Avaliação como Prática de Investigação (alguns apontamentos)

The main goal of this paper is to present some remarks on how assessment of school learning in mathematics can be taken as an investigative practice. In order to do this, the analysis of students´ written work and some aspects related to the kinds of questions they usually use to carry out the assessment (exploring mathematization and context) are taken into account. Assessment of school learning as an investigative activity is a practice that seeks answers regarding how the processes involved in it take place. One might ask what is directly observable and try to understand these processes by following clues that leadsto an examination of what is not observable – in other words, an investigation. From this perspective, assessment is then performed as a practice that broadens teachers’ possibilities to investigate students' learning processes, as well as to follow and participate in that process. Key words: Mathematics Education. School Assessment Process as an Investigative Practice. Analysis of Written Production.Este artigo visa a apresentar alguns apontamentos sobre avaliação da aprendizagem escolar em matemática como prática de investigação realizada por meio da análise da produção escrita, focalizando alguns dos aspectos relacionados ao tipo de questão que se utiliza para efetivar essa avaliação (matematização e contexto). Entendendo a avaliação da aprendizagem escolar como prática que busca respostas sobre como se dão os processos envolvidos com ela, interroga-se o que é diretamente observável, percorrem-se caminhos, busca-se compreender esses mesmos processos, seguem-se vestígios e, com isso, infere-se sobre o que não é diretamente observável, ou seja – investiga-se. Sob esta perspectiva, a avaliação é então realizada como uma prática que possibilita ao professor a busca por desvelar o processo de aprendizagem dos estudantes, bem como acompanhar e participar dele. Palavras-chave: Educação Matemática. Avaliação como Prática de Investigação. Análise da Produção Escrita

The RRM domain in GW182 proteins contributes to miRNA-mediated gene silencing

Proteins of the GW182 family interact with Argonaute proteins and are required for miRNA-mediated gene silencing. These proteins contain two structural domains, an ubiquitin-associated (UBA) domain and an RNA recognition motif (RRM), embedded in regions predicted to be unstructured. The structure of the RRM of Drosophila melanogaster GW182 reveals that this domain adopts an RRM fold, with an additional C-terminal α-helix. The helix lies on the β-sheet surface, generally used by these domains to bind RNA. This, together with the absence of aromatic residues in the conserved RNP1 and RNP2 motifs, and the lack of general affinity for RNA, suggests that the GW182 RRM does not bind RNA. The domain may rather engage in protein interactions through an unusual hydrophobic cleft exposed on the opposite face of the β-sheet. We further show that the GW182 RRM is dispensable for P-body localization and for interaction of GW182 with Argonaute-1 and miRNAs. Nevertheless, its deletion impairs the silencing activity of GW182 in a miRNA target-specific manner, indicating that this domain contributes to silencing. The conservation of structural and surface residues suggests that the RRM domain adopts a similar fold with a related function in insect and vertebrate GW182 family members

AChBP-targeted α-conotoxin correlates distinct binding orientations with nAChR subtype selectivity

Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel α-conotoxin (α-TxIA) in the venom of Conus textile. α-TxIA bound with high affinity to AChBPs from different species and selectively targeted the α3β2 nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20° backbone tilt compared to other AChBP–conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases

Induction of autophagy by spermidine promotes longevity.

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Eingeschränkte Mundöffnung - was nun?: Diagnostik und Therapie bei progredientem Trismus: Ein Fallbericht.

Eine 28-jährige Patientin stellte sich mit einer seit Jahren bestehenden progredient eingeschränkten Mundöffnung vor. Die initial klinische Diagnostik zeigte keine pathologischen intraartikulären Befunde. Trotzdem blieb eine konservative Therapie fruchtlos. Erst die weitere bildgebende Diagnostik führte zur Diagnose gleich mehrerer struktureller Veränderungen: einer Hyperplasie der Processus coronoidei und einer hypertrophen Kaumuskulatur mit verdickten Aponeurosen. Zusätzlich fand sich auch eine typische quadratische Unterkieferform, bedingt durch eine Hypertrophie der Kieferwinkel. Beim hier illustrierten Fall zeigen sich alle typischen Zeichen dieser bis anhin noch wenig beschriebenen Kaumuskel-Aponeurosen-Hyperplasie. Eine chirurgische Behandlung mit Coronoidektomie und Aponeurektomie verhalf schliesslich zu einer deutlichen Verbesserung der Mundöffnung. Wenngleich die eingeschränkte Mundöffnung ein Symptom vieler Erkrankungen des stomatognathen Systems ist, kann eine über längere Zeit bestehende oder auch progrediente eingeschränkte Mundöffnung diagnostisch und therapeutisch eine Herausforderung darstellen. Bei adäquater Diagnostik und Therapie ist die Prognose des oben genannten Symptomenkomplexes günstig und führt zu einer Verbesserung der mundgesundheitsbezogenen Lebensqualität.This case report illustrates a rare complex of symptoms leading to limited mouth opening in a young woman. The 28-year old suffered from a progressively limited mouth opening over several years that finally resulted in restricted alimentation and made dental treatment impossible. Clinical findings suggest a structural alteration, including a hyperplastic mandibular angle and marked hypertrophy of the masseter muscle. Further radiologic investigations reveal a thickened aponeurosis of the masticatory muscles and hyperplastic coronoid processes that are not interfering with the zygomatic bone. Primary therapeutic options for such conditions are mainly surgical, including reduction of the masseter muscles volume and aponeurorectomy as well as bony reductions, such as coronoidectomy and mandibular angle reduction. With this treatment, the outcome and prognosis are good. Long-term results depend on concomitant physical therapy. A uniform nomenclature for this condition is yet lacking and propositions such as masticatory muscle tendon-aponeurosis hyperplasia have been made. However, knowledge of this condition and its typical clinical signs can make the diagnosis and treatment straightforward, thus leading to an improved quality of life of affected patients

Augmented Reality Training for Industrial Assembly Work – Are Projection-based AR Assistive Systems an Appropriate Tool for Assembly Training?

Augmented Reality (AR) systems are on their way to industrial application, e.g. projection-based AR is used to enhance assembly work. Previous studies showed advantages of the systems in permanent-use scenarios, such as faster assembly times. In this paper, we investigate whether such systems are suitable for training purposes. Within an experiment, we observed the training with a projection-based AR system over multiple sessions and compared it with a personal training and a paper manual training. Our study shows that projection-based AR systems offer only small benefits in the training scenario. While a systematic mislearning of content is prevented through immediate feedback, our results show that the AR training does not reach the personal training in terms of speed and recall precision after 24 hours. Furthermore, we show that once an assembly task is properly trained, there are no differences in the long-term recall precision, regardless of the training method

CLL-cells induce IDOhi CD14+HLA-DRlo myeloid derived suppressor cells that inhibit T-cell responses and promote TRegs

Myeloid derived suppressor cells (MDSCs) represent a heterogeneous population that shares certain characteristics including an aberrant myeloid phenotype and the ability to suppress T-cells. MDSCs have been predominantly studied in malignant diseases and findings suggest involvement in tumor-associated immune suppression. Chronic lymphocytic leukemia (CLL) is the leukemia with the highest incidence among adults. Immune defects occur already at early disease stages and impact the clinical course. We assessed presence, frequency, association to other immune parameters, and functional properties of circulating CD14+ cells lacking HLA-DR expression (HLA-DRlo) in patients with untreated CLL. These monocytic cells represent one of the best-defined human MDSC subsets. Frequency of CD14+HLA-DRlo cells was significantly increased in CLL patients. Furthermore, MDSCs suppressed in vitro T-cell activation and induced suppressive regulatory T-cells (TRegs). The MDSC-mediated modulation of T-cells could be attributed to their increased indoleamine 2,3-dioxygenase (IDO) activity. CLL-cells induced IDOhi MDSCs from healthy donor monocytes suggesting bidirectional crosstalk between CLL-cells, MDSCs, and TRegs. Overall, we identified a MDSC population that expands in CLL. The exact mechanisms responsible for such accumulation remain to be elucidated and it will be of interest to test whether antagonizing suppressive functions of CLL MDSCs could represent a mean for enhancing immune responses

Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma

Metastatic renal cell carcinoma (RCC) exhibits poor prognosis. Better knowledge of distant metastases is crucial to foster personalized treatment strategies. Here, we aimed to investigate the genetic landscape of metastases, including synchronous and/or recurrent metastases to elucidate potential drug target genes and clinically relevant mutations in a real-world setting of patients. We assessed 81 metastases from 56 RCC patients, including synchronous and/or recurrent metastases of 19 patients. Samples were analysed through next-generation sequencing with a high coverage (~1000× mean coverage). We therefore established a novel sequencing panel comprising 32 genes with impact on RCC development. We observed a high frequency of mutations in known RCC driver genes (e.g., >40% carriers of VHL and PBRM1 mutations) in metastases irrespective of the metastatic site. The somatic mutational composition was significantly associated with cancer-specific survival (p(logrank) = 0.03). Moreover, we identified in 34 patients at least one drug target gene as well as clinically relevant mutations listed in the VICC Meta-Knowledgebase in 7%. In addition to significantly higher mutational burden in recurrent metastases compared to earlier ones, synchronous and/or recurrent metastases of individual patients, even after a time-period >2 yrs, shared a high proportion of somatic events. Our data demonstrate the importance of somatic profiling in metastases for precision medicine in RCC