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"Zhang, Y K"
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إنتاج الطاقة الحيوية والوقود الحيوي من النفايات والكتلة الحيوية
توفر فصول هذا الكتاب أحدث استعراض ومسح للبحوث والتطورات التقنية، فيما يتعلق بالجيلين الثاني والثالث من الوقود الحيوي والطاقة الحيوية، كما تعرض الاتجاهات البحثية الحالية والمستقبلية في نهاية كل فصل ويغطي هذا الكتاب في المقام الأول، التحويل البيولوجي والكيميائي الحيوي لإنتاج الوقود الحيوي والطاقة الحيوية، باعتباره خيارا معلنا ورخيصا لإنتاج الوقود الحيوي والطاقة الحيوية. يعد هذا الكتاب مرجعا قيما، لطلاب المرحلة الجامعية والدراسات العليا والباحثين في الكيمياء والكيمياء الحيوية والبيئة والمجالات الهندسية وصناع القرار والمهنيين الممارسين وغيرهم من المهتمين بمجال الوقود الحيوي والطاقة الحيوية.
Book
A bimodal burst energy distribution of a repeating fast radio burst source
The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown
1
,
2
. As the first precisely localized source, FRB 121102 (refs.
3
–
5
) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution
6
–
8
. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h
−1
, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 10
37
erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.
For FRB 121102, 1,652 burst events are detected over 47 days, with a peak burst rate of 122 per hour, a bimodal burst rate energy distribution, and no periodicity or quasi-periodicity.
Journal Article
A repeating fast radio burst associated with a persistent radio source
The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium
1
, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs
2
, in at least one case there is evidence for an extreme magneto-ionic local environment
3
,
4
and a compact persistent radio source
5
. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately
903
−
111
+
72
parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies
2
,
6
, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.
A repeating fast radio burst co-located with a persistent radio source and associated with a dwarf host galaxy of a high star-formation rate has been detected.
Journal Article
Activation and expansion of human T cells using artificial antigen-presenting cell scaffolds
Synthetic antigen-presenting cells (APCs) are used to mediate scalable ex vivo T-cell expansion for adoptive cell therapy. Recently, we developed APC-mimetic scaffolds (APC-ms), which present signals to T cells in a physiological manner to mediate rapid and controlled T-cell expansion. APC-ms are composed of individual high-aspect-ratio silica microrods loaded with soluble mitogenic cues and coated with liposomes of defined compositions, to form supported lipid bilayers. Membrane-bound ligands for stimulation and co-stimulation of T-cell receptors are presented via the fluid, synthetic membranes, while mitogenic cues are released slowly from the microrods. In culture, interacting T cells assemble the individual APC-ms microrods into a biodegradable 3D matrix. Compared to conventional methods, APC-ms facilitates several-fold greater polyclonal T-cell expansion and improved antigen-specific enrichment of rare T-cell subpopulations. Here we provide a detailed protocol for APC-ms synthesis and use for human T-cell activation, and discuss important considerations for material design and T-cell co-culture. This protocol describes the facile assembly of APC-ms in ~4 h and rapid expansion or enrichment of relevant T-cell clones in <2 weeks, and is applicable for T-cell manufacturing and assay development.
This protocol describes the synthesis and applications of artificial antigen-presenting cell scaffolds. The scaffolds can be used for efficient ex vivo polyclonal T-cell expansion and antigen-specific enrichment of rare T-cell subpopulations.
Journal Article
Enhancing CAR-T cell functionality in a patient-specific manner
Patient responses to autologous CD19 chimeric antigen receptor (CAR) T-cell therapies are limited by insufficient and inconsistent cellular functionality. Here, we show that controlling the precise level of stimulation during T-cell activation to accommodate individual differences in the donor cells will dictate the functional attributes of CAR-T cell products. The functionality of CAR-T cell products, consisting of a diverse set of blood samples derived from healthy donors, acute lymphoblastic leukemia (ALL), and chronic lymphocytic lymphoma (CLL) patient samples, representing a range of patient health status, is tested upon culturing on artificial antigen-presenting cell scaffolds to deliver T-cell stimulatory ligands (anti-CD3/anti-CD28) at highly defined densities. A clear relationship is observed between the dose of stimulation, the phenotype of the T-cell blood sample prior to T-cell activation, and the functionality of the resulting CAR-T cell products. We present a model, based on this dataset, that predicts the precise stimulation needed to manufacture a desired CAR-T cell product, given the input T-cell attributes in the initial blood sample. These findings demonstrate a simple approach to enhance CAR-T functionality by personalizing the level of stimulation during T-cell activation to enable flexible manufacturing of more consistent and potent CAR-T cells.
‘Manufacturing CAR-T cells is a streamlined and highly regulated procedure involving T-cell-expansion and activation on a standardised platform. Here, the authors show that a personalized approach, taking the phenotypic attributes of individual patients’ T cells into account, leads to more efficient CAR-T cell manufacturing and better CAR-T cell functionality.
Journal Article
How does the two-child policy affect the sex ratio at birth in China? A cross-sectional study
Background
The One-Child Policy led to the imbalance of the sex ratio at birth (SRB) in China. After that, Two-Child Policy was introduced and gradually liberalized at three stages. If both the husband and wife of one couple were the only child of their parents, they were allowed to have two children in policy (BTCP). If only one of them was the only child, they were allowed to have two children in policy (OTCP). The Universal Two-Child Policy (UTCP) allowed every couple to have two children. The objective of this study was to explore the changing trend of SRB at the stages of Two-Child Policy, to analyze the effect of population policy on SRB in terms of maternal age, delivery mode, parity, maternal education, delivery hospital, and to figure out what factors have greater impact on the SRB.
Methods
The data of the study came from Hebei Province Maternal Near Miss Surveillance System, covered the parturients delivered at 28 gestation weeks or more in 22 hospitals from January 1, 2013 to December 31, 2017. We compared the SRB at different policy stages, analyzed the relationship between the SRB and population policy by logistic regression analysis.
Results
Total 270,878 singleton deliveries were analyzed. The SRB, 1.084 at BTCP, 1.050 at OTCP, 1.047 at UTCP, declined rapidly (χ
2
= 15.97,
P
< 0.01). With the introduction of Two-Child Policy, the percentage of parturients who were 30–34, ≥35 years old rose significantly, and the percentage of multiparous women increased significantly (40.7, 47.2, 56.6%). The neonatal mortality declined significantly (8.4‰, 6.7‰, 5.9‰,
χ
2
=
44.49,
P
< 0.01), the mortality rate of female infant gradually declined (48.2, 43.7, 43.9%). The logistic regression analysis showed the SRB was correlated to the three population policy stages in terms of maternal age, delivery mode, parity, maternal education, delivery hospital.
Conclusions
The SRB has declined to normal level with the gradually liberalizing of Two-Child Policy in China. Advanced maternal age, cesarean delivery, multiparous women, middle level education, rural hospital are the main factors of effect on the decline of the SRB.
Journal Article
SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis
Human African trypanosomiasis (HAT) is an important public health problem in sub-Saharan Africa, affecting hundreds of thousands of individuals. An urgent need exists for the discovery and development of new, safe, and effective drugs to treat HAT, as existing therapies suffer from poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. We have discovered and optimized a novel class of small-molecule boron-containing compounds, benzoxaboroles, to identify SCYX-7158 as an effective, safe and orally active treatment for HAT.
A drug discovery project employing integrated biological screening, medicinal chemistry and pharmacokinetic characterization identified SCYX-7158 as an optimized analog, as it is active in vitro against relevant strains of Trypanosoma brucei, including T. b. rhodesiense and T. b. gambiense, is efficacious in both stage 1 and stage 2 murine HAT models and has physicochemical and in vitro absorption, distribution, metabolism, elimination and toxicology (ADMET) properties consistent with the compound being orally available, metabolically stable and CNS permeable. In a murine stage 2 study, SCYX-7158 is effective orally at doses as low as 12.5 mg/kg (QD×7 days). In vivo pharmacokinetic characterization of SCYX-7158 demonstrates that the compound is highly bioavailable in rodents and non-human primates, has low intravenous plasma clearance and has a 24-h elimination half-life and a volume of distribution that indicate good tissue distribution. Most importantly, in rodents brain exposure of SCYX-7158 is high, with C(max) >10 µg/mL and AUC(0-24 hr) >100 µg*h/mL following a 25 mg/kg oral dose. Furthermore, SCYX-7158 readily distributes into cerebrospinal fluid to achieve therapeutically relevant concentrations in this compartment.
The biological and pharmacokinetic properties of SCYX-7158 suggest that this compound will be efficacious and safe to treat stage 2 HAT. SCYX-7158 has been selected to enter preclinical studies, with expected progression to phase 1 clinical trials in 2011.
Journal Article
Adoptive T cell transfer and host antigen-presenting cell recruitment with cryogel scaffolds promotes long-term protection against solid tumors
Although adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a hydrogel that locally delivers adoptively transferred T cells to the tumor site while recruiting and activating host antigen-presenting cells with GMCSF or FLT3L and CpG, respectively. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. T cell delivery combined with biomaterial-driven accumulation and activation of host immune cells prolonged the activation of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. These findings highlight how this integrated approach provide both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape.
Adoptive T cell therapy has shown remarkable promise for the treatment of haematological malignancies. Here, the authors show that a cryogel platform for the simultaneous delivery of autologous T cells and recruitment of local antigen-presenting cells promotes long-lasting responses against solid tumours in mice.
Journal Article
Exotic spin-dependent interactions through unparticle exchange
A
bstract
The potential discovery of unparticles could have far-reaching implications for particle physics and cosmology. For over a decade, high-energy physicists have extensively studied the effects of unparticles. In this study, we derive six types of nonrelativistic potentials between fermions induced by unparticle exchange in coordinate space. We consider all possible combinations of scalar, pseudo-scalar, vector, and axial-vector couplings to explore the full range of possibilities. Previous studies have only examined scalar-scalar (SS), pseudoscalar-pseudoscalar (PP), vector-vector (VV), and axial-axial-vector (AA) type interactions, which are all parity even. We propose SP and VA interactions to extend our understanding of unparticle physics, noting that parity conservation is not always guaranteed in modern physics. We explore the possibilities of detecting unparticles through the long-range interactions they may mediate with ordinary matter. Dedicated experiments using precision measurement methods can be employed to search for such interactions. We discuss the properties of these potentials and estimate constraints on their coupling constants based on existing experimental data. Our findings indicate that for some particular values of the scaling dimension
d
U
, the coupling between scalar or vector unparticles and fermions is constrained by several orders of magnitude more tightly than the previous limits. The underlying reason for this improvement is analyzed. Limits are also set on the newly proposed SP and VA interactions for continuous
d
U
values, allowing the exploration of the
d
U
dependence of the constraints. It turns out that the bounds exhibit an exponential decay trend with the increasing
d
U
.
Journal Article
Analyses of uncertainties and scaling of groundwater level fluctuations
Analytical solutions were derived for the variance, covariance, and spectrum of groundwater level, h(x, t), in an unconfined aquifer described by a linearized Boussinesq equation, with random source/sink and initial and boundary conditions. It was found that in a typical aquifer, the error in h(x, t) at an early point in time is mainly caused by the random initial condition, and the error reduces as time progresses to reach a constant error at a later time. The duration for which the effect of the random initial condition is significant may be a few hundred days in most aquifers. The constant error in h(x, t) at a later time is due to the combined effects of the uncertainties in the source/sink and flux boundary: the closer to the flux boundary, the larger the error. The error caused by the uncertain head boundary is limited to a narrow zone near the boundary and remains more or less constant over time. The aquifer system behaves as a low-pass filter which filters out high-frequency noises and keeps low-frequency variations. Temporal scaling of groundwater level fluctuations exists in most parts of a low permeable aquifer whose horizontal length is much larger than its thickness, caused by the temporal fluctuations of areal source/sink.
Journal Article