Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
4,988
result(s) for
"Rainer, M."
Sort by:
ثورة المجر 1956 : يوميات الثورة \مذكرات طفل\
قلما نجد طفلا لم يتجاوز الثانية عشرة من عمره يفطن إلى الأهمية التاريخية والسياسية لثورة ما تجري رحاها وأحداثها في بلاده. فيسجل بقلمه البريء وبعين طفولية -بيد أنها فريدة ومتميزة-كل الأحداث الحقيقية لهذه الثورة من صياغة هذا الطفل - نقا عما رآه بأم عينيه، ومما سمعه من أبويه وجيرانه ومحطات الراديو، ومن حواره مع صديقه، ومما قرأه على صفحات الجرائد وقتها. من كل هذا-تشكلت صورة لها خصوصيتها لم يرها أحد من قبل عن هذه الثورة. ظلت هذه اليوميات رهينة الأدراج قرابة الخمسين عاما لم تر النور، فقد كتبها صاحبها الطفل جولا تشتش عام 1956، لكنها لم تنشر ولم يرها أحد قبل عام 2006. ويعد هذا الكتاب أول ترجمة عربية لهذه اليوميات.
BOOK
The BACE‐1 inhibitor CNP520 for prevention trials in Alzheimer's disease
The beta‐site amyloid precursor protein cleaving enzyme‐1 (BACE‐1) initiates the generation of amyloid‐β (Aβ), and the amyloid cascade leading to amyloid plaque deposition, neurodegeneration, and dementia in Alzheimer's disease (AD). Clinical failures of anti‐Aβ therapies in dementia stages suggest that treatment has to start in the early, asymptomatic disease states. The BACE‐1 inhibitor CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Aβ in rats and dogs, and Aβ plaque deposition in APP‐transgenic mice. Animal toxicology studies of CNP520 demonstrated sufficient safety margins, with no signs of hair depigmentation, retina degeneration, liver toxicity, or cardiovascular effects. In healthy adults ≥ 60 years old, treatment with CNP520 was safe and well tolerated and resulted in robust and dose‐dependent Aβ reduction in the cerebrospinal fluid. Thus, long‐term, pivotal studies with CNP520 have been initiated in the Generation Program.
Synopsis
Alzheimer's disease (AD) is a chronic neurodegenerative disorder with increasing incidence in the aging societies, but without any disease‐modifying treatment. Deposition of toxic forms of the protein Aβ in the brain is pathologic. Treatment with a BACE‐1 inhibitor may prevent Aβ deposition.
Recent BACE inhibitor clinical trials in patients at early or mild‐to‐moderate disease stage have failed, indicating that treatment needs to start earlier, before the onset of clinical symptoms.
BACE inhibitor CNP520 was designed to meet the requirements of prevention treatment.
CNP520 in preclinical models showed acute and chronic Aβ reduction, and a favorable safety profile.
CNP520 is safe and well tolerated in humans, and dose‐dependently reduced Aβ in cerebrospinal fluid.
Prevention studies Generation I and II are underway in patients at enhanced risk to develop symptoms of AD.
Graphical Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disorder with increasing incidence in the aging societies, but without any disease‐modifying treatment. Deposition of toxic forms of the protein Aβ in the brain is pathologic. Treatment with a BACE‐1 inhibitor may prevent Aβ deposition.
Journal Article
Characteristics of colored dissolved organic matter (CDOM) in the Arctic outflow in the Fram Strait: Assessing the changes and fate of terrigenous CDOM in the Arctic Ocean
Absorption coefficients of colored dissolved organic matter (CDOM) were measured together with salinity, δ18O, and inorganic nutrients across the Fram Strait. A pronounced CDOM absorption maximum between 30 and 120 m depth was associated with river and sea ice brine enriched water, characteristic of the Arctic mixed layer and upper halocline waters in the East Greenland Current (EGC). The lowest CDOM concentrations were found in the Atlantic inflow. We show that the salinity‐CDOM relationship is not suitable for evaluating conservative mixing of CDOM. The strong correlation between meteoric water and CDOM is indicative of the riverine/terrigenous origin of CDOM in the EGC. Based on CDOM absorption in Polar Water and comparison with an Arctic river discharge weighted mean, we estimate that a 49–59% integrated loss of CDOM absorption across 250–600 nm has occurred. A preferential removal of absorption at longer wavelengths reflects the loss of high molecular weight material. In contrast, CDOM fluxes through the Fram Strait using September velocity fields from a high‐resolution ocean–sea ice model indicate that the net southward transport of terrigenous CDOM through the Fram Strait equals up to 50% of the total riverine CDOM input; this suggests that the Fram Strait export is a major sink of CDOM. These contrasting results indicate that we have to constrain the (C)DOM budgets for the Arctic Ocean much better and examine uncertainties related to using tracers to assess conservative mixing in polar waters. Key Points Terrigenous CDOM absorption loss is significant within Arctic Ocean Export of CDOM through Fram Strait could be up to 50% of inputs Results imply that terms in the CDOM budget need to be better constrained
Journal Article
The use of PARAFAC modeling to trace terrestrial dissolved organic matter and fingerprint water masses in coastal Canadian Arctic surface waters
The optical properties of chromophoric dissolved organic matter (CDOM) were investigated in the Canadian Archipelago and coastal Beaufort Sea surface waters using fluorescence spectroscopy coupled with parallel factor analysis (PARAFAC). Environmental dynamics of individual components were evaluated and compared to salinity, in situ fluorescence, absorption at 312 nm (a312), dissolved organic carbon, and lignin phenol concentrations. A positive linear relationship between four fluorescent components and lignin phenols suggests a terrestrial origin, whereas two components were unrelated to a river source, suggesting an autochthonous source. Elevated concentrations of terrestrial components were observed in the Mackenzie River plume near the coast of Alaska and decreased as water was transported to the Canadian Archipelago. The two nonterrestrial components exhibited only background levels in concentrations along the transect, suggesting minimal productivity within plume and archipelago surface waters. The relative abundance of terrestrial components in relation to nonterrestrial components allowed us to distinguish water masses including Atlantic, Archipelago, and Mackenzie River plume, respectively. This study illustrates the usefulness of PARAFAC to fingerprint water masses based on the optical characteristics of CDOM and shows promise to improve our understanding of upper Arctic Ocean ventilation.
Journal Article
Adaptive compliant structures for flow regulation
This paper introduces conceptual design principles for a novel class of adaptive structures that provide both flow regulation and control. While of general applicability, these design principles, which revolve around the idea of using the instabilities and elastically nonlinear behaviour of post-buckled panels, are exemplified through a case study: the design of a shape-adaptive air inlet. The inlet comprises a deformable post-buckled member that changes shape depending on the pressure field applied by the surrounding fluid, thereby regulating the inlet aperture. By tailoring the stress field in the post-buckled state and the geometry of the initial, stress-free configuration, the deformable section can snap through to close or open the inlet completely. Owing to its inherent ability to change shape in response to external stimuli—i.e. the aerodynamic loads imposed by different operating conditions—the inlet does not have to rely on linkages and mechanisms for actuation, unlike conventional flow-controlling devices.
Journal Article
Origins and transformations of dissolved organic matter in large Arctic rivers
Arctic river watersheds are important components of the global climate system and show an amplified response to climate change. Here, we characterize origins and transformations of dissolved organic matter (DOM) in five major Arctic rivers (Kolyma, Lena, Yenisei, Ob, Mackenzie) over 3 years with seasonal sampling periods using measurements of carbohydrates, amino acids, bacterial biomarkers (D-amino acids), and plant protein biomarkers (hydroxyproline). A strong seasonal cycle of bioavailable DOM export was observed that correlated with discharge, vegetation, river morphology and water residence time. The chemical composition of bioavailable DOM was different among rivers reflecting unique characteristics of Arctic river watersheds. Trends in specific bacterial biomarkers were synchronous to changes in bacterial community compositions demonstrating that bacterial communities responded to the seasonal shifts in organic matter quality and chemical composition. Extensive heterotrophic processing of plant and soil-derived DOM resulted in major inputs of bacterial detritus, and bacterial organic matter accounted for 21–42% of DOC in all watersheds. Dissolved organic nitrogen sources were dominated by bacterially-derived nitrogen and important contributions of soluble plant protein during the Spring freshet. Overall, our results demonstrated the importance of watershed characteristics and bacterial metabolism in regulating DOM composition, reactivity and carbon fluxes in Arctic river watersheds.
Journal Article
Body mass index may predict the response to ipilimumab in metastatic melanoma: An observational multi-centre study
Immunotherapy is a well-established treatment option in patients with metastatic melanoma. However, biomarkers that can be used to predict a response in these patients have not yet been found, putting patients at risk of severe side effects.
In this retrospective analysis, we investigated the association between the body mass index and ipilimumab treatment response in patients with metastatic melanoma. Patients with metastatic melanoma who received a monotherapy of up to 4 doses of ipilimumab (3 mg/kg) every 3 weeks from 2011 to 2014 in three major hospitals in Austria were included. Patients were classified into two groups: normal group (BMI<25) and overweight group (BMI≥25).
40 patients had a normal BMI, and 36 had a BMI above normal. Patients with a BMI that was above normal showed significantly higher response rates (p = 0.024, χ2), and lower likelihood of brain metastases (p = 0.012, χ2). No differences were found between both groups with respect to gender (p = 0.324, χ2), T-stage (p = 0.197, χ2), or the occurrence of side effects (p = 0.646, χ2). Patients with a BMI above normal showed a trend towards longer overall survival (p = 0.056, Log-Rank), but no difference was found regarding progression-free survival (p = 0.924, Log-Rank).
The BMI correlated with the response to ipilimumab treatment in a cohort of metastatic melanoma patients.
Journal Article
Pan-Arctic distributions of continental runoff in the Arctic Ocean
Continental runoff is a major source of freshwater, nutrients and terrigenous material to the Arctic Ocean. As such, it influences water column stratification, light attenuation, surface heating, gas exchange, biological productivity and carbon sequestration. Increasing river discharge and thawing permafrost suggest that the impacts of continental runoff on these processes are changing. Here, a new optical proxy was developed and implemented with remote sensing to determine the first pan-Arctic distribution of terrigenous dissolved organic matter (tDOM) and continental runoff in the surface Arctic Ocean. Retrospective analyses revealed connections between the routing of North American runoff and the recent freshening of the Canada Basin and indicated a correspondence between climate-driven changes in river discharge and tDOM inventories in the Kara Sea. By facilitating the real-time, synoptic monitoring of tDOM and freshwater runoff in surface polar waters, this novel approach will help understand the manifestations of climate change in this remote region.
Journal Article
Role of cochlear reserve in adults with cochlear implants following post-lingual hearing loss
Introduction
Pre-operative assessments before cochlear implantation (CI) includes the examination of both tone hearing, and the level of the cochlear reserve indicated by speech understanding. The goal of this study was to explore the predictive influence of tone hearing and cochlear reserve in CI.
Methods
We did a retrospective cohort study, which included adult patients who had undergone CI between January 2012 and December 2019 in a tertiary care center. The pre-operative tone hearing, unaided maximum monosyllabic word recognition score (WRSmax), aided hearing gain, aided monosyllabic word recognition score at 65 dB (WRS65(HA)), and speech perception gap (SPG) were measured. The duration of unaided hearing loss (UHL) was also assessed. These variables were compared with post-operative monosyllabic word recognition score after CI at 65 dB (WRS65(CI)).
Results
103 patients and 128 ears were included in this study. Regardless of tone hearing, patients with better pre-operative WRSmax and WRS65(HA) performed better post-operatively. WRSmax was found to be the most important factor that was statistically significantly associated with WRS65(CI). SPG was statistically significantly associated with WRSmax and SPG ≥ 20% group performed better post-operatively. Any duration of unaided hearing loss was statistically significantly inversely associated with WRSmax above 0%.
Conclusion
Cochlear reserve represented by WRSmax may play the most important role as a predictive factor in outcomes after CI. SPG should be considered for indicating CI in patients, when WRS65(HA) does not reach WRSmax. Early rehabilitation with hearing aids and duration of hearing aid usage might play an important role in preserving cochlear reserve in adults.
Journal Article
Circumpolar synchrony in big river bacterioplankton
Natural bacterial communities are extremely diverse and highly dynamic, but evidence is mounting that the compositions of these communities follow predictable temporal patterns. We investigated these patterns with a 3-year, circumpolar study of bacterioplankton communities in the six largest rivers of the pan-arctic watershed (Ob', Yenisey, Lena, Kolyma, Yukon, and Mackenzie), five of which are among Earth's 25 largest rivers. Communities in the six rivers shifted synchronously over time, correlating with seasonal shifts in hydrology and biogeochemistry and clustering into three groups: winter/spring, spring freshet, and summer/fall. This synchrony indicates that hemisphere-scale variation in seasonal climate sets the pace of variation in microbial diversity. Moreover, these seasonal communities reassembled each year in all six rivers, suggesting a long-term, predictable succession in the composition of big river bacterioplankton communities.
Journal Article