Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical characterization of Sintilimab, a fully human anti-PD-1 therapeutic monoclonal antibody for cancer

ABSTRACT Background Programmed cell death 1 (PD-1) is an inhibitory immune checkpoint expressed on activatedT cells. Upon the formation of T cell receptor (TCR)-pMHC complexes, concomitant PD-1 ligation to its ligands programmed death-ligand 1 (PD-L1) or programmed death-ligand 2 (PD-L2) downregulates TCR signaling and effector function. Here we describe the preclinical characterization of Sintilimab, a fully human IgG4 antibody that potently blocks PD-1 interactions with PD-L1 and PD-L2. Methods The binding affinity and blockade function were detected by using surface plasmon resonance (SPR), Enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biology function properties were measured with luciferase assay and mixed lymphocyte reaction assay. In vivo anti-tumor function and preclinical pharmacokinetic (PK) were identified with human PD-1 transgenic mice and non-human primates separately. Results Sintilimab can specifically and strongly bind to human PD-1 (hPD-1) and cynomolgus PD-1 and the affinity of Sintilimab to human PD-1 was measured at 0.3 nm via surface SPR, and displayed slow dissociation kinetics. Sintilimab can block the interaction of PD-1 to PD-L1 and PD-L2 and induce high secretion levels of interferon (IFN)-γ and interleukin (IL)-2 in primary T cell assays. In humanized hPD-1 knock-in mouse models, Sintilimab showed potent anti-tumor activity and increased tumor-infiltrating CD8/CD4 T cell and CD8/ Treg ratios. Preclinical experimentation in non-human primates following a single intravenous infusion of Sintilimab at 1, 6 and 30 mg/kg presented with no signs of drug-related toxicity, and showed typical PK characteristics of an IgG antibody. Conclusions Sintilimab has desirable preclinical attributes that supports its clinical development for cancer treatment.
Kahoot! Quizzes: A Formative Assessment Tool to Promote Students’ Self- Regulated Learning Skills

Gamified student response systems (GSRSs) have been increasingly used for formative assessment (FA) purposes in higher education. While previous studies on Kahoot! have given empirical evidence of the effectiveness of its gamified features in increasing students’ motivation, enhancing classroom dynamics and providing immediate feedback on students’ learning, the present study mainly investigates the students’ ratings of Kahoot! Quizzes (KQs) as a FA tool that facilitates the development of self-regulatory learning (SRL) skills. The study uses the seven principles of effective feedback to design a FA model that promotes students’ self- regulatory skills by defining the teacher’s role and students’ responsibilities while administering KQs. The study is a classroom action research that was done during a summer course and involved (n =70) female students in two linguistics courses. The researchers used a questionnaire and a focus group discussion to get students’ feedback on the effectiveness of KQs in enhancing their self-regulated learning. The results consistently showed positive evaluation of KQs along three dimensions: effective feedback, classroom environment and developing students’ meta-cognitive skills, the three essential ingredients of self-regulated learning. The model proved to be extremely effective in designing effective KQs that enhance students’ self- regulatory skills.
Segmentation and characterization of tourists by spending composition in World Heritage Cities

ABSTRACT Spending has been one of the most frequently analyzed economic variables over the past decades in studies on tourism, and especially those related to cultural destinations. Over time, researchers have focused on identifying and understanding the factors that condition tourism spending as a key variable to ensure the multiplier effect of tourism on the territories and, therefore, the competitiveness of tourism destinations at a global level. Despite this, there are few studies on tourism segmentation according to tourists’ spending patterns, and even fewer when it comes to World Heritage Sites. Using model-based Gaussian clustering, this study identifies six clusters, which are subsequently characterized according to the socio-demographic characteristics of the tourists, the characteristics of these tourists’ trip and their level of satisfaction with different aspects of the destination. The study has focused on Úbeda and Baeza (Spain), based on information from 2126 surveys conducted between June and September 2016.
Reproductive potential of Ucides cordatus (Linnaeus, 1763) (Decapoda: Brachyura: Ocypodidae) from two mangrove areas subject to different levels of contaminants

Ocypodid crabs are common in mangrove areas, and the uçá, Ucides cordatus (Linnaeus, 1763), is a key species. It is abundant and economically relevant in these marine wetlands on the southeastern Atlantic coast of Brazil. Mangroves suffer from intense anthropogenic impact by pollutants affecting the reproductive biology of the animals inhabiting this ecosystem. We analyzed the reproductive potential of U. cordatus, comparing fecundity and fertility equations between two mangroves with distinct pollution levels in São Paulo state, Brazil: a pristine (Juréia-Itatins Ecological Station) and a contaminated (Cubatão) area. There was no difference in egg production (fecundity) between crabs from both areas, possibly due to tolerance mechanisms exhibited by the crabs. There was, however, a substantial difference in larval production, which was three times higher in crabs from the contaminated mangrove than in those from the pristine mangrove. These results are explained by different reproductive conditions of the ovigerous females arising from the fertility analysis: primiparous (first spawning from the contaminated area) and multiparous females (second or subsequent spawning from the pristine area). Multiple spawning in the same reproductive season had not been previously reported for this species. Results, however, do not explain the relationship between environmental contaminants and fertility, which should be investigated in the future.
Isolating syntax in natural language: MEG evidence for an early contribution of left posterior temporal cortex

Syntax is the engine that allows us to create an infinitude of linguistic expressions, and the construction of syntactic structures, such as noun phrases and verb phrases, is considered a fundamental component of language processing. Nevertheless, insights concerning the neurobiological basis of syntax have remained elusive, in part because it is difficult to isolate syntax from semantic composition. Consequently, many studies of syntax have relied on meaningless artificial stimuli, such as jabberwocky expressions or artificial grammars. However, while pure manipulations of syntax are challenging to design, natural language grammars do have a sparse set of constructions presenting this possibility. Here we examined one such case, English post-nominal adjectives (mountain TALL enough for a strenuous hike), which were contrasted with semantically parallel but structurally simpler noun-adjective sequences in an MEG experiment. We observed a sharp activity increase in the left posterior temporal lobe (PTL) when syntactic composition was more straightforward, approximately 200 ms after adjective onset. The semantic fit between the noun and adjective was also varied, but this affected anterior temporal cortex, consistent with prior work. These findings offer a unique demonstration of the relevance of posterior temporal cortex for syntactic processing in natural language. We also present connectivity evidence that the syntax-related PTL responses were relayed to ipsilateral inferior frontal and anterior temporal regions. The combined results draw an initial picture of the rapid spatio-temporal dynamics of the syntactic and semantic composition network in sentence processing.
Effect of Temperature on Morphology, Phase Transformations and Thermal Expansions of Coal Fly Ash Cenospheres

Cenospheres are small, hard-shelled hollow spheres with high silica and alumina content. These micron-sized aluminosilicate hollow spheres constitute only a small percentage of the coal fly ash (CFA) obtained from the coal combustion processes. In this study, cenospheres were separated from CFA obtained from a coal-fired power plant located in Kapar, Malaysia. The cenospheres were heated at 1000, 1200 and 1400 °C to study the changes in morphologies, compositions, phase formation and thermal expansion. The sintering temperatures were selected based on the differential scanning calorimetry (DSC) curve results. X-ray diffractometry (XRD), field emission electron microscopy (FESEM), energy dispersive spectroscopy (EDS) as well as thermogravimetry and differential scanning calorimetry analysis (TG–DSC) were used for the characterization study. The study found that the cenospheres have excellent weight stability but are thermally unstable as a result of crystallization and melting. The phase ordering process and devitrification of the amorphous aluminosilicate glass phase at high temperatures lead to the increment and enrichment of the mullite phase in cenospheres. It is suggested that a preheating treatment at 1100 °C could be used to enhance the mechanical properties and thermally stabilize the cenospheres, which make it more suitable for use as a pore-forming agent in ceramics.
Effect of fertility levels on growth, yield and soil fertility status of maize (Zea mays L.) in vertisol of Maharashtra

A field experiment was conducted at the experimental farm, AICRP on Integrated Farming Systems, Vasantrao Naik Marathwada Krishi Vidyapeeth, Parbhani during 2014-15 to assess the nitrogen, phosphorus and zinc requirement for maize crop. The experiment was laid out in a split plot design using eight treatments with three replications. The main plot consists of three levels of Nitrogen i.e., 100 kg ha-1(N1), 125 kg ha-1(N2),150 kg ha-1(N3) with two Zinc levels viz.,25 kg ha-1(Z1), 35 kg ha-1(Z2) and sub plot comprised of three levels of 50 kg ha-1(P1), 75 kg ha-1(P2)and 100 kg ha-1(P3). Application of 150 kg N ha-1, 100 kg P ha-1 and 35 kg Zn ha-1 recorded significantly higher growth at 5% level of significance attributes viz., plant height (218.64), no. of functional leaves (11.30), leaf area plant-1 (65.07 cm2), total dry matter plant-1 (269.08) and grain yield (6705.8 kg ha-1), husk yield (1378.2 ha-1), spindle yield (1642.6 ha-1), stover yield (7161.0 ha-1) and biological yield (13866.8 ha-1). The nutrient status after harvest of maize was highest in the treatment combination of N3P3Z2 receiving 150 kg N ha-1, 75 kg P ha-1 and 35 kg ZnSO4 ha-1. But the result were at par with the treatment combination N2P2Z1 which received 125 kg N ha-1, 75 kg P ha-1 and 25 kg ZnSO4 ha-1. From the results, it was concluded that the maximum growth, yield, & post harvest nutrient status could be achieved by judicious application of chemical fertilizers (N, P & Zn).
PENGARUH HOTS, PEER GROUP, CLASSROOM MANAGEMENT, MOTIVASI DIRI PADA PROSES BELAJAR SISWA SEKOLAH MENENGAH ATAS JURUSAN SOSIAL

The study is conducted to understand the relation of HOTS (High Order Thinking Skills), peer group, and class-room management to self-motivation; and the relation of self-motivation to learning process of student. The proposition of the study is development of self-motivation through external and internal factors of the student. The internal factor in the study is HOTS, while external factors comprise of peer group and class-room management. Furtherly, developed self-motivation will have significant impact to the learning process. The data of the study was collected from social science student XII class of one private school located in Jakarta. The data was processed by using SmartPLS program. The study findings are learning process is strongly influenced by self-motivation, and self-motivation is influenced by HOTS, peer group, and class-room management. HOTS and peer group gave strong influence and class-room management have less influence.
Comparative study between two media on in vitro maturation rate of local buffalo oocytes

Availability of developmentally competent buffalo oocytes is critical for in vitro embryo production and application of related biotechniques. The present study has been undertaken to study the effect of TCM-199 and synthetic oviduct fluid (SOF) medium with supplements (10% Bovine serum albumen (BSA), 10 IU/ml follicle stimulating hormone FSH) with100 IU/mL penicillin, 100 mg/mL streptomycin and 100 IU/mL Nystatin on maturation of buffalo oocytes in vitro. Buffalo ovaries (n= 300) were collected from local abattoir of Basrah within two hours of slaughter and transported immediately to the laboratory under septic condition. Follicular oocytes (n= 215) were recovered by aspiration and slicing method. Only normal grades(A and B) cumulus-oocyte-complexes (COCs) were incubating under 5 % CO2 in air at 38.5 C for 24 hours in two media TCM199 media (n= 105) or SOF media( n =110) oocytes adding same supplements which mention above. The percentage of oocytes maturation when using TCM-199 medium was (33.33%) was significantly higher (P<0.01) compared to those obtained with SOF medium 13.91(%).
Study the effect of spraying growth regulators on flowering, fruit set and yield of Haied and Amal apricot cultivars

This study was conducted during two successive seasons of 2016 and 2017 on Haied and Amal apricot cultivars trees (5 years old) grown at 5 x 4 meters apart in Sandy soil of a private orchard at Nobaria, Beheira governorate. The treatments including Hockley Alpha the commercial name of (Naphthyl acetic acid 45%, Naphthyl acetamide 1.20%) sprayed alone at 120 g / 200 L of water and Nano Bloom the commercial name of (Naphthyl acetic acid 2%, Naphsoxy acetic acid 3%, Cytokinin 1.40%, Gibberellin 0.75%, Oxyinat 0.009%, Vitamin B, H, K 20%, Phosphorus 20%, Boron 3%, Cobalt 0.1%, Molybdium 0.01% and improved substances and its fillings 52.89%) sprayed alone at 20 g / 100 L of water and the control (sprayed with water) all of them were sprayed twice (at 50 to 60 % of the flowering and Initial fruit set each season) on both apricot cultivars. Hockley Alpha and Nano Bloom treatments reduced percentage of fruit drop, increased percentage of retained fruit and increased fruit yield (kg/tree) of the two cultivars compared with control in the two studied seasons. Economic study cleared, spraying Hockley Alpha or Nano Bloom increased yield and total income /feddan (feddan = 1.038 acres) LE of Haied and Amal cvs. with lowest coast.
Sentinel: A Hyper-Heuristic for the Generation of Mutant Reduction Strategies

Mutation testing is an effective approach to evaluate and strengthen software test suites, but its adoption is currently limited by the mutants’ execution computational cost. Several strategies have been proposed to reduce this cost (a.k.a. mutation cost reduction strategies), however none of them has proven to be effective for all scenarios since they often need an ad-hoc manual selection and configuration depending on the software under test (SUT). In this paper, we propose a novel multi-objective evolutionary hyper-heuristic approach, dubbed Sentinel, to automate the generation of optimal cost reduction strategies for every new SUT. We evaluate Sentinel by carrying out a thorough empirical study involving 40 releases of 10 open-source real-world software systems and both baseline and state-of-the-art strategies as a benchmark. We execute a total of 4,800 experiments, and evaluate their results with both quality indicators and statistical significance tests, following the most recent best practice in the literature. The results show that strategies generated by Sentinel outperform the baseline strategies in 95 percent of the cases always with large effect sizes. They also obtain statistically significantly better results than state-of-the-art strategies in 88 percent of the cases, with large effect sizes for 95 percent of them. Also, our study reveals that the mutation strategies generated by Sentinel for a given software version can be used without any loss in quality for subsequently developed versions in 95 percent of the cases. These results show that Sentinel is able to automatically generate mutation strategies that reduce mutation testing cost without affecting its testing effectiveness (i.e., mutation score), thus taking off from the tester’s shoulders the burden of manually selecting and configuring strategies for each SUT.
¿Cuántos inmigrantes han abandonado España por la crisis? Un ejercicio de estimación (indirecta) mediante la encuesta de población activa

Spain received one of the highest international migration flows during the years before the economic recession. The change of cycle could have led to an intense migration outflow. Nevertheless, using the Spanish Labour Force Survey (LFS) it is found that this re-emigration is not produced. The paper seeks to establish what reasons there are behind the immigrants´ decision to stay in the country despite the worsening conditions of the labour market and the deterioration of their living conditions.
Intrinsic Spine Dynamics Are Critical for Recurrent Network Learning in Models With and Without Autism Spectrum Disorder

It is often assumed that Hebbian synaptic plasticity forms a cell assembly, a mutually interacting group of neurons that encodes memory. However, in recurrently connected networks with pure Hebbian plasticity, cell assemblies typically diverge or fade under ongoing changes of synaptic strength. Previously assumed mechanisms that stabilize cell assemblies do not robustly reproduce the experimentally reported unimodal and long-tailed distribution of synaptic strengths. Here, we show that augmenting Hebbian plasticity with experimentally observed intrinsic spine dynamics can stabilize cell assemblies and reproduce the distribution of synaptic strengths. Moreover, we posit that strong intrinsic spine dynamics impair learning performance. Our theory explains how excessively strong spine dynamics, experimentally observed in several animal models of autism spectrum disorder, impair learning associations in the brain.
Financial access, governance and the persistence of inequality in Africa: Mechanisms and policy instruments

The aim of this paper is to investigate policy instruments by which the persistence of inequality is affected through financial development channels in 48 African countries for the period 1996 â€“ 2014. Financial dynamic channels of depth (money supply and liquid liabilities), efficiency (at banking and financial system levels), activity (from banking and financial system perspectives) and stability are used. Political (â€œvoice and accountabilityâ€ and political stability), economic (government effectiveness and regulation quality) and institutional (rule of law and corruption-control) governance policy instruments are also involved. The empirical evidence is based on the Generalised Method of Moments (GMM). The results show that financial depth and financial stability are the best channels of reducing inequality. Moreover, the relevance of these financial channels is significantly apparent when policy instruments are exclusively governance variables. The comparative relevance of governance dynamics in the persistence of inequality is discussed. The study responds to two recent policy and scholarly challenges, notably: the persistence of inequality in Africa and the relevance of governance in addressing income inequality by means of financial access.
Effect of supplementation of multi-species probiotic on production performance of Japanese quail

An experiment was conducted to study the effect of multi-species probiotic on production performance of Japanese Quails. Three hundred Japanese quail day old chicks were randomly divided into a control and three treatment groups with three replicates of 25 each and reared in cages for six weeks. The basal diets were supplemented with multi-species probiotic to control, T1, T2, and T3 diets @ 0, 0.005, 0.01, and 0.02 % level respectively. The parameters such as bi-weekly body weight, FCR, and livability were recorded and analyzed. The groups supplemented with multi-species probiotic at 0.01, and 0.02 % level had resulted in significantly (P < 0.01) higher mean body weight (185.62±2.51g and195.05±2.12g), better FCR (2.84±0.03 and 2.69±0.04) respectively than other groups. It can be concluded that the supplementation of multi-species probiotic in diet at 0.01, and 0.02% levels were found to be beneficial for higher production performance of Japanese quail.
The European trade ban on wild birds reduced invasion risks

International wildlife trade is a major source of current biological invasions. However, the power of trade regulations to reduce invasion risks at large, continental scales has not been empirically assessed. The European wild bird trade ban was implemented in 2005 to counter the spread of the avian flu. We tested whether the ban reduced invasion risk in two European countries, where 398 nonnative bird species were introduced into the wild from 1912 to 2015. The number of newly introduced species per year increased exponentially until 2005 (in parallel with the volume of wild bird importations), and then sharply decreased in subsequent years. Interestingly, a rapid trade shift from wild‐caught birds to captive‐bred birds, which have lower invasive potential than wild‐caught birds, allowed the maintenance of bird availability in markets. Our results demonstrate the effectiveness of a trade ban for preventing biological invasions without impacting the ability to meet societal demands.