Drivers of abrupt Holocene shifts in West Antarctic ice stream direction from combined ice sheet modelling and geologic signatures

Determining the millennial-scale behaviour of marine-based sectors of the West Antarctic Ice Sheet (WAIS) is critical to improve predictions of the future contribution of Antarctica to sea level rise. Here high-resolution ice sheet modelling was combined with new terrestrial geological constraints (in situ14C and 10Be analysis) to reconstruct the evolution of two major ice streams entering the Weddell Sea over 20 000 years. The results demonstrate how marked differences in ice flux at the marine margin of the expanded Antarctic ice sheet led to a major reorganization of ice streams in the Weddell Sea during the last deglaciation, resulting in the eastward migration of the Institute Ice Stream, triggering a significant regional change in ice sheet mass balance during the early to mid Holocene. The findings highlight how spatial variability in ice flow can cause marked changes in the pattern, flux and flow direction of ice streams on millennial timescales in this marine ice sheet setting. Given that this sector of the WAIS is assumed to be sensitive to ocean-forced instability and may be influenced by predicted twenty-first century ocean warming, our ability to model and predict abrupt and extensive ice stream diversions is key to a realistic assessment of future ice sheet sensitivity

Opposing effects of high- and low-molecular weight hyaluronan on CXCL12-induced CXCR4 signaling depend on CD44

The tumor microenvironment makes a decisive contribution to the development and dissemination of cancer, for example, through extracellular matrix components such as hyaluronan (HA), and through chemokines that regulate tumor cell behavior and angiogenesis. Here we report a molecular link between HA, its receptor CD44 and the chemokine CXCL12 in the regulation of cell motility and angiogenesis. High-molecular-weight HA (hHA) was found to augment CXCL12-induced CXCR4 signaling in both HepG2iso cells and primary human umbilical vein endothelial cells, as evidenced by enhanced ERK phosphorylation and increased cell motility. The augmentation of CXCR4 signaling translated into increased vessel sprouting and angiogenesis in a variety of assays. Small HA oligosaccharides (sHA) efficiently inhibited these effects. Both siRNA-mediated reduction of CD44 expression and antibodies that block the interaction of CD44 with HA provided evidence that CXCL12-induced CXCR4 signaling depends on the binding of hHA to CD44. Consistently, CD44 and CXCR4 were found to physically interact in the presence of CXCL12, an interaction that could be inhibited by sHA. These findings provide novel insights into how microenvironmental components interact with cell surface receptors in multi-component complexes to regulate key aspects of tumor growth and progression

Radiographic Findings and Association With Clinical Severity and Outcomes in Critically Ill Patients With COVID-19

PURPOSE: To describe evolution and severity of radiographic findings and assess association with disease severity and outcomes in critically ill COVID-19 patients. MATERIALS AND METHODS: This retrospective study included 62 COVID-19 patients admitted to the intensive care unit (ICU). Clinical data was obtained from electronic medical records. A total of 270 chest radiographs were reviewed and qualitatively scored (CXR score) using a severity scale of 0-30. Radiographic findings were correlated with clinical severity and outcome. RESULTS: The CXR score increases from a median initial score of 10 at hospital presentation to the median peak CXR score of 18 within a median time of 4 days after hospitalization, and then slowly decreases to a median last CXR score of 15 in a median time of 12 days after hospitalization. The initial and peak CXR score was independently associated with invasive MV after adjusting for age, gender, body mass index, smoking, and comorbidities (Initial, odds ratio [OR]: 2.11 per 5-point increase, confidence interval [CI] 1.35-3.32, P= 0.001; Peak, OR: 2.50 per 5-point increase, CI 1.48-4.22, P= 0.001). Peak CXR scores were also independently associated with vasopressor usage (OR: 2.28 per 5-point increase, CI 1.30-3.98, P= 0.004). Peak CXR scores strongly correlated with the duration of invasive MV (Rho = 0.62, P\u3c 0.001), while the initial CXR score (Rho = 0.26) and the peak CXR score (Rho = 0.27) correlated weakly with the sequential organ failure assessment score. No statistically significant associations were found between radiographic findings and mortality. CONCLUSIONS: Evolution of radiographic features indicates rapid disease progression and correlate with requirement for invasive MV or vasopressors but not mortality, which suggests potential nonpulmonary pathways to death in COVID-19

Drivers of abrupt Holocene shifts in West Antarctic ice stream direction determined from combined ice sheet modelling and geologic signatures

Determining the millennial-scale behaviour of marine-based sectors of the West Antarctic Ice Sheet (WAIS) is critical to improve predictions of the future contribution of Antarctica to sea level rise. Here high-resolution ice sheet modelling was combined with new terrestrial geological constraints (in situ 14C and 10Be analysis) to reconstruct the evolution of two major ice streams entering the Weddell Sea over 20 000 years. The results demonstrate how marked differences in ice flux at the marine margin of the expanded Antarctic ice sheet led to a major reorganization of ice streams in the Weddell Sea during the last deglaciation, resulting in the eastward migration of the Institute Ice Stream, triggering a significant regional change in ice sheet mass balance during the early to mid Holocene. The findings highlight how spatial variability in ice flow can cause marked changes in the pattern, flux and flow direction of ice streams on millennial timescales in this marine ice sheet setting. Given that this sector of the WAIS is assumed to be sensitive to ocean-forced instability and may be influenced by predicted twenty-first century ocean warming, our ability to model and predict abrupt and extensive ice stream diversions is key to a realistic assessment of future ice sheet sensitivit

Proximal tibiofibular synostosis as a possible cause of a pseudoradicular syndrome: a case report

This paper presents a case report of persistent low back pain and suspected lumbar radiculopathy. A synostosis at the level of the proximal tibiofibular joint was diagnosed. After successful resection of the synostosis, the low back symptoms resolved completely. This is the first report of a proximal tibiofibular synostosis as a possible cause of referred pain proximally

π\pi-KK scattering lengths at finite temperature in the Nambu--Jona-Lasinio model

The transition amplitude for $\pi K$ scattering is evaluated within the SU(3) Nambu--Jona-Lasinio model. Ordering terms according to the expansion in $1/N_c$ leads to a box-like diagram, $t$ channel diagrams that admit scalar isoscalar $(\sigma,\sigma')$ exchanges, and a $u$ channel exchange of a scalar isodoublet $\sigma_K$ that has quantum numbers corresponding to the $K_0^*(1430)$. Both the Pauli-Villars and O(3) regularization procedures are used to evaluate the T=0 values of the $l=0$ scattering lengths $a_0^{3/2}$ and $a_0^{1/2}$. The finite temperature dependence is studied. We find that the variation in the $t$ channel in the calculation of $a_0^{3/2}$ leads to a change in $a_0^{3/2}$ of a factor of about two over the temperature range of T=150 MeV

The human capital transition and the role of policy

Along with information and communication technology, infrastructure, and the innovation system, human capital is a key pillar of the knowledge economy with its scope for increasing returns. With this in mind, the purpose of this chapter is to investigate how industrialized economies managed to achieve the transition from low to high levels of human capital. The first phase of the human capital transition was the result of the interaction of supply and demand, triggered by technological change and boosted by the demands for (immaterial) services. The second phase of the human capital transition (i.e., mass education) resulted from enforced legislation and major public investment. The state’s aim to influence children’s beliefs appears to have been a key driver in public investment. Nevertheless, the roles governments played differed according to the developmental status and inherent socioeconomic and political characteristics of their countries. These features of the human capital transition highlight the importance of understanding governments’ incentives and roles in transitions

Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation with CFTR whereas PKA inhibitors attenuate complex formation. Furthermore, an NDPK-B derived peptide (but not its NDPK-A equivalent) disrupts the NDPK-B/CFTR complex in vitro (19-mers comprising amino acids 36-54 from NDPK-B or NDPK-A). Overlay (Far-Western) and Surface Plasmon Resonance (SPR) analysis both demonstrate that NDPK-B binds CFTR within its first nucleotide binding domain (NBD1, CFTR amino acids 351-727). Analysis of chloride currents reflective of CFTR or outwardly rectifying chloride channels (ORCC, DIDS-sensitive) showed that the 19-mer NDPK-B peptide (but not its NDPK-A equivalent) reduced both chloride conductances. Additionally, the NDPK-B (but not NDPK-A) peptide also attenuated acetylcholine-induced intestinal short circuit currents. In silico analysis of the NBD1/NDPK-B complex reveals an extended interaction surface between the two proteins. This binding zone is also target of the 19-mer NDPK-B peptide, thus confirming its capability to disrupt NDPK-B/CFTR complex. We propose that NDPK-B forms part of the complex that controls chloride currents in epithelia