Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase 0 first-in-human study using NU-0129: A gold base spherical nucleic acid (SNA) nanoconjugate targeting BCL2L12 in recurrent glioblastoma patients.

3012 Background: Glioblastoma is a difficult to treat tumor with therapeutics limited by their ability to cross the blood brain barrier. SNAs, i.e., gold nanoparticle cores covalently conjugated with a corona of densely packed, highly oriented siRNA oligonucleotides targeted to the GBM oncogene BCL2L12, represent a novel class of blood-brain and blood-tumor barrier-permeable nanomedicinal conjugates, for suppressing gene expression in the tumors of GBM patients. Methods: This is a single-arm, open-label, “window of opportunity” phase 0 first-in-human trial to determine the safety and bioavailability of a novel nanotherapeutic compound, NU-0129. Enrolled patients were treated with intravenous NU-0129 at the dose of 0.04mg/kg. This treatment dosing was considered microdosing defined as 1/50ththe NOAEL (no observed adverse event level) from non-human primate studies. Treatment was followed by tumor resection 8-48 hours later. Primary outcome patient safety and toxicity was monitored weekly for 3 weeks post-infusion. Secondary objectives included biodistribution of NU0129 in tissue, evaluation of pharmacokinetics of NU0129 and the feasibility of NU0129 administration. Exploratory objectives included Bcl2L12 expression and post treatment apoptotic markers as well as progression free survival and overall survival rates. Results: 8 patients were enrolled, treated and subsequently underwent surgical resection. No significant treatment related toxicities were seen. Severe ( > grade 3) adverse events were observed in two patients: hypophosphatemia (one grade 3, one grade 4) and one patient with grade 3 lymphopenia, all were considered as “possibly related” by treating oncologists. In 6 of the 8 patients sufficient tumor tissue was available for analysis of gold accumulation by ICP-MS (inductively coupled plasma-mass spectrometry), and gold accumulation was seen in the tumor tissue of all 6 of these patients. Conclusions: Macrodosing of the nanotherapeutic NU-0129 was well tolerated in glioblastoma patients with no unexpected adverse effects and showed initial evidence of crossing blood brain barrier. Immunohistochemistry for Bcl2L12 expression, apoptotic markers, and PK studies are pending. The demonstration of gold nanoparticles in the tumor tissue validates this approach for drug delivery. Clinical trial information: NCT03020017.
Decentralized Smart City SurveillanceData Processing Middleware for On-Premises Video Data Analysis

Surveillance cameras are nowadays pervasive elements in our cities: they act as a deterrent against illegal activities or traffic violations, they help investigating crimes, and they can provide useful traffic and people analytics. Collecting video streams from multiple sources, possibly in real-time, poses a number of ethical, legal and technical challenges. As engineers we mainly focus on the latter issue, leaving the first two to politicians and lawyers. On the one hand, we recognize that the infrastructure needed to stream data needs to be sufficiently capable, robust and scalable; on the other hand, we know that plentiful of raw processing power and a vast stor- age capacity are required to analyze multiple video streams in real time and save the resulting information. In this paper we aim attention at those technical issues and present an on-going project focused at providing real-time information by means of a flexible processing infrastruc- ture. We tackle the robustness concern through a decentralized middleware solution, and we aim at improving the scalability of the system by using machine learning techniques to extrapolate structured knowledge as soon as possible, so that only the relevant data needs to be transmitted further in the network and stored on remote servers. This approach enables surveillance oper- ators to quickly inquire the system by means of morphological or color search criteria instead of watching hundreds of video streams, then select and automatically track interesting items within different video streams.
Functional mapping of primary visual cortex in awake mice

Cortical circuits consist of interconnected excitatory and inhibitory neurons. These neurons have highly diverse morphologies. Even in the same cortical layer, the dendritic and axonal arbors of a given class of inhibitory interneurons, for example, have highly distinct structures. The functional specificity of the various types of cortical neurons is largely unclear. Here, by using electrophysiological recordings combined with two-photon calcium imaging in the in vivo mouse brain, we first characterized the response properties of different types of interneurons of the primary visual cortex in awake behaving mice, and then we analyzed the response properties of defined, single neurons during distinct cortical states. The results reveal that the response properties of the three major interneuron groups, that is, parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine3A receptor (5HT3aR) positive interneurons were distinctly different in terms of baseline firing rates, sensory stimulation-evoked firing rates, peak response latencies and orientation selectivity indices. Moreover, we identified a new class of 5HT3aR positive interneurons, which was characterized by a unique and highly distinct activity profile. Morphological analyses demonstrated that this is a new type of giant basket cell (GBC) of the mouse visual cortex, which receives synaptic input from cortical layers 1 and 2/3 and provides synaptic output through a huge axonal arbor exclusively to layer 2/3 neurons. The immunohistochemical analysis demonstrated that GBCs are positive not only for 5HT3aR but also for Vasoactive intestinal peptide (VIP), Reelin and Cholecystokinin (CCK). We demonstrate that GBCs act as inhibitory hub cells that effectively control motions detection in L2/3 of awake animals. In conclusion, this study demonstrates that the structural diversity of inhibitory interneurons is associated with highly distinct functional features. This functional diversity was not anticipated in previous studies and emphasizes the need for systematic structure-function analyses of neurons in awake, behaving animals.
BISAM: From small mammals to a four-legged walking machine

In this paper we apply principles of mammalian locomotion to the development of an autonomous robot. The relevance of biological analyses to the fields of kinematics, construction and locomotor control is discussed. The control architecture presented here is based on coupled neuro-oscillators and models the locomotor behaviour of the machine on different levels. The locomotion of animals is controlled by only a small set of parameters.
A queueing model for airport capacity and delay analysis

Air traffic, worldwide, keeps growing strongly, creating critical capacity situations and traffic congestion. Large delays are suffered by airlines, passengers and airport authorities alike. When a rough estimate is needed, the results of queuing theory can be used to analyse airport runway systems, but when airports are too congested or a more realistic description of the system behaviour is necessary, a simulation approach is a good alternative. This research outlines the limits of the analytical approach and shows how to build a simulation procedure. This procedure is able to measure the performance of an airport runway used only for arrivals, with different traffic mixes and operational variables. The impact of future technological systems is also considered.
Modeling weight round robin packet scheduler with Petri nets

This paper introduces a model using Petri nets for weight round robin (WRR) packet scheduler for Ethernet switches. This model uses the IEEE 802.1Q specification to schedule seven different classes of services in order to support quality of service at link layer. The proposed model can be used in performance analysis simulations and to educational purpose.
Response of Soybeans to 2,4-D, Dicamba, and Picloram

Field experiments were conducted for 2 years at Urbana, Illinois, to evaluate the response of soybeans (Glycine max (L.) Merr. , var. Harosoy 63) to soil and foliar applications of 3,6-dichloro-o-anisic acid (dicamba), 4-amino-3,5,6-trichloropicolinic acid (picloram), and (2,4-dichlorophenoxy)acetic acid (2,4-D). Soil incorporated applications of 2,4-D or dicamba at rates up to 8 oz/A or 4 oz/A, respectively, just before planting soybeans did not reduce soybean yields significantly. Picloram, applied under the same conditions, reduced soybean yield almost 40% at ½ oz/A. Picloram at rates from ½ to 2 oz/A caused slight to moderate leaf malformation on soybeans planted the following year but did not reduce yield. Foliar applications of 2,4-D up to 2 oz/A on soybeans had little effect on yield when applied at the prebloom stage and only slightly reduced yield when applied during flowering. Dicamba and picloram injured soybeans at the prebloom stage considerably more than did 2,4-D. Dicamba and picloram severely restricted soybean development, and reduced yield markedly when applied during flowering; ½ oz/A of dicamba or ⅛ oz/A of picloram reduced soybean yield about 50%.
The distribution and unexpected genetic diversity of the non-indigenous annelid Ficopomatus enigmaticus in California

The non-indigenous annelid Ficopomatus enigmaticus has been established in San Francisco Bay since at least 1921, but in the past 30 years it has also been found in other parts of California. In the summer of 2017 we surveyed 136 sites to determine its current distribution in the state. We found F. enigmaticus at 23 sites ranging from San Francisco Bay in the north to Newport Bay in the south. Populations were concentrated in four regions: San Francisco Bay, Monterey Bay, Santa Barbara, and sites in Los Angeles and Orange Counties. Presence sites did not differ systematically in salinity or temperature from absence sites, but all presence sites appeared to have restricted exchange of water with nearby oceanic habitats. Data on the timing of first discovery in each region is roughly consistent with the hypothesis of southward spread of propagules from the San Francisco Bay population. To further test this hypothesis, we obtained mitochondrial DNA sequences from individuals collected from four sites nearly spanning the current latitudinal range of F. enigmaticus in California. Recent work from Australia suggests that there is substantial withinpopulation cryptic genetic diversity in F. enigmaticus, with individual aggregations containing individuals whose mitochondrial cytochrome B haplotypes fall into one of two very distinct (~ 19% uncorrected genetic distance) haplotype groups, Clades 1 and 2. We found a similar pattern in California, with Clade 1 and Clade 2 individuals co-occurring at two of the four sites we sampled. Three of ten known F. enigmaticus haplotypes occurring in Australia were observed in California populations; four haplotypes observed in California have not previously been reported. Analysis of haplotype distributions suggests that central California populations may be derived from the San Francisco Bay population, while unique haplotypes present in the Long Beach population suggest the possibility of a second independent introduction in that region. Additional genetic data from populations of F. enigmaticus around the globe are needed to resolve the invasion history and systematics of these widespread serpulids.
Relations spatiales en Réalité Augmentée sur dispositifs mobiles

Handheld devices processing power increases and they embed more and more sensors. It is now possible on such devices to overlay the view of the physical surrounding provided by the back-facing camera with computer graphics. This technique has been coined as \Augmented Reality" and it is used in dierent areas. Augmented Reality creates a mixed environment composed of the view of the physical surrounding augmented with digital content displayed on the handheld device’s screen. In this context, this paper studies the spatial relations involved while the user is interacting with this mixed environment. We focus on two spatial relations : (1) between the object of interest in the physical world and the handheld device, and (2) between the handheld device and the user. We present some handheld Augmented Reality application examples that make use of those spatial relations for interaction.
A study to assess impact of teaching proper case history taking of the most common psychiatric disorder - Major Depressive Disorder (MDD) in Interns

Background and Objectives: Psychiatry lectures & clinical posting are the only learning experience of psychiatry for Medical Graduates. Only interns attend their compulsory psychiatry posting. The aim is to make Interns competent to elicit & write proper history of MDD and able to describe different components of history taking, diagnostic criteria, to demonstrate communication skills. Methods: It was a Prospective Interventional Study done in 45 Interns posted consecutively in Psychiatry. On Day1, Interns were asked to take and write history of MDD patient and evaluated on Checklist for history taking (10 components), SMCQ (15) and Mini-CEX. Then Interns were taught about MDD by CBL, SGL and Role Play. On Day 7, they were again evaluated on Mini-CEX. On term ending, they were again evaluated as per Day1. Feedback of Interns and faculties were taken. Appropriate Statistical Tests were used using SPSS Version 16. Results: On Checklist for history taking of MDD apart from Negative History and Mental Status Examination, Interns’ skills improved significantly. Mean score on SMCQ got doubled from 6±0.83 to 12±0.83. On Mini-CEX, apart from clinical judgement, counselling skills and overall clinical competence, Interns improved from unsatisfactory to superior level. Feedback was positive on most of the components of study but few were satisfied completely with their history writing & communication skills and diagnosing ability. Faculties’ perceptions were very encouraging. Conclusion: Teaching of MDD case history taking was well taken & perceived by interns. Knowledge about MDD & competency to take history and identifying patients of MDD improved satisfactorily.
Application of pharmacogenomics and bioinformatics to exemplify the utility of human ex vivo organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response.
Distribution of Arsenic in Soil Profiles after Repeated Applications of MSMA

Arsenic as MSMA (monosodium methanearsonate) was applied to three soil types over a 6-year period. Percentage recovery of applied arsenic averaged 67, 57, and 39% in Hart-sells fine sandy loam, Decatur silt loam, and Dothan loamy sand soils, respectively. Essentially all of the arsenic recovered in the soils occurred in the plow layer with no evidence of leaching into deeper zones. Batch-equilibrium and soil-column studies in the laboratory indicated that the rate of MSMA movement through the surface horizon would be fastest in Dothan loamy sand and slowest in Decatur silt loam.
Molecular and functional characterization of genes involved in setting up and reading histone methylation in Arabidopsis thaliana

Histone methylation is one of the keys epigenetic marks evolutionarily conserved in eukaryotes. My study focuses on the characterization of factors potentially involved in the deposition and reading of lysine (K) methylation to appreciate its role and underlying mechanisms in the regulation of transcription and plant development, using Arabidopsis thaliana as a model organism. In the first part of my thesis, I report on our study of SET DOMAIN GROUP7 (SDG7), a protein containing the evolutionarily conserved SET domain, which is generally recognized as a signature of K-methyltransferases. We found that SDG7 plays an important role in the regulation of VIN3 induction associated with cold duration measure during vernalization treatment. Intriguingly, levels of several different histone methylations were found unchanged in the sdg7 mutant plants and the recombinant SDG7 protein failed to show a histone-methyltransferase activity in vitro. We thus conclude that SDG7 might methylate a yet unknown non-histone protein to regulate transcription and proper measurement of the duration of cold exposure in the vernalization process. In the second part, I studied interaction between SDG8 and HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2. My results unravel that H3K36me3 and H2Bub1 are deposited largely independently in Arabidopsis, which is in contrast to the dependent crosstalk of these two different epigenetic marks previously reported in yeast. In the last part of my thesis, I report on the identification of the PWWP-domain proteins HUA2/HULK2 as readers of H3K36me3 and demonstrate that sdg8 and hua2 genetically interacts in the regulation of flowering time.
Results of a phase 2a, multicenter, open-label, study of RM-1929 photoimmunotherapy (PIT) in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).

6014 Background: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmunotherapy (PIT) with a targeted drug RM-1929, consisting of the EGFR-directed antibody cetuximab conjugated to a photoactivatable dye (IRDye 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with nonthermal red light induces selective and rapid necrosis of the cancer cells, with minimal damage to surrounding tissue. Methods: A phase 2a, multicenter, open-label, study of RM-1929 PIT in patients with locoregional, rHNSCC who could not be satisfactorily treated with surgery, radiation, or platinum chemotherapy was conducted to evaluate the safety and efficacy of the drug, RM-1929. For each treatment, nonthermal red light (690 nm) was applied to the tumors 24 hours post IV infusion of the drug. Surface illumination was administered for superficial tumors and interstitial illumination via intratumoral placement of fiber optic diffusers for deep tumors. Therapeutic response was assessed using CT RECIST 1.1 by an independent blinded radiologist. Results: Thirty rHNSCC patients were enrolled. There were no dose-limiting toxicities and one Grade 1 photosensitivity reaction. Most reported AEs were mild to moderate in severity with 96.7% (29/30) of patients with Grade 1 and 83.3% (25/30) with Grade 2, respectively. There were 13 (43.3%) patients who had at least one SAE. 86% (19/22) of SAEs were deemed unlikely related to treatment, including all 3 fatal SAEs. Three SAEs were reported to be possibly/probably related to treatment (site/oral pain, tumor hemorrhage, and airway obstruction). ORR was 50% (15/30) with 16.7% (5/30) CR and 86.7% (26/30) DCR. Median PFS and OS results will be forthcoming. Conclusions: These data indicate that RM-1929 PIT treatment was generally well tolerated with majority of AEs as mild to moderate in severity. Preliminary data showed favorable response rates in a heavily pre-treated population. A global phase 3 clinical trial is currently underway. Clinical trial information: NCT02422979.
Periprosthetic joint infection in orthopaedic surgical oncology

The use of tumor megaprostheses in patients with bone tumors has provided a successful limb salvaging treatment option in oncology patients. Unfortunately, the prevalence of periprosthetic infection is much higher after oncologic joint arthroplasty than after regular joint arthroplasty, ranging from 7% to 28%. This increased risk of infection is caused by local and systemic immunodeficiency due to chemotherapy and radiotherapy, long duration of surgery, large wound areas and the use of large implants. This review focused on specific issues regarding infected megaprostheses in oncology patients, aiming to give directions for the prevention, diagnosis and treatment of infected megaprostheses.
Effects of Prometryn, Diuron, Fluometuron, and MSMA on Chlorella and Two Fungi

The effects of prometryn [2,4-bis(isopropylamino)-6-(methylthio)-s-triazine], diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea], fluometuron [1,1-dimethyl-3-(a,a,a-trifluoro-m-tolyl)urea], and MSMA (monosodium methanearsonate) on Chlorella pyrenoidosa Chick ‘Strain 252′, Trichoderma viride Pers. ex Fr. , and Aspergillus terreus Thom were investigated. Minimum herbicide concentrations necessary to decrease C. pyrenoidosa growth after exposure for 35 generations were 10-8M diuron, 10-7M prometryn, and 10-6M fluometuron. MSMA had no effect. C. pyrenoidosa photosynthesis was essentially stopped by a 2-hr exposure to 5 × 10-6M prometryn or diuron and by 5 × 10-5M fluometuron. Prometryn (5 × 10-5M) or diuron (5 × 10-7M) increased respiration by 70 and 44%, respectively after an 80-min treatment. Maximum fluometuron inhibition of respiration was ca 25% and MSMA had little or no effect. Herbicide concentrations of 0, 10-6, 10-5, and 10-4M were used to measure their effects on colony diameter growth, gain in mycelial dry weight, sporulation, and respiration of the two fungi. No concentration of any of the herbicides had any major effect on any of these parameters except sporulation. T. viride sporulation was increased approximately 20, 30, 35, and 50% by 10-6M concentrations of prometryn, diuron, fluometuron, and MSMA, respectively. Sporulation of A. terreus was also somewhat increased by these herbicides.
Impact of exercise training and/or diet on the lipoprotein–lipid profiles in young overweight women

This study examined the independent and combined effects of exercise training, weight loss and changes in dietary quality on the serum lipid profile in sedentary, healthy and overweight young women. 83 women 18-25 years with body mass index>25 were randomly assigned to four groups, control (C), diet (D), exercise (E) and exercise and diet (ED). Height, weight, per cent body fat (BF%), TC, HDL-C, TG and LDL-C were measured before and after an 8-week intervention period. Subjects in the two exercise groups walked five times a week, 45 min per session, at 60%-80% of maximum heart rate (MHR). Duration and intensity of exercise were gradually increased over a 3-week period from 25 to 30 min/sessions at 60%-65% of MHR during week 1 to 45 min at 70% to 80% MHR from weeks 4 through 8. Subjects in the two nonwalking groups (C and D) reported to the exercise facility 5 days per week for 45 min of stretching and mild range of motion calisthenics. The intent was to keep heart rate below 100 beats per minute. One-way ANOVA was the statistical test (α=0.05). Relative to control group, the ED and D groups displayed a 4.2% and 4.1% reduction in body mass, 9% and 7% reduction in BF%, 29% and 26% reduction in TG. LDL-C fell by 12% in ED group. For each kg of weight loss there was a decrease of 0.05, 0.02 and 0.015 mg/dl in TC, LDL-C and TG respectively. No change of body mass occurred in E group. Exercise alone was insufficient to stimulate change in any lipid or lipoprotein measures. These results demonstrated that weight loss mostly was due to diet, because the exercise was the same in groups E and ED. The lipid profile improved and body mass decreased.