Miracle-dz/UniFAR-FTUs huggingface dataset:
Ts 66 Yah , a refined Ts 65 Dn DS mouse model , unravels genetic 1 interaction between regions homologous to Human chromosome 21 2 and the Scaf 8-Pde 10 a genetic interval

25 Down syndrome is the consequence of trisomy of human chromosome 21 (Hsa21). The 26 understanding of phenotype-genotype relationships, the identification of driver genes and 27 various proof-of-concepts for therapeutic improvement have benefited from the 28 development of mouse models. The premier model, named Ts(1716)65Dn/J (Ts65Dn), 29 corresponds to an additional minichromosome with the Mir155 to Zbtb21 region of mouse 30 chromosome 16 (Mmu16), homologous to Hsa21, encompassing around 90 genes, fused to 31 the centromeric part of mouse chromosome 17 (Mmu17). The Ts65Dn line displayed several 32 phenotypes related to the human features found in people with DS. The detailed analysis of 33 the Ts65Dn minichromosome unraveled the presence of 46 trisomic genes from the 34 centromeric region of Mmu17, from Pisd-ps2/Scaf8 to Pde10a, not related to Hsa21. Here, we 35 report the investigation of a new model, Ts66Yah, generated by CrispR/Cas9 to remove the 36 genomic region unrelated to Hsa21 on the minichromosome. Not surprisingly, the sole 37 presence of 3 copies of the Mir155-Zbtb21 interval in Ts66Yah induces DS related features. 38 However, the loss of certain phenotypes related to increased activity, spatial learning and 39 specific molecular signatures suggest strong genetic interactions between the Mir155-Zbtb21 40 and the Scaf8-Pde10a interval. Thus, Ts66Yah mice have a stronger construct and face validity 41 for mimicking specific consequences of DS genetic overdosage, certainly more translatable to 42 humans and with potential better proof-of-concept studies for therapeutics. Furthermore, 43 this report is the first to demonstrate genetic interactions between triplicated regions 44 homologous to Hsa21 and others unrelated to Hsa21. 45
Induction of senescence renders cancer cells highly immunogenic

Cellular senescence is a stress response that activates innate immunity. However, the interplay between senescent cells and the adaptive immune system remains largely unexplored. Here, we show that senescent cells display enhanced MHC class I (MHC-I) antigen processing and presentation. Immunization of mice with senescent syngeneic fibroblasts generates CD8 T cells reactive against both normal and senescent fibroblasts, some of them targeting senescence-associated MHC-I-peptides. In the context of cancer, we demonstrate that senescent cancer cells trigger strong anti-tumor protection mediated by antigen-presenting cells and CD8 T cells. This response is superior to the protection elicited by cells undergoing immunogenic cell death. Finally, induction of senescence in patient-derived cancer cells exacerbates the activation of autologous tumor-reactive CD8 tumor-infiltrating lymphocytes (TILs) with no effect on non-reactive TILs. Our study indicates that immunization with senescent cancer cells strongly activates anti-tumor immunity, and this can be exploited for cancer therapy. STATEMENT OF SIGNIFICANCE Our study shows that senescent cells are endowed with a high immunogenic potential, superior to the gold standard of immunogenic cell death. The induction of senescence in cancer cells can be exploited to develop efficient and protective CD8-dependent anti-tumor immune responses.
Plant-based Production and Characterization of a Promising Fc-fusion Protein against Bone Mass Density Loss

Microgravity-induced bone loss is a main obstacle for long term space missions as it is difficult to maintain bone mass when loading stimuli is reduced. With a typical bone mineral density loss of 1.5% per month of microgravity exposure, the chances for osteoporosis and fractures may endanger astronauts’ health. Parathyroid Hormone or PTH (1-34) is an FDA approved treatment for osteoporosis, and may reverse microgravity-induced bone loss. However, PTH proteins requires refrigeration, daily subcutaneous injection, and have a short shelf-life, limiting its use in a resource-limited environment, like space. In this study, PTH was produced in an Fc-fusion form via transient expression in plants, to improve the circulatory half-life which reduces dosing frequency and to simplify purification if needed. Plant-based expression is well-suited for space medicine application given its low resource consumption and short expression timeline. The PTH-Fc accumulation profile in plant was established with a peak expression on day 5 post infiltration of 373 ± 59 mg/kg leaf fresh weight. Once the PTH-Fc was purified, the amino acid sequence and the binding affinity to its target, PTH 1 receptor (PTH1R), was determined utilizing biolayer interferometry (BLI). The binding affinity between PTH-Fc and PTH1R was 2.30 × 10−6 M, similar to the affinity between PTH (1–34) and PTH1R (2.31 × 10−6 M). Its function was also confirmed in a cell-based receptor stimulation assay, where PTH-Fc was able to stimulate the PTH1R producing cyclic adenosine monophosphate (cAMP) with an EC50 of (8.54 ± 0.12) × 10−9 M, comparable to the EC50 from the PTH (1-34) of 1.49 × 10−8 M. These results suggest that plant recombinant PTH-Fc exhibits a similar potency compared to PTH. Furthermore, it can be produced rapidly at high levels with minimal resources and reagents, making it ideal for production in low resource environments such as space.
Revisiting Leishmania GP63 host cell targets reveals a limited spectrum of substrates

Colonization of host phagocytic cells by Leishmania metacyclic promastigotes involves several parasite effectors, including the zinc-dependent metalloprotease GP63. The major mode of action of this virulence factor entails the cleavage/degradation of host cell proteins. Given the potent proteolytic activity of GP63, identification of its substrates requires the adequate preparation of cell lysates to prevent artefactual degradation during cell processing. In the present study, we re-examined the cleavage/degradation of reported GP63 substrates when GP63 activity was efficiently neutralized during the preparation of cell lysates. To this end, we infected bone marrow-derived macrophages with either wild type, Δgp63, and Δgp63+GP63 L. major metacyclic promastigotes for various time points. We prepared cell lysates in the absence or presence of the zinc-metalloprotease inhibitor 1,10-phenanthroline and examined the levels and integrity of ten previously reported host cell GP63 substrates. Inhibition of GP63 activity with 1,10-phenanthroline during the processing of macrophages prevented the cleavage/degradation of several previously described GP63 targets, including PTP-PEST, mTOR, p65RelA, c-Jun, VAMP3, and NLRP3. Conversely, we confirmed that SHP-1, Synaptotagmin XI, VAMP8, and Syntaxin-5 are bona fide GP63 substrates. These results point to the importance of efficiently inhibiting GP63 activity during the preparation of Leishmania-infected host cell lysates. In addition, our results indicate that the role of GP63 in Leishmania pathogenesis must be re-evaluated. AUTHOR’S SUMMARY In the protozoan parasite Leishmania, the abundant zinc-dependent metalloprotease GP63 is expressed at high levels at the surface of the promastigotes forms of the parasite. Upon phagocytosis by host macrophages, this metalloprotease is released from the parasite’s surface and spreads across the cytosol of infected cells. There, GP63 cleaves a number of host cell proteins involved in the control of host microbicidal function and in the regulation of immune responses, thereby contributing the ability of Leishmania to impair host defence mechanisms against infection. Given the abundance and powerful proteolytic activity of GP63, it is crucial to prevent artefactual proteolysis during processing of infected cells to identify genuine GP63 substrates. In this study, we found that inhibition of GP63 activity with 1,10-phenanthroline during the processing of macrophages prevented the degradation of several of previously identified GP63 substrates. These results uncover the importance of efficiently inhibiting GP63 activity during the preparation of Leishmania-infected host cell lysates.
Adaptive Extended Kalman Filter for Speed-Sensorless Control of Induction Motors

This paper presents an adaptive extended Kalman filter (AEKF) algorithm estimating the stator stationary axis components of stator currents, the stator stationary axis components of rotor fluxes, the rotor mechanical speed, and the load torque for speed-sensorless control applications of induction motors (IMs). The performance of a standard extended Kalman filter (SEKF) algorithm depends on the correct selection of system and measurement noise covariance matrices. In SEKF algorithms, these matrices are generally assumed as constant and determined by the trial-and-error method. However, they are affected by the operating conditions of IM and should be updated considering the operating conditions. For this purpose, instead of the time-consuming trial-and-error method for determining these matrices, an innovation-based adaptive estimation approach having the capability of online update is used in this paper. Finally, in order to verify the superiority of the AEKF algorithm, estimation performances of AEKF and SEKF algorithms are compared under challenging scenarios for a wide speed range considering computational burdens and parameter variations.
Serum lipoproteins and lipoarabinomannan suppress the inflammatory response induced by the mycolactone toxin

Mycobacterium ulcerans is the causative agent of the chronic and debilitating neglected tropical disease Buruli ulcer (BU) which mostly affects children. The early detection and treatment of M. ulcerans infections can significantly minimize life-long disability resulting from surgical intervention. However, the disease is characterized by relatively few systemic systems as a result of complex host-pathogen interactions that have yet to be fully characterized, which has limited the development of both diagnostic and therapeutic approaches to treat BU. In this work, we study the interactions of the host immune system with two principle M. ulcerans virulence factors: mycolactone, an amphiphilic macrolide toxin, and lipoarabinomannan (LAM), a cell wall component of most mycobacterial pathogens. We observe that human lipoproteins have a profound effect on the interaction of both mycolactone and LAM with the immune system. Individually, both molecules are pro-inflammatory in the absence of serum and immunosuppressive in the presence of serum. When combined, mycolactone and LAM are immunosuppressive regardless of serum conditions. We also show that Toll-like receptor 2 (TLR2), a macrophage pathogen pattern recognition receptor, is critical for LAM immune stimulation but aids in mycolactone immunosuppression. These findings are a first step towards unraveling mycolactone-mediated immunosuppression during BU disease and may facilitate the development of effective diagnostics and therapeutics in the future. Author Summary Buruli ulcer (BU) is a neglected tropical disease caused by the pathogen Mycobacterium ulcerans. The principal virulence factors associated with it are the macrolide toxin mycolactone and the major cell wall component lipoarabinomannan (LAM). Here, we examine the impact of the amphiphilic biochemistry of mycolactone and LAM on their interaction with the human immune system. We show that both mycolactone and LAM associate with serum lipoproteins, and that this association is critical for the immune evasion seen in early-stage M. ulcerans infections. In the absence of serum, mycolactone is pro-inflammatory. Immunosuppression occurs only in the presence of human serum lipoproteins. In the presence of LAM, mycolactone is immunosuppressive, regardless of serum conditions. Immunosuppression is a hallmark of BU disease, and understanding the mechanisms of this immunosuppression can support the development of effective diagnostic and therapeutic strategies.
IOT Based Environmental Monitoring System using Arduino UNO and Thingspeak

The changes in climate led to the increased importance of environmental monitoring. In order to determine the quality of the environment, continuous tracking of the environmental parameter is needed. As the IoT is the most emerging technology, it plays an important role in collecting the information from the sensing unit. Generally sensing unit is composed of different sensors like temperature, humidity, moisture etc., the paper uses an Arduino UNO, Wi-Fi module that helps in processing and transferring the sensed data to the Thingspeak cloud. Thus the parameters received is stored in the cloud platform (Thing speak). The changes in the environment is updated in the form of a database through the cloud computing method. Thing speak also provide a feature to create a public based channel to analyze and estimate it through the public. An Android application is created for the direct access of the measured parameters
Multimedia in Satellites: Achieving Reliable Interactive Video Transmission over Broadband Satellite Channels

This talk will focus on methods for achieving reliable multimedia transmission over future broadband satellite communications systems. Problems encountered in video transmission in Ka-band systems operating in geostationary orbit are emphasized, where high reliability must be achieved, coding delay must be minimized and where ARQ-type data transmission protocols cannot be easily integrated with >interactive applications. Although being transported by packet-based networks, compressed voice and/or video should ideally exploit the fact that lossy compression can be tolerated. After reviewing certain aspects of broadband multimedia satellite transmission, we introduce a novel video transmission approach that seems promising in this context, called "transmitter receiver identical reference frame" (TRIRF) based coding. This scheme is being considered as an additional inter-frame mode compatible with motion-compensation based predictive coding standards.
A Pilot Interdisciplinary Robotic Mentorship Project to Study Engineering Soft Skill Development

As the complexity and diversity of general engineering practices continues to increase, it is becoming apparent that simply providing technical knowledge within the chosen discipline is insufficient to prepare our engineering students for related employment opportunities. The engineering workforce today is expected to perform effectively in a multi-disciplinary environment, underlining the importance of soft skills that include interdisciplinary communication, teamwork and leadership. Despite the increasing awareness, the gap between graduates’ soft skills prepared by academics and those required in the job force stays significant, if not continues to widen. In collaboration between the engineering and education departments at the State University of New York (SUNY) at New Paltz, a robotics mentorship program was designed as a platform to foster soft skill development of engineering students. The program entails participation from three groups: mechanical and electrical engineering students, adolescence mathematics teacher candidates, and high school students in an after-school robotics club. A two-semester pilot project was conducted for feasibility study, comprising weekly planning and training between engineering students and adolescence mathematics teacher candidates. Furthermore, a resulting workshop series to mentor the robotics club at John Jay High School in Wappingers Central School District was developed to cover topics ranging from CAD and microcontrollers to the competition engineering notebook and general advice based on the mentors’ previous experience in robotics. Even though the execution was abruptly interrupted by the COVID-19 pandemic in the first semester and completely moved to online in the second semester , survey and interview data was collected on five undergraduate engineering students and three mathematics teacher candidates, which offer encouraging qualitative evidence of their soft skills development, particularly for the engineering mentors . In this paper, we will introduce the collaborative mentorship program and the differentiating design considerations, then discuss the results with focus on 1) the journey of these engineering students as they collaborate with mathematics teacher candidates and serve as mentors in the afterschool program, and 2) the impact of the interdisciplinary model on fostering their soft skills.
Field and laboratory trials of 400GBASE‐LR8 over fibre distances up to 35 km

Successful experimental demonstration and field trial of 400GBASE-LR8 is reported based on 4-level pulse amplitude modulation format over standard G.652 single-mode fibre using CFP8 pluggable optical transceivers. Stable long-term error-free performance of 400GBASE-LR8 optical signal over fibre spools of varying lengths up to 35 km is demonstrated, which is significantly longer than the IEEE standard 802.3bs specification of 10 km reach. For the first time, error-free full throughput performance of 400GBASE-LR8 over a 27 km field fibre link including optical patch panels through operational exchanges is also demonstrated. The results demonstrate that this early 400GBASE-LR8 client technology is suitable for practical network deployment scenarios and has potential for even longer reach beyond the 10 km specification.
Least squares regression: graduation and filters

1 Introduction 22 Local polynomial regression 53 Henderson ﬁlters 84 The treatment of the extremes of the series - Real time estimation 104.1 Revision of preliminary estimates . 134.2 The use of exogenous forecasts . 135 Inference 145.1 Bias-Variance Trade-off . 145.2 Cross validation . 155.3 Error variance and interval estimates . 166 Other approaches and generalisations 187 Splines and Trend models 197.1 The Local Level model . 217.2 The Local Linear model . 217.3 Cubic splines . 227.4 Inference . 248 The properties of the ﬁlters 309 Discussion 349.1 Accuracy . 349.1. 1 Validity . 359.1. 2 Reliability . 369.2 Trends and cycles in economic time series . 389.3 Spurious cycles and the Sluztky-Yule effect . 39
Best practices for underplatform damper designers

The purpose of this paper is to offer a practical demonstration of how essential preoptimization is in the design of underplatform dampers for turbine blades. Preoptimization can be thought of as a “prescreening” which allows excluding, since the early design stages, a high number of poorly performing damper–platform configurations. This concept, previously presented by the authors, is here extended and its generality for all blade bending modes is rigorously demonstrated. The paper addresses a test case where the introduction of curved-flat underplatform dampers is necessary to avoid a dangerous resonance crossing in the operating rotational speed range of a real turbine disk. It is shown how preoptimized dampers are the only ones that manage to satisfy all functional requirements, including those in the nonlinear operating regime. The same set of dampers may have been identified by exploring, through hundreds of computationally intensive nonlinear calculations, the performance of all possible damper configurations. The latter approach, i.e. iterative design, is unpractical and has to be repeated for each new set of blades since it is based on a test case-specific trial-and-error procedure. Preoptimization substitutes iterations with knowledge of the damper behavior and can therefore be considered as “informed design”: viable damper configurations are instantly singled out through simple but insightful considerations on the damper equilibrium of forces and moments.
System Engineering Implementation Process for Super-Systems

System engineering is one of the most powerful tool s f r comprehensive project management and control. This tool emphasized the life cycle of the projects, manages every single activity and helps manage the main elements of the project through a s et of management and engineering processes. The goal of the current study is to use a system en gin ering approach in design phase in order or to meet operational needs. This study proposes a conce ptual design process with system engineering approach which institutionalizes configuration mana gement, risk management, change management, requirements management and integration duri g the entire design process. The results indicate a significant increase in meeting customer requirements and a positive increase in project quality. Finally, the indicators of design documents created using this approach are provided as an example.
Optimal Dimensioning of Pipes Above Ground

Structural optimization is one of the most developing design method in structural design. The aim of this kind of design is to find the lowest cost or weight for a loaded structure. In this paper CO2 transportation pipelines are investigated which is the part of e.g. CCS technology [Figure 1. ]. The countries that have accepted Kyoto Protocol’s directives have been studying the reduction of CO2 emission [1], and CCS is a possibility for that.
Reconstruction of Illumination Functions using Bicubic Hermite Interpolation

An interpolation technique based on Hermite bicubic surfaces is proposed to improve the accuracy of the reconstruction of illumination functions and avoid Mach band artifacts. The information of radiosity at vertices is used to evaluate approximate tangent planes to the illumination function and determine partials and mixed partials of that function. Typical discontinuities of intensity or derivative in the illumination function are preserved in the reconstructed image. The additional computation involved is modest and the result of real importance.
Exceptions in Optimality Theory: Typology and Learnability

(2) a. Diacritic approaches: i. Lexically specific ranking lexical items are specified for the ranking of two or more constraints: A. Lexical items are specified for a ranking of constraints that differs from the ‘core’ ranking of the language (McCarthy and Prince 1993, Nouveau 1994; Pater 1994; Ito and Mester 1995a,b; Inkelas, Orgun and Zoll 1997; cf. Paradis and Lebel 1994) B. Lexical items are specified to choose a particular ranking of unranked constraints (Antilla 2002) ii. Lexically specific constraints a lexically specific version of a constraint, ranked differently from the general one: A. Only faithfulness constraints (Fukuzawa 1997; Kraska-Szelenk 1997, 1999; Ito and Mester 1999) B. Markedness and faithfulness constraints (Pater 2000) C. Only markedness constraints (? )
Finding Electron-Hole Interaction in Quantum Kinetic Framework

Abstract The article presents a quantum kinetic framework to study interacting quan¬tum systems. Having the constituting model Hamiltonians of two-band semiconductor and the photoexcited electron-hole pair, their quantum kinetic evolution has been revi-sited. Solution to this nonlinear problem of electron-hole interaction is obtained making use of the self-consistency loop between the densities of photoexcited electrons and holes and the pairwise interaction terms in the constituting model Hamiltonians. In the leading order, this approach supports the required isomorphism between the pairwise interaction and the birth and annihilation operators of the photoexcited electrons and holes as a desirable property. The approach implies the Hilbert space and the tensor product mathematical techniques as an appropriate generalization of the noninteracting electron-hole pair toward several-body systems.
On a class of multiplicative arithmetic functions.

(l1) f(n)f(m) = f(nm) whenever (ra, m) = 1. It follows that a multiplicative function f(n) (or briefly f) is determined if the values of f(p), p a prime and e an integer Ξ> l, are known. Further, if f(ri) Φ 0 identically, then /(l) — 1. If the relation (1. 1) holds for all pairs of values of n, m, then f is referred to s a completely multiplicative function. For a completely multiplicative function f and for a prime p, f(p) = {f(p)}. In this note, we confine ourselves to the class of multiplicative functions f which satisfy