Miracle-dz/UniFAR-FTUs huggingface dataset:
Transdermal Delivery of Chloroquine by Amidated Pectin Hydrogel Matrix Patch in the Rat

The aim of the present study was to investigate the suitability of amidated pectin matrix patch for transdermal chloroquine delivery in an effort to mask the bitter taste when orally administered. Chloroquine has easily measurable outputs that are linked to increased renal Na+ excretion. We thus monitored urinary Na+ output in separate groups intravenously administered chloroquine or topically applied pectin hydrogel chloroquine matrix patch. Male groups of anesthetized Sprague-Dawley rats were placed on a continuous jugular infusion of 0.077 M NaCl at 150 µL min−1. After 3 h equilibration period, consecutive 20 min urine collections were made over the subsequent 4 h of 1 h control, 1 h 20 min treatment, and 1 h 40 min recovery periods for measurements of urine flow and Na+ and K+ excretion rates. The effects of intravenous chloroquine infusion or topical application of pectin hydrogel chloroquine matrix patch were examined in rats in which the drug was added to the infusate or patch applied onto the shaved area during the 1 h 20 min treatment period. The animals were switched back to the infusate alone for the final 1 h 40 min recovery period. Vehicle infused animals acted as controls. Trunk blood was collected after the treatment period from parallel groups for chloroquine measurements. The plasma chloroquine concentrations following iv chloroquine or application of pectin chloroquine hydrogel matrix patch were 9.3 ± 0.8 mg L−1 and 7.3 ± 1.1 mg L−1, respectively (n = 7 in both groups). Chloroquine infusion and pectin chloroquine patch significantly (p<0.01) increased Na+ excretion to peak values of 14.1 ± 0.9 µmol min−1, and 20.35 ± 1.0 µmol min−1, respectively by comparison with controls (9.1 ± 0.9 µmol min−1), at the corresponding period. The results suggest that the pectin chloroquine patch matrix preparation has potential applications for transdermal delivery of chloroquine and perhaps in the management of malaria.
Scots pine needle longevity and other shoot characteristics along pollution gradients

Branches of adult Scots pine (Pinus sylvestris L.) trees were sampled from boreal dry pine forests to study needle longevity, its variation and its relation to other shoot characteristics. The stands studied were located along transects from two smelters and one city, e.g. along gradients of pollution impact. Constant needle age structures were assumed and static life-tables generated. Mean needle longevity was calculated as the sum of the proportions of living needle fascicles on the successive annual shoots. It fully incorporated the information of the static life-tables and was preferred to median or maximum ages because of its significantly lower variation. The first half of the shedding span, the duration of the period when the needle survival gradually dropped from 90 to 50 %, proved to validly reflect the changes in the needle age structure. Needle longevity decreased 15-40 % towards the pollution sources along the transects studied. Near the smelters, needle longevity decreased with the increasing needle Fe, or Fe, Ni and Cu concentration that represented the main constituents of the airborne particle emissions. Near the city, needle longevity decreased with the increasing needle N and P concentrations, annual needle mass and needle mass packing and decreasing needle area packing. In the urban forests, needle Mg, P and K concentrations decreased linearly with the decreasing needle survival from the second to the fourth needle age class. Concentrations in the living needles of the fourth age class stayed over 80 % of the average for all the age classes, though needle survival dropped below 50 %. A decreasing needle Mn concentration was detected towards all the emission sources. Leaching, especially from the soil, as a possible cause was discussed. Needle longevity had the lowest variation among the shoot characteristics, which increases its value as a tool in ecological monitoring. Low plasticity in needle longevity could be an acclimation to the ambient environmental conditions and length of the growing season and to maximise the carbon gain per time. Needle longevity decreased and annual needle mass and leaf mass per area increased upwards in the crowns of mature Scots pines, reflecting the acclimation to irradiance.
Estimation of Global Wind Energy Input to the Surface Waves Based on the Scatterometer

Mechanical energy input into the ocean from the atmosphere is primarily produced via the ocean surface waves. First, the total wind generation surface wave energy is estimated as nearly 80 TW (1 TM = 1012 W), based on an empirical formulation and the wave age (β) retrieved from the Earth Remote Sensing-1/2 satellite scatterometer observations. Second, the distribution of the wind-generated surface wave energy density shows that the main input occurs in the westerlies in the Southern Hemisphere and could reach up to 3.58 W/m2 with an average value of 0.24 W/m2 in the global ocean during a seven-day period. Third, we find that the downward energy flux rate from wind to surface waves can reach around 24% in the Southern Ocean and storm tracks in the northwest Pacific and Atlantic Oceans where the wind waves dominate, but a low downward rate of around 7% in tropical oceans with an average of 11% over the global oceans is observed.
Laboratory Investigations of the Electrical Performance of Ice-covered Insulators and a Metal Oxide Surge Arrester

This review paper summarizes the main results of the laboratory investigations conducted at Tampere University of Technology (Finland) on ice-covered insulators and a metal oxide surge arrester (MOA). The most important factors affecting the dielectric strength of high voltage (HV) insulators in freezing rain conditions are the resistivity of the freezing water, the length and the number of icicles between insulator sheds and electrodes and the state of the ice deposit (i.e. how wet it is). The studies verify that most of the commercially available HV insulators may flashover even with a normal phase-to-ground ac voltage in rather light salty (or otherwise slightly contaminated), but long-duration freezing rain conditions. The ac strength of a clean insulator string under rime ice during melting period was approximately 75% of the ac strength in dry conditions. Accordingly, the ac strength of the contaminated (ESDD ap 0.3 mg/cm2 NaCl) insulator strings during the melting period of rime was on average 65% of the AC strength in dry conditions. The icing of an MOA consisting of two or more units in series may have harmful effects on the electrical performance of the MOA. With ac voltage stress an unevenly ice-coated MOA may be thermally stressed due to the leakage current transition from the ice covering of one unit to the interior of another unit not covered with so much ice. With switching impulse current surges the residual voltage across an ice-covered unit rather easily causes an external flashover. This leads to a sudden increase in the surge current: with the MOA of two units studied the current peak reached as much as twice the peak value in normal operation without ice covering.
Noise-induced slope distortion in 2-D phase unwrapping by linear estimators with application to SAR interferometry

This paper explains the underestimation of phase slope and the consequent distortion of the phase surface, observed in two-dimensional (2-D) phase unwrapping by linear estimators, like least squares methods applied to synthetic aperture radar (SAR) interferometry. These methods minimize the difference between the gradient of the unwrapped phase and the wrapped differences of the measured wrapped phase. Using the probability distributions of phase noise and phase differences for a given coherence, the probability of a phase gradient error giving rise to a nonconservative vector field is derived. It is shown that this phase gradient error has nonzero mean in the presence of phase slopes. Linear phase estimators cannot distinguish the mean phase gradient error from a true phase slope; hence, the unwrapped phase shows a slope bias. This bias is quantified as a function of coherence and the number of independent samples that are averaged. The theoretical results are confirmed by simulations.
A New Decision Rule for Lateral Transshipments in Inventory Systems

This paper deals with a single-echelon inventory system consisting of a number of parallel local warehouses facing compound Poisson demand. There are standard holding and backorder costs as well as ordering costs at all warehouses. Normally, the warehouses replenish from an outside supplier. However, lateral transshipments between the warehouses are also possible. Such transshipments take no time but incur additional costs. When a demand occurs at a warehouse, the question is whether the whole demand or part of it should be covered by a lateral transshipment from another warehouse. Given a set of alternative decisions, our decision rule minimizes the expected costs under the assumption that no further transshipments will take place. This rule is then used repeatedly as a heuristic. A simulation study illustrates how the suggested technique performs under different conditions.
Model for Selecting Project Members to Minimize Project Uncertainties

ABSTRACT Project risks come mainly from the future uncertainties, and new product and service development projects possess the most uncertainty and therefore the highest risk. However, if the project team has gained experiences from previous similar projects, the risk to the project drastically declines. In other words, an inverse correlation exists between member experiences and project risk. Therefore, the guiding principle would be to assign an experienced member to execute familiar work for that member. This study aims to establish a mathematical model that uses member experience to minimize project uncertainty. The nonlinear model assigns members with different experiences to the most suitable tasks to minimize project risk, and thus maximize project success rates under constraints of project costs and communication complexities. An experimental case is used to demonstrate the applicability of the proposed model, and results indicated that under cost and communication complexity constraints, project uncertainty can truly be minimized by allocating an adequate member to the suitable task.
VNCOP-B plus rituximab in the treatment of diffuse large B-cell lymphoma in the elderly

The conventional treatment included CHOP and several age-adapted regimens, from first to third generation, designed and tested for their feasibility and efficacy in elderly patients. Recently, some trials demonstrated that CHOP-rituximab was superior to CHOP alone. Between February 2003 and November 2005, 24 untreated patients 60 years and older with DLBCL were treated with a combination therapy including cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (VNCOP-B) plus four rituximab administrations. Nineteen of the 24 patients (80%) obtained a CR, four achieved a PR, and the remaining patient had a disease progression. The overall response rate was 96%. Sixteen of the 19 complete responders remain in continuous CR at a median of 24 months (range 12 – 42). Three CRs relapsed within 12 months from the completion of treatment. Clinical and hematological toxicity was moderate. This regimen was effective in inducing a good remission rate with moderate toxic effects in elderly DLBCL patients.
Initial evaluation of the Consent Support Tool: A structured procedure to facilitate the inclusion and engagement of people with aphasia in the informed consent process

Abstract This study evaluated the Consent Support Tool (CST), a procedure developed to identify the optimum format in which to present research information to people with different severities of aphasia, in order to support their understanding during the informed consent process. Participants were a convenience sample of 13 people with aphasia who had mixed comprehension ability. The CST was used to profile each participant's language ability and identify an information format that should maximize her/his understanding. Next, participants were shown information presented in three formats: standard text and two ‘aphasia-friendly’ versions providing different levels of support. Participants’ understanding of the information was measured for each format. The format recommended by the CST was compared with the format observed to maximize understanding for each participant. The CST accurately predicted the optimum format for 11/13 participants and differentiated people who could understand fully with support from those who could not in 12/13 cases. All participants interviewed (10/10) found the adapted formats helpful and 9/10 preferred them to the standard version. These findings suggest that the CST could usefully support researchers to determine whether a person with aphasia is likely to be able to provide informed consent, and which information format will maximize that individual's understanding. The CST and different information formats are available as Supplementary Appendices to be found online at http://www.informahealthcare. com/doi/abs/10.3109/17549507.2013. 795999.
Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

BACKGROUND the role of autologous stem cell transplantation (ASCT) in treatment of acute myeloid leukemia (AML) remains unsettled. AIMS retrospective analysis to evaluate the role of ASCT in patients with AML without HLA-matched donor. METHODS between December 19, 1994 and August 1, 2012, a total of 63 patients with AML without HLA-matched donor in the department of Hematology and Transfusion Medicine, University Hospital, Bratislava, received an ASCT. Median age was 41 years (20-61 years). There were 35 (56%) males and 28 (44%) females. At the time of ASCT, 50 (79%) patients were in first complete remission (CR), 11 (18%) patients were in second CR and 2 (3%) patients were in relapse. RESULTS with a median follow-up of 115 months (34-214 months), the 10 year overall survival (OS) and disease free survival (DFS) of all patients was 55% and 51%, respectively. Transplant-related mortality was 6%. The relapse rate was 38% and 9 years probability of relapse was 44%. CONCLUSION ASCT is still an effective post-remission treatment in AML patients without HLA-matched donor; with the possibility of long-term survival or even cure in remarkable proportion of patients with AML, particularly in patients with favorable and intermediate cytogenetic risk.
Depression and the risk of severe infections: prospective analyses on a nationwide representative sample.

BACKGROUND Preliminary research suggests an association between depression and subsequent increased risk of infections, yet little is known on this topic. This study investigated the association between depression and risk of various types of infections, including temporal and dose-response relationships. METHODS A prospective population-based study including 976,398 individuals, of whom 142,169 had a history of depression between 1995 and 2012, was conducted using linked Danish registries. Survival analyses were used to estimate the relative risk of infections among those with depression, compared with those without depression, while adjusting for gender and age. RESULTS Depression was associated with increased risk of a wide range of infections [incidence rate ratio (IRR) = 1.61, 95% confidence interval (CI) = 1.49-1.74, P = 0.000, for any infection]. There was no evidence of a specific temporal effect but rather a general increased risk of infection subsequent to the onset of depression, as the risk during first year (IRR = 1.67, 95% CI = 1.25-2.22, P = 0.000) remained elevated for the ensuing 11 years and beyond (IRR = 1.61, 95% CI = 1.39-1.85, P = 0.000). Dose-response analyses revealed that the risk of infection increased by 59% (IRR = 1.59, 95% CI = 1.45-1.75, P = 0.000) following a single depressive episode and was elevated even further (IRR = 1.97, 95% CI = 0.92-4.22, P = 0.082) following four or more depressive episodes. However, results did not indicate a perfect linear association. CONCLUSIONS Findings suggest the presence of depression may confer an increased risk of infection and that this increased susceptibility is not confined to a specific time period following the onset of depression. A dose-response relationship may be present, but more research is needed to further examine and confirm a link between depression and risk of infection.
Long-Term Outcomes of Pediatric Ischemic Stroke in Adulthood

This population-based study assesses the long-term impact of childhood stroke on function and independence in young adults. We undertook a cross-sectional outcome study of patients with arterial ischemic stroke and cerebral sinovenous thrombosis, beyond 18 years of age. We studied 26 patients; 21 arterial stroke, 5 cerebral sinovenous thrombosis, with 16 females. Mean age at assessment was 21.5 years, and mean follow-up time was 10.8 years. According to the modified Rankin Scale, final outcomes were 37% normal, 42% mild, 8% moderate, and 15% severe deficits. Risk factors for abnormal functional outcome included arterial ischemic stroke, presence of arteriopathy, and 1-year poststroke Pediatric Stroke Outcome Measure score ≥ 2 (P < .05). Most (77-84%) were independent in driving, relationships, and employment. Functional status at 1 year poststroke strongly predicts long-term outcome. Mental illness in one-quarter of young adults surviving childhood stroke represents an important direction for research.
Disruption of Bcr-Abl Coiled Coil Oligomerization by Design*

Oligomerization is an important regulatory mechanism for many proteins, including oncoproteins and other pathogenic proteins. The oncoprotein Bcr-Abl relies on oligomerization via its coiled coil domain for its kinase activity, suggesting that a designed coiled coil domain with enhanced binding to Bcr-Abl and reduced self-oligomerization would be therapeutically useful. Key mutations in the coiled coil domain of Bcr-Abl were identified that reduce homo-oligomerization through intermolecular charge-charge repulsion yet increase interaction with the Bcr-Abl coiled coil through additional salt bridges, resulting in an enhanced ability to disrupt the oligomeric state of Bcr-Abl. The mutations were modeled computationally to optimize the design. Assays performed in vitro confirmed the validity and functionality of the optimal mutations, which were found to exhibit reduced homo-oligomerization and increased binding to the Bcr-Abl coiled coil domain. Introduction of the mutant coiled coil into K562 cells resulted in decreased phosphorylation of Bcr-Abl, reduced cell proliferation, and increased caspase-3/7 activity and DNA segmentation. Importantly, the mutant coiled coil domain was more efficacious than the wild type in all experiments performed. The improved inhibition of Bcr-Abl through oligomeric disruption resulting from this modified coiled coil domain represents a viable alternative to small molecule inhibitors for therapeutic intervention.
Modified TIME-H: a simplified scoring system for chronic wound management.

OBJECTIVE Chronic wound assessment requires a systematic approach in order to guide management and improve prognostication. Following a pilot study using the original TIME-H scoring system in chronic wound management, modifications were suggested leading to the development of the Modified TIME-H scoring system. This study investigates the feasibility and reliability of chronic wound prognostication applying the Modified TIME-H score. METHOD Patients referred to the hospital's outpatient wound clinic over a 9-month period were categorised into one of three predicted outcome categories based on their Modified TIME-H score. RESULTS This study shows a higher proportion of patients in the certain healing category achieved healed wounds, with a higher rate of reduction in wound size, when compared with the other categories. The three categories defined in this study are certain healing, uncertain healing and difficult healing. CONCLUSION The Modified TIME-H score could be a useful tool for assessment, patient-centred management and prognostication of chronic wounds in clinical practice and requires further validation from other institutions. DECLARATION OF INTEREST The authors have no conflict of interest to declare.
A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins.