Miracle-dz/UniFAR-FTUs huggingface dataset:
Methylene blue protects primary rat retinal ganglion cells from cellular senescence.

PURPOSE Glaucoma is a progressive optic neuropathy characterized by loss of retinal ganglion cells (RGCs) and optic nerve degradation. Existing treatments focus on lowering IOP; however, vision loss may still progress. Neuroprotective drugs may be useful as an adjunct approach to prevent further loss of RGCs, although efficacious drugs are lacking. One agent, methylene blue, protects neurons during several neurodegenerative models. Methylene blue potentiates the electron transport chain by shuttling elections from NADH and FADH2 to coenzyme Q (CoQ) and cytochrome c. The purpose of this study was to determine if methylene blue could protect RGCs from noxious stimuli. METHODS Primary rat RGCs were isolated and cultured following a sequential immunopanning technique using P3-P7 Sprague-Dawley rats. Approximately 25,000 RGCs were seeded per coverslip and cultured for 3 days before testing. The RGCs were treated for 24 hours with rotenone or staurosporine or for 72 hours of hypoxia. Methylene blue was then assessed for protection of RGCs during each of these insults. Cell viability was measured using calcein Am and ethidium homodimer-1. Cytochrome c oxidase activity was measured using a cytochrome c oxidase assay kit to monitor the health of mitochondria. RESULTS Methylene blue (1 μM and 10 μM) significantly protected RGCs against 24 hours of 1 μM rotenone. Methylene blue (1 μM and 10 μM) significantly protected RGCs against 24 hours of treatment with 1 μM staurosporine and protected RGCs against 72 hours of hypoxia. Methylene blue increased cytochrome c oxidase activity in the presence of hydrogen peroxide. CONCLUSIONS Methylene blue is a neuroprotective compound that can protect RGCs from toxic insults. Methylene blue's ability to increase cytochrome c oxidase and protect RGCs against these noxious stimuli supports its suggested mechanism of action, which is to preserve the electron transport chain. Further testing is needed to determine if methylene blue would be an efficacious treatment for the protection of neurodegeneration that occurs during optic neuropathy.
Functional Characterization of N297A, A Murine Surrogate for low-Fc Binding Anti-Human CD3 Antibodies

Several low- or non-FcR binding anti-human CD3 monoclonal antibodies have been under investigation for the treatment of autoimmune diseases. To model the mechanism of action of these anti-human CD3 mAbs in the murine system, an Fc-modified anti-mouse CD3 antibody (N297A) was generated. N297A exhibited similar biological effects as Fc-modified anti-human CD3 antibodies including rapid, reversible reduction in peripheral leukocyte numbers, differential modulation of activated versus resting T cells, and reduced levels of induced cytokine release compared to the non-Fc-modified parent antibody. In an in vivo model of colitis induced by adoptive transfer of IL–10-deficient cells, administration of N297A significantly reduced body weight loss. As N297A shared many functional characteristics of non-FcR binding anti-human CD3 mAbs both in vitro and in vivo, it provides a means to model the mechanisms of action of Fc-modified anti-human CD3 antibodies in mouse.
Rickettsial Agents in Slovakian Ticks (Acarina, Ixodidae) and Their Ability to Grow in Vero and L929 Cell Lines

A total of 80 adult ticks (55 Haemaphysalis inermis, 12 Dermacentor reticulatus, 11 D. marginatus, 2 Ixodes ricinus) were collected from vegetation in three areas of Slovakia (forest and pasture habitat) in central Europe. Forty‐six (46 ticks) (57.5%) of all species tested were positive by the hemocyte test, PCR assays based on the gltA and ompA genes showed a Rickettsiaceae infection in 77.5% of the ticks, whereas only one H. inermis tick was positive for Anaplasmataceae on a 16S rRNA‐based PCR. Isolation of rickettsiae was attempted on all collected ticks by means of the shell vial technique, 52 isolates of which were inoculated into Vero cells and 28 into L929 cells. Rickettsiae were detected in 50% (40/80) of the cell lines using the Gimenez staining method, whereas 33.8% (27/80) of the cell lines were PCR‐positive for Rickettsia species. The presence of rickettsiae was shown by PCR to be around 30.8% (16/52) in Vero and 39.3% (11/28) in L929 cell lines. Sequencing results showed that detected infections were Rickettsia sp. , R. raoultii, and Anaplasma phagocytophilum in ticks, and R. slovaca in cell lines. This is the first report of R. raoultii in Slovakia. Observations by electron microscopy of the R. slovaca isolate from Vero cell lines showed a microcapsular layer, typical Gram‐negative cell wall, and a cytoplasmic membrane.
Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans.

BACKGROUND Renal hypodysplasia, characterized by a decrease in nephron number, small overall kidney size, and maldeveloped renal tissue, is a leading cause of chronic renal failure in young children. Familial clustering and renal hypodysplasia phenotypes observed in transgenic animal models suggest a genetic contribution. Uroplakin IIIa (encoded by UPIIIA) is an integral membrane protein present in urothelial plaques, and the murine UPIIIa knockout is associated with urothelial anomalies and vesicoureteral reflux. De novo UPIIIA mutations recently were identified in 4 of 17 patients with severe bilateral renal adysplasia. METHODS To evaluate the overall role of UPIIIA in human renal hypodysplasia pathogenesis, we performed UPIIIA mutation analysis in a cohort of 170 pediatric patients affected by severe unilateral or bilateral renal hypodysplasia. Eighty-one patients were affected by bilateral nonobstructive renal hypodysplasia; of these, 61 were without vesicoureteral reflux. Eighty-four patients presented with unilateral nonobstructive renal hypodysplasia, including 24 patients with unilateral multicystic dysplastic kidneys. Family history was positive in 11%. RESULTS Mutation analysis showed 2 heterozygous mutations not observed in 200 race-matched control chromosomes. In only 1 family was distribution of the UPIIIA mutation consistent with a disease-causing effect. This de novo missense mutation (Gly202Asp) was identified in a patient with unilateral multicystic dysplastic kidneys. The second (intronically located) mutation appeared unlikely to be disease causing because it did not segregate with an obvious disease phenotype in the affected family. CONCLUSION Our results indicate that de novo mutations in UPIIIA can be involved in defective early kidney development, but probably constitute only a rare cause of human renal hypodysplasia in a minor subset of individuals.
Upper bounds in quantum dynamics

Of course, the case of main interest is where H is given by L2(Rd) or ? 2(Zd), H is a Schr? dinger operator of the form ? A + V, and ip(0) is a localized wavepacket. Under the time evolution (1), the wavepacket i? )(t) will in general spread out with time. Finding quantitative bounds for this spreading in concrete cases and developing methods for proving such bounds has been the objective of a great number of papers in recent years. One is often interested in the growth behavior of the moments of the position operator, that is, the function 11? |||X|p/2^(i)||2. These questions are particularly complicated and interesting in situations where singular continuous spectra occur. The discovery of the occurrence of such spectra for many models of physical relevance has triggered some activity on the quantum dynamical side. For models with absolutely continuous spectra, on the other hand, quantum dynamical questions have been investigated much earlier in the context of scattering theory and have been answered to a great degree of satisfaction. Models with point spectrum, or more restrictively, models exhibiting Anderson localization, have also been investigated from a quantum dynamical point of view. While it is not true in general that spectral localization implies dynamical localization [26, 73], it has been shown that the three main approaches to spectral localization, the fractional moment method [3, 4, 5], multi-scale analysis [28, 27, 75], and the Bourgain-Goldstein-Schlag method [12, 37], yield dynamical localization as a by product [2, 13, 22, 31, 34]. Quantum dynamics for Schr? dinger operators with singular continuous spectra is much less understood. The two primary examples motivated by physics are the Harper model, also known as the almost Mathieu operator at critical cou pling, which describes a Bloch electron in a constant magnetic field with irrational flux through a unit cell, and the Fibonacci model, which describes a standard one-dimensional quasicrystal. Both models have been studied heavily in both the physics and mathematics communities.
Securing Abstention in an Electronic Legislature

The reasons for developing an electronic legislature (e-legislature) include: an improved legislature, increasing the constituent's access to the legislator, improving participation in government and providing our goverment with a mobile distributed legislature that will be able to continue to meet even in the face of some drastic activity like terrorism. The essence of a legislature is political and consequently its members will certainly act in such a way. Thus one must assume that legislators would take advantage of the lack of physical presence in a legislature if it was not secured. In [IFIP TC6/TC11 Joint Working Conference on Communications and Multimedia Security (CMS'99)], [Verifiable democracy a protocol to secure an Perspectives] an electronic legislation scheme was proposed that secured the government from malicious behavior of legislators. The protocol described in [IFIP TC6/TC11 Joint Working Conference on Communications and Multimedia Security (CMS'99)], [Verifiable democracy a protocol to secure an Perspectives] provided only minimal legislative voting options, to create a realistic e-legislature one must support all likely functions. Most legislatures allow their members to abstain. The process of introducing abstention into an e-legislature can be formative especially in the case when the legislature passes statutes by simple majority. Here we discuss how to secure an e-legislature which supports abstention.
Highly sensitive piezoelectric micromachined ultrasonic transducer (pMUT) operated in air

Piezoelectric micromachined ultrasonic transducer (pMUT) gains increasing interests from researchers. It overcomes the inherent shortcomings of conventional bulk ultrasonic transducers such as acoustic impedance mismatching. In addition, pMUT does not require the extremely large input voltage as capacitive micromachined ultrasonic transducer (cMUT), which is potential to be integrated into portable electronics. The lead zirconate titanate (PZT) based pMUT has the best performance. Leveraging on our newly developed pulse poling process, the morphotropic phase boundary composition PZT (MPB-PZT) thin film is of high piezoelectric constant (d31=105pm/V) and low dielectric loss (~0.06). Benefited from such high performance PZT thin film and optimized design, the fabricated pMUT (500×300μm) achieves a displacement sensitivity of 807nm/V at its resonant frequency (482kHz) without DC offset. Compared to previously reported PZT pMUTs, even the dimension is much smaller; the sensitivity is still superior to them. The in-air transmitting performance is evaluated as well. A single pMUT element is able to generate 63.7dB sound pressure level (SPL) at 10 mm in air with only 2V input. The low input voltage not only provides low power consumption, but also prevents the unwanted PZT repolarization. The proposed highly sensitive pMUT shows its promise for integration with portable electronics.
A scoping literature review of collaboration between primary care and public health

Aim The purpose of this scoping literature review was to determine what is known about: 1) structures and processes required to build successful collaborations between primary care (PC) and public health (PH); 2) outcomes of such collaborations; and 3) markers of their success. Background Collaboration between PC and PH is believed to enable more effective individual and population services than what might be achieved by either alone. Methods The study followed established methods for a scoping literature review and was guided by a framework that identifies systemic, organizational and interactional determinants for collaboration. The review was restricted to articles published between 1988 and 2008. Published quantitative and qualitative primary studies, evaluation research, systematic and other types of reviews, as well as descriptive accounts without an explicit research design, were included if they addressed either the structures or processes to build collaboration or the outcomes or markers of such collaboration, and were published in English. Findings The combined search strategy yielded 6125 articles of which 114 were included. Systemic-level factors influencing collaboration included: government involvement, policy and fit with local needs; funding and resource factors, power and control issues; and education and training. Lack of a common agenda; knowledge and resource limitations; leadership, management and accountability issues; geographic proximity of partners; and shared protocols, tools and information sharing were influential at the organizational level. Interpersonal factors included having a shared purpose; philosophy and beliefs; clear roles and positive relationships; and effective communication and decision-making strategies. Reported benefits of collaboration included: improved chronic disease management; communicable disease control; and maternal child health. More research is needed to explore the conditions and contexts in which collaboration between PC and PH makes most sense and potential gains outweigh the associated risks and costs.
An Enhanced Analytical Framework Integrating aspects of Network and Application performance, Psychology, and Content in QoE Assessment for Web browsing

—Evaluation of Quality of Experience (QoE) for web browsing is a challenging topic as it involves many different factors related to human as well as technical issues. To understand such a large number of human and technical metrics is both difficult and tricky. Two main objectives of the research presented in this paper are to propose and develop a new QoE assessment approach based on a comprehensive set of key metrics for web browsing. The paper starts by evaluating each metric related to users’ score before integrating them all into the assessment. Then, the proposed QoE assessment of Web based services uses a comprehensive set of metrics in order to construct a full and detailed understanding of users’ experiences in a web based service environment. Finally, the paper presents an investigation into the applicability of a mixed effect model for prediction of QoE based on the proposed set of metrics. The analysis of objective factors and Psychological Support of Content is presented with an emphasis on fixed and random effects. The analysis and validation of QoE assessment of Web based traffic using both objective parameters from networking, application, and content perspectives have shown the efficacy of the proposed assessment. The paper aims at getting better understanding of how users experience web browsing by applying a comprehensive set of metrics which has been computed to determine the overall web user QoE.
Gene movement and genetic association with regional climate gradients in California valley oak (Quercus lobata Née) in the face of climate change

Rapid climate change jeopardizes tree populations by shifting current climate zones. To avoid extinction, tree populations must tolerate, adapt, or migrate. Here we investigate geographic patterns of genetic variation in valley oak, Quercus lobata Née, to assess how underlying genetic structure of populations might influence this species’ ability to survive climate change. First, to understand how genetic lineages shape spatial genetic patterns, we examine historical patterns of colonization. Second, we examine the correlation between multivariate nuclear genetic variation and climatic variation. Third, to illustrate how geographic genetic variation could interact with regional patterns of 21st Century climate change, we produce region‐specific bioclimatic distributions of valley oak using Maximum Entropy (MAXENT) models based on downscaled historical (1971–2000) and future (2070–2100) climate grids. Future climatologies are based on a moderate‐high (A2) carbon emission scenario and two different global climate models. Chloroplast markers indicate historical range‐wide connectivity via colonization, especially in the north. Multivariate nuclear genotypes show a strong association with climate variation that provides opportunity for local adaptation to the conditions within their climatic envelope. Comparison of regional current and projected patterns of climate suitability indicates that valley oaks grow in distinctly different climate conditions in different parts of their range. Our models predict widely different regional outcomes from local displacement of a few kilometres to hundreds of kilometres. We conclude that the relative importance of migration, adaptation, and tolerance are likely to vary widely for populations among regions, and that late 21st Century conditions could lead to regional extinctions.
Regulation of SpeB in Streptococcus pyogenes by pH and NaCl: a Model for In Vivo Gene Expression

ABSTRACT For a pathogen such as Streptococcus pyogenes, ecological success is determined by its ability to sense the environment and mount an appropriate adaptive transcriptional response. Thus, determining conditions for analyses of gene expression in vitro that are representative of the in vivo environment is critical for understanding the contributions of transcriptional response pathways to pathogenesis. In this study, we determined that the gene encoding the SpeB cysteine protease is up-regulated over the course of infection in a murine soft-tissue model. Conditions were identified, including growth phase, acidic pH, and an NaCl concentration of <0.1 M, that were required for expression of speB in vitro. Analysis of global expression profiles in response to these conditions in vitro identified a set of coregulated genes whose expression patterns showed a significant correlation with that of speB when examined during infection of murine soft tissues. This analysis revealed that a culture medium that promotes high levels of SpeB expression in vitro produced an expression profile that showed significant correlation to the profile observed in vivo. Taken together, these studies establish culture conditions that mimic in vivo expression patterns; that growth phase, pH, and NaCl may mimic relevant cues sensed by S. pyogenes during infection; and that identification of other environmental cues that alter expression of speB in vitro may provide insight into the signals that direct global patterns of gene expression in vivo.
A Meta-Analysis of Studies of Treatments for Feline Urine Spraying

Feline urine spraying inside the home is a common problem behaviour that owners seek advice for from veterinarians. Individual trials relating to a variety of interventions produce variable results, and to date, no consensus on the value of different treatments has emerged. This study therefore aimed to meta-analyse, current data from appropriate published clinical trials that evaluate treatments for feline urine spraying. Inclusion and exclusion criteria for study selection were predefined and methodological quality was assessed by two independent reviewers. Ten studies in nine publications that either evaluated pharmacotherapy or pheromonatherapy (the use of a synthetic analogue of the F3 facial fraction in the cat) were suitable for analysis. There was a significant (P<0.001) association between the use of any intervention and the number of cats that ceased or reduced urine spraying by at least 90%. Analysis by intervention type indicated that fluoxetine, clomipramine and pheromonatherapy may each assist in managing urine spraying beyond a placebo based intervention. This is the first time meta-analytical techniques have been used and reported to evaluate the efficacy of interventions used in veterinary behavioural medicine, and it has established confidence in the value of both conventional treatments (pharmacotherapy) and a more recently developed treatment modality (pheromonatherapy) as an adjunct to the management of this problem. It is suggested that future research into treatment efficacy for this problem uses the benchmark standard of randomised, controlled trials lasting for at least 8 weeks, with the outcome criteria of cessation of feline urine spraying or reduction by at least 90%.
Site and nature of H bonding on Ti (0001)

The site and nature of the bonding of H at a Ti (0001) surface are established via the analysis of new angle-resolved photoemission measurements by self-consistent electronic-structure calculations. Experimentally observed H-induced surface states are identified with calculated bonding and antibonding combinations of H $1s$ and Ti $3d$, $4s$ orbitals. The positions of these levels are strongly dependent on local bonding geometry. The H site which minimizes the total energy gives a very good account of the observed spectrum. Ignoring the total energy leads to a more ambiguous structure determination.
Genetic engineering of Lactococcus lactis to produce an amylase inhibitor for development of an anti-diabetes biodrug.

Diabetes is known as a multifactorial disease. The treatment of diabetes is complicated due to its inherent pathophysiological factors related to the disease. One of the complications of diabetes is postprandial hyperglycemia. Glucosidase inhibitors, particularly ? -amylase inhibitors can help manage postprandial hyperglycemia. The low molecular weight inhibitor of ? -amylases called PAMI (peptide amylase inhibitor) inhibits the ? -amylase. In this study we cloned this amylase blocker PAMI in Lactococcus lactis. Using this Lactococcus lactis expressing the PAMI, we prepared yogurt and fed it to diabetic mice models. There was decrease in the blood glucose level after 20 days of oral administration of the yogurt. This product be used as a biodrug in maintaining the blood glucose level in diabetic patients.
Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure

Background: This study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer (MPC). Methods: We studied 18 histopathologically proven MPC patients. The schedule was 85 mg/m2 oxaliplatin, irinotecan, and 400 mg/m2 leucovorin, followed by 400 mg/m2 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m2 5-FU as a 46-hour continuous infusion biweekly. The dose of irinotecan was defined as follows: level 0: 100 mg/m2, level 1: 125 mg/m2, level 2: 150 mg/m2, and level 3: 180 mg/m2. The doses of other drugs were fixed. The primary endpoint of phase II study was the response rate (RR). Results: We initially evaluated 6 patients in a phase I study. One patient developed neutropenia and 1 patient developed hyperglycemia and severe infection. Accordingly, level 1 was chosen as the MTD. According to a phase II study, the RR was 22.2% and the disease control rate was 61.1%. The progression-free survival and overall survival were 2.8 (range, 0.7–19.1) and 9.8 (2.4–19.8) months, respectively. The most common severe adverse event was neutropenia (66.7%). Febrile neutropenia occurred in 1 (5.6%) case. Conclusion: The recommended dose was 85 mg/m2 oxaliplatin, 100 mg/m2 irinotecan, and 400 mg/m2 leucovorin, followed by 400 mg/m2 5-FU as a bolus on day 1 and 2400 mg/m2 5-FU as a 46-hour continuous infusion. These results indicate that second-line FOLFIRINOX is a marginally effective treatment for GEM-based chemotherapy failure cases.