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مأزق البورجوازية الوطنية الصناعية في العالم الثالث : تجربة بنك مصر 1920-1941
يتناول كتاب (مأزق البورجوازية الوطنية الصناعية في العالم الثالث : تجربة بنك مصر 1920-1941) والذي قام بتأليفه (إريك دافيز) في حوالي (282) صفحة من القطع المتوسط موضوع (التصنيع في مصر) مستعرضا المحتويات التالية : اندماج مصر في السوق العالمية 1760-1882، تناقضات التطور التابع 1882-1920، محمد طلعت حرب والحركة الوطنية، الاشتباك مع الإستعمار 1920-1930، بنك مصر والاستعمار الجديد 1930-1941، بنك مصر والتطور الاقتصادي العربي، الاقتصاد السياسي للتصنيع التابع.
BOOK
Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas
Autologous chimeric antigen receptor (CAR) T cell therapies targeting CD19 have high efficacy in large B cell lymphomas (LBCLs), but long-term remissions are observed in less than half of patients, and treatment-associated adverse events, such as immune effector cell-associated neurotoxicity syndrome (ICANS), are a clinical challenge. We performed single-cell RNA sequencing with capture-based cell identification on autologous axicabtagene ciloleucel (axi-cel) anti-CD19 CAR T cell infusion products to identify transcriptomic features associated with efficacy and toxicity in 24 patients with LBCL. Patients who achieved a complete response by positron emission tomography/computed tomography at their 3-month follow-up had three-fold higher frequencies of CD8 T cells expressing memory signatures than patients with partial response or progressive disease. Molecular response measured by cell-free DNA sequencing at day 7 after infusion was significantly associated with clinical response (
P
= 0.008), and a signature of CD8 T cell exhaustion was associated (
q
= 2.8 × 10
−149
) with a poor molecular response. Furthermore, a rare cell population with monocyte-like transcriptional features was associated (
P
= 0.0002) with high-grade ICANS. Our results suggest that heterogeneity in the cellular and molecular features of CAR T cell infusion products contributes to variation in efficacy and toxicity after axi-cel therapy in LBCL, and that day 7 molecular response might serve as an early predictor of CAR T cell efficacy.
Single-cell transcriptomics reveals that the heterogeneity of anti-CD19 CAR T cell infusion products contributes to variability in clinical response, early molecular response and development of immune effector cell-associated neurotoxicity syndrome in patients with large B cell lymphomas.
Journal Article
Animation
With an introduction by John Lasseter-- and very little else in the way of words-- this second book in The Artist Series lavishly showcases the most brilliant animation created by such luminaries as Ub Iwerks, Norm Ferguson, Ben Sharpsteen, Hamilton Luske, Dick Huemer, Grim Natwick, Art Babbitt, Fred Moore, Bill Tytla, Frank Thomas, Ollie Johnston, Milt Kahl, Marc Davis, John Lounsbery, Ward Kimball, Eric Larson, Les Clark, Wolfgang Reitherman, John Sibley, Bill Justice, Clyde Geronimi, Ted Berman, Glen Keane, Andreas Deja, Eric Goldberg, Mark Henn and Tony Bancroft. The artwork-- much of which has never before been published-- offers the opportunity to marvel at the those magical lines of pencil that brought life to so many unforgettable Disney characters. Animation represents a rare opportunity to enjoy a glimpse into the truly spectacular trove of treasures from the Walt Disney Animation Research Library.
Book
Evaluation of e-liquid toxicity using an open-source high-throughput screening assay
The e-liquids used in electronic cigarettes (E-cigs) consist of propylene glycol (PG), vegetable glycerin (VG), nicotine, and chemical additives for flavoring. There are currently over 7,700 e-liquid flavors available, and while some have been tested for toxicity in the laboratory, most have not. Here, we developed a 3-phase, 384-well, plate-based, high-throughput screening (HTS) assay to rapidly triage and validate the toxicity of multiple e-liquids. Our data demonstrated that the PG/VG vehicle adversely affected cell viability and that a large number of e-liquids were more toxic than PG/VG. We also performed gas chromatography-mass spectrometry (GC-MS) analysis on all tested e-liquids. Subsequent nonmetric multidimensional scaling (NMDS) analysis revealed that e-liquids are an extremely heterogeneous group. Furthermore, these data indicated that (i) the more chemicals contained in an e-liquid, the more toxic it was likely to be and (ii) the presence of vanillin was associated with higher toxicity values. Further analysis of common constituents by electron ionization revealed that the concentration of cinnamaldehyde and vanillin, but not triacetin, correlated with toxicity. We have also developed a publicly available searchable website (www.eliquidinfo.org). Given the large numbers of available e-liquids, this website will serve as a resource to facilitate dissemination of this information. Our data suggest that an HTS approach to evaluate the toxicity of multiple e-liquids is feasible. Such an approach may serve as a roadmap to enable bodies such as the Food and Drug Administration (FDA) to better regulate e-liquid composition.
Journal Article
The effect of carbon fertilization on naturally regenerated and planted US forests
Over the last half century in the United States, the per-hectare volume of wood in trees has increased, but it is not clear whether this increase has been driven by forest management, forest recovery from past land uses, such as agriculture, or other environmental factors such as elevated carbon dioxide, nitrogen deposition, or climate change. This paper uses empirical analysis to estimate the effect of elevated carbon dioxide on aboveground wood volume in temperate forests of the United States. To accomplish this, we employ matching techniques that allow us to disentangle the effects of elevated carbon dioxide from other environmental factors affecting wood volume and to estimate the effects separately for planted and natural stands. We show that elevated carbon dioxide has had a strong and consistently positive effect on wood volume while other environmental factors yielded a mix of both positive and negative effects. This study, by enabling a better understanding of how elevated carbon dioxide and other anthropogenic factors are influencing forest stocks, can help policymakers and other stakeholders better account for the role of forests in Nationally Determined Contributions and global mitigation pathways to achieve a 1.5 degree Celsius target.
The CO2 fertilisation effect in forests remains controversial. Here, the authors disentangle the effect of CO2 on forest wood volume from other environmental factors, showing that elevated CO2 had a positive effect on wood volume in planted and natural US temperate forests.
Journal Article
FGL2 promotes tumor progression in the CNS by suppressing CD103+ dendritic cell differentiation
Few studies implicate immunoregulatory gene expression in tumor cells in arbitrating brain tumor progression. Here we show that fibrinogen-like protein 2 (FGL2) is highly expressed in glioma stem cells and primary glioblastoma (GBM) cells. FGL2 knockout in tumor cells did not affect tumor-cell proliferation in vitro or tumor progression in immunodeficient mice but completely impaired GBM progression in immune-competent mice. This impairment was reversed in mice with a defect in dendritic cells (DCs) or CD103
+
DC differentiation in the brain and in tumor-draining lymph nodes. The presence of FGL2 in tumor cells inhibited granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced CD103
+
DC differentiation by suppressing NF-κB, STAT1/5, and p38 activation. These findings are relevant to GBM patients because a low level of
FGL2
expression with concurrent high
GM-CSF
expression is associated with higher
CD8B
expression and longer survival. These data provide a rationale for therapeutic inhibition of FGL2 in brain tumors.
Fibrinogen-like protein 2 (FGL2) mediates immune suppression in glioblastoma (GBM). Here, the authors show that FGL-2 expressed by GBM cancer cells acts by suppressing the differentiation of CD103+ DC cells required to activate the anti-tumor CD8+ T cell response via blocking GM-CSF signalling at NFKB, STAT1/5 and p38 level.
Journal Article
Chronic E-Cigarette Exposure Alters the Human Bronchial Epithelial Proteome
E-cigarettes vaporize propylene glycol/vegetable glycerin (PG/VG), nicotine, and flavorings. However, the long-term health effects of exposing lungs to vaped e-liquids are unknown.
To determine the effects of chronic vaping on pulmonary epithelia.
We performed research bronchoscopies on healthy nonsmokers, cigarette smokers, and e-cigarette users (vapers) and obtained bronchial brush biopsies and lavage samples from these subjects for proteomic investigation. We further employed in vitro and murine exposure models to support our human findings.
Visual inspection by bronchoscopy revealed that vaper airways appeared friable and erythematous. Epithelial cells from biopsy samples revealed approximately 300 proteins that were differentially expressed in smoker and vaper airways, with only 78 proteins being commonly altered in both groups and 113 uniquely altered in vapers. For example, CYP1B1 (cytochrome P450 family 1 subfamily B member 1), MUC5AC (mucin 5 AC), and MUC4 levels were increased in vapers. Aerosolized PG/VG alone significantly increased MUC5AC protein in human airway epithelial cultures and in murine nasal epithelia in vivo. We also found that e-liquids rapidly entered cells and that PG/VG reduced membrane fluidity and impaired protein diffusion.
We conclude that chronic vaping exerts marked biological effects on the lung and that these effects may in part be mediated by the PG/VG base. These changes are likely not harmless and may have clinical implications for the development of chronic lung disease. Further studies will be required to determine the full extent of vaping on the lung.
Journal Article
BETP degradation simultaneously targets acute myelogenous leukemic stem cells and the microenvironment
The antileukemic effect of inhibiting bromodomain and extra-terminal domain-containing (BET-containing) proteins (BETPs) such as BRD4 has largely been largely attributed to transcriptional downregulation of cellular anabolic and antiapoptotic processes, but its effect on the bone marrow microenvironment, a sanctuary favoring the persistence of leukemic stem/progenitor cells, is unexplored. Sustained degradation of BETP with the small-molecule BET proteolysistargeting chimera (PROTAC) ARV-825 resulted in a marked downregulation of surface CXCR4 and CD44, key proteins in leukemia-microenvironment interactions, in acute myeloid leukemia (AML) cells. Abrogation of surface CXCR4 expression impaired SDF-1[alpha]-directed migration and was mediated through transcriptional downregulation of PIM1 kinase, which in turn phosphorylates CXCR4 and facilitates its surface localization. Downregulation of CD44, including isoforms CD44v8- 10 impaired cystine uptake, lowered intracellular reduced glutathione, and increased oxidative stress. More important, BETP degradation markedly decreased the [CD34.sup.+][CD38.sup.-][CD90.sup.-][CD45RA.sup.+] leukemic stem cell population and, alone or in combination with cytarabine, prolonged survival in a mouse model of human leukemia that included AML patient-derived xenografts (AML-PDX). Gene expression profiling and single-cell proteomics confirmed a downregulation of the gene signatures associated with \"sternness\" in AML and Wnt/[beta]-catenin and Myc pathways. Hence, BETP degradation by ARV-825 simultaneously targets cell-intrinsic signaling, stromal interactions, and metabolism in AML.
Journal Article
Nematode effector proteins: an emerging paradigm of parasitism
Phytonematodes use a stylet and secreted effectors to modify host cells and ingest nutrients to support their growth and development. The molecular function of nematode effectors is currently the subject of intense investigation. In this review, we summarize our current understanding of nematode effectors, with a particular focus on proteinaceous stylet-secreted effectors of sedentary endoparasitic phytonematodes, for which a wealth of information has surfaced in the past 10 yr.Weprovide an update on the effector repertoires of several of the most economically important genera of phytonematodes and discuss current approaches to dissecting their function. Lastly, we highlight the latest breakthroughs in effector discovery that promise to shed new light on effector diversity and function across the phylum Nematoda.
Journal Article
Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations
Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuroblastoma samples. Forty percent of samples harbor at least one recurrent driver gene alteration and most aberrations, including
MYCN
,
ATRX
, and
TERT
alterations, differ in frequency by age.
MYCN
alterations occur at median 2.3 years of age,
TERT
at 3.8 years, and
ATRX
at 5.6 years. COSMIC mutational signature 18, previously associated with reactive oxygen species, is the most common cause of driver point mutations in neuroblastoma, including most
ALK
and Ras-activating variants. Signature 18 appears early and is continuous throughout disease evolution. Signature 18 is enriched in neuroblastomas with
MYCN
amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent
FGFR1
variants in six patients, and
ALK
N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.
Genomic analysis of neuroblastoma has revealed important disease etiology. In this study, the authors assembled whole genome, exome and transcriptome data from over 700 neuroblastomas and identified molecular signatures correlated with age, and rare, potentially targetable variants overlooked in smaller cohorts.
Journal Article