Miracle-dz/UniFAR-FTUs huggingface dataset:
Antitumor effects of duvelisib on Epstein–Barr virus‐associated lymphoma cells

Epstein–Barr virus (EBV) is a ubiquitous oncogenic virus that is associated with B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous studies have shown that the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway is activated in EBV‐associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of PI3Kγ and PI3Kδ, duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the PI3K/Akt signaling pathway and if it has antitumor effects in EBV‐associated lymphoma cell lines. We found that the PI3K/Akt signaling pathway was activated in most of the B and T cell lymphoma cell lines tested. Additionally, duvelisib treatment inhibited cellular growth in the tested cell lines. Overall, B cell lines were more susceptible to duvelisib than T and NK cell lines in vitro regardless of EBV infection. However, the additional influence of duvelisib on the tumor microenvironment was not assessed. Duvelisib treatment induced both apoptosis and cell cycle arrest in EBV‐positive and ‐negative B cell lines, but not in T cell lines. Furthermore, duvelisib treatment reduced the expression of EBV lytic genes (BZLF1 and gp350/220) in EBV‐positive B cell lines, suggesting that duvelisib suppresses the lytic cycle of EBV induced by B cell receptor signaling. However, duvelisib did not induce a remarkable change in the expression of EBV latent genes. These results may indicate that there is therapeutic potential for duvelisib administration in the treatment of EBV‐associated B cell lymphomas and other B cell malignancies.
High-throughput biochemical profiling reveals sequence determinants of dCas9 off-target binding and unbinding

Significance Cas9, a protein derived from the bacterial CRISPR/Cas9 immune system, relies on a programmable single-guide RNA (sgRNA) to bind specific genomic sequences. Cas9 complexed with sgRNA readily binds on-target DNA, but models that can predict the specificity of this process have proven elusive. To investigate this system from a biophysical perspective, we applied a massively parallel method for profiling protein–DNA interactions to quantify nuclease-dead Cas9 (dCas9) binding across thousands of off-target sequences. We observe that mismatches at certain positions of the guide lead to complex dCas9 dissociation patterns, and multiple mismatches between the gRNA and DNA at nonseed bases can produce substantial changes in observed association and dissociation, suggesting the possibility of kinetic and thermodynamic tuning of Cas9 behavior. The bacterial adaptive immune system CRISPR–Cas9 has been appropriated as a versatile tool for editing genomes, controlling gene expression, and visualizing genetic loci. To analyze Cas9’s ability to bind DNA rapidly and specifically, we generated multiple libraries of potential binding partners for measuring the kinetics of nuclease-dead Cas9 (dCas9) interactions. Using a massively parallel method to quantify protein–DNA interactions on a high-throughput sequencing flow cell, we comprehensively assess the effects of combinatorial mismatches between guide RNA (gRNA) and target nucleotides, both in the seed and in more distal nucleotides, plus disruption of the protospacer adjacent motif (PAM). We report two consequences of PAM-distal mismatches: reversal of dCas9 binding at long time scales, and synergistic changes in association kinetics when other gRNA–target mismatches are present. Together, these observations support a model for Cas9 specificity wherein gRNA–DNA mismatches at PAM-distal bases modulate different biophysical parameters that determine association and dissociation rates. The methods we present decouple aspects of kinetic and thermodynamic properties of the Cas9–DNA interaction and broaden the toolkit for investigating off-target binding behavior.
Dynamic flow analysis using an OpenFOAM based CFD tool: Validation of Turbulence Intensity in a testing site

The presenting paper investigates on the validation of the turbulence intensity (TI) modeled by a CFD tool. Six meteorological masts, equipped with cup anemometers, have been used for the purpose. Three different turbulence closure schemes, which are the SST k-omega and the k-epsilon in two different configurations, have been tested. The flow analysis shows a qualitative agreement between measurements and models, which are capable to simulate the turning of the wind towards South when it comes from SSE. Furthermore, the simulations predict a zone of high turbulence in the northern part of the site that is confirmed by the local measurements. The scores for TI have been quantified by considering the observed directional frequencies in the validation analysis. For the testing site, the SST k-omega scheme achieves the best performance when using the TI definition which is representative of the longitudinal fluctuations of the velocity vector, against the other one, which considers the fluctuation of the horizontal vector. Lastly, the model errors have been used to correct the simulated values using two approaches; the analysis shows that, for the presented case, these correction methods do not always improve the accuracy of the simulations.
Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies

Analysis of muscle biopsies allowed to characterize the pathophysiological changes of Duchenne and Becker muscular dystrophies (D/BMD) leading to the clinical phenotype. Muscle tissue is often investigated during interventional dose finding studies to show in situ proof of concept and pharmacodynamics effect of the tested drug. Less invasive readouts are needed to objectively monitor patients' health status, muscle quality, and response to treatment. The identification of serum biomarkers correlating with clinical function and able to anticipate functional scales is particularly needed for personalized patient management and to support drug development programs.
Effects of N-Glycosylation Site Removal in Archaellins on the Assembly and Function of Archaella in Methanococcus maripaludis

In Methanococcus maripaludis S2, the swimming organelle, the archaellum, is composed of three archaellins, FlaB1S2, FlaB2S2 and FlaB3S2. All three are modified with an N-linked tetrasaccharide at multiple sites. Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). Of the 6 double-site mutation complementations all were archaellated except D1,3. Of the 4 triple-site mutation complements, only D2,3,4 was archaellated. Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation.
A study on the processing and reinforcement of message digest through two-dimensional array masking

Hash algorithms have been widely used for cryptography. It has been impossible to decrypt the ciphertexts generated through hash algorithms, as an operation that damages the original text is performed. The vulnerability of SHA1 (an old hash algorithm) has been revealed, and there has been a great deal of data available for dictionary attacks. Although the industry has been gradually refraining from using SHA1, it remains in use in some existing systems for various reasons. In particular, when problems resulting from medical service interruption or mass update are directly related to a person's life, updating the encryption algorithm can be a burden. In this study, we aim to increase the complexity of ciphertexts by postprocessing hash ciphertext by masking message digest to a two-dimensional array constructed using an image processing technique. This will allow the use of hash ciphertexts with increased complexity in some medical devices that are forced to use old hash algorithms for various reasons.
A scale-up nanoporous membrane centrifuge for reverse osmosis desalination without fouling

A scale-up nanoporous membrane centrifuge is designed and modeled. It can be used for nanoscale scale separation including reverse osmosis desalination. There are micron-size pores on the wall of the centrifuge and nanoscale pores on local graphene membrane patches that cover the micron-size pores. In this work, we derived the critical angular velocity required to counter-balance osmosis force, so that the reverse-osmosis (RO) desalination process can proceed. To validate this result, we conducted a large scale (four million atoms) full atom molecular dynamics (MD) simulation to examine the critical angular velocity required for reverse osmosis at nanoscale. It is shown that the analytical results derived based on fluid mechanics and the simulation results observed in MD simulation are consistent and well matched. The main advantage of such nanomaterial based centrifuge is its intrinsic anti-fouling ability to clear Na+ and Cl− ions accumulated at the vicinity of the pores due to the Coriolis effect. Anal.
CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL‐10 production by regulatory B cells

CD38 is a transmembrane protein expressed in B lymphocytes, and is able to induce responses as proliferation, differentiation or apoptosis. Several reports propose that CD38 deficiency accelerates autoimmune processes in murine models of autoimmune diabetes, lymphoproliferation and rheumatoid arthritis. Other reports have shown elevated CD38 expression in B and T cells from patients with autoimmunity; however, the role of CD38 is still unclear in the development of autoimmunity. Recently, it has been characterized as CD1dhi CD5+ regulatory B cell subpopulation able to produce IL‐10, and the loss of these cells exacerbates the autoimmunity in murine models. Here, we report that CD38−/− mice exhibited elevated titres of ANAS, anti‐dsDNA autoantibodies from 12 months of age and were higher by 16 months of age and mice presented kidney damage. Interestingly, there is a reduction in the survival of CD38−/− mice compared to the WT. Furthermore, CD38 is highly expressed by CD1dhigh CD5+ regulatory B cells, and the agonistic anti‐CD38 stimulus plus LPS was able to increase the percentage of this cell subset and its ability to induce IL‐10 production. Together, these results suggest that CD38 could play a role in the control of autoimmune diseases through their expression on regulatory B cells.
Seasonal changes in the ion-mediated increase of xylem hydraulic conductivity in stems of three evergreens: any functional role?

Changes in hydraulic conductivity (K h ) were measured monthly in stems of Laurus nobilis between July 2005 and June 2006 and in March and June 2006 in stems of Prunus laurocerasus and Phillyrea latifolia. Percent enhancement of K h (ΔK h ) was recorded as KCI injected into stems compared with deionized water. Stems of L. nobilis perfused with increasing [KCl] saturated the hydraulic effect at 50 mM KCI, while P. laurocerasus and Ph. latifolia showed saturation at 17 and less than 5 mM KCI, respectively. Impressive seasonal changes in ΔK h were recorded in L. nobilis, from +120% in February to +20% during the growth period. ΔK h was negatively correlated to minimum air temperatures and was highest during winter frost. Negative correlation also existed between ΔK h and conduit lengths as detected during transition of plants from activity to winter rest and from winter to spring. In the winter, the thermal effect was prevailing. High cavitation-induced K h loss coincided with high ΔK h . Similar but much smaller seasonal effects on ΔK h were recorded in the other two species where, however, also smaller seasonal changes in conduit lengths were recorded. We conclude that (1) the K + -induced effect on K h was because of interference of the cation with pectins of intervessel pit membranes (increasingly crossed by the ionic solution in stems with shorter conduits); (2) winter frost might have an effect on ΔK h and (3) seasonal changes in ΔK h because of possible change in pectic composition may represent a mechanism to regulate water flows in planta.
A study on code clone evolution analysis

It is believed that identical or similar code fragments in source code, also known as code clones, result from copy-paste activity of programming, increase the complexity of software maintenance. Information provided by single code clone cannot effectively represent the features of clone maintenance, so it needs to be extracted from different perspective of clone evolution. Analysis of clone evolution provides strong support to improve the maintainability. In this paper, we present various methods that researchers have used to study clone evolution and summarize the advantages and disadvantages of relevant research on clone evolution. Finally we also summarize and prospect the development trend of clone evolution analysis.
Incidence and natural history of preeclampsia/eclampsia at the university maternity of Antananarivo, Madagascar: high prevalence of the early-onset condition

Abstract Objectives: To investigate the incidence of early − (delivery <34 weeks) (EOP) versus late-onset (delivery ≥34 weeks) (LOP) in Madagascar. Study design: Eight months observational study of all preeclamptic/eclamptic women delivering at the maternity of the University Hospital of Befelatanana, Antananarivo, Madagascar. Sociodemographical and obstetrical risk factors are analyzed. Results: Over the study period, we found 142 combined preeclampsia/eclampsia among 4316 births (incidence 3.3% for singleton pregnancies), of which 65 eclampsia (1.5% of all deliveries). The rate of delivery <34 weeks of gestation in preeclamptic women was 37.3% and 38.5% in eclamptic ones. The overall rate of fetal and neonatal mortality was of 50% (71/142). In EO forms the infant death rate was 83% (44/53), of which approximately 33% were due to intrauterine fetal death. In LO forms, the infant death rate was 20% in preeclampsia (15% of fetal deaths), while in case of maternal eclamptic seizures the infant mortality rate was doubled (40%). There were seven maternal deaths (of which four were eclamptic women). Conclusions: We have in Madagascar a high rate of early-onset preeclampsia/eclampsia EOP (37% versus approximately 10% in international literature) and a consequent worrying rate of maternal–fetal mortality. We could find other high incidence of EOP in nine other geographical locations: Guadeloupe (31%), Réunion (31%), Mauritius (34%), Cameroon (37.4%), China (38%), Zimbabwe (58%), Thailand (34%), Turkey (29%), and India (26%). Emerging and tropical countries may belong to the “high rate of EOP standard. ” There is an urgent need to have additional data from these areas to confirm the hypothesis.
Maternal and perinatal outcomes of uterine rupture in a tertiary care hospital: a cross-sectional study

Abstract Objective: The current study aims to evaluate the incidence, maternal and perinatal outcomes in cases presented with uterine rupture (UR) and to explore the differences in presentation, management and outcome of UR in patients with scarred versus unscarred uterus. Materials and methods: A cross-sectional study conducted in a tertiary care hospital over a period of 2 years. The study included all women diagnosed with UR and admitted to the emergency unit between January 2016 and December 2017. A structured questionnaire was used to collect the preoperative demographic and clinical data. An observation checklist was used for intraoperative findings and management. Postoperative data were collected about maternal and fetal outcomes. Data were analyzed using SPSS software. Qualitative variables were compared between groups using chi-square test while quantitative variables were compared using the Mann–Whitney test. Results: Sixty two women were diagnosed with uterine rupture (0.32% of all deliveries). The mean age of the included patients was 29.6 ± 5.6 years while the mean parity was 3.0 ± 1.8. Uterine repair was successful in 52 cases (83.9%). There were four (6.5%) maternal deaths and 42 (67.8%) perinatal deaths. Ten patients (16.1%) were transferred to the postoperative intensive care unit (ICU). Re-exploration was carried out in three cases. The most common complication of UR was disseminated intravascular coagulopathy (DIC) occurred in eight women (12.9%). Maternal and perinatal mortality were significantly higher in patients with unscarred uterus (p = .0001 and .026, respectively). Conclusions: The incidence of UR is 32/10,000 deliveries in our tertiary hospital. Rupture of unscarred uterus is associated with more maternal and fetal mortality. However, rupture of scarred uterus was more common due to the rising rate of cesarean sections.
Studying the determinant factors leading to congenital heart disease in newborns

CONTEXT: Congenital heart disease (CHD) is an important cause of death during the 1st year of life and includes a special group of cardiac diseases that exist from birth. These conditions arise due to the abnormal development of an embryo's normal structures. AIMS: A case–control study was conducted to investigate the determinant factors leading to CHD. MATERIALS AND METHODS: All newborns who have been diagnosed with CHD upon echocardiography in 2013 were considered as cases. The number of samples required was randomly selected from the newborns who lacked CHD on cardiography. The mothers of both groups were handed the questionnaires. STATISTICAL ANALYSIS USED: SPSS 23 was employed to analyze the data. RESULTS: A statistically significant association was seen between CHD and a positive family history (FH) (P < 0.001), consanguinity (P < 0.001), maternal diabetes (P = 0.004), the use of antiepileptics during the first 45 days of gestation (P = 0.002), and the mother's education status (P > 0.001). No significant association was observed between CHD in the newborn and the age below 20 and above 35 years and (P = 0.11), maternal body mass index (BMI) (P = 0.44), smoking during the first 45 days of gestation (P = 0.017), and maternal rheumatologic diseases (P = 0.4). CONCLUSIONS: Newborns are at a greater risk of having CHD born from mothers with a FH of CHD, from consanguineous marriages, history of diabetes, antiepileptic use, and lack of folic acid use. However, no significant associations were found between newborn CHD and maternal age, BMI, or cigarette smoking.
Achievable Moderate Deviations Asymptotics for Streaming Compression of Correlated Sources

Motivated by streaming multi-view video coding and wireless sensor networks, we consider the problem of blockwise streaming compression of a pair of correlated sources, which we term streaming Slepian-Wolf coding. We study the moderate deviations regime in which the rate pairs of a sequence of codes converge, along a straight line, to various points on the boundary of the Slepian-Wolf region at a speed slower than the inverse square root of the blocklength <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>, while the error probability decays subexponentially fast in <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>. Our main result focuses on the directions of approaches to corner points of the Slepian-Wolf region. It states that for each correlated source and all corner points, there exists a non-empty subset of directions of approaches, such that the moderate deviations constant (the constant of proportionality for the subexponential decay of the error probability) is enhanced (over the non-streaming case) by at least a factor of <inline-formula> <tex-math notation="LaTeX">$T$ </tex-math></inline-formula>, the block delay of decoding source block pairs. We specialize our main result to the setting of streaming lossless source coding and generalize this result to the setting, where we have different delay requirements for each of the two source blocks. The proof of our main result involves the use of various analytical tools and amalgamates several ideas from the recent information-theoretic streaming literature. We adapt the so-called truncated memory encoding idea from Draper and Khisti (2011) and Lee, Tan, and Khisti (2016) to ensure that the effect of error accumulation is nullified in the limit of large block lengths. We also adapt the use of the so-called minimum weighted empirical suffix entropy decoder, which was used by Draper, Chang, and Sahai (2014) to derive achievable error exponents for symbolwise streaming Slepian-Wolf coding.
Voice Interfaces in Everyday Life

Voice User Interfaces (VUIs) are becoming ubiquitously available, being embedded both into everyday mobility via smartphones, and into the life of the home via 'assistant' devices. Yet, exactly how users of such devices practically thread that use into their everyday social interactions remains underexplored. By collecting and studying audio data from month-long deployments of the Amazon Echo in participants' homes-informed by ethnomethodology and conversation analysis-our study documents the methodical practices of VUI users, and how that use is accomplished in the complex social life of the home. Data we present shows how the device is made accountable to and embedded into conversational settings like family dinners where various simultaneous activities are being achieved. We discuss how the VUI is finely coordinated with the sequential organisation of talk. Finally, we locate implications for the accountability of VUI interaction, request and response design, and raise conceptual challenges to the notion of designing 'conversational' interfaces.