Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenoviral production of interleukin‐2 at the tumor site removes the need for systemic postconditioning in adoptive cell therapy

Systemic high dose interleukin‐2 (IL‐2) postconditioning has long been utilized in boosting the efficacy of T cells in adoptive cell therapy (ACT) of solid tumors. The resulting severe off‐target toxicity of these regimens renders local production at the tumor an attractive concept with possible safety gains. We evaluated the efficacy and safety of intratumorally administered IL‐2‐coding adenoviruses in combination with tumor‐infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16.OVA melanoma bearing C57BL/6 mice. The models are complementary: hamsters are semi‐permissive for human oncolytic adenovirus, whereas detailed immunological analyses are possible in mice. In both models, local production of IL‐2 successfully replaced the need for systemic recombinant IL‐2 (rIL‐2) administration and increased the efficacy of the cell therapy. Furthermore, vectored delivery of IL‐2 significantly enhanced the infiltration of CD8+ T cells, M1‐like macrophages, and B‐cells while systemic rIL‐2 increased CD25 + FoxP3+ T cells at the tumor. In contrast with vectored delivery, histopathological analysis of systemic rIL‐2‐treated animals revealed significant changes in lungs, livers, hearts, spleens, and kidneys. In summary, local IL‐2 production results in efficacy and safety gains in the context of ACT. These preclinical assessments provide the rationale for ongoing clinical translation.
High-Dimensional MVDR Beamforming: Optimized Solutions Based on Spiked Random Matrix Models

Minimum variance distortionless response (MVDR) beamforming (or Capon beamforming) is among the most popular adaptive array processing strategies due to its ability to provide noise resilience while nulling out interferers. A practical challenge with this beamformer is that it involves the inverse covariance matrix of the received signals, which must be estimated from data. Under modern high-dimensional applications, it is well known that classical estimators can be severely affected by sampling noise, which compromises beamformer performance. Here, we propose a new approach to MVDR beamforming, which is suited to high-dimensional settings. In particular, by drawing an analogy with the MVDR problem and the so-called “spiked models” in random matrix theory, we propose robust beamforming solutions that are shown to outperform classical approaches (e.g., matched filters and sample matrix inversion techniques), as well as more robust solutions, such as methods based on diagonal loading. The key to our method is the design of an optimized inverse covariance estimator, which applies eigenvalue clipping and shrinkage functions that are tailored to the MVDR application. Our proposed MVDR solution is simple, in closed form, and easy to implement.
The effect of multiple pass cutting on surface integrity when hard turning of AISI D2 cold work tool steel

A judicious choice of insert material, tool geometry and cutting conditions can make hard turning produce better surfaces than grinding. AISI D2 is the most extensively used cold work tool steel in the tool and die industry. This steel of 60 HRC hardness was turned with PVD TiN coated ceramic tools (Al2O3/TiCN). Intragranular cracks were observed with single pass turning, while transgranular cracks occurred with multiple pass turning that was also accompanied by an increase in compressive stresses. In both passes, the white layer was observed, but in single pass, there was no subsurface deformed grain orientation, whereas in multiple passes, there was a distinct orientation.
Effect of Intracameral Dexamethasone Injection at Conclusion of Cataract Surgery on Macular Thickness in Diabetics

Context: To measure central macular thickness (CMT) in diabetic patients after instilling intracameral dexamethasone at the end of cataract surgery and compare this measure with control group. Design: Prospective case-control study. Participants: 100 eyes of 100 diabetic patients undergoing cataract extraction. Methods: 50 eyes received intracameral dexamethasone 0.4mg/0.1ml at the end of surgery and 50 eyes received sham treatment as a control group. The CMT was measured before, one month, and three months after the surgery Results: The mean CMT in was 261.32 ± 9. 45μm in the dexamethasone injected group while in the control group was 275.76 ± 21. 36μm (p < 0.05) at the end of first month postoperatively. At the end of the third postoperative month the mean CMT was 262.34 ± 10. 77μm and 264.82 ± 9. 73μm in the dexamethasone injected group and the control group, respectively, (p > 0.05). The mean Intraocular Pressure (IOP) in the dexamethasone injected eyes was 14.98 ± 2.82 and 15.1 ± 2.82mmHg before and at the end of the first month following the surgery, respectively, (p > 0.05). Conclusion: The CMT of eyes which received intracameral dexamethasone is significantly lower than the control group at the end of first postoperative month, suggesting a possible role of intracameral dexamethasone in suppressing the early inflammatory response that can be linked to post cataract surgery macular edema in diabetics. A non significant increase in the IOP has been observed in the dexamethasone injected group this makes intracameral dexamethasone injection a possible safe practice at the end of cataract extraction in diabetics.
Skeleton-based matching for animation transfer and joint detection

In this paper we present a new algorithm for establishing correspondence between objects based on matching of extracted skeletons. First, a point cloud of an input model is scanned. Second, a skeleton is extracted from the scanned point cloud. In the last step, all the extracted skeletons are matched based on valence of vertices and segment lengths. The matching process yields into two direct applications - topological mapping and segment mapping. Topological mapping can be used for detection of joint positions from multiple scans of articulated figures in different poses. Segment mapping can be used for animation transfer and for transferring of arbitrary surface per-vertex properties. Our approach is unique, because it is based on matching of extracted skeletons only and does not require vertex correspondence.
Late Glacial Demographic Expansion Motivates a Clock Overhaul for Population Genetics.

The molecular clock hypothesis is fundamental in evolutionary biology as by assuming constancy of the molecular rate it provides a timeframe for evolution. However, increasing evidence shows time dependence of inferred molecular rates with inflated values obtained using recent calibrations. As recent demographic calibrations are virtually non-existent in most species, older phylogenetic calibration points (>1 Ma) are commonly used, which overestimate demographic parameters. To obtain more reliable rates of molecular evolution for population studies, I propose the calibration of demographic transition (CDT) method, which uses the timing of climatic changes over the late glacial warming period to calibrate expansions in various species. Simulation approaches and empirical data sets from a diversity of species (from mollusk to humans) confirm that, when compared with other genealogy-based calibration methods, the CDT provides a robust and broadly applicable clock for population genetics. The resulting CDT rates of molecular evolution also confirm rate heterogeneity over time and among taxa. Comparisons of expansion dates with ecological evidence confirm the inaccuracy of phylogenetically derived divergence rates when dating population-level events. The CDT method opens opportunities for addressing issues such as demographic responses to past climate change and the origin of rate heterogeneity related to taxa, genes, time, and genetic information content.
Stratospheric ozone response to sulfate geoengineering: Results from the Geoengineering Model Intercomparison Project (GeoMIP)

Geoengineering with stratospheric sulfate aerosols has been proposed as a means of temporarily cooling the planet, alleviating some of the side effects of anthropogenic CO2 emissions. However, one of the known side effects of stratospheric injections of sulfate aerosols under present‐day conditions is a general decrease in ozone concentrations. Here we present the results from two general circulation models and two coupled chemistry‐climate models within the experiments G3 and G4 of the Geoengineering Model Intercomparison Project. On average, the models simulate in G4 an increase in sulfate aerosol surface area density similar to conditions a year after the Mount Pinatubo eruption and a decrease in globally averaged ozone by 1.1−2.1 DU (Dobson unit, 1 DU = 0.001 atm cm) during the central decade of the experiment (2040–2049). Enhanced heterogeneous chemistry on sulfate aerosols leads to an ozone increase in low and middle latitudes, whereas enhanced heterogeneous reactions in polar regions and increased tropical upwelling lead to a reduction of stratospheric ozone. The increase in UV‐B radiation at the surface due to ozone depletion is offset by the screening due to the aerosols in the tropics and midlatitudes, while in polar regions the UV‐B radiation is increased by 5% on average, with 12% peak increases during springtime. The contribution of ozone changes to the tropopause radiative forcing during 2040–2049 is found to be less than −0.1 W m−2. After 2050, because of decreasing ClOx concentrations, the suppression of the NOx cycle becomes more important than destruction of ozone by ClOx, causing an increase in total stratospheric ozone.
The influence of pigment particle shape on the in-plane tensile strength properties of kaolin-based coating layers

The mechanical properties of paper coating layers are critical to converting and printing operations. These include stiffness, resistance to fold cracking, dusting, and pick resistance. For this study, we prepared unsupported coating layers and measured the in-plane tensile strength as a function of the kaolin particle shape factor. We found that, for kaolin pigments having a similar particle size by sedimentation, in-plane tensile strength and stiffness of the coating layer increases as the shape factor of the clay particles increases. Conversely, elongation to break decreases. These observations are interpreted in terms of the microstructure of the coating layers. A second observation is that elongation increases exponentially with latex level.This suggests that at latex levels normally used in paper coating, the polymer chains are constrained by adhesion onto pigment surfaces and are less extensible than in the bulk latex film.
Dental Caries and Developmental Defects of Enamel in the Primary Dentition of Preterm Infants: Case-Control Observational Study

Aim: Assessment of dental health in the primary dentition of preterm infants (PTI) including investigation of mother- and infant-related risk factors in a case-control study design. Material and Methods: One hundred twenty-eight infants aged 3-4 years were included. Sixty-four PTI (27 males) were randomly selected from the preterm registry of the Jena University Hospital. As a control group served 64 full-term infants (FTI) recruited from the Department of Paediatric Dentistry, matched for age and sex. Dental examinations were provided by one dentist under standard clinical conditions. Caries was scored using the International Caries Detection and Assessment System (ICDAS II) and the DMFT, gingival health using the Periodontal Screening Index, and developmental defects of enamel using the DDE index. Mother- and infant-related factors were collected via a questionnaire and from medical records. Results: The caries prevalence was 50.0% (ICDAS II >0) in PTI and 12.5% (ICDAS II >0) in FTI. The caries experience was higher in PTI (DMFT 1.0 ± 3.1) than in FTI (DMFT 0.3 ± 1.0). PTI had a higher risk of caries (OR 7.0), initial lesions (OR 6.2), DDE (OR 7.5), and gingivitis (OR 6.5) than FTI. The highest risk occurred in PTI with an extremely low birth weight (<1,000 g). A higher risk of DDE was present when mothers suffered from illness during pregnancy (OR 3.9). A higher risk of caries was revealed in infants with respiratory syndrome (OR 6.2) or when their mothers had a lower socioeconomic status (OR 6.3). Conclusions: PTI had less healthy teeth than FTI and are at a higher risk for DDE, caries, and gingivitis. The poorer dental health in PTI is associated with a low birth weight, a low socioeconomic status, and mothers' illness during pregnancy.
Mass Drug Administration for Trachoma: How Long Is Not Long Enough?

Background Blinding trachoma is targeted for elimination by 2020 using the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements). Annual mass drug administration (MDA) with azithromycin is a cornerstone of this strategy. If baseline prevalence of clinical signs of trachomatous inflammation – follicular among 1-9 year-olds (TF1-9) is ≥10% but <30%, the World Health Organization guidelines are for at least 3 annual MDAs; if ≥30%, 5. We assessed the likelihood of achieving the global elimination target of TF1-9 <5% at 3 and 5 year evaluations using program reports. Methodology/Principal Findings We used the International Trachoma Initiative’s prevalence and treatment database. Of 283 cross-sectional survey pairs with baseline and follow-up data, MDA was conducted in 170 districts. Linear and logistic regression modeling was applied to these to investigate the effect of MDA on baseline prevalence. Reduction to <5% was less likely, though not impossible, at higher baseline TF1-9 prevalences. Increased number of annual MDAs, as well as no skipped MDAs, were significant predictors of reduced TF1-9 at follow-up. The probability of achieving the <5% target was <50% for areas with ≥30% TF1-9 prevalence at baseline, even with 7 or more continuous annual MDAs. Conclusions Number of annual MDAs alone appears insufficient to predict program progress; more information on the effects of baseline prevalence, coverage, and underlying environmental and hygienic conditions is needed. Programs should not skip MDAs, and at prevalences >30%, 7 or more annual MDAs may be required to achieve the target. There are five years left before the 2020 deadline to eliminate blinding trachoma. Low endemic settings are poised to succeed in their elimination goals. However, newly-identified high prevalence districts warrant immediate inclusion in the global program. Intensified application of the SAFE strategy is needed in order to guarantee blinding trachoma elimination by 2020.
MYC-family protein overexpression and prominent nucleolar formation represent prognostic indicators and potential therapeutic targets for aggressive high-MKI neuroblastomas: a report from the children’s oncology group

Neuroblastomas with a high mitosis-karyorrhexis index (High-MKI) are often associated with MYCN amplification, MYCN protein overexpression and adverse clinical outcome. However, the prognostic effect of MYC-family protein expression on these neuroblastomas is less understood, especially when MYCN is not amplified. To address this, MYCN and MYC protein expression in High-MKI cases (120 MYCN amplified and 121 non-MYCN amplified) was examined by immunohistochemistry. The majority (101) of MYCN-amplified High-MKI tumors were MYCN(+), leaving one MYC(+), 2 both(+), and 16 both(−)/(+/−), whereas non-MYCN-amplified cases appeared heterogeneous, including 7 MYCN(+), 36 MYC(+), 3 both(+), and 75 both(−)/(+/−) tumors. These MYC-family proteins(+), or MYC-family driven tumors, were most likely to have prominent nucleolar (PN) formation (indicative of augmented rRNA synthesis). High-MKI neuroblastoma patients showed a poor survival irrespective of MYCN amplification. However, patients with MYC-family driven High-MKI neuroblastomas had significantly lower survival than those with non-MYC-family driven tumors. MYCN(+), MYC-family protein(+), PN(+), and clinical stage independently predicted poor survival. Specific inhibition of hyperactive rRNA synthesis and protein translation was shown to be an effective way to suppress MYC/MYCN protein expression and neuroblastoma growth. Together, MYC-family protein overexpression and PN formation should be included in new neuroblastoma risk stratification and considered for potential therapeutic targets.
A simplified guide to randomized controlled trials

A randomized controlled trial is a prospective, comparative, quantitative study/experiment performed under controlled conditions with random allocation of interventions to comparison groups. The randomized controlled trial is the most rigorous and robust research method of determining whether a cause–effect relation exists between an intervention and an outcome. High‐quality evidence can be generated by performing an randomized controlled trial when evaluating the effectiveness and safety of an intervention. Furthermore, randomized controlled trials yield themselves well to systematic review and meta‐analysis providing a solid base for synthesizing evidence generated by such studies. Evidence‐based clinical practice improves patient outcomes and safety, and is generally cost‐effective. Therefore, randomized controlled trials are becoming increasingly popular in all areas of clinical medicine including perinatology. However, designing and conducting an randomized controlled trial, analyzing data, interpreting findings and disseminating results can be challenging as there are several practicalities to be considered. In this review, we provide simple descriptive guidance on planning, conducting, analyzing and reporting randomized controlled trials.
Meta-Analysis of the Structural Equation Models' Parameters for the Estimation of Brain Connectivity with fMRI

Structural Equation Models (SEM) is among of the most extensively applied statistical techniques in the study of human behavior in the fields of Neuroscience and Cognitive Neuroscience. This paper reviews the application of SEM to estimate functional and effective connectivity models in work published since 2001. The articles analyzed were compiled from Journal Citation Reports, PsycInfo, Pubmed, and Scopus, after searching with the following keywords: fMRI, SEMs, and Connectivity. Results: A 100 papers were found, of which 25 were rejected due to a lack of sufficient data on basic aspects of the construction of SEM. The other 75 were included and contained a total of 160 models to analyze, since most papers included more than one model. The analysis of the explained variance (R2) of each model yields an effect of the type of design used, the type of population studied, the type of study, the existence of recursive effects in the model, and the number of paths defined in the model. Along with these comments, a series of recommendations are included for the use of SEM to estimate of functional and effective connectivity models.
Broiler chicken body weights, feed intakes, plasma lipid and small-intestinal bile acid concentrations in response to feeding of chitosan and pectin

One-day-old broiler chickens were fed on a control diet based on maize and maize starch or diets containing 30g/kg of 89 % deacetylated chitin (chitosan) or low-methoxyl (34 % degree of esterification) pectin. Feeding of the chitosan diet to chickens significantly reduced body weights and feed intakes compared with animals fed on control or pectin diets on days 5 and 11 of the experiment. On day 12, significant reductions in total plasma cholesterol and HDL-cholesterol concentrations were observed among birds fed on the chitosan but not the pectin diet in relation to control-fed animals. A concomitant increase in the plasma HDL-cholesterol:total cholesterol ratio was observed among chitosan-fed chickens. The generally reduced concentrations of primary and total bile acids in the duodenum of birds fed on the fibre-containing diets on day 13 may have been an indication of a delay in the production and/or secretion of bile. Viscosity of the three broiler-chicken diets was measured after suspension in water, acidification and finally neutralization of the suspensions, in an attempt to simulate the effect of changes in pH and dilution of diets occurring in the gizzard and small intestine of chickens. Viscosity of the chitosan diet was significantly elevated after acidification and significantly reduced at neutralization in comparison with the control and pectin-containingdiets suggesting that the hypolipidaemic influence of chitosan observed in the present study may be due to interruption of enterohepatic bile acid circulation rather than increased viscosity in the small intestine of chickens. The low viscosity of the pectin diet in vitro together with the absence of a hypocholesterolaemic effect of this diet when fed in vivo precludes any conclusion regarding the hypocholesterolaemic mechanism of pectin observed in earlier studies.
Nanotechnology in dentistry

Technology has continuously improved along with the complexity of devices. Nowadays, it is widely accepted that micro-technology, which is defined as a further reduction in the size of interconnections and components, is achieved by a conventional “top-down” method. We have now moved to a new concept and approach for fabrication from small to bigger building-block elements, which is called nanotechnology. Nanotechnology is the fabrication technology of tiny parts that is achieved by a “bottom-up” method. Nanotechnology has been developed in many areas of life sciences, such as in dentistry. This presentation provides some examples that illustrate the progress in technological growth, especially in the nanoscale. In the developments of nanotechnology, we are also concerned in many ways about its ethics and the laws of physics. The expansion in nanotechnology shows that much multidisciplinary research is being done in the nanoscale area. In dentistry, one of the examples is research in dental materials such as nanoleakage types in the use of various adhesives with resin composition. Nanodiagnostics are nanotechnology in applied molecular diagnostics. All these fields have applications in diagnostics and in point-of-care hand-held devices.
NBER WORKING PAPER SERIES WHAT DRIVES HOME MARKET ADVANTAGE ? A . Kerem Cosar

In the automobile industry, as in many tradable goods markets, firms usually earn their highest market share within their domestic market. The goal of this paper is to disentangle the supplyand demand-driven sources of the home market advantage. While trade costs, foreign production costs, and taste heterogeneity all matter for market outcomes, we find that a preference for home brands is the single most important driver of home market advantage even after controlling for brand histories and dealer networks. Furthermore, we also find that consumers favor domestically producing brands regardless of the historical brand origin. A. Kerem Cosar Stockholm School of Economics Sveavägen 65, 113 83 Stockholm, Sweden kerem.cosar@gmail.com Paul L. E. Grieco The Pennsylvania State University Department of Economics 509 Kern Building University Park Pennsylvania, PA 16802, USA paul.grieco@gmail.com Shengyu Li Business School Durham University Mill Hill Lane Durham, DH1 3LB UK shengyu.li@durham.ac. uk Felix Tintelnot Department of Economics University of Chicago 5757 South University Avenue Chicago, IL 60637 and NBER tintelnot@uchicago.edu