Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of Oritavancin in Plasma and Skin Blister Fluid following Administration of a 200-Milligram Dose for 3 Days or a Single 800-Milligram Dose

ABSTRACT Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUCblister fluid/AUCplasma ratios) were evaluated using a t test (α = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUCblister fluid/AUCplasma ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (P = 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of Staphylococcus aureus (2 μg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.
Immunocytochemical Localization of Chymase to Cytoplasmic Vesicles After Rat Peritoneal Mast Cell Stimulation by Compound 48/80

The subcellular events responsible for release of mediators by mast cells may help to clarify roles for mast cells in health and disease. In this study we show that the granule-associated protease chymase is also within cytoplasmic vesicles in appropriately stimulated rat peritoneal mast cells. Rat peritoneal mast cells were recovered before or 1–10 sec after exposure to the secretogogue compound 48/80 (10 μg/ml) and then were examined by radioimmunoassay to quantify histamine release or were processed, using routine methods for postembedding immunoelectron microscopy, to identify the subcellular localization of chymase. In comparison to unstimulated cells, compound 48/80 stimulated cells in two independent experiments showed an increase (15%, 28%) in the surface area of the cell and a decrease (12%, 6%) in the surface area of the total granule compartment before degranulation channel formation. These global cellular changes occurred in a background of transient but significant (p<0.01) increases in the area and number of chymase-immunoreactive vesicles per μ2 cytoplasm. These changes were detectable at 5 or 7 sec after stimulation with compound 48/80 but returned to near prestimulation levels by 9 or 10 sec after addition of compound 48/80 (total cumulative histamine release was 28% by 8 sec and 47% by 14 sec). These observations suggest that vesicles participate in the early stages of regulated secretion of chymase from rat peritoneal mast cells.
Effects of zaprinast and rolipram on platelet aggregation and arrhythmias following myocardial ischaemia and reperfusion in anaesthetized rabbits

1 This study was designed to compare the effects of two selective inhibitors of certain phosphodiesterase (PDE) isoenzymes on arrhythmias induced by coronary artery occlusion and reperfusion. The drugs used were zaprinast which inhibits guanosine 3′: 5′‐cyclic monophosphate (cyclic GMP)‐specific PDE (PDE V) and rolipram which inhibits cyclic GMP‐insensitive, adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP)‐specific PDE (PDE IV). 2 Pretreatment of anaesthetized rabbits with zaprinast (300 μg kg−1 plus 30 μg kg−1 min−1) had no significant effect on ischaemia‐ or reperfusion‐induced ST‐segment changes, or arrhythmias. In contrast, rolipram (30 μg kg−1 plus 3μg kg−1 min−1) and (100 μg kg−1 plus 10μg kg−1min−1) increased the severity of arrhythmias. With the higher dose of rolipram, ST‐segment changes were increased in magnitude and mortality due to ventricular fibrillation during ischaemia or reperfusion was increased to 80% compared with 30% in controls (n = 10 per group). 3 Zaprinast caused small but significant increases in heart rate and arterial blood pressure whereas rolipram decreased diastolic arterial pressure, increased left ventricular (LV) dP/dtmax and substantially increased heart rate. 4 At the end of each experiment platelet aggregation was measured ex vivo. Pretreatment of rabbits with either dose of rolipram had no significant effect on platelet aggregation induced by adenosine diphosphate (ADP), collagen, arachidonic acid or thrombin or on isoprenaline‐ or prostacyclin‐induced inhibition of aggregation. Aggregatory responses to ADP and collagen were increased in platelets obtained from rabbits which had received zaprinast. 5 These results indicate that in the dose used here, the PDE V inhibitor zaprinast had no significant effect on arrhythmias. The effects of the PDE IV inhibitor rolipram on haemodynamics, combined with its lack of antiplatelet activity, may have contributed to the exacerbation of arrhythmias observed during myocardial ischaemia and reperfusion.
Within-field damage and distribution patterns of the stalk borer, Eldana saccharina (Lepidoptera: Pyralidae), in sugarcane and a comparison with nematode damage

Abstract The occurrence of Eldana saccharina (Lepidoptera: Pyralidae) was monitored in grids represented by plots in 12 nematicide trials in South African sugarcane fields. The trials encompassed a total of eight plant cane crops and 22 ratoon crops and were situated within commercial cane fields. Several measurements were made to characterize the damage caused by E. saccharina. These included the number of internodes per stalk, the percentage of internodes damaged and the percentage of stalks damaged. The mapping of E. saccharina infestation in plant crops of sugarcane showed that the borders of the trials were as infested as the centre, indicating invasion from outside the field plus internal spread within the field. Ratoon crops were less infested than plant crops. This could be explained by a shorter ratoon crop cycle and by the fields having areas that were more suitable for the borer than elsewhere. The location of these preferred areas could be predicted from one ratoon crop to the next but was not related to the distribution of the borer in the plant crop. This situation was thought to explain the apparent stabilization of E. saccharina infestation in ratoon cane. Because the borer was found at harvest only in stalks with more than 14 to 16 internodes, it appeared that the oldest shoots, or the shoots with the greatest growth potential, attracted the insect, possibly due to their higher nitrogen content, which would stimulate growth. All the trials were on sandy soil, and crop loss from nematodes was greater than that caused by E. saccharina.
Capacity and Robustness Tradeoffs in Bloom Filters for Distributed Applications

The Bloom filter is a space-efficient data structure often employed in distributed applications to save bandwidth during data exchange. These savings, however, come at the cost of errors in the shared data, which are usually assumed low enough to not disrupt the application. We argue that this assumption does not hold in a more hostile environment, such as the Internet, where attackers can send a carefully crafted Bloom filter in order to break the application. In this paper, we propose the concatenated Bloom filter (CBF), a robust Bloom filter that prevents the attacker from interfering on the shared information, protecting the application data while still providing space efficiency. Instead of using a single large filter, the CBF concatenates small subfilters to improve both the filter robustness and capacity. We propose three CBF variants and provide analytical results that show the efficacy of the CBF for different scenarios. We also evaluate the performance of our filter in an IP traceback application and simulation results confirm the effectiveness of the proposed mechanism in the face of attackers.
Phase 0 and phase III transport in various organs: Combined concept of phases in xenobiotic transport and metabolism

Abstract The historical phasing concept of drug metabolism and elimination was introduced to comprise the two phases of metabolism: phase I metabolism for oxidations, reductions and hydrolyses, and phase II metabolism for synthesis. With this concept, biological membrane barriers obstructing the accessibility of metabolism sites in the cells for drugs were not considered. The concept of two phases was extended to a concept of four phases when drug transporters were detected that guided drugs and drug metabolites in and out of the cells. In particular, water soluble or charged drugs are virtually not able to overcome the phospholipid membrane barrier. Drug transporters belong to two main clusters of transporter families: the solute carrier (SLC) families and the ATP binding cassette (ABC) carriers. The ABC transporters comprise seven families with about 20 carriers involved in drug transport. All of them operate as pumps at the expense of ATP splitting. Embedded in the former phase concept, the term “phase III” was introduced by Ishikawa in 1992 for drug export by ABC efflux pumps. SLC comprise 52 families, from which many carriers are drug uptake transporters. Later on, this uptake process was referred to as the “phase 0 transport” of drugs. Transporters for xenobiotics in man and animal are most expressed in liver, but they are also present in extra-hepatic tissues such as in the kidney, the adrenal gland and lung. This review deals with the function of drug carriers in various organs and their impact on drug metabolism and elimination.
Fine Mapping of a QTL for Fertility on BTA7 and Its Association With a CNV in the Israeli Holsteins

A quantitative trait locus (QTL) affecting female fertility, scored as the inverse of the number of inseminations to conception, on Bos taurus chromosome 7 was detected by a daughter design analysis of the Israeli Holstein population (P < 0.0003). Sires of five of the 10 families analyzed were heterozygous for the QTL. The 95% confidence interval of the QTL spans 27 cM from the centromere. Seven hundred and four SNP markers on the Illumina BovineSNP50 BeadChip within the QTL confidence interval were tested for concordance. A single SNP, NGS-58779, was heterozygous for all the five QTL heterozygous patriarchs, and homozygous for the remaining five QTL homozygous sires. A significant effect on fertility was associated with this marker in the sample of 900 sires genotyped (P < 10−6). Haplotype phase was the same for four of the five segregating sires. Thus concordance was obtained in nine of the ten families. We identified a common haplotype region associated with the rare and economically favorable allele of the SNP, spanning 270 kbp on BTA7 upstream to 4.72 Mbp. Eleven genes found in the common haplotype region should be considered as positional candidates for the identification of the causative quantitative trait nucleotide. Copy number variation was found in one of these genes, KIAA1683. Four gene variants were identified, but only the number of copies of a specific variant (V1) was significantly associated with breeding values of sires for fertility.
Survey of training in geriatric medicine in UK undergraduate medical schools.

SIR—The view that the study of human ageing and healthcare needs of older people should form part of the undergraduate medical curriculum is supported by the World Health Organization, the Royal College of Physicians of London and the General Medical Council [1–3]. Surveys in the 1980s showed that geriatric medicine was being taught in almost all medical schools, most commonly by a compulsory attachment to a hospital-based department of geriatric medicine [4, 5]. Since then, many changes have taken place both in the way in which services for older people are provided and in the organisation of medical schools. For example, acute hospital care of older people is now integrated with general medicine, and the growth of academic departments of geriatric medicine has been stalled [6]. Furthermore, General Medical Council guidance is that student-selected components should comprise a quarter to a third of the curriculum [7]. The continuing demand for geriatricians and others required to treat the increasing numbers of older people [8], coupled with concerns that training opportunities for undergraduates have been reduced, suggested it was timely to undertake this review. We report the results of a survey of the teaching of geriatric medicine and human ageing in UK medical schools.
Stereocilia versus kinocilia part III: the efferent innervation

About 1946 Rasmussen began to publish his findings in the anatomy of the efferents in the acoustic system. He described the crossed and uncrossed olivo-cochlear bundles and their terminals on the O.H. C and I.H. C. , and their origins from the olivo-cochlear ganglion and the higher neurons in the colliculus and the medial trapezoid nucleus. In the years that followed anatomists described those efferents in all available animals, but they threw no light on the possible functions of the innervation. Later physiologists studied the responses of the afferents evoked by various stimuli via the efferents. They also threw no light on the functions of the innervation. So much so that Klinke and Galley (1974), having scrutinized all the available data from both acoustic and vestibular systems, sadly reported that: 'Nothing definite is known about the functional significance of the efferent innervation in any sense organ in the acoustico-lateralis system. ' In the following analysis I start by defining the meaning of the word efferent. I take it to mean travelling from the C.N. S. to the periphery, as opposed to the afferents that travel from the periphery to the C.N. S. On that basis the efferents can be divided as follows: (1) the primaries, in which the conscious cortex sends instructions to the periphery to evoke voluntary behaviour; (2) the secondaries, in which the peripheral sensors send their responses (evoked by external stimuli) via their afferents to the C.N. S. , and the C.N. S. sends instructions to the periphery via the efferents.
Aggressive Transmissions of Short Messages Over Redundant Paths

Fault-tolerant computer systems have redundant paths connecting their components. Given these paths, it is possible to use aggressive techniques to reduce the average value and variability of the response time for short, critical messages. One technique is to send a copy of a packet over an alternate path before it is known whether the first copy failed or was delayed. A second technique is to split a single stream of packets over multiple paths. The authors analyze both approaches and show that they can provide significant improvements over conventional, conservative mechanisms. >
Performance analysis of forward error correcting codes in IPTV

In recent years the forward error correction (FEC) schemes at the binary erasure channel have been researched for many applications including DVB-H and IPTV systems. In most cases the packet-level FEC strategies are implemented by either Reed-Solomon (RS) codes at the link layer or Raptor codes at the application layer. Recently an enhanced decoding method for RS codes was presented. The enhanced-decoding scheme is a combination of erasure and error decoding. In this paper we consider the performance comparison of the enhanced-decoding RS code at the link layer and Raptor code at the application layer in the burst mode transmission to give a guidance of FEC scheme for IPTV application. It is noted that the efficient Raptor decoding algorithm makes it possible to broadcast multimedia data more reliable and faster.
Thermal Protection / Light Weight Materials Development for Future Air Force Vehicles

Abstract : The overall goals of this program are to develop fast thermal dissipation mechanisms for light weight polymer matrix fibrous composites based on moisture evaporative cooling, superconducting heat pipe arrays and thermal ceramic protective coatings for future Air Force vehicles, and associated propulsion systems. In the first year of the program the following technical areas were pursued and their progress is reported on (i) Moisture diffusion modeling and experimental liquid water capillary flow evaporative cooling together with water soluble chemicals that limit surface emission IR signatures. (ii) Ultrafast heat pipes as integrated structural members.
Notch signaling promotes airway mucous metaplasia and inhibits alveolar development

The airways are conduits that transport atmospheric oxygen to the distal alveolus. Normally, airway mucous cells are rare. However, diseases of the airway are often characterized by mucous metaplasia, in which there are dramatic increases in mucous cell numbers. As the Notch pathway is known to regulate cell fate in many contexts, we misexpressed the active intracellular domain of the mouse Notch1 receptor in lung epithelium. Notch misexpression resulted in an increase in mucous cells and a decrease in ciliated cells in the airway. Similarly, mouse embryonic tracheal explants and adult human airway epithelium treated with Notch agonists displayed increased mucous cell numbers and decreased ciliated cell numbers. Notch antagonists had the opposite effect. Notably, Notch antagonists blocked IL13-induced mucous metaplasia. IL13 has a well-established role as an inflammatory mediator of mucous metaplasia and functions through Stat6-mediated gene transcription. We found that Notch ligands, however, are able to cause mucous metaplasia in Stat6-null cultured trachea, thus identifying a novel pathway that stimulates mucous metaplasia. Notch signaling may therefore play an important role in airway disease and, by extension, Notch antagonists may have therapeutic value. Conversely, in the distal lung, Notch misexpression prevented the differentiation of alveolar cell types. Instead, the distal lung formed cysts composed of cells that were devoid of alveolar markers but that expressed some, but not all, markers of proximal airway epithelium. Occasional distal cystic cells appeared to differentiate into normal proximal airway cells, suggesting that ectopic Notch signaling arrests the normal differentiation of distal lung progenitors before they initiate an alveolar program.
Photodetector Selection Aided Multiuser MIMO Optical OFDM Imaging Visible Light Communication System

While playing an important role in radio frequency (RF)-based wireless systems, multiple-input multiple-output (MIMO) techniques have also found viable applications in visible light communication (VLC) systems. However, how to effectively reduce the inherent strong correlations between optical MIMO channels remains a typical issue for VLC. In this paper, we propose an MIMO-aided multiuser optical orthogonal frequency division multiplexing VLC system employing an imaging receiver (ImR). The proposed new scheme efficiently mitigates the optical MIMO channel correlations across the multiple photodetectors (PDs) of the same user equipment (UE) or those between different UEs, through invoking a new technique called photodetector selection (PDS). Two possible PDS designs, namely random PDS and modified maximum minimum singular value PDS are investigated. Through both analytical analysis and numerical simulations, we show that the proposed PDS-aided ImR system is capable of outperforming its conventional non-imaging receiver and non-PDS ImR counterparts, especially when UEs are close to each other. Results demonstrate that the proposed system offers a stably low bit error rate in most areas of the room.
A deterministic call admission control protocol for bursty traffic in high-speed networks: modeling and analysis

We present the development, modeling, analysis and performance evaluation of a deterministic call admission control (CAC) protocol for bursty traffic in high-speed broadband integrated services digital networks. This CAC protocol simultaneously satisfies two quality of service (QoS) parameters, namely cell loss ratio (CLR) and delay. The protocol presented is suitable for "on-line" application and provides efficient network resource (buffer space and link capacity) utilization. The end-to-end delay and CLR values are divided among the nodes of the connection. Deterministic models that capture the bursty nature of the traffic supported by the ATM network are developed for the source and the network node. These models satisfy the deterministic burstiness constraint required by ATM usage parameter control (UPC). Analytical expressions at nodes for CLR and delay are developed based on these models. These analytical expressions are used to develop a CAC protocol. This CAC protocol for bursty sources is evaluated by using queuing models.
An Out-of-frame Overlapping Reading Frame in the Ataxin-1 Coding Sequence Encodes a Novel Ataxin-1 Interacting Protein*

Background: The spinocerebellar ataxia type 1 (SCA1) gene encoding ataxin-1 (ATXN1) contains an alternative open reading frame overlapping the ATXN1 coding sequence. Results: The alternative ATXN1 protein is constitutively co-expressed and interacts with ATXN1 N terminus. Alternative ATXN1 is also an RNA binding protein. Conclusion: ATXN1 is a genuine dual coding gene. Significance: Alternative ATXN1 may regulate the function of ATXN1 in physiological and pathological conditions. Spinocerebellar ataxia type 1 is an autosomal dominant cerebellar ataxia associated with the expansion of a polyglutamine tract within the ataxin-1 (ATXN1) protein. Recent studies suggest that understanding the normal function of ATXN1 in cellular processes is essential to decipher the pathogenesis mechanisms in spinocerebellar ataxia type 1. We found an alternative translation initiation ATG codon in the +3 reading frame of human ATXN1 starting 30 nucleotides downstream of the initiation codon for ATXN1 and ending at nucleotide 587. This novel overlapping open reading frame (ORF) encodes a 21-kDa polypeptide termed Alt-ATXN1 (Alternative ATXN1) with a completely different amino acid sequence from ATXN1. We introduced a hemagglutinin tag in-frame with Alt-ATXN1 in ATXN1 cDNA and showed in cell culture the co-expression of both ATXN1 and Alt-ATXN1. Remarkably, Alt-ATXN1 colocalized and interacted with ATXN1 in nuclear inclusions. In contrast, in the absence of ATXN1 expression, Alt-ATXN1 displays a homogenous nucleoplasmic distribution. Alt-ATXN1 interacts with poly(A)+ RNA, and its nuclear localization is dependent on RNA transcription. Polyclonal antibodies raised against Alt-ATXN1 confirmed the expression of Alt-ATXN1 in human cerebellum expressing ATXN1. These results demonstrate that human ATXN1 gene is a dual coding sequence and that ATXN1 interacts with and controls the subcellular distribution of Alt-ATXN1.
Tiles that Talk: Tangible Templates for Networked Objects

Fine art and design students face a novel set of challenges when asked to realize their creative vision with code-based projects. In this paper, we discuss the development of a system of tangible tiles and integrated software code factory that is intended to help students build bridges of understanding between proposed interactive and networked experiences and the required computer syntax, software libraries and hardware that animate those proposals. Our tiles help students see relationships between artistic concept and programmatic code by giving them intuitive tools that can be directly manipulated.