Miracle-dz/UniFAR-FTUs huggingface dataset:
Summer Abundance and Distribution of Proteorhodopsin Genes in the Western Arctic Ocean

Proteorhodopsins (PR) are phylogenetically diverse and highly expressed proton pumps in marine bacterial communities. The phylogenetic diversity and in situ expression of the main PR groups in polar off-shore, coastal and estuarine waters is poorly known and their abundance has not yet been reported. Here, we show that PR gene sequences of the southern Beaufort Sea including MacKenzie shelf and estuary are mainly affiliated to Gammaproteobacteria, Alphaproteobacteria, and Bacteroidetes. Substantial overlap (78%) between DNA- and cDNA-based librairies indicated in situ PR transcription within a large fraction of PR-containing community. Sets of specific qPCR primers were designed to measure the absolute abundances of the major PR types. Spatial and depth profiles showed that PR-containing bacteria were abundant throughout the photic zone, comprising up to 45% of total bacteria. Although their abundance varied greatly with location and depth, Alphaproteobacteria predominated in the PR community in all water masses, with SAR11 as the major PR type. Low nutrient concentrations rather than light were the environmental drivers that best explained the abundance and distribution of arctic PR types. Together, our data suggests that PR-based phototrophy could be the major phototrophic prokaryotic process during the Arctic Ocean summer.
Challenges in the application of quantitative approaches in risk assessment: a case study with di-(2-ethylhexyl)phthalate

The constantly evolving science of risk assessment is currently faced with many challenges, not only from the interpretation of the volume of data being generated with new innovative technologies, but also in attempting to quantitatively incorporate this information into understanding potential risk of adverse events in human populations. The objective of the case study described was to use the more recent data for di-(2-ethylhexyl)phthalate (DEHP) to investigate the impact of innovative quantitative approaches on the risk assessment of a compound, specifically as it can be used to move towards the new vision of risk assessment involving the integration of the available toxicological data to understand underlying biological processes. What emerged were several outcomes that demonstrated clearly the importance of the integration of the toxicological data, specifically to understand the biological processes being impacted, because standard statistical modeling approaches may not be adequate to describe the dose–response relationships observed. Alternative approaches demonstrate that a definitive mode of action is not needed to justify the shape of the low-dose region or a threshold, when the integration of the available data assist risk assessors in understanding the shape of the dose–response curve for both noncancer and cancer endpoints. Many of the challenges described as part of this case study would likely be encountered with compounds other than DEHP, especially other receptor-mediated compounds or compounds that “perturb” biological pathways, such as endocrine disruptors. This case study also highlights the importance of communication between risk assessors and the research community to focus on the generation of data most relevant for assessing the potential for chemicals to impact biological systems in the human.
Identification and Characterization of Cathepsin B as the Cellular MARCKS Cleaving Enzyme*

The importance of regulating the cellular concentrations of the myristoylated alanine-rich C kinase substrate (MARCKS), a major cellular substrate of protein kinase C, is indicated by the fact that mice lacking MARCKS exhibit gross abnormalities of central nervous system development and die shortly after birth. We previously identified a novel means of regulating cellular MARCKS concentrations that involved a specific proteolytic cleavage of the protein and implicated a cysteine protease in this process (Spizz, G., and Blackshear, P. J. (1996) J. Biol. Chem. 271, 553–562). Here we show that p40, the carboxyl-terminal fragment resulting from this cleavage of MARCKS, was associated with the mitochondrial/lysosomal pellet fraction of human diploid fibroblasts and that its generation in cells was sensitive to treatment with NH4Cl. These data suggest the involvement of lysosomes in the generation and/or stability of p40. The MARCKS-cleaving enzyme (MCE) activity was peripherally associated with a 10,000 ×g pellet fraction from bovine liver, and it co-purified with the activity and immunoreactivity of a lysosomal protease, cathepsin B. Cathepsin B catalyzed the generation of p40 from MARCKS in a cell-free system and behaved similarly to the MCE with respect to mutants of MARCKS previously shown to be poor substrates for the MCE. Treatment of fibroblasts with a cell-permeable, specific inhibitor of cathepsin B, CA074-Me, resulted in parallel time- and concentration-dependent inhibition of cathepsin B and MCE activity. Incubation of a synthetic MARCKS phosphorylation site domain peptide with purified cathepsin B resulted in cleavage of the peptide at sites consistent with preferred cathepsin B substrate sites. These data provide evidence for the identity of the MCE as cathepsin B and suggest that this cleavage most likely takes place within lysosomes, perhaps as a result of specific lysosomal targeting sequences within the MARCKS primary sequence. The data also suggest a direct interaction between MARCKS and cathepsin B in cells and leave open the possibility that MARCKS may in some way regulate the protease for which it is a substrate.
Error Analysis for Dual‐Beam Optical Linear Polarimetry

In this paper we present an error analysis for polarimetric data obtained with dual‐beam instruments. After recalling the basic concepts, we introduce the analytical expressions for the uncertainties of polarization degree and angle. These are then compared with the results of Monte Carlo simulations, which are also used to briefly discuss the statistical bias. We then approach the problem of background subtraction and the errors introduced by an imperfect Wollaston prism, flat‐fielding, and retarder plate defects. Finally, we investigate the effects of instrumental polarization and propose a simple test to detect and characterize it. The application of this method to real VLT‐FORS1 data has shown the presence of a spurious polarization that is of the order of ∼1.5% at the edges of the field of view. The cause of this problem has been identified as the presence of rather curved lenses in the collimator, combined with the incomplete removal of reflections by the coatings. This problem is probably common to all focal‐reducer instruments equipped with a polarimetric mode. An additional spurious and asymmetric polarization field, whose cause is still unclear, is visible in the B band.
Thai Sentence-Breaking for Large-Scale SMT

Thai language text presents challenges for integration into large-scale multilanguage statistical machine translation (SMT) systems, largely stemming from the nominal lack of punctuation and inter-word space. For Thai sentence breaking, we describe a monolingual maximum entropy classifier with features that may be applicable to other languages such as Arabic, Khmer and Lao. We apply this sentence breaker to our largevocabulary, general-purpose, bidirectional Thai-English SMT system, and achieve BLEU scores of around 0.20, reaching our threshold of releasing it as a free online service.
Colitogenic CD4+ effector‐memory T cells actively recirculate in chronic colitic mice

Background: Although the clinical usefulness of leukocytapheresis for patients with inflammatory bowel disease (IBD) has been reported as a selective removal therapy targeting pathogenic immune cells in blood circulation, it remains unclear whether colitogenic CD4+ T cells continuously recirculate in peripheral blood during the chronic phase of colitis. Methods: To resolve this question we conducted a series of in vivo experiments using a murine chronic colitis model induced by adoptive transfer of CD4+CD45RBhigh cells into SCID mice in combination with a parabiosis system. Results: In colitic SCID recipients, first, almost all CD4+ CD45RBhigh donor cells were converted to CD4+CD44highCD62L− IL‐7R&agr;high effector‐memory T (TEM) cells at 8 weeks after transfer and were distributed throughout the whole body, including colonic lamina propria, mesenteric lymph nodes, thoracic duct, peripheral blood, spleen, and bone marrow. Second, SCID mice retransferred with the colitic peripheral blood CD4+ T cells developed colitis that is identical to the original colitis. Third, CD4+ cells in parabionts between established colitic RAG‐2−/− mice induced by adoptive transfer of Ly5.1+ or Ly5.2+ CD4+CD45RBhigh T cells were well mixed in almost equal proportions at various sites 2 weeks after parabiosis surgery, and the redistribution of Ly5.1+ and Ly5.2+ CD4+ T cells was significantly suppressed in FTY720‐treated parabionts. Conclusions: Together, these findings indicate that colitogenic CD4+ TEM cells continuously recirculate in established colitic mice, suggesting that therapeutic approaches targeting systemic CD4+ TEM cells, such as bone marrow transplantation, rather than those targeting only intestinal CD4+ T cells, may be feasible for the treatment of IBD.
Role of Peroxisomes in Isoprenoid Biosynthesis

Our group and others have recently demonstrated that peroxisomes contain a number of enzymes involved in cholesterol biosynthesis that previously were considered to be cytosolic or located in the endoplasmic reticulum (ER). Peroxisomes have been shown to contain HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, phosphomevalonate decarboxylase, isopentenyl diphosphate isomerase, and FPP synthase. Four of the five enzymes required for the conversion of mevalonate to FPP contain a conserved putative PTS1 or PTS2, supporting the concept of targeted transport into peroxisomes. To date, no information is available regarding the function of the peroxisomal HMG-CoA reductase in cholesterol/isoprenoid metabolism, and the structure of the peroxisomal HMG-CoA reductase has yet to be determined. We have identified a mammalian cell line that expresses only one HMG-CoA reductase protein, and which is localized exclusively to peroxisomes, to facilitate our studies on the function, regulation, and structure of the peroxisomal HMG-CoA reductase. This cell line was obtained by growing UT2 cells (which lack the ER HMG-CoA reductase) in the absence of mevalonate. The surviving cells exhibited a marked increase in a 90-kD HMG-CoA reductase that was localized exclusively to peroxisomes. The wild-type CHO cells contain two HMG-CoA reductase proteins, the well-characterized 97-kD protein localized in the ER, and a 90-kD protein localized in peroxisomes. We have also identified the mutations in the UT2 cells responsible for the lack of the 97-kD protein. In addition, peroxisomal-deficient Pex2 CHO cell mutants display reduced HMG-CoA reductase levels and have reduced rates of sterol and nonsterol biosynthesis. These data further support the proposal that peroxisomes play an essential role in isoprenoid biosynthesis.
Extracellular Activity of Cyclic AMP–Dependent Protein Kinase as a Biomarker for Human Cancer Detection: Distribution Characteristics in a Normal Population and Cancer Patients

The overexpression of cyclic AMP (cAMP)–dependent protein kinase (PKA) has been reported in patients with cancer, and PKA inhibitors have been tested in clinical trials as a novel cancer therapy. The present study was designed to characterize the population distribution of extracellular activity of cAMP-dependent protein kinase (ECPKA) and its potential value as a biomarker for cancer detection and monitoring of cancer therapy. The population distribution of ECPKA activity was determined in serum samples from a Chinese population consisting of a total of 603 subjects (374 normal healthy volunteers and 229 cancer patients). The serum ECPKA was determined by a validated sensitive radioassay, and its diagnostic values (including positive and negative predictive values) were analyzed. The majority of normal subjects (>70%) have undetectable or very low levels of serum ECPKA. In contrast, the majority of cancer patients (>85%) have high levels of ECPKA. The mean ECPKA activity in the sera of cancer patients was 10.98 units/mL, 5-fold higher than that of the healthy controls (2.15 units/mL; P < 0.001). In both normal subjects and cancer patients, gender and age had no significant influence on the serum ECPKA. Among factors considered, logistic analysis revealed that the disease (cancer) is the only factor contributing to the elevation of ECPKA activity in cancer patients. In conclusion, ECPKA may function as a cancer marker for various human cancers and can be used in cancer detection and for monitoring response to therapy with other screening or diagnostic techniques. (Cancer Epidemiol Biomarkers Prev 2007;16(4):789–95)
Crossing the Reality Gap: a Short Introduction to the Transferability Approach

In robotics, gradient-free optimization algorithms (e.g. evolutionary algorithms) are often used only in simulation because they require the evaluation of many candidate solutions. Nevertheless, solutions obtained in simulation often do not work well on the real device. The transferability approach aims at crossing this gap between simulation and reality by making the optimization algorithm aware of the limits of the simulation. In the present paper, we first describe the transferability function, that maps solution descriptors to a score representing how well a simulator matches the reality. We then show that this function can be learned using a regression algorithm and a few experiments with the real devices. Our results are sup- ported by an extensive study of the reality gap for a simple quadruped robot whose control parameters are optimized. In particular, we mapped the whole search space in reality and in simulation to understand the differences between the fitness landscapes.
Online Algorithms for Information Aggregation From Distributed and Correlated Sources

There is a fundamental tradeoff between the communication cost and the latency in information aggregation. Aggregating multiple communication messages over time can alleviate overhead and improve energy efficiency on one hand, but inevitably incurs information delay on the other hand. In the presence of uncertain future inputs, this tradeoff should be balanced in an online manner, which is studied by the classical dynamic TCP ACK problem for a single information source. In this paper, we extend dynamic TCP ACK problem to a general setting of collecting aggregate information from distributed and correlated information sources. In this model, distributed sources observe correlated events, whereas only a small number of reports are required from the sources. The sources make online decisions about their reporting operations in a distributed manner without prior knowledge of the local observations at others. Our problem captures a wide range of applications, such as in-situ sensing, anycast acknowledgement, and distributed caching. We present simple threshold-based competitive distributed online algorithms under different settings of intercommunication. Our algorithms match the theoretical lower bounds in order of magnitude. We observe that our algorithms can produce satisfactory performance in simulations and practical test bed.
Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase

SUMMARY Fragile X syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1) product (FMRP), is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP) inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1) null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ), clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP) in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity between the single dfmr1 mutants and controls. These results support minocycline as a promising potential FXS treatment and suggest that it might act via MMP inhibition. We conclude that FMRP and TIMP pathways interact in a reciprocal, bidirectional manner.
Interpersonal influences on male drug use and drug use intentions.

The relationship between (1) the respondent's perception of the drug behavior of his father, mother, siblings, current friends, and wife/female partner; and (2) past drug use and future drug use intentions for tobacco, alcohol, marijuana, psychedelics, stimulants, sedatives, heroin, other opiates, and cocaine is examined among a representative sample of men in the U.S. population who were 20-30 years old in 1974 (N = 2,510). For each drug the results indicated that current friends' and wife/partner's drug behaviors are the factors most strongly associated with the respondent's past drug use as well as his intentions of future drug use. Although substantially less important, siblings' drug behavior also appears to be a source of influence, while the drug behavior of mothers and fathers is only minimally associated with drug use and future intentions.
Nutrients and bacteria in common contiguous Mississippi soils with and without broiler litter fertilization.

In Mississippi, spent poultry litter is used as fertilizer. Nutrient and bacterial levels in litter and nutrient levels in litter-fertilized (L+) soil are known, but less is known of bacterial levels in L+ soil. This study compared contiguous L+ and non-litter-fertilized (L-) soils comprising 15 soil types on five farms in April through May 2009. Levels of pH; NO-N; and Mehlich-3-extractable (M3) and water-extractable (WE) P, Ca, K, and Cu were higher in L+ than in L- soil. Total C; total N; NH-N; and M3 and WE Na, Fe, and Zn did not differ in L+ and L- soil. Bacterial levels were higher in 0- to 5-cm than in 5- to 10-cm cores. Levels were higher in L+ than in L- soil for culturally determined heterotrophic plate counts and staphylococci and were lower for total bacteria estimated by quantitative polymerase chain reaction (qPCR) of 16S rRNA, but cultural levels of thermotolerant coliforms, , , and enterococci were not different. Cultural presence/absence (CPA) tests and qPCR for spp. , spp. , and spp. detected only spp. , which did not differ in L+ (CPA = 77% positive samples; mean qPCR = 0.65 log genomic units [gu] g) and L- (CPA = 70% positive samples; mean qPCR = 0 log gu g) soils. Litter applications were associated with higher levels of pH, P, Cu, heterotrophic plate counts, and staphylococci. Fecal indicator and enteric pathogen levels were not affected. We conclude that, although some litter-derived nutrients and bacteria persisted between growing seasons in L+ soils, enteric pathogens did not.
Remedy or cure? Lay beliefs about over-the-counter medicines for coughs and colds.

BACKGROUND Over 500 million is spent in the United Kingdom every year on over-the-counter medicines for coughs and colds. Evidence for their pharmacological efficacy is lacking. AIM To examine lay beliefs about over-the-counter medicines for coughs and colds. To explore whether the distinction between symptom relief and cure has the same relevance to lay people as it does to medical professionals. DESIGN OF STUDY Small pilot study using qualitative techniques. SETTING Variety sample of 11 patients attending the National Health Service walk-in centre, Birmingham, England. METHOD In-depth semi-structured interviews, including pile-sorting and fictional case histories, were used to explore participants' beliefs about the effects of over-the-counter medicines on coughs and colds. RESULTS Eight of the 11 participants believed that at least one over the-counter cough medicine (most frequently Benylin for Chesty Coughs) could shorten, or "cure", an illness. Five participants thought that the majority of the medicines that they recognised would speed recovery rather than just relieve symptoms. CONCLUSIONS There is a common confusion in the lay person's mind between the ability of a medicine to relieve symptoms, and its ability to cure a disease or to hasten recovery. This misunderstanding may affect the demand for primary care consultations.
The Role of Viscosity and Fermentability of Dietary Fibers on Satiety- and Adiposity-Related Hormones in Rats

Dietary fiber may contribute to satiety. This study examined the effect of two dietary fiber characteristics, small intestinal contents viscosity and large intestinal fermentability, on satiety-and adiposity-related hormones in rats. Diets contained fiber sources that were non-viscous, somewhat viscous, or highly viscous, and either highly fermentable or non-fermentable, in a 2 × 3 factorial design. In the fed state (2 h postprandial), rats fed non-fermentable fibers had significantly greater plasma GLP-1 concentration than fermentable fibers. In the fasted state, among non-fermentable fibers, viscosity had no effect on GLP-1 concentration. However, among fermentable fibers, greater viscosity reduced GLP-1 concentration. Plasma peptide tyrosine tyrosine (PYY) concentrations in the fasted state were not influenced by the fermentability of the fiber overall, however animals consuming a fructooligosaccharide greater PYY concentration. In both the fed and fasted states, rats fed non-fermentable fibers had a significantly lower plasma ghrelin concentration than rats fed fermentable fibers. In the fasted state, rats fed non-fermentable fibers had a significantly lower plasma leptin concentration than rats fed fermentable fibers. Thus, fermentability and viscosity of dietary fiber interacted in complex ways to influence satiety- and adiposity-related plasma hormone concentrations. However, the results suggest that highly viscous, non-fermentable fibers may limit weight gain and reduce adiposity and non-fermentable fibers, regardless of viscosity, may promote meal termination.
Crack Width and Crack Spacing In Reinforced Concrete Members

A SIMPLE METHOD IS DEVELOPED FOR CALUCLATION OF CRACK WIDTH AND CRACK SPACING IN REINFORCED CONCRETE MEMBERS. THE CRACK WIDTHS DETERMINED BY THIS METHOD WERE COMPARED WITH TEST DATA OBTAINED FROM FLEXURAL AND TENSILE MEMBERS REINFORCED WITH ONE BAR. THE SHAPE OF THE MAIN CRACKS WAS INVESTIGATED BY MEANS OF SHORT TENSION MEMBERS OF A LENGTH EQUAL TO THE SPACING OF THE MAIN TENSION CRACKS. THE INTERNAL CRACK FORMATION WAS DETERMINED DURING LOADING THROUGH INJECTION OF RESIN INTO A FEW TEST SPECIMENS. AFTER THE RESIN HAD HARDENED AND THE TEST MEMBERS WERE CUT OPEN, THE INTERNAL CRACK FORMATION WAS STUDIED. /RRL/A/