Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mu Subunit of Plasmodium falciparum Clathrin-Associated Adaptor Protein 2 Modulates In Vitro Parasite Response to Artemisinin and Quinine

ABSTRACT The emergence of drug-resistant parasites is a serious threat faced by malaria control programs. Understanding the genetic basis of resistance is critical to the success of treatment and intervention strategies. A novel locus associated with antimalarial resistance, ap2-mu (encoding the mu chain of the adaptor protein 2 [AP2] complex), was recently identified in studies on the rodent malaria parasite Plasmodium chabaudi (pcap2-mu). Furthermore, analysis in Kenyan malaria patients of polymorphisms in the Plasmodium falciparum ap2-mu homologue, pfap2-mu, found evidence that differences in the amino acid encoded by codon 160 are associated with enhanced parasite survival in vivo following combination treatments which included artemisinin derivatives. Here, we characterize the role of pfap2-mu in mediating the in vitro antimalarial drug response of P. falciparum by generating transgenic parasites constitutively expressing codon 160 encoding either the wild-type Ser (Ser160) or the Asn mutant (160Asn) form of pfap2-mu. Transgenic parasites carrying the pfap2-mu 160Asn allele were significantly less sensitive to dihydroartemisinin using a standard 48-h in vitro test, providing direct evidence of an altered parasite response to artemisinin. Our data also provide evidence that pfap2-mu variants can modulate parasite sensitivity to quinine. No evidence was found that pfap2-mu variants contribute to the slow-clearance phenotype exhibited by P. falciparum in Cambodian patients treated with artesunate monotherapy. These findings provide compelling evidence that pfap2-mu can modulate P. falciparum responses to multiple drugs. We propose that this gene should be evaluated further as a potential molecular marker of antimalarial resistance.
Saw Cut Accuracy in Knee Arthroplasty-An Experimental Case-Control Study

Introduction: Navigated TKA (Total Knee Arthroplasty) has heightened awareness of mal-alignment in conventional TKA, as well as providing an accurate means of measuring alignment intra-operatively. Debate as to the importance and significance of alignment versus knee balance continues. Aim: To assess cutting error, and examine the hypothesises: • ‘Slotted osteotomies are more accurate than non-slotted’ • ‘Second pass of the saw blade improves the accuracy of osteotomies’ Method: Three pairs of fresh frozen human knees were prepared, exposed, and positioned as for primary TKA. Standard cutting guides were used in conjunction with a clinical navigation system, and the error (difference between the achieved resection, and the planned resection) in each osteotomy was measured. A second, tidying, pass of the saw blade was made and the error re-measured. Cutting guides were used with a slotted and un-slotted technique in left and right knees respectively. A single experienced surgeon performed all 96 osteotomies. Results: Slotted tibial osteotomies are significantly more accurate in the sagittal (p=0.01) and coronal (p=0.04) planes. Second pass osteotomies reduce variability in femoral (p=0.07) and tibial (p=0.17) osteotomies. Discussion: The bone cutting process is prone to high levels of random error that can result in implant malalignment, and thus predispose to aseptic loosening. Navigated TKA gives the operating surgeon the opportunity to check each osteotomy, and correct any error where necessary. In conventional TKA the use of dual pass, slotted osteotomies should provide improved accuracy.
Electoral System and Public Spending

We study the effects of electoral institutions on the size and composition of public expenditure in OECD and Latin American countries. We present a model emphasizing the distinction between purchases of goods and services, which are easier to target geographically, and transfers, which are easier to target across social groups. Voters have an incentive to elect representatives more prone to transfer spending in proportional systems. The model also predicts higher primary spending in proportional systems when the share of transfer spending is high. After defining rigorous measures of proportionality, we find considerable empirical support for our predictions.
Temperature Impacts the Development and Survival of Common Cutworm (Spodoptera litura): Simulation and Visualization of Potential Population Growth in India under Warmer Temperatures through Life Cycle Modelling and Spatial Mapping

The common cutworm, Spodoptera litura, has become a major pest of soybean (Glycine max) throughout its Indian range. With a changing climate, there is the potential for this insect to become an increasingly severe pest in certain regions due to increased habitat suitability. To examine this possibility, we developed temperature-based phenology model for S. litura, by constructing thermal reaction norms for cohorts of single life stages, at both constant and fluctuating temperatures within the ecologically relevant range (15–38°C) for its development. Life table parameters were estimated stochastically using cohort updating and rate summation approach. The model was implemented in the geographic information system to examine the potential future pest status of S. litura using temperature change projections from SRES A1B climate change scenario for the year 2050. The changes were visualized by means of three spatial indices demonstrating the risks for establishment, number of generations per year and pest abundance according to the temperature conditions. The results revealed that the development rate as a function of temperature increased linearly for all the immature stages of S. litura until approximately 34–36°C, after which it became non-linear. The extreme temperature of 38°C was found lethal to larval and pupal stages of S. litura wherein no development to the next stage occurred. Females could lay no eggs at the extreme low (15°C) and high (> 35°C) test temperatures, demonstrating the importance of optimum temperature in determining the suitability of climate for the mating and reproduction in S. litura. The risk mapping predicts that due to temperature increase under future climate change, much of the soybean areas in Indian states like Madhya Pradesh, Maharashtra and Rajasthan, will become suitable for S. litura establishment and increased pest activity, indicating the expansion of the suitable and favourable areas over time. This has serious implication in terms of soybean production since these areas produce approximately 95% of the total soybeans in India. As the present model results are based on temperature only, and the effects of other abiotic and biotic factors determining the pest population dynamics were excluded, it presents only the potential population growth parameters for S. litura. However, if combined with the field observations, the model results could certainly contribute to gaining insight into the field dynamics of S. litura.
A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer.

342 Background: Rigosertib (ON 01910.Na), a dual non-ATP inhibitor of polo-like kinase 1 (Plk1) and phosphoinositide 3-kinase (PI3K) pathways, was assessed in patients with treatment-naive metastatic pancreatic adenocarcinoma. Methods: Patients with metastatic adenocarcinoma of the pancreas were randomized in a 2:1 fashion to gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4-week cycle plus rigosertib 1800mg/m2 via 2-hr CIV infusions given twice weekly for 3 weeks of a 4-week cycle versus gemcitabine 1000mg/m2 weekly for 3 weeks in a 4-week cycle. Results: A total of 160 patients were enrolled globally and randomly assigned to rigosertib plus gemcitabine (106 patients) or gemcitabine (54). The most common grade 3 or higher adverse events were neutropenia (8% in the rigosertib plus gemcitabine group vs. 6% in the gemcitabine group), hyponatremia (17% vs. 4%), and anemia (8% vs. 4%). The primary outcome of the study, median OS, was 6.1 months in the gemcitabine plus rigosertib arm versus 6.4 months with gemc.
A Survey of Collaborative Recommendation and the Robustness of Model-Based Algorithms

The open nature of collaborative recommender systems allows attackers who inject biased profile data to have a significant impact on the recommendations produced. Standard memory-based collaborative filtering algorithms, such as k-nearest neighbor, are quite vulnerable to profile injection attacks. Previous work has shown that some model-based techniques are more robust than standard k-nn. Model abstraction can inhibit certain aspects of an attack, providing an algorithmic approach to minimizing attack effectiveness. In this paper, we examine the robustness of several recommendation algorithms that use different model-based techniques: user clustering, feature reduction, and association rules. In particular, we consider techniques based on k-means and probabilistic latent semantic analysis (pLSA) that compare the profile of an active user to aggregate user clusters, rather than the original profiles. We then consider a recommendation algorithm that uses principal component analysis (PCA) to calculate the similarity between user profiles based on reduced dimensions. Finally, we consider a recommendation algorithm based on the data mining technique of association rule mining using the Apriori algorithm. Our results show that all techniques offer large improvements in stability and robustness compared to standard k-nearest neighbor. In particular, the Apriori algorithm performs extremely well against lowknowledge attacks, but at a cost of reduced coverage, and the PCA algorithm performs extremely well against focused attacks. Furthermore, our results show that all techniques can achieve comparable recommendation accuracy to standard k-nn.
Microwave observations and modeling of O3, H2O, and HO2 in the mesosphere

Microwave (wave ∼1.2 mm) spectral line observations of HO2, H218O, and O3 were obtained at the Kitt Peak National Radio Astronomy Observatory (NRAO) on April 10–12, 1992. The spectral bandwidth and resolution of the observed collisional line shapes are appropriate to retrieving profile abundances for O3, H2O, and HO2 in the upper stratosphere and mesosphere (45- to 70-km altitude) with 20–30% uncertainties. The derived profile for O3 exhibits 20–30% larger mesospheric ozone abundances than indicated by the April 30°N average profiles from Solar Mesosphere Explorer (SME) and Stratosphere Aerosol Gas Experiment (SAGE) II and 60–80% larger than a photochemical model employing current photochemical rate constants and an H2O profile constrained by the microwave H218O observations. Surprisingly, the microwave measurement of HO2 yields mesospheric HO2 abundances roughly twice those predicted by the standard model photochemistry. As HOx(OH, HO2, H) is the primary agent for catalytic destruction of ozone in the mesosphere, the model underpredictions of both HO2 and O3 suggest a change in the model photochemistry that is distinct from errors in Ox production and HOx loss rates. Increases in Ox production and/or increases in HOx loss rates have been considered as the likely sources for the persistent data-model disagreement in upper stratospheric/mesospheric ozone abundances. Based on the microwave measurements of O3 and HO2, we propose changes to model rates for partitioning between OH and HO2.Specifically, a large (60–80%) decrease in the rate coefficient for the reaction O + HO2 → OH + O2 is shown to be uniquely capable of increasing model abundances for O3 and HO2, in accordance with the microwave observations as well as the outstanding underprediction of upper stratospheric/mesospheric ozone by photochemical modeling.
Reactions between molten iron and silicate melts at high pressure: Implications for the chemical evolution of Earth's core

Reactions between molten iron and silicate melt were investigated with mixtures of pure iron and silicates (1Fe + 3MgSiO3 enstatite and 1Fe + 3(Mg0.9Fe0.1)2SiO4 olivine in volumetric ratio) as starting materials at pressures of 10–26 GPa and temperatures of about 2500°C. The results show that a certain amount of Si (up to about 2%) dissolves in molten iron from silicate melt and that the dissolution is enhanced with increasing pressure. Many small spherical blobs composed of SiO2 and FeO present in coalesced iron grains were interpreted as quenched immiscible liquid formed during cooling. Therefore O also dissolves in molten iron under the experimental conditions. No evidence for dissolution of Mg was obtained. The present study also indicates that Si and O are important light elements of Earth's core if core segregation occurred in the deep magma ocean. The chemical evolution of Earth's core is discussed on the bases of the current core formation model and the present experimental results.
Membrane Cholesterol Depletion by Methyl-β-Cyclodextrin Enhances the Expression of Cardiac Differentiation Markers

Cholesterol is a sterol lipid that plays pleiotropic roles in the plasma membrane; it is involved in maintaining membrane fluidity and permeability and the structure of lipid microdomains. Despite its importance, the consequences of membrane cholesterol depletion during cardiac differentiation have not been described. Therefore, we investigated the cellular and molecular mechanisms associated with cholesterol depletion in cultures of chick cardiac cells. We used methyl-β-cyclodextrin (MCD) to deplete membrane cholesterol and investigate its role in cardiac differentiation by following the expression of several markers including the transcriptional factor Nkx2.5, the myofibrillar protein tropomyosin, the cytoskeletal intermediate filament protein desmin, the caveolar protein caveolin-3, the cadherin/β-catenin adhesion complex, and the junctional protein connexin 43. Confocal microscopy showed that desmin-positive cells were located more externally in the aggregates in relation to the more internally located caveolin-3-positive cells. Desmin and caveolin-3 were co-localized in filamentous structures in the subsarcolemmal region of well-spread cells outside the aggregates. β-Catenin was concentrated in regions of cell-cell contact, and tropomyosin in sarcomeric structures. Western blot tests showed that immediately following cholesterol depletion, there was a slight decrease in the expression of caveolin-3 and desmin, and at the same time there was a sharp increase in the expression of cadherin, tropomyosin, Nkx2.5 and connexin 43. Further, we found an increase in the expression of cardiac β-myosin heavy chain 7, a marker of the cardiac hypertrophic phenotype. These observations suggest that membrane cholesterol plays a significant role in regulating cardiomyocyte differentiation.
The effect of a fixed vertical barrier on surface waves in deep water

In this paper the two-dimensional reflection of surface waves from a vertical barrier in deep water is studied theoretically. It can be shown that when the normal velocity is prescribed at each point of an infinite vertical plane extending from the surface, the motion on each side of the plane is completely determined, apart from a motion consisting of simple standing waves. In the cases considered here the normal velocity is prescribed on a part of the vertical plane and is taken to be unknown elsewhere. From the condition of continuity of the motion above and below the barrier an integral equation for the normal velocity can be derived, which is of a simple type, in the case of deep water. We begin by considering in detail the reflection from a fixed vertical barrier extending from depth a to some point above the mean surface.
Induced stresses and fault potential in eastern Canada due to a realistic load: a preliminary analysis

SUMMARY In order to understand the causal relation between postglacial rebound and earthquakes, a simple disc load model is used to: (1) calculate stresses induced in the lithosphere and mantle by glacial loading, melting and postglacial rebound; and (2) evaluate the effect of glacial loading/rebound on the failure potential for earthquakes in the upper crust. The dependence of the failure potential and the actual mode of failure on the coefficient of friction, the ambient tectonic stress magnitude/direction, the stress due to the overlying rocks, and lithospheric thickness are investigated. Prominent features of this paper are the inclusion of: (1) a viscoelastic mantle and thus the migration of stress; and (2) the ambient tectonic stress and overburden stress contributions in the calculation of the total stress field. It is assumed that, throughout the Earth, there are optimally oriented pre-existing virtual faults that are initially close to but not at failure; thus, a time-dependent quantity called dFSM (related to the Coulomb-Mohr failure criterion) can be defined such that a negative value of dFSM would advocate faulting or earthquake activities whereas a positive value of dFSM would promote stability. The results indicate that, under all combinations of tectonic stress magnitude and overburden stress, crustal loading promotes fault stability directly underneath the load. Upon the removal of the load, thrust faulting is predicted within the ice margin if the horizontal stress (S,) induced by the overburden is greater than or equal to the vertical component (S,) of the overburden stress (121, where (=SJS,). Under this condition, theory predicts that faulting or earthquake activity should have reached a maximum immediately after deglaciation. If the horizontal stress induced by the overburden is less than the vertical component of the overburden stress (1 < l), then theory predicts fault stability within the ice margin. The theory predicts fault instability both north and south of the ice margin. The mode of failure, however, is completely determined by the value of i. The trade-off between the tectonic stress magnitude and the overburden stress parameter (1) is also investigated. It is shown that a larger tectonic stress magnitude can be used to compensate a smaller value of 1. The results of this analysis show that variations in the coefficient of friction, lithospheric thickness and a ductile zone below the upper crust do not significantly affect the above conclusions.
Inactivation in Lung Squamous Cell Carcinomas Impairs STAT 3 and Promotes Malignant Invasion

Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the cell polarity regulator PARD3 to the development of lung squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in the ability to mediate formation of tight junctions and actinbased protrusions, bind atypical protein kinase C, activate RAC1, and activate STAT3 at cell confluence. Thus, PARD3 alterations prevented the formation of contacts between neighboring cells and the subsequent downstream signaling. Notably, reconstituting PAR3 activity in vivo reduced tumorinvasive and metastatic properties. Our findings define PARD3 as a recurrently inactivated cell polarity regulator in LSCC that affects tumor aggressiveness and metastasis. Cancer Res; 75(7); 1287–97. 2015 AACR.
Boundary-layer analysis for effects of viscosity of the irrotational flow on the flow induced by a rapidly rotating cylinder in a uniform stream

We study the streaming flow past a rapidly rotating circular cylinder. The starting point is the full continuity and momentum equations without any approximations. We assume that the solution is a boundary-layer flow near the cylinder surface with the potential flow outside the boundary layer. The order of magnitude of the terms in the continuity and momentum equations can be estimated inside the boundary layer. When terms of the order of $\delta/a$ and higher are dropped, where $\delta$ is the boundary-layer thickness and $a$ is the radius of the cylinder, the equations used by M. B. Glauert (Proc. R. Soc. Lond. A, vol. 242, 1957, p. 108) are recovered. Glauert's solution ignores the irrotational rotary component of the flow inside the boundary layer, which is consistent with dropping $\delta/a$ terms in the governing equations. We propose a new solution to this problem, in which the velocity field is decomposed into two parts. Outside the boundary layer, the flow is irrotational and can be decomposed into a purely rotary flow and a potential flow past a fixed cylinder. Inside the boundary layer, the velocity is decomposed into an irrotational purely rotary flow and a boundary-layer flow. Inserting this decomposition of the velocity field inside the boundary layer into the governing equations, we obtain a new set of equations for the boundary-layer flow, in which we do not drop the terms of the order of $\delta/a$ or higher. The pressure can no longer be assumed to be a constant across the boundary layer, and the continuity of shear stress at the outer edge of the boundary layer is enforced. We solve this new set of equations using Glauert's method, i.e. to expand the solutions as a power series of $\alpha \,{=}\, 2 U_0 /Q$, where $U_0$ is the uniform stream velocity and $Q$ is the circulatory velocity at the outer edge of the boundary layer. The pressure from this boundary-layer solution has two parts, an inertial part and a viscous part. The inertial part comes from the inertia terms in the momentum equations and is in agreement with the irrotational pressure; the viscous part comes from the viscous stress terms in the momentum equations and may be viewed as a viscous pressure correction, which contributes to both drag and lift. Our boundary-layer solution is in reasonable to excellent agreement with the numerical simulation in the companion paper by Padrino & Joseph (2006).