Miracle-dz/UniFAR-FTUs huggingface dataset:
A Cytochrome b562 Variant with a c-Type Cytochrome CXXCH Heme-binding Motif as a Probe of the Escherichia coli Cytochrome c Maturation System*

Cytochrome b562 is a periplasmic Escherichia coli protein; previous work has shown that heme can be attached covalently in vivo as a consequence of introduction of one or two cysteines into the heme-binding pocket. A heterogeneous mixture of products was obtained, and it was not established whether the covalent bond formation was catalyzed or spontaneous. Here, we show that coexpression from plasmids of a variant of cytochrome b562 containing a CXXCH heme-binding motif with the E. coli cytochrome c maturation (Ccm) proteins results in an essentially homogeneous product that is a correctly matured c-type cytochrome. Formation of the holocytochrome was accompanied by substantial production of its apo form, in which, for the protein as isolated, there is a disulfide bond between the two cysteines in the CXXCH motif. Following addition of heme to reduced CXXCH apoprotein, spontaneous covalent addition of heme to polypeptide occurred in vitro. Strikingly, the spectral properties were very similar to those of the material obtained from cells in which presumed uncatalyzed addition of heme (i.e. in the absence of Ccm) had been observed. The major product from uncatalyzed heme attachment was an incorrectly matured cytochrome with the heme rotated by 180° relative to its normal orientation. The contrast between Ccm-dependent and Ccm-independent covalent attachment of heme indicates that the Ccm apparatus presents heme to the protein only in the orientation that results in formation of the correct product and also that heme does not become covalently attached to the apocytochrome b562 CXXCH variant without being handled by the Ccm system in the periplasm. The CXXCH variant of cytochrome b562 was also expressed in E. coli strains deficient in the periplasmic reductant DsbD or oxidant DsbA. In the DsbA- strain under aerobic conditions, c-type cytochromes were made abundantly and correctly when the Ccm proteins were expressed. This contrasts with previous reports indicating that DsbA is essential for cytochrome c biogenesis in E. coli.
Anti-forensics of contrast enhancement in digital images

The blind detection of contrast enhancement in digital images has attracted much attention of the forensic analyzers. In this paper, we propose new variants of contrast enhancement operators which are undetectable by the existing contrast enhancement detectors based on the peak-gap artifacts of the pixel graylevel histogram. Local random dithering is introduced into the design of contrast enhancement mapping for removing such artifacts. Effectiveness of the proposed anti-forensic scheme is validated by experimental results on a large image database for various parameter settings. Both detectability and the resulting image quality are evaluated via comparison with the traditional contrast enhancement. The developed anti-forensic techniques could verify the reliability of existing contrast enhancement forensic tools against sophisticated attackers and serve as the targets for developing more reliable and secure forensic techniques.
Reduced exposure to calcineurin inhibitors in renal transplantation.

n engl j med 358;23 www.nejm. org june 5, 2008 2518 Achilles’ heel of drug-eluting stents as compared with bare-metal stents, before our study, there was little information about the shortand longterm comparative safety and efficacy of these devices for off-label indications. Our study has filled the short-term knowledge gap with data from 1 year of follow-up, and with the recent receipt of funding from the National Heart, Lung, and Blood Institute Dynamic Registry for continued follow-up of these patients, it is our goal to help fill the knowledge gap regarding the long-term safety and efficacy of these devices. Oscar C. Marroquin, M.D. Suresh R. Mulukutla, M.D.
Human Computation for Object Detection

Object detection is a key component of many computer vision systems. This paper investigates human computation as a platform for object detection. We investigate and report on the quality of raw labels obtained from several sources of human labor. We find that the performance is not the same in all cases. We investigate and report on the quality of a simple aggregation algorithm. Finally, we compare our human computation based object detector against existing computer vision based approaches.
Development of neuropeptide Y (NPY) immunoreactive neurons in the rat occipital cortex: A combined immunohistochemical‐autoradiographic study

The postnatal development of neuropeptide Y (NPY)‐immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14–E21, has been studied in the rat occipital cortex. Immunohistochemistry combined with autoradiography showed evidence of a modified “inside‐‐out” pattern of maturation. NPY‐neurons are generated between E14 and E20 and are found in layers II–VI of the cortex and the subcortical white matter. NPY neurons from all these birthdates are overproduced at first, although cells generated at E16 produce the greatest excess, followed by E15 and E17. Some of these transient neurons are found in the “wrong” layer for their birthdates, and their elimination produces a more “correct” alignment at maturity. However, most of the NPY neurons that survive are generated at E17, and these cells are found throughout layers II–VI with a preponderance in layer VI. This evidence is strongly suggestive of cell death rather than merely cessation of production of NPY.
Vancomycin: we can't get there from here.

BACKGROUND We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. METHODS A series of Monte Carlo simulations was performed for vancomycin regimens ranging from . 5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from . 5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. RESULTS At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%(.) At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. CONCLUSIONS This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin.
Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria

Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) was originally identified as a positive regulator of drug detoxifying enzyme gene expression during exposure to environmental electrophiles. Currently, Nrf2 is known to regulate the expression of hundreds of cytoprotective genes to counteract endogenously or exogenously generated oxidative stress. Furthermore, when activated in human tumors by somatic mutations, Nrf2 confers growth advantages and chemoresistance by regulating genes involved in various processes such as the pentose phosphate pathway and nucleotide synthesis in addition to antioxidant proteins. Interestingly, increasing evidence shows that Nrf2 is associated with mitochondrial biogenesis during environmental stresses in certain tissues such as the heart. Furthermore, SKN-1, a functional homolog of Nrf2 in C. elegans, is activated by mitochondrial reactive oxygen species and extends life span by promoting mitochondrial homeostasis (i.e., mitohormesis). Similarly, Nrf2 activation was recently observed in the heart of surfeit locus protein 1 (Surf1) -/- mice in which cellular respiration was decreased due to cytochrome c oxidase defects. In this review, we critically examine the relationship between Nrf2 and mitochondria and argue that the Nrf2 stress pathway intimately communicates with mitochondria to maintain cellular homeostasis during oxidative stress.
Using Semantic Features Derived from Word-Space Models for Swedish Coreference Resolution

We investigate the effect of using wordspace models as an approximation of the kind of lexico-semantic and commonsense knowledge needed for coreference resolution of definite descriptions, that is, definite NPs with a common noun as head, for Swedish news text. We contrast a system using semantic knowledge from the word-space models with a semantically ignorant system and another system drawing its semantic information from a semantic dictionary called SynLex. We demonstrate an improvement in the results for two different evaluation tasks for the system using word space-derived semantic information over both other systems.
A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer

Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences contain multiple regulatory motifs and hence are capable of influencing expression of host genes. TEs are known to be released from epigenetic repression and can become transcriptionally active in cancer. Such activation could also lead to lineage-inappropriate activation of oncogenes, as previously described in lymphomas. However, there are few reports of this mechanism occurring in non-blood cancers. Here, we re-analyzed whole transcriptome data from a large cohort of patients with colon cancer, compared to matched normal colon control samples, to detect genes or transcripts ectopically expressed through activation of TE promoters. Among many such transcripts, we identified six where the affected gene has described role in cancer and where the TE-driven gene mRNA is expressed in primary colon cancer, but not normal matched tissue, and confirmed expression in colon cancer-derived cell lines. We further characterized a TE-gene chimeric transcript involving the Interleukin 33 (IL-33) gene (termed LTR-IL-33), that is ectopically expressed in a subset of colon cancer samples through the use of an endogenous retroviral long terminal repeat (LTR) promoter of the MSTD family. The LTR-IL-33 chimeric transcript encodes a novel shorter isoform of the protein, which is missing the initial N-terminus (including many conserved residues) of Native IL-33. In vitro studies showed that LTR-IL-33 expression is required for optimal CRC cell line growth as 3D colonospheres. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in colon cancer.
Fuzzy logic based coordinated voltage regulation method for distribution system with multiple synchronous generators

The continued interest in the distributed generation (DG) sources in recent years is leading to the growth of a number of generators connected to distribution network. One of the major concern due to connection of these generators is the rise in steady state voltage level of distribution system. Present network design practice is to limit the generator capacity to a level at which the upper voltage limit is not exceeded. This reduces the efficiency of DG system. This paper proposes a coordinated voltage control scheme using fuzzy logic based power factor controller, for distribution network with multiple synchronous generators. In the proposed scheme individual generators participate in voltage regulation of the distribution system, based on their participation factor determined using sensitivity analysis. The simulation results presented in the paper show the effectiveness of the method.
Phenotypic variability in familial hypercholesterolaemia: an update

Heterozygous familial hypercholesterolaemia is among the most common inherited dominant disorders, and is characterized by severely elevated LDL-cholesterol levels and premature cardiovascular disease. Although the cause of familial hypercholesterolaemia is monogenic, there is a substantial variation in the onset and severity of atherosclerotic disease symptoms. Additional atherogenic risk factors of environmental, metabolic and genetic origin, in conjunction with the LDL receptor defect, are presumed to influence the clinical phenotype in familial hypercholesterolaemia. The present review discusses recent developments in this field.
Concentration Dependence of the Binding of Ouabain to Isolated Guinea Pig Atria

The influence of eight concentrations of ouabain (6 X 10-9 to 3 X 10-6 M) on force of contraction and on cellular Na, K contents of isolated guinea pig left atria was determined and compared to he binding of the drug. Rate and amount of ouabain binding were found to be concentration dependent. At a frequency of 1 Hz ouabain was bound but remained ineffective with regard to contractile force up to a concentration of 3 X 10-8 M, corresponding to an occupation of about 20% of available binding sites. From 1 to 4 X 10-7 M the occupied binding sites ranged between 20 and 80%, respectively. Over this range the drug exerted positive inotropic effects, yet cellular Na and K concentrations remained unaltered for as long as the inotropic effect was maintained. Greater than 80% occupation of binding sites at concentrations between 4 X 10-7 and 3 X 10-6 M was followed by an intoxication of the muscle, the ionic gradients deteriorated, and the binding process was counteracted by a spontaneous release of ouabain. Under the prevailing conditions a total amount of 9 X 10-7 moles of binding sites were determined per kilogram of tissue. The observation that the number of binding sites varies with different frequencies results from different overall pump rates. The concentration of Na, K-ATPase, however, available for mediating the positive inotropic effect decreased with increasing frequency of contraction. The results suggest that constant Na and K gradients are prerequisites for a maintained positive inotropic effect by cardiac glycosides and that the positive inotropic effect is not the consequence of an inhibition of the Na, K transport.
Aspherical manifolds, relative hyperbolicity, simplicial volume and assembly maps

This paper contains examples of closed aspherical manifolds obtained as a by-product of recent work by the author [arXiv:math.GR/0509490] on the relative strict hyperbolization of polyhedra. The following is proved. (I) Any closed aspherical triangulated n-manifold M^n with hyperbolic fundamental group is a retract of a closed aspherical triangulated (n+1)-manifold N^(n+1) with hyperbolic fundamental group. (II) If B_1,. ,B_m are closed aspherical triangulated n-manifolds, then there is a closed aspherical triangulated manifold N of dimension n+1 such that N has nonzero simplicial volume, N retracts to each B_k, and \pi_1(N) is hyperbolic relative to \pi_1(B_k)'s. (III) Any finite aspherical simplicial complex is a retract of a closed aspherical triangulated manifold with positive simplicial volume and non-elementary relatively hyperbolic fundamental group.
Non-Structural Proteins of Arthropod-Borne Bunyaviruses: Roles and Functions

Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA viruses. The family includes several emerging and re-emerging viruses of humans, animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus. Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and the different structural proteins, one or several non-structural proteins. These non-structural proteins are not always essential for virus growth and replication but can play an important role in viral pathogenesis through their interaction with the host innate immune system. In this review, we will summarize current knowledge and understanding of insect-borne bunyavirus non-structural protein function(s) in vertebrate, plant and arthropod.
Functional Expression of a Fungal Laccase in Saccharomyces cerevisiae by Directed Evolution

ABSTRACT Laccase from Myceliophthora thermophila (MtL) was expressed in functional form in Saccharomyces cerevisiae. Directed evolution improved expression eightfold to the highest yet reported for a laccase in yeast (18 mg/liter). Together with a 22-fold increase in kcat, the total activity was enhanced 170-fold. Specific activities of MtL mutants toward 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and syringaldazine indicate that substrate specificity was not changed by the introduced mutations. The most effective mutation (10-fold increase in total activity) introduced a Kex2 protease recognition site at the C-terminal processing site of the protein, adjusting the protein sequence to the different protease specificities of the heterologous host. The C terminus is shown to be important for laccase activity, since removing it by a truncation of the gene reduces activity sixfold. Mutations accumulated during nine generations of evolution for higher activity decreased enzyme stability. Screening for improved stability in one generation produced a mutant more stable than the heterologous wild type and retaining the improved activity. The molecular mass of MtL expressed in S. cerevisiae is 30% higher than that of the same enzyme expressed in M. thermophila (110 kDa versus 85 kDa). Hyperglycosylation, corresponding to a 120-monomer glycan on one N-glycosylation site, is responsible for this increase. This S. cerevisiae expression system makes MtL available for functional tailoring by directed evolution.
Epidemiology and Management of Liver Metastases From Colorectal Cancer

Objective/Background:Little is known about the epidemiology and the management of liver metastases from colorectal cancer at a population level. The aim of this population-based study was to report on the incidence, treatment, and prognosis of synchronous and metachronous liver metastases. Methods:Data were obtained from the population-based cancer registry of Burgundy (France). Results:The proportion of patients with synchronous liver metastases was 14.5%. Age-standardized incidence rates were 7.6 per 100,000 in males, 3.7 per 100,000 in females. The 5-year cumulative metachronous liver metastasis rate was 14.5%. It was 3.7% for TNM stage I tumors, 13.3% for stage II, and 30.4% for stage III (P < 0.001). The risk of liver metastasis was also associated to gross features. Resection for cure was performed in 6.3% of synchronous liver metastases and 16.9% of metachronous liver metastases. Age, presence of another site of recurrence, and period of diagnosis were independent factors associated with the performance of a resection for cure. The 1- and 5-year survival rates were 34.8% and 3.3% for synchronous liver metastases. Their corresponding rates were, respectively, 37.6% and 6.1% for metachronous liver metastases. Conclusion:Liver metastases from colorectal cancer remain a substantial problem. More effective treatments and mass screening represent promising approaches to decrease this problem.
Mismatch Negativity (MMN) y esquizofrenia: Una revisión

El componente Mismatch Negativity (MMN) es un Potencial Relacionado con Eventos (PRE) de tipo auditivo, que es generado por la respuesta cerebral automatica a cualquier cambio en la estimulacion auditiva que excede un limite correspondiente al umbral de discriminacion. Se ha reportado amplia y consistentemente menor amplitud de MMN en pacientes con esquizofrenia reciente y cronica, por lo que se ha propuesto que este componente se relaciona con alteraciones en la memoria sensorial y en las capacidades de integracion del estimulo, las cuales parecen progresar a lo largo de la enfermedad. Recientemente se han abierto nuevas lineas de investigacion al respecto, y se han realizado estudios con familiares de pacientes con esquizofrenia para evaluar la eficacia de la MMN como endofenotipo. Asimismo, se han llevado a cabo estudios de MMN en prodromos o sujetos en riesgo clinico de desarrollar esquizofrenia, con la finalidad de conocer si existen alteraciones en el procesamiento cerebral previas al inicio de la enfermedad. Los resultados de estos trabajos han arrojado resultados prometedores, que sugieren la presencia de alteraciones sutiles en el procesamiento de estimulos auditivos en esta poblacion, las cuales parecen aumentar con la aparicion de la enfermedad. Es asi como el componente MMN puede ser una herramienta electrofisiologica eficaz para proporcionar informacion sobre el procesamiento automatico auditivo relacionado con la esquizofrenia y su cronicidad, asi como para indicar la vulnerabilidad genetica y riesgo clinico para desarrollarla. Sin embargo, es necesario realizar estudios futuros comparables y replicables que permitan confirmar tales hallazgos. Palabras clave: Mismatch Negativity (MMN), Esquizofrenia, Prodromos, Sujetos en riesgo clinico, Endofenotipo, Memoria sensorial auditiva
Hardware task scheduling and placement in operating systems for dynamically reconfigurable SoC

Existing operating systems can manage the execution of software tasks efficiently, however the manipulation of hardware tasks is very limited. In the research on the design and implementation of an embedded operating system that manages both software and hardware tasks in the same framework, two major issues are the dynamic scheduling and the dynamic placement of hardware tasks into a reconfigurable logic space in an SoC . The distinguishing criteria for good dynamic scheduling and placement methods include the total schedule length and the amount of fragmentation incurred while tasks are dynamically placed and replaced. Existing methods either do not take fragmentation into consideration or postpone the consideration of fragmentation to a later stage of space allocation. In our method, we try to reduce fragmentation during placement itself. The advantage of such an approach is that not only the reconfigurable space is utilized more efficiently, but the total schedule length is also reduced, that is, hardware tasks complete faster. Experimental results on large random tasks sets have shown that the proposed improvement is as much as 23.3% in total fragmentation and 2.0% in total schedule time.