Miracle-dz/UniFAR-FTUs huggingface dataset:
The long-term clinical impact of biochemical recurrence of prostate cancer 5 or more years after radical prostatectomy.

PURPOSE Information regarding the clinical impact of delayed (5 years or greater) biochemical failure (BF) after radical prostatectomy (RP) is lacking. We undertook an investigation to differentiate the innocuous recurrence of serum prostate specific antigen (PSA) from that which heralds an eventual clinical failure (CF), and to determine if there is a period following RP when a patient is cured of clinical disease. MATERIALS AND METHODS Men with clinically localized prostate cancer (PCA) undergoing RP (1987 to 1995) were identified from our longitudinal PCA registry. Outcome measurements were based on the detection of post-RP serum PSA 0.4 ng/ml or greater, clinical identification of cancer recurrence and disease related death. RESULTS Following RP in 3,903 eligible men, 33% had a detectable PSA (median followup 8.8 years). Of these BFs 27% occurred after 5 or more disease-free years. Currently, 29% of all men with BF have clinical evidence of PCA, with 8% dying of PCA (median actuarial survival time from CF to death 9.8 years). Progression from BF to CF was not significantly altered by the disease-free interval (p = 0.544). A PSA doubling time less than 12 months significantly increased the risk of CF regardless of the interval from surgery. Risk factors for BF were significant throughout the duration of followup. CONCLUSIONS Patients are at prolonged risk for BF and CF following RP. Regardless of the timing of the initial PSA recurrence the PSA doubling time is the most powerful predictor of progression, stratifying patients with BF into high and low risk groups for CF.
A Mutation within the β Subunit of Escherichia coli RNA Polymerase Impairs Transcription from Bacteriophage T4 Middle Promoters

ABSTRACT During infection of Escherichia coli, bacteriophage T4 usurps the host transcriptional machinery, redirecting it to the expression of early, middle, and late phage genes. Middle genes, whose expression begins about 1 min postinfection, are transcribed both from the extension of early RNA into middle genes and by the activation of T4 middle promoters. Middle-promoter activation requires the T4 transcriptional activator MotA and coactivator AsiA, which are known to interact with σ70, the specificity subunit of RNA polymerase. T4 motA amber [motA(Am)] or asiA(Am) phage grows poorly in wild-type E. coli. However, previous work has found that T4 motA(Am)does not grow in the E. coli mutant strain TabG. We show here that the RNA polymerase in TabG contains two mutations within its β-subunit gene: rpoB(E835K) and rpoB(G1249D). We find that the G1249D mutation is responsible for restricting the growth of either T4 motA(Am)or asiA(Am) and for impairing transcription from MotA/AsiA-activated middle promoters in vivo. With one exception, transcription from tested T4 early promoters is either unaffected or, in some cases, even increases, and there is no significant growth phenotype for the rpoB(E835K G1249D) strain in the absence of T4 infection. In reported structures of thermophilic RNA polymerase, the G1249 residue is located immediately adjacent to a hydrophobic pocket, called the switch 3 loop. This loop is thought to aid in the separation of the RNA from the DNA-RNA hybrid as RNA enters the RNA exit channel. Our results suggest that the presence of MotA and AsiA may impair the function of this loop or that this portion of the β subunit may influence interactions among MotA, AsiA, and RNA polymerase.
Rethinking Development Space in Emerging Countries: Turkey's Conservative Countermovement

type="main"> Despite an increasingly flexible global policy context, most emerging countries refuse to venture beyond their pre-existing development strategies. This article contends that in some cases domestic political constraints under liberalized markets might preclude policy dynamism. In particular, it draws attention to the tension between market expansion and social cohesion as a formative influence over policy patterns. This tension is sometimes addressed through a conservative countermovement whereby liberally-oriented governments entice sections of the poor into broad electoral coalitions by employing palliative interventions alongside market-expanding policies. Turkey's ruling Justice and Development Party (AKP) is one example. Central to the Turkish case has been the redeployment of the country's historic foreign capital-dependent pattern of growth in the service of selective redistribution and credit-fuelled consumerism. The ensuing deficit-led neoliberal populism assured stable and equitable growth in the extraordinary international and domestic context of the mid-2000s, but has proven unfeasible since the global crisis. However, this coupling of market and social preferences has become politically so firmly entrenched in time that it now constrains the policy options to address Turkey's developmental impasse.
Comparison of gyrA Mutations, Cyclohexane Resistance, and the Presence of Class I Integrons in Salmonella enterica from Farm Animals in England and Wales

ABSTRACT This study is focused on real-time detection of gyrA mutations and of the presence of class I integrons in a panel of 100 veterinary isolates of Salmonella enterica from farm animals. The isolates were selected on the basis of resistance to nalidixic acid, representing a variety of the most prevalent serotypes in England and Wales. In addition, organic solvent (cyclohexane) resistance in these isolates was investigated in an attempt to elucidate the presence of efflux pump mechanisms. The most prevalent mutation among the isolates studied was Asp87-Asn (n = 42), followed by Ser83-Phe (n = 38), Ser83-Tyr (n = 12), Asp87-Tyr (n = 4), and Asp87-Gly (n = 3). Two distinct subpopulations were identified, separated at the 1-mg/liter breakpoint for ciprofloxacin: 86% of isolates with mutations in codon 83 showed MICs of ≥1 mg/liter, while 89.8% of isolates with mutations in codon 87 presented MICs of ≤0.5 mg/liter. Cyclohexane resistance was more prevalent among Ser83 mutants than among Asp87 mutants (34.7 and 4%, respectively), and in 79% of isolates that presented both gyrA mutations and cyclohexane resistance, the level of ciprofloxacin resistance was ≥2.0 mg/liter. Thirty-four isolates contained class I integrons, with 71% of the S. enterica serovar Typhimurium isolates and 6.9% of isolates belonging to other serotypes containing such elements. The methods used represent sensitive ways of investigating the presence of gyrA mutations and of detecting class-I integrons in Salmonella isolates. The results can be obtained in less than 1 h from single colonies without the need for purifying DNA.
Outbreak of 2009 pandemic influenza A (H1N1) at a New York City school.

BACKGROUND In April 2009, an outbreak of novel swine-origin influenza A (2009 H1N1 influenza) occurred at a high school in Queens, New York. We describe the outbreak and characterize the clinical and epidemiologic aspects of this novel virus. METHODS The New York City Department of Health and Mental Hygiene characterized the outbreak through laboratory confirmation of the presence of the 2009 H1N1 virus in nasopharyngeal and oropharyngeal specimens and through information obtained from an online survey. Detailed information on exposure and the onset of symptoms was used to estimate the incubation period, generation time, and within-school reproductive number associated with 2009 H1N1 influenza, with the use of established techniques. RESULTS From April 24 through May 8, infection with the 2009 H1N1 virus was confirmed in 124 high-school students and employees. In responses to the online questionnaire, more than 800 students and employees (35% of student respondents and 10% of employee respondents) reported having an influenza-like illness during this period. No persons with confirmed 2009 H1N1 influenza or with influenza-like illness had severe symptoms. A linkage with travel to Mexico was identified. The estimated median incubation period for confirmed 2009 H1N1 influenza was 1.4 days (95% confidence interval [CI], 1.0 to 1.8), with symptoms developing in 95% of cases by 2.2 days (95% CI, 1.7 to 2.6). The estimated median generation time was 2.7 days (95% CI, 2.0 to 3.5). We estimate that the within-school reproductive number was 3.3. CONCLUSIONS The findings from this investigation suggest that 2009 H1N1 influenza in the high school was widespread but did not cause severe illness. The reasons for the rapid and extensive spread of influenza-like illnesses are unknown. The natural history and transmission of the 2009 H1N1 influenza virus appear to be similar to those of previously observed circulating pandemic and interpandemic influenza viruses.
MyD88 mediates the decision to die by apoptosis or necroptosis after UV irradiation

UV irradiation-induced cellular damage is classically associated with apoptosis and is known to result in systemic immunosuppression. How the decision to undergo apoptosis is made following UV is not fully understood. We hypothesize that a central mediator of TLR signaling, MyD88, determines cell fate after UV exposure. Survival after UV of immortalized bone marrow-derived macrophages (BMDM) and ex vivo peritoneal macrophages (PM) from MyD88 germline-deficient mice (MyD88-/-) was significantly higher than wild type (WT) PM. UV-induced apoptosis (DNA laddering) in PM and epidermis of MyD88-/- animals versus WT was decreased. In MyD88-/- PM, decreased cleavage of caspase 3, as well as pro-necroptotic protein, RIP1, and a significant increase in transcription and release of pro-inflammatory TNF-α, suggest that necroptosis, rather than apoptosis, has been initiated. In vivo studies confirm this hypothesis after UV, showing low apoptosis by TUNEL and inflammation in MyD88-/- skin sections. Considering that MyD88 participates in many TLR pathways, BMDM from TLR2-/-, TLR4-/- and WT mice were compared for evidence of UV-induced apoptosis. Only TLR4-/- BMDM and PM had a similar phenotype to MyD88-/-, suggesting that the TLR4–MyD88 axis importantly contributes to cell fate decision. Our study describes a new cellular consequence of MyD88 signaling after UV, and may provide rationale for therapies to mitigate UV-induced immunosuppression.
Role of the Adventitia in the Cyclic GMP-Mediated Relaxant Effect of Nω-Hydroxy-L-Arginine in Rat Aorta

Nω-hydroxy-L-arginine (L-NOHA), the stable intermediate of the nitric oxide synthase (NOS)-catalyzed reaction, can induce NO/cyclic GMP-dependent relaxation in the rat aorta, in an endothelium- and NOS-independent manner. In this study, the role of the adventitia in the endothelium-independent effect of L-NOHA was investigated. Despite a decrease in norepinephrine (NE)-induced precontraction, adventitia removal in the rat aorta did not markedly alter the relaxant effect of forskolin, S-nitroso-N-acetylpenicillamine or glyceryl trinitrate. In contrast, both inhibition of NE-induced contraction and relaxation of NE-precontracted rings produced by L-NOHA were diminished in the absence of adventitia. Moreover, exposure to L-NOHA significantly enhanced the cyclic GMP level in the media of the aorta with, but not without adventitia. These findings demonstrate the role of the adventitia in the L-NOHA-induced decrease in tone and increase in cyclic GMP in the endothelium-denuded rat aorta. They suggest that NO or an NO-related compound formed from L-NOHA in the adventitia may produce paracrine effects.
Spatial cognition and the human navigation network in AD and MCI

Background: The mechanisms underlying navigation impairments in Alzheimer disease (AD) are unknown. We characterized navigation in AD and mild cognitive impairment (MCI) to test the hypothesis that navigation disability reflects selective impairments in spatial cognition and relates to atrophy of specific brain regions. Methods: We compared 13 mild AD and 21 MCI patients with 24 controls on a route-learning task that engaged various spatial processes. Using structural MRI and optimized voxel-based morphometry, we also investigated the neural correlates of spatial abilities in a subset of subjects (10 AD, 12 MCI, 21 controls). Results: AD and MCI patients recognized landmarks as effectively as controls, but could not find their locations on maps or recall the order in which they were encountered. Half of AD and one-quarter of MCI patients got lost on the route, compared with less than 10% of controls. Regardless of diagnosis, patients who got lost had lower right posterior hippocampal and parietal volumes than patients and controls who did not get lost. The ability to identify locations on a map correlated with right posterior hippocampal and parietal volumes, whereas order memory scores correlated with bilateral inferior frontal volumes. Conclusions: The navigation disability in Alzheimer disease and mild cognitive impairment (MCI) involves a selective impairment of spatial cognition and is associated with atrophy of the right-lateralized navigation network. Extensive spatial impairments in MCI suggest that navigation tests may provide early markers of cognitive and neural damage.
Risks and returns in hedge funds – econometric and austrian economic perspectives

Hedge funds and funds of hedge funds are some of the preferred ways to access capital market opportunities by institutional investors and high net worth individuals seeking vehicles of absolute return. Risks and returns are difficult to assess because of skewness and kurtosis so that traditional mean and variance analyses are inappropriate. I assess the possible implications of high leverage finance and financial innovations from an Austrian economic viewpoint on the basis of an econometric analysis of hedge fund risk adjusted returns and a historical consideration of asset price shocks in Thailand and Japan.
A multiplication-free digital architecture for 16×16 2-D DCT/DST transform for HEVC

The discrete cosine transform (DCT) is widely employed in image and video coding applications due to its high energy compaction. In addition to 4×4 and 8×8 transforms utilized in earlier video coding standards, the proposed HEVC standard suggests the use of larger transform sizes including 16 × 16 and 32×32 transforms in order to obtain higher coding gains. Further, it also proposes the use of non-square transform sizes as well as the use of the discrete sine transform (DST) in certain intra-prediction modes. The decision on the type of transform used in a given prediction scenario is dynamically made, to obtain required compression rates. This motivated the proposed digital VLSI architecture for a multitransform engine capable of computing 16×16 approximate 2-D DCT/DST transform, with null multiplicative complexity. The relationship between DCT-II and DST-II is employed to compute both transforms using the same digital core, leading to reductions in both area and power. Closed-form relationship between the 16×16 transform and arbitrary smaller sized transform is presented, enabling the usability of this architecture to compute transforms of size 4 · 2P × 4 · 2q where 0 ≤ p, q ≤ 2.
Suppression of a yeast cyclic AMP-dependent protein kinase defect by overexpression of SOK1, a yeast gene exhibiting sequence similarity to a developmentally regulated mouse gene

Saccharomyces cerevisiae cyclic AMP-dependent protein kinase (A kinase) activity is essential for growth and cell cycle progression. Dependence on A kinase function can be partially relieved by the inactivation of a second kinase encoded by the gene YAK1. We have isolated two new genes, SOK1 and SOK2 (suppressor of kinase), as gene dosage suppressors of the conditional growth defect of several temperature-sensitive A kinase mutants. Overexpression of SOK1, like lesions in YAK1, also restores growth to a strain (tpk1 tpk2 tpk3) lacking all A kinase activity. The SOK1 gene is not essential, but a sok1::HIS3 disruption abrogates suppression of an A kinase defect by yak1. These results suggest that Yak1 and Sok1 define a linear pathway that is partially redundant with that of the A kinase. Activation of Sok1, by SOK1 overexpression or by inactivation of the negative regulator Yak1, renders a cell independent of A kinase function. The implications of such a model are particularly intriguing in light of the nuclear localization pattern of the overexpressed Sok1 protein and the primary sequence homology between SOK1 and a recently described, developmentally regulated mouse gene.
Morphological diversity of sperm: A mini review

Sperms are highly specialized cells for delivering DNA from male to the ovum. Incredibly, wide degree of diversity in sperm morphology in their basic structures i.e. head, middle piece and tail is found across species. Differences in terms of overall size of the sperm, shape and number of sperm produced are also incredible. One of the key for this variations or diversity in sperm may be associated with female reproductive tract, sperm competition, testicular size and sperm size and number. Establishing a correlation between sperm morphology and factors influencing them is a phenomenal task. In this mini-review these associations and the anatomical and functional adaptations among different from of sperm cells that have evolved to optimize fertilization success are discussed. Nevertheless, explaining these morphological diversities in sperm cells is a challenging question and it seems that evolutionary biologists have only recently engaged in exploring its links and patterns. From the literatures it seems that there is no causal relationship between sperm size and testicular size, however, the accumulated knowledge do indicates evolution of sperm morphology across species has some associations with female reproductive tract, sperm competition and sperm size and number, however interpreting these results for phylogentic correlations should be approached with caution.
In vitro resistance mechanisms of Neisseria meningitidis against neutrophil extracellular traps

Neisseria meningitidis (Nm) is a leading cause of septicemia in childhood. Nm septicemia is unique with respect to very quick disease progression, high in vivo bacterial replication rate and its considerable mortality. Nm circumvents major mechanisms of innate immunity such as complement system and phagocytosis. Neutrophil extracellular traps (NETs) are formed from neutrophils during systemic infection and are suggested to contain invading microorganisms. Here, we investigated the interaction of Nm with NETs. Both, meningococci and spontaneously released outer membrane vesicles (SOMVs) were potent NET inducers. NETs were unable to kill NET bound meningococci, but slowed down their proliferation rate. Using Nm as model organism we identified three novel mechanisms how bacteria can evade NET‐mediated killing: (i) modification of lipid A of meningococcal LPS with phosphoethanolamine protected Nm from NET‐bound cathepsin G; (ii) expression of the high‐affinity zinc uptake receptor ZnuD allowed Nm to escape NET‐mediated nutritional immunity; (iii) binding of SOMVs to NETs saved Nm from NET binding and the consequent bacteriostatic effect. Escape from NETs may contribute to the most rapid progression of meningococcal disease. The induction of NET formation by Nm in vivo might aggravate thrombosis in vessels ultimately directing to disseminated intravascular coagulation (DIC).
Resistance of Herpes Simplex Viruses to Nucleoside Analogues: Mechanisms, Prevalence, and Management

ABSTRACT Herpes simplex viruses (HSV) type 1 and type 2 are responsible for recurrent orolabial and genital infections. The standard therapy for the management of HSV infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valacyclovir and famciclovir. These compounds are phosphorylated by the viral thymidine kinase (TK) and then by cellular kinases. The triphosphate forms selectively inhibit the viral DNA polymerase (DNA pol) activity. Drug-resistant HSV isolates are frequently recovered from immunocompromised patients but rarely found in immunocompetent subjects. The gold standard phenotypic method for evaluating the susceptibility of HSV isolates to antiviral drugs is the plaque reduction assay. Plaque autoradiography allows the associated phenotype to be distinguished (TK-wild-type, TK-negative, TK-low-producer, or TK-altered viruses or mixtures of wild-type and mutant viruses). Genotypic characterization of drug-resistant isolates can reveal mutations located in the viral TK and/or in the DNA pol genes. Recombinant HSV mutants can be generated to analyze the contribution of each specific mutation with regard to the drug resistance phenotype. Most ACV-resistant mutants exhibit some reduction in their capacity to establish latency and to reactivate, as well as in their degree of neurovirulence in animal models of HSV infection. For instance, TK-negative HSV mutants establish latency with a lower efficiency than wild-type strains and reactivate poorly. DNA pol HSV mutants exhibit different degrees of attenuation of neurovirulence. The management of ACV- or PCV-resistant HSV infections includes the use of the pyrophosphate analogue foscarnet and the nucleotide analogue cidofovir. There is a need to develop new antiherpetic compounds with different mechanisms of action.
Activating tourists' citizenship behavior for the environment: the roles of CSR and frontline employees' citizenship behavior for the environment

ABSTRACTTourists can serve as contributors to the sustainability of tourist destinations. Thus, tourists’ citizenship behavior for the environment (customer CBE), which contributes to the sustainable greening of tourist destinations, should be activated. The primary aim of our research is to assess the predictive role of corporate social responsibility (CSR) for tourists’ CBE. This research also seeks to investigate the effect of CSR on employees’ organizational citizenship behavior for the environment (employee OCBE). Our research model was tested using the data-set from tour guides and their tourists in tourism industry in the Vietnamese business setting. The findings from our research provided evidence for the positive effect of CSR on customer CBE. In addition, CSR was found to foster employee OCBE, which in turn promoted customer CBE as well as intensified the CSR-customer CBE relationship. Customer CBE was also found to play a role in amplifying employee OCBE as well as the CSR-employee OCBE linkage.
Distribution of α‐Galactosyl‐Containing Epitopes on Trypanosoma cruzi Trypomastigote and Amastigote Forms from Infected Vero Cells Detected by Chagasic Antibodies

Reactivity of different Trypanosoma cruzi developmental forms with purified Chagasic anti‐α‐galactosyl antibodies (anti‐Gal) was studied using epimastigotes from axenic cultures, trypomastigotes and amastigotes from infected Vero cell cultures, and an immunogold labeling method as observed by electron microscopy. Epimastigotes were poorly labeled, whereas extracellular trypomastigotes and amastigotes bound heterogeneously to the antibody with many cells being intensely labeled at the cell surface, including the membrane lining the cell body, the flagellum and the flagellar pocket. Parasites with poor labeling at the cell surface generally had several gold particles within the cell, mostly in cytoplasmic vacuoles. The Golgi complex of trypomastigotes was strongly labeled. Intracellular parasites were labeled at the parasite cell surface or within vacuolar structures. The expression in T. cruzi‐infected Vero cells of α‐galactosyl antigenic structures acquired from the parasite was shown by moderate labeling with Chagasic anti‐Gal of the membrane lining parasite‐free outward cell projections. The reactivity with purified anti‐Gal from healthy individuals at the same concentrations of Chagasic anti‐Gal was poor, with gold particles appearing in the nucleus and cytoplasm but not at the cell surface. It paralleled the labeling with Bandeireae simplicifolia IB‐4 lectin. The results provide a basis for autoimmune reactions involving anti‐Gal from chronic Chagasic patients.