Miracle-dz/UniFAR-FTUs huggingface dataset:
Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability

Significance The malaria parasite Plasmodium falciparum actively invades host cells, using a mechanism that relies on the interaction of the motor protein myosin and actin filaments which serve as tracks. We determined the structure of stabilized P. falciparum actin 1 filaments at near-atomic resolution using single-particle electron cryomicroscopy. The high resolution of the structure allowed us to identify important positions in the filament that are essential for the temporal and spatial control of actin polymerization and play a pivotal role in host cell invasion, and thus infectivity. In general, our study provides important insights into the structural design of actin filaments. During their life cycle, apicomplexan parasites, such as the malaria parasite Plasmodium falciparum, use actomyosin-driven gliding motility to move and invade host cells. For this process, actin filament length and stability are temporally and spatially controlled. In contrast to canonical actin, P. falciparum actin 1 (PfAct1) does not readily polymerize into long, stable filaments. The structural basis of filament instability, which plays a pivotal role in host cell invasion, and thus infectivity, is poorly understood, largely because high-resolution structures of PfAct1 filaments were missing. Here, we report the near-atomic structure of jasplakinolide (JAS)-stabilized PfAct1 filaments determined by electron cryomicroscopy. The general filament architecture is similar to that of mammalian F-actin. The high resolution of the structure allowed us to identify small but important differences at inter- and intrastrand contact sites, explaining the inherent instability of apicomplexan actin filaments. JAS binds at regular intervals inside the filament to three adjacent actin subunits, reinforcing filament stability by hydrophobic interactions. Our study reveals the high-resolution structure of a small molecule bound to F-actin, highlighting the potential of electron cryomicroscopy for structure-based drug design. Furthermore, our work serves as a strong foundation for understanding the structural design and evolution of actin filaments and their function in motility and host cell invasion of apicomplexan parasites.
Diffuse low-grade gliomas.

Description : Diffuse low-grade gliomas (WHO grade II) are a sub-group of rare and heterogeneous primary brain tumors that usually occur in young patients living a normal life until the onset of a first seizure. A good understanding of the natural history of these gliomas namely: their steady progression, infiltration along white matter fibers and especially the risk of malignant transformation-which endangers the functional and vital prognosis, associated with the minimization of the risk of treatment, has led to a therapeutic change from the "classic" conservative attitude to a more rigorous therapeutic strategy. Current goal is to elaborate dynamic and individualized treatment; that is; to define the sequence and timing of each treatment option (single to multiple safe
Low-temperature dynamic precipitation in a supersaturated Al± Zn± Mg alloy and related strain hardening

Abstract Dynamic precipitation during low-temperature deformation of a supersaturated Al-Zn-Mg alloy has been studied by small-angle X-ray scattering and in-situ resistivity in the temperature range 4.2–300 K. At 300 K, dynamic precipitation is observed both for the material strained in the form of a solid solution and for the material strained in the partially aged state, that is containing Guinier-Preston (GP) zones. In the first case, dynamic precipitation occurs by nucleation of precipitates 5 A in diameter, and in the second case it occurs by coarsening of existing precipitates. In all cases the dynamic precipitation results in an unusual-strain hardening behaviour in which the work-hardening rate is very high and essentially temperature independent.
Accountability Policies and Teacher Decision Making: Barriers to the Use of Data to Improve Practice.

One assumption underlying accountability policies is that results from standardized tests and other sources will be used to make decisions about school and classroom practice. We explore this assumption using data from a longitudinal study of nine high schools nominated as leading practitioners of Continuous Improvement (CI) practices. We use the key beliefs underlying continuous improvement-derived from educational applications of Demning's TQM models -and organizational learning to analyze teachers' responses to district expectations thl.t they would use data to assess their own, their colleagues', and their schools' effectiveness and to make improvements. The findings suggest that most teachers are willing, but they have significant concerns about the kind of information that is available and how it is used to judge their own and colleagues' performance. Our analysis reveals some cultural assumptions that are inconsistent with accountability policies and with theories of continuous improvement and organizational learning. We also identify barriers to use of testing and other data that help to account for the limited impacts.
Bring your own coding style

Coding style is a representation of source code, which does not affect the behavior of program execution. The choice of coding style is purely a matter of developer preference. Inconsistency of coding style not only decreased readability but also can cause frustration during programming. In this paper, we propose a novel tool, called StyleCoordinator, to solve both of the following problems, which would appear to contradict each other: ensuring a consistent coding style for all source codes managed in a repository and ensuring the ability of developers to use their own coding styles in a local environment. In order to validate the execution performance, we apply the proposed tool to an actual software repository.
Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System

The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids.
Epigenetic regulation in alcoholic liver disease

Alcoholic liver disease (ALD) is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcohol-induced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such as histone acetyltransferases, histone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ame-
Regulation of Gelatinase Activity in Mice with Targeted Inactivation of Components of the Plasminogen/Plasmin System

Summary To investigate a potential physiological role of the plasminogen/ plasmin system in activation of the matrix metalloproteinase (MMP) system, the distribution of latent and active MMP-2 (gelatinase A) or MMP-9 (gelatinase B) was monitored in aorta extracts and in serum-free conditioned cell culture medium obtained from wild-type (WT) mice and from mice with deficiency of tissue-type plasminogen activator (t-PA–/–), urokinase-type plasminogen activator (u-PA–/–), plasminogen activator inhibitor-1 (PAI-1–/–) or plasminogen (Plg–/–). In aorta extracts, the contribution of active MMP-2 to the total MMP-2 level ranged between 7 and 16% for the different genotypes, whereas active MMP-9 was not detected. The contribution of active 58 kDa MMP-2 to the total MMP-2 level (active plus latent) ranged between 14 and 29% (mean of 3 experiments) for fibroblasts of the different genotypes, and between 18 and 32% for smooth muscle cells, and was relatively constant in time (7-72 h). The contribution of active 83 kDa MMP-9 to the total MMP-9 level ranged between 15 and 29% for fibroblasts of the different genotypes and was relatively constant in time (24-72 h); corresponding values were 17 to 57% for smooth muscle cells, with the exception of Plg–/– smooth muscle cells which had undetectable levels of active MMP-9. Addition of plasmin(ogen) to the cell culture medium of fibroblasts did not significantly affect the distribution of active and latent MMP-2, but resulted in an approximately two-fold enhancement of the contribution of active MMP-9. In macrophages of Plg–/– mice, active MMP-9 was detected only when the cells were cultured in the presence of plasminogen. These data indicate that activation of proMMP-2 occurs independently of the physiological plasminogen activators and of plasmin(ogen) in all the cell types evaluated. Activation of proMMP-9 was enhanced in the presence of plasmin(ogen), but active MMP-9 was also detected in fibroblasts of Plg–/– mice, indicating that in vivo activation may occur via plasmin(ogen)-independent mechanisms.
Practical analytical solutions for benchmarking of 2-D and 3-D geodynamic Stokes problems with variable viscosity

Geodynamic modeling is often related with challenging computations involving solution of the Stokes and continuity equations under the condition of highly variable viscosity. Based on a new analytical approach we have developed particular analytical solutions for 2-D and 3-D incompressible Stokes flows with both linearly and exponentially variable viscosity. We demonstrate how these particular solutions can be converted into 2-D and 3-D test problems suitable for benchmarking numerical codes aimed at modeling various mantle convection and lithospheric dynamics problems. The Main advantage of this new generalized approach is that a large variety of benchmark solutions can be generated, including relatively complex cases with open model boundaries, non-vertical gravity and variable gradients of the viscosity and density fields, which are not parallel to the Cartesian axes. Examples of respective 2-D and 3-D MatLab codes are provided with this paper.
Structure Control of V2O5/CNFs/Cordierite Monolith Catalyst and Its Catalytic Performance on NO Removal from Flue Gas

Carbon nanofibers (CNFs) were grown on Al2O3-coated cordierite monolith by chemical vapor deposi- tion. The microstructure of V2O5 catalyst supported on cordierite monolith with CNFs layer was investigated by us- ing scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray powder diffraction (XRD) and X-ray photoelectron spectroscope (XPS) techniques, as well as its activity for the selective catalytic reduction (SCR) of NO by NH3. The compressive strength of prepared CNFs/cordierite monolith composite was 34.46 MPa and the thickness of CNFs layer was 0.74 μm. The V2O5/CNFs/cordierite monolith catalysts had high NO removal activity in the temperature range of 150−250℃. When the CNFs yield and V2O5 loading were 12.5% and 1%, re- spectively, the NO conversion of the catalyst could reach 95% at 250℃.
Bending modes of DNA directly addressed by cryo-electron microscopy of DNA minicircles

We use cryo-electron microscopy (cryo-EM) to study the 3D shapes of 94-bp-long DNA minicircles and address the question of whether cyclization of such short DNA molecules necessitates the formation of sharp, localized kinks in DNA or whether the necessary bending can be redistributed and accomplished within the limits of the elastic, standard model of DNA flexibility. By comparing the shapes of covalently closed, nicked and gapped DNA minicircles, we conclude that 94-bp-long covalently closed and nicked DNA minicircles do not show sharp kinks while gapped DNA molecules, containing very flexible single-stranded regions, do show sharp kinks. We corroborate the results of cryo-EM studies by using Bal31 nuclease to probe for the existence of kinks in 94-bp-long minicircles.
Search Process as Transitions Between Neural States

Search is one of the most performed activities on the World Wide Web. Various conceptual models postulate that the search process can be broken down into distinct emotional and cognitive states of searchers while they engage in a search process. These models significantly contribute to our understanding of the search process. However, they are typically based on self-report measures, such as surveys, questionnaire, etc. and therefore, only indirectly monitor the brain activity that supports such a process. With this work, we take one step further and directly measure the brain activity involved in a search process. To do so, we break down a search process into five time periods: a realisation of Information Need, Query Formulation, Query Submission, Relevance Judgment and Satisfaction Judgment. We then investigate the brain activity between these time periods. Using functional Magnetic Resonance Imaging (fMRI), we monitored the brain activity of twenty-four participants during a search process that involved answering questions carefully selected from the TREC-8 and TREC 2001 Q/A Tracks. This novel analysis that focuses on transitions rather than states reveals the contrasting brain activity between time periods - which enables the identification of the distinct parts of the search process as the user moves through them. This work, therefore, provides an important first step in representing the search process based on the transitions between neural states. Discovering more precisely how brain activity relates to different parts of the search process will enable the development of brain-computer interactions that better support search and search interactions, which we believe our study and conclusions advance.
Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study.

IMPORTANCE Pronounced inflammatory reactions occurring shortly after intracerebral hemorrhage (ICH) contribute to the formation and progression of perihematomal edema (PHE) and secondary brain injury. We hypothesized that modulation of brain inflammation reduces edema, thus improving clinical outcomes in patients with ICH. OBJECTIVE To investigate whether oral administration of fingolimod, a Food and Drug Administration-approved sphingosine 1-phosphate receptor modulator for multiple sclerosis, is safe and effective in alleviating PHE and neurologic deficits in patients with ICH. DESIGN, SETTING, AND PARTICIPANTS In this 2-arm, evaluator-blinded study, we included 23 patients with primary supratentorial ICH with hematomal volume of 5 to 30 mL. Clinical and neuroimaging feature-matched patients were treated with standard care with or without oral fingolimod. The study was conducted in Tianjin Medical University General Hospital, Tianjin, China. INTERVENTIONS All patients received standard management alone (control participants) or combined with fingolimod (FTY720, Gilenya), 0.5 mg, orally for 3 consecutive days. Treatment was initiated within 1 hour after the baseline computed tomographic scan and no later than 72 hours after the onset of symptoms. MAIN OUTCOMES AND MEASURES Neurologic status and hematomal and PHE volumes (Ev) and relative PHE, defined as Ev divided by hematomal volume, were monitored by clinical assessment and magnetic resonance imaging, respectively, for 3 months. RESULTS Patients treated with fingolimod exhibited a reduction of neurologic impairment compared with control individuals, regained a Glasgow Coma Scale score of 15 by day 7 (100% vs 50%, P = .01), and had a National Institutes of Health Stroke Scale score reduction of 7.5 vs 0.5 (P < .001). Neurologic functions improved in these patients in the first week coincident with a reduction of circulating lymphocyte counts. At 3 months, a greater proportion of patients receiving fingolimod achieved full recovery of neurologic functions (modified Barthel Index score range, 95-100; 63% vs 0%; P = .001; modified Rankin Scale score range, 0-1; 63% vs 0%; P = .001), and fewer reported ICH-related lung infections. Perihematomal edema volume and rPHE were significantly smaller in fingolimod-treated patients than in control individuals (Ev at day 7, 47 mL vs 108 mL, P = .04; Ev at day 14, 55 mL vs 124 mL, P = .07; rPHE at day 7, 2.5 vs 6.4, P < .001; rPHE at day 14, 2.6 vs 7.7, P = .003, respectively). We recorded no differences between groups in the occurrence of adverse events. CONCLUSIONS AND RELEVANCE In patients with small- to moderate-sized deep primary supratentorial ICH, administration of oral fingolimod within 72 hours of disease onset was safe, reduced PHE, attenuated neurologic deficits, and promoted recovery. The efficacy of fingolimod in preventing secondary brain injury in patients with ICH warrants further investigation in late-phase trials. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT02002390.
The Effect of CHAMP on Physical Activity and Lesson Context in Preschoolers: A Feasibility Study

ABSTRACT Purpose: This feasibility study compared the effects of 2 movement programs, traditional and mastery climate (i.e., the Children’s Health Activity Motor Program [CHAMP]), on lesson context and children’s physical activity (PA) levels. A secondary aim was to examine sex differences in PA levels in both programs. Method: Seventy-two preschoolers served as participants and were assigned to a movement program. Physical activity levels and lesson context were assessed with the System for Observing Fitness Instruction Time. Results: Preschoolers in CHAMP spent more time walking (p < .05, d = 3.3), more time in moderate-to-vigorous PA (MVPA; p < .05, d = 3.6), and less time standing (p < .05, d = 3.8) compared with those in a traditional movement program. Boys in both programs spent less time standing (p < .05, d = 4.8) and more time in vigorous activity (p < .05, d = 5.8) and MVPA (p < .05, d = 4.4) compared with girls. During CHAMP, children spent less time engaged in management and knowledge (p < .05, d = 1.4, and p < .001, d = 0.9, respectively) and more time in skill practice (p < .05, d = 1.5). Conclusion: The findings support that participation in CHAMP elicits more MVPA in preschool-age children compared with a traditional movement program. The Children’s Health Activity Motor Program provided children with more class time devoted to skill practice. The program appears to be an innovative approach that is beneficial for PA engagement and could contribute positively to children’s health.
A Human-Perceived Softness Measure of Virtual 3D Objects

We introduce the problem of computing a human-perceived softness measure for virtual 3D objects. As the virtual objects do not exist in the real world, we do not directly consider their physical properties but instead compute the human-perceived softness of the geometric shapes. In an initial experiment, we find that humans are highly consistent in their responses when given a pair of vertices on a 3D model and asked to select the vertex that they perceive to be more soft. This motivates us to take a crowdsourcing and machine learning framework. We collect crowdsourced data for such pairs of vertices. We then combine a learning-to-rank approach and a multi-layer neural network to learn a non-linear softness measure mapping any vertex to a softness value. For a new 3D shape, we can use the learned measure to compute the relative softness of every vertex on its surface. We demonstrate the robustness of our framework with a variety of 3D shapes and compare our non-linear learning approach with a linear method from previous work. Finally, we demonstrate the accuracy of our learned measure with user studies comparing our measure with the human-perceived softness of both virtual and real objects, and we show the usefulness of our measure with some applications.
Parental investment in Tibetan populations does not reflect stated cultural norms

&NA; In this paper, we examined both stated norms of sex preference and actual sex‐biases in parental investment in a Tibetan pastoralist society. We collected detailed demographic data on infant mortality, infant feeding, the length of interbirth intervals, and a decision when giving gifts, to examine sex‐biased parental investment. Our results indicate a mismatch between self‐reported son preference and measures of actual parental investment that favor daughters. We interpret this female‐biased parental investment as a possible response to daughters generating more economic resources. However, the stated sex preferences of both sexes reflect cultural norms that appear to have remained unchanged over a long period, which may reflect the importance of male roles in the past. Our behavioral measures of parental investment are those most likely to be in the control of women (such as breastfeeding and interbirth interval), so this mismatch between stated and actual investment may be especially true of women.