Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment

Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly.
This Work Is Licensed under a Creative Commons Attribution 4.0 International License Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Abstract Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein-induced neuro-degeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.
Higher levels of CO2 during late incubation alter the hatch time of chicken embryos

Abstract 1. It has been reported that the increasing CO2 tension triggers the embryo to pip the air cell and emerge from the egg. However, the mechanism by which higher CO2 concentrations during the last few days of incubation affect chick physiology and the hatching process is unclear. This study investigated the effect of CO2 concentrations up to 1% during pipping, on the onset and length of the hatch window (HW) and chick quality. 2. Four batches of Ross 308 broiler eggs (600 eggs per batch) were incubated in two small-scale custom-built incubators (Petersime NV). During the final 3 d of incubation, control eggs were exposed to a lower CO2 concentration (0.3%), while the test eggs experienced a higher CO2 concentration programme (peak of 1%). 3. There were no significant differences in blood values, organ weight and body weight. There was also no difference in hatchability between control and test groups. However, a small increase in the chick weight and the percentage of first class chicks was found in the test groups. Furthermore, plasma corticosterone profiles during hatching were altered in embryos exposed to higher CO2; however, they dropped to normal levels at d 21 of incubation. Importantly, the hatching process was delayed and synchronised in the test group, resulting in a narrowed HW which was 2.7 h shorter and 5.3 h later than the control group. 4. These results showed that exposing chicks to 1% CO2 concentration during pipping did not have negative impacts on physiological status of newly hatched chicks. In addition, it may have a significant impact on the physiological mechanisms controlling hatching and have benefits for the health and welfare of chickens by reducing the waiting time after hatching.
GSK 3 β expression and phosphorylation during neuronal maturation in the rat dorsal root ganglion

Glycogen synthase kinase 3β (GSK-3β) protein is a key regulator of neurogenesis, neuronal differentiation and polarisation during neurodevelopment. Sensory neurons in dorsal root ganglion (DRG) undergo a series of development stages during its maturation. In this study, we investigated the dynamic changes in GSK-3β expression and phosphorylation of its N-terminal serine-9 residue (p-GSK-3β (S9)) during DRG development. Sprague-Dawley (SD) rats were divided according to the following ages: Embryonic 13th (E13), E15, E19, Postnatal 1st (P1), P3, P7, P14, P21 and P60 days. GSK-3β was detected by immunohistochemistry and double immunofluorescence on DRGs. Western blotting was used to determine the quantity of GSK-3β and p-GSK-3β (S9) expression. It was found that GSK-3β immunopositive cells in the DRG appeared as early as E13 development phase, and gradually increased to a peak level at P3, at which almost all neurons were GSK-3β positive, and then stayed at a high level to the experiment day 60. GSK3β expression was cell-type-specific during DRG maturation and exhibited cytoplasmic staining in the neuronal cell body and the axon. Glial cells consistently remained negative in DRGs at all stages. Western blot analysis revealed that GSK3β expression stayed the same during DRG maturation. In contrast, p-GSK-3β (S9) expression was stage-specific and decreased from E13 to P60 (P < 0.01). Taken together, these results suggest that GSK-3β expression is stage-specific and cell-type-specific during DRG maturation.
Inducible, Dose-Adjustable and Time-Restricted Reconstitution of Stat1 Deficiency In Vivo

Signal transducer and activator of transcription (STAT) 1 is a key player in interferon (IFN) signaling, essential in mediating host defense against viruses and other pathogens. STAT1 levels are tightly regulated and loss- or gain-of-function mutations in mice and men lead to severe diseases. We have generated a doxycycline (dox) -inducible, FLAG-tagged Stat1 expression system in mice lacking endogenous STAT1 (i.e. Stat1ind mice). We show that STAT1 expression depends on the time and dose of dox treatment in primary cells and a variety of organs isolated from Stat1ind mice. In bone marrow-derived macrophages, a fraction of the amount of STAT1 present in WT cells is sufficient for full expression of IFN-induced genes. Dox-induced STAT1 established protection against virus infections in primary cells and mice. The availability of the Stat1ind mouse model will enable an examination of the consequences of variable amounts of STAT1. The model will also permit the study of STAT1 dose-dependent and reversible functions as well as of STAT1's contributions to the development, progression and resolution of disease.
Teachers’ technology adoption and practices: lessons learned from the IWB phenomenon

Abstract The twenty-first century has seen unprecedented investment from governments around the world in educational technologies in schools. This paper investigates Australian teachers’ adoption and use of a popular technology that has been extensively supported by governments and school systems: the interactive whiteboard (IWB). The study suggests that a number of the barriers identified in the early days of adoption and use of this technology, such as professional support and access, still remain for many teachers, thereby impeding effective practices. The research also found that primary school teachers were using the technology in diverse ways, in contrast to secondary teachers who were using the IWB mainly for instructionist, presentational purposes. We conclude by considering various ways of reducing the effect of the identified barriers to support implementation of educational technologies in the classroom, especially the next generation of technologies promoted by governments and systems.
The site for initiation of action potential discharge over the somatodendritic axis of rat hippocampal CA1 pyramidal neurons

Early electrophysiological studies in the mammalian hippocampus reported that orthodromic depolarization of pyramidal cells evoked action potential discharge (presumed Na+ dependent) both at the axon hillock and at one or more sites in the dendritic arborization (Cragg and Hamlyn, 1955; Andersen, 1959, 1960; Spencer and Kandel, 1961; Andersen and Lomo, 1966). Although tetrodotoxin (TTX)-sensitive spikes have been recorded at the dendritic level (Wong et al., 1979; Benardo et al., 1982; Miyakawa and Kato, 1986; Turner et al., 1989), the site for initiation of these potentials has not yet been determined. In this study, we examine the site for initiation of Na+ spike discharge over the cell axis of rat hippocampal CA1 pyramidal neurons. Intrasomatic and intradendritic recordings were obtained from pyramidal neurons of hippocampal slices maintained in vitro. Spike discharge was evoked by alvear (antidromic) stimulation or orthodromically by stimulation of afferent inputs in stratum oriens (SO) or stratum radiatum (SR). Antidromic and orthodromic spikes were greatest in amplitude in somatic recordings and declined over the apical dendritic axis, while spike half-width was shortest at the cell body and increased with distance from stratum pyramidale. Measurements of orthodromic spike threshold revealed that the only location at which spikes discharged at a consistent membrane potential at threshold intensity (voltage threshold) was the cell body region. Finally, at threshold intensity, SR-evoked intradendritic spikes were blocked by local application of TTX in stratum pyramidale, while spike blockade at suprathreshold intensity required the diffusion of TTX into the apical dendritic region. These results indicate that, for threshold intensities of stimulation, antidromic and orthodromic spike discharge in CA1 pyramidal cells is initiated in the region of the cell body layer, subsequently conducting over the apical dendrites in a retrograde fashion. In contrast, SR-evoked orthodromic spike discharge exhibits an intensity-dependent shift in the site of origin up to 200 microns within the apical dendritic arborization.
Evaluation of Commercially Available Anti–Dengue Virus Immunoglobulin M Tests

Anti–dengue virus immunoglobulin M kits were evaluated. Test sensitivities were 21%–99% and specificities were 77%–98% compared with reference ELISAs. False-positive results were found for patients with malaria or past dengue infections. Three ELISAs showing strong agreement with reference ELISAs will be included in the World Health Organization Bulk Procurement Scheme.
Content-Aware DataGuides for Indexing Large Collections of XML Documents

XML is well-suited for modelling structured data with textual content. However, most indexing approaches perform structure and content matching independently, combining the retrieved path and keyword occurrences in a third step. This paper shows that retrieval in XML documents can be accelerated significantly by processing text and structure simultaneously during all retrieval phases. To this end, the Content-Aware DataGuide (CADG) enhances the wellknown DataGuide with (1) simultaneous keyword and path matching and (2) a precomputed content/structure join. Extensive experiments prove the CADG to be 50-90% faster than the DataGuide for various sorts of query and document, including difficult cases such as poorly structured queries and recursive document paths. A new query classification scheme identifies precise query characteristics with a predominant influence on the performance of the individual indices. The experiments show that the CADG is applicable to many real-world applications, in particular large collections of heterogeneously structured XML documents.
Automatic intrusion response system based on aggregation and cost

One of the most significant issues in intrusion detection is automating responses to intrusions, but has so far been largely overlooked and therefore requires further research in its own right. And another main weakness of current intrusion detection systems is that they often generate too many same or similar alerts for one intrusion and system immune alerts. This will use a lot of time to respond repeatedly. As a result, a better method to solve above problem is making use of the aggregation to classify the alerts and the Response Cost to decrease the system immune alerts. At last, this paper presents a modal of automatic intrusion response system and introduces the implement in detail.
Validation of the Psychological Research Inventory of Concepts

The current set of three studies further evaluates the validity and application of the Psychological Research Inventory of Concepts (PRIC). In Study 1, we administered the PRIC to a sample of introductory psychology students and online (Mechanical Turk) participants along with measures assessing theoretically related concepts. We found evidence of concurrent validity by demonstrating that PRIC scores relate to education, cognitive effort, and general psychological knowledge. In Study 2, we demonstrated that advanced psychology majors score higher on the PRIC than college graduates who did not major in psychology, suggesting that the PRIC assesses domain-specific knowledge and may be useful in assessment of the undergraduate psychology major. Finally, in Study 3, we demonstrated that scores on the PRIC increase from the start to the end of a research methods course. Together, these studies provide further evidence that the PRIC may be a useful index of learning research methods and statistical knowledge important for the undergraduate psychology degree.
Enhanced Manual and Oral Motor Reaction Time in Young Adult Female Fragile X Premutation Carriers

Abstract A previous study reported preliminary results of enhanced processing of simple visual information in the form of faster reaction times, in female fragile X premutation carriers (fXPCs). In this study, we assessed manual and oral motor reaction times in 30 female fXPCs and 20 neurotypical (NT) controls. Participants completed two versions of the reaction time task; one version required a manual motor response and the other version required an oral motor response. Results revealed that the female fXPCs displayed faster reaction times for both manual and oral motor responses relative to NT controls. Molecular measures including CGG repeat length, FMR1 mRNA levels, and age were not associated with performance in either group. Given previously reported age and CGG repeat modulated performance on a magnitude comparison task in this same group of premutation carriers, results from the current study seem to suggest that female fXPCs may have spared basic psychomotor functionality. (JINS, 2011, 17, 746–750)
‘The world is best experienced at 18 mph’. The psychological wellbeing effects of cycling in the countryside: an Interpretative Phenomenological Analysis

Abstract Green Exercise (GE) refers to physical activity conducted whilst simultaneously engaging the natural environment. A substantial body of literature has now been accumulated that establishes that carrying out exercise in this way has significantly greater psychological wellbeing benefits than the non-GE equivalent. Hitherto, seldom has consideration been given to the individual meanings that doing GE has. This study, therefore, sought to understand the lived experience of the phenomenon amongst a group of serious male recreational road bicyclists aged between mid-30s and early 50s who routinely rode in the countryside. Eleven bicyclists participated in semi-structured interviews. Data were analysed using Interpretative Phenomenological Analysis. This revealed themes of mastery and uncomplicated joys; my place to escape and rejuvenate; and alone but connected. Findings indicate that green-cycling served to enhance the participants’ sense of wellbeing and in doing so helped them cope with the mental challenges associated with their lives. It is suggested that green-cycling merges the essential qualities of natural surroundings – including its aesthetic, feelings of calm and a chance for exploration – with the potential for physical challenge and, facilitated by modern technology, opportunities for prosocial behaviours. It also identifies how green-cycling may influence self-determined behaviours towards exercise regulation, suggesting more satisfying and enduring exercise experiences.
Discovering User Perceptions of Semantic Similarity in Near-duplicate Multimedia Files

We address the problem of discovering new notions of userperceived similarity between near-duplicate multimedia files. We focus on file-sharing, since in this setting, users have a well-developed understanding of the available content, but what constitutes a near-duplicate is nonetheless nontrivial. We elicited judgments of semantic similarity by implementing triadic elicitation as a crowdsourcing task and ran it on Amazon Mechanical Turk. We categorized the judgments and arrived at 44 different dimensions of semantic similarity perceived by users. These discovered dimensions can be used for clustering items in search result lists. The challenge in performing elicitations in this way is to ensure that workers are encouraged to answer seriously and remain engaged.
High-Throughput Sequencing of Microbial Community Diversity and Dynamics during Douchi Fermentation

Douchi is a type of Chinese traditional fermented food that is an important source of protein and is used in flavouring ingredients. The end product is affected by the microbial community present during fermentation, but exactly how microbes influence the fermentation process remains poorly understood. We used an Illumina MiSeq approach to investigate bacterial and fungal community diversity during both douchi-koji making and fermentation. A total of 181,443 high quality bacterial 16S rRNA sequences and 221,059 high quality fungal internal transcribed spacer reads were used for taxonomic classification, revealing eight bacterial and three fungal phyla. Firmicutes, Actinobacteria and Proteobacteria were the dominant bacterial phyla, while Ascomycota and Zygomycota were the dominant fungal phyla. At the genus level, Staphylococcus and Weissella were the dominant bacteria, while Aspergillus and Lichtheimia were the dominant fungi. Principal coordinate analysis showed structural separation between the composition of bacteria in koji making and fermentation. However, multivariate analysis of variance based on unweighted UniFrac distances did identify distinct differences (p <0.05), and redundancy analysis identified two key genera that are largely responsible for the differences in bacterial composition between the two steps. Staphylococcus was enriched in koji making, while Corynebacterium was enriched in fermentation. This is the first investigation to integrate douchi fermentation and koji making and fermentation processes through this technological approach. The results provide insight into the microbiome of the douchi fermentation process, and reveal a structural separation that may be stratified by the environment during the production of this traditional fermented food.
Textual CBR Authoring using Case Cohesion

During the design phase of a textual case-based reasoning (TCBR) system, decisions have to be made regarding the internal representation of the cases and the similarity metrics. Such decisions have a significant impact on the performance of the resulting TCBR system. We believe that guidance should be provided to the designer during the authoring process. Unfortunately most of the metrics proposed in the CBR literature either require subjective human evaluation or do not apply when both problem and solution parts of the cases are textual in nature. In this paper, we propose a metric, case cohesion that can be used to provide guidance in the configuration of a case base and in the selection of appropriate similarity schemes. Case cohesion is defined from the neighborhood of textual cases and allows to estimate whether both problem and solution descriptions are well aligned. Our experimental results indicate that case cohesion can discriminate among the performances of different retrieval schemes and can also help in the unsupervised selection of the parameters required for these retrieval metrics.
Functional Characterization of 8-Oxoguanine DNA Glycosylase of Trypanosoma cruzi

The oxidative lesion 8-oxoguanine (8-oxoG) is removed during base excision repair by the 8-oxoguanine DNA glycosylase 1 (Ogg1). This lesion can erroneously pair with adenine, and the excision of this damaged base by Ogg1 enables the insertion of a guanine and prevents DNA mutation. In this report, we identified and characterized Ogg1 from the protozoan parasite Trypanosoma cruzi (TcOgg1), the causative agent of Chagas disease. Like most living organisms, T. cruzi is susceptible to oxidative stress, hence DNA repair is essential for its survival and improvement of infection. We verified that the TcOGG1 gene encodes an 8-oxoG DNA glycosylase by complementing an Ogg1-defective Saccharomyces cerevisiae strain. Heterologous expression of TcOGG1 reestablished the mutation frequency of the yeast mutant ogg1−/− (CD138) to wild type levels. We also demonstrate that the overexpression of TcOGG1 increases T. cruzi sensitivity to hydrogen peroxide (H2O2). Analysis of DNA lesions using quantitative PCR suggests that the increased susceptibility to H2O2 of TcOGG1-overexpressor could be a consequence of uncoupled BER in abasic sites and/or strand breaks generated after TcOgg1 removes 8-oxoG, which are not rapidly repaired by the subsequent BER enzymes. This hypothesis is supported by the observation that TcOGG1-overexpressors have reduced levels of 8-oxoG both in the nucleus and in the parasite mitochondrion. The localization of TcOgg1 was examined in parasite transfected with a TcOgg1-GFP fusion, which confirmed that this enzyme is in both organelles. Taken together, our data indicate that T. cruzi has a functional Ogg1 ortholog that participates in nuclear and mitochondrial BER.
Violations of Fitts’ Law in a Ballistic Task

ABSTRACT The authors explored changes in the postural preparation and movement times during jumps into targets of different sizes placed at different distances from the participant. Both movement and preparation times scaled with movement distance. Neither movement nor preparation time showed an effect of target size, although preparation time showed a tendency to increase for smaller targets. These observations show that the classical Fitts’ law can be violated in tasks that involve a ballistic component. The data corroborate a hypothesis that Fitts’ law originates at the level of movement planning.