the lesions of human pulmonary arterial hypertension. We propose that fumagillin may be an effective adjunctive therapy for treating PH in patients

    Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

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    Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

    Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

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    With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches
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