The Time Is Now! - En intervjustudie kring begreppet time utifrån en afroamerikansk musikkontext

Begreppet time används ofta av musiker och pedagoger verksamma inom den afroamerikanska musiktraditionen. Trots att begreppet är används frekvent finns det ingen vedertagen uppfattning kring vad time egentligen innefattar. Därför har vi undersökt innebörden av begreppet, samt hur det används i en pedagogisk kontext. Undersökningen har skett genom en kombinerad intervjustudie och enkätundersökning. Resultatet visar att time för många är själva förhållandet mellan det som spelas och en puls. Bra time kan alltså på intet sätt likställas med metronomisk exakthet, utan är snarare ett kontrollerat förhållningssätt till en puls i ett organiskt skeende. Många framhåller också bristen på undervisningsmaterial inom time, samtidigt som begreppet förväntas få ökad uppmärksamhet inom den musikpedagogiska världen i framtiden.Musicians and educators active in the tradition of afroamerican music often use the term time. Despite that the term is frequently used, there is no convention of what the term really comprises. Therefore, the meaning of this study is to investigate the meaning of the term time, and how it is used in an educational context. The study is built upon a combination of interviews and a survey. The result show that according to a majority of our participants, time is the relationship between what is played and a given pulse. Therefore, great time should not be equal to the accuracy of a metronome, but rather a controlled approach to a pulse in an organic flow. The participants also emphasises the lack of educational material about time, at the same time they predict time to get increased attention in the future

Computationally Efficient Approach for Preheating of Battery Electric Vehicles before Fast Charging in Cold Climates

This paper investigates battery preheating before fast charging, for a battery electric vehicle (BEV) driving in a cold climate. To prevent the battery from performance degradation at low temperatures, a thermal management (TM) system has been considered, including a high-voltage coolant heater (HVCH) for the battery and cabin compartment heating. Accordingly, an optimal control problem (OCP) has been formulated in the form of a nonlinear program (NLP), aiming at minimising the total energy consumption of the battery. The main focus here is to develop a computationally efficient approach, mimicking the optimal preheating behavior without a noticeable increase in the total energy consumption. The proposed algorithm is simple enough to be implemented in a low-level electronic control unit of the vehicle, by eliminating the need for solving the full NLP in the cost of only 1Wh increase in the total energy consumption

Optimal Thermal Management and Charging of Battery Electric Vehicles over Long Trips

This paper studies optimal thermal management and charging of a battery electric vehicle driving over long distance trips. The focus is on the potential benefits of including a heat pump in the thermal management system for waste heat recovery, and charging point planning, in a way to achieve optimality in time, energy, or their trade-off. An optimal control problem is formulated, in which the objective function includes the energy delivered by the charger(s), and the total charging time including the actual charging time and the detour time to and from the charging stop. To reduce the computational complexity, the formulated problem is then transformed into a hybrid dynamical system, where charging dynamics are modelled in the domain of normalized charging time. Driving dynamics can be modelled in either of the trip time or travel distance domains, as the vehicle speed is assumed to be known a priori, and the vehicle is only stopping at charging locations. Within the hybrid dynamical system, a binary variable is introduced for each charging location, in order to decide to use or skip a charger. This problem is solved numerically, and simulations are performed to evaluate the performance in terms of energy efficiency and time. The simulation results indicate that the time required for charging and total energy consumption are reduced up to 30.6% and 19.4%, respectively, by applying the proposed algorithm

Time-resolved imaging-based CRISPRi screening

Our ability to connect genotypic variation to biologically important phenotypes has been seriously limited by the gap between live-cell microscopy and library-scale genomic engineering. Here, we show how in situ genotyping of a library of strains after time-lapse imaging in a microfluidic device overcomes this problem. We determine how 235 different CRISPR interference knockdowns impact the coordination of the replication and division cycles of Escherichia coli by monitoring the location of replication forks throughout on average >500 cell cycles per knockdown. Subsequent in situ genotyping allows us to map each phenotype distribution to a specific genetic perturbation to determine which genes are important for cell cycle control. The single-cell time-resolved assay allows us to determine the distribution of single-cell growth rates, cell division sizes and replication initiation volumes. The technology presented in this study enables genome-scale screens of most live-cell microscopy assays

Lack of detectable neoantigen depletion signals in the untreated cancer genome.

Somatic mutations can result in the formation of neoantigens, immunogenic peptides that are presented on the tumor cell surface by HLA molecules. These mutations are expected to be under negative selection pressure, but the extent of the resulting neoantigen depletion remains unclear. On the basis of HLA affinity predictions, we annotated the human genome for its translatability to HLA binding peptides and screened for reduced single nucleotide substitution rates in large genomic data sets from untreated cancers. Apparent neoantigen depletion signals become negligible when taking into consideration trinucleotide-based mutational signatures, owing to lack of power or to efficient immune evasion mechanisms that are active early during tumor evolution

Functional loss of IKBE leads to NF-KB deregulation in aggressive chronic lymphocytic leukemia

NF-?B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-?B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I?B?, a negative regulator of NF-?B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I?B? protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I?B? loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-?B deregulation during lymphomagenesis. <br/

Inactivation of Pmel Alters Melanosome Shape But Has Only a Subtle Effect on Visible Pigmentation

PMEL is an amyloidogenic protein that appears to be exclusively expressed in pigment cells and forms intralumenal fibrils within early stage melanosomes upon which eumelanins deposit in later stages. PMEL is well conserved among vertebrates, and allelic variants in several species are associated with reduced levels of eumelanin in epidermal tissues. However, in most of these cases it is not clear whether the allelic variants reflect gain-of-function or loss-of-function, and no complete PMEL loss-of-function has been reported in a mammal. Here, we have created a mouse line in which the Pmel gene has been inactivated (Pmel−/−). These mice are fully viable, fertile, and display no obvious developmental defects. Melanosomes within Pmel−/− melanocytes are spherical in contrast to the oblong shape present in wild-type animals. This feature was documented in primary cultures of skin-derived melanocytes as well as in retinal pigment epithelium cells and in uveal melanocytes. Inactivation of Pmel has only a mild effect on the coat color phenotype in four different genetic backgrounds, with the clearest effect in mice also carrying the brown/Tyrp1 mutation. This phenotype, which is similar to that observed with the spontaneous silver mutation in mice, strongly suggests that other previously described alleles in vertebrates with more striking effects on pigmentation are dominant-negative mutations. Despite a mild effect on visible pigmentation, inactivation of Pmel led to a substantial reduction in eumelanin content in hair, which demonstrates that PMEL has a critical role for maintaining efficient epidermal pigmentation

Poor food and nutrient intake among Indigenous and non-Indigenous rural Australian children

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to describe the food and nutrient intake of a population of rural Australian children particularly Indigenous children. Participants were aged 10 to 12 years, and living in areas of relative socio-economic disadvantage on the north coast of New South Wales.</p> <p>Methods</p> <p>In this descriptive cross-sectional study 215 children with a mean age of 11.30 (SD 0.04) years (including 82 Indigenous children and 93 boys) completed three 24-hour food recalls (including 1 weekend day), over an average of two weeks in the Australian summer of late 2005.</p> <p>Results</p> <p>A high proportion of children consumed less than the Australian Nutrient Reference Values for fibre (74-84% less than Adequate Intake (AI)), calcium (54-86% less than Estimated Average Requirement (EAR)), folate and magnesium (36% and 28% respectively less than EAR among girls), and the majority of children exceeded the upper limit for sodium (68-76% greater than Upper Limit (UL)). Energy-dense nutrient-poor (EDNP) food consumption contributed between 45% and 49% to energy. Hot chips, sugary drinks, high-fat processed meats, salty snacks and white bread were the highest contributors to key nutrients and sugary drinks were the greatest <it>per capita </it>contributor to daily food intake for all. <it>Per capita </it>intake differences were apparent by Indigenous status. Consumption of fruit and vegetables was low for all children. Indigenous boys had a higher intake of energy, macronutrients and sodium than non-Indigenous boys.</p> <p>Conclusions</p> <p>The nutrient intake and excessive EDNP food consumption levels of Australian rural children from disadvantaged areas are cause for concern regarding their future health and wellbeing, particularly for Indigenous boys. Targeted intervention strategies should address the high consumption of these foods.</p

Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia

NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis