Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau

Tau is a developmentally regulated microtubule-associated protein that influences microtubule behavior by directly associating with tubulin. The carboxyl terminus of tau contains multiple 18-amino acid repeats that bind microtubules and are separated by 13-14-amino acid inter- repeat (IR) regions previously thought to function as "linkers. " Here, we have performed a high resolution deletion analysis of tau and identified the IR region located between repeats 1 and 2 (the R1-R2 IR) as a unique microtubule binding site with more than twice the binding affinity of any individual repeat. Truncation analyses and site- directed mutagenesis reveal that the binding activity of this site is derived primarily from lys265 and lys272, with a lesser contribution from lys271. These results predict strong, discrete electrostatic interactions between the R1-R2 IR and tubulin, in contrast to the distributed array of weak interactions thought to underlie the association between 18-amino acid repeats and microtubules (Butner, K. A., and M. W. Kirschner. J. Cell Biol. 115:717-730). Moreover, competition assays suggest that the R1-R2 IR associates with microtubules at tubulin site(s) distinct from those bound by the repeats. Finally, a synthetic peptide corresponding to just 10 amino acids of the R1-R2 IR is sufficient to promote tubulin polymerization in a sequence-dependent manner. Since the R1-R2 IR is specifically expressed in adult tau, its action may underlie some of the developmental transitions observed in neuronal microtubule organization. We suggest that the R1-R2 IR may establish an adult- specific, high affinity anchor that tethers the otherwise mobile tau molecule to the tubulin lattice, thereby increasing microtubule stability. Moreover, the absence of R1-R2 IR expression during early development may allow for the cytoskeletal plasticity required of immature neurons.
Controlled Multi-Batch Self-Assembly of Micro Devices

A technique is described for assembly of multiple batches of micro components onto a single substrate. The substrate is prepared with hydrophobic alkanethiol-coated gold binding sites. To perform assembly, a hydrocarbon oil is applied to the substrate and wets exclusively the hydrophobic binding sites in water. Micro components are then added to the water, and assembled on the oil-wetted binding sites. Moreover, assembly can be controlled to take place on desired binding sites by using an electrochemical method to de-activate specific substrate binding sites. By repeatedly applying this technique, different batches of micro components can be assembled to a single substrate sequentially. As a post assembly procedure, electroplating is incorporated into the technique to establish electrical connections for assembled components. Important issues presented are: substrate fabrication techniques, electrochemical modulation by using suitable alkanethiol (dodecanethiol), electroplating of tin and lead alloy and binding site design simulations. Finally, we demonstrate a two-batch assembly of silicon square parts, and electrical connectivity by electroplating contacts to surface-mount light emitting diodes.
A multi-level control architecture for the bionic handling assistant

The bionic handling assistant is one of the largest soft continuum robots and very special in being a pneumatically operated platform that is able to bend, stretch, and grasp in all directions. It nevertheless shares many challenges with smaller continuum and other soft robots such as parallel actuation, complex movement dynamics, slow pneumatic actuation, non-stationary behavior, and a lack of analytic models. To master the control of this challenging robot, we argue for a tight integration of standard analytic tools, simulation, control, and state-of-the-art machine learning into an overall architecture that can serve as blueprint for control design also beyond the BHA. To this aim, we show how to integrate specific modes of operation and different levels of control in a synergistic manner, which is enabled by using modern paradigms of software architecture and middleware. We thereby achieve an architecture with unique overall control abilities for a soft continuum robot that allow for flexible experimentation toward compliant user-interaction, grasping, and online learning of internal models. Graphical Abstract
Geometric and discrete path planning for interactive virtual worlds

Path planning and navigation are indispensable components for controlling autonomous agents in interactive virtual worlds. Given the growing demands on the size and complexity of modern virtual worlds, a number of new techniques have been developed for achieving intelligent navigation for the next generation of interactive multi-agent simulations. This course reviews the evolution of the several related techniques, from classical planning algorithms and computational geometry techniques to more advanced topics with focus on recent developments from the work of the authors. The covered topics range from discrete search and geometric representations to planning under different types of constraints and harnessing the power of graphics hardware in order to address Euclidean shortest paths and discrete search for multiple agents under limited time budgets. The use of planning algorithms beyond path planning is also discussed in the areas of crowd animation and whole-body motion planning for virtual characters.
Early Revelation of Leprosy in China by Sequential Antibody Analyses with LID-1 and PGL-I

Leprosy is a disabling chronic infection, with insidious onset that often evades early detection. In order to detect new leprosy cases in a timely manner, we conducted surveillance visits in some difficult-to-reach mountain areas in South West China where the disease is still prevalent. Our data confirm that Chinese multibacillary (MB) leprosy patients have strong antibody responses against Mycobacterium leprae antigens ND-O-BSA and LID-1. Contacts of clinically diagnosed patients were then monitored at regular intervals by both physical examinations and the laboratory determination of antibody responses in sera collected during these examinations. Elevations in antibody titers indicated the onset of MB leprosy in one of the contacts, and diagnosis was subsequently confirmed on physical examination. Our data indicate that rising antibody titers can be used as a trigger for physical examination or increased monitoring of particular individuals in order to provide early leprosy diagnosis.
Retinal ganglion cell morphology after optic nerve crush and experimental glaucoma.

PURPOSE To study sequential changes in retinal ganglion cell (RGC) morphology in mice after optic nerve crush and after induction of experimental glaucoma. METHODS Nerve crush or experimental glaucoma was induced in mice that selectively express yellow fluorescent protein (YFP) in RGCs. Mice were euthanized 1, 4, and 9 days after crush and 1, 3, and 6 weeks after induction of glaucoma by bead injection. All YFP-RGCs were identified in retinal whole mounts. Then confocal images of randomly selected RGCs were quantified for somal fluorescence brightness, soma size, neurite outgrowth, and dendritic complexity (Sholl analysis). RESULTS By 9 days after crush, 98% of RGC axons died and YFP-RGCs decreased by 64%. After 6 weeks of glaucoma, 31% of axons died, but there was no loss of YFP-RGC bodies. All crush retinas combined had significant decreases in neurite outgrowth parameters (P ≤ 0.036, generalized estimating equation [GEE] model) and dendritic complexity was lower than controls (P = 0.017, GEE model). There was no change in RGC soma area after crush. In combined glaucoma data, the RGC soma area was larger than control (P = 0.04, GEE model). At 3 weeks, glaucoma RGCs had significantly larger values for dendritic structure and complexity than controls (P = 0.044, GEE model), but no statistical difference was found at 6 weeks. CONCLUSIONS After nerve crush, RGCs and axons died rapidly, and dendritic structure decreased moderately in remaining RGCs. Glaucoma caused an increase in RGC dendrite structure and soma size at 3 weeks.
Novel APC-like properties of human NK cells directly regulate T cell activation

Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane–enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell–mediated cytotoxicity and specific ligand recognition by cell surface–activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell–activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV–infected uterine decidual samples, and from transporter-associated processing antigen 2–deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell–activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells. Nonstandard abbreviations used ANK activated NK dNK decidual NK HA hemagglutinin ImDC immature DC MDC mature DC MFI mean fluorescence intensity NCR natural cytotoxicity receptor TAP2 transporter-associated processing antigen 2 UaNK unactivated NK
The Faces in Infant-Perspective Scenes Change over the First Year of Life

Mature face perception has its origins in the face experiences of infants. However, little is known about the basic statistics of faces in early visual environments. We used head cameras to capture and analyze over 72,000 infant-perspective scenes from 22 infants aged 1-11 months as they engaged in daily activities. The frequency of faces in these scenes declined markedly with age: for the youngest infants, faces were present 15 minutes in every waking hour but only 5 minutes for the oldest infants. In general, the available faces were well characterized by three properties: (1) they belonged to relatively few individuals; (2) they were close and visually large; and (3) they presented views showing both eyes. These three properties most strongly characterized the face corpora of our youngest infants and constitute environmental constraints on the early development of the visual system.
A Convex Approach to Analysis, State and Output Feedback Control Parabolic PDEs Using Sum-of-Squares

In this paper we use optimization-based methods to analyze the stability and design state and output-feedback controllers for a class of one-dimensional parabolic partial differential equations. The output may be the complete state measurement or the boundary measurement of the state. The input considered is Neumann boundary actuation. We use Lyapunov operators, duality, and the Luenberger observer framework to reformulate the synthesis problem as a convex optimization problem expressed as a set of Linear-Operator-Inequalities (LOIs). We then show how feasibility of these LOIs may be tested using Semidefinite Programming (SDP) and the Sum-of-Squares methodology. Moreover, we provide numerical results which prove that the method can be generalized for application to systems with other types of boundary conditions.
DNA Polymerases of Low-GC Gram-Positive Eubacteria: Identification of the Replication-Specific Enzyme Encoded by dnaE

ABSTRACT dnaE, the gene encoding one of the two replication-specific DNA polymerases (Pols) of low-GC-content gram-positive bacteria (E. Dervyn et al., Science 294:1716-1719, 2001; R. Inoue et al., Mol. Genet. Genomics 266:564-571, 2001), was cloned from Bacillus subtilis, a model low-GC gram-positive organism. The gene was overexpressed in Escherichia coli. The purified recombinant product displayed inhibitor responses and physical, catalytic, and antigenic properties indistinguishable from those of the low-GC gram-positive-organism-specific enzyme previously named DNA Pol II after the polB-encoded DNA Pol II of E. coli. Whereas a polB-like gene is absent from low-GC gram-positive genomes and whereas the low-GC gram-positive DNA Pol II strongly conserves a dnaE-like, Pol III primary structure, it is proposed that it be renamed DNA polymerase III E (Pol III E) to accurately reflect its replicative function and its origin from dnaE. It is also proposed that DNA Pol III, the other replication-specific Pol of low-GC gram-positive organisms, be renamed DNA polymerase III C (Pol III C) to denote its origin from polC. By this revised nomenclature, the DNA Pols that are expressed constitutively in low-GC gram-positive bacteria would include DNA Pol I, the dispensable repair enzyme encoded by polA, and the two essential, replication-specific enzymes Pol III C and Pol III E, encoded, respectively, by polC and dnaE.
FEMALE DOMINANCE AND SOCIAL STRUCTURE IN ALAOTRAN GENTLE LEMURS

Summary Lemur social systems have the striking social feature, that adult females consistently evoke submissive behaviour of adult males. In the Alaotran gentle lemur, Hapalemur griseus alaotrensis , however, female dominance has not been studied yet. Here we cone rm female dominance over males on the basis of a 5-month e eld study of the social behaviour of four groups, in the Lake Alaotra marshland of eastern Madagascar. Further, we found that dominant individuals initiated aggressive interactions signie cantly more often than lowerranking ones, they initiatedgroup movements more often and higher-ranking individuals were groomed more often. The spatial cone guration was remarkable, since individuals were closer in space to those more distant in rank.
The Determinants of Customer Satisfaction after Service Failure and Recovery

The customer satisfaction after service failure and recovery is one of the most important issues of service marketing research. A deep literature suggests that most researchers have tried to explain customer satisfaction after service failure and recovery from perceived justice, perceived quality or perceived value. In this research, we integrate these three viewpoints into a single framework, and try to compare their explanation power. Research shows that perceived justice and perceived value influence satisfaction directly, while perceived quality only effects satisfaction indirectly. We also reveal the relationships among these three factors.
Development of a Novel Tool for Engaging Children and Parents in Asthma Self-Management

This paper describes the development and evaluation of an innovative application designed to engage children and their parents in weekly asthma self-monitoring and self-management to prompt an early response to deteriorations in chronic asthma control, and to provide their physicians with longitudinal data to assess the effectiveness of asthma therapy and prompt adjustments. The evaluation included 2 iterative usability testing cycles with 6 children with asthma and 2 parents of children with asthma to assess user performance and satisfaction with the application. Several usability problems were identified and changes were made to ensure acceptability of the application and relevance of the content. This novel application is unique compared to existing asthma tools and may shift asthma care from the current reactive, acute care model to a preventive, proactive patient-centered approach where treatment decisions are tailored to patients' individual patterns of chronic asthma control to prevent acute exacerbations.
Processing of a Psoralen DNA Interstrand Cross-link by XPF-ERCC1 Complex in Vitro*

The processing of stalled forks caused by DNA interstrand cross-links (ICLs) has been proposed to be an important step in initiating mammalian ICL repair. To investigate a role of the XPF-ERCC1 complex in this process, we designed a model substrate DNA with a single psoralen ICL at a three-way junction (Y-shaped DNA), which mimics a stalled fork structure. We found that the XPF-ERCC1 complex makes an incision 5′ to a psoralen lesion on Y-shaped DNA in a damage-dependent manner. Furthermore, the XPF-ERCC1 complex generates an ICL-specific incision on the 3′-side of an ICL. The ICL-specific 3′-incision, along with the 5′-incision, on the cross-linked Y-shaped DNA resulted in the separation of the two cross-linked strands (the unhooking of the ICL) and the induction of a double strand break near the cross-linked site. These results implicate the XPF-ERCC1 complex in initiating ICL repair by unhooking the ICL, which simultaneously induces a double strand break at a stalled fork.
Modeling the Mutualistic Interactions between Tubeworms and Microbial Consortia

The deep-sea vestimentiferan tubeworm Lamellibrachia luymesi forms large aggregations at hydrocarbon seeps in the Gulf of Mexico that may persist for over 250 y. Here, we present the results of a diagenetic model in which tubeworm aggregation persistence is achieved through augmentation of the supply of sulfate to hydrocarbon seep sediments. In the model, L. luymesi releases the sulfate generated by its internal, chemoautotrophic, sulfide-oxidizing symbionts through posterior root-like extensions of its body. The sulfate fuels sulfate reduction, commonly coupled to anaerobic methane oxidation and hydrocarbon degradation by bacterial–archaeal consortia. If sulfate is released by the tubeworms, sulfide generation mainly by hydrocarbon degradation is sufficient to support moderate-sized aggregations of L. luymesi for hundreds of years. The results of this model expand our concept of the potential benefits derived from complex interspecific relationships, in this case involving members of all three domains of life.
A computationally adequate model for overloading via domain-valued functors

We give a denotational semantics to a calculus λ[otimes ] with overloading and subtyping. In λ[otimes ], the interaction between overloading and subtyping causes self application, and non-normalizing terms exist for each type. Moreover, the semantics of a type depends not on that type alone, but also on infinitely many others. Thus, we need to consider infinitely many domains, which are related by an infinite number of mutually recursive equations. We solve this by considering a functor category from the poset of types modulo equivalence to a category in which each type is interpreted. We introduce a categorical constructor corresponding to overloading, and formalize the equations as a single equation in the functor category. A semantics of λ[otimes ] is then expressed in terms of the minimal solution of this equation. We prove the adequacy theorem for λ[otimes ] following the construction in Pitts (1994) and use it to derive some syntactic properties.
Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium

Intestinal epithelial cells (IEC) are organised as a single cell layer which covers the intestine. Their primary task is to absorb nutrients present in the intestinal lumen. However, IEC also play an important role in the immune defence of our body by building a barrier that separates the bowel wall from potentially hazardous bacteria present in the gut lumen. The life cycle of IEC is determined by the time span in which cells migrate from their place of origin at the crypt base to the villus tip, from where they are shed into the lumen. Cell death in the intestinal epithelium has to be tightly regulated and irregularities might cause pathologies. Excessive cell death has been associated with chronic inflammation as seen in patients with Crohn's disease and ulcerative colitis. While until recently apoptosis was discussed as being essential for epithelial turnover and tissue homeostasis in the intestinal epithelium, recent data using gene deficient mice have challenged this concept. Moreover, an apoptosis-independent mode of programmed cell death, termed necroptosis, has been identified and described in the intestinal epithelium. The following article reviews previous studies on cell death regulation in IEC and a potential role of necroptosis for gut homeostasis.
Natural History of Venous Thromboembolism

Abstract Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post‐thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. About 50% of diagnosed PEs are associated with right ventricular dysfunction, which is associated with a ≈5‐fold greater in‐hospital mortality. There is ≈50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. About 5% of treated patients with PE develop pulmonary hypertension as a result of poor resolution. After a course of treatment, the risk of recurrent thrombosis is higher (ie, ≈10% per patient‐year) in patients without reversible risk factors, in those with cancer, and in those with prothrombotic biochemical abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden. (Circulation. 2003;107:I‐22‐I‐30.)
THE CELL GENERATION CYCLE OF THE ELEVEN-DAY MOUSE EMBRYO

The incorporation of tritiated thymidine into the DNA of erythroblasts, primitive ependymal cells, and mesenchymal cells of 11-day mouse embryos was studied by radioautography at different times between 25 minutes and 18 hours after injection intraperitoneally. There was no labeling of mitotic figures until 1 hour after injection. Following this, mitotic figures were labeled for about 5.5 hours in primitive ependymal cells and mesenchymal cells, and for a longer period in erythroblasts. The percentage of the labeled primitive ependymal cells at various times after injection indicate a periodic migration into and out of the mitotic zone. The cell generation cycle of primitive ependymal cells and mesenchymal cells is similar to some kinds of adult cells. The cycle of the erythroblasts is more like that of the cells of aging mice.