Miracle-dz/UniFAR-FTUs huggingface dataset:
Methicillin distribution in serum and extravascular fluid and its relevance to normal and damaged heart valves

We evaluated the distribution of methicillin into normal and damaged heart valves and the accuracy with which subcutaneous plastic chambers reflected tissue uptake of this antibiotic. A total of 24 male New Zealand rabbits were given constant infusion doses of methicillin through central venous catheters. Five of these animals had their aortic and mitral valves damaged by catheterization of the left ventricle. A total of 19 rabbits had perforated plastic chambers inserted subcutaneously 7 to 10 days before methicillin infusion. In all animals more than 80% of the total infused dose of methicillin was accounted for in the serum, urine, and tissues. In the 12 animals infused to steady state (less than 7 h), the steady-state serum concentrations (11 to 120 micrograms/ml) were equal to the concentrations attained in either peritoneal or tissue chamber fluids. In the 12 animals sacrificed before 7 h, tissue chamber concentrations lagged behind serum and heart tissue concentrations in attaining steady state. Steady-state concentrations in normal heart valves and heart muscles failed to increase proportionally to increased constant infusion doses (8.7 to 87.2 mg/kg per h). The steady-state methicillin concentrations in fibrin-scarred heart valves were invariably higher than the steady-state concentrations in the normal right heart of the same animals (P less than 0.05). Tissue uptake of methicillin was altered in scarred heart valves as compared to normal heart valves, and large-volume subcutaneous tissue chambers misrepresented the uptake rate of methicillin into heart tissues and valves.
Force-velocity relations and fiber composition in human knee extensor muscles.

Standardized measurements of dynamic strength of the kneee extensor muscles were performed in 25 healthy male subjects (17-37 yr) by means of isokinetic contractions, i.e., knee extensions with constant angular velocities. Overall variation between double determinations of maximal torque throughout the 90 degrees arc of motion (0 degrees = fully extended leg) averaged 10% for the different constant velocities chosen. At any given angle of the knee the torque produced was higher for isometric than for dynamic contractions. Dynamic torque decreased gradually with increased speed of shortening. Peak dynamic torque was reached at knee angles in the range: 55-66 degrees, with a displacement toward smaller knee angles with higher angular velocities. Correlations were demonstrated between peak torque produced at the highest speed of muscle shortening and percent as well as relative area of fast twitch fibers in the contracting muscle. In addition muscles with a high percentage of fast twitch fibers had the highest maximal contraction speeds. These observations on intact human skeletal muscle are consistent with earlier findings in animal skeletal muscle preparations.
Making therapeutic decisions in inflammatory bowel disease: the role of patients

Purpose of review The treatment of inflammatory bowel disease (IBD) is becoming more complex due to the introduction of new medications and evolving treatment algorithms. Data suggest that more aggressive treatment will yield improved clinical results. Although promising, it is not clear if patients will agree to this new approach. This review aims to describe what we know about patients' perceptions of risks and benefits of treatment, how much risk IBD patients are willing to accept, and to introduce ideas to facilitate better patient communication. Recent findings Patients and parents of children with IBD appear to be willing to accept the known risks associated with IBD therapies, but demand substantial treatment benefit to make this tradeoff. As patients with IBD have misperceptions about the risks and benefits of treatment, it is important to develop better methods of communicating medical information. Summary There are now more treatment options for patients with IBD. To increase patients' participation in medical decisions, it is critical to fairly present the tradeoffs of risks versus benefits of treatment. Tools are being developed to more clearly present clinical trial data, risks of medication side effects and for calculating individualized risks of disease complications and response to therapy.
Neuroprotection at the Nanolevel—Part I

Nanoneurosurgery demands a departure from the traditional “excise what you can see and touch” role of neurosurgeons. Moreover, there is a conceptual leap necessary for neuroscientists as well as neurosurgeons in developing and applying nanotechniques to neurosurgery at the nanolevel. After introducing the realm of nanotechnology and some unique properties of nanomaterials, I review several of the nanotechniques in development that are most likely to affect neuroprotection at the nanolevel. These techniques include quantum dot “nanobarcode” labeling of cellular and subcellular entities, as well as nanotechniques for following enzymatic reactions in real time. Nanoscaffolds offer mechanical enhancement of neurorepair; carbon nanotube electrode arrays can provide nanolevel electrical and chemical enhancement. Even traditional “cut and sew” surgery is being taken down to the micron, if not nano, level for single axon repair, and the technology can use capillaries to deliver therapeutics to virtually any portion of the nervous system with greater than pinpoint accuracy. In this report, I use these nanotechniques to introduce the multiplex nanodevices under development.
Synthesis, accumulation, and excretion of trehalose in osmotically stressed Escherichia coli K-12 strains: influence of amber suppressors and function of the periplasmic trehalase

It has been reported previously that Escherichia coli K-12 carries an amber mutation that prevents osmotic stress-dependent accumulation of trehalose (M. L. Rod, K. Y. Alam, P. R. Cunningham, and D. P. Clark, J. Bacteriol. 170:3601-3610, 1988). We report that E. coli K-12 and W1485 (sup0) accumulated trehalose but that they required a higher osmotic strength in the growth medium than that required by their sup+ derivatives. Furthermore, the sup+ derivatives displayed both strongly increased trehalose-6-phosphate synthase activity and expression of otsA-lacZ and otsB-lacZ operon fusions compared with their parental strains. It is suggested that the amber mutation in question may be in a gene system encoding a transcriptional activator of the ots genes which govern the synthase. The much-used sup0 strain MC4100 behaved like the sup+ derivatives of W1485 with respect to trehalose synthesis. treA mutants with a defective periplasmic trehalase accumulated trehalose extracellularly under osmotic stress. The amount of trehalose excreted correlated with their synthase activity. Strains with an intact trehalase did not display extracellular trehalose accumulation. Thus, stressed E. coli cells regulate the cytoplasmic level of trehalose by a futile cycle involving overproduction, excretion, and degradation to glucose, which is reutilized.
Delay in indexing articles published in major pharmacy practice journals.

PURPOSE The delay in time from entry in the PubMed database to indexing with medical subject heading (MeSH) terms for articles published in three major pharmacy practice journals was evaluated. METHODS In April 2013, MEDLINE data were retrieved for articles published in the American Journal of Health-System Pharmacy (AJHP), the Annals of Pharmacotherapy, and Pharmacotherapy between January 1, 2010, and December 31, 2011. Data collected for each article included the PubMed entry date, MeSH indexing date, and publication type. The PubMed entry date was defined as the Entrez date, the date the citation was added to the PubMed database. Medians and interquartile ranges (IQRs) were calculated for the time to indexing of articles and for the age of unindexed articles. The proportion of unindexed articles was also calculated. RESULTS A total of 1626 publications were reviewed. Overall, the median time to indexing with MeSH terms was 114 days (IQR, 98-141 days): 107 days (IQR, 94-129 days) for AJHP, 131 days (IQR, 104-157 days) for Annals of Pharmacotherapy, and 114 days (IQR, 99-128 days) for Pharmacotherapy. The median age of unindexed articles was 807 days (IQR, 671-807 days). CONCLUSION An analysis of three major pharmacy practice journals showed that the median time to indexing articles published in 2010 and 2011 was 114 days. While all articles from AJHP and Pharmacotherapy were indexed, 40 articles from Annals of Pharmacotherapy remained unindexed.
EXCITATION‐CONTRACTION COUPLING IN SINGLE MUSCLE FIBERS AND THE CALCIUM CHANNEL IN SARCOPLASMIC RETICULUM *

Mechanisms of excitation-contraction (EC) coupling in muscle are still obscure, particularly the processes whereby depolarization of the plasma membrane and T-system results in the intracellular release of free calcium from the calcium stores in sarcoplasmic reticulum (SR). 5 We studied single barnacle giant muscle fibers that were injected with the photoprotein aequorin to determine the light emission in the resting fiber (resting glow) as well as the increase of light emission elicited by membrane depolarization (calcium transient). ' Intracellular axial electrodes served to record the membrane potential and to deliver constant current pulses. Various intensities (not eliciting any action potentials) were applied in order to quantitate the relation between membrane depolarization and area of calcium transient or isometric force of the resulting contraction.3 EC coupling was analyzed under several experimental conditions.
An electrical design and fabrication of a 12-channel optical transceiver with SiP packaging technology

This paper presents an electrical design of a 6.25Gbps×12-channel parallel optical transceiver with SiP packaging technology. Considering such high speed, a low impedance and low noise power distribution network (PDN) is designed to suppress simultaneous switching noise (SSN) and a novel embedded capacitor filter is used to replace the conventional power supply filter. To minimize the impedance discontinuity of electrical channels, a signal integrity (SI) design flow based on Electromagnetic Analysis Method and Circuit Analysis Method is proposed. Following this design flow, the high speed link performs on a large bandwidth. With the electrical design, the optical transceiver is fabricated and tested.
Enhanced recovery of avian influenza virus isolates by a combination of chicken embryo inoculation methods.

Since 1993, 14 cases of avian influenza from four different states in the U.S.A. have been diagnosed by virus isolation from eight avian species. Only 11 of the 14 avian influenza virus (AIV) primary isolations would have been successful if only the standard protocol for AIV isolation, i.e., inoculation of specific-pathogen-free embryonating chicken eggs (ECEs) by the chorioallantoic sac (CAS) route, had been followed. Primary isolation attempts were negative for AIV in three cases in which ECEs were inoculated by the CAS route; AIV could not be detected by hemagglutinating activity, agar gel immunodiffusion test or negative stain electron microscopy. However, in these three cases, primary isolations of AIV were achieved by inoculation of ECEs into either the yolk sac or onto the chorioallantoic membrane.
Desarrollo del sistema de información sobre el litoral y el medio marino de la red de información ambiental de Andalucía (REDIAM)

The Coastal and Marine Environment Subsystem (SSLyMM) has arise by the need of rationalization from a previous project, the SIGLA, which was developed between the University of Sevilla and the Regional Governments in Environment and Works in Andalusia. The SIGLA must be transformed in an integrated system in the REDIAM (Red de Información Ambiental de Andalucía) capable to link spatial coastal and marine data with others subsystems that shape this network (biodiversity, climatology, wetlands, etc.) guaranteeing a continuous and joint updating, and taking into account the grounds from the last european directives. So, the subsystem must achieve the aim of normalization, metadata production and exploitation relating to spatial information in those environments, giving coverage, in this way, to the ICZM strategy (Integrated Coastal Zone Management). With that purpose, it is putting in practice several SIG tools, OGC services generators and web applications.
Blood clotting defect in hibernating ground squirrels (Citellus tridecemlineatus).

In investigating the hypocoagulability of the blood during hibernation, multiple plasma-clotting factors, numbers of platelets, and hematocrits were determined in 17 hibernating 13-lined ground squirrels and compared with levels in 23 nonhibernating ground squirrels. Human plasma was used as the standard in procoagulant assays. At the time of withdrawal of the blood from the aortas of hibernating animals, their rectal temperatures ranged from 6.9 to 8.6 C. Significant differences between active and hibernating animals were found in the whole-blood clotting times (210 and 315 sec), partial thromboplastin times (45.5 and 109.3 sec), plasma prothrombin (443 and 698 U/ml), 1-hr serum residual prothrombin (27 and 449 U/ml), factor VIII (165 and 35%), factor IX (359 and 188%), and blood platelet concentration (445,150 and 47,940/mm3). No decisive changes were demonstrated in the prothrombin times or levels of factors V, VII, X, XI, XII, or fibrinogen. Inhibitors were not detected. Both thrombocytopenia and plasma defects seemed to contribute to the impairment of the blood-clotting mechanism during hibernation.
Differentiation-Dependent Chromatin Rearrangement Coincides with Activation of Human Papillomavirus Type 31 Late Gene Expression

ABSTRACT The life cycle of human papillomaviruses (HPVs) is tightly linked to the differentiation status of the host cell. While early genes are expressed during the initial stages of viral infection, late gene expression occurs in the suprabasal layers of the cervical epithelium. Late genes encode E1^E4, a cytosolic protein, and capsid proteins L1 and L2. We have mapped over 30 initiation sites for late transcripts and show that the transcripts initiate in a 200-nucleotide region within the E7 open reading frame. The mechanisms regulating the activation of late gene expression, however, are not yet understood. DNase I hypersensitivity analysis of HPV-31 chromatin in cell lines that maintain viral genomes extrachromosomally indicates that a major shift in nuclease digestion occurs upon differentiation. In undifferentiated cells, hypersensitive regions exist in the upstream regulatory region proximal to the E6 open reading frame. Upon differentiation, a region between nucleotides 659 and 811 in the E7 open reading frame becomes accessible to DNase I. These results indicate that the late transcript initiation region becomes accessible to transcription factor binding upon differentiation. Several complexes mediate chromatin rearrangement, and we tested whether histone acetylation was sufficient for late transcript activation. Treatment with the histone deacetylase inhibitor trichostatin A was found to be insufficient to activate late gene expression in undifferentiated cells. However, it did activate expression of early transcripts. These results suggest that chromatin remodeling around the late promoter occurs upon epithelial differentiation and that mechanisms in addition to histone deacetylation contribute to activation of late gene expression.
Methylation status analysis of cell cycle regulatory genes (p16INK4A, p15INK4B, p21Waf1/Cip1, p27Kip1 and p73) in natural killer cell disorders

Abstract: Natural killer (NK) cell disorders are rare diseases. Genetic abnormalities of the several tumor suppressor genes, including p15INK4B, p16INK4A/p14ARF, p53, p73, and Rb genes have been reported. Deletions and point mutations of these genes are frequently detected in these diseases. It has been reported that tumor suppressor genes are inactivated by DNA methylation of the promoter region and/or first exon of the genes in a variety of human cancers. In this study we analyze the methylation status of the genes associated with cell cycle regulation, including p16INK4A, p15INK4B, p21/Waf1/Cip1, p27/Kip1, p73, and p14ARF, by methylation specific (MS) PCR and/or bisulfite sequencing. We examined 29 cases of NK cell disorders (five aggressive NK cell leukemia/lymphoma, three blastic NK cell lymphoma/leukemia, five nasal NK cell lymphoma, three myeloid/NK cell precursor acute leukemia, 13 chronic NK lymphocytosis). We found methylation of the first exon of the p16INK4A gene in two cases (one aggressive, one blastic), and methylation of the p14ARF gene in one aggressive NK cell leukemia. Bisulfite sequencing revealed that methylation of the p15 and p27 genes was rare in these disorders. MS‐PCR suggested that the p73 and p21 genes were methylated in seven cases, respectively (p73: one blastic, one nasal, five chronic; p21: one myeloid/NK, one aggressive, one nasal, and four chronic); bisulfite sequencing confirmed that methylated alleles of these genes were dominant in the samples except three cases (one myeloid/NK, one aggressive, and one chronic) in which methylated alleles of the p21 genes were less than 34% of all alleles. These results suggested that inactivation of the cell cycle regulatory genes by DNA methylation could be associated with tumorigenesis in NK cell disorders, not only aggressive subtypes but also chronic subtype.
Structural Health Monitoring system based on strain gauge enabled wireless sensor nodes

Strain gauges are widely used in structural health monitoring (SHM) systems because they are inexpensive, easy to install, and sensitive enough to detect the potential danger of collapse of a building or structure. However, off-the-shelf equipment for the strain gauges is usually either wired to the sensors or wireless with very limited range, which significantly increases the total cost as well as restricting the performance of the deployment. In this paper, we propose a structural health monitoring system based on wireless sensor nodes equipped with inexpensive strain gauges. The performance of the system is not limited, because multi-hop deployment is possible. Our system consists of a sensor board, which properly amplifies and converts the signal from the strain gauges, and communication software, written in TinyOS, that is in charge of reliable transport of the strain data. We evaluated our system in comparison with the commercial equipment. The experiment results show that the proposed system is reliable and effective for use in structural health monitoring.
On-Chip NRZ-to-PRZ Format Conversion Using Narrow-Band Silicon Microring Resonator-Based Notch Filters

We report experimental demonstration and modeling of all-optical on-chip non-return-to-zero (NRZ) to pseudo-return-to-zero (PRZ) format conversion using narrow-band silicon microring resonator-based notch filters. Our proof-of-principle experiment using a carrier-injection-based tunable silicon microring resonator demonstrates NRZ-to-PRZ conversion at 3.6 Gbit/s. Our Fourier-transform-based modeling reveals in detail the format conversion dependence on the microring resonance Q factor, extinction ratio, phase response, and NRZ signal transition times, assuming signal format conversion of 40 Gbit/s.
Nek6 overexpression antagonizes p53-induced senescence in human cancer cells

Nek6 is an NIMA-related kinase that plays a critical role in mitotic cell cycle progression. Recent studies have shown that Nek6 is upregulated in various human cancers, but the function of Nek6 in tumorigenesis is largely unknown. Here, we examined the role of Nek6 in cellular senescence. Our data revealed that Nek6 expression is decreased both in both the replicative senescence of human normal fibroblasts and premature senescence induced by p53 expression in EJ human bladder cancer cells and H1299 human lung cancer cells. Interestingly, the enforced expression of Nek6 in EJ and H1299 cells completely suppresses p53-induced senescence, whereas the expression of kinase-dead Nek6 did not affect p53-induced senescence. Mechanistic studies revealed that cell cycle arrest in the G1 and G2/M phases, as well as the reduction of cyclin B and cdc2 protein level upon p53 expression were significantly reduced by Nek6 overexpression. In addition, p53-induced increases in intracellular levels of ROS were also inhibited in cells overexpressing Nek6. These results suggest that the downregulation of Nek6 expression is required for the onset of p53-induced cellular senescence and imply a possible role of Nek6 in tumorigenesis.
Comparative Efficacy and Safety of Prasugrel, Ticagrelor, and Standard-Dose and High-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Network Meta-analysis

Authors aimed to compare efficacy and safety of prasugrel, ticagrelor, and standard-dose (SD) and high-dose (HD) clopidogrel in patients undergoing percutaneous coronary intervention (PCI). PubMed, EMBASE, CENTRAL, and clinicaltrials.gov were searched for studies comparing prasugrel, ticagrelor, SD and HD clopidogrel in patients undergoing PCI. Frequentist and Bayesian network meta-analyses were performed besides direct pairwise comparisons. Thirty trials, comprising 34,563 person-year data, were included. Prasugrel emerged as a best drug to prevent definite or probable stent thrombosis, followed by HD clopidogrel and ticagrelor, with SD clopidogrel being the worst. Myocardial infarction was least likely to be prevented by SD clopidogrel after PCI, and remaining 3 were superior to it with little difference among them. SD clopidogrel was least effective in preventing cardiovascular deaths after PCI. Prasugrel was most effective in preventing cardiovascular deaths, although having only small advantage over ticagrelor and HD clopidogrel. Ticagrelor reduced all-cause mortality by a small margin compared with rest of treatments. SD clopidogrel, followed by ticagrelor, resulted in significantly lower thrombolysis in myocardial infarction major bleeding complications compared with prasugrel. Analysis of any bleeding revealed similar trend. HD clopidogrel performed better than prasugrel in terms of bleeding complications. In conclusion, Prasugrel is likely most effective drug to prevent post-PCI ischemic events but at the expense of higher bleeding. Ticagrelor followed by HD clopidogrel seems to strike the right balance between efficacy and safety. HD clopidogrel can be considered as an alternative to newer P2Y12 inhibitors.
Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Diabetic kidney disease is the predominant cause of end stage kidney disease in North America, estimated to be 152 per million population in 2010. New guidelines published by KDIGO on Chronic Kidney Disease classification are discussed. In light of recent clinical trials, better insight has been gained on how improve management of diabetic patients to prevent renal disease and its progression, especially with regards to metabolic and blood pressure control. Unfortunately, studies of newer therapies such as endothelin 1 antagonists and bardoxolone methyl have been disappointing, but several other possible therapeutic agents are under investigation and may provide hope for patients with diabetes mellitus in the future.