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محاضرات تمهيدية في أمراض الدم
يحتوي هذا الكتاب على 113 شكلا وصورة فوتوغرافية ملونة و 54 جدولا ونظرا للزيادة في معرفة وفهم الآليات المتعددة والعلاقات المرضية التي تخص أورام العقد اللمفاوية (اللمفومة) والأورام الأخرى في نقي العظم فقد جعلت من الأهمية التوسع في مناقشة وشرح هذه المواضيع في هذا الكتاب بالإضافة لذلك فإنه يوجد في هذا الكتاب فصل قصير حول زراعة نقي العظم.
BOOK
Induction of myelinating oligodendrocytes in human cortical spheroids
Cerebral organoids provide an accessible system for investigations of cellular composition, interactions, and organization but have lacked oligodendrocytes, the myelinating glia of the central nervous system. Here we reproducibly generated oligodendrocytes and myelin in ‘oligocortical spheroids’ derived from human pluripotent stem cells. Molecular features consistent with those of maturing oligodendrocytes and early myelin appeared by week 20 in culture, with further maturation and myelin compaction evident by week 30. Promyelinating drugs enhanced the rate and extent of oligodendrocyte generation and myelination, and spheroids generated from human subjects with a genetic myelin disorder recapitulated human disease phenotypes. Oligocortical spheroids provide a versatile platform for studies of myelination of the developing central nervous system and offer new opportunities for disease modeling and therapeutic development.
Journal Article
Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination
Regeneration of myelin is mediated by oligodendrocyte progenitor cells—an abundant stem cell population in the central nervous system (CNS) and the principal source of new myelinating oligodendrocytes. Loss of myelin-producing oligodendrocytes in the CNS underlies a number of neurological diseases, including multiple sclerosis and diverse genetic diseases
1
–
3
. High-throughput chemical screening approaches have been used to identify small molecules that stimulate the formation of oligodendrocytes from oligodendrocyte progenitor cells and functionally enhance remyelination in vivo
4
–
10
. Here we show that a wide range of these pro-myelinating small molecules function not through their canonical targets but by directly inhibiting CYP51, TM7SF2, or EBP, a narrow range of enzymes within the cholesterol biosynthesis pathway. Subsequent accumulation of the 8,9-unsaturated sterol substrates of these enzymes is a key mechanistic node that promotes oligodendrocyte formation, as 8,9-unsaturated sterols are effective when supplied to oligodendrocyte progenitor cells in purified form whereas analogous sterols that lack this structural feature have no effect. Collectively, our results define a unifying sterol-based mechanism of action for most known small-molecule enhancers of oligodendrocyte formation and highlight specific targets to propel the development of optimal remyelinating therapeutics.
Many small molecules that stimulate oligodendrocyte formation act not through their canonical pathways but by inhibiting enzymes within the cholesterol biosynthesis pathway and thereby inducing the accumulation of 8,9-unsaturated sterols.
Journal Article
Rapid custom prototyping of soft poroelastic biosensor for simultaneous epicardial recording and imaging
The growing need for the implementation of stretchable biosensors in the body has driven rapid prototyping schemes through the direct ink writing of multidimensional functional architectures. Recent approaches employ biocompatible inks that are dispensable through an automated nozzle injection system. However, their application in medical practices remains challenged in reliable recording due to their viscoelastic nature that yields mechanical and electrical hysteresis under periodic large strains. Herein, we report sponge-like poroelastic silicone composites adaptable for high-precision direct writing of custom-designed stretchable biosensors, which are soft and insensitive to strains. Their unique structural properties yield a robust coupling to living tissues, enabling high-fidelity recording of spatiotemporal electrophysiological activity and real-time ultrasound imaging for visual feedback. In vivo evaluations of custom-fit biosensors in a murine acute myocardial infarction model demonstrate a potential clinical utility in the simultaneous intraoperative recording and imaging on the epicardium, which may guide definitive surgical treatments.
Printed biosensors are important for health monitoring and research purposes. Here, the authors report on the development of a soft poroelastic silicone based sensor which can be easily printed and is resistant to mechanical strain hysteresis, allowing for more accurate electrophysiology readings and imaging.
Journal Article
Biodegradation Studies of Polyhydroxybutyrate and Polyhydroxybutyrate-co-Polyhydroxyvalerate Films in Soil
Due to increased environmental pressures, significant research has focused on finding suitable biodegradable plastics to replace ubiquitous petrochemical-derived polymers. Polyhydroxyalkanoates (PHAs) are a class of polymers that can be synthesized by microorganisms and are biodegradable, making them suitable candidates. The present study looks at the degradation properties of two PHA polymers: polyhydroxybutyrate (PHB) and polyhydroxybutyrate-co-polyhydroxyvalerate (PHBV; 8 wt.% valerate), in two different soil conditions: soil fully saturated with water (100% relative humidity, RH) and soil with 40% RH. The degradation was evaluated by observing the changes in appearance, chemical signatures, mechanical properties, and molecular weight of samples. Both PHB and PHBV were degraded completely after two weeks in 100% RH soil conditions and showed significant reductions in mechanical properties after just three days. The samples in 40% RH soil, however, showed minimal changes in mechanical properties, melting temperatures/crystallinity, and molecular weight over six weeks. By observing the degradation behavior for different soil conditions, these results can pave the way for identifying situations where the current use of plastics can be replaced with biodegradable alternatives.
Journal Article
Experimental and theoretical evaluation of Cu–Al–Ni shape memory alloys shielding properties at the 511–1333 keV gamma energy range
This study used the gamma transmission method to present a systematic experimental analysis of the mass (µ
m
)and linear attenuation coefficients (µ) of Cu–Al–Ni shape memory alloys. Gamma rays with energies of 0.511 MeV, 0.661 MeV, 1.173 MeV, and 1.333 MeV were, respectively, emitted from point sources
22
Na,
137
Cs, and
60
Co. The results revealed a significant decrease in both the mass attenuation coefficient from 0.08 to 0.05 cm
2
g
−1
and the linear attenuation coefficient from 0.65 to 0.40 cm
−1
as the incident gamma energy increased from 0.511 to 1.333 MeV. The obtained experimental results were compared with theoretical data from established databases such as WinXCom and the Photon Shielding and Dosimetry (Phy-X / PSD). Moreover, seven further vital shielding parameters were calculated utilizing the µ
m
and µ of experimental and theoretical values including total atomic cross-section (σ
a
), total electronic cross-section (σ
e
), effective atomic number (Z
eff
), effective electron number (N
eff
), half (HVL), tenth value (TVL) layer, and mean free path (MFP) for the alloys at different photon energies. Comparative analysis indicated that these Cu–Al–Ni SMAs exhibit promising potential for nuclear applications, closely aligning with the alloys widely discussed in existing.
Journal Article
Predicting the Mechanical Response of Polyhydroxyalkanoate Biopolymers Using Molecular Dynamics Simulations
Polyhydroxyalkanoates (PHAs) have emerged as a promising class of biosynthesizable, biocompatible, and biodegradable polymers to replace petroleum-based plastics for addressing the global plastic pollution problem. Although PHAs offer a wide range of chemical diversity, the structure–property relationships in this class of polymers remain poorly established. In particular, the available experimental data on the mechanical properties is scarce. In this contribution, we have used molecular dynamics simulations employing a recently developed forcefield to predict chemical trends in mechanical properties of PHAs. Specifically, we make predictions for Young’s modulus, and yield stress for a wide range of PHAs that exhibit varying lengths of backbone and side chains as well as different side chain functional groups. Deformation simulations were performed at six different strain rates and six different temperatures to elucidate their influence on the mechanical properties. Our results indicate that Young’s modulus and yield stress decrease systematically with increase in the number of carbon atoms in the side chain as well as in the polymer backbone. In addition, we find that the mechanical properties were strongly correlated with the chemical nature of the functional group. The functional groups that enhance the interchain interactions lead to an enhancement in both the Young’s modulus and yield stress. Finally, we applied the developed methodology to study composition-dependence of the mechanical properties for a selected set of binary and ternary copolymers. Overall, our work not only provides insights into rational design rules for tailoring mechanical properties in PHAs, but also opens up avenues for future high throughput atomistic simulation studies geared towards identifying functional PHA polymer candidates for targeted applications.
Journal Article
Perceived barriers and facilitators to participating in the North Carolina Healthy Food Small Retailer Program: a mixed-methods examination considering investment effectiveness
The North Carolina Legislature appropriated funds in 2016-2019 for the Healthy Food Small Retailer Program (HFSRP), providing small retailers located in food deserts with equipment to stock nutrient-dense foods and beverages. The study aimed to: (1) examine factors facilitating and constraining implementation of, and participation in, the HFSRP from the perspective of storeowners and (2) measure and evaluate the impact and effectiveness of investment in the HFSRP.
The current analysis uses both qualitative and quantitative assessments of storeowner perceptions and store outcomes, as well as two innovative measures of policy investment effectiveness. Qualitative semi-structured interviews and descriptive quantitative approaches, including monthly financial reports and activity forms, and end-of-programme evaluations were collected from participating HFSRP storeowners.
Eight corner stores in North Carolina that participated in the two cohorts (2016-2018; 2017-2019) of the HFSRP.
Owners of corner stores participating in the HFSRP.
All storeowners reported that the HFSRP benefitted their stores. In addition, the HFSRP had a positive impact on sales across each category of healthy food products. Storeowners reported that benefits would be enhanced with adjustments to programme administration and support. Specific suggestions included additional information regarding which healthy foods and beverages to stock; inventory management; handling of perishable produce; product display; modified reporting requirements and a more efficient process of delivering and maintaining equipment.
All storeowners reported several benefits of the HFSRP and would recommend that other storeowners participate. The barriers and challenges they reported inform potential approaches to ensuring success and sustainability of the HFSRP and similar initiatives underway in other jurisdictions.
Journal Article
Characterization of Polyhydroxybutyrate-Based Composites Prepared by Injection Molding
The waste generated by single-use plastics is often non-recyclable and non-biodegradable, inevitably ending up in our landfills, ecosystems, and food chain. Through the introduction of biodegradable polymers as substitutes for common plastics, we can decrease our impact on the planet. In this study, we evaluate the changes in mechanical and thermal properties of polyhydroxybutyrate-based composites with various additives: Microspheres, carbon fibers or polyethylene glycol (2000, 10,000, and 20,000 MW). The mixtures were injection molded using an in-house mold attached to a commercial extruder. The resulting samples were characterized using microscopy and a series of spectroscopic, thermal, and mechanical techniques. We have shown that the addition of carbon fibers and microspheres had minimal impact on thermal stability, whereas polyethylene glycol showed slight improvements at higher molecular weights. All of the composite samples showed a decrease in hardness and compressibility. The findings described in this study will improve our understanding of polyhydroxybutyrate-based composites prepared by injection molding, enabling advancements in integrating biodegradable plastics into everyday products.
Journal Article
Gamma irradiation induced stabilisation in CuAlNi shape memory alloys
After annealing, gamma irradiation was applied to CuAlNi shape memory alloy samples at different doses and investigated how the stabilization was affected by irradiation. Conversion temperatures and thermodynamic parameters were determined by thermal measurements. Non-regular increases in these parameters were observed depending on the irradiation dose. Depending on the irradiation dose, the structural analyzes of the alloy samples were made with X-ray diffraction. The changes in microhardness and crystallite size of the alloy samples with increasing irradiation dose were investigated. The crystallite size tends to decrease with increasing irradiation dose, and the increase in microhardness favors the change in crystallite size. In results are discussed to the stabilization of martensite by increased irradiation dose in CuAlNi alloys.
Journal Article