Expert

Bangladesh: The Trade-Off Between Economic Prosperity and Human Rights 11 March 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 28 February 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

Bangladesh’s recent gains in economic and social indices, set against its record of corruption and poor civil rights, has at times been termed the ‘Bangladesh Paradox’. Yet this label is overly simplistic; the current situation proves that these trends can coexist.

The Awami League government, in power since 2009, has increased political stability, delivered unprecedented economic and social advances, and adopted a counter-terrorism strategy to stamp out extremist groups. At the same time, it is criticized for curbing civil rights and failing to hold credible elections. However, as the two previous regimes have demonstrated, the rights situation is unlikely to improve even if the Awami League were replaced.

How did worsening rights become a feature of the state irrespective of its political dispensation? An unresolved contest between political and non-political state actors may hold the key to that puzzle. The perils of the current dispensation have recently manifested in weakening economic indicators, which jeopardize the very stability and social progress for which the country has garnered much praise.

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

2 July 2020

Africa Aware: Relations between Ethiopia and Sudan Audio bhorton.drupal 9 April 2022

This episode of Africa Aware examines the relationship between Ethiopia and Sudan.

Ahmed Soliman provides an overview of the Africa Programme’s work on cross-border conflict as part of the XCEPT project.

First, we speak to Kholood Khair on the steady deterioration in relations between Sudan and Ethiopia. Then Abel Abate Demissie discusses how recent political developments in Ethiopia and Sudan have impacted relations between the two countries.

This podcast was produced with support from the Cross-Border Conflict Evidence, Policy and Trends (XCEPT) project, funded by UK Aid from the UK government. The views expressed do not necessarily reflect the UK government’s official policies.

It is also part of a series of outputs on Ethiopia’s political transition.

Visual Abstract

Tricia Rowlison
Dec 1, 2020; 19:2090-2103
Research

Juntuo Zhou
Nov 30, 2020; 0:RA120.002384v1-mcp.RA120.002384
Research

Post-transcriptional modifications of pre-mRNAs expand the diversity of proteomes in higher eukaryotes. In the brain, these modifications diversify the functional output of many critical neuronal signal molecules. In this study, we identified a brain-specific A-to-I RNA editing that changed glutamine to arginine (Q/R) at exon 20 and an alternative splicing of exon 4 in Tmem63b, which encodes a ubiquitously expressed osmosensitive cation channel. The channel isoforms lacking exon 4 occurred in ∼80% of Tmem63b mRNAs in the brain but were not detected in other tissues, suggesting a brain-specific splicing. We found that the Q/R editing was catalyzed by Adar2 (Adarb1) and required an editing site complementary sequence located in the proximal 5' end of intron 20. Moreover, the Q/R editing was almost exclusively identified in the splicing isoform lacking exon 4, indicating a coupling between the editing and the splicing. Elimination of the Q/R editing in brain-specific Adar2 knockout mice did not affect the splicing efficiency of exon 4. Furthermore, transfection with the splicing isoform containing exon 4 suppressed the Q/R editing in primary cultured cerebellar granule neurons. Thus, our study revealed a coupling between an RNA editing and a distant alternative splicing in the Tmem63b pre-mRNA, in which the splicing plays a dominant role. Finally, physiological analysis showed that the splicing and the editing coordinately regulate Ca2+ permeability and osmosensitivity of channel proteins, which may contribute to their functions in the brain.

Ryunosuke Ohkawa
Dec 1, 2020; 61:1577-1588
Research Articles

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1^+/+ and Abca1^–/– mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.

Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information may likely improve the ability to design vaccines with broader effectiveness against evolving strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between WT IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.

Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer to spermatozoa key proteins that are essential in promoting motility and subsequent fertilization success. Using the domestic cat model, the objectives were to (1) characterize and compare protein content of EVs between segments of the epididymis, and (2) compare EV protein compositions between normo- and teratospermic individuals (producing >60% of abnormal spermatozoa). Epididymal EVs from adult cats were isolated and assessed via liquid chromatography tandem MS. Both male types shared 3008 proteins in total, with 98 and 20 EV proteins unique to normospermic and teratospermic males, respectively. Expression levels of several proteins changed between epididymal segments in both male types. Several proteins in both groups were related to sperm motility (e.g. hexokinase 1, adenylate kinase isoenzyme) and zona pellucida or oolemma binding (e.g. disintegrin and metalloproteinase domain proteins, zona binding proteins 1 and 2). Interestingly, seven cauda-derived EV proteins trended downward in teratospermic compared with normospermic males, which may relate to poor sperm quality. Collective results revealed, for the first time, EV proteins related to sequential sperm maturation with differences observed between normospermic and teratospermic individuals.

No abstract

Mass spectrometry-based glycoproteomics has gone through some incredible developments over the last few years. Technological advances in glycopeptide enrichment, fragmentation methods, and data analysis workflows have enabled the transition of glycoproteomics from a niche application, mainly focused on the characterization of isolated glycoproteins, to a mature technology capable of profiling thousands of intact glycopeptides at once. In addition to numerous biological discoveries catalyzed by the technology, we are also observing an increase in studies focusing on global protein glycosylation and the relationship between multiple glycosylation sites on the same protein. It has become apparent that just describing protein glycosylation in terms of micro- and macro-heterogeneity, respectively the variation and occupancy of glycans at a given site, is not sufficient to describe the observed interactions between sites. In this perspective we propose a new term, meta-heterogeneity, to describe a higher level of glycan regulation: the variation in glycosylation across multiple sites of a given protein. We provide literature examples of extensive meta-heterogeneity on relevant proteins such as antibodies, erythropoietin, myeloperoxidase and a number of serum and plasma proteins. Furthermore, we postulate on the possible biological reasons and causes behind the intriguing meta-heterogeneity observed in glycoproteins.

The histopathological subtype of lung adenocarcinoma (LUAD) is closely associated with prognosis. Micropapillary or solid predominant LUAD tends to relapse after surgery at an early stage, whereas lepidic pattern shows a favorable outcome. However, the molecular mechanism underlying this phenomenon remains unknown. Here, we recruited 31 lepidic predominant LUADs (LR: low-risk subtype group) and 28 micropapillary or solid predominant LUADs (HR: high-risk subtype group). Tissues of these cases were obtained and label-free quantitative proteomic and bioinformatic analyses were performed. Additionally, prognostic impact of targeted proteins was validated using The Cancer Genome Atlas databases (n=492) and tissue microarrays composed of early-stage LUADs (n=228). A total of 192 differentially expressed proteins were identified between tumor tissues of LR and HR and three clusters were identified via hierarchical clustering excluding eight proteins. Cluster 1 (65 proteins) showed a sequential decrease in expression from normal tissues to tumor tissues of LR and then to HR and was predominantly enriched in pathways such as tyrosine metabolism and ECM-receptor interaction, and increased matched mRNA expression of 18 proteins from this cluster predicted favorable prognosis. Cluster 2 (70 proteins) demonstrated a sequential increase in expression from normal tissues to tumor tissues of LR and then to HR and was mainly enriched in pathways such as extracellular organization, DNA replication and cell cycle, and high matched mRNA expression of 25 proteins indicated poor prognosis. Cluster 3 (49 proteins) showed high expression only in LR, with high matched mRNA expression of 20 proteins in this cluster indicating favorable prognosis. Furthermore, high expression of ERO1A and FEN1 at protein level predicted poor prognosis in early-stage LUAD, supporting the mRNA results. In conclusion, we discovered key differentially expressed proteins and pathways between low-risk and high-risk subtypes of early-stage LUAD. Some of these proteins could serve as potential biomarkers in prognostic evaluation.

The Phillies have been the favorites in the Bryce Harper sweepstakes for months, and that speculation heated up over the weekend.

The tumor marker cancer antigen 15-3 (CA 15-3) is that most commonly used to monitor metastatic breast cancer during active therapy and surveillance for disease recurrence after treatment. The association of CA 15-3 and ¹⁸F-FDG PET/CT findings can be considered complementary, since any significant rise may indicate the presence of disease and imaging is able to map the tumor sites. Although current guidelines do not recommend the routine performance of CA 15-3 in asymptomatic patients being followed up after definitive breast cancer treatment, most oncologists perform serial assessment of the tumor markers as part of routine follow-up of patients. The aim of this study was to evaluate the correlation between CA 15-3 levels and ¹⁸F-FDG PET/CT scan findings in patients with recurrent breast cancer. Methods: This was a cross-sectional study with data collected retrospectively. Patients being evaluated for breast cancer recurrence with ¹⁸F-FDG PET/CT imaging and CA 15-3 level were included. Evaluation of the association between CA 15-3 levels and ¹⁸F-FDG PET/CT scan findings was then done. Results: In total, 154 cases were included in this study; 62 patients had recurrence (positive) on the ¹⁸F-FDG PET/CT scans, whereas 92 patients had normal (negative) findings on follow-up ¹⁸F-FDG PET/CT scans. There was an association between CA 15-3 levels and the presence or absence of recurrence on ¹⁸F-FDG PET/CT scans, with 84.4% (27/32) of patients who had elevated CA 15-3 levels having disease recurrence on ¹⁸F-FDG PET/CT and 84.4% (27/32) of patients who had elevated CA 15-3 levels having disease recurrence on ¹⁸F-FDG PET/CT as well as a correlation with the burden of metastases. Most patients with disease recurrence on ¹⁸F-FDG PET/CT, however, had normal CA 15-3 levels. Conclusion: Higher CA 15-3 levels correlate with breast cancer recurrence on ¹⁸F-FDG PET/CT as well as with burden of metastasis. Notably, CA 15-3 levels within the reference range do not exclude breast cancer disease recurrence since more than half of patients with recurrence had normal CA 15-3 levels. ¹⁸F-FDG PET/CT should therefore be considered in patients with suspected breast cancer recurrence but normal CA 15-3 levels.

Pennsylvania's rejection of a formal complaint from the state Catholic Conference over COVID aid and private school students highlights a messy dispute taking place in many states.

A statewide survey of educators in Tennessee provides critical insights into connections that exist between standards, curriculum, professional development, and ultimately student success.

Jesse J. Langille
Jul 3, 2019; 39:5244-5246
Journal Club

Randy L. Buckner
Aug 24, 2005; 25:7709-7717
Neurobiology of Disease

AP Georgopoulos
Nov 1, 1982; 2:1527-1537
Articles

Looking at the future of geopolitics, the author reveals the surprising results of his research. Read more at http://www.smithsonianmag.com/specialsections/40th-anniversary/George-Friedman-on-World-War-III.html

The answer…and why you should care

‘Let’s Go Design’ TV Debuts Today

An English teacher, who has lived in North Africa for many years, has the opportunity to share with students about Easter and what it means.

Creating a getaway for Christian workers in tough places can make all the difference.

Couple goes to the Arabian Gulf for three years of adventure and income; over 30 years later, they’re still serving in the Arabian Peninsula.

Ashley Patterson, associate professor of education and women’s, gender and sexuality studies at Penn State, explored the intersection between social justice, equity and education during a JEDI Collaborative speaker series event at Penn State Lehigh Valley. 

Three educators share ways to connect their students to community engagement, including through project-based learning and community-service projects.

Apple unveiled its first mixed-reality headset Vision Pro at WWDC last year. Rumours about its successor have been circulating online for a while, and now Bloomberg's Mark Gurman has suggested the launch timeline for the next generation Apple Vision Pro. Gurman claims that the upcoming model will have a similar design as the current model.

On view from November 5-24, 2021 Wilmington, Del. (November 1, 2021) – The Delaware Division of the Arts’ Mezzanine Gallery is pleased to present visual artist Denise Eno Ernest’s exhibition, In the Between, November 5-24, 2021. Ernest was named a 2021 Emerging Artist Fellow in Painting by the Delaware Division of the Arts. The artist […]

Drawing inspiration from the beauty inherent in everyday life and the human form, Whiddon’s paintings transcend specific places and times, evoking feelings and memories rather than representing them. Her pieces celebrate human sensuality, employing compelling subjects, a vibrant palette, and bold, painterly textures.

1. South Africa vs India Match Prediction - Who will win today’s 3rd T20I match between SA vs IND?  CricTracker
2. SA look to break spin stranglehold while India worry about depth  ESPNcricinfo
3. South Africa vs India 3rd T20 Playing 11, live match time (IST), streaming  Business Standard
4. Time running out for Abhishek, Avesh as Ramandeep-Vyshak waiting in wings: India vs South Africa 3rd T20I Probable XIs  Hindustan Times
5. India, SA eye series lead in Centurion before decisive T20I in Johannesburg  Cricbuzz

Hi there

I am trying to make cross-probe btw layout and schematic view.

so when I execute the code in schematic using bindkey, the code will raise the layout view (hiRaiseWindow)

and then I want to descend to the same hierarchy as schematic. (geSelectFig, leHiEditInPlace)

But looks like current cellview still stays at schematic view.

I got this error msg, and when I print current cell view name at where I got this msg, it replys schematic.

*Error* geSelectFig: argument #1 should be a database object (type template = "d") - nil

is there any way to change the current cellview to layout view?

I also added this code, but didn't work.

geGetEditCellView(geGetCellViewWindow(cvId)) ;cvId is layout view

I don't want to close the schematic view, just want to move the focus or make geSelectFig works.

Thanks in advance.

Microwave Office is Cadence’s tool-of-choice for RF and microwave designers designing everything from III-V 5G chips, to RF systems in board and package technologies. These types of designs require close interaction between the schematic and its layout. A new Training Byte demonstrates how the schematic-layout connections is built into Microwave Office.(read more)

Please give me some ideas. Thank you very much.

Hello everyone,

I hope you're all doing well. I’ve set up two testbenches (TB1 and TB2) for my Design Under Test (DUT) using Cadence IC6.1.8-64b.500.21 tools, as shown in the attached figure. The DUT has multiple views available: schematic, Calibre, Maestro, and Symbol, and each testbench uses the same DUT in different scenarios. Currently, I have to manually switch between these views, but I would like to streamline this process.

My goal is to use a single config view that allows me to switch between the schematic and the extracted (Calibre) views. Ideally, I would like to have a configuration file where making changes once would update both testbenches (TB1 and TB2) automatically. In other words, when I modify one config, both testbenches should reflect this update for a single simulation run.

I would really appreciate it if you could guide me on the following:

1. How to create a config view for my DUT that can be used to easily switch between the schematic and extracted views, impacting both TB1 and TB2.
2. Where to specify view priorities or other settings to control which view is used during simulation.
3. Best practices for using a config file in this scenario, so that it ensures consistency across multiple testbenches.

Please refer to the attached figure to get a better understanding of the setup I’m using, where both TB1 and TB2 include the same DUT with multiple available views.

Thank you so much for your time and assistance!

I'm working on the code coverage. Doing a metrics analysis by default we see overall average grade and overall covered. But when i do a block analysis on an instance i see overall covered grade, code covered grade, block covered grade, statement covered grade, expression covered grade, toggle covered grade.

As I dont know the difference I started to read the IMC user guide and came to know there are 3 things we come across while doing a code coverage local, covered, average

From my understanding

local - child instances metrics doesnt reach the parent level. For example, we have an instance Q and its sub instances like Q.a, Q.b. Block Local grade of Q can be 100% even when its instances Q.a and Q.b a block local grades isnt at 100%.

In the attached image there is formula 

The key difference between average and covered is the weights.

Average : Mathematically taking the above scenario where Q.a, and Q.b has 10 blocks each. Q.a has covered 8 blocks and q.b has covered 2 blocks. Now if we take the normal average it should be total covered/ totatl number = 8+2/10+10 yielding 50%. But when we add weights saying Q.a is 70% and Q.b is 30% the new number would be (8*0.7+2*0.3) / (10*0.7+10*0.3) resulting 62%. Because of the weights we see 12% bump.

Covered: there is no role of weights.

Among these 3 metrics i've changed my default view to this in the image to get more realistic picture when i do analyze metrics. Do you guys agree with the approach?

Hai Community,

What are the differences between the Cadence OrCAD / Allegro 24.1 with the Altium Designer 24.

Can I get the grid matrix difference between these two tools?

Regards,

Rohit Rohan

DOHA, Qatar — A top Qatari official involved in the country's World Cup organization has put the number of worker deaths for the tournament "between 400 and 500" for the first time, a drastically higher number than any other previously offered by Doha. The comment by Hassan al-Thawadi, the secretary-general of Qatar's Supreme Committee for Delivery and Legacy, appeared to come off the cuff during an interview with British journalist Piers Morgan. It also threatened to reinvigorate criticism by human rights groups over the toll of hosting the Middle East's first World Cup for the migrant labor that built over $200 billion worth of stadiums, metro lines and new infrastructure needed for the tournament. The Supreme Committee and Qatar's government did not immediately respond to a request for comment Tuesday. In the interview, portions of which Morgan posted online, the British journalist asks al-Thawadi: "What is the honest, realistic total do you think of migrant workers who died from — as a result of work they're doing for the World Cup in totality?" "The estimate is around 400, between 400 and 500," al-Thawadi responds. "I don't have the exact number. That's something that's been discussed." But that figure hasn't been discussed publicly by Qatari officials previously. Reports from the Supreme Committee dating from 2014 through the end of 2021 only include the number of deaths of workers involved in building and refurbishing the stadiums now hosting the World Cup. Those released figures put the total number of deaths at 40. They include 37 from what the Qataris describe as nonwork incidents such as heart attacks and three from workplace incidents. One report also separately lists a worker death from the coronavirus amid the pandemic. Al-Thawadi pointed to those figures when discussing work just on stadiums in the interview, right before offering the "between 400 to 500" death toll for all the infrastructure for the tournament. Since FIFA awarded the tournament to Qatar in 2010, the country has taken some steps to overhaul the country's employment practices. That includes eliminating its so-called kafala employment system, which tied workers to their employers, who had say over whether they could leave their jobs or even the country. Qatar also has adopted a minimum monthly wage of 1,000 Qatari riyals ($275) for workers and required food and housing allowances for employees not receiving those benefits directly from their employers. It also has updated its worker safety rules to prevent deaths. "One death is a death too many. Plain and simple," al-Thawadi adds in the interview. Activists have called on Doha to do more, particularly when it comes to ensuring workers receive their salaries on time and are protected from abusive employers. Al-Thawadi's comment also renews questions on the veracity of both government and private business reporting on worker injuries and deaths across the Gulf Arab states, whose skyscrapers have been built by laborers from South Asia nations like India, Pakistan and Sri Lanka. Mustafa Qadri, the executive director of Equidem Research, a labor consultancy that has published reports on the toll of the construction on migrant laborers, said he was surprised by al-Thawadi's remark. "For him now to come and say there is hundreds, it's shocking," he told The Associated Press. "They have no idea what's going on."  

Since Israel restricted Muslim access to a holy site in Jerusalem, Israelis and Palestinians have plunged into a new battle in their eternal war.

How will Israel respond to Iran’s recent ballistic missiles barrage? “Strategic patience” is the best course. Israel has its hands full with Hamas and Hezbollah. Now is not the time to escalate a new major war with Iran, which could have nuclear implications. Israeli intelligence is still chafing from its failure to preempt Hamas’ attack […]