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排序方式: 共有339条查询结果,搜索用时 15 毫秒
301.
Bart Kesteleyn Katie Amssoms Wim Schepens Geerwin Hache Wim Verschueren Wim Van De Vreken Klara Rombauts Greet Meurs Patrick Sterkens Bart Stoops Lieven Baert Nigel Austin Jörg Wegner Chantal Masungi Inge Dierynck Stina Lundgren Daniel Jönsson Kevin Parkes Jan Willem Thuring 《Bioorganic & medicinal chemistry letters》2013,23(1):310-317
The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1–22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe–Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R3) at the para-position of the P1′ benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R1) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16–22) with EC50s on wild-type HIV-1 in the range of 0.8–1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS. 相似文献
302.
Giorgio Tamburlini Klara Yadgarova Asamidin Kamilov Alberta Bacci for the The Maternal Neonatal Care Quality Improvement Working Group 《PloS one》2013,8(10)
Background
Gaps in quality of care are seriously affecting maternal and neonatal health globally but reports of successful quality improvement cycles implemented at large scale are scanty. We report the results of a nation-wide program to improve quality of maternal and neonatal hospital care in a lower-middle income country focusing on the role played by standard-based participatory assessments.Methods
Improvements in the quality of maternal and neonatal care following an action-oriented participatory assessment of 19 areas covering the whole continuum from admission to discharge were measured after an average period of 10 months in four busy referral maternity hospitals in Uzbekistan. Information was collected by a multidisciplinary national team with international supervision through visit to hospital services, examination of medical records, direct observation of cases and interviews with staff and mothers. Scores (range 0 to 3) attributed to over 400 items and combined in average scores for each area were compared with the baseline assessment.Results
Between the first and the second assessment, all four hospitals improved their overall score by an average 0.7 points out of 3 (range 0.4 to 1), i.e. by 22%. The improvements occurred in all main areas of care and were greater in the care of normal labor and delivery (+0.9), monitoring, infection control and mother and baby friendly care (+0.8) the role of the participatory action-oriented approach in determining the observed changes was estimated crucial in 6 out of 19 areas and contributory in other 8. Ongoing implementation of referral system and new classification of neonatal deaths impede the improved process of care to be reflected in current statistics.Conclusions
Important improvements in the quality of hospital care provided to mothers and newborn babies can be achieved through a standard-based action-oriented and participatory assessment and reassessment process. 相似文献303.
Gene expression during the induction, maintenance, and release of dormancy in apical buds of poplar 总被引:2,自引:0,他引:2
Rohde A Ruttink T Hostyn V Sterck L Van Driessche K Boerjan W 《Journal of experimental botany》2007,58(15-16):4047-4060
304.
Huang S Salituro J Tang N Luk KC Hackett J Swanson P Cloherty G Mak WB Robinson J Abravaya K 《Nucleic acids research》2007,35(16):e101
Real-time PCR assays have recently been developed for diagnostic and research purposes. Signal generation in real-time PCR is achieved with probe designs that usually depend on exonuclease activity of DNA polymerase (e.g. TaqMan probe) or oligonucleotide hybridization (e.g. molecular beacon). Probe design often needs to be specifically tailored either to tolerate or to differentiate between sequence variations. The conventional probe technologies offer limited flexibility to meet these diverse requirements. Here, we introduce a novel partially double-stranded linear DNA probe design. It consists of a hybridization probe 5'-labeled with a fluorophore and a shorter quencher oligo of complementary sequence 3'-labeled with a quencher. Fluorescent signal is generated when the hybridization probe preferentially binds to amplified targets during PCR. This novel class of probe can be thermodynamically modulated by adjusting (i) the length of hybridization probe, (ii) the length of quencher oligo, (iii) the molar ratio between the two strands and (iv) signal detection temperature. As a result, pre-amplification signal, signal gain and the extent of mismatch discrimination can be reliably controlled and optimized. The applicability of this design strategy was demonstrated in the Abbott RealTime HIV-1 assay. 相似文献
305.
Klara Papouskova Michaela Moravcova Gal Masrati Nir Ben‐Tal Hana Sychrova Olga Zimmermannova 《Molecular microbiology》2021,115(1):41-57
Erv14, a conserved cargo receptor of COPII vesicles, helps the proper trafficking of many but not all transporters to the yeast plasma membrane, for example, three out of five alkali‐metal‐cation transporters in Saccharomyces cerevisiae. Among them, the Nha1 cation/proton antiporter, which participates in cell cation and pH homeostasis, is a large membrane protein (985 aa) possessing a long hydrophilic C‐terminus (552 aa) containing six conserved regions (C1–C6) with unknown function. A short Nha1 version, lacking almost the entire C‐terminus, still binds to Erv14 but does not need it to be targeted to the plasma membrane. Comparing the localization and function of ScNha1 variants shortened at its C‐terminus in cells with or without Erv14 reveals that only ScNha1 versions possessing the complete C5 region are dependent on Erv14. In addition, our broad evolutionary conservation analysis of fungal Na+/H+ antiporters identified new conserved regions in their C‐termini, and our experiments newly show C5 and other, so far unknown, regions of the C‐terminus, to be involved in the functionality and substrate specificity of ScNha1. Taken together, our results reveal that also relatively small hydrophilic parts of some yeast membrane proteins underlie their need to interact with the Erv14 cargo receptor. 相似文献
306.
Svensson Elisabeth Mor Anil Rungby Jørgen Berencsi Klara Nielsen Jens Steen Stidsen Jacob V Friborg Søren Brandslund Ivan Christiansen Jens Sandahl Beck-Nielsen Henning Toft Sørensen Henrik Thomsen Reimar W 《BMC endocrine disorders》2014,14(1):1-7
The involvement of the testis by metastatic medullary thyroid carcinoma has never been described before. We describe the first case of metastatic medullary thyroid carcinoma affecting testis and inguinal lymph nodes. A 73-year-old Caucasian man was referred to undergo urologic surgery due to a painless nodule in the right testis and an homolateral inguinal lymphoadenomegaly. The patient had a history of medullary thyroid carcinoma with relapsing disease to the spine and lung nodules. Serum calcitonin and CEA levels were 175 pg/ml and 22 ng/ml, respectively. With suspected testicular cancer, the patient underwent radical right orchiectomy with the excision biopsy of the right inguinal lymph node. Histopathology and immunohistochemistry revealed that both the lesions were due to metastases from medullary thyroid carcinoma. Metastases to the testis and inguinal lymph nodes may be due to various solid and hematological tumors. This case, despite its rarity, suggests that testis and inguinal lymph nodes should be considered as potential secondary sites of medullary thyroid carcinoma as well. 相似文献
307.
Sandsdalen Erling Haug Tor Stensvåg Klara Styrvold Olaf B. 《World journal of microbiology & biotechnology》2003,19(8):777-782
An antibacterial compound was isolated from the brown alga Fucus vesiculosus. Purification consisted of extraction of plant material with 0.05% trifluoroacetic acid, concentration on a C18 cartridge, and reverse-phase high performance liquid chromatography on a C18 semi-preparative column. The isolated compound exhibited antibacterial activity against both the Gram-positive and the Gram-negative bacteria tested. Killing studies conducted indicated that the activity was bactericidal. The compound showed no haemolytic effect against human red blood cells. Results obtained by electrospray ionization mass spectrometry indicated that the antibacterial activity was caused by a polyhydroxylated fucophlorethol. 相似文献
308.
Nitrate-Regulated Auxin Transport by NRT1.1 Defines a Mechanism for Nutrient Sensing in Plants 总被引:1,自引:0,他引:1
309.
310.
Investigating the effects of age‐related spatial structuring on the transmission of a tick‐borne virus in a colonially breeding host
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Klara M. Wanelik Sarah J. Burthe Mike P. Harris Miles A. Nunn H. Charles J. Godfray Ben C. Sheldon Angela R. McLean Sarah Wanless 《Ecology and evolution》2017,7(24):10930-10940
Higher pathogen and parasite transmission is considered a universal cost of colonial breeding due to the physical proximity of colony members. However, this has rarely been tested in natural colonies, which are structured entities, whose members interact with a subset of individuals and differ in their infection histories. We use a population of common guillemots, Uria aalge, infected by a tick‐borne virus, Great Island virus, to explore how age‐related spatial structuring can influence the infection costs borne by different members of a breeding colony. Previous work has shown that the per‐susceptible risk of infection (force of infection) is different for prebreeding (immature) and breeding (adult) guillemots which occupy different areas of the colony. We developed a mathematical model which showed that this difference in infection risk can only be maintained if mixing between these age groups is low. To estimate mixing between age groups, we recorded the movements of 63 individually recognizable, prebreeding guillemots in four different parts of a major colony in the North Sea during the breeding season. Prebreeding guillemots infrequently entered breeding areas (in only 26% of watches), though with marked differences in frequency of entry among individuals and more entries toward the end of the breeding season. Once entered, the proportion of time spent in breeding areas by prebreeding guillemots also varied between different parts of the colony. Our data and model predictions indicate low levels of age‐group mixing, limiting exposure of breeding guillemots to infection. However, they also suggest that prebreeding guillemots have the potential to play an important role in driving infection dynamics. This highlights the sensitivity of breeding colonies to changes in the behavior of their members—a subject of particular importance in the context of global environmental change. 相似文献