Miracle-dz/UniFAR-FTUs huggingface dataset:
SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer

Immunotherapeutic strategies including the blockade of programmed death 1 (PD-1) receptors hold promise for the treatment of various cancers including non-small cell lung carcinoma (NSCLC). Preclinical data suggest that pre-existing tumor immunity is important for disease regression upon checkpoint blockade-based therapies. However, the nature of antigen-specific T-cell responses that correlate with the clinical response to immunotherapy in NSCLC patients is not known. The embryonic stem cell gene SRY (sex determining region Y)-box 2 (SOX2) has recently emerged as a major oncogenic driver in NSCLC. Here, we show that nearly 50% of a cohort of NSCLC patients mounted both CD4+ and CD8+ T-cell responses against SOX2, which could be readily detected among peripheral blood mononuclear cells. T-cell responses against SOX2 were associated with NSCLC regression upon immunotherapy with anti-PD-1 monoclonal antibodies, whereas none of the patients lacking SOX2-specific T cells experienced disease regression following immune checkpoint blockade. Conversely, cellular and humoral responses against viral antigens or another tumor-associated antigen (NY-ESO-1) failed to correlate with the clinical response of NSCLC patients to immunotherapy. Of note, the administration of PD-1-blocking antibodies was associated with intramolecular epitope spread as well as with the amplification of SOX2-specific immune responses in vivo. These findings identify SOX2 as an important tumor-associated antigen in NSCLC and link the presence of SOX2-specific T cells with the clinical response of lung cancer patients to immunotherapy.
Evaluation of Automatically Generated Hint Feedback

This work explores the effects of using automatically generated hints in problem solving tutor environments. Generating hints automatically removes a large amount of development time for new tutors, and it also useful for already existing computer-aided instruction systems that lack intelligent feedback. We focus on a series of problems, after which, previous analysis showed the control group is to be 3.5 times more likely to cease logging onto an online tutor when compared to the group who were given hints. We found a consistent trend in which students without hints spent more time on problems when compared to students that were provided hints.
A motivic conjecture of Milne

Let k be an algebraically closed field of characteristic p>0. Let W(k) be the ring of Witt vectors with coefficients in k. We prove a motivic conjecture of Milne that relates, in the case of abelian schemes, the \'etale cohomology with $\dbZ_p$ coefficients to the crystalline cohomology with integral coefficients, in the more general context of p-divisible groups endowed with {\it arbitrary} families of crystalline tensors over a finite, discrete valuation ring extension of W(k). This extends a result of Faltings in [Fa2]. As a main new tool we construct global deformations of p-divisible groups endowed with crystalline tensors over certain regular, formally smooth schemes over W(k) whose special fibers over k have a Zariski dense set of k-valued points.
Pulmonary resection for patients with multidrug-resistant tuberculosis: systematic review and meta-analysis.

OBJECTIVES Multidrug-resistant tuberculosis (MDR-TB) has become an emerging global public health crisis. Several studies have suggested that pulmonary resection has efficacy in the treatment of MDR-TB. A systematic review of the available therapeutic studies was conducted to determine the treatment outcome among patients with MDR-TB who underwent pulmonary resection. METHODS To evaluate pulmonary resection for MDR-TB, a random-effect meta-analysis of the available studies was used to assess the overall treatment outcome. Subgroup analyses were also conducted by separating studies based on each characteristic independently. RESULTS After screening 4996 articles, 15 clinical reports with a mean of 63 patients per report met the inclusion criteria. Analysis of the studies showed that the estimated pooled treatment success rate of pulmonary resection for patients with MDR-TB was 84% [95% confidence interval (CI) 78%-89%]. The rates of failure, relapse, death and default were 6% (95% CI 4%-8%), 3% (95% CI 1%-4%), 5% (95% CI 2%-8%) and 3% (95% CI 1%-5%), respectively. The proportion of patients treated successfully did not differ significantly on the basis of any of the individual study characteristics. CONCLUSIONS Substantial heterogeneity in the study characteristics prevented a more conclusive determination of what factors had the greatest effect on the proportion of patients that achieve treatment success and limited the validity of this analysis. Some important variables, including patient HIV status, were inconsistently reported between studies. These results underscore the importance of strong patient support and treatment follow-up systems to develop successful MDR-TB treatment programmes.
Examination of Throughflow in a Radial ESF Clutch

A prototype clutch having horizontal rotational axis and a narrow gap between its two parallel radial disks is examined using computational fluid dynamics (CFD). The narrow gap between the discs is filled with an unexcited electrostructured fluid (ESF); the throughflow of electrorheological (ERF) or magnetorheological (MRF) fluid that would arise is contemplated as a means of contributing towards the cooling of the clutch. The throughflow, caused by body/centrifugal force action, is examined first when both plates rotate together at a speed, Ω. The aim is to estimate the flow rates arising under conditions of different rotational velocities, clutch geometries, and fluid properties. Following this, the cooling of the clutch is examined for the case of one plate fixed and the other rotating at a constant speed throughout. The inlet and outlet port pressures are made the same and the fluid is taken to be unexcited/Newtonian with viscosity μ.
The Coulomb branch of gauge theory from rotating branes

At zero temperature the Coulomb Branch of = 4 super Yang-Mills theory is described in supergravity by multi-center solutions with D3-brane charge. At finite temperature and chemical potential the vacuum degeneracy is lifted, and minima of the free energy are shown to have a supergravity description as rotating black D3-branes. In the extreme limit these solutions single out preferred points on the moduli space that can be interpreted as simple distributions of branes - for instance, a uniformly charged planar disc. We exploit this geometrical representation to study the thermodynamics of rotating black D3-branes. The low energy excitations of the system appear to be governed by an effective string theory which is related to the singularity in spacetime.
Information transfer and aggregation in an uninformed committee: A model for the selection and use of biased expert advice

A committee of five uses majority rule for decisions on two public goods. Individual committee member preferences depend on a state of nature that is unknown to the committee members but the state of nature is known to two experts who have preferences about committee decisions. Experts have no vote on the committee but provide a recommendation to the committee at the opening of a meeting. Two experts who have known, opposing biases are selected – a dyadic mechanism. The results reveal that experts do not tell the truth but committee decisions are as if committee members know what the experts know. The information transfer occurs because committee members anticipate the biases and properly infer the information held by the experts.
de Travail du Centre d ’ Economie de la Sorbonne How costly is rent-seeking to diversification : an empirical approach

The empirical U-shaped pattern between product diversification and economic development has been widely examined, but here we analyze the determinants of diversification. We find that a high level of rent-seeking activities has a large impact on the diversification of nations: in countries where rent-seeking is a widespread practice, the number of products being exported will be smaller and its value more concentrated in certain goods. Our analysis embraces a large sample of more than 130 countries between 1995 and 2007, using a highly disaggregated export database comprising more than 5000 products. To establish this relationship we use a Generalized Method of Moments estimation, controlling for endogeneity originated from reverse causality. These empirical predictions contribute to the idea that resources allocated to harm diversification are an important binding constraint for developing countries.
New Sensitive One-Step Real-Time Duplex PCR Method for Group A and B HIV-2 RNA Load

ABSTRACT The Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) previously developed a widely used method for HIV-1 RNA quantification (Biocentric). Here, we report the development of a new specific and sensitive method for HIV-2 RNA quantification, based on an adaptation of the existing HIV-1 protocol. The new test is based on TaqMan one-step reverse transcription-quantitative PCR (qRT-PCR) targeting two conserved consensus regions of HIV-2 (long terminal repeat [LTR] and gag). Analytic performances were determined in three laboratories. Clinical performances were evaluated on 100 plasma samples from HIV-2-infected patients (groups A, B, and H) by comparison with the assay currently used for the ANRS HIV-2 cohort. The specificity was 100%. Sensitivity was 50 copies/ml (cp/ml) and was optimized to 10 cp/ml. The within-run coefficients of variation in the three laboratories varied from 0.54% to 1.61% at 4 log10 copies/ml and from 7.24% to 14.32% at 2 log10 cp/ml. The between-run coefficients of variation varied from 2.28% to 6.43%. Of the 39 clinical samples below 2 log10 in the current assay, the new test improved the detection or quantification of 17 samples, including eight group B samples. For quantifiable samples, similar loads were obtained with the two assays for group A samples. The median difference between the two assays for group B samples was +0.18 but with greater heterogeneity than for group A. The HIV-2 group H sample had similar results with the two assays. This new assay is highly sensitive and accurately quantifies the most prevalent HIV-2 groups. This test will be useful for monitoring low viral loads in HIV-2-infected patients.
An optimality proof of the LRU-K page replacement algorithm

This paper analyzes a recently published algorithm for page replacement in hierarchical paged memory systems [O'Neil et al. 1993]. The algorithm is called the LRU-<italic>K</italic> method, and reduces to the well-known LRU (Least Recently Used) method for <italic>K</italic> = 1. Previous work [O'Neil et al. 1993; Weikum et al. 1994; Johnson and Shasha 1994] has shown the effectiveness for <italic>K</italic> > 1 by simulation, especially in the most common case of <italic>K</italic> = 2. The basic idea in LRU-<italic>K</italic> is to keep track of the times of the last <italic>K</italic> references to memory pages, and to use this statistical information to rank-order the pages as to their expected future behavior. Based on this the page replacement policy decision is made: which memory-resident page to replace when a newly accessed page must be read into memory. In the current paper, we prove, under the assumptions of the independent reference model, that LRU-<italic>K</italic> is optimal. Specifically we show: given the times of the (up to) <italic>K</italic> most recent references to each disk page, no other algorithm <italic>A</italic> making decisions to keep pages in a memory buffer holding <italic>n</italic> - 1 pages based on this infomation can improve on the expected number of I/Os to access pages over the LRU-<italic>K</italic> algorithm using a memory buffer holding <italic>n</italic> pages. The proof uses the Bayesian formula to relate the space of actual page probabilities of the model to the space of observable page numbers on which the replacement decision is acutally made.
Diagnostic and Predictive Capability of Routine Laboratory Tests for the Diagnosis and Staging of Equine Inflammatory Disease

Background A wide spectrum of laboratory tests is available to aid diagnosis and classification of equine inflammatory disease. Objectives To compare diagnostic efficacy and combined predictive capability of the myeloperoxidase index (MPXI), and plasma fibrinogen, iron and serum amyloid A (SAA) concentrations for the diagnosis of inflammation. Animals Twenty‐six hospitalized horses with systemic inflammation (SI), 114 with local inflammation (LI) and 61 healthy horses or those with noninflammatory disease (NI) were included. Methods A retrospective study was performed; clinicopathologic data from horses were compared between groups. Receiver‐operator characteristic (ROC) curves were used to evaluate diagnostic efficacy; classification and regression tree analysis (CART) and logistic regression analysis were used to generate diagnostic algorithms. Results Horses with SI had significantly higher SAA than horses with LI (P = .007) and NI (P < .001) and lower iron concentrations than horses with LI (P < .001) and NI (P < .001). Fibrinogen concentration was higher in horses with inflammation than in those without inflammation (P = .002). There was no difference between the SI and LI groups. White blood cell count, neutrophil count and MPXI were similar between groups. SAA had the highest accuracy for diagnosing inflammation (area under ROC curve [AUC], 0.83 ± 0.06) and iron and SAA concentration had the highest accuracy for differentiating SI from LI (AUC, 0.80 ± 0.09 and 0.73 ± 0.10 respectively). Predictive modeling failed to generate useful algorithms and classification of cases was moderate. Conclusions and Clinical Importance Very high SAA and low iron concentrations may reflect SI, but diagnostic guidelines based on quantitative results of inflammatory markers could not be formulated.
Disc galaxy evolution models in a hierarchical formation scenario: structure and dynamics

We predict the internal structure and dynamics of present-day disc galaxies using galaxy evolution models within a hierarchical formation scenario. The halo mass aggregation histories, for a flat cold dark matter model with cosmological constant, were generated and used to calculate the virialization of dark matter haloes. A diversity of halo density profiles were obtained, the most typical one being close to that suggested by Navarro, Frenk & White. We modelled the way in which discs in centrifugal equilibrium are built within the evolving dark haloes, using gas accretion rates proportional to the halo mass aggregation rates, and assuming detailed angular momentum conservation. We calculated the gravitational interactions between halo and disc – including the adiabatic contraction of the halo due to disc formation – and the hydrodynamics, star formation and evolution of the galaxy discs. We find that the slope and zero-point of the Tully–Fisher (TF) relation in the infrared bands may be explained as a direct consequence of the cosmological initial conditions. This relation is almost independent of the assumed disc mass fraction, when the disc component in the rotation curve decomposition is non-negligible. Thus, the power spectrum of fluctuations can be normalized at galaxy scales through the TF relation independently of the disc mass fraction assumed. The rms scatter of the model TF relation originates mainly from the scatter in the dark halo structure and, to a minor extension, from the dispersion of the primordial spin parameter λ. The scatter obtained from our models does not disagree with the observational estimates. Our models allow us to understand why the residuals of the TF relation do not correlate significantly with disc size or surface brightness. We can also explain why low and high surface brightness galaxies have the same TF relation; the key point is the dependence of the star formation efficiency on the disc surface density. The correlations between gas fraction and surface brightness, and between scalelength and Vmax obtained with our models agree with those observed. Discs formed within the growing haloes, where λ is assumed to be time independent, have nearly exponential surface density distributions. The shape of the rotation curves changes with disc surface brightness and is nearly flat for most cases. The rotation curve decompositions show a dominance of dark matter down to very small radii, in conflict with some observational inferences. The introduction of shallow cores in the dark halo attenuates this difficulty and produces haloes with slightly smaller rotation velocities. Other features of our galaxy models are not strongly influenced by the shallow core.
Stacking fault energies of Ni-Co-Cr alloys

Abstract The stacking-fault energies of a number of Ni–Co–Cr alloys are determined using the node method. The results are based on the calculations by Brown (1964). Contours of constant stacking-fault energy are shown, which evidently have a certain tendency to follow the boundary of the f.c. c. region.
Potential chemoprotective effects of selenium on diazinon-induced DNA damage in rat peripheral blood lymphocyte

The purpose of this study was to investigate the protective effects of selenium (Se) against genotoxicity induced by diazinon (DZN) in rat peripheral blood lymphocytes by micronucleus (MN) test. Animals were concurrently administered intraperitoneally with DZN in proper solvent (20 mg/kg body weight (b.w.)) and Se at three different doses (0.5, 1, and 2 mg/kg b.w.) for 30 consecutive days. The positive control group received DZN at the same dose without Se. After 24 h of last injection, 0.5 ml blood of each rat was received and cultured in culture medium for 44 h. The lymphocyte cultures were mitogenically stimulated with cytochalasin B to allow the evaluation of number of MNs in cytokinesis-blocked binucleated cells. Incubation of lymphocytes with DZN induced additional genotoxicity and is shown by increase in MNs frequency in human lymphocytes. Se at low dose of 0.5 mg/kg had a maximum effect and significantly reduced the MNs frequency in cultured lymphocytes (p < 0.0001) that reduced the frequency of MN from 12.78 ± 0.24% for DZN group to 4.40 ± 0.36. The present study revealed that Se particularly at low doses has a potent antigenotoxic effect against DZN -induced toxicity in rats, which may be due to the scavenging of free radicals and increased antioxidant status.
CORPORATE FINANCE WHEN MONETARY POLICY TIGHTENS: HOW DO BANKS AND NON-BANKS AFFECT ACCESS TO CREDIT?

The evolving financial environment facing the corporate sector provides many non-bank external finance options as an alternative to bank finance and this paper examines the relationship between UK firms’ choices over bank versus non-bank finance under different monetary conditions. We look at the external finance 'mix' using a panel of 16,000 UK firm records taken from the FAME database for the years 1990 through 1999 taking into account firm-specific characteristics. The paper provides support for a credit channel by demonstrating evidence consistent with a bank lending channel, accelerator effects and a broad credit channel for small, risky and young firms that shows all types of lending are reduced for these groups when monetary policy tightens.
Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery.
Pharmacophore Fingerprinting. 1. Application to QSAR and Focused Library Design

A new method of rapid pharmacophore fingerprinting (PharmPrint method) has been developed. A basis set of 10,549 three-point pharmacophores has been constructed by enumerating several distance ranges and pharmacophoric features. Software has been developed to assign pharmacophoric types to atoms in chemical structures, generate multiple conformations, and construct the binary fingerprint according to the pharmacophores that result. The fingerprint is used as a descriptor for developing a quantitative structure-activity relationship (QSAR) model using partial least squares. An example is given using sets of ligands for the estrogen receptor (ER). The result is compared with previously published results on the same data to show the superiority of a full 3D, conformationally flexible approach. The QSAR model can be readily interpreted in structural/chemical terms. Further examples are given using binary activity data and some of our novel in-house compounds, which show the value of the model when crossing compound classes.
Complex study of zirconia-silica and niobia-silica composite coatings produced by ion beam sputtering

In this study, we report on our recent progress in research of single layer mixed zirconia-silica and niobia-silica composite coatings prepared by Ion Beam Sputtering technique. All coatings of the same optical thickness were characterized in terms of reflection/transmission spectrometry, X-ray diffraction, atomic force and optical microscopy, optical back-scattering and optical resistance (laser-induced damage threshold - LIDT) in subpicosecond mode. The optical resistance, TIS and LIDT results reveal clear dependence on high refractive index material content in composite coating and its crystalline structure. The results are interpreted and discussed by the means of different models available in literature.