Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer.

BACKGROUND In several epidemiologic investigations, folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption. However, data relating plasma folate levels to breast cancer risk are sparse. We investigated the association between plasma folate and other vitamins with breast cancer in a prospective, nested case-control study. METHODS Blood samples were obtained during 1989 and 1990 from 32 826 women in the Nurses' Health Study who were followed through 1996 for the development of breast cancer. We identified 712 breast cancer case patients and selected 712 individually matched control subjects. Dietary information was obtained using food frequency questionnaires given in 1980, 1984, 1986, and 1990. Logistic regression was used to estimate the relative risks (RRs) of breast cancer (after adjustment for potential risk factors), and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate, vitamin B(6), vitamin B(12), and homocysteine, and intakes of folate, vitamin B(6), and vitamin B(12). All statistical tests were two-sided. RESULTS The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 (95% confidence interval [CI] = 0.50 to 1.07; P(trend) =. 06). The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day (i.e., approximately 1 drink/day) of alcohol (multivariable RR = 0.11, 95% CI = 0.02 to 0.59 for highest versus lowest quintile) in contrast with that of women consuming less than 15 g/day (multivariable RR = 0.72, 95% CI = 0.49 to 1.05). The multivariable RR comparing women in the highest quintile of plasma vitamin B(6) levels with those in the lowest quintile was 0.70 (95% CI = 0.48 to 1.02; P(trend) =. 09). Plasma vitamin B(12) levels were inversely associated with breast cancer risk among premenopausal women (multivariable RR = 0.36, 95% CI = 0.15 to 0.86 for highest versus lowest quintile) but not among postmenopausal women. Plasma homocysteine was not associated with breast cancer risk. CONCLUSIONS Higher plasma levels of folate and possibly vitamin B(6) may reduce the risk of developing breast cancer. Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption.
MutL traps MutS at a DNA mismatch

Significance DNA mismatch repair is the process by which errors generated during DNA replication are corrected. Mutations in the proteins that initiate mismatch repair, MutS and MutL, are associated with greater than 80% of hereditary nonpolyposis colorectal cancer (HNPCC) and many sporadic cancers. The assembly of MutS and MutL at a mismatch is an essential step for initiating repair; however, the nature of these interactions is poorly understood. Here, we have discovered that MutL fundamentally changes the properties of mismatch-bound MutS by preventing it from sliding away from the mismatch, which it normally does when isolated. This finding suggests a mechanism for localizing the activity of repair proteins near the mismatch. DNA mismatch repair (MMR) identifies and corrects errors made during replication. In all organisms except those expressing MutH, interactions between a DNA mismatch, MutS, MutL, and the replication processivity factor (β-clamp or PCNA) activate the latent MutL endonuclease to nick the error-containing daughter strand. This nick provides an entry point for downstream repair proteins. Despite the well-established significance of strand-specific nicking in MMR, the mechanism(s) by which MutS and MutL assemble on mismatch DNA to allow the subsequent activation of MutL’s endonuclease activity by β-clamp/PCNA remains elusive. In both prokaryotes and eukaryotes, MutS homologs undergo conformational changes to a mobile clamp state that can move away from the mismatch. However, the function of this MutS mobile clamp is unknown. Furthermore, whether the interaction with MutL leads to a mobile MutS–MutL complex or a mismatch-localized complex is hotly debated. We used single molecule FRET to determine that Thermus aquaticus MutL traps MutS at a DNA mismatch after recognition but before its conversion to a sliding clamp. Rather than a clamp, a conformationally dynamic protein assembly typically containing more MutL than MutS is formed at the mismatch. This complex provides a local marker where interaction with β-clamp/PCNA could distinguish parent/daughter strand identity. Our finding that MutL fundamentally changes MutS actions following mismatch detection reframes current thinking on MMR signaling processes critical for genomic stability.
Flaring Activity of Sagittarius A* at 43 and 22 GHz: Evidence for Expanding Hot Plasma

We have carried out Very Large Array (VLA) continuum observations to study the variability of Sgr A* at 43 GHz (λ = 7 mm) and 22 GHz (λ = 13 mm). A low level of flare activity has been detected with a duration of ~2 hr at these frequencies, showing the peak flare emission at 43 GHz leading the 22 GHz peak flare by ~20-40 minutes. The overall characteristics of the flare emission are interpreted in terms of the plasmon model of van der Laan by considering the ejection and adiabatic expansion of a uniform, spherical plasma blob due to flare activity. The observed peak of the flare emission with a spectral index, ν-α, of α = 1.6 is consistent with the prediction that the peak emission shifts toward lower frequencies in an adiabatically expanding self-absorbed source. We present the expected synchrotron light curves for an expanding blob, as well as the peak frequency emission, as a function of the energy spectral index constrained by the available flaring measurements in near-IR, submillimeter, millimeter, and radio wavelengths. We note that the blob model is consistent with the available measurements; however, we cannot rule out the jet of Sgr A*. If expanding material leaves the gravitational potential of Sgr A*, the total mass-loss rate of nonthermal and thermal particles is estimated to be ≤2 × 10-8 M☉ yr-1. We discuss the implication of the mass-loss rate, since this value matches closely the estimated accretion rate based on polarization measurements.
Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits.

In conscious rabbits, a sequence of six 4-min coronary occlusion/4-min reperfusion cycles, which elicits late preconditioning (PC), caused rapid activation of calcium-dependent nitric oxide (NO) synthase (NOS) [cNOS; endothelial NOS (eNOS) and/or neuronal NOS (nNOS)], whereas calcium-independent NOS [inducible NOS (iNOS)] activity remained unchanged. The enhanced cNOS activity was associated with increased myocardial levels of NO(2) and/or NO(3) (NO(x)). Twenty-four hours after ischemic PC was induced, the opposite pattern was observed, i.e., there was a pronounced increase in cytosolic iNOS activity but no change in cNOS activity. The initial burst of ischemia-induced cNOS activity was not affected by pretreatment with the antioxidant N-2-mercaptopropionyl glycine (MPG), the protein kinase C (PKC) inhibitor chelerythrine, or the tyrosine kinase inhibitor lavendustin A, indicating that it is independent of the generation of oxidant species and the activation of PKC and tyrosine kinases. In contrast, the delayed upregulation of iNOS 24 h after PC was prevented by pretreatment with N(omega)-nitro-L-arginine, MPG, or chelerythrine before the PC ischemia, indicating that it is triggered by a signaling mechanism that involves the generation of NO, the formation of oxidant species, and the activation of PKC. Taken together, these results demonstrate that, in conscious animals, ischemic PC elicits a biphasic response in cardiac NOS activity, i. e. , an immediate activation of cNOS (most likely eNOS) followed 24 h later by a delayed upregulation of iNOS. To our knowledge, this is the first study to directly measure NOS activity after brief myocardial ischemia in vivo. In conjunction with previous functional studies, the data support a distinctive role of NOS isoforms in late PC, with eNOS serving as the trigger on day 1 and iNOS as the mediator on day 2.
Monte Carlo limit cycle characterization

The fixed point implementation of IIR digital filters usually leads to the appearance of zero-input limit cycles, which degrade the performance of the system. In this paper, we develop an efficient Monte Carlo algorithm to detect and characterize limit cycles in fixed-point IIR digital filters. The proposed approach considers filters formulated in the state space and is valid for any fixed point representation and quantization function. Numerical simulations on several high-order filters, where an exhaustive search is unfeasible, show the effectiveness of the proposed approach.
Aerosol delivery of chemotherapy in an orthotopic model of lung cancer

The aim of this study was to evaluate the effect on tumour growth of gemcitabine delivered by aerosol in an orthotopic model of lung carcinoma. Large cell carcinoma (NCI-H460) cells were implanted intrabronchially in 24 male BALB/c nude mice on day (d) 0. Aerosols were delivered once a week from d1 to d29 using an endotracheal sprayer. Altogether, 16 animals received gemcitabine at 8 (n = 8) and 12 mg·kg−1 (n = 8), and eight received a vehicle aerosol. Animals were sacrificed on d36 for histological examination. All animals in the vehicle group developed a large infiltrating carcinoma. Comparatively, four of 13 (31%) animals treated with gemcitabine had no visible tumour and nine of 13 (69%) had a smaller carcinoma with a mean±sem largest tumour diameter of 2.05±0.7 versus 5±0.3 mm in the vehicle group. Gemcitabine was well tolerated at 8 mg·kg−1. At 12 mg·kg−1, three cases of fatal pulmonary oedema were observed, prompting a dose reduction to 8 mg·kg−1 in the remaining animals. A dose effect was observed, with more marked tumour growth inhibition in the animals treated at 12 mg·kg−1 on d1 and d8. In conclusion, in this study, an animal model of aerosolised chemotherapy in lung cancer was developed and demonstrated inhibition of orthotopic tumour growth by aerosol delivery of gemcitabine.
Erratum to: "The covering spectrum of a compact length space''

We define a new spectrum for compact length spaces and Riemannian manifolds called the “covering spectrum” which roughly measures the size of the one dimensional holes in the space. More specifically, the covering spectrum is a set of real numbers δ> 0 which identify the distinct δ covers of the space. We investigate the relationship between this covering spectrum, the length spectrum, the marked length spectrum and the Laplace spectrum. We analyze the behavior of the covering spectrum under Gromov– Hausdorff convergence and study its gap phenomenon.
Sympathetic sprouting and changes in nociceptive sensory innervation in the glabrous skin of the rat hind paw following partial peripheral nerve injury

Previous studies have suggested that sympathetic sprouting in the periphery may contribute to the development and persistence of sympathetically maintained pain in animal models of neuropathic pain. In the present study, we examined changes in the cutaneous innervation in rats with a chronic constriction injury to the sciatic nerve. At several periods postinjury, hind paw skin was harvested and processed by using a monoclonal antibody against dopamine‐β‐hydroxylase to detect sympathetic fibers and a polyclonal antibody against calcitonin gene‐related peptide to identify peptidergic sensory fibers. We observed migration and branching of sympathetic fibers into the upper dermis of the hind paw skin, where they were normally absent. This migration was first detected at 2 weeks, peaked at 4–6 weeks, and lasted for at least 20 weeks postlesion. At 8 weeks postlesion, there was a dramatic increase in the density of peptidergic fibers in the upper dermis. Quantification revealed that densities of peptidergic fibers 8 weeks postlesion were significantly above levels in sham animals. The ectopic sympathetic fibers did not innervate blood vessels but formed a novel association and wrapped around sprouted peptidergic nociceptive fibers. Our data show a long‐term sympathetic and sensory innervation change in the rat hind paw skin after the chronic constriction injury. This novel fiber arrangement after nerve lesion may play an important role in the development and persistence of sympathetically maintained neuropathic pain after partial nerve lesions. J. Comp. Neurol. 495:679–690, 2006. © 2006 Wiley‐Liss, Inc.
FUZZY CLASSIFICATION, IMAGE SEGMENTATION AND SHAPE ANALYSIS FOR HUMAN FACE DETECTION

In this paper, we describe a new algorithm for human face detection. The algorithm uses both color and shape analysis. Color analysis is based on the novel idea of fuzzy classification that manipulates ambiguity in colors; using this technique we can robustly classify skin region and non-skin region. In order to decide whether the skin region is a face or not, we test its shape by applying an edge detection using Canny operator and an ellipse detection using Hough transform. We show with experimental results how the important detection ratio makes our system an effective tool for face detection
A simple algorithm for camera pose estimation

In this paper, we present a simple algorithm for calibrated camera pose estimation. The algorithm is based on the object space error, and capable of iteratively determining the pose by solving a group of linear equations from the correspondences of arbitrary n reference points and their image projections. Experimental results show that our algorithm is more likely to converge to correct pose than currently accepted iterative algorithms, and suitable for both centered and uncentered reference points. Furthermore, our algorithm can maintain high estimation accuracy in a short runtime, which makes it more applicable for real time applications.
Vectorcardiographic loop alignment and the measurement of morphologic beat-to-beat variability in noisy signals

The measurement of subtle morphologic beat-to-beat variability in the electrocardiogram (ECG)/vectorcardiogram (VCG) is complicated by the presence of noise which is caused by, e.g., respiration and muscular activity. A method was recently presented which reduces the influence of such noise by performing spatial and temporal alignment of VCG loops. The alignment is performed in terms of scaling, rotation and time synchronization of the loops. Using an ECG simulation model based on propagation of action potentials in cardiac tissue, the ability of the method to separate morphologic variability of physiological origin from respiratory activity was studied. Morphologic variability was created by introducing a random variation in action potential propagation between different compartments. The results indicate that the separation of these two activities can be done accurately at low to moderate noise levels (less than 10 /spl mu/V). At high noise levels, the estimation of the rotation angles was found to break down in an abrupt manner. It was also shown that the breakdown noise level is strongly dependent on loop morphology; a planar loop corresponds to a lower breakdown noise level than does a nonplanar loop.
Design of the pCASE Platform for enabling Context Aware Services

In order to deliver intelligent context-aware services (e.g. notifications of nearby points of interest), location based services are getting a lot of interest. However, deploying these services efficiently is currently hampered by the lack of enabling platforms, especially platforms taking advantage of easy service composition and flexible management. In this paper we detail the design of pCASE, a platform for enabling context aware services. This platform allows easy deployment in both home and business premises and flexible management of complex services taking into account context information such as location and presence. A use case is presented: an intelligent call redirection service which dynamically (re)routes communication sessions depending on the location, occupation and social networks of users.
Developmental Change in the Function of Movement Systems: Transition of the Pectoral Fins between Respiratory and Locomotor Roles in Zebrafish

An animal may experience strikingly different functional demands on its body’s systems through development. One way of meeting those demands is with temporary, stage-specific adaptations. This strategy requires the animal to develop appropriate morphological states or physiological pathways that address transient functional demands as well as processes that transition morphology, physiology, and function to that of the mature form. Recent research on ray-finned (actinopterygian) fishes is a developmental transition in function of the pectoral fin, thereby providing an opportunity to examine how an organism copes with changes in the roles of its morphology between stages of its life history. As larvae, zebrafish alternate their pectoral fins in coordination with the body axis during slow swimming. The movements of their fins do not appear to contribute to the production of thrust or to stability but instead exchange fluid near the body for cutaneous respiration. The morphology of the larval fin includes a simple stage-specific endoskeletal disc overlaid by fan-shaped adductor and abductor muscles. In contrast, the musculoskeletal system of the mature fin consists of a suite of muscles and bones. Fins are extended laterally during slow swimming of the adult, without the distinct, high-amplitude left-right fin alternation of the larval fin. The morphological and functional transition of the pectoral fin occurs through juvenile development. Early in this period, at about 3 weeks post-fertilization, the gills take over respiratory function, presumably freeing the fins for other roles. Kinematic data suggest that the loss of respiratory function does not lead to a rapid switch in patterns of fin movement but rather that both morphology and movement transition gradually through the juvenile stage of development. Studies relating structure to function often focus on stable systems that are arguably well adapted for the roles they play. Examining how animals navigate transitional periods, when the link of structure to function may be less taut, provides insight both into how animals contend with such change and into the developmental pressures that shape mature form and function.
Router selfishness in community wireless mesh networks: Cross-layer benefits and harms

In community wireless mesh (CWM) networks following the IEEE 802.11s standard, wireless nodes combine the functionality of a client application host and a transit packet router. Not being subjected to tight administrative control, CWM nodes may act selfishly by refusing to forward transit packets along (selected) established routes or to participate in the route creation process. Unlike in a mobile ad hoc network (MANET), a CWM node is typically connected to mains electricity, hence unconcerned about energy expenditure; the only rational (as distinct from malicious) motivation behind selfish behavior is then to prevent the incoming transit traffic from competing with the source traffic and thereby achieve a higher source throughput. We examine through simulation the benefits and harms of selfish behavior with a cross-layer view and relate them to the router density, selfish routers' location and details of their behavior. We find many conclusions and intuitions valid in MANET environments incorrect in CWMs.
Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland

Objective:Early initiation of antiretroviral treatment (ART) at CD4+ cell count ≥500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. Design:A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. Methods:Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4+ cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. Results:Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4+ count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4+ criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4+ criterion of <500 cells per microliter. Conclusions:A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.
Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere.
Field testing a rare species bioacoustic smartphone application: Challenges and future considerations

The New Forest cicada is a declining species native to the UK, and the last unconfirmed sighting was in 2000. One of the difficulties in identifying the cicada is that it sings at a high frequency typically inaudible to adults. In this paper we describe a field test of a novel citizen science smartphone application designed to detect and classify the cicada's call. We discuss some of the obstacles to studying this novel technology, and describe the results from a user trial with a simulated cicada. Our observations are then used to inform a series of design considerations for those developing a similar class of application, and improvements for the application itself.