Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromatin occupancy and epigenetic analysis reveal new insights into the function of GATA1 N-terminus in erythropoiesis.

Mutations in GATA1, which lead to expression of the GATA1s isoform that lacks the GATA1 N-terminus, are seen in patients with Diamond-Blackfan Anemia (DBA). In our efforts to better understand the connection between GATA1s and DBA, we comprehensively studied erythropoiesis in Gata1smice. Defects in yolks sac and fetal liver hematopoiesis included impaired terminal maturation and reduced numbers of erythroid progenitors. RNA-sequencing revealed that both erythroid and megakaryocytic gene expression patterns were altered by the loss of the N-terminus, including aberrant up-regulation of Gata2and Runx1 Dysregulation of global H3K27 methylation was found in the erythroid progenitors upon loss of N-terminus of GATA1. Chromatin binding assays revealed that, despite similar occupancy of GATA1 and GATA1s, there was a striking reduction of H3K27me3 at regulatory elements of the Gata2and Runx1genes. Consistent with the observation that overexpression of GATA2 has been reported to impair erythropoiesis, we found that haploinsufficiency of Gata2rescued the erythroid defects of Gata1sfetuses. Together, our integrated genomic analysis of transcriptomic and epigenetic signatures reveals that, Gata1smice provide novel insights into the role of the N-terminus of GATA1 in transcriptional regulation and red blood cell maturation which may potentially be useful for DBA patients.
Current status of umbilical cord blood transplantation in children

The first umbilical cord blood (UCB) transplantation was performed 30 years ago. UCB transplantation (UCBT) is now widely used in children with malignant and non‐malignant disorders who lack a matched family donor. UCBT affords a lower incidence of graft‐versus‐host disease compared to alternative stem cell sources, but also presents a slower immune recovery and a high risk of infections if serotherapy is not omitted or targeted within the conditioning regimen. The selection of UCB units with high cell content and good human leucocyte antigen match is essential to improve the outcome. Techniques, such as double UCBT, ex vivo stem cell expansion and intra‐bone injection of UCB, have improved cord blood engraftment, but clinical benefit remains to be demonstrated. Cell therapies derived from UCB are under evaluation as potential novel strategies to reduce relapse and viral infections following transplantation. In recent years, improvements within haploidentical transplantation have reduced the overall use of UCBT as an alternative stem cell source; however, each may have its relative merits and disadvantages and tailored use of these alternative stem cell sources may be the optimal approach.
Analysis of risk factors and predictors of pregnancy loss and strategies for the management of cervical insufficiency in pregnant women at a high risk of preterm birth

Abstract Aim To identify risk factors and predictors of pregnancy loss and to compare the efficacy of Arabin’s pessary with cervical cerclage in women at a high risk of pregnancy loss. Materials and methods This was a two-center retrospective case-control study that included 240 women at a high risk of preterm delivery. Group I (n = 161) included women who underwent insertion of the Arabin’s pessary between 14 and 24 weeks of pregnancy. Group II (n = 79) included women who had undergone circular cervical cerclage during the current pregnancy. All women included in the study received micronized vaginal progesterone at the dose of 200 mg/day until and including 34 weeks of gestation. Results Threatened pregnancy loss defined as spotting or vaginal bleeding in the first trimester was diagnosed in 29.8% (48/161) of patients in Group I versus 37.9% in Group II (p = .448). Postpartum bleeding occurred in 8.1% (13/161) in women in Group I versus 22.8% in Group II (χ 2 = 6.500; p = .011). Our study showed that cervical cerclage was most suitable for patients with history of obstetric complications, cervical length <15 mm, and large isthmic uterine fibroids. The use of the Arabin’s pessary reduced the rate of preterm births by 1.7-fold. A cluster analysis demonstrated that predictors of preterm birth in women with a high risk of pregnancy loss included: threatened pregnancy loss associated with chorionic/placental abruption, cervical incompetence, uterine fibroid growth to a large size, history of multiple spontaneous pregnancy losses, cervical tears during past labor, and gestational diabetes diagnosed for the first time during the current pregnancy. Conclusions Women with a high risk of pregnancy loss treated with Arabin’s pessary or cerclage plus vaginal progesterone had a term delivery rate of 70.4% (169/240). The combined strategy of pregnancy management allowed to markedly reduce the number of preterm births.
Cytochrome P450: genotype to phenotype

Abstract The cytochromes P450 comprise a family of enzymes that are responsible for around three-quarters of all drug metabolism reactions that occur in human populations. Many isoforms of cytochrome P450 exist but most reactions are undertaken by CYP2C9, CYP2C19, CYP2D6 and CYP3A4. This brief review focusses on the first three isozymes which exhibit polymorphism of phenotype. If there is a wide variation in drug metabolising capacity within the population, this may precipitate clinical consequences and influence the drug treatment of patients. Such problems range from a lack of efficacy to unanticipated toxicity. In order to minimise untoward events and “personalise” a patient’s treatment, efforts have been made to discover an individual’s drug metabolism status. This requires knowledge of the subject’s phenotype at the time of clinical treatment. Since such testing is difficult, time-consuming and costly, the simpler approach of genotyping has been advocated. However, the correlation between genotype and phenotype is not good, with values of up to 50% misprediction being reported. Genotype-assisted forecasts cannot therefore be used with confidence to replace actual phenotype measurements. Obfuscating factors discussed include gene splicing, single nucleotide polymorphisms, epigenetics and microRNA, transcription regulation and multiple gene copies.
The “other” 15–40%: The Role of Non‐Collagenous Extracellular Matrix Proteins and Minor Collagens in Tendon

Extracellular matrix (ECM) determines the physiological function of all tissues, including musculoskeletal tissues. In tendon, ECM provides overall tissue architecture, which is tailored to match the biomechanical requirements of their physiological function, that is, force transmission from muscle to bone. Tendon ECM also constitutes the microenvironment that allows tendon‐resident cells to maintain their phenotype and that transmits biomechanical forces from the macro‐level to the micro‐level. The structure and function of adult tendons is largely determined by the hierarchical organization of collagen type I fibrils. However, non‐collagenous ECM proteins such as small leucine‐rich proteoglycans (SLRPs), ADAMTS proteases, and cross‐linking enzymes play critical roles in collagen fibrillogenesis and guide the hierarchical bundling of collagen fibrils into tendon fascicles. Other non‐collagenous ECM proteins such as the less abundant collagens, fibrillins, or elastin, contribute to tendon formation or determine some of their biomechanical properties. The interfascicular matrix or endotenon and the outer layer of tendons, the epi‐ and paratenon, includes collagens and non‐collagenous ECM proteins, but their function is less well understood. The ECM proteins in the epi‐ and paratenon may provide the appropriate microenvironment to maintain the identity of distinct tendon cell populations that are thought to play a role during repair processes after injury. The aim of this review is to provide an overview of the role of non‐collagenous ECM proteins and less abundant collagens in tendon development and homeostasis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:23–35, 2020
The Indenoisoquinoline TOP1 Inhibitors Selectively Target Homologous Recombination-Deficient and Schlafen 11-Positive Cancer Cells and Synergize with Olaparib

Purpose: Irinotecan and topotecan are used to treat a variety of different cancers. However, they have limitations, including chemical instability and severe side effects. To overcome these limitations, we developed the clinical indenoisoquinolines: LMP400 (indotecan), LMP776 (indimitecan), and LMP744. The purpose of the study is to build the molecular rationale for phase II clinical trials. Experimental Design: CellMinerCDB (http://discover.nci.nih.gov/cellminercdb) was used to mine the cancer cell lines genomic databases. The causality of Schlafen11 (SLFN11) was validated in isogenic cell lines. Because topoisomerase I (TOP1)-mediated replication DNA damage is repaired by homologous recombination (HR), we tested the “synthetic lethality” of HR-deficient (HRD) cells. Survival and cell-cycle alterations were performed after drug treatments in isogenic DT40, DLD1, and OVCAR cell lines with BRCA1, BRCA2, or PALB2 deficiencies and in organoids cultured from prostate cancer patient-derived xenografts with BRCA2 loss. We also used an ovarian orthotopic allograft model with BRCA1 loss to validate the efficacy of LMP400 and olaparib combination. Results: CellMinerCDB reveals that SLFN11, which kills cells undergoing replicative stress, is a dominant drug determinant to the clinical indenoisoquinolines. In addition, BRCA1-, BRCA2-, and PALB2-deficient cells were hypersensitive to the indenoisoquinolines. All 3 clinical indenoisoquinolines were also synergistic with olaparib, especially in the HRD cells. The synergy between LMP400 and olaparib was confirmed in the orthotopic allograft model harboring BRCA1 loss. Conclusions: Our results provide a rationale for molecularly designed clinical trials with the indenoisoquinolines as single agents and in combination with PARP inhibitors in HRD cancers expressing SLFN11.
Latitude-associated evolution and drivers of thermal response curves in body stoichiometry.

1.Trait-based studies are needed to understand the plastic and genetic responses of organisms to warming. A neglected organismal trait is elemental composition, despite its potential to cascade into effects on the ecosystem level. 2.Warming is predicted to shape elemental composition through shifts in storage molecules associated with responses in growth, body size, and metabolic rate. Our goals were to quantify thermal response patterns in body composition, and to obtain insights in their underlying drivers and their evolution across latitudes. 3.We reconstructed the thermal response curves (TRCs) for body elemental composition [C(carbon), N(nitrogen), and the C:N ratio] of damselfly larvae from high- and low-latitude populations. Additionally, we quantified the TRCs for survival, growth and development rates and body size to assess local thermal adaptation, as well as the TRCs for metabolic rate and key macromolecules (proteins, fat, sugars, and cuticular melanin and chitin) as these may underlie the elemental TRCs. 4.All larvae died at 36°C. Up to 32°C, low-latitude larvae increased growth and development rates and did not suffer increased mortality. Instead, growth and development rates of high-latitude larvae were lower and levelled off at 24°C, and mortality increased at 32°C. This latitude-associated thermal adaptation pattern matched the 'hotter-is-better' hypothesis. With increasing temperatures, low-latitude larvae decreased C:N, while high-latitude larvae increased C:N. These patterns were driven by associated changes in N contents while C contents did not respond to temperature. Consistent with the temperature-size-rule and the thermal melanism hypothesis, body size and melanin levels decreased with warming. While all traits and associated macromolecules (except for metabolic rate that showed thermal compensation) assumed to underlie thermal responses in elemental composition showed thermal plasticity, these were largely independent and none could explain the stoichiometric TRCs. 5.Our results highlight that thermal responses in elemental composition cannot be explained by traditionally assumed drivers, asking for a broader perspective including the thermal dependence of elemental fluxes. Another key implication is that thermal evolution can reverse the plastic stoichiometric thermal responses, hence reverse how warming may shape food web dynamics through changes in body composition at different latitudes. This article is protected by copyright. All rights reserved.
The Blood is Rich in Different Types of Mesoderm Derived Stem and Progenitor Cells

Abstract The blood and bone marrow have been thoroughly investiagated for more than a century, but we are still gaining surprising new informations. Blood transports different mature cells such as erythrocytes, platelets and granulocytes, but curiously, the blood is also transporting a number of non-differentiated cells of various mesodermal lineages: hematopoietic and mesenchymal stem and progenitor cells, endothelial progenitor cells and very small embryonal like cells are some of the most impressive examples. In adults the bone marrow is the source of practiclly all cells that could be found in the blood. Stem and progenitor cells egress from the bone marrow and home to the bone marrow or various tissues in a highly regulated manner. The fact that the hematopoetic stem and progenitor cells traffic through the blood and repopulate the bone marrow niche is largely explored in stem cell therapy in human medicine. In this review we will briefly describe the main characteristics of stem and progenitor cells, the mechanisms of their mobilization from the bone marrow and homing to target tissues. Also, the history and importance of the fact that different stem, progenitor and precursor cells could be isolated from the blood circulation will be discussed in the light of informations concerning their use in human and veterinary medicine. Abstract Ispitivanja krvi i koštane srži se sistematski sprovode duže od sto godina, ali su ova tkiva i dalje izvor novih podataka od značaja za humanu i veterinarsku medicinu. Krvlju cirkulišu različite zrele ćelije kao što su eritrociti, trombociti i granulociti, ali i mali broj nediferenciranih ćelija mezodermalnog porekla: hematopoteske i mezenhimske matične ćelije i ćelije progenitori, progenitori endotelnih ćelija i jako male ćelije nalik embrionalnim. Kod odraslih organizama, koštana srž je izvor praкtično svih ćelija koje se mogu naći u krvi. Mobilizacija matičnih ćelija i ćelija progenitora iz koštane srži u krv, i njihov povratak u koštanu srž ili odlazak u druga tkiva je regulisan kompleksnim procesima. Upotreba matičnih ćelija hematopoeze i ćelija progenitora u humanoj medicini, zasniva se na činjenici da mogu da se mobilišu u krv i da repopulišu koštanu srž proizvodeći zrele ćelije krvi. U ovom preglednom članku će biti opisane osnovne karakteristike matičnih ćelija i ćelija progenitora, mehanizmi mobilizacije i prelaska u tkiva. Takođe, značaj činjenice da se u krvi mogu naći različite matične ćelije i progenitorske i prekursorske ćelije je stvaljena u kontekst njihove primene u humanoj i veterinarskoj medicini.
Examining Industry Wage Differentials in the Palestinian Territories

Abstract It has been widely documented that there is a high level of inter-industry wage dispersion in the United States and several other developed countries. Unfortunately, due to the lack of data availability, industry wage differentials in developing countries have been examined in only a few studies and have been constrained by data limitations. Identifying the causes of industry wage differentials is crucial because it has policy implications toward mitigating wage inequality and unemployment. In this paper, I investigate industry wage differentials in the Palestinian territories – the West Bank and the Gaza Strip – using a rich dataset that allows cross-sectional and longitudinal analyses. I find that observed labor quality, unobserved labor quality, and labor market segmentation along the public and private sector represent the most suitable explanations for inter-industry wage dispersion in the Palestinian territories. Additionally, there is (limited) evidence of a shirking model especially in Gaza.
Toward a Dynamic Understanding of Entrepreneurship Education Research across the Campus – Social Cognition and Action Research

Abstract To date, there is little consensus about which types of educational methods, approaches, and support systems best facilitate entrepreneurial learning. By looking at entrepreneurship education through a socio-cognitive lens, this article presents a theory-based practical model that characterizes entrepreneurship education as a dynamic field of inquiry that considers the triadic reciprocal relationship of personal, behavioral and environmental factors of entrepreneurial learning. Based on this dynamic model and understanding of entrepreneurship education, action research is proposed as a new way of inquiry in order to facilitate the continuous improvement and evolution of educational methods and pedagogies across entrepreneurship programs in both academic and non-academic learning environments across the campus.
Sub and superharmonics of the lunar nodal tides and the solar radiative forcing in global sea level changes

Abstract: The working hypothesis of this study is that periodic lunar nodal tides and almost periodic solar radiation variations influence sea level changes through their harmonic beating of nearby natural and/or forced broadband oscillations of the sea level atmulti-decadal frequencies. The presence of the harmonics of the lunar nodal tides and the solar radiation variations, including the pole tides, is investigated by modeling and estimating the amplitudes of the corresponding periodicities in 27 globally distributed long tide gauge records. Statistically significant signatures of sub and superharmonics of lunar nodal tides and forced sea level variations due to solar radiation are detected in all station records.Meta-analysis of theharmonic amplitudes from all stations reveals that the effect sizes are statistically significant and provide evidence for the harmonic beating of sea level changes as a global phenomenon. Consequently, the compounding of the lunar nodal tides and forced sea level changes due to solar radiation with other broadband natural and forced sea level oscillations is a plausible explanation for the recent sea level accelerations and decelerations detected by satellite altimetry measurements and long tidal records.
Temporal aggregation and estimated monetary policy rules

Abstract Temporal aggregation alters time-series properties of high-frequency data, thereby affecting the estimation of models based on time-aggregated low-frequency data. This paper examines the effect of temporal aggregation of interest rates on forward-looking Taylor-type monetary policy rules. Results show that using quarterly-averaged interest rates in standard forward-looking structures adds a spurious bias to parameters that measure the extent of interest rate smoothing and serial correlation of shocks. Consequently, empirical interpretations of persistence in policy interest rate changes are distorted.
Coupled charge and spin dynamics in high-density ensembles of nitrogen-vacancy centers in diamond

We studied the spin depolarization of ensembles of nitrogen-vacancy (NV) centers in nitrogen-rich single crystal diamonds. We found a strong dependence of the evolution of the polarized state in the dark on the concentration of NV centers. At low excitation power, we observed a simple exponential decay profile in the low-density regime and a paradoxical inverted exponential profile in the high-density regime. At higher excitation power, we observed complex behavior, with an initial sharp rise in luminescence signal after the preparation pulse followed by a slower exponential decay. Magnetic field and excitation laser power-dependent measurements suggest that the rapid initial increase of the luminescence signal is related to recharging of the nitrogen-vacancy centers (from neutral to negatively charged) in the dark. The slow relaxing component corresponds to the longitudinal spin relaxation of the NV ensemble. The shape of the decay profile reflects the interplay between two mechanisms: the NV charge state conversion in the dark and the longitudinal spin relaxation. These mechanisms, in turn, are influenced by ionization, recharging and polarization dynamics during excitation. Interestingly, we found that charge dynamics are dominant in NV-dense samples even at very feeble excitation power. These observations may be important for the use of ensembles of NV centers in precession magnetometry and sensing applications.
Jets, bubbles, and heat pumps in galaxy clusters

Feedback from active galactic nucleus (AGN) jets has been proposed to counteract the catastrophic cooling in many galaxy clusters. However, it is still unclear which physical processes are acting to couple the energy from the bi-directional jets to the intra-cluster medium (ICM). We study the long-term evolution of rising bubbles that were inflated by AGN jets using magnetohydrodynamic simulations. In the wake of the rising bubbles, a significant amount of low-entropy gas is brought into contact with the hot cluster gas. We assess the energy budget of the uplifted gas and find it comparable to the total energy injected by the jets. Although our simulation does not include explicit thermal conduction, we find that, for reasonable assumptions about the conduction coefficient, the rate is fast enough that much of the uplifted gas may be thermalized before it sinks back to the core. Thus, we propose that the AGN can act like a geothermal heat pump to move low-entropy gas from the cluster core to the heat reservoir and will be able to heat the inner cluster more efficiently than would be possible by direct energy transfer from jets alone. We show that the maximum efficiency of this mechanism, i.e. the ratio between the conductive thermal energy and the work needed to lift the gas, ξmax, can exceed 100 per cent. While ξ < ξmax in realistic scenarios, AGN-induced thermal conduction has the potential to significantly increase the efficiency with which AGN can heat cool-core clusters and transform the bursty AGN activities into a smoother and enduring heating process.
Least-Square Approximation for a Distributed System

Abstract In this work, we develop a distributed least-square approximation (DLSA) method that is able to solve a large family of regression problems (e.g., linear regression, logistic regression, and Cox’s model) on a distributed system. By approximating the local objective function using a local quadratic form, we are able to obtain a combined estimator by taking a weighted average of local estimators. The resulting estimator is proved to be statistically as efficient as the global estimator. Moreover, it requires only one round of communication. We further conduct a shrinkage estimation based on the DLSA estimation using an adaptive Lasso approach. The solution can be easily obtained by using the LARS algorithm on the master node. It is theoretically shown that the resulting estimator possesses the oracle property and is selection consistent by using a newly designed distributed Bayesian information criterion. The finite sample performance and computational efficiency are further illustrated by an extensive numerical study and an airline dataset. The airline dataset is 52 GB in size. The entire methodology has been implemented in Python for a de-facto standard Spark system. The proposed DLSA algorithm on the Spark system takes 26 min to obtain a logistic regression estimator, which is more efficient and memory friendly than conventional methods. Supplementary materials for this article are available online.