3,127 research outputs found
Recommended from our members
Plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria.
Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi - macaque model systems and summarizing exciting new progress in this area of research
Management and perinatal outcomes of hypertensive disorders of pregnancy in a low-resource setting in Indonesia
Objectives: To provide up-to-date data concerning hypertensive disorders of pregnancy on maternal and neonatal profiles in Indonesia. Methods: Retrospective clinical audit on all pregnancy-associated hypertensive women between 1 January 2020 and 31 March 2020 at Cianjur General District Hospital. Results: Preeclampsia accounts for 66.8% (235/352) of hypertensive disorders of pregnancy, gestational hypertension 29% (102/352) and chronic hypertension 4.3% (15/352). Compared to other pregnant women, those with preeclampsia, on average, had higher systolic and diastolic blood pressures and poorer kidney (ureum and creatinine) and liver function (aspartate transaminase enzyme and alanine transaminase enzyme) profiles (p < 0.001, < 0.001, < 0.001, 0.003, 0.033 and 0.002, respectively), and required more intensive care admission. Neonates from women with severe forms of preeclampsia (eclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)) had, on average, lower birthweight (p = 0.015 and 0.048, respectively) and birth length (p = 0.021, 0.017). Neonates from eclamptic mothers had poorer APGAR (appearance, pulse, grimace, activity and respiration) scores (p = 0.006 and 0.005, respectively). Conclusion: Hypertensive disorders of pregnancy exerts adverse maternal and neonatal outcomes, particularly among eclampsia and HELLP-syndrome neonates. Various challenges remain for optimal management
A new method for experimental characterisation of scattered radiation in 64-slice CT scanner
PURPOSE: The consummate 64-slice CT scanner that spawns a new generation of non-invasive diagnostic tool, however revolutionary, brings with it the incidental by-product that is scattered radiation. The extended detector aperture capability in the 64-slcie CT scanner allows the effects of scattered radiation to be more pronounced and therefore demands that the magnitude and spatial distribution of scatter component be addressed during the imaging process. To this end, corrective algorithms need to be formulated on a basis of a precise understanding of scatter distribution. Relative to a 64-slice CT scanner, here now a unique solution is based upon dedicated blockers operative within various detector rows, calculating scatter profiles and scatter to primary ratios (SPR). MATERIALS AND METHODS: A single dimension blocker array was installed beneath the collimator, and the extrapolated shadow area on the detectors revealed the scatter radiation after exposure. The experiment was conducted using a 64-slice CT scanner manufactured by GE Healthcare Technologies. RESULTS: Variables such as tube voltage, phantom size and phantom-off centring on the scatter profile and the SPR was measured using the dedicated blocker method introduced above. When tube voltage is increased from 80kVp to 140kVp in a 21.5 cm water phantom, the SPR is found to reduce from 219.9 to 39.9 respectively. CONCLUSION: The method developed within this study is applicable to any measurement and is direct with minimal complexity
Recommended from our members
PacBio assembly of a Plasmodium knowlesi genome sequence with Hi-C correction and manual annotation of the SICAvar gene family.
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features. Today, long-read PacBio and chromatin conformation technologies are overcoming such obstacles. Here, based on the use of these technologies, we present a highly refined de novo P. knowlesi genome sequence of the Pk1(A+) clone. This sequence and annotation, referred to as the 'MaHPIC Pk genome sequence', includes manual annotation of the SICAvar gene family with 136 full-length members categorized as type I or II. This sequence provides a framework that will permit a better understanding of the SICAvar repertoire, selective pressures acting on this gene family and mechanisms of antigenic variation in this species and other pathogens
Limits of minimal models and continuous orbifolds
The lambda=0 't Hooft limit of the 2d W_N minimal models is shown to be
equivalent to the singlet sector of a free boson theory, thus paralleling
exactly the structure of the free theory in the Klebanov-Polyakov proposal. In
2d, the singlet sector does not describe a consistent theory by itself since
the corresponding partition function is not modular invariant. However, it can
be interpreted as the untwisted sector of a continuous orbifold, and this point
of view suggests that it can be made consistent by adding in the appropriate
twisted sectors. We show that these twisted sectors account for the `light
states' that were not included in the original 't Hooft limit. We also show
that, for the Virasoro minimal models (N=2), the twisted sector of our orbifold
agrees precisely with the limit theory of Runkel & Watts. In particular, this
implies that our construction satisfies crossing symmetry.Comment: 33 pages; v2: minor improvements and references added, published
versio
The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus
BACKGROUND: At sites of cell adhesion, proteins exist that not only perform structural tasks but also have a signaling function. Previously, we found that the Lipoma Preferred Partner (LPP) protein is localized at sites of cell adhesion such as focal adhesions and cell-cell contacts, and shuttles to the nucleus where it has transcriptional activation capacity. LPP is a member of the zyxin family of proteins, which contains five members: ajuba, LIMD1, LPP, TRIP6 and zyxin. LPP has three LIM domains (zinc-finger protein interaction domains) at its carboxy-terminus, which are preceded by a proline-rich pre-LIM region containing a number of protein interaction domains. RESULTS: To catch the role of LPP at sites of cell adhesion, we made an effort to identify binding partners of LPP. We found the tumor suppressor protein Scrib, which is a component of cell-cell contacts, as interaction partner of LPP. Human Scrib, which is a functional homologue of Drosophila scribble, is a member of the leucine-rich repeat and PDZ (LAP) family of proteins that is involved in the regulation of cell adhesion, cell shape and polarity. In addition, Scrib displays tumor suppressor activity. The binding between Scrib and LPP is mediated by the PDZ domains of Scrib and the carboxy-terminus of LPP. Both proteins localize in cell-cell contacts. Whereas LPP is also localized in focal adhesions and in the nucleus, Scrib could not be detected at these locations in MDCKII and CV-1 cells. Furthermore, our investigations indicate that Scrib is dispensable for targeting LPP to focal adhesions and to cell-cell contacts, and that LPP is not necessary for localizing Scrib in cell-cell contacts. We show that all four PDZ domains of Scrib are dispensable for localizing this protein in cell-cell contacts. CONCLUSIONS: Here, we identified an interaction between one of zyxin's family members, LPP, and the tumor suppressor protein Scrib. Both proteins localize in cell-cell contacts. This interaction links Scrib to a communication pathway between cell-cell contacts and the nucleus, and implicates LPP in Scrib-associated functions
Inelastic cyclic response of RBS connections with jumbo sections
This paper examines the cyclic performance of reduced beam section (RBS) moment connections incorporating larger member sizes than those allowed in the current seismic provisions for prequalified steel connections, through experimentally validated three-dimensional nonlinear numerical assessments. Validations of the adopted nonlinear finite element procedures are carried out against experimental results from two test series, including four full-scale RBS connections comprising large structural members, outside the prequalification limits. After gaining confidence in the ability of the numerical models to predict closely the full inelastic response and failure modes, parametric investigations are undertaken. Particular attention is given to assessing the influence of the RBS-to-column capacity ratio as well as the RBS geometry and location on the overall response. The numerical results and test observations provide a detailed insight into the structural behavior, including strength, ductility, and failure modes of large RBS connections. It is shown that connections which consider sections beyond the code limits, by up to two times the weight or beam depth limits, developed a stable inelastic response characterized by beam flexural yielding and inelastic local buckling. However, connections with very large beam sections, up to three-times the typically prescribed limits, exhibited significant hardening resulting in severe demands at the welds, hence increasing susceptibility to weld fracture and propagation through the column. The findings from this study point to the need, in jumbo sections with thick flanges, for a deeper RBS cut than currently specified in design, to about 66% of the total beam width. This modification would be required to promote a response governed by extensive yielding at the RBS while reducing the excessive strain demands at the beam-to-column welds. Moreover, for connections incorporating relatively deep columns, it is shown that more stringent design requirements need to be followed, combined with appropriate bracing outside the RBS, to avoid out-of-plane rotation
Current progress on removal of recalcitrance coloured particles from anaerobically treated effluent using coagulation–flocculation
The palm oil industry is the most important agro industries in Malaysia and most of the mills adopt anaerobic digestion as their primary treatment for palm oil mill effluent (POME). Due to the public concern, decolourisation of anaerobically treated POME (AnPOME) is becoming a great concern. Presence of recalcitrant-coloured particles hinders biological processes and coagulation–flocculation may able to remove these coloured particles. Several types of inorganic and polymers-based coagulant/flocculant aids for coagulation–flocculation of AnPOME have been reviewed. Researchers are currently interested in using natural coagulant and flocculant aids. Modification of the properties of natural coagulant and flocculant aids enhanced coagulation–flocculation performance. Modelling and optimization of the coagulation–flocculation process have also been reviewed. Chemical sludge has the potential for plant growth that can be evaluated through pot trials and phytotoxicity test
Revealing the electronic structure of a carbon nanotube carrying a supercurrent
Carbon nanotubes (CNTs) are not intrinsically superconducting but they can
carry a supercurrent when connected to superconducting electrodes. This
supercurrent is mainly transmitted by discrete entangled electron-hole states
confined to the nanotube, called Andreev Bound States (ABS). These states are a
key concept in mesoscopic superconductivity as they provide a universal
description of Josephson-like effects in quantum-coherent nanostructures (e.g.
molecules, nanowires, magnetic or normal metallic layers) connected to
superconducting leads. We report here the first tunneling spectroscopy of
individually resolved ABS, in a nanotube-superconductor device. Analyzing the
evolution of the ABS spectrum with a gate voltage, we show that the ABS arise
from the discrete electronic levels of the molecule and that they reveal
detailed information about the energies of these levels, their relative spin
orientation and the coupling to the leads. Such measurements hence constitute a
powerful new spectroscopic technique capable of elucidating the electronic
structure of CNT-based devices, including those with well-coupled leads. This
is relevant for conventional applications (e.g. superconducting or normal
transistors, SQUIDs) and quantum information processing (e.g. entangled
electron pairs generation, ABS-based qubits). Finally, our device is a new type
of dc-measurable SQUID
Evidence for F(uzz) Theory
We show that in the decoupling limit of an F-theory compactification, the
internal directions of the seven-branes must wrap a non-commutative four-cycle
S. We introduce a general method for obtaining fuzzy geometric spaces via toric
geometry, and develop tools for engineering four-dimensional GUT models from
this non-commutative setup. We obtain the chiral matter content and Yukawa
couplings, and show that the theory has a finite Kaluza-Klein spectrum. The
value of 1/alpha_(GUT) is predicted to be equal to the number of fuzzy points
on the internal four-cycle S. This relation puts a non-trivial restriction on
the space of gauge theories that can arise as a limit of F-theory. By viewing
the seven-brane as tiled by D3-branes sitting at the N fuzzy points of the
geometry, we argue that this theory admits a holographic dual description in
the large N limit. We also entertain the possibility of constructing string
models with large fuzzy extra dimensions, but with a high scale for quantum
gravity.Comment: v2: 66 pages, 3 figures, references and clarifications adde
- …