Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive characterization and optimization of anti-LRRK2 (leucine-rich repeat kinase 2) monoclonal antibodies

Missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a major cause of PD (Parkinson's disease). Several antibodies against LRRK2 have been developed, but results using these polyclonal antibodies have varied widely leading to conflicting conclusions. To address this challenge, the Michael J. Fox Foundation for Parkinson's Research generated a number of monoclonal antibodies targeting epitopes across the LRRK2 protein. In the present paper, we report optimized protocols and results for ten monoclonal antibodies for immunoblotting, immunohistochemistry, immunoprecipitation and kinase activity assays, in rat, mouse and human brain tissue. Several efficacious antibodies were identified, but results demonstrate that the mouse monoclonal N241A/34 is suitable for most applications, with the best overall rabbit monoclonal antibody being c41-2. These antibodies produced a dominant band of the expected size via immunoblotting and a lack of labelling in tissue derived from LRRK2-knockout animals under optimized conditions. A significant proportion of LRRK2 protein localizes to insoluble fractions and no evidence of truncated LRRK2 protein was detected in any fraction from rodent or human tissues. An assay was developed for the robust detection of LRRK2 kinase activity directly from frozen mouse and human brain tissue, but precipitous declines in activity were observed that corresponded to increasing post-mortem intervals and processing times. Finally, we demonstrate the highest levels of brain-localized LRRK2 in the striatum, but note differential expression patterns between rat and mouse in both striatum and cortex. Anti-LRRK2 monoclonal antibodies that are unlimited in availability together with the proposed standardized protocols should aid in the definition of LRRK2 function in both health and disease.
Features and Contexts in Technology Research: A Modest Proposal for Research and Reporting

Technology research has long faced difficulties in consistently defining technology, establishing cause-effect relations, and generating research results that generalize across technologies, users, contexts, and time (Barley, 1998). In this essay we (1) identify three of the many contributors to these difficulties, (2) mention some ambitious responses that have been suggested in the literature, and (3) propose a smaller but more concrete first step by asking researchers and theorists to attend to both features of technologies and the contexts in which they are used, and in so doing to improve our ability as a field to accumulate knowledge in the face of these challenges.
Giant gravitons—with strings attached (I)

In this article, the free field theory limit of operators dual to giant gravitons with open strings attached, are studied. We introduce a graphical notation, which employs Young diagrams, for these operators. The computation of two point correlation functions is reduced to the application of three simple rules, written as graphical operations performed on the Young diagram labels of the operators. Using this technology, we have studied gravitational radiation by giant gravitons and bound states of giant gravitons, transitions between excited giant graviton states and joining of open strings attached to the giant.
Identification of Major Factors Influencing ELISpot-Based Monitoring of Cellular Responses to Antigens from Mycobacterium tuberculosis

A number of different interferon-γ ELISpot protocols are in use in laboratories studying antigen-specific immune responses. It is therefore unclear how results from different assays compare, and what factors most significantly influence assay outcome. One such difference is that some laboratories use a short in vitro stimulation period of cells before they are transferred to the ELISpot plate; this is commonly done in the case of frozen cells, in order to enhance assay sensitivity. Other differences that may be significant include antibody coating of plates, the use of media with or without serum, the serum source and the number of cells added to the wells. The aim of this paper was to identify which components of the different ELISpot protocols influenced assay sensitivity and inter-laboratory variation. Four laboratories provided protocols for quantifying numbers of interferon-γ spot forming cells in human peripheral blood mononuclear cells stimulated with Mycobacterium tuberculosis derived antigens. The differences in the protocols were compared directly. We found that several sources of variation in assay protocols can be eliminated, for example by avoiding serum supplementation and using AIM-V serum free medium. In addition, the number of cells added to ELISpot wells should also be standardised. Importantly, delays in peripheral blood mononuclear cell processing before stimulation had a marked effect on the number of detectable spot forming cells; processing delay thus should be minimised as well as standardised. Finally, a pre-stimulation culture period improved the sensitivity of the assay, however this effect may be both antigen and donor dependent. In conclusion, small differences in ELISpot protocols in routine use can affect the results obtained and care should be given to conditions selected for use in a given study. A pre-stimulation step may improve the sensitivity of the assay, particularly when cells have been previously frozen.
Feasibility of High-Resolution Soil Erosion Measurements by Means of Rainfall Simulations and SfM Photogrammetry

The silty soils of the intensively used agricultural landscape of the Saxon loess province, eastern Germany, are very prone to soil erosion, mainly caused by water erosion. Rainfall simulations, and also increasingly structure-from-motion (SfM) photogrammetry, are used as methods in soil erosion research not only to assess soil erosion by water, but also to quantify soil loss. This study aims to validate SfM photogrammetry determined soil loss estimations with rainfall simulations measurements. Rainfall simulations were performed at three agricultural sites in central Saxony. Besides the measured data runoff and soil loss by sampling (in mm), terrestrial images were taken from the plots with digital cameras before and after the rainfall simulation. Subsequently, SfM photogrammetry was used to reconstruct soil surface changes due to soil erosion in terms of high resolution digital elevation models (DEMs) for the pre- and post-event (resolution 1 × 1 mm). By multi-temporal change detection, the digital elevation model of difference (DoD) and an averaged soil loss (in mm) is received, which was compared to the soil loss by sampling. Soil loss by DoD was higher than soil loss by sampling. The method of SfM photogrammetry-determined soil loss estimations also include a comparison of three different ground control point (GCP) approaches, revealing that the most complex one delivers the most reliable soil loss by DoD. Additionally, soil bulk density changes and splash erosion beyond the plot were measured during the rainfall simulation experiments in order to separate these processes and associated surface changes from the soil loss by DoD. Furthermore, splash was negligibly small, whereas higher soil densities after the rainfall simulations indicated soil compaction. By means of calculated soil surface changes due to soil compaction, the soil loss by DoD achieved approximately the same value as the soil loss by rainfall simulation.
Revitalizing human virtue by restoring organic morality*

Abstract Most of human history and prehistory was lived in economic poverty but with social and ecological wealth, both of which are diminishing as commodification takes over most everything. Human moral wealth has also deteriorated. Because humans are biosocially, dynamically, and epigenetically shaped, early experience is key for developing one’s moral capital. When early experience is species-atypical, meaning that it falls outside the evolved developmental niche (EDN), which is often the case in modern societies, biopsychosocial moral development is undermined, shifting one’s nature and worldview to self-protectionism. Individuals develop into self-regarding shadows of their potential selves, exhibiting threat-reactive moral mindsets that promote unjust treatment of other humans and nonhumans. Humanity’s moral wealth can be re-cultivated by taking up what indigenous people all over the world know: that a good life, a virtuous life, is a one that is led by a well-cultivated heart, embodied in action that includes partnership with nonhumans. Moral educators can help students to revamp their capacities with self-calming skills, the development of social pleasure and communal ecological imagination.
Performance Comparison of Routing Protocols in Opportunistic Networks

In Opportunistic Networks (OppNets), mobile devices transmit messages by exploiting the direct contacts, without the need of an end-to-end infrastructure. Disconnections of nodes and high churn rates are normal features of opportunistic networks. Hence, routing is one of the main challenges in this environment. In this paper, we provide a survey of the main routing approaches in OppNets and classify them into two classes: context-oblivious and context-based routing. We emphasize the role of context information in forwarding data in OppNets, and evaluate the relative performance of Epidemic and PROPHET routing protocols.
Stem Cell-Based Cell Therapy for Glomerulonephritis

Glomerulonephritis (GN), characterized by immune-mediated inflammatory changes in the glomerular, is a common cause of end stage renal disease. Therapeutic options for glomerulonephritis applicable to all cases mainly include symptomatic treatment and strategies to delay progression. In the attempt to yield innovative interventions fostering the limited capability of regeneration of renal tissue after injury and the uncontrolled pathological process by current treatments, stem cell-based therapy has emerged as novel therapy for its ability to inhibit inflammation and promote regeneration. Many basic and clinical studies have been performed that support the ability of various stem cell populations to ameliorate glomerular injury and improve renal function. However, there is a long way before putting stem cell-based therapy into clinical practice. In the present article, we aim to review works performed with respect to the use of stem cell of different origins in GN, and to discuss the potential mechanism of therapeutic effect and the challenges for clinical application of stem cells.
Detailed Survey on Exemplar Based Image Inpainting Techniques

Image inpainting is a technique which is used to patch up the missing area in an image. In early years image inpainting techniques gained the high popularity in the field of image processing, used for restoration of damaged images. The aim of image inpainting is to fill in the missing area in an image which is visible to human eyes. Image inpainting is also applied for reinstallation of old images/films, correction of red-eye, object elimination in digital photographs, removal of spots of dust in image/film, creative effect by removing objects etc. There are different types of image inpainting techniques such asexemplar based image inpainting, texture synthesis based image inpainting, PDE based image inpainting, hybrid inpainting and Semi-automatic and Fast Inpainting. In this paper we provide a detailed survey on Exemplar based image inpainting. Keywords-Inpainting, Exemplar Based Inpainting, PDE Based Inpainting, Texture Synthesis, Hybrid Inpainting, Object Removal, Filling Area.
Joint polarization-DOA estimation for SIMO radar using single receiver

The recovery of polarization and direction of arrivals (DOAs) of multiple targets locating at the same range but different angles in the forward-looking direction is of great trouble for conventional active radar. Based on compressive sensing (CS) framework, a joint polarization-DOA estimation strategy for single-input-multiple-output (SIMO) radar is proposed, which can reconstruct the sparse target scenario on joint polarization-angle domain. Being different from traditional SIMO radar demanding multiple receiving channels, the proposed strategy needs single receiver in an economic way. Numerical experiments show the effectiveness of the proposed strategy.
Mrs: High Performance MapReduce for Iterative and Asynchronous Algorithms in Python

Mrs [1] is a lightweight Python-based MapReduce implementation designed to make MapReduce programs easy to write and quick to run, particularly useful for research and academia. A common set of algorithms that would benefit from Mrs are iterative algorithms, like those frequently found in machine learning; however, iterative algorithms typically perform poorly in the MapReduce framework, meaning potentially poor performance in Mrs as well.Therefore, we propose four modifications to the original Mrs with the intent to improve its ability to perform iterative algorithms. First, we used direct task-to-task communication for most iterations and only occasionally write to a distributed file system to preserve fault tolerance. Second, we combine the reduce and map tasks which span successive iterations to eliminate unnecessary communication and scheduling latency. Third, we propose a generator-callback programming model to allow for greater flexibility in the scheduling of tasks. Finally, some iterative algorithms are naturally expressed in terms of asynchronous message passing, so we propose a fully asynchronous variant of MapReduce.We then demonstrate Mrs' enhanced performance in the context of two iterative applications: particle swarm optimization (PSO), and expectation maximization (EM).
THE INFORMATION CONTENT OF AN OPEN LIMIT-ORDER BOOK

Lehmann, Mark Lipson, Chris Muscarella, Gideon Saar, Chester Spatt, Avanidhar Subrahmanyam, Robert Webb (the Editor), an anonymous referee, and seminar participants at Penn State, Rutgers, George Washington Universities, the Western Finance Association Meetings, the NBER-JFM Microstructure Conference, the American Finance Association Meetings, and the 15th Annual Asia Pacific Futures Research Symposium for their helpful comments. The authors are grateful to the Australian Stock Exchange and the Securities Industry Research Centre Asia-Pacific for providing the data used in this study. The authors also thank Morgan Stanley for providing the equity market microstructure research grant for this study.
Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth

Summary Target of rapamycin complex 1 (TORC1), which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not.
Canine Length in Wild Male Baboons: Maturation, Aging and Social Dominance Rank

Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04–20.45 years) from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge) with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank), but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.
Brief Sounds Evoke Prolonged Responses in Anesthetized Ferret Auditory Cortex

Neurons in the auditory cortex of anesthetized animals are generally considered to generate phasic responses to simple stimuli such as tones or noise bursts. In this paper, we show that under ketamine/medetomidine anesthesia, neurons in ferret auditory cortex usually exhibit complex sustained responses. We presented 100-ms broad-band noise bursts at a range of interaural level differences (ILDs) and average binaural levels (ABLs), and used extracellular electrodes to monitor evoked activity over 700 ms poststimulus onset. We estimated the degree of randomness (noise) in the response functions of individual neurons over poststimulus time; we found that neural activity was significantly modulated by sound for up to ∼500 ms following stimulus offset. Pooling data from all neurons, we found that spiking activity carries significant information about stimulus identity over this same time period. However, information about ILD decayed much more quickly over time compared with information about ABL. In addition, ILD and ABL are coded independently by the neural population even though this is not the case at individual neurons. Though most neurons responded more strongly to ILDs corresponding to the opposite side of space, as a population, they were equally informative about both contra- and ipsilateral stimuli.
Itone: a japanese text input method for a dual joystick game controller

In this paper, we report the design and evaluation of a Japanese text input method called IToNe. It uses a dual joystick game controller to input Japanese text. The left and right joysticks are respectively assigned to the left and right halves of the Japanese syllabary chart. The combination of left and right joystick signals selects a character. IToNe is theoretically faster than the Japanese selection chart. Results of a preliminary user study show that users prefer IToNe to EGCONVERT: its smoothness during operation and accuracy measures are significantly higher. In addition, the learning curve of IToNe suggests that it can be learned easily and that it potentially provides higher performance.
The Timing of the Circadian Clock and Sleep Differ between Napping and Non-Napping Toddlers

The timing of the internal circadian clock shows large inter-individual variability across the lifespan. Although the sleep-wakefulness pattern of most toddlers includes an afternoon nap, the association between napping and circadian phase in early childhood remains unexplored. This study examined differences in circadian phase and sleep between napping and non-napping toddlers. Data were collected on 20 toddlers (34.2±2.0 months; 12 females; 15 nappers). Children followed their habitual napping and non-napping sleep schedules (monitored with actigraphy) for 5 days before an in-home salivary dim light melatonin onset (DLMO) assessment. On average, napping children fell asleep during their nap opportunities on 3.6±1.2 of the 5 days before the DLMO assessment. For these napping children, melatonin onset time was 38 min later (p = 0.044; d = 0.93), actigraphically-estimated bedtime was 43 min later (p = 0.014; d = 1.24), sleep onset time was 59 min later (p = 0.006; d = 1.46), and sleep onset latency was 16 min longer (p = 0.030; d = 1.03) than those not napping. Midsleep and wake time did not differ by napping status. No difference was observed in the bedtime, sleep onset, or midsleep phase relationships with DLMO; however, the wake time phase difference was 47 min smaller for napping toddlers (p = 0.029; d = 1.23). On average, nappers had 69 min shorter nighttime sleep durations (p = 0.006; d = 1.47) and spent 49 min less time in bed (p = 0.019; d = 1.16) than non-nappers. Number of days napping was correlated with melatonin onset time (r = 0.49; p = 0.014). Our findings indicate that napping influences individual variability in melatonin onset time in early childhood. The delayed bedtimes of napping toddlers likely permits light exposure later in the evening, thereby delaying the timing of the clock and sleep. Whether the early developmental trajectory of circadian phase involves an advance associated with the decline in napping is a question necessitating longitudinal data as children transition from a biphasic to monophasic sleep-wakefulness pattern.
Research of architecture for grid manufacturing

Architecture for grid manufacturing system was provided. The evolution of manufacturing mode and the naissance of grid manufacturing were analyzed, and the typical architecture for grid was introduced, they are the layered sandglass structure and the open grid service architecture (OGSA). Then we analyzed the scheme of grid manufacturing for Shaoxing spinning region, based on which, architecture for grid manufacturing system was proposed. The manufacturing grid architecture absorbed the five-level framework of grid and the grid services idea in OGSA, and integrated many supporting toolboxes and protocols of Globus, which is a helpful exploration to the development of grid manufacturing system.
Bulk Synaptic Vesicle Endocytosis Is Rapidly Triggered during Strong Stimulation

Bulk endocytosis in central nerve terminals is activated by strong stimulation; however, the speed at which it is initiated and for how long it persists is still a matter of debate. To resolve this issue, we performed a characterization of bulk endocytic retrieval using action potential trains of increasing intensity. Bulk endocytosis was monitored by the loading of the fluorescent dyes FM2-10 and FM1-43, uptake of tetramethylrhodamine-dextran (40 kDa), or morphological analysis of uptake of the fluid-phase marker horseradish peroxidase. When neuronal cultures were subjected to mild stimulation (200 action potentials at 10 Hz), bulk endocytosis was not observed using any of our assay systems. However, when more intense trains of action potentials (400 or 800 action potentials at 40 and 80 Hz, respectively) were applied to neurons, bulk endocytosis was activated immediately, with the majority of bulk endocytosis complete by the end of stimulation. This contrasts with single synaptic vesicle endocytosis, the majority of which occurred after stimulation was terminated. Thus, bulk endocytosis is a fast event that is triggered during strong stimulation and provides the nerve terminal with an appropriate mechanism to meet the demands of synaptic vesicle retrieval during periods of intense synaptic vesicle exocytosis.