Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Analysis of the K5 Gene of Kaposi's Sarcoma-Associated Herpesvirus

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), belongs to the gammaherpesvirus subfamily and encodes ∼80 open reading frames (ORFs). Among them are a few candidates for immediate-early genes (e.g., K5). We developed a monoclonal antibody (MAb), 328C7, against the K5 antigen. This MAb reacted with the K5 gene product by immunoscreening of a cDNA library from BCBL-1 cells, and this result was confirmed by transfection of the K5 ORF into Cos-7 cells. After induction of lytic infection by treatment with 12-O-tetradecanoylphorbol-13-acetate, MAb 328C7 reacted with an antigen in the cytoplasm of BCBL-1 and BC-3 cells as early as after 4 h of induction. Immunoelectron microscopy showed that the K5 antigen was situated mainly in the endoplasmic reticulum but was not present on the virion or in the nucleus. Northern blotting with a K5-specific probe revealed a single transcript of 1.2 kb, while Western blotting showed the antigen to be a 36-kDa polypeptide. The 5′ and 3′ ends were then determined by rapid amplification of cDNA, followed by sequencing of RACE products, and a splice was revealed upstream of the K5 ORF. K5 expression was unaffected by the respective DNA and protein synthesis inhibitors phosphonoformic acid and cycloheximide plus actinomycin D, confirming its immediate-early nature. Transient-transfection assays showed that the K5 promoter was transactivated by ORF 50 (KSHV Rta), a homolog of Epstein-Barr virus Rta, but the K5 gene product exhibited no transregulation of its own promoter or those of DNA polymerase and the human immunodeficiency virus type 1 long terminal repeat. This is the first such analysis of an immediate-early gene product; determination of its specific biological function requires further investigation.
Episodic corticosterone treatment accelerates kindling epileptogenesis and triggers long‐term changes in hippocampal CA1 cells, in the fully kindled state

We tested the effect of episodic (≈ 10 days) corticosterone treatment on: (i) behavioural symptoms during kindling epileptogenesis; and (ii) electrical activity in the CA1 hippocampal area during epileptogenesis, and later on, in the fully kindled state. Male rats received a corticosterone‐releasing pellet (100 mg/day) shortly before kindling was started, resulting in elevated hormone levels during the early and middle stages of epileptogenesis. The appearance of moderate behavioural signs of epilepsy and severe tonic–clonic seizures was significantly accelerated in corticosterone‐treated animals compared to placebo controls. During epileptogenesis, corticosterone treatment did not affect the amplitude and paired‐pulse characteristics of in vivo‐recorded CA1 field responses, or the duration of the afterdischarge following tetanic stimulation of the Schaffer collaterals. However, other properties of CA1 cells studied in vitro, in the fully kindled state, were altered by the earlier episodic corticosterone treatment. Thus, in kindled rats, the amplitude of the population spike in the CA1 area was significantly enhanced after prior exposure to high corticosterone levels. Prior episodic steroid treatment resulted furthermore in a significantly increased amplitude of voltage‐gated Ca currents, in kindled rats. At that time, corticosterone levels of animals which had received a corticosterone‐releasing pellet earlier were no longer elevated compared to the placebo controls; the corticosteroid‐treated rats did also not differ from the controls with respect to the mRNA expression levels for the two corticosteroid receptor subtypes in the hippocampus. The data suggest that exposure of animals to a period of stressful experiences during a critical phase in epileptogenesis could impose lasting deleterious effects on the course of epilepsy, even when CORT levels have been normalized again.
The randomized physiologic assessment of thrombus aspiration in patients with acute ST-segment elevation myocardial infarction trial (PATA STEMI): study rationale and design.

INTRODUCTION Routine thrombus aspiration is proposed to be superior to conventional primary percutaneous coronary intervention (PCI) in terms of improved myocardial perfusion, in patients with ST-segment elevation acute myocardial infarction (STEMI). However, myocardial perfusion after thrombus aspiration has not been evaluated by a quantitative, invasive method. We intend to determine whether manual thrombus aspiration in the infarct-related coronary artery increases myocardial perfusion assessed by index of microcirculatory resistance (IMR) compared with conventional primary PCI. STUDY DESIGN PATA STEMI is a single-center, prospective, randomized trial with a planned inclusion of 128 patients with the first STEMI. Prior to coronary angiography, patients are randomly assigned to thrombus aspiration using the Eliminate aspiration catheter (Terumo Medical Supply, Japan) or to conventional primary PCI. After completion of primary PCI, IMR is determined both in infarct-related artery and in noninfarct-related arteries without critical stenoses. The primary end-point is a group mean value of IMR after thrombus aspiration compared with conventional primary PCI. Secondary end-points are myocardial perfusion grade, resolution of ST-segment elevation, enzymatic estimation of infarct size, left ventricular remodeling assessed by echocardiographic indices, and major adverse cardiac events rate at 1, 6, and 12 months. CONCLUSION If manual thrombus aspiration significantly reduces microcirculatory resistance, thereby improving myocardial perfusion, it may become the routine strategy in primary PCI.
On the complexity of scheduling real-time tasks with self-suspensions on one processor

Integrating practical factors in scheduling theory is a major issue. Efficient schedulability tests (polynomial time or pseudo-polynomial time algorithms) are known for preemptive, independent tasks. In this paper, tasks are allowed to self-suspend. In practice, the real-time kernel suspends a task when it requests an external blocking operation. We study feasibility analysis problems from the computational complexity point of view. The problem is proved NP-hard in the strong sense for periodic, preemptive or non-preemptive task sets. If we allow tasks to have several flows of control (multi-threaded tasks), then the corresponding feasibility problem is shown to be NP-hard in the strong sense in the case of unit execution time threads.
Performance improvement of ABT protocols with combined bandwidth/buffer reservation

ABT (ATM block transfer) is expected for effectively transferring highly bursty data traffic in ATM networks. In the past work, ABT/IT has been shown to be robust in that its performance is not much affected by the propagation delay when compared with ABT/DT. However, when the traffic load becomes heavy and/or when the number of hop counts of the connection becomes large, the throughput of ABT/IT is drastically decreased. We propose a new protocol, buffered ABT/IT, which makes reservation on the buffer as well as the bandwidth. The approximate analysis method is then developed for buffered ABT/IT. Through numerical examples, we show that it can much improve the performance even in the above conditions by comparison with the exiting ABT protocols.
Performance and sensitivity evaluation of 3D spot detection methods in confocal microscopy

Reliable 3D detection of diffraction‐limited spots in fluorescence microscopy images is an important task in subcellular observation. Generally, fluorescence microscopy images are heavily degraded by noise and non‐specifically stained background, making reliable detection a challenging task. In this work, we have studied the performance and parameter sensitivity of eight recent methods for 3D spot detection. The study is based on both 3D synthetic image data and 3D real confocal microscopy images. The synthetic images were generated using a simulator modeling the complete imaging setup, including the optical path as well as the image acquisition process. We studied the detection performance and parameter sensitivity under different noise levels and under the influence of uneven background signal. To evaluate the parameter sensitivity, we propose a novel measure based on the gradient magnitude of the F1 score. We measured the success rate of the individual methods for different types of the image data and found that the type of image degradation is an important factor. Using the F1 score and the newly proposed sensitivity measure, we found that the parameter sensitivity is not necessarily proportional to the success rate of a method. This also provided an explanation why the best performing method for synthetic data was outperformed by other methods when applied to the real microscopy images. On the basis of the results obtained, we conclude with the recommendation of the HDome method for data with relatively low variations in quality, or the Sorokin method for image sets in which the quality varies more. We also provide alternative recommendations for high‐quality images, and for situations in which detailed parameter tuning might be deemed expensive. © 2015 International Society for Advancement of Cytometry
Giant cell arteritis: a rare disease in Asians.

A 69-year-old, Han Chinese, male patient attended the Headache Clinic with a 4-month history of gradually worsening, daily headache. The headache was described as a constant, dull, bilateral, temporal area pain. On examination, his temporal arteries were palpable, tender, sinuous, and enlarged (Fig. 1). The rest of the physical examination was unremarkable. His erythrocyte sedimentation rate (ESR) was 103 mm/h (normal 20 mm/h), C-reactive protein (CRP) was 119 mg/L (normal 10 mg/L), and a brain computed tomography scan was normal. Temporal artery biopsy was performed and revealed multinucleated giant cell infiltration of the vessel with areas of thickening and inflammation, thus verifying the diagnosis of giant cell arteritis (GCA) (Fig. 2). After 8 days of treatment with prednisolone, his headache and tenderness of temporal arteries both disappeared. GCA is a granulomatous inflammatory vasculopathy usually occurring in white individuals aged over 50 years, and it is a rare disease in Asians. A Japanese nationwide survey showed that the prevalence of GCA in Japan is extremely low (1.47 per 100,000 population). All available evidences suggested that GCA is an antigen-driven disease with local T-cell and macrophage activation in the vessel wall, and both environmental and genetic factors play important roles. The pathologic change of GCA is characterized by nodular granulomatous inflammation of the involved vessels. The reversible vision loss is the most-feared complication. The classification criteria for the diagnosis of GCA are well established, and patients were classified as suffering GCA if they met at least 3 of the criteria. In this case, the patient met all the 5 characteristics of the criteria, so it was an extremely rare case in Asians. Corticosteroids should be given as early as possible to minimize the inreversible complications.
A 0.05-mm2 110-μW 10-b self-calibrating successive approximation ADC core in 0.18-μm CMOS

We present a 10-bit 1-MS/s successive approximation analog-to-digital converter core including a charge redistribution digital-to-analog converter and a comparator. A new linearity calibration technique enables use of a nearly minimum capacitor limited by kT/C noise. The ADC core without digital blocks has been fabricated in a 0.18-mum CMOS process and consumes 110muW at 1.8 V power supply. With the calibration it achieves 9.0-dB improvement of SNDR and 23.3dB improvement of SFDR. The measured SNDR and SFDR are 51.1 dB and 69.8 dB respectively.
Method of synthesized phase objects for Fourier-Mellin invariant pattern recognition

We present a development of the method of synthesized phase objects (SPO-method) [1] for the rotation invariant pattern recognition. For the conventional method of recognition and the SPO-method, the comparison of the parameters of correlation signals for a number of amplitude objects is executed under the realization of a rotation in an optical-digital joint Fourier transform correlator.
Metalloprotease-Disintegrin MDC9: Intracellular Maturation and Catalytic Activity*

Metalloprotease disintegrins are a family of membrane-anchored glycoproteins that are known to function in fertilization, myoblast fusion, neurogenesis, and ectodomain shedding of tumor necrosis factor (TNF)-α. Here we report the analysis of the intracellular maturation and catalytic activity of the widely expressed metalloprotease disintegrin MDC9. Our results suggest that the pro-domain of MDC9 is removed by a furin-type pro-protein convertase in the secretory pathway before the protein emerges on the cell surface. The soluble metalloprotease domain of MDC9 cleaves the insulin B-chain, a generic protease substrate, providing the first evidence that MDC9 is catalytically active. Soluble MDC9 appears to have distinct specificities for cleaving candidate substrate peptides compared with the TNF-α convertase (TACE/ADAM17). The catalytic activity of MDC9 can be inhibited by hydroxamic acid-type metalloprotease inhibitors in the low nanomolar range, in one case with up to 50-fold selectivity for MDC9 versus TACE. Peptides mimicking the predicted cysteine-switch region of MDC9 or TACE inhibit both enzymes in the low micromolar range, providing experimental evidence for regulation of metalloprotease disintegrins via a cysteine-switch mechanism. Finally, MDC9 is shown to become phosphorylated when cells are treated with the phorbol ester phorbol 12-myristate 13-acetate, a known inducer of protein ectodomain shedding. This work implies that removal of the inhibitory pro-domain of MDC9 by a furin-type pro-protein convertase in the secretory pathway is a prerequisite for protease activity. After pro-domain removal, additional steps, such as protein kinase C-dependent phosphorylation, may be involved in regulating the catalytic activity of MDC9, which is likely to target different substrates than the related TNF-α-convertase.
Molecular cloning and sequencing of ama-1, the gene encoding the largest subunit of Caenorhabditis elegans RNA polymerase II

Two genomic sequences that share homology with Rp11215, the gene encoding the largest subunit of RNA polymerase II in Drosophila melanogaster, have been isolated from the nematode Caenorhabditis elegans. One of these sequences was physically mapped on chromosome IV within a region deleted by the deficiency mDf4, 25 kilobases (kb) from the left deficiency breakpoint. This position corresponds to ama-1 (resistance to alpha-amanitin), a gene shown previously to encode a subunit of RNA polymerase II. Northern (RNA) blotting and DNA sequencing revealed that ama-1 spans 10 kb, is punctuated by 11 introns, and encodes a 5.9-kb mRNA. A cDNA clone was isolated and partially sequenced to confirm the 3' end and several splice junctions. Analysis of the inferred 1,859-residue ama-1 product showed considerable identity with the largest subunit of RNAP II from other organisms, including the presence of a zinc finger motif near the amino terminus, and a carboxyl-terminal domain of 42 tandemly reiterated heptamers with the consensus Tyr Ser Pro Thr Ser Pro Ser. The latter domain was found to be encoded by four exons. In addition, the sequence oriented ama-1 transcription with respect to the genetic map. The second C. elegans sequence detected with the Drosophila probe, named rpc-1, was found to encode a 4.8-kb transcript and hybridized strongly to the gene encoding the largest subunit of RNA polymerase III from yeast, implicating rpc-1 as encoding the analogous peptide in the nematode. By contrast with ama-1, rpc-1 was not deleted by mDf4 or larger deficiencies examined, indicating that these genes are no closer than 150 kb. Genes flanking ama-1, including two collagen genes, also have been identified.
The Distribution of Rates of Spontaneous Mutation over Viruses, Prokaryotes, and Eukaryotes

ABSTRACT: Although mutation has chaotic aspects, spontaneous mutation rates assume certain characteristic values when expressed per genome per genome duplication. The rate among lytic RNA viruses is roughly 1, while the rate among retroelements is roughly 0.2. The rate among viral and cellular microbes with DNA chromosomes is close to 0.0034. Mutation rates among higher eukaryotes, estimated from specific‐locus studies, vary greatly. Most of this variation can be suppressed if the rates are expressed per cell division instead of per sexual generation, and if the genome size is taken to be only a little larger than the sum of the protein‐encoding sequences; then, the mutation rate is roughly 0.01. The reasons for different characteristic mutation rates among different organism groups remain mysterious and pose a substantial challenge to students of evolution.
Clinical outcomes of and patient satisfaction with different incision methods for donor hepatectomy in living donor liver transplantation

With the decrease in the average donor age and the increase in the proportion of female donors, both donor safety and cosmetic appearance are major concerns for some living donors in living donor liver transplantation (LDLT) because a large abdominal incision is needed that may influence the donor's quality of life. In all, 429 donors who underwent donor hepatectomy for LDLT from April 2010 to February 2013 were included in the study. Donors were divided into 3 groups based on the type of incision: conventional inverted L incision (n = 268; the C group), upper midline incision (n = 147; the M group), and transverse incision with laparoscopy (n = 14; the T group). Demographics, perioperative outcomes, postoperative complications for donors and recipients, and questionnaire‐derived donor satisfaction with cosmetic appearance were compared. The mean age was lower (P < 0.001), the female ratio was higher (P < 0.001), and the body mass index (BMI) was lower (P = 0.017) in the M and T groups versus the C group. The operation time (P < 0.001) and the hospital stay duration (P = 0.010) were lowest in the M group. The postoperative complications did not differ by the type of incision and also did not show any significant effect in a multivariate analysis (P = 0.867). In the assessment of questionnaire‐derived donor satisfaction matched by age (±5 years), sex, graft, height, weight, and BMI, a more satisfactory cosmetic result and more self‐confidence were noted in the M and T groups versus the C group. In conclusion, the use of a minimal incision is technically feasible for some donor hepatectomy cases with a favorable safety profile. The patient satisfaction levels were greater with improved cosmetic outcomes in cases of minimal incision versus cases of conventional incision. Liver Transpl 21:72‐78, 2015. © 2014 AASLD.
Metapopulation Dynamics and Amphibian Conservation

Abstract: In many respects, amphibian spatial dynamics resemble classical metapopulation models, in which subpopulations in breeding ponds blink in and out of existence and extinction and colonization rates are functions of pond spatial arrangement. This “ponds‐as‐patches” view of amphibian spatial dynamics is useful in several respects. First, it highlights the importance of regional and landscape processes in determining local patterns of abundance. Second, it offers a straightforward, pond‐based approach to monitoring and managing amphibian populations. For many species, however, the ponds‐as‐patches view may be an oversimplification and metapopulation structure may be more apparent than real. Changes in distribution may be caused by processes other than extinction and recolonization, and most extinctions probably result from deterministic factors, not stochastic processes. In addition, the effects of pond isolation appear to be important primarily in disturbed environments, and in many cases these isolation effects may be better explained by the distribution of terrestrial habitats than by the distribution of breeding ponds. These complications have important implications for both researchers and managers. For researchers, future efforts need to determine the mechanisms underlying patterns of abundance and distributional change and patterns in amphibian populations. For managers, effective conservation strategies must successfully balance metapopulation considerations with careful attention to local habitat quality. Furthermore, translocations and active management may be indispensable tools for conserving amphibians in landscapes containing multiple breeding ponds.
Sensitizers in inelastic electron tunneling spectroscopy: a first-principles study of functional aromatics on Cu(111)

Low sensitivity is a key problem in inelastic electron tunneling spectroscopy (IETS) with the scanning tunneling microscope. Using first-principles simulations, we predict different means to tune the IETS sensitivity of symmetrical functional aromatics on a Cu(111) surface. We show how the IET-spectra of phenyl-NO2 compounds can be greatly enhanced as compared to pristine phenyl. More precisely, the NO2 substituent qualifies as a sensitizer of low-frequency wagging modes, but also as a quencher of high-frequency stretching modes. At variance, the CO2 substituent is found to suppress the whole IET-activity. The head-up (non-anchoring) and head-down (anchoring) configurations of the functional group lead to minor changes in the signals, nevertheless allowing access to discriminate configurational features. It is shown how to disentangle the electronic and steric effects of the substituent in the STM junction.
Patients with Systemic Lupus Erythematosus Nucleotide-Releasing Protein 1 in a Subset of Defective Expression of Ras Guanyl

Dysregulation of Ras guanyl nucleotide-releasing protein 1 (RasGRP1) in mice results in a systemic lupus erythematosus (SLE)-like disorder. We therefore looked for defective isoforms and/or diminished levels of human RasGRP1 in a cohort of SLE patients. PBMCs were collected from twenty healthy individuals and thirty-two patients with SLE. mRNA was isolated and ﬁve RasGRP1 cDNAs from each subject were sequenced. T cell lysates from healthy controls and SLE patients also were evaluated for their levels of RasGRP1 protein. The accumulated data led to the identiﬁcation of 13 new splice variants of the human RasGRP1 gene. Not only did our SLE patients have increased levels and types of these defective transcripts relative to normal individuals, two SLE patients were identiﬁed whose PBMCs and T cells contained very little, if any, functional RasGRP1 mRNA and protein. The presence of aberrantly spliced RasGRP1 transcripts also was correlated with lower levels of RasGRP1 protein in the patients’ T cells. The lack of the normal isoform of RasGRP1 in some SLE patients and the increased prevalence of defective isoforms of RasGRP1 in others raise the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients. The Journal of Immunology, 2007, 179: 4890–4900.