Miracle-dz/UniFAR-FTUs huggingface dataset:
Grb7 knockout mice develop normally but litters born to knockout females fail to thrive

Growth factor receptor-bound 7 (Grb7) is an adaptor protein involved in signal transduction downstream of multiple receptor tyrosine kinases, including ERBB, FGFR and PDGFR pathways. Experimental studies have implicated Grb7 in regulating cell proliferation, survival, migration and invasion through its large repertoire of protein-protein interactions. Here, we describe the generation and characterization of a Grb7 knockout mouse. These mice are viable and fertile. A lacZ knock-in reporter was used to visualize Grb7 promoter activity patterns in adult tissues, indicating widespread Grb7 expression in glandular epithelium, the central nervous system and other tissues. The sole defect observed in these animals was a failure of Grb7 knockout females to successfully raise pups to weaning age, a phenotype that was independent of both paternal and pup genotypes. These data suggest a regulatory role for Grb7 in mammary lactational physiology.
Engagement of sialylated glycans with Siglec receptors on myeloid suppressor cells inhibit anti-cancer immunity via CCL2

Overexpression of sialic acids on glycans, called hypersialylation is a common alteration found in cancer. Hypersialylation can, for example, enhance immune evasion via interaction with sialic acid-binding immunoglobulin-like lectin (Siglec) receptors on tumor-infiltrating immune cells. Here, we tested the role of sialic acid on myeloid-derived suppressor cells (MDSCs) and their interaction with Siglec receptors. We found that MDSCs derived from the blood of lung cancer patients and tumor-bearing mice strongly express inhibitory Siglec receptors. In murine cancer models of emergency myelopoiesis, Siglec-E knockout on myeloid cells resulted in prolonged survival and increased infiltration of activated T cells. Targeting suppressive myeloid cells by blocking Siglec receptors or desialylation led to strong reduction of their suppressive potential. We further identified CCL2 as mediator involved in T cell suppression upon interaction of sialoglycans and Siglec receptors on MDSCs. Our results provide mechanistic insights how sialylated glycans inhibit anti-cancer immunity by facilitating CCL2 expression.
The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers' Disease

Alpers’ syndrome is an early-onset neurodegenerative disorder usually caused by biallelic pathogenic variants in the gene encoding the catalytic subunit of polymerase-gamma (POLG), which is essential for mitochondrial DNA (mtDNA) replication. The disease is progressive, incurable, and inevitably it leads to death from drug-resistant status epilepticus. The neurological features of Alpers’ syndrome are intractable epilepsy and developmental regression, with no effective treatment; the underlying mechanisms are still elusive, partially due to lack of good experimental models. Here, we generated the patient-derived induced pluripotent stem cells from one Alpers’ patient carrying the compound heterozygous mutations of A467T (c.1399G>A) and P589L (c.1766C>T), and further differentiated them into cortical organoids and neural stem cells (NSCs) for mechanistic studies of neural dysfunction in Alpers’ syndrome. Patient cortical organoids exhibited a phenotype that faithfully replicated the molecular changes found in patient postmortem brain tissue, as evidenced by cortical neuronal loss and depletion of mtDNA and complex I (CI). Patient NSCs showed mitochondrial dysfunction leading to ROS overproduction and downregulation of the NADH pathway. More importantly, the NAD+ precursor nicotinamide riboside (NR) significantly ameliorated mitochondrial defects in patient brain organoids. Our findings demonstrate that the iPSC model and brain organoids are good in vitro models of Alpers’ disease; this first-in-its-kind stem cell platform for Alpers’ syndrome enables therapeutic exploration and has identified NR as a viable drug candidate for Alpers’ disease and, potentially, other mitochondrial diseases with similar causes.
Efficient Formation of Single-copy Human Artificial Chromosomes

Large DNA assembly methodologies underlie milestone achievements in synthetic prokaryotic and budding yeast chromosomes. While budding yeast control chromosome inheritance through ∼125 bp DNA sequence-defined centromeres, mammals and many other eukaryotes use large, epigenetic centromeres. Harnessing centromere epigenetics permits human artificial chromosome (HAC) formation but is not sufficient to avoid rampant multimerization of the initial DNA molecule upon introduction to cells. Here, we describe an approach that efficiently forms single-copy HACs. It employs a ∼750 kb construct that is sufficiently large to house the distinct chromatin types present at the inner and outer centromere, obviating the need to multimerize. Delivery to mammalian cells is streamlined by employing yeast spheroplast fusion. These developments permit faithful chromosome engineering in the context of metazoan cells. One-Sentence Summary A quarter century after the first human artificial chromosomes, a solution to their uncontrolled multimerization is achieved.
Designing a Dataflow Hardware Accelerator with an Abstract Machine

This paper motivates the use of domain-specific abstract machines for designing hardware accelerators. Specifically, we describe how we built a reconfigurable dataflow accelerator for sparse tensor algebra, a relatively complex domain, using the Sparse Abstract Machine (SAM). We show that leveraging an abstract dataflow representation (and its compiler) lead to a slew of benefits, including computational generality within the application domain, easier verification and debugging, boosted design productivity, and decoupled development of the toolchain from the hardware design and generation. These benefits allowed us to build the accelerator within a short time-frame with only two designers.
Least-squares versus LMS parametric approaches for power quality events segmentation

Power quality monitoring requires knowing when the start of the perturbation takes place, and also when it ends; in this way, the voltage or current signals are divided into segments. In this work, we follow previously developed ideas in the literature and resort to parametric modelling to achieve the perturbed signal segmentation. What we propose here is the use of adaptive AR modelling identification, in particular Recursive Least Squares and Least Mean Squares, as opposed to a block-based approach used elsewhere. Overdetermined systems, both block-wise and adaptively are also included among the analysed methods. Simulations show that although being computationally lighter, and hence more suitable to real-time implementations, segments limits are accurately located by adaptive algorithms most of the cases.
Optimal reinsurance and investment problem in a defaultable market

ABSTRACT This article investigates the optimal reinsurance and investment problem involving a defaultable security. The insurer can purchase reinsurance and allocate his wealth among three financial securities: a money account, a stock, and a defaultable corporate bond. The objective of the insurer is to maximize the expected exponential utility of terminal wealth. Using techniques of stochastic control theory, we derive the corresponding Hamilton–Jacobi–Bellman equation and decompose the original optimization problem into a predefault case and a postdefault case. Explicit expressions for optimal strategies and the corresponding value functions are derived, and the verification theorem is given. Finally, we present numerical examples to illustrate our results.
Blockchain Privacy Notions Using the Transaction Graph Model Master Thesis

Considerable work explores blockchain privacy notions. Yet, it usually employs entirely different models and notations, complicating potential comparisons. In this work, we use the Transaction Directed Acyclic Graph (TDAG) and extend it to capture blockchain privacy notions (PDAG). We give consistent definitions for untraceability, unlinkability, and confidentiality. Moreover, we specify conditions on a blockchain system to achieve each aforementioned privacy notion. Thus, we can compare the two most prominent privacy-preserving blockchains – Monero and Zcash, in terms of privacy guarantees. Finally, we unify linking heuristics from the literature with our graph notation and review a good portion of research on blockchain privacy.
Toward An Understanding of Curriculum as Spiritual Text

This article illustrates how the dual processes of autobiographical reflection and academic study ( currere ) have contributed to my understanding of the spirituality of education. It begins with a short autobiographical account of my experience as a secondary school student which serves as a reference point for the rest of the paper. I then endeavour to untangle the multi-stranded concept of spirituality, based on a synthesis of appropriate literature. From this synthesis, I identify three constructs which, for me, have been most salient in the development of my understanding of the concept of spirituality of education: transcendence, sense of self and attunement. There follows sequential analysis of the how these constructs have contributed to my understanding, together with clarification of the coherence across them.
Nanosecond to picosecond fiber bragg grating compression of giant-chirped pulses from an ultra-long mode-locked fiber laser

R. I. Woodward,1 E. J. R. Kelleher,1 T. H. Runcorn,1 S. Loranger,2 D. Popa,3 V. J. Wittwer,3 A. C. Ferrari,3 S. V. Popov,1 R. Kashyap,2,4 and J. R. Taylor1 1. Femtosecond Optics Group, Department of Physics, Imperial College London, SW7 2AZ, UK 2. Fabulas Laboratory, Department of Engineering Physics, Polytechnique Montréal, H3T 1J4, Canada 3. Cambridge Graphene Centre, University of Cambridge, Cambridge, CB3 0FA, UK 4. Fabulas Laboratory, Department of Electrical Engineering, Polytechnique Montréal, H3T 1J4, Canada
Smooth Sub-Phases Based Trajectory Planning for Exoskeleton System

Trajectory is a crucial part of exoskeleton robot design. The appropriate trajectory will affect wearer's safety, health and comfort. The trajectory profile of angular position can be generated as same as actual trajectory profile in term of shape. However, the problem of unreachable intermediate points increases the error between the polynomial trajectory profile and real human trajectory profile. This error directly can affect to generate a less accurate profile that can’t be accurately matched to the human trajectory profile. Based on the aforementioned problem, the objectives of this paper is to investigate the effect of having a different number of sub-phases trajectories on the error related to the real human trajectory profile. Also, this paper presents trajectory generation method that is called quintic polynomial segment with 6th polynomial blend (6-5-6 PSPB). The 6-5-6 PSPB trajectory includes the via points at initial and final of each phase in order to solve the problem of unreachable intermediate points. The result shows a good improvement (almost 8%) in term of error based on the proposed 6-5-6 PSPB technique compared to the three categories of gait analysis. The 6-5-6 PSPB technique shows a good result based on the root mean square error (RMSE) and average difference (AD) error of angular position (0.3146 and 0.031310 Degree respectively). At the end, 6-5-6 PSPB can improve the error and generate a trajectory motion profile that accurately matches to human trajectory profile.
Analysis of an M/G/1 Stochastic Clearing Queue in a 3-Phase Environment

Abstract This paper studies a single server M/G/1 stochastic clearing queue operating in a 3-phase environment, where the time length of the first and third phase are assumed to follow exponential distributions, and the time length of the second phase is a constant value. At the completion of phase 1, the system moves to phase 2, and after a fixed time length, the system turns to phase 3. At the end of phase 3, all present customers in the system are forced to leave the system, then the system moves to phase 1 and restarts a new service cycle. Using the supplementary variable technique, we obtain the distribution for the stationary queue at an arbitrary epoch. We also derive the sojourn time distribution and the length of the server’s working time in a cycle.
GaN Nanowire MISFETs for Low-Power Applications

Gallium nitride (GaN) nanowire metal-insulator-semiconductor field-effect transistors (MISFETs) have been demonstrated experimentally. The large bandgap and high electron mobility of GaN, in addition to the 1-dimensional wrap-gate geometry, make GaN nanowire MISFETs promising for both low-power logic as well as RF applications. The fabricated GaN nanowire MISFETs exhibit an off-current (I OFF ) below 0.2 pA/ µ m, an on-off ratio (I ON / I OFF ) above 10 8 , and a subthreshold slope (SS) of 265 mV/decade. The GaN nanowire MISFET performance can be improved by the optimization of the nanowire growth and gate oxide deposition processing, as well as more aggressive device scaling.
Wrist-Based Survival Swimming Activity Recognition System

According to the World Health Organization, over 300,000 drowning deaths occur worldwide each year. One of the main contributors is lack of survival swimming knowledge; for example, the Redcross indicates that 50% of the population in the United States does not know how to swim. In this work, we explore the potential of using wearable technology to help address the lack of swimming training. Wearable technology like Fitbit or Apple Watch are smart devices that recognize people’s activities and are increasingly integral to tracking one’s health and well-being. When it comes to swimming or other aquatic activities, wearables have focused on professional and elite swimmers where devices support lap swimming strokes (backstroke, breaststroke, butterfly, freestyle) which are common in Olympic competitions. Our research expands lap swimming activity recognition by incorporating two survival swimming activities: treading water and sidestroke. We present a study which collects all six stroke types from a wrist-worn device, and we develop a machine learning algorithm that classifies activities with an F-measure of 0.94.
Assistive robotic hand with bi-directional soft actuator for hand impaired patients

Soft wearable robotic hand can assist with hand function for the performance of activities of daily living (ADL). However, existing robotic hands lack a mathematical way to quantify the grip force generated for better controlling the grasp of objects during the performance of ADL. To address this issue, this article presents a soft wearable robotic hand with active control of finger flexion and extension through an elastomeric-based bi-directional soft actuator. This actuator bends and extends by pneumatic actuation at lower air pressure, and a flex sensor embedded inside the actuator measures the angles of the fingers in real-time. Analytical models are established to quantify the kinematic and tip force for gripping of the actuator in terms of the relationship between the input pressure and the bending angle, as well as the output force, and are validated experimentally and by the finite element method. Furthermore, the ability of the soft robotic hand to grasp objects is validated with and without being worn on a human hand. The robotic hand facilitates hand opening and closing by the wearer and successfully assists with grasping objects with sufficient force for ADL-related tasks, and the grip force provided by the actuator is further estimated by the analytical models on two healthy subjects. Results suggest the possibility of the soft robotic hand in providing controllable grip strength in rehabilitation and ADL assistance.
Insights into structural, spectroscopic, and hydrogen bonding interaction patterns of nicotinamide–oxalic acid (form I) salt by using experimental and theoretical approaches

In the present work, nicotinamide–oxalic acid (NIC-OXA, form I) salt was crystallized by slow evaporation of an aqueous solution. To understand the molecular structure and spectroscopic properties of NIC after co-crystallization with OXA, experimental infrared (IR), Raman spectroscopic signatures, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) techniques were used to characterize and validate the salt. The density functional theory (DFT) methodology was adopted to perform all theoretical calculations by using the B3LYP/6-311++G (d, p) functional/basis set. The experimental geometrical parameters were matched in good correlation with the theoretical parameters of the dimer than the monomer, due to the fact of covering the nearest hydrogen bonding interactions present in the crystal structure of the salt. The IR and Raman spectra of the dimer showed the red (downward) shifting and broadening of bands among (N15-H16), (N38-H39), and (C13=O14) bonds of NIC and (C26=O24), (C3=O1), and (C26=O25) groups of OXA, hence involved in the formation of NIC-OXA salt. The atoms in molecules (AIM) analysis revealed that (N8-H9···O24) is the strongest (conventional) intermolecular hydrogen bonding interaction in the dimer model of salt with the maximum value of interaction energy −12.1 kcal mol−1. Furthermore, the natural bond orbital (NBO) analysis of the Fock matrix showed that in the dimer model, the (N8-H9···O24) bond is responsible for the stabilization of the salt with an energy value of 13.44 kcal mol−1. The frontier molecular orbitals (FMOs) analysis showed that NIC-OXA (form I) salt is more reactive and less stable than NIC, as the energy gap of NIC-OXA (form I) salt is less than that of NIC. The global and local reactivity descriptor parameters were calculated for the monomer and dimer models of the salt. The electrophilic, nucleophilic, and neutral reactive sites of NIC, OXA, monomer, and dimer models of salt were visualized by plotting the molecular electrostatic potential (MESP) surface. The study provides valuable insights into combining both experimental and theoretical results that could define the physicochemical properties of molecules.
How many strong earthquakes will there be tomorrow?

In this note, we study the distribution of earthquake numbers in both worldwide and regional catalogs: in the Global Centroid Moment Tensor catalog, from 1980 to 2019 for magnitudes Mw 5. 5+ and 6.5+ in the first case, and in the Italian instrumental catalog from 1960 to 2021 for magnitudes Mw 4.0+ and 5.5+ in the second case. A subset of the global catalog is also used to study the Japanese region. We will focus our attention on short-term time windows of 1, 7, and 30 days, which have been poorly explored in previous studies. We model the earthquake numbers using two discrete probability distributions, i.e., Poisson and Negative Binomial. Using the classical chi-squared statistical test, we found that the Poisson distribution, widely used in seismological studies, is always rejected when tested against observations, while the Negative Binomial distribution cannot be disproved for magnitudes Mw 6.5+ in all time windows of the global catalog. However, if we consider the Japanese or the Italian regions, it cannot be proven that the Negative Binomial distribution performs better than the Poisson distribution using the chi-squared test. When instead we compared the performances of the two distributions using the Akaike Information Criterion, we found that the Negative Binomial distribution always performs better than the Poisson one. The results of this study suggest that the Negative Binomial distribution, largely ignored in seismological studies, should replace the Poisson distribution in modeling the number of earthquakes.
Novel kinetoplastid-specific cAMP binding proteins identified by RNAi screening for cAMP resistance in Trypanosoma brucei

Cyclic AMP signalling in trypanosomes differs from most eukaryotes due to absence of known cAMP effectors and cAMP independence of PKA. We have previously identified four genes from a genome-wide RNAi screen for resistance to the cAMP phosphodiesterase (PDE) inhibitor NPD-001. The genes were named cAMP Response Protein (CARP) 1 through 4. Here, we report an additional six CARP candidate genes from the original sample, after deep sequencing of the RNA interference target pool retrieved after NPD-001 selection (RIT-seq). The resistance phenotypes were confirmed by individual RNAi knockdown. Highest level of resistance to NPD-001, approximately 17-fold, was seen for knockdown of CARP7 (Tb927.7.4510). CARP1 and CARP11 contain predicted cyclic AMP binding domains and bind cAMP as evidenced by capture and competition on immobilised cAMP. CARP orthologues are strongly enriched in kinetoplastid species, and CARP3 and CARP11 are unique to Trypanosoma. Localization data and/or domain architecture of all CARPs predict association with the T. brucei flagellum. This suggests a crucial role of cAMP in flagellar function, in line with the cell division phenotype caused by high cAMP and the known role of the flagellum for cytokinesis. The CARP collection is a resource for discovery of unusual cAMP pathways and flagellar biology.
Interferon alpha and beta receptor 1 knockout in human embryonic kidney 293 cells enhances the production efficiency of proteins or adenoviral vectors related to type I interferons

Human embryonic kidney (HEK) 293 cells are widely used in protein and viral vector production owing to their high transfection efficiency, rapid growth, and suspension growth capability. Given their antiviral, anticancer, and immune-enhancing effects, type I interferons (IFNs) have been used to prevent and treat human and animal diseases. However, the binding of type I IFNs to the IFN-α and-β receptor (IFNAR) stimulates the expression of IFN-stimulated genes (ISGs). This phenomenon induces an antiviral state and promotes apoptosis in cells, thereby impeding protein or viral vector production. In this study, we generated an IFNAR subtype 1 knockout (KO) HEK 293 suspension (IFNAR-KO) cell line by using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) technology. Upon treatment with human IFN-α, the IFNAR-KO cells showed a constant expression of ISGs, including 2ʹ-5ʹ-oligoadenylate synthetase 1 (OAS1), myxovirus resistance 1 (Mx1), protein kinase RNA-activated (PKR), and IFN-induced transmembrane protein 1 (IFITM1), when compared with the wild-type HEK 293 (WT) cells, wherein the ISGs were significantly upregulated. As a result, the titer of recombinant adenovirus expressing porcine IFN-α was significantly higher in the IFNAR-KO cells than in the WT cells. Furthermore, the IFNAR-KO cells continuously produced higher amounts of IFN-α protein than the WT cells. Thus, the CRISPR-Cas9-mediated IFNAR1 KO cell line can improve the production efficiency of proteins or viral vectors related to IFNs. The novel cell line may be used for producing vaccines and elucidating the type I IFN signaling pathway in cells.