Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab35 is required for embryonic development and kidney and ureter homeostasis through regulation of epithelial cell junctions

Background Rab35 is a member of a GTPase family of endocytic trafficking proteins. Studies in cell lines have indicated that Rab35 participates in cell adhesion, polarity, cytokinesis, and primary cilia length and composition. Additionally, sea urchin Rab35 regulates actin organization and is required for gastrulation. In mice, loss of Rab35 in the CNS disrupts hippocampal development and neuronal organization. Outside of the CNS, the functions of mammalian Rab35 in vivo are unknown. Methods We generated and analyzed the consequences of both congenital and conditional null Rab35 mutations in mice. Using a LacZ reporter allele, we assessed Rab35 expression during development and postnatally. We assessed Rab35 loss in the kidney and ureter using histology, immunofluorescence microscopy, and western blotting. Results Congenital Rab35 loss of function caused embryonic lethality: homozygous mutants arrested at E7.5 with cardiac edema. Conditional loss of Rab35, either during gestation or postnatally, caused hydronephrosis. The kidney and ureter phenotype were associated with disrupted actin cytoskeletal architecture, altered Arf6 epithelial polarity, reduced adherens junctions, loss of tight junction formation, defects in EGFR expression and localization, disrupted cell differentiation, and shortened primary cilia. Conclusion Rab35 is essential for mammalian development and the maintenance of kidney and ureter architecture. Loss of Rab35 leads to non-obstructive hydronephrosis, making the Rab35 mutant mouse a novel mammalian model to study mechanisms underlying this disease. Significance Statement Hydronephrosis, distention of the renal calyces and pelvis, affects 1 in 100 infants. Most cases of hydronephrosis are associated with obstruction. Non-obstructive hydronephrosis is typically associated with impaired ureter development, and requires surgical intervention. Here, we describe a mouse model of non-obstructive hydronephrosis caused by mutations in Rab35. Hydronephrosis in Rab35 mutants is associated with the inability to maintain epithelial cell junctions, defects in EGFR expression, and altered urothelium and smooth muscle integrity of the ureter. The Rab35 mutant mouse is a novel model to study mechanisms and treatment strategies for non-obstructive hydronephrosis.
Your Name and Passport please: How the Data Privacy Myth fails to Withstand Reality – A Field-Level Perspective

Data privacy is commonly believed to be an issue of highest priority, and something deserved to be defended by all means. Over the past 50 years increasingly complex legislation has been born out of this assumption; the European GDPR being one such example. While data privacy advocates and lawyers celebrate the increasingly hard to comprehend and to comply with requirements, normal people largely do not care. We describe a field-level case in which utmost intimate data is regularly requested from and happily shared by a large number of applicants to a guestlist-only event. The absence of privacy concerns raised by the applicants might indicate that such concerns are largely a myth that fails to withstand reality.
Warped-MC: An Efficient Memory Controller Scheme for Massively Parallel Processors

The performance of GPU’s external memories is becoming more critical since a modern GPU runs thousands of concurrent threads that demand a huge volume of data. In order to utilize resources in the memory hierarchy more efficiently, GPU employs a memory coalescing scheme to reduce the number of demand requests created from a group of threads (i.e. a warp). However, GPU’s memory coalescing does not work well for applications that exhibit irregular memory access patterns, thus a single warp can generate multiple memory transactions. Since memory requests are serviced by different hierarchy levels and/or memory partitions, multiple outstanding requests from a single warp exhibit diverged fetch latency. Considering the execution time of a load warp is decided by the slowest memory transaction, the diverged memory latency within a warp is a critical performance factor for load warps. In this paper, we propose a warp-aware memory controller scheme, called Warped-MC, to mitigate the memory latency divergence issues. Based on the in-depth analysis, we reveal the memory latency divergence within a warp is mainly caused by GPU memory controllers. While the conventional FR-FCFS memory controller can maximize the effective bandwidth of DRAM channels, the scheduling scheme of the conventional memory controller can exacerbate the memory latency divergence of a warp. Warped-MC employs a warp-aware scheduling scheme to alleviate the memory latency divergence, thus Warped-MC can tackle the long tail of the load warp execution time to improve the performance of memory-intensive applications. We implement Warped-MC on GPGPU-Sim configured with the modern GPU architecture, and our evaluation results exhibit Warped-MC can improve the performance of memory-intensive applications by 8.9% on average with a maximum of 45.8%.
DArray: A High Performance RDMA-Based Distributed Array

This paper presents DArray, a high performance RDMA-based distributed memory system. DArray achieves high performance through three key designs. First, DArray is designed with an object array abstraction, which captures the high-level application semantics and provides a rich set of optimized interfaces with object granularity. Second, DArray adopts distributed cache to absorb remote data accesses. In order to reduce the performance overhead incurred by the cache layer and increase the parallelism, DArray devises a lock-free data access path to the local cache which utilizes reference counters to prevent data races. Finally, based on the observation that most data update operators are associative and commutative, DArray proposes a new "Operate" interface, which enables concurrent data operations on multiple nodes, and extends existing distributed cache coherence protocol to support the new "Operate" semantics. A graph analytics engine and a distributed key-value store (KVS) are built on top of DArray to demonstrate its versatility. The experiment results on graph applications show that DArray achieves two to three orders of magnitude better performance than GAM (a state-of-the-art distributed memory), also with a maximum speedup of 2.1x compared to Gemini (a state-of-the-art distributed graph engine). Furthermore, the DArray-based KVS outperforms the GAM-based KVS by up to 41x (from 2x).
Applying Nudge Theory to Foster the SDGs in Smart Cities

Smart cities are associated with huge potential to facilitate achieving of the Sustainable Development Goals (SDGs). The global reach of the SDGs by the citizens needs a synergy including the grass root individual level of decision-making. The nudge theory, a behavioral economics concept, is considered in terms of its application to smart city planning, implementation and policy making. The paper examines the basis and cases of practical embodiment of the nudge theory in smart cities. Through various strategies nudge theory can help to create more sustainable and resilient urban communities, and thus contribute to the achievement of the SDGs. The smart city planners may practically apply certain elements of the nudge approach. However, it may create not only positives but certain risks as well. The author analyses the potential of the nudge theory in smart cities, providing the recommendations to local and regional authorities and laying down the framework for its ethical, transparent and non-manipulative embodiment.
Integrative Genomic Analyses Reveal Putative Cell Type-specific Targets of the Drosophila Ets Transcription Factor Pointed

The Ets domain transcription factors direct diverse biological processes throughout all metazoans and are implicated in development as well as in tumor initiation, progression and metastasis. The Drosophila Ets transcription factor Pointed (Pnt) is required for several aspects of eye development and regulates cell cycle progression, specification, and differentiation. Despite its critical role in development, very few targets of Pnt have been reported previously. Here, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) to determine the genome-wide occupancy of Pnt in late larval eye discs. We identified enriched regions that mapped to an average of 6,941 genes, the vast majority of which are novel putative Pnt targets. Integrating ChIP-seq data with two other larval eye single cell genomics datasets (scRNA-seq and snATAC-seq) reveals genes that may be putative cell type-specific genes regulated by Pnt. Finally, our ChIP-seq data predict cell type-specific functional enhancers that were not reported previously. Our study provides a greatly expanded list of putative Pnt targets in the eye and is a resource for future studies that will allow mechanistic insights into complex developmental processes regulated by Pnt.
On Global Brain Reconfiguration after Local Manipulations

Understanding how localized brain interventions translate into whole-brain dynamics is crucial for deciphering neural function and tailoring therapeutic strategies. Combining mouse experimental datasets of focal interventions (thalamic lesion and chemogenetic silencing of cortical hubs), we demonstrate both local and global effects. Using whole-brain simulations of experimental data, we not only confirm the distributed nature of local manipulations but also offer mechanistic insights into these processes. Our simulations predict specific alterations in firing rates and spectral characteristics across specific brain networks, leading to structured changes in functional connectivity patterns. Some of these predictions have been empirically validated. Notably, the affected brain subnetworks—and their resultant ‘signatures’ of change—are contingent on the original intervention site, suggesting a method to accurately localize the source of alteration. Our results provide a general framework for interpreting localized intervention effects, offering insights that could refine clinical interventions for focal brain disorders by enabling targeted circuit-level neuromodulation strategies.
The relationship between tree canopy and crime rates across an urban–rural gradient in the greater Baltimore region - nrs_2012_troy_001

The extent to which urban tree cover influences crime is in debate in the literature. This research took advantage of geocoded crime point data and high resolution tree canopy data to address this question in Baltimore City and County, MD, an area that includes a significant urban–rural gradient. Using ordinary least squares and spatially adjusted regression and controlling for numerous potential confounders, we found that there is a strong inverse relationship between tree canopy and our index of robbery, burglary, theft and shooting. The more conservative spatially adjusted model indicated that a 10% increase in tree canopy was associated with a roughly 12% decrease in crime. When we broke down tree cover by public and private ownership for the spatial model, we found that the inverse relationship continued in both contexts, but the magnitude was 40% greater for public than for private lands. We also used geographically weighted regression to identify spatial non-stationarity in this relationship, which we found for trees in general and trees on private land, but not for trees on public land. Geographic plots of pseudo-t statistics indicated that while there was a negative relationship between crime and trees in the vast majority of block groups of the study area, there were a few patches where the opposite relationship was true, particularly in a part of Baltimore City where there is an extensive interface between industrial and residential properties. It is possible that in this area a significant proportion of trees is growing in abandoned lands between these two land uses. © 2012 Elsevier B.V. All rights reserved.
HASpGEMM: Heterogeneity-Aware Sparse General Matrix-Matrix Multiplication on Modern Asymmetric Multicore Processors

Sparse general matrix-matrix multiplication (SpGEMM) is an important kernel in computational science and engineering, and has been widely studied on homogeneous processors, e.g., CPUs and GPUs. Recently, the asymmetric multicore processors (AMPs), composed of big and LITTLE cores from ARM, or of performance and efficient cores from Apple and Intel, are becoming the mainstream processors of modern computers. However, directly running the existing SpGEMM algorithms on AMPs easily leads to load imbalance problems due to the irregularity from both the sparse matrix side and the AMP side, and there is still a lack of parallel SpGEMM algorithm that can efficiently exploit the different cores on AMPs. In this paper, we propose a parallel algorithm called heterogeneity-aware SpGEMM (HASpGEMM). To motivate our algorithm design, we first obtain the performance characteristics of a variety of kernels (i.e., SPA, HASH and ESC) on P- and E-cores of Intel 12th and 13th Gen AMPs through micro-benchmarking. On top of the large amount of kernel-level testing data, we design a row-wise mapping technique to better select kernels and cores for rows of different characteristics and develop a task assignment scheme to better balance workload in terms of compute and memory access on the two kinds of cores. Based on the experimental data, compared to the SPA, HASH, ESC, and the latest Intel oneMKL library on Intel Core i9-12900KF and i9-13900KF AMPs, our algorithm HASpGEMM achieves an average speedup of 2.83x, 1.85x, 3.85x, 1.88x (with a maximum speedup of 46.50x, 37.48x, 106.31x, 113.17x) on the i9-12900KF processor. On the i9-13900KF processor, it achieves an average speedup of 4.06x, 2.21x, 4.56x, 2.23x (with a maximum speedup of 52.51x, 78.08x, 161.68x, 131.48x).
Learning site-invariant features of connectomes to harmonize complex network measures

Multi-site diffusion MRI data is often acquired on different scanners and with distinct protocols. Differences in hardware and acquisition result in data that contains site dependent information, which confounds connectome analyses aiming to combine such multi-site data. We propose a data-driven solution that isolates site-invariant information whilst maintaining relevant features of the connectome. We construct a latent space that is uncorrelated with the imaging site and highly correlated with patient age and a connectome summary measure. Here, we focus on network modularity. The proposed model is a conditional, variational autoencoder with three additional prediction tasks: one for patient age, and two for modularity trained exclusively on data from each site. This model enables us to 1) isolate site-invariant biological features, learn site context, and 3) re-inject site context and project biological features to desired site domains. We tested these hypotheses by projecting 77 connectomes from two studies and protocols (Vanderbilt Memory and Aging Project (VMAP) and Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) to a common site. We find that the resulting dataset of modularity has statistically similar means (p-value <0.05) across sites. In addition, we fit a linear model to the joint dataset and find that positive correlations between age and modularity were preserved.
miR-137 conferred robustness to the territorial restriction of the neural plate border

The neural plate border (NPB) of vertebrate embryos segregated from the neural plate (NP) and epidermal regions, and comprised an intermingled group of progenitors with multiple fate potential. Recent studies have shown that during the gastrula stage, TFAP2A acts as a pioneer factor in remodeling the epigenetic landscape required to activate components of the NPB induction program. Here we show that Tfap2a has two highly conserved binding sites for miR-137 and both display a reciprocal expression pattern at the NPB and NP respectively. In addition, ectopic miR-137 expression reduced TFAP2A, whereas its functional inhibition expanded their territorial distribution overlapping with PAX7. Furthermore, we demonstrated that loss of the de novo DNA methyltransferase DNMT3A expanded miR-137 expression to the NPB. Bisulfite sequencing showed a significantly higher level of non-canonical CpH methylation at the promoter of miR-137 when we compared NPB and NP samples. Our finding shows that miR-137 contributes to the robustness of NPB territorial restriction in vertebrate development.
Overexpression of Rheb, a positive Tor regulator, reveals principles of rod outer segment size control

The outer segment of retinal rod photoreceptors is a highly modified cilium with the typical ciliary microtubular axoneme but additionally there are hundreds of densely packed, stacked, discrete intramembranous discs containing phototransduction machinery. The outer segment is continuously regenerated or renewed throughout the life of the animal through the combined processes of proximal growth and distal shedding. Since the pioneering experiments decades ago that demonstrated the process of rod outer segment renewal very little research has been directed towards understanding mechanistic principles of renewal and homeostasis, and many important questions remain unaddressed. The rod outer segment is a prime example of tight size control that is amenable to experimental and computational analyses. This study uses zebrafish molecular genetics with high resolution imaging, quantitative analyses, and computational modeling to uncover principles that regulate rod outer segment homeostatic length control. By genetically increasing rod outer segment growth, we show that outer segments lengthen and shedding does not accelerate to offset this added growth.
Post-Mating Inhibition of Female Sexual Drive via Heterogeneous Neuronal Ensembles in the Medial Preoptic Area

The completion of mating acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how the completion of mating affects sexual motivation and sexual behavior in female mice. How the brain responds to completion of mating is also unclear. Here, by using self-paced mating assay, we first demonstrate that female mice show decreased sexual motivation after the completion of mating. By using brain-wide analysis of activity-dependent labeling, we next pin-pointed the medial preoptic area as a brain region strongly responding to mating completion. Furthermore, using freely moving in vivo calcium imaging to compare neural activity of inhibitory and excitatory neurons in the medial preoptic area, we revealed that a subset of neurons responds significantly and specifically to mating completion but not to appetitive or consummatory behaviors. While there were excitatory and inhibitory neurons that showed positive response to the completion of mating, the response magnitude as well as the proportion of neurons responding to the event was significantly larger in the inhibitory neuron population. Next, by unbiased classification of their responses, we also found a subpopulation of neurons that increase their activity late after the onset of the completion of mating. These neurons were all inhibitory indicating that the completion of mating induces a prolonged inhibitory activity in the medial preoptic area. Lastly, we found that chemogenetic activation of medial preoptic area neurons that respond to mating completion, but not to appetitive behaviors, was sufficient to suppress female sexual motivation. Together, our data illuminate the importance of medial preoptic area as a brain node which encodes a negative signal that sustains low sexual motivation state after the completion of mating in female mice. Highlights Female mice show decreased sexual motivation after mating completion. A subset of MPOA neurons respond specifically to mating completion. Mating completion evokes persistent activity in MPOA inhibitory neurons. Activation of a subset of MPOA neurons is sufficient to suppress female sexual motivation.
Spatiospectral image processing workflow considerations for advanced MR spectroscopy of the brain

Magnetic resonance spectroscopy (MRS) is one of the few non-invasive imaging modalities capable of making neurochemical and metabolic measurements in vivo. Traditionally, the clinical utility of MRS has been narrow. The most common use has been the “single-voxel spectroscopy” variant to discern the presence of a lactate peak in the spectra in one location in the brain, typically to evaluate for ischemia in neonates. Thus, the reduction of rich spectral data to a binary variable has not classically necessitated much signal processing. However, scanners have become more powerful and MRS sequences more advanced, increasing data complexity and adding 2 to 3 spatial dimensions in addition to the spectral one. The result is a spatially- and spectrally-variant MRS image ripe for image processing innovation. Despite this potential, the logistics for robustly accessing and manipulating MRS data across different scanners, data formats, and software standards remain unclear. Thus, as research into MRS advances, there is a clear need to better characterize its image processing considerations to facilitate innovation from scientists and engineers. Building on established neuroimaging standards, we describe a framework for manipulating these images that generalizes to the voxel, spectral, and metabolite level across space and multiple imaging sites while integrating with LCModel, a widely used quantitative MRS peak-fitting platform. In doing so, we provide examples to demonstrate the advantages of such a workflow in relation to recent publications and with new data. Overall, we hope our characterizations will lower the barrier of entry to MRS processing for neuroimaging researchers.
Genome-wide Perturbation Analysis Screening System for Exosomes-Related Genes Based on the CRISPR/Cas9 Platform

As reported previously, exosomes have significant impacts on the physiological and pathological state in vivo. Exosomes have been extensively studied as a drug delivery carrier and some exosomes drugs have been undergoing clinical research. The mechanisms of exosome production, transport, and secretion remain to be studied in depth. Thus, here, we developed a novel CRISPR-UMI-based gene screening system, with which we can reveal the exosomes biogenesis, transport, and uptake mechanisms on a genome-wide scale. This system consists of two parts: one is a gene knockout component; the other part is a unique molecular identifiers (UMI) labeling component that can label the exosomes produced by the knockout cells, in which each sgRNA corresponds to a specific UMI. In this way, by detecting the UMI loaded in the exosomes, we can trace the knockout gene. In this study, we first verified the function of each component using plasmids and lentiviruses respectively. Next, we simulated the infection of cells with lentiviral libraries using a single lentivirus to validate the functionality of the screening system. Finally, we constructed a CRISPR-UMI-based library targeting 15 genes (genes with clear effects on exosomes biogenesis) to further validate the reliability of the screening system. The development of this screening system is of indispensable importance for the in-depth study of the mechanisms of exosome production and secretion, as well as for the improvement of exosomes production and the advancement of exosomes industrialization.