To Root or Not to Root? The Economics of Jailbreak

We construct a structural model that allows us to jointly estimate the demand for smartphones and paid apps using a Bayesian approach. Our data comes from more than 500 college students in Hong Kong and Shanghai. We find that the moral cost rather than the monetary cost of jailbreaking smartphones determines its prevalence. Users mainly jailbreak smartphones to use paid apps for free, a reason more important among Android users than iPhone users. Paid apps contribute the lion's share of the profits (between 53% and 71%) for both the Android and iPhone. Strictly prohibiting jailbreaking would decrease the aggregate market share of smartphones in the cell phone market. Apple, however, would sell even more iPhones at the expense of Android smartphones

Metabolic compensation activates pro-survival mTORC1 signaling upon 3-phosphoglycerate dehydrogenase inhibition in osteosarcoma

Osteosarcoma is the most common pediatric and adult primary malignant bone cancer. Curative regimens target the folate pathway, downstream of serine metabolism, with high-dose methotrexate. Here, the rate-limiting enzyme in the biosynthesis of serine from glucose, 3-phosphoglycerate dehydrogenase (PHGDH), is examined, and an inverse correlation between PHGDH expression and relapse-free and overall survival in osteosarcoma patients is found. PHGDH inhibition in osteosarcoma cell lines attenuated cellular proliferation without causing cell death, prompting a robust metabolic analysis to characterize pro-survival compensation. Using metabolomic and lipidomic profiling, cellular response to PHGDH inhibition is identified as accumulation of unsaturated lipids, branched chain amino acids, and methionine cycle intermediates, leading to activation of pro-survival mammalian target of rapamycin complex 1 (mTORC1) signaling. Increased mTORC1 activation sensitizes cells to mTORC1 pathway inhibition, resulting in significant, synergistic cell death in vitro and in vivo. Identifying a therapeutic combination for PHGDH-high cancers offers preclinical justification for a dual metabolism-based combination therapy for osteosarcoma

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Synthesis of Hyperbranched Poly(vinyleneboride)s with Aggregation-Induced Emission Characteristics by Alkyne Hydroboration

Institute of Textiles and ClothingRefereed conference pape

Sorption Behavior, Speciation, and Toxicity of Microplastic-Bound Chromium in Multisolute Systems

The unexpectedly high affinity of microplastics (MPs) for heavy metals has attracted increasing attention in recent years. However, there is a scarcity of information on the effects of coexisting constituents on plastic–metal interactions, especially in terms of metal speciation. This study aimed to explore the role of benzophenone-type UV filters on the sorption, oxidation state, and toxicity of chromium (Cr) by pristine and UV-irradiated polystyrene MPs (PSMPs). Results showed that Cr uptake by PSMPs was remarkably higher when UV filters were present. This enhanced affinity was attributed to the formation of Cr–UV filter complexes together with multilayer sorption on PSMPs’ surfaces. Subsequent chemical state measurements indicated alteration of the oxidation state of MP-bound metals as a higher Cr­(VI) abundance was identified on the PSMPs with coexisting UV filters. More importantly, our toxicity assessments found that PSMP-bound Cr with a higher oxidation state displayed more severely inhibited microalgae growth. It is noteworthy that toxicological effects of Cr–UV filter complexes were observed only with PSMPs, which thus reaffirms the unique role of MPs in accumulating and transforming contaminants in natural environments. Overall, this study provides the first evidence into the effects of coexisting constituents on the oxidation states and toxicities of MP-bound heavy metals

Analysis of hsp27 and the autophagy marker LC3B \u3csup\u3eþ\u3c/sup\u3e puncta following preoperative chemotherapy identifies high-risk osteosarcoma patients

Chemotherapy-induced autophagy is a proposed mechanism of chemoresistance and potential therapeutic target in osteosarcoma. We evaluated heat shock protein 27 (HSP27) and autophagy-related proteins as predictors of pathologic treatment response and prognostic markers among osteosarcoma patients who received standard chemotherapy. We analyzed 394 tumor specimens (pre-treatment, post-treatment, and metastases) from 260 osteosarcoma patients by immunohistochemistry for cytoplasmic light chain 3B (LC3B)-positive puncta, sequestosome 1 (SQSTM1), high mobility group box 1 (HMGB1), and HSP27 expression. The staining percentage and intensity for each marker were scored and the extent to which marker expression was correlated with pathologic response, relapse-free survival (RFS), and overall survival (OS) was assessed. LCB3 þ puncta in post-treatment primary tumors (50%) and metastases (67%) was significantly higher than in pre-treatment biopsy specimens (30%; P ¼ 0.023 and \u3c0.001). Among 215 patients with localized osteosarcoma, both pretreatment [multivariate hazard ratio (HR), 26.7; 95% confidence interval (CI), 1.47–484; P ¼ 0.026] and post-treatment HSP27 expression (multivariate HR, 1.85; 95% CI, 1.03–3.33; P ¼ 0.039) were associated with worse OS. Lack of LC3B þ puncta at resection was an independent poor prognostic marker in both univariate (HR, 1.78; 95% CI, 1.05–3.03; P ¼ 0.034) and multivariate models (HR, 1.75; 95% CI, 1.01–3.04; P ¼ 0.045). Patients with LC3B þ / HSP27 tumors at resection had the best 10-year OS (75%) whereas patients with LC3B/HSP27 þ tumors had the worst 10-year survival (25%). Neither HSP27 expression nor the presence of LCB3 þ puncta was correlated with pathologic treatment response. Our findings establish HSP27 expression and LC3B þ puncta as independent prognostic markers in osteosarcoma patients receiving standard chemotherapy and support further investigation into strategies targeting HSP27 or modulating autophagy in osteosarcoma treatment