Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Granuloma In Vitro Model, for TB Dormancy and Resuscitation

Tuberculosis (TB) is responsible for death of nearly two million people in the world annually. Upon infection, Mycobacterium tuberculosis (Mtb) causes formation of granuloma where the pathogen goes into dormant state and can live for decades before resuscitation to develop active disease when the immune system of the host is weakened and/or suppressed. In an attempt to better understand host-pathogen interactions, several groups have been developing in vitro models of human tuberculosis granuloma. However, to date, an in vitro granuloma model in which Mtb goes into dormancy and can subsequently resuscitate under conditions that mimic weakening of the immune system has not been reported. We describe the development of a biomimetic in vitro model of human tuberculosis granuloma using human primary leukocytes, in which the Mtb exhibited characteristics of dormant mycobacteria as demonstrated by (1) loss of acid-fastness, (2) accumulation of lipid bodies (3) development of rifampicin-tolerance and (4) gene expression changes. Further, when these micro granulomas were treated with immunosuppressant anti-tumor necrosis factor-alpha monoclonal antibodies (anti-TNFα mAbs), resuscitation of Mtb was observed as has been found in humans. In this human in vitro granuloma model triacylglycerol synthase 1deletion mutant (Δtgs1) with impaired ability to accumulate triacylglycerides (TG), but not the complemented mutant, could not go into dormancy. Deletion mutant of lipY, with compromised ability to mobilize the stored TG, but not the complemented mutant, was unable to come out of dormancy upon treatment with anti-TNFα mAbs. In conclusion, we have developed an in vitro human tuberculosis granuloma model that largely exhibits functional features of dormancy and resuscitation observed in human tuberculosis.
Distribution and biological implications of plastic pollution on the fringing reef of Mo’orea, French Polynesia

Coral reef ecosystems of the South Pacific are extremely vulnerable to plastic pollution from oceanic gyres and land-based sources. To describe the extent and impact of plastic pollution, the distribution of both macro- (>5 mm) and microplastic (plastic < 5 mm) of the fringing reef of an isolated South Pacific island, Mo’orea, French Polynesia was quantified. Macroplastic was found on every beach on the island that was surveyed. The distribution of this plastic was categorized by site type and by the presence of Turbinaria ornata, a common macroalgae on Mo’orea. Microplastics were discovered in the water column of the fringing reef of the island, at a concentration of 0.74 pieces m−2. Additionally, this study reports for the first time the ingestion of microplastic by the corallimorpha Discosoma nummiforme. Microplastics were made available to corallimorph polyps in a laboratory setting over the course of 108 h. Positively and negatively buoyant microplastics were ingested, and a microplastic particle that was not experimentally introduced was also discovered in the stomach cavity of one organism. This study indicates that plastic pollution has the potential to negatively impact coral reef ecosystems of the South Pacific, and warrants further study to explore the broader potential impacts of plastic pollution on coral reef ecosystems.
Performance of interFoam on the simulation of progressive waves

ABSTRACT The performance of interFoam (a widely used solver within OpenFOAM®) in simulating the propagation of a nonlinear (stream function solution) regular wave is investigated in this work. It is demonstrated that over time there is a tendency for surface elevations to increase, wiggles to appear in the free surface, and crest velocities to become (severely) overestimated. It is shown that increasing the temporal and spatial resolution can mitigate these undesirable effects, but that a relatively small Courant number is required and fine discretization is needed, indicating that many past simulations have not converged. It is further demonstrated that discretization schemes and solver settings (often treated as a “black box” by users) can have a major impact on the results. This impact is documented, and it is shown that obtaining a “diffusive balance” is crucial to accurately propagate a surface wave over long distances without requiring exceedingly high temporal and spatial resolutions. Finally, the new code isoAdvector is demonstrated to produce comparably accurate results to interFoam, while maintaining a sharper surface. It is hoped that the present study will raise awareness of potential shortcomings of interFoam and enable a more accurate and optimal use, in CFD simulation of free surface waves.
Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

Gonadotropin releasing hormone-III (GnRH-III), a native isoform of the human GnRH isolated from sea lamprey, specifically binds to GnRH receptors on cancer cells enabling its application as targeting moieties for anticancer drugs. Recently, we reported on the identification of a novel daunorubicin–GnRH-III conjugate (GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] with efficient in vitro and in vivo antitumor activity. To get a deeper insight into the mechanism of action of our lead compound, the cellular uptake was followed by confocal laser scanning microscopy. Hereby, the drug daunorubicin could be visualized in different subcellular compartments by following the localization of the drug in a time-dependent manner. Colocalization studies were carried out to prove the presence of the drug in lysosomes (early stage) and on its site of action (nuclei after 10 min). Additional flow cytometry studies demonstrated that the cellular uptake of the bioconjugate was inhibited in the presence of the competitive ligand triptorelin indicating a receptor-mediated pathway. For comparative purpose, six novel daunorubicin–GnRH-III bioconjugates have been synthesized and biochemically characterized in which 6Asp was replaced by D-Asp, D-Glu and D-Trp. In addition to the analysis of the in vitro cytostatic effect and cellular uptake, receptor binding studies with 125I-triptorelin as radiotracer and degradation of the GnRH-III conjugates in the presence of rat liver lysosomal homogenate have been performed. All derivatives showed high binding affinities to GnRH receptors and displayed in vitro cytostatic effects on HT-29 and MCF-7 cancer cells with IC50 values in a low micromolar range. Moreover, we found that the release of the active drug metabolite and the cellular uptake of the bioconjugates were strongly affected by the amino acid exchange which in turn had an impact on the antitumor activity of the bioconjugates.
Age wise distribution of colorectal cancer: An institutional observational study

Background: Overall, the incidence of colorectal cancer appears to be stable or diminishing. However, based on our regional cancer institute’s datas, we have observed the increasing incidence of colorectal cancer in patients ≤40 age. The aim of this study was to verify the rising trend, clinico-pathological features and survival in colorectal cancer in patients ≤40,in comparison to patients >40 age. Materials and methods: A retrospective study was conducted to review all patients≤ 40 age and more than 40 year of age separatly with a diagnosis of colorectal cancer from January 2004 to December 2012. Results: Young patients were 24.17% of total 1096 colorectal cases. In young patients 60.37% were male and 39.63% were female. 9% young had family history & only 8% had history of alcohol intake. Onset of symptoms to reaching diagnosis period is longer in younger patients. (Range 3 months to 1 year in young, while 1 months to 6 months in older). Higher pathological T stage was seen in the younger age group when compared with patients above 40 years. Also the younger age group showed more advanced N stage when compared with patients above 40 years. With final TNM staging, in younger age group 66% were in stage IV and 30% were in stage III. Eighty percent of all young cancer deaths were within 22 months (from 8months to 22 months). Conclusion: Above results show the aggressive nature and late diagnosis of carcinoma colorectal in young. These data highlight a need for thorough evaluation of young with colorectal symptoms and in high risk population, also life style modification agenda by Govt . or non Govt. organization.
Nitrogen isotopes in bulk marine sediment: linking seafloor observations with subseafloor records

The stable isotopes of nitrogen offer a unique perspective on changes in the nitrogen cycle, past and present. However, the presence of multiple forms of nitrogen in marine sediments can complicate the interpretation of bulk nitrogen isotope measurements. Although the large-scale global patterns of seafloor δ 15 N have been shown to match process-based expectations, small-scale heterogeneity on the seafloor, or alterations of isotopic signals during translation into the subseafloor record, could obscure the primary signals. Here, a public database of nitrogen isotope measurements is described, including both seafloor and subseafloor sediment samples ranging in age from modern to the Pliocene, and used to assess these uncertainties. In general, good agreement is observed between neighbouring seafloor sites within a 100 km radius, with 85% showing differences of 15 N of the shallowest ( R 2 = 0.83), which suggests a reliable translation of sediments into the buried sediment record. Meanwhile, gradual δ 15 N decreases over multiple glacial–interglacial cycles appear to reflect post-depositional alteration in records from the deep sea (below 2000 m). We suggest a simple conceptual model to explain these 100-kyr-timescale changes in well-oxygenated, slowly accumulating sediments, which calls on differential loss rates for pools of organic N with different δ 15 N. We conclude that bulk sedimentary nitrogen isotope records are reliable monitors of past changes in the marine nitrogen cycle at most locations, and could be further improved with a better understanding of systematic post-depositional alteration. Furthermore, geochemical or environmental criteria should be developed in order to effectively identify problematic locations and to account for confounding influences where possible.
To Preserve or Not to Preserve the Orbit in Paranasal Sinus Neoplasms: A Meta-Analysis

Abstract Context The effect on survival of orbital evisceration on patients with paranasal sinus neoplasms has not been well established. Objective To review systematically the available literature concerning survival in patients who undergo surgery for paranasal sinus neoplasm with and without preservation of the eye. Data Source A retrospective meta-analysis of English and non-English articles using Medline and the Cochrane database. Eligibility Criteria Studies analyzing 5-year survival rates in patients who had orbital evisceration compared with orbital preservation for the treatment of paranasal sinus neoplasms were included in the final analysis. Data Extraction Independent review by two authors using predefined data fields. Data Synthesis A meta-analysis of four articles involving 443 patients was performed using the DerSimonian-Laird random-effects method. Results Our analysis revealed a total effect size of 0.964 in favor of preservation of the eye; however, these results are not robust, having a true effect size anywhere from 0.785 to 1.142 with a 95% confidence interval. Limitations Only retrospective observational studies were included because a prospective randomized study cannot be performed in this population. Conclusion Our study supports the notion that in select patients preservation of the eye may yield a different outcome when compared with orbital evisceration.
Endovascular therapy for ischemic stroke with perfusion-imaging selection.

BACKGROUND Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. METHODS We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. RESULTS The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. CONCLUSIONS In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).
Dispersal sinks and handling effects: interpreting the role of immigration in common brushtail possum populations

Summary 1. An evaluation of the potentially adverse effects of measurement must be made before concluding that one is dealing with a ‘dispersal sink’. 2. We conducted a spatially and temporally replicated removal experiment on common brushtail possums ( Trichosurus vulpecula ) in uniformly suitable old-growth eucalypt forest in south-eastern Australia, that was designed to address the question: does immigration ‘rescue’ populations from extinction? 3. Despite taking precautions to minimize potential harm, analyses indicated some evidence of an adverse effect of handling on the survival of pouch-young and strong evidence of effects on adult survival. In addition, symptoms of stress associated with handling observed at our site, corresponded to symptoms reported in connection with the long-term (15 + years) trapping study on possums conducted by Efford et al . in the Orongorongo Valley (OV) of New Zealand. 4. Initial projections from a demographic model indicated that the resident population at our site was not replacing itself (births < deaths), suggesting that the site was a dispersal sink. This was inconsistent with the fact that the site was in prime habitat. Moreover, the measured rate of true immigration in response to experimental removals was not sufficient to maintain the population density. Using data from Efford (1998), our model confirmed his suggestion that the OV site also appears to be a dispersal sink for possums, despite being in prime habitat. 5. When otherwise undiagnosable deaths among adults were assumed to be due to hand ling and ‘right-censored’ (excluded), the projection was that the resident population at our site was stable ( r ≅ 0), and therefore not in need of ‘rescue’ by immigration. Similarly, when survival estimates for the OV site were corrected by the same amounts, the projection was that the population at that site was also stable. 6. Most vacancies created by our experimental removals were filled by neighbouring residents that expanded their ranges into the removal areas. We suggest that the artificial ‘removal’ of residents as a consequence of deaths due to handling, may often induce an influx of such apparent immigrants, thereby giving the impression that immigration is ‘rescuing’ populations from extinction.
Effect of gemigliptin on glycaemic variability in patients with type 2 diabetes (STABLE study)

The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycaemic variability and to assess the correlation between glycaemic variability reduction and the dipeptidyl peptidase‐4 (DPP‐4) inhibition in patients with type 2 diabetes. This multicentre, randomized, active‐controlled, open‐label exploratory study included 69 patients with HbA1c > 7.5%. Subjects were randomized to receive gemigliptin 50 mg (n = 24), sitagliptin 100 mg (n = 23) or glimepiride 2 mg (n = 22) for 12 weeks. After 12 weeks, the change in mean amplitude of glycaemic excursion (MAGE) compared with baseline was significantly lower in the DPP‐4 inhibitor groups compared with that in patients who received glimepiride. Furthermore, the standard deviation (SD) of glucose was significantly lower in patients who received gemigliptin than that in patients who received sitagliptin or glimepiride. The DPP‐4 inhibition was significantly correlated with changes in MAGE and SD of glucose. In conclusion, gemigliptin and sitagliptin were more effective than glimepiride in reducing glycaemic variability as initial combination therapy with metformin in patients with type 2 diabetes, and the DPP‐4 inhibition was associated with a reduction in glycaemic variability.
Electrophysiological Correlates of Similarity-based Interference during Detection of Visual Forms

Illusory figure completion demonstrates the ability of the visual system to integrate information across gaps. Mechanisms that underlie figural emergence support the interpolation of contours and the filling-in of form information [Grossberg, S. , & Mingolla, E. Neural dynamics of form perception: Boundary completion, illusory figures and neon colour spreading. Psychological Review, 92, 173211, 1985]. Although both processes contribute to figure formation, visual search for an illusory target configuration has been shown to be susceptible to interfering form, but not contour, information [Conci, M. , Mller, H. J., & Elliott, M. A. The contrasting impact of global and local object attributes on Kanizsa figure detection. Submitted]. Here, the physiological basis of form interference was investigated by recording event-related potentials elicited from contour- and surface-based distracter interactions with detection of a target Kanizsa figure. The results replicated the finding of form interference and revealed selection of the target and successful suppression of the irrelevant distracter to be reflected by amplitude differences in the N2pc component (240340 msec). In conclusion, the observed component variations reflect processes of target selection on the basis of integrated form information resulting from figural completion processes.
Multidimensionality of Entrepreneurial Firm-level Processes: Do the Dimensions Covary?

INTRODUCTION TYPOLOGY OF MULTIDIMENSIONAL CONSTRUCTS ENTREPRENEURIAL PROCESSES CONSTRUCTS, SAMPLE, AND MODELS RESULTS DISCUSSION OF RESULTS LIMITATIONS OF STUDY CONTRIBUTIONS NOTES CONTACT REFERENCES APPENDIX FIGURE 1 FIGURE 2 TABLE 1 TABLE 2 TABLE 3 TABLE 4
Backscattering and Nonparaxiality Arrest Collapse of Damped Nonlinear Waves

The critical nonlinear Schrodinger equation (NLS) models the propagation of intense laser light in Kerr media. This equation is derived from the more comprehensive nonlinear Helmholtz equation (NLH) by employing the paraxial approximation and neglecting the backscattered waves. It is known that if the input power of the laser beam (i.e., L2 norm of the initial solution) is sufficiently high, then the NLS model predicts that the beam will self-focus to a point (i.e., collapse) at a finite propagation distance. Mathematically, this behavior corresponds to the formation of a singularity in the solution of the NLS. A key question which has been open for many years is whether the solution to the NLH, i.e., the "parent" equation, may nonetheless exist and remain regular everywhere, particularly for those initial conditions (input powers) that lead to blowup in the NLS. In the current study we address this question by introducing linear damping into both models and subsequently comparing the numerical solutions of the damped NLH (boundary-value problem) with the corresponding solutions of the damped NLS (initial-value problem) for the case of one transverse dimension. Linear damping is introduced in much the same way as is done when analyzing the classical constant-coefficient Helmholtz equation using the limiting absorption principle. Numerically, we have found that it provides a very efficient tool for controlling the solutions of both the NLH and NLS. In particular, we have been able to identify initial conditions for which the NLS solution does become singular, while the NLH solution still remains regular everywhere. We believe that our finding of a larger domain of existence for the NLH than for the NLS is accounted for by precisely those mechanisms that have been neglected when deriving the NLS from the NLH, i.e., nonparaxiality and backscattering.
Operation of a quantum-dot cellular automata (QCA) shift register and analysis of errors

Quantum-dot cellular automata (QCA) is a digital logic architecture that uses single electrons in arrays of quantum dots to perform binary operations. A QCA latch is an elementary building block which can be used to build shift registers and logic devices for clocked QCA architectures. We discuss the operation of a QCA latch and a shift register and present an analysis of the types and properties of errors encountered in their operation.
Infant formulas with increased concentrations of α-lactalbumin

: Human and bovine milk differ substantially in the ratio of whey to casein protein (approximately 60:40 in human milk and approximately 20:80 in bovine milk) and in the proportions of specific proteins. Although current infant formulas closely mimic the ratio of total whey to casein inhuman milk, the concentration of a-lactalbumin (the dominant protein in human milk) is relatively low in formula, whereas beta-lactoglobulin, a protein not found in human milk, is the most dominant whey protein in formula. Because of the differences in the protein profiles of human milk and infant formula, amino acid profiles also differ. To meet all essential amino acid requirements of infants, formula concentrations of protein must be higher than those in human milk. Recently, whey sources with elevated concentrations of alpha-lactalbumin have become available, which permitted the development of formulas with increased concentrations of this protein and decreased concentrations of beta-lactoglobulin. alpha-Lactalbumin is rich in tryptophan, which is typically the limiting amino acid in formula, and as a result, formulas have been developed with lower protein but higher tryptophan concentrations. This type of formula may offer a number of advantages to the neonate, which include producing plasma tryptophan concentrations equal to those found in breastfed infants and obviating the need for the body to dispose of excess nitrogen loads.