Activating teaching methods, studying responses and learning

Students’ study strategies when exposed to activating teaching methods are measured, analysed and compared to study strategies in more traditional lecture-based teaching. The resulting learning outcome is discussed.Peer Reviewe

Repertoire and classification of non-song calls in Southeast Alaskan humpback whales (Megaptera novaeangliae)

On low-latitude breeding grounds, humpback whales produce complex and highly stereotyped songs as well as a range of non-song sounds associated with breeding behaviors. While on their Southeast Alaskan foraging grounds, humpback whales produce a range of previously unclassified non-song vocalizations. This study investigates the vocal repertoire of Southeast Alaskan humpback whales from a sample of 299 non-song vocalizations collected over a 3-month period on foraging grounds in Frederick Sound, Southeast Alaska. Three classification systems were used, including aural spectrogram analysis, statistical cluster analysis, and discriminant function analysis, to describe and classify vocalizations. A hierarchical acoustic structure was identified; vocalizations were classified into 16 individual call types nested within four vocal classes. The combined classification method shows promise for identifying variability in call stereotypy between vocal groupings and is recommended for future classification of broad vocal repertoires

Fast and Furious: Energetic Tradeoffs and Scaling of High-Speed Foraging in Rorqual Whales

Although gigantic body size and obligate filter feeding mechanisms have evolved in multiple vertebrate lineages (mammals and fishes), intermittent ram (lunge) filter feeding is unique to a specific family of baleen whales: rorquals. Lunge feeding is a high cost, high benefit feeding mechanism that requires the integration of unsteady locomotion (i.e., accelerations and maneuvers); the impact of scale on the biomechanics and energetics of this foraging mode continues to be the subject of intense study. The goal of our investigation was to use a combination of multi-sensor tags paired with UAS footage to determine the impact of morphometrics such as body size on kinematic lunging parameters such as fluking timing, maximum lunging speed, and deceleration during the engulfment period for a range of species from minke to blue whales. Our results show that, in the case of krill-feeding lunges and regardless of size, animals exhibit a skewed gradient between powered and fully unpowered engulfment, with fluking generally ending at the point of both the maximum lunging speed and mouth opening. In all cases, the small amounts of propulsive thrust generated by the tail were unable to overcome the high drag forces experienced during engulfment. Assuming this thrust to be minimal, we predicted the minimum speed of lunging across scale. To minimize the energetic cost of lunge feeding, hydrodynamic theory predicts slower lunge feeding speeds regardless of body size, with a lower boundary set by the ability of the prey to avoid capture. We used empirical data to test this theory and instead found that maximum foraging speeds remain constant and high (∼4 m s–1) across body size, even as higher speeds result in lower foraging efficiency. Regardless, we found an increasing relationship between body size and this foraging efficiency, estimated as the ratio of energetic gain from prey to energetic cost. This trend held across timescales ranging from a single lunge to a single day and suggests that larger whales are capturing more prey—and more energy—at a lower cost

Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study

Purpose: Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. Methods: A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells in direct contact with tumor). Results: A total of 20 patients were enrolled. Their median age was 64 years, and most patients (60%) had platinum-resistant/refractory disease. Of 19 evaluable patients, two were observed to have partial or complete responses (10.5%), including a patient with EGFR-transformed SCLC. Clinical benefit was observed in four patients (21.1% [95% confidence interval: 6.1%–45.6%]) with confirmed responses or prolonged stable disease (≥8 months). The most common treatment-related adverse events were anemia (80%), lymphopenia (60%), and leukopenia (50%). Nine of 14 tumors (64%) exhibited an excluded phenotype; 21% and 14% of tumors exhibited the inflamed and desert phenotypes, respectively. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Of the five tumors without an inflamed phenotype at baseline, no during-treatment increase in T-cell infiltration or programmed death ligand 1 expression on tumor-infiltrating immune cells was observed. Conclusions: The study combination did not meet the preset bar for efficacy. Pretreatment and during-treatment biopsy specimens suggested that tumor immune phenotypes may be relevant for SCLC responses to immune checkpoint blockade combinations. The predictive value of preexisting CD8-positive T-cell infiltrates observed in this study needs to be confirmed in larger cohorts

Altered Retinoic Acid Metabolism in Diabetic Mouse Kidney Identified by 18O Isotopic Labeling and 2D Mass Spectrometry

Numerous metabolic pathways have been implicated in diabetes-induced renal injury, yet few studies have utilized unbiased systems biology approaches for mapping the interconnectivity of diabetes-dysregulated proteins that are involved. We utilized a global, quantitative, differential proteomic approach to identify a novel retinoic acid hub in renal cortical protein networks dysregulated by type 2 diabetes.Total proteins were extracted from renal cortex of control and db/db mice at 20 weeks of age (after 12 weeks of hyperglycemia in the diabetic mice). Following trypsinization, (18)O- and (16)O-labeled control and diabetic peptides, respectively, were pooled and separated by two dimensional liquid chromatography (strong cation exchange creating 60 fractions further separated by nano-HPLC), followed by peptide identification and quantification using mass spectrometry. Proteomic analysis identified 53 proteins with fold change >or=1.5 and p<or=0.05 after Benjamini-Hochberg adjustment (out of 1,806 proteins identified), including alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (RALDH1/ALDH1A1). Ingenuity Pathway Analysis identified altered retinoic acid as a key signaling hub that was altered in the diabetic renal cortical proteome. Western blotting and real-time PCR confirmed diabetes-induced upregulation of RALDH1, which was localized by immunofluorescence predominantly to the proximal tubule in the diabetic renal cortex, while PCR confirmed the downregulation of ADH identified with mass spectrometry. Despite increased renal cortical tissue levels of retinol and RALDH1 in db/db versus control mice, all-trans-retinoic acid was significantly decreased in association with a significant decrease in PPARbeta/delta mRNA.Our results indicate that retinoic acid metabolism is significantly dysregulated in diabetic kidneys, and suggest that a shift in all-trans-retinoic acid metabolism is a novel feature in type 2 diabetic renal disease. Our observations provide novel insights into potential links between altered lipid metabolism and other gene networks controlled by retinoic acid in the diabetic kidney, and demonstrate the utility of using systems biology to gain new insights into diabetic nephropathy

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Multipore zeolites: synthesis and catalytic applications

[EN] In the last few years, important efforts have been made to synthesize so-called "multipore" zeolites, which contain channels of different dimensions within the same crystalline structure. This is a very attractive subject, since the presence of pores of different sizes would favor the preferential diffusion of reactants and products through those different channel systems, allowing unique catalytic activities for specific chemical processes. In this Review we describe the most attractive achievements in the rational synthesis of multipore zeolites, containing small to extra-large pores, and the improvements reported for relevant chemical processes when these multipore zeolites have been used as catalysts.Financial support by the Spanish Government-MINECO through “Severo Ochoa” (SEV 2012-0267), Consolider Ingenio 2010-Multicat, MAT2012-37160, MAT2012-31657 and Intramural-201480I015 is acknowledged.Moliner Marin, M.; Martínez, C.; Corma Canós, A. (2015). Multipore zeolites: synthesis and catalytic applications. Angewandte Chemie International Edition. 54(12):3560-3579. https://doi.org/10.1002/anie.201406344S35603579541