Capital Punishment in Singapore: A Critical Analysis of State Justifications From 2004 to 2018

This article examines state justifications for capital punishment in Singapore. Singapore is a unique case study because capital punishment has largely been legitimised and justified by state officials. It illustrates how Singapore justifies capital punishment by analysing official discourse. Discussion will focus on the government’s narrative on capital punishment, which has been primarily directed against drug trafficking. Discussion will focus on Singapore’s death penalty regime and associated official discourse that seeks to justify state power to exercise such penalties, rather than the ethics and proportionality of capital punishment towards drug-related crimes. Critical analysis from a criminological perspective adds to the growing body of literature that seeks to conceptualise social and political phenomena in South-East Asia. &nbsp

Low Molecular Weight Components in Aqueous Echinacea Purpurea Leaf Extract Inhibit Melanoma Cell Growth

Melanoma is a skin cancer associated with high mortality. The three year survival rate from advanced melanoma is between 10-15%. One reason for this high mortality rate is that melanoma cells are resistant to traditional chemotherapeutics. Echinacea is a plant genus native to North America with putative anticancer properties. Here, we examined effects of aqueous Echinacea purpurea leaf extract on the growth of melanoma cells and nontransformed fibroblasts. This aqueous extract reduced B16 mouse melanoma cell growth at concentrations that did not inhibit the growth of nontransformed NIH3T3 fibroblasts, suggesting that the extract had biological specificity against transformed cells. We also examined the effect of different fractions of the extract on melanoma cell growth. These data indicate that components less than 3 kD in size exhibited the greatest inhibitory action on melanoma cell growth. In addition, these data indicated that larger components in the extract ameliorate the ability of these low molecular weight compounds to inhibit melanoma cell growth. Furthermore, Echinacea extract inhibited the growth of v-Src transformed LA25 cells without reducing Src kinase activity. Taken together, these results suggest that aqueous Echinacea purpurea extract contains low molecular weight compounds that preferentially inhibit tumor cell growth in the face of oncogenic tyrosine kinase activity. These data suggest future studies to better define bioactive compounds in Echinacea purpurea and evaluate their therapeutic efficacy in vivo

Towards Understanding the Effect of Pretraining Label Granularity

In this paper, we study how pretraining label granularity affects the generalization of deep neural networks in image classification tasks. We focus on the "fine-to-coarse" transfer learning setting where the pretraining label is more fine-grained than that of the target problem. We experiment with this method using the label hierarchy of iNaturalist 2021, and observe a 8.76% relative improvement of the error rate over the baseline. We find the following conditions are key for the improvement: 1) the pretraining dataset has a strong and meaningful label hierarchy, 2) its label function strongly aligns with that of the target task, and most importantly, 3) an appropriate level of pretraining label granularity is chosen. The importance of pretraining label granularity is further corroborated by our transfer learning experiments on ImageNet. Most notably, we show that pretraining at the leaf labels of ImageNet21k produces better transfer results on ImageNet1k than pretraining at other coarser granularity levels, which supports the common practice. Theoretically, through an analysis on a two-layer convolutional ReLU network, we prove that: 1) models trained on coarse-grained labels only respond strongly to the common or "easy-to-learn" features; 2) with the dataset satisfying the right conditions, fine-grained pretraining encourages the model to also learn rarer or "harder-to-learn" features well, thus improving the model's generalization

Knowledge-based planning in robotic intracranial stereotactic radiosurgery treatments

PURPOSE: To develop a knowledge-based planning (KBP) model that predicts dosimetric indices and facilitates planning in CyberKnife intracranial stereotactic radiosurgery/radiotherapy (SRS/SRT). METHODS: Forty CyberKnife SRS/SRT plans were retrospectively used to build a linear KBP model which correlated the equivalent radius of the PTV (req_PTV ) and the equivalent radius of volume that receives a set of prescription dose (req_Vi , where Vi = V10% , V20% ... V120% ). To evaluate the model\u27s predictability, a fourfold cross-validation was performed for dosimetric indices such as gradient measure (GM) and brain V50% . The accuracy of the prediction was quantified by the mean and the standard deviation of the difference between planned and predicted values, (i.e., DeltaGM = GMpred - GMclin and fractional DeltaV50% = (V50%pred - V50%clin )/V50%clin ) and a coefficient of determination, R(2) . Then, the KBP model was incorporated into the planning for another 22 clinical cases. The training plans and the KBP test plans were compared in terms of the new conformity index (nCI) as well as the planning efficiency. RESULTS: Our KBP model showed desirable predictability. For the 40 training plans, the average prediction error from cross-validation was only 0.36 +/- 0.06 mm for DeltaGM, and 0.12 +/- 0.08 for DeltaV50% . The R(2) for the linear fit between req_PTV and req_vi was 0.985 +/- 0.019 for isodose volumes ranging from V10% to V120% ; particularly, R(2) = 0.995 for V50% and R(2) = 0.997 for V100% . Compared to the training plans, our KBP test plan nCI was improved from 1.31 +/- 0.15 to 1.15 +/- 0.08 (P \u3c 0.0001). The efficient automatic generation of the optimization constraints by using our model requested no or little planner\u27s intervention. CONCLUSION: We demonstrated a linear KBP based on PTV volumes that accurately predicts CyberKnife SRS/SRT planning dosimetric indices and greatly helps achieve superior plan quality and planning efficiency

Cost-effectiveness of a Multicomponent Intervention for Hypertension Control in Low-Income Settings in Argentina

Importance: Hypertension is highly prevalent in low- and middle-income countries, and it is an important preventable risk factor for cardiovascular diseases (CVDs). Understanding the economic benefits of a hypertension control program is valuable to decision-makers. Objective: To evaluate the long-term cost-effectiveness of a multicomponent hypertension management program compared with usual care among patients with hypertension receiving care in public clinics in Argentina from a health care system perspective. Design, Setting, and Participants: This economic evaluation used a Markov model to estimate the cost-effectiveness of a hypertension management program among adult patients with uncontrolled hypertension in a low-income setting. Patient-level data (743 individuals for multicomponent intervention; 689 for usual care) from the Hypertension Control Program in Argentina trial (HCPIA) were used to estimate treatment effects and the risk of CVD. Three health states were included in each strategy: (1) low risk of CVD, (2) high risk of CVD, and (3) death. The total time horizon was the lifetime, and each cycle lasted 6 months. Main Outcomes and Measures: Model inputs were based on trial data and other published sources. Cost and utilities were discounted at a rate of 5% annually. The incremental cost-effectiveness ratio (ICER) between the multicomponent intervention and usual care was calculated using the difference in costs in 2017 international dollars (INT $) divided by the difference in effectiveness in quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the uncertainty and robustness of the results. Results: In the original trial, the 743 participants in the intervention group (349 [47.0$3096 discounted costs, while usual care yielded 8.29 discounted QALYs and accrued INT $2473 discounted costs. The ICER for the HCPIA program was INT$4907/QALY gained. The model results remained robust in sensitivity analyses, and the model was most sensitive to parameters of program costs. Conclusions and Relevance: In this study, the HCPIA multicomponent intervention vs usual care was a cost-effective strategy to improve hypertension management and reduce the risk of associated CVD among patients with hypertension who received services at public clinics in Argentina. This intervention program is likely transferable to other settings in Argentina or other lower- and middle-income countries.Fil: Zhang, Yichen. University of Tulane; Estados UnidosFil: Yin, Lei. University of Tulane; Estados UnidosFil: Mills, Katherine. University of Tulane; Estados UnidosFil: Chen, Jing. University of Tulane; Estados UnidosFil: He, Jiang. University of Tulane; Estados UnidosFil: Palacios, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Pichón-riviere, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Shi, Lizheng. University of Tulane; Estados Unido

linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells

Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains have recently been found to contain cryptic open-reading frames and are speculated to encode micropeptides. However, systematic identification and functional assessment of these transcripts have been hindered by technical challenges caused by their small size. Here, we show that two putative lincRNAs (linc-mipep, also called lnc-rps25, and linc-wrb) encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, and demonstrate that they are required for development of vertebrate-specific brain cell types. Specifically, we show that NMDA receptor-mediated pathways are dysregulated in zebrafish lacking these micropeptides and that their loss preferentially alters the gene regulatory networks that establish cerebellar cells and oligodendrocytes - evolutionarily newer cell types that develop postnatally in humans. These findings reveal a key missing link in the evolution of vertebrate brain cell development and illustrate a genetic basis for how some neural cell types are more susceptible to chromatin disruptions, with implications for neurodevelopmental disorders and disease

N-Cadherin Expression Level Distinguishes Reserved versus Primed States of Hematopoietic Stem Cells

SummaryOsteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherinhi) are not stem cells, being largely devoid of a Lineage−Sca1+cKit+ population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherinint) or low (N-cadherinlo) levels. The minority N-cadherinlo population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherinint population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherinint cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations

The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the \u27venom-ome\u27 and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 \u27venom-ome-specific toxins\u27 (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery

Glomerulocystic kidney disease

Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease