This book analyzes how Israel's priestly institutions are represented in Hellenistic-era Aramaic Jewish literature so as to make a fresh proposal about the social location of this understudied but ...fascinating literary tradition.
This review considers the origins of the errorless learning (EL) concept, its application in memory rehabilitation, the evidence for its effectiveness, and the theoretical basis for the observed ...findings. The evidence suggests that EL offers valuable benefits for at least some people with memory impairments when teaching certain types of tasks. However, the benefits are not evident for all groups, some findings are equivocal, and there are some limitations associated with this approach. We discuss methodological issues impacting on these mixed findings, consider which theoretical explanations might account for the findings regarding benefits and limitations of EL, and comment on the implications for rehabilitation practitioners of the current state of evidence in this area.
The solute carrier family 16 (SLC16) is comprised of 14 members of the monocarboxylate transporter (MCT) family that play an essential role in the transport of important cell nutrients and for ...cellular metabolism and pH regulation. MCTs 1-4 have been extensively studied and are involved in the proton-dependent transport of L-lactate, pyruvate, short-chain fatty acids, and monocarboxylate drugs in a wide variety of tissues. MCTs 1 and 4 are overexpressed in a number of cancers, and current investigations have focused on transporter inhibition as a novel therapeutic strategy in cancers. MCT1 has also been used in strategies aimed at enhancing drug absorption due to its high expression in the intestine. Other MCT isoforms are less well characterized, but ongoing studies indicate that MCT6 transports xenobiotics such as bumetanide, nateglinide, and probenecid, whereas MCT7 has been characterized as a transporter of ketone bodies. MCT8 and MCT10 transport thyroid hormones, and recently, MCT9 has been characterized as a carnitine efflux transporter and MCT12 as a creatine transporter. Expressed at the blood brain barrier, MCT8 mutations have been associated with an X-linked intellectual disability, known as Allan-Herndon-Dudley syndrome. Many MCT isoforms are associated with hormone, lipid, and glucose homeostasis, and recent research has focused on their potential roles in disease, with MCTs representing promising novel therapeutic targets. This review will provide a summary of the current literature focusing on the characterization, function, and regulation of the MCT family isoforms and on their roles in drug disposition and in health and disease. SIGNIFICANCE STATEMENT: The 14-member solute carrier family 16 of monocarboxylate transporters (MCTs) plays a fundamental role in maintaining intracellular concentrations of a broad range of important endogenous molecules in health and disease. MCTs 1, 2, and 4 (L-lactate transporters) are overexpressed in cancers and represent a novel therapeutic target in cancer. Recent studies have highlighted the importance of MCTs in glucose, lipid, and hormone homeostasis, including MCT8 in thyroid hormone brain uptake, MCT12 in carnitine transport, and MCT11 in type 2 diabetes.
We describe a high throughput gene expression platform based on microfluidic dynamic arrays. This system allows 2,304 simultaneous real time PCR gene expression measurements in a single chip, while ...requiring less pipetting than is required to set up a 96 well plate. We show that one can measure the expression of 45 different genes in 18 tissues with replicates in a single chip. The data have excellent concordance with conventional real time PCR and the microfluidic dynamic arrays show better reproducibility than commercial DNA microarrays.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metastases to the brain remain a significant problem in lung cancer, as treatment by most small-molecule targeted therapies is severely limited by efflux transporters at the blood-brain barrier ...(BBB). Here, we report the discovery of a selective, orally bioavailable, epidermal growth factor receptor (EGFR) inhibitor,
, that exhibits high brain penetration and potent activity in osimertinib-resistant cell lines bearing L858R/C797S and exon19del/C797S EGFR resistance mutations.
,
induced tumor regression in an intracranial patient-derived xenograft (PDX) murine model suggesting it as a potential lead for the treatment of localized and metastatic non-small-cell lung cancer (NSCLC) driven by activating mutant bearing EGFR. Overall, we demonstrate that an underrepresented functional group in medicinal chemistry, the trisubstituted hydroxylamine moiety, can be incorporated into a drug scaffold without the toxicity commonly surmised to accompany these units, all while maintaining potent biological activity and without the molecular weight creep common to drug optimization campaigns.
Aquaculture of bivalve shellfish and seaweed represents a global opportunity to simultaneously advance coastal ecosystem recovery and provide substantive benefits to humanity. To identify marine ...ecoregions with the greatest potential for development of shellfish and seaweed aquaculture to meet this opportunity, we conducted a global spatial analysis using key environmental (e.g., nutrient pollution status), socioeconomic (e.g., governance quality), and human health factors (e.g., wastewater treatment prevalence). We identify a substantial opportunity for strategic sector development, with the highest opportunity marine ecoregions for shellfish aquaculture centered on Oceania, North America, and portions of Asia, and the highest opportunity for seaweed aquaculture distributed throughout Europe, Asia, Oceania, and North and South America. This study provides insights into specific areas where governments, international development organizations, and investors should prioritize new efforts to drive changes in public policy, capacity-building, and business planning to realize the ecosystem and societal benefits of shellfish and seaweed aquaculture.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Determining actinides in urine is vital for occupational exposure monitoring and radiological emergency response because of the toxicity and radiological dose effects of actinides on human health. ...Traditional radiochemistry analytical methods used to determine actinide concentrations in urine are time-consuming (sample analysis takes several days) and are hindered by a variety of technical and instrumentation-related obstacles. A high-throughput, fully automated, precise, and accurate in-line method was developed for determining five actinides (241Am, 239Pu, 237Np, 232Th, and 238U) at ng/L levels in urine using extraction chromatography combined with quadrupole inductively coupled plasma mass spectrometry (EC-ICP-MS). In this method, the five actinides were successfully separated with the required sensitivity, peak shape, and resolution using a simplified single Eichrom TRU column with a Dionex ICS-5000 system. The separated actinides were subsequently injected into an in-line PerkinElmer (PE) NexION 300D ICP-MS for quantitative determination. The sample-to-sample run time was 23 min for automatic chemical separation and quantification using only 0.5 mL of urine. The limits of detection (LOD) obtained using this method were 0.015, 0.022, 0.039, 4.5, and 2.4 ng/L for 241Am, 239Pu, 237Np, 232Th, and 238U, respectively. The method routinely had a chemical yield of >84% as well as a linearity (R 2) coefficient of ≥0.999 for the calibrators. The method proved to be rapid, reliable, and effective for actinide quantification in urine and therefore is appropriate for radiological emergency response incidents.
Wing theory Jones, Robert T; Jones, Robert T
2014., 20140701, 1990, 2014, Letnik:
1052
eBook
Originator of many of the theories used in modern wing design, Robert T. Jones surveys the aerodynamics of wings from the early theories of lift to modern theoretical developments. This work covers ...the behavior of wings at both low and high speeds, including the range from very low Reynolds numbers to the determination of minimum drag at supersonic speed. Emphasizing analytical techniques, Wing Theory provides invaluable physical principles and insights for advanced students, professors, and aeronautical engineers, as well as for scientists involved in computational approaches to the subject. This book is based on over forty years of theoretical and practical work performed by the author and other leading researchers in the field of aerodynamics.
Originally published in 1990.
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