Firming Up Inequality Song, Jae; Price, David J; Guvenen, Fatih ...
The Quarterly journal of economics,
02/2019, Letnik:
134, Številka:
1
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Abstract
We use a massive, matched employer-employee database for the United States to analyze the contribution of firms to the rise in earnings inequality from 1978 to 2013. We find that one-third ...of the rise in the variance of (log) earnings occurred within firms, whereas two-thirds of the rise occurred due to a rise in the dispersion of average earnings between firms. However, this rising between-firm variance is not accounted for by the firms themselves but by a widening gap between firms in the composition of their workers. This compositional change can be split into two roughly equal parts: high-wage workers became increasingly likely to work in high-wage firms (i.e., sorting increased), and high-wage workers became increasingly likely to work with each other (i.e., segregation rose). In contrast, we do not find a rise in the variance of firm-specific pay once we control for the worker composition in firms. Finally, we find that two-thirds of the rise in the within-firm variance of earnings occurred within mega (10,000+ employee) firms, which saw a particularly large increase in the variance of earnings compared with smaller firms.
Systemic corticosteroid use to manage uncontrolled asthma and its associated healthcare burden may account for important health-related adverse effects. We conducted a systematic literature review to ...investigate the real-world extent and burden of systemic corticosteroid use in asthma. We searched MEDLINE and Embase databases to identify English-language articles published in 2010-2017, using search terms for asthma with keywords for oral corticosteroids and systemic corticosteroids. Observational studies, prescription database analyses, economic analyses, and surveys on oral/systemic corticosteroid use in children (>5 yr old), adolescents (12-17 yr old), and adults with asthma were included. We identified and reviewed 387 full-text articles, and our review included data from 139 studies. The included studies were conducted in Europe, North America, and Asia. Overall, oral/systemic corticosteroids were commonly used for asthma management and were more frequently used in patients with severe asthma than in those with milder disease. Long-term oral/systemic corticosteroid use was, in general, less frequent than short-term use. Compared with no use, long-term and repeated short-term oral/systemic corticosteroid use were associated with an increased risk of acute and chronic adverse events, even when doses were comparatively low. Greater oral/systemic corticosteroid exposure was also associated with increased costs and healthcare resource use. This review provides a comprehensive overview of oral/systemic corticosteroid use and associated adverse events for patients with all degrees of asthma severity and exposure duration. We report that oral/systemic corticosteroid use is prevalent in asthma management, and the risks of acute and chronic complications increase with the cumulative oral corticosteroid dosage.
RNA polymerase II elongation control Zhou, Qiang; Li, Tiandao; Price, David H
Annual review of biochemistry,
01/2012, Letnik:
81
Journal Article
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Regulation of the elongation phase of transcription by RNA polymerase II (Pol II) is utilized extensively to generate the pattern of mRNAs needed to specify cell types and to respond to environmental ...changes. After Pol II initiates, negative elongation factors cause it to pause in a promoter proximal position. These polymerases are poised to respond to the positive transcription elongation factor P-TEFb, and then enter productive elongation only under the appropriate set of signals to generate full-length properly processed mRNAs. Recent global analyses of Pol II and elongation factors, mechanisms that regulate P-TEFb involving the 7SK small nuclear ribonucleoprotein (snRNP), factors that control both the negative and positive elongation properties of Pol II, and the mRNA processing events that are coupled with elongation are discussed.
The importance of Indonesia’s Corruption Eradication Commission (Komisi Pemberantasan Korupsi KPK), has once again been brought into focus during the 2024 presidential election campaign period when ...politics and corruption collide. This article suggests that legislative and political actions since 2019 to the KPK’s purpose and structure severely limit its capacity and independence making it susceptible to greater political interference and coercion. The KPK was established by Law 30/2002, as a response to and recognition of rampant corruption throughout the governmental, political and public sectors, business communities, and society in general, which became common practice during President Suharto’s New Order Regime. The KPK’s commission encompasses conducting investigations, indictments, and prosecutions. However, in late 2019, the People’s Representative Council enacted amending legislation to weaken its authority and ability to operate independently. Crucial legislative changes included creating a government-appointed supervisory body overseeing the KPK’s internal operations and changing KPK employee status from independent agents to public servants. These two provisions alone seriously weaken the KPK’s autonomy and create the risk of turning it into a politically controlled auxiliary state agency. In some respects, KPK has become a victim of its own successes, having achieved convictions of senior ministers, politicians, government officials, and business leaders, which in turn has produced enemies. Without political protection, the KPK faces the prospect of not only becoming, in essence, a nonentity but also facing further deterioration of its credibility and authority.
Extremely brachycephalic, or short-muzzled, dog breeds such as pugs, French bulldogs, and bulldogs are prone to the conformation-related respiratory disorder-brachycephalic obstructive airway ...syndrome (BOAS). Affected dogs present with a wide range of clinical signs from snoring and exercise intolerance, to life-threatening events such as syncope. In this study, conformational risk factors for BOAS that could potentially aid in breeding away from BOAS were sought. Six hundred and four pugs, French bulldogs, and bulldogs were included in the study. Soft tape measurements of the head and body were used and the inter-observer reproducibility was evaluated. Breed-specific models were developed to assess the associations between the conformational factors and BOAS status based on functional grading. The models were further validated by means of a BOAS index, which is an objective measurement of respiratory function using whole-body barometric plethysmography. The final models have good predictive power for discriminating BOAS (-) and BOAS (+) phenotypes indicated by the area under the curve values of >80% on the receiver operating curves. When other factors were controlled, stenotic nostrils were associated with BOAS in all three breeds; pugs and bulldogs with higher body condition scores (BCS) had a higher risk of developing BOAS. Among the standardized conformational measurements (i.e. craniofacial ratio (CFR), eye width ratio (EWR), skull index (SI), neck girth ratio (NGR), and neck length ratio (NLR)), for pugs EWR and SI, for French bulldogs NGR and NLR, and for bulldogs SI and NGR showed significant associations with BOAS status. However, the NGR in bulldogs was the only significant predictor that also had satisfactory inter-observer reproducibility. A NGR higher than 0.71 in male bulldogs was predictive of BOAS with approximately 70% sensitivity and specificity. In conclusion, stenotic nostrils, BCS, and NGR were found to be valid, easily applicable predictors for BOAS (+).
The Future of Peptide-based Drugs Craik, David J.; Fairlie, David P.; Liras, Spiros ...
Chemical biology & drug design,
January 2013, Letnik:
81, Številka:
1
Journal Article
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The suite of currently used drugs can be divided into two categories – traditional ‘small molecule’ drugs with typical molecular weights of <500 Da but with oral bioavailability, and much larger ...‘biologics’ typically >5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size, conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side‐effects, whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them, but this comes at a cost of low bioavailability, poor membrane permeability, and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes, with the goal of combining advantages of small molecules (cost, conformational restriction, membrane permeability, metabolic stability, oral bioavailability) with those of proteins (natural components, target specificity, high potency). This article uses selected examples of peptides to highlight the importance of peptide drugs, some potential new opportunities for their exploitation, and some difficult challenges ahead in this field.
Peptides fill a gap between traditional ‘small molecule’ drugs with molecular weights <500 Da and usually favorable oral bioavailability, and much larger ‘biologics’, typically >5000 Da, that are not orally bioavailable and need to be delivered via injection. Peptides in this size range are large enough to modulate protein:protein interactions, an increasingly important target class. Strategies to achieve the necessary stability and bioavailability of peptide drugs include the use of secondary structure mimics and stable cyclic peptide frameworks.
Mitochondria in health, disease, and aging Harrington, John S; Ryter, Stefan W; Plataki, Maria ...
Physiological reviews,
10/2023, Letnik:
103, Številka:
4
Journal Article
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Mitochondria are well known as organelles responsible for the maintenance of cellular bioenergetics through the production of ATP. Although oxidative phosphorylation may be their most important ...function, mitochondria are also integral for the synthesis of metabolic precursors, calcium regulation, the production of reactive oxygen species, immune signaling, and apoptosis. Considering the breadth of their responsibilities, mitochondria are fundamental for cellular metabolism and homeostasis. Appreciating this significance, translational medicine has begun to investigate how mitochondrial dysfunction can represent a harbinger of disease. In this review, we provide a detailed overview of mitochondrial metabolism, cellular bioenergetics, mitochondrial dynamics, autophagy, mitochondrial damage-associated molecular patterns, mitochondria-mediated cell death pathways, and how mitochondrial dysfunction at any of these levels is associated with disease pathogenesis. Mitochondria-dependent pathways may thereby represent an attractive therapeutic target for ameliorating human disease.
Transient pausing by RNA polymerase II Price, David H.
Proceedings of the National Academy of Sciences - PNAS,
05/2018, Letnik:
115, Številka:
19
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Price comments on a study that questions RNA polymerase II (Pol II) elongation control utilized during transcription of most metazoan genes. Researchers generated a human cell line solely expressing ...GFP-tagged Pol II and then used fluorescence recovery after photobleaching (FRAP) to identify and characterize four distinguishable kinetic states for Pol II. Besides the very rapid recovery due to diffusion of free Pol II, they found three bound states, each with about an order of magnitude slower recovery than the preceding one. These kinetic states were assigned to initiation, pausing, and productive elongation by observing how well-characterized compounds affected the FRAP measurements.
While entities as different as armed groups, multinational corporations, political parties, megacities, labour unions, terrorist organisations, or indigenous peoples are mentioned as non-state actors ...in the relevant literature, rural communities are never referred to. This book addresses the role of rural communities as non-state actors, lifting this invisibility veil with arguments coming from three theories of/scholarly approaches to international law: positivism, sociolegal realism (the New Haven School), and constitutionalism. It argues, first, that rural communities are recognised by the community of states as derived subjects of international law since they are made bearers of rights and duties in some major multilateral treaties. Second, rural communities have the ability to affect international lawmaking as they acquire the tools to influence decision-making in international arbitration and court litigation. Finally, the book highlights the need to recognise the status of rural communities when seeking global justice, as these are the communities that benefit the least from globalisation, while paying the highest price in terms of damage to the natural and sociocultural environment. Advocating for the existence of some supreme norms above the will of the states and the recognition of rural communities as non-state actors, this book will be of interest to academics, policy-makers, and non-governmental organisations working in the field of public international law and rural social matters.
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