Miracle-dz/UniFAR-FTUs huggingface dataset:
A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor (TCR) Targeting of a Human Melanoma Antigen*

Human CD8+ cytotoxic T lymphocytes can mediate tumor regression in melanoma through the specific recognition of HLA-restricted peptides. Because of the relatively weak affinity of most anti-cancer T-cell receptors (TCRs), there is growing emphasis on immunizing melanoma patients with altered peptide ligands in order to induce strong anti-tumor immunity capable of breaking tolerance toward these self-antigens. However, previous studies have shown that these immunogenic designer peptides are not always effective. The melanocyte differentiation protein, glycoprotein 100 (gp100), encodes a naturally processed epitope that is an attractive target for melanoma immunotherapies, in particular peptide-based vaccines. Previous studies have shown that substitutions at peptide residue Glu3 have a broad negative impact on polyclonal T-cell responses. Here, we describe the first atomic structure of a natural cognate TCR in complex with this gp100 epitope and highlight the relatively high affinity of the interaction. Alanine scan mutagenesis performed across the gp100280–288 peptide showed that Glu3 was critically important for TCR binding. Unexpectedly, structural analysis demonstrated that the Glu3 → Ala substitution resulted in a molecular switch that was transmitted to adjacent residues, abrogating TCR binding and T-cell recognition. These findings help to clarify the mechanism of T-cell recognition of gp100 during melanoma responses and could direct the development of altered peptides for vaccination.
An Experimental Study on Risk Effects in a Dwarf Antelope, Madoqua guentheri

Risk of predation shapes the physiology, behavior, and demography of prey. Among the many studies that have examined effects of risk in ungulates, most have focused on large (> 40kg) and gregarious species. Much less is known about the effect of risk on smaller or territorial ungulates, which is a diverse group of species that can have pronounced effects on plant communities in tropical ecosystems. Using GPS telemetry, we examined spatial responses of Guenther's dik-dik (Madoqua guentheri) to scent marks from a common predator (African wild dogs, Lycaon pictus) or cattle. In response to predator scent marks, dik-diks increased fidelity within territories, avoided scent marks, and decreased use of overstory cover. Similar behaviors occurred in response to cattle scent marks, with the exception that use of overstory cover relative to controls did not change. Total amount (length) of movement did not change in response to either type of scent mark. Thus, an increase in perceived risk of predation changed the pattern and distribution of dik-dik movement but did not change total amount of movement. Our results suggest that territoriality may constrain the options available for prey to avoid predation risk.
Romidepsin Promotes Osteogenic and Adipocytic Differentiation of Human Mesenchymal Stem Cells through Inhibition of Histondeacetylase Activity

Bone marrow mesenchymal stem cells (BMSCs) are adult multipotent stem cells that can differentiate into mesodermal lineage cells, including adipocytes and osteoblasts. However, the epigenetic mechanisms governing the lineage-specific commitment of BMSCs into adipocytes or osteoblasts are under investigation. Herein, we investigated the epigenetic effect of romidepsin, a small molecule dual inhibitor targeting HDAC1 and HDAC2 identified through an epigenetic library functional screen. BMSCs exposed to romidepsin (5 nM) exhibited enhanced adipocytic and osteoblastic differentiation. Global gene expression and signaling pathway analyses of differentially expressed genes revealed a strong enrichment of genes involved in adipogenesis and osteogenesis in romidepsin-treated BMSCs during induction into adipocytes or osteoblasts, respectively. Pharmacological inhibition of FAK signaling during adipogenesis or inhibition of FAK or TGFβ signaling during osteogenesis diminished the biological effects of romidepsin on BMSCs. The results of chromatin immunoprecipitation combined with quantitative polymerase chain reaction indicated a significant increase in H3K9Ac epigenetic markers in the promoter regions of peroxisome proliferator-activated receptor gamma (PPARγ) and KLF15 (related to adipogenesis) or SP7 (Osterix) and alkaline phosphatase (ALP) (related to osteogenesis) in romidepsin-treated BMSCs. Our data indicated that romidepsin is a novel in vitro modulator of adipocytic and osteoblastic differentiation of BMSCs.
Quality assessment of Zeus faber (Peter’s fish) ovaries regularly commercialized for human consumption

In the last few years, the consumption of fish eggs has increased rapidly, finding widespread use also in mass catering. This increase has involved also those of the Peter’s fish (Zeus faber). Females of this species, by their reproductive characteristics, have highly developed gonads in different periods of the year, making the raw material easy to find. The aim of the present study was to perform a quality assessment of Zeus faber ovaries regularly commercialized for human consumption. A total number of 34 samples, divided in fresh (11) and frozen (23), were processed for microbiological characterization, parasitological and histological evaluations. Fresh and frozen samples have significant (P<0.01) differences in total bacterial charge, with values of 4.75±0.5 Log CFU/g and 3.65±0.7 Log CFU/g respectively. The mean value of Enterobacteriaceae was 2.58±0.7 Log CFU/g in fresh products, while 52.17% (12) of frozen samples reported loads of <1 Log CFU/g. No Salmonella spp. and Listeria monocytogenes were found. Aeromonas spp. was detected in two frozen sample (with loads of 2.2 and <1 Log CFU/g) and in 5 fresh ovaries with value ranged from 1.70 to 3.48 Log CFU/g. Vibrio spp. was found in 4 (36.36%) and 3 (13.04%) of fresh and frozen samples respectively, with loads always <1 Log CFU/g. All 31 Vibrio strains isolated, were identified as Vibrio alginolyticus, and 61.29% (19) of them was positive for the ToxRS factor and 6.45% (2) for ToxR. The 47.06% (16) of total samples showed infestations by larvae of Anisakis Type 1 in the serous and inside the ovary. In this last case, histologically it was found to be free larvae. This study attested satisfactory hygiene conditions for Zeus faber ovaries currently marked for human consumption. The presence of potentially pathogenic strains of V. alginolyticus and Aeromonas spp. , but above all the frequent infestation by Anisakis larvae, represent a potentially hazard for the consumer.
Detecting Distributed SQL Injection Attacks in a Eucalyptus Cloud Environment

The cloud computing environment offers malicious users the ability to spawn multiple instances of cloud nodes that are similar to virtual machines, except that they can have separate external IP addresses. In this paper we demonstrate how this ability can be exploited by an attacker to distribute his/her attack, in particular SQL injection attacks, in such a way that an intrusion detection system (IDS) could fail to identify this attack. To demonstrate this, we set up a small private cloud, established a vulnerable website in one instance, and placed an IDS within the cloud to monitor the network traffic. We found that an attacker could quite easily defeat the IDS by periodically altering its IP address. To detect such an attacker, we propose to use multi-agent plan recognition, where the multiple source IPs are considered as different agents who are mounting a collaborative attack. We show that such a formulation of this problem yields a more sophisticated approach to detecting SQL injection attacks within a cloud computing environment.
Adaptive E-Learning Technologies for Sustained Learning Motivation in Engineering Science - Acquisition of Motivation through Self-Reports and Wearable Technology

Surveys show besides the number of students also the drop-out rates are increasing, especially in early phases of studying natural or engineering sciences. The research project “SensoMot Sensor Measures of Motivation for Adaptive Learning” tries to counter this development by means of improving the quality of teaching in the department of micro technology with the help of an adaptive e-learning system. For that purpose, the mediated learning content should be better adapted to the individual prior knowledge, competencies and motivational profiles of the learners. Furthermore, the continuous sensory data acquisition of physiological parameters of the learner shall be accomplished by current wearable technology. The paper presents first results in the form of conceptual determinations concerning self-reports and physiological measures, instructional design and adaptation techniques and further includes the early involvement of the subsequent users in the development process through an iterative, formative evaluation of prototypical solutions.
Comparison of preemptive effect of intravenous ketorolac versus meperidine on postoperative shivering and pain in patients undergoing cesarean section under spinal anesthesia: A prospective, randomized, double-blind study

Background: Pain and shivering are two unpleasant problems in postoperative period. Various techniques are used to alleviate the postoperative shivering and pain. We compared the preemptive prescription of a single dose of intravenous meperidine and ketorolac on postoperative pain and shivering in patients undergoing cesarean section with spinal anesthesia. Methods: One hundred and fifty patients who were scheduled for elective cesarean section under spinal anesthesia were randomly allocated to one of three study groups to receive intravenous ketorolac (group K), meperidine (group M) or normal saline (group P). Time to first analgesic request, analgesic requirement in the first 24 hours after surgery, body tympanic temperature, hemodynamic variables and incidence of shivering were assessed as outcome variables. Results: There was no significant difference between meperidine and ketorolac groups in terms of prevalence of shivering, although both groups were different from the placebo group (p<0.04). The mean time to first analgesic request was longer in group k (3.8±1.4) and groups M (3.3±1.2) than in group P (2.1±0.8) hours (p<0.001). Conclusions: The preemptive prescription of a single dose of intravenous meperidine and ketorolac can provide a satisfying analgesia immediately after surgery and decrease shivering prevalence without any serious side effects.
Fiber optic liquid level monitoring system using microstructured polymer fiber Bragg grating array sensors: performance analysis

A highly sensitive liquid level monitoring system based on microstructured polymer optical fiber Bragg grating (mPOFBG) array sensors is reported for the first time. The configuration is based on five mPOFBGs inscribed in the same fiber in the 850 nm spectral region, showing the potential to interrogate liquid level by measuring the strain induced in each mPOFBG embedded in a silicone rubber (SR) diaphragm, which deforms due to hydrostatic pressure variations. The sensor exhibits a highly linear response over the sensing range, a good repeatability, and a high resolution. The sensitivity of the sensor is found to be 98 pm/cm of water, enhanced by more than a factor of 9 when compared to an equivalent sensor based on a silica fiber around 1550 nm. The temperature sensitivity is studied and a multi-sensor arrangement proposed, which has the potential to provide level readings independent of temperature and the liquid density.
Comparison between presepsin and procalcitonin in early diagnosis of neonatal sepsis

Abstract Background: Neonatal sepsis remains worldwide one of the leading causes of morbidity and mortality in both term and preterm infants. Lower mortality rates are related to timely diagnostic evaluation and prompt initiation of empiric antibiotic therapy. Blood culture, as gold standard examination for sepsis, has several limitations for early diagnosis, so that sepsis biomarkers could play an important role in this regard. This study was aimed to compare the value of the two biomarkers presepsin and procalcitonin in early diagnosis of neonatal sepsis. Methods: This was a prospective cross-sectional study performed in Saiful Anwar General Hospital Malang, Indonesia, in 51 neonates that fulfill the criteria of systemic inflammatory response syndrome (SIRS) with blood culture as diagnostic gold standard for sepsis. Results: At reviewer operating characteristic (ROC) curve analyses, using a presepsin cutoff of 706.5 pg/mL, the obtained area under the curve (AUCs) were sensitivity = 85.7%, specificity = 68.8%, positive predictive value = 85.7%, negative predictive value = 68.8%, positive likelihood ratio = 2.75, negative likelihood ratio = 0.21, and accuracy = 80.4%. On the other hand, with a procalcitonin cutoff value of 161.33 pg/mL the obtained AUCs showed: sensitivity = 68.6%, specificity = 62.5%, positive predictive value = 80%, negative predictive value = 47.6%, positive likelihood ratio = 1.83, the odds ratio negative = 0.5, and accuracy = 66.7%. Conclusions: In early diagnosis of neonatal sepsis, compared with procalcitonin, presepsin seems to provide better early diagnostic value with consequent possible faster therapeutical decision making and possible positive impact on outcome of neonates.
Efficient Distributed Computation of MIS and Generalized MIS in Linear Hypergraphs

Given a graph, a maximal independent set (MIS) is a maximal subset of pairwise non-adjacent vertices. Finding an MIS is a fundamental problem in distributed computing. Although the problem is extensively studied and well understood in simple graphs, our knowledge is still quite limited when solving it in hypergraphs, especially in the distributed CONGEST model. In this paper, we focus on linear hypergraphs---a class of hypergraphs in which any two hyperedges overlap on at most one node. We first present a randomized algorithm for computing an MIS in linear hypergraphs. It has poly-logarithmic runtime and it works in the CONGEST model. The algorithm uses a network decomposition to achieve fast parallel processing. Within each cluster of the decomposition, we run a distributed variant of a parallel hypergraph MIS algorithm by Luczak and Szymanska. We then propose the concept of a generalized maximal independent set (GMIS) as an extension to the classical MIS in hypergraphs. More specifically, in a GMIS, for each hyperedge $e$ in a hypergraph $\mathcal{H}$, we associate an integer threshold $t_e$ in the range $[1, |e|-1]$, and the goal is to find a maximal subset $\mathcal{I}$ of vertices that do not violate any threshold constraints: $\forall e \in E(\mathcal{H}), |e \cap \mathcal{I}| \leq t_e$. We hope that GMIS might capture a broader class of real-world problems than MIS; we also believe that GMIS is an interesting and challenging symmetry breaking problem on its own. Our second upper bound result is a distributed algorithm for computing a GMIS in linear hypergraphs, subject to the constraint that the maximum hyperedge size is bounded by some constant. Again, the algorithm has poly-logarithmic runtime and it works in the CONGEST model. It is obtained by generalizing our previous (linear) hypergraph MIS algorithm.
Rule-based deduplication of article records from bibliographic databases

We recently designed and deployed a metasearch engine, Metta, that sends queries and retrieves search results from five leading biomedical databases: PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Central Register of Controlled Trials. Because many articles are indexed in more than one of these databases, it is desirable to deduplicate the retrieved article records. This is not a trivial problem because data fields contain a lot of missing and erroneous entries, and because certain types of information are recorded differently (and inconsistently) in the different databases. The present report describes our rule-based method for deduplicating article records across databases and includes an open-source script module that can be deployed freely. Metta was designed to satisfy the particular needs of people who are writing systematic reviews in evidence-based medicine. These users want the highest possible recall in retrieval, so it is important to err on the side of not deduplicating any records that refer to distinct articles, and it is important to perform deduplication online in real time. Our deduplication module is designed with these constraints in mind. Articles that share the same publication year are compared sequentially on parameters including PubMed ID number, digital object identifier, journal name, article title and author list, using text approximation techniques. In a review of Metta searches carried out by public users, we found that the deduplication module was more effective at identifying duplicates than EndNote without making any erroneous assignments.
Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure

The molecular basis of Fetal Alcohol Spectrum Disorders (FASD) is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and persistent gene expression changes. Epigenetic marks may maintain expression changes over a mouse’s lifetime, an area few have explored. Here, mice were injected with saline or ethanol on postnatal days four and seven. At 70 days of age gene expression microarray, methylated DNA immunoprecipitation microarray, H3K4me3 and H3K27me3 chromatin immunoprecipitation microarray were performed. Following extensive pathway analysis of the affected genes, we identified the top affected gene expression pathway as “Free radical scavenging”. We confirmed six of these changes by droplet digital PCR including the caspase Casp3 and Wnt transcription factor Tcf7l2. The top pathway for all methylation-affected genes was “Peroxisome biogenesis”; we confirmed differential DNA methylation in the Acca1 thiolase promoter. Altered methylation and gene expression in oxidative stress pathways in the adult hippocampus suggests a novel interface between epigenetic and oxidative stress mechanisms in FASD.
Textural equilibrium melt geometries around tetrakaidecahedral grains

In textural equilibrium, partially molten materials minimize the total surface energy bound up in grain boundaries and grain–melt interfaces. Here, numerical calculations of such textural equilibrium geometries are presented for a space-filling tessellation of grains with a tetrakaidecahedral (truncated octahedral) unit cell. Two parameters determine the nature of the geometries: the porosity and the dihedral angle. A variety of distinct melt topologies occur for different combinations of these two parameters, and the boundaries between different topologies have been determined. For small dihedral angles, wetting of grain boundaries occurs once the porosity has exceeded 11%. An exhaustive account is given of the main properties of the geometries: their energy, pressure, mean curvature, contiguity and areas on cross sections and faces. Their effective permeabilities have been calculated, and demonstrate a transition between a quadratic variation with porosity at low porosities to a cubic variation at high porosities.
DNA metabarcoding of littoral hard-bottom communities: high diversity and database gaps revealed by two molecular markers

Biodiversity assessment of marine hard-bottom communities is hindered by the high diversity and size-ranges of the organisms present. We developed a DNA metabarcoding protocol for biodiversity characterization of structurally complex natural marine hard-bottom communities. We used two molecular markers: the “Leray fragment” of mitochondrial cytochrome c oxidase (COI), for which a novel primer set was developed, and the V7 region of the nuclear small subunit ribosomal RNA (18S). Eight different shallow marine littoral communities from two National Parks in Spain (one in the Atlantic Ocean and another in the Mediterranean Sea) were studied. Samples were sieved into three size fractions from where DNA was extracted separately. Bayesian clustering was used for delimiting molecular operational taxonomic units (MOTUs) and custom reference databases were constructed for taxonomic assignment. Despite applying stringent filters, we found high values for MOTU richness (2,510 and 9,679 MOTUs with 18S and COI, respectively), suggesting that these communities host a large amount of yet undescribed eukaryotic biodiversity. Significant gaps are still found in sequence reference databases, which currently prevent the complete taxonomic assignment of the detected sequences. In our dataset, 85% of 18S MOTUs and 64% of COI MOTUs could be identified to phylum or lower taxonomic level. Nevertheless, those unassigned were mostly rare MOTUs with low numbers of reads, and assigned MOTUs comprised over 90% of the total sequence reads. The identification rate might be significantly improved in the future, as reference databases are further completed. Our results show that marine metabarcoding, currently applied mostly to plankton or sediments, can be adapted to structurally complex hard bottom samples. Thus, eukaryotic metabarcoding emerges as a robust, fast, objective and affordable method to comprehensively characterize the diversity of marine benthic communities dominated by macroscopic seaweeds and colonial or modular sessile metazoans. The 18S marker lacks species-level resolution and thus cannot be recommended to assess the detailed taxonomic composition of these communities. Our new universal primers for COI can potentially be used for biodiversity assessment with high taxonomic resolution in a wide array of marine, terrestrial or freshwater eukaryotic communities.
QSAR Applicability Domain Estimation by Projection of the Training Set in Descriptor Space: A Review

As the use of Quantitative Structure Activity Relationship (QSAR) models for chemical management increases, the reliability of the predictions from such models is a matter of growing concern. The OECD QSAR Validation Principles recommend that a model should be used within its applicability domain (AD). The Setubal Workshop report provided conceptual guidance on defining a (Q)SAR AD, but it is difficult to use directly. The practical application of the AD concept requires an operational definition that permits the design of an automatic (computerised), quantitative procedure to determine a model's AD. An attempt is made to address this need, and methods and criteria for estimating AD through training set interpolation in descriptor space are reviewed. It is proposed that response space should be included in the training set representation. Thus, training set chemicals are points in n-dimensional descriptor space and m-dimensional model response space. Four major approaches for estimating interpolation regions in a multivariate space are reviewed and compared: range, distance, geometrical, and probability density distribution.