Miracle-dz/UniFAR-FTUs huggingface dataset:
Leishmania donovani Requires Functional Cdc42 and Rac1 To Prevent Phagosomal Maturation

ABSTRACT Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase Cα. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation.
A GaN photonic crystal membrane laser

The implementation of a series of optically pumped GaN photonic crystal (PhC) membrane lasers is demonstrated at room temperature. The photonic crystal is composed of a scalene-triangular arrangement of circular holes in GaN. Three defect structures are fabricated for comparing their lasing characteristics with those of perfect PhC. It is observed that all the lasing defect modes have lasing wavelengths very close to the band-edge modes in the perfect PhC structure. Although those lasing modes, including band-edge and defect modes, have different optical pump thresholds, different lasing spectral widths, different quality factors (Q factors), and different polarization ratios, all their polarization distributions show maxima in the directions around one of the hole arrangement axes. The similar lasing characteristics between the band-edge and defect modes are attributed to the existence of extremely narrow partial band gaps for forming the defect modes. Also, the oriented polarization properties are due to the scalene-triangle PhC structure. In one of the defect lasing modes, the lasing threshold is as low as 0.82 mJ cm − 2, the cavity Q factor is as large as 1743, and the polarization ratio is as large as 25.4. Such output parameters represent generally superior lasing behaviors when compared with previously reported implementations of similar laser structures.
A case study in class testing

In contrast to the explosion of activity in object-oriented design and programming, little attention has been given to object testing. In our approach, a driver class and an oracle class are developed for each class-under-test (CUT). The driver class is based on a testgraph which partially models the CUT as a state machine, but with vastly fewer states and transitions. The oracle class provides essentially the same operations as the CUT, but supports only the testgraph states and transitions. Surprisingly thorough testing is achievable with simple test graphs and oracles. The key is designing the two together, to avoid tests for which input generation and output checking are unaffordable. We illustrate our approach with a test suite developed for a class from a commercial library.
Applied Issues in Treatment Outcome Assessment

It is an exciting time to conduct alcoholism treat­ ment outcome evaluation. Advancements in statis­ tical software for personal computers, for example, have dramatically increased the type and complexity of techniques available to the evalua­ tor. Although some concern has been raised about how the democratization of the tools of evaluation may precipitate their inappropriate use (e.g., Pedhazur 1982), indirect evidence suggests that increased accessibility has had an overall positive effect in the field. Miller et al. (1995a) found, for example, that the methodological quality of research outcome studies has improved signifi­ cantly in the past 20 years, much of this due to selection of assessment instruments with known psychometric properties and the appropriate use of multivariate techniques. Software advances for personal computers have also spawned an audiencefriendly revolution in how findings are presented, with time-to-event outcomes, hierarchical linear modeling findings, and structural equation model­ ing findings now presented in an understandable and graphic format. It is also a critical time for doing rigorous outcome evaluation. In many States evaluation is now legislatively mandated, with future program appropriations tied to demonstration of treatment effectiveness. Programs and jobs can hinge on how well an evaluation report communicates find­ ings to audiences unfamiliar with research methodology and the multifaceted nature of alcohol treatment outcome(s). Under these condi­ tions the evaluator has a clear responsibility to select assessment tools with demonstrated reliabil­ ity and validity that are also sensitive to, and theo­ retically consistent with, treatment program objectives. The purpose of this chapter is to familiarize the reader with a variety of fundamental issues that arise in the conduct of outcome evaluation in alcoholism treatment. The relative merits of specific measures of alcohol consumption (see the chapter by Sobell and Sobell) and biological markers (see the chapter by Allen et al.) are reviewed elsewhere in this Guide and will not be reiterated. This chapter begins with a general discussion of the importance of using assessments with strong psychometric properties. Reliability theory is described from an applied perspective, with examples provided using assessment tools reviewed in this Guide. The next section briefly addresses the goals of summative and formative alcohol-related outcome evaluation, highlighting the differences between individual and groupbased evaluation. This is followed by a section that reviews alternative perspectives of alco­ holism, with attention directed to how these defin­ itions of alcoholism suggest relevant measures of change; a section that discusses the measurement of behavior change across time, noting how commonly observed patterns of behavioral change differ across particular domains of functioning;
Knee Pain During Daily Tasks, Knee Osteoarthritis Severity, and Widespread Pain

Background The presence of widespread pain is easily determined and is known to increase the risk for persistent symptoms. Objective The study hypothesis was that people with no or minimal knee osteoarthritis (OA) and high Western Ontario and McMaster Universities (WOMAC) Pain Scale scores would be more likely than other subgroups to report widespread pain. Design A cross-sectional design was used. Methods Data were obtained from the Multicenter Osteoarthritis Study, which includes people with or at high risk for knee OA. The inclusion criteria were met by 755 people with unilateral knee pain and 851 people with bilateral knee pain. Widespread pain was assessed with body diagrams, and radiographic Kellgren-Lawrence grades were recorded for each knee. Knee pain during daily tasks was quantified with WOMAC Pain Scale scores. Results Compared with people who had high levels of pain and knee OA, people with a low level of pain and a high level of knee OA, and people with low levels of pain and knee OA, a higher proportion of people with a high level of knee pain and a low level of knee OA had widespread pain. This result was particularly true for people with bilateral knee pain, for whom relative risk estimates ranged from 1.7 (95% confidence interval=1.2–2.4) to 2.3 (95% confidence interval=1.6–3.3). Limitations The cross-sectional design was a limitation. Conclusions People with either no or minimal knee OA and a high level of knee pain during daily tasks are particularly likely to report widespread pain. This subgroup is likely to be at risk for not responding to knee OA treatment that focuses only on physical impairments. Assessment of widespread pain along with knee pain intensity and OA status may assist physical therapists in identifying people who may require additional treatment.
Unbalanced learning in content-based image classification and retrieval

Nowadays very large archives of digital images can be easily produced thanks to the availability of digital cameras as standalone devices, or embedded into a number of portable devices. Each personal computer is typically a repository for thousands of images, while the Internet can be seen as a very large repository. One of the most severe problems in the classification and retrieval of images from very large repositories is the very limited number of elements belonging to each semantic class compared to the number of images in the repository. As a consequence, an even smaller fraction of images per semantic class can be used as training set in a classification problem, or as a query in a content-based image retrieval problem. In this paper we propose a technique aimed at artificially increasing the number of examples in the training set in order to improve the learning capabilities, reducing the unbalance between the semantic class of interest, and all other images. The proposed approach is tailored to classification and relevance feedback techniques based on the Nearest-Neighbor paradigm. A number of new points in the feature space are created based on the available training patterns, so that they better represent the distribution of the semantic class of interest. These new points are created according to the k-NN paradigm, and take into account both relevant and non-relevant images with respect to the semantic class of interest. The proposed approach allows increasing the generalization capability of NN techniques, and mitigates the risk of classifier over-training on few patterns. Reported experiments show the effectiveness of the proposed technique in Content-Based Image Retrieval tasks, where the Nearest-Neighbor approach is used to exploit user's relevance feedback. The improvement in precision and recall gained in one feature space allows also to outperform the improvement in performances attained by combining different feature spaces.
The secondary structure of protein G', a robust molecule.

The secondary structure of recombinant streptococcal Protein G' was predicted and compared with spectropolarimetric data. The predicted secondary structure consisted of 37 +/- 4% alpha-helix and 30 +/- 5% beta-sheet, whereas the values obtained from c.d. data were 29 +/- 2% alpha-helix and 41 +/- 3% beta-sheet. An alpha-helix-beta-sheet/turn-alpha-helix motif is conjectured to comprise the Fc-binding unit. The c.d. spectra in the near u.v. and far u.v. show that the Protein G' molecule is stable to heating at 100 degrees C and to extremes of pH (pH 1.5 to 11.0). The protein retained biological activity at these extremes. The molecule uncoils above pH 11.5 in a time-dependent fashion. Unfolding of the molecule in guanidinium chloride was monitored by c.d. and fluorescence emission; 3 M-guanidinium chloride was required to unfold the protein by 50%. The protein was completely unfolded in 5.5 M-guanidinium chloride and fully refolded with restoration of activity after removal of guanidinium chloride.
VECTOR ANALYSES OF NONDIFFRACTING BESSEL BEAMS

An increasing attention has been concentrated on nondiffracting Bessel beams, due to their novel properties and prospective applications. In order to study their properties entirely, including the transverse modes, the polarization states and the flow of energy, vector analyses are necessary. In this paper, based on auxiliary functions of Hertzian vector potential, nondiffracting Bessel beams are analyzed. The useful results are obtained and presented in this paper.
Static Code Analysis of C + + in LLVM

Just like the release of the Clang compiler, the advent of LLVM in the field of static code analysis already shows great promise. When given the task of covering rules not ideally covered by a commercial contender, the end result is not only overwhelmingly positive, the implementation time is only a fraction of what was initially expected. While LLVM’s support for sophisticated AST analysis is remarkable, being the main reason these positive results, it’s support for data flow analysis is not yet up to par. Despite this, as well as a lack of thorough documentation, LLVM should already be a strong rival for any commercial tool today.
Fast T rack Protein Conformational Diversity Correlates with Evolutionary Rate

Native state of proteins is better represented by an ensemble of conformers in equilibrium than by only one structure. The extension of structural differences between conformers characterizes the conformational diversity of the protein. In this study, we found a negative correlation between conformational diversity and protein evolutionary rate. Conformational diversity was expressed as the maximum root mean square deviation (RMSD) between the available conformers in Conformational Diversity of Native State database. Evolutionary rate estimations were calculated using 16 different species compared with human sharing at least 700 orthologous proteins with known conformational diversity extension. The negative correlation found is independent of the protein expression level and comparable in magnitude and sign with the correlation between gene expression level and evolutionary rate. Our findings suggest that the structural constraints underlying protein dynamism, essential for protein function, could modulate protein divergence.
Deaf adults without attention deficit hyperactivity disorder display reduced perceptual sensitivity and elevated impulsivity on the Test of Variables of Attention (T.O.V.A.).

The Test of Variables of Attention (T.O.V.A.; R. A. Leark, T. R. Dupuy, L. M. Greenberg, C. L. Corman, & C. L. Kindeschi, 1996) is a continuous performance test used widely to help diagnose attention deficit hyperactivity disorder (ADHD) in both hearing and deaf people. The T.O. V.A. previously has been normed only on the hearing population. The T.O. V.A. performance of 38 prelingually and severely-to-profoundly deaf young adults and 34 hearing young adults who did not have ADHD was examined in this study. Deaf and hearing participants did not differ on the T.O. V.A. omission variables. However, deaf participants had significantly lower d' scores than hearing participants, indicating reduced perceptual sensitivity to the distinction between target and distractor stimuli. Consistent with the existing literature on attentional reorganization in the deaf population, this result was interpreted as indicating a deafness-related reduction in attention to centrally presented stimuli. Deaf participants also showed 2 to 3 times more commission errors than hearing participants and displayed a higher incidence of anticipatory errors. These results suggest a deafness-related increase in impulsivity at the time of response initiation. Beta score analysis confirmed that deaf participants adopted an overall less conservative (more impulsive) response criterion that contributed to their total elevated commission errors. However, a portion of the commission errors was secondary to their reduced d', not to increased behavioral impulsivity. Separate factor analyses of the standard T.O. V.A. variables revealed highly similar factor structures for deaf and hearing participants, indicating similar construct validity of the T.O. V.A. for both groups. The evidence for increased inattention and impulsivity in a non-ADHD deaf sample are interpreted in the context of an adaptive attentional reorganization due to deafness. Along with the factor analytic results, these considerations suggest that separate T.O. V.A. norms must be developed for the deaf population to avoid overdiagnosis of ADHD in deaf individuals.
An Apoplastic &bgr;-Glucosidase is Essential for the Degradation of Flavonol 3-O-&bgr;-Glucoside-7-O-&agr;-Rhamnosides in Arabidopsis

Flavonol bisglycosides accumulate in plant vegetative tissues in response to abiotic stress, including simultaneous environmental perturbations (i.e. nitrogen deficiency and low temperature, NDLT), but disappear with recovery from NDLT. Previously, we determined that a recombinant Arabidopsis β-glucosidase (BGLU), BGLU15, hydrolyzes flavonol 3-O-β-glucoside-7-O-α-rhamnosides and flavonol 3-O-β-glucosides, forming flavonol 7-O-α-rhamnosides and flavonol aglycones, respectively. In this study, the transient expression of a BGLU15-Cherry fusion protein in onion epidermal cells demonstrated that BGLU15 was localized to the apoplast. Analysis of BGLU15 T-DNA insertional inactivation lines (bglu15-1 and bglu15-2) revealed negligible levels of BGLU15 transcripts, whereas its paralogs BGLU12 and BGLU16 were expressed in wild-type and bglu15 plants. The recombinant BGLU16 did not hydrolyze quercetin 3-O-β-glucoside-7-O-α-rhamnoside or rhamnosylated flavonols, but was active with the synthetic substrate, p-nitrophenyl-β-d-glucoside. In addition, shoots of both bglu15 mutants contained negligible flavonol 3-O-β-glucoside-7-O-α-rhamnoside hydrolase activity, whereas this activity increased by 223% within 2 d of NDLT recovery in wild-type plants. The levels of flavonol 3-O-β-glucoside-7-O-α-rhamnosides and quercetin 3-O-β-glucoside were high and relatively unchanged in shoots of bglu15 mutants during recovery from NDLT, whereas rapid losses were apparent in wild-type shoots. Moreover, losses of two flavonol 3-O-β-neohesperidoside-7-O-α-rhamnosides and kaempferol 3-O-α-rhamnoside-7-O-α-rhamnoside were evident during recovery from NDLT, regardless of whether BGLU15 was present. A spike in a kaempferol 7-O-α-rhamnoside occurred with stress recovery, regardless of germplasm, suggesting a contribution from hydrolysis of kaempferol 3-O-β-neohesperidoside-7-O-α-rhamnosides and/or kaempferol 3-O-α-rhamnoside-7-O-α-rhamnoside by hitherto unknown mechanisms. Thus, BGLU15 is essential for catabolism of flavonol 3-O-β-glucoside-7-O-α-rhamnosides and flavonol 3-O-β-glucosides in Arabidopsis.
Handgrip weakness and mortality risk in COPD: a multicentre analysis

Handgrip strength is a simple measure of upper limb muscle function that is associated with mortality in the general population and in patients with COPD.1 ,2 Recently, normative values for handgrip strength have been proposed based on centile scores in >224 000 healthy adults between 39 and 73 years of age, adjusted for age, sex, height and measurement side.3 As an illustration, in a typical 65-year-old male patient 5th and 10th centile of right handgrip strength range 18–28 kg and 20–30 kg, respectively, depending on the patient's height. It is unclear whether the identification of handgrip weakness based on these centiles has prognostic value in addition to known prognostic parameters like FEV1, age, dyspnoea symptoms (combined in the validated ADO index4) and body mass index (BMI). Therefore, we performed an a posteriori analysis of prospectively collected multicentre data in patients with stable COPD, followed for a median of 3.9 years.2 ,5–7 Handgrip strength was assessed using …
Past, present, and future spatial distributions of deep-sea coral and sponge microbiomes revealed by predictive models

Knowledge of the spatial distribution patterns of biodiversity in the ocean is key to evaluate and ensure ocean integrity and resilience. Especially for the deep ocean, where in situ monitoring requires sophisticated instruments and considerable ﬁnancial investments, modelling approaches are crucial to move from scattered data points to predictive continuous maps. Those modelling approaches are commonly run on the macrobial level, but spatio-temporal predictions of host-associated microbiomes are not being targeted. This is especially problematic as previous research has highlighted that host-associated microbes (microbiomes) may display distribution patterns that are not perfectly correlated with host animal biogeographies, but also with other factors such as prevailing environmental conditions. We here establish a new simulation approach and present predicted spatio-temporal distribution patterns of deep-sea sponge and coral microbiomes, making use of a combination of environmental data, host data and microbiome data to advance our understanding of deep-sea microbiomes. This approach allows predictions of microbiome spatio-temporal distribution patterns on scales that are currently not covered by classical sampling approaches at sea. This includes both predictions in space within regional oceanic provinces off eastern North America, and also in time, with predictions into the past and future, covering a time span of 214 years. In summary, our presented predictions allow (i) identiﬁcation of microbial biodiversity hotspots in the past, present, and future, (ii) evaluation of microbial-macrobial connections at case-study sites through trait-based predictions, and (iii) identiﬁcation of shifts in microbial community composition (key taxa) across environmental gradients and shifting environmental conditions.
Autoregulation of cerebral blood flow during normocapnia and hypocapnia in dogs.

The effect of hypocapnia on autoregulation of cerebral blood flow (CBF) and the lower limit of autoregulation (LLA) was determined in dogs anesthetized with nitrous oxide (66%) and halothane (0.2%, end-expired concentration). CBF and cerebral vascular resistance (CVR) were determined during both normocapnia and hypocapnia (PaCO2 21-22 mmHg) at control cerebral perfusion pressure (CPP) and after reducing CPP (by hemorrhage) to 80%, 60%, 50%, and 40% of control. At control CPP hypocapnia decreased CBF from 75 +/- 5 to 48 +/- 3 ml.100 g-1.min-1 (mean +/- SEM, P less than 0.05). During both normocapnia and hypocapnia CVR decreased and CBF did not change as CPP was reduced to 60% of control. When CPP was reduced to 50% or 40% of control, CVR remained decreased and CBF fell sharply. The LLA during hypocapnia, 61 +/- 2% of control CPP, was not different than that during normocapnia, 59 +/- 3% of control CPP. Below the LLA the CBF-CPP slopes differed from zero but did not differ between hypocapnia and normocapnia. Hypocapnia does not produce a substantial shift of the LLA, and over the range of CPP values studied here, autoregulatory cerebral vasodilation only partially abolishes hypocapnia-induced cerebral vasoconstriction. The results suggest that when cerebral autoregulation is intact and in the absence of cerebrovascular disease, hypocapnia does not reduce global CBF to a level that is likely to produce ischemia and remains a useful therapeutic treatment so long as CPP remains above the LLA.