Glocal Routes in British Asian Drama: Between Adaptation and Tradaption

In the context of British Asian theatre and the search for a diasporic theatre aesthetics the practice of adaptation has emerged as a recurring feature. Over the last decades, British Asian theatre has sought to create a language of the theatre that can reflect the cultural heritage of Asians in Britain; this search has taken different directions testified also by the plurality of voices that today make up British Asian theatre and has responded to the need to challenge the conceptual binary of British and Asian, aiming to affirm South Asian culture on the stage as an integral part of British culture. As the article argues, adaptation also plays a role in highlighting the dialectic between local and the global particularly in those cases where regions of Britain such as the Northwest of England can be recreated on stage as South Asian British cultural spaces

Development and characterization of an in vitro culture system as a physiological model for chronic Hepatitis B infection

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.Includes bibliographical references (p. 152-164).Human Hepatitis B virus (HBV) is the prototype member of the family Hepadnaviridae that consists of enveloped, partially double stranded DNA viruses that specifically target hepatocytes for viral replication. Although a vaccine has been available for more than 20 years chronic HBV infection afflicts 350-400 million worldwide. It is estimated that 0.5-1.2 million people die each year from HBV-attributable cases of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Significant disadvantages exist among currently available therapeutics (e.g. IFNca, lamivudine, adefovir, etc.) that include limited efficacy and the promotion of drug-resistant viral strains. These therapeutics are the research products of the HBV molecular biology that can be manipulated in the laboratory setting. Future antiviral drug therapy is dependent upon the development of better cell culture systems that will allow the study of the complete viral life cycle. The use of primary human and primate hepatocytes is restricted by multiple experimental limitations including a rapid loss of susceptibility to infection in culture, lot-to-lot variability inherent in primary cell culture, and the necessity of treatment with chemical agents such as DMSO for reproducible infection.(cont.) Permissive cell lines are capable of supporting viral replication upon transfection with the HBV genome. These cell lines have helped to elucidate the later events in the viral life cycle. However, there is less understanding of the early stages that include virus attachment, internalization, uncoating, nuclear transport, and genome repair. Our group has developed an in vitro system that recreates many of the features of a perfused capillary bed structure. Various metrics (e.g. biochemical production, tissue morphology, liver-enriched mRNA expression, and drug metabolism) confirm that this system maintains a well-differentiated liver phenotype. Using DHBV as a surrogate model, this study has attempted to demonstrate that hepatocytes maintained in a more sophisticated culture system retain susceptibility to infection. This study has endeavored to establish the perfused three-dimensional culture system as potential tool to study early events of the viral life cycle. This research lays the foundation for the future development of a human HBV infection model in which early stages of the viral life cycle can be studied and therapeutic targets identified.by Alexandria V. Sams.Ph.D

Loss-of-function genetic diseases and the concept of pharmaceutical targets

The biomedical world relies heavily on the definition of pharmaceutical targets as an essential step in the drug design process. It is therefore tempting to apply this model to genetic diseases as well. However, whereas the model applies well to gain-of-function genetic diseases, it is less suited to most loss-of-function genetic diseases. Most common diseases, as well as gain-of-function genetic diseases, are characterized by the activation of specific pathways or the ectopic activity of proteins, which make well identified targets. By contrast, loss-of-function genetic diseases are caused by the impairment of one protein, with potentially distributed consequences. For such diseases, the definition of a pharmaceutical target is less precise, and the identification of pharmaceutically-relevant targets may be difficult. This critical but largely ignored aspect of loss-of-function genetic diseases should be taken into consideration to avoid the commitment of resources to inappropriate strategies in the search for treatments

Severe Tracheobronchomalacia after Prolonged Intubation of Multitrauma Patient

Tracheobronchomalacia is a condition with significant morbidity with many etiologies including iatrogenic ones and should be considered in critically ill ventilated trauma patients. We present a case of a multitrauma patient who had difficulty weaning from the ventilator after prolonged intubation followed by tracheostomy tube placement. We describe her presentation, diagnosis, and management provide and as well a discussion of the condition

Comment on "Radiative forcings for 28 potential Archean greenhouse gases" by Byrne and Goldblatt (2014)

In the recent article by Byrne and Goldblatt, "Radiative forcing for 28 potential Archean greenhouse gases", Clim. Past. 10, 1779–1801 (2014), the authors employ the HITRAN2012 spectroscopic database to evaluate the radiative forcing of 28 Archean gases. As part of the evaluation of the status of the spectroscopy of these gases in the selected spectral region (50–1800 cm−1), the cross sections generated from the HITRAN line-by-line parameters were compared with those of the PNNL database of experimental cross sections recorded at moderate resolution. The authors claimed that for NO2, HNO3, H2CO, H2O2, HCOOH, C2H4, CH3OH and CH3Br there exist large or sometimes severe disagreements between the databases. In this work we show that for only three of these eight gases a modest discrepancy does exist between the two databases and we explain the origin of the differences. For the other five gases, the disagreements are not nearly at the scale suggested by the authors, while we explain some of the differences that do exist. In summary, the agreement between the HITRAN and PNNL databases is very good, although not perfect. Typically differences do not exceed 10 %, provided that HITRAN data exist for the bands/wavelengths of interest. It appears that a molecule-dependent combination of errors has affected the conclusions of the authors. In at least one case it appears that they did not take the correct file from PNNL (N2O4 (dimer)+ NO2 was used in place of the monomer). Finally, cross sections of HO2 from HITRAN (which do not have a PNNL counterpart) were not calculated correctly in BG, while in the case of HF misleading discussion was presented there based on the confusion by foreign or noise features in the experimental PNNL spectra

End-to-end deep learning for directly estimating grape yield from ground-based imagery

Yield estimation is a powerful tool in vineyard management, as it allows growers to fine-tune practices to optimize yield and quality. However, yield estimation is currently performed using manual sampling, which is time-consuming and imprecise. This study demonstrates the application of proximal imaging combined with deep learning for yield estimation in vineyards. Continuous data collection using a vehicle-mounted sensing kit combined with collection of ground truth yield data at harvest using a commercial yield monitor allowed for the generation of a large dataset of 23,581 yield points and 107,933 images. Moreover, this study was conducted in a mechanically managed commercial vineyard, representing a challenging environment for image analysis but a common set of conditions in the California Central Valley. Three model architectures were tested: object detection, CNN regression, and transformer models. The object detection model was trained on hand-labeled images to localize grape bunches, and either bunch count or pixel area was summed to correlate with grape yield. Conversely, regression models were trained end-to-end to predict grape yield from image data without the need for hand labeling. Results demonstrated that both a transformer as well as the object detection model with pixel area processing performed comparably, with a mean absolute percent error of 18% and 18.5%, respectively on a representative holdout dataset. Saliency mapping was used to demonstrate the attention of the CNN model was localized near the predicted location of grape bunches, as well as on the top of the grapevine canopy. Overall, the study showed the applicability of proximal imaging and deep learning for prediction of grapevine yield on a large scale. Additionally, the end-to-end modeling approach was able to perform comparably to the object detection approach while eliminating the need for hand-labeling

Decoding brain basis of laughter and crying in natural scenes

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66–77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others’ bonding and distress signals

A centrosome clustering protein, KIFC1, predicts aggressive disease course in serous ovarian adenocarcinomas

Background Amplified centrosomes are widely recognized as a hallmark of cancer. Although supernumerary centrosomes would be expected to compromise cell viability by yielding multipolar spindles that results in death-inducing aneuploidy, cancer cells suppress multipolarity by clustering their extra centrosomes. Thus, cancer cells, with the aid of clustering mechanisms, maintain pseudobipolar spindle phenotypes that are associated with low-grade aneuploidy, an edge to their survival. KIFC1, a nonessential minus end-directed motor of the kinesin-14 family, is a centrosome clustering molecule, essential for viability of extra centrosome-bearing cancer cells. Given that ovarian cancers robustly display amplified centrosomes, we examined the overexpression of KIFC1 in human ovarian tumors. Results We found that in clinical epithelial ovarian cancer (EOC) samples, an expression level of KIFC1 was significantly higher when compared to normal tissues. KIFC1 expression also increased with tumor grade. Our In silico analyses showed that higher KIFC1 expression was associated with poor overall survival (OS) in serous ovarian adenocarcinoma (SOC) patients suggesting that an aggressive disease course in ovarian adenocarcinoma patients can be attributed to high KIFC1 levels. Also, gene expression levels of KIFC1 in high-grade serous ovarian carcinoma (HGSOC) highly correlated with expression of genes driving centrosome amplification (CA), as examined in publically-available databases. The pathway analysis results indicated that the genes overexpressed in KIFC1 high group were associated with processes like regulation of the cell cycle and cell proliferation. In addition, when we performed gene set enrichment analysis (GSEA) for identifying the gene ontologies associated to KIFC1 high group, we found that the first 100 genes enriched in KIFC1 high group were from centrosome components, mitotic cell cycle, and microtubule-based processes. Results from in vitro experiments on well-established in vitro models of HGSOC (OVSAHO, KURAMOCHI), OVCAR3 and SKOV3) revealed that they display robust centrosome amplification and expression levels of KIFC1 was directly associated (inversely correlated) to the status of multipolar mitosis. This association of KIFC1 and centrosome amplification with HGSOC might be able to explain the increased aggressiveness in this disease. Conclusion These findings compellingly underscore that KIFC1 can be a biomarker that predicts an aggressive disease course in ovarian adenocarcinomas

Local and global modes of drug action in biochemical networks

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties

Spin observables of the reactions NN -> DeltaN and pd -> Delta (pp)(1S0) in collinear kinematics

A general formalism for double and triple spin-correlations of the reaction NN -> DeltaN is developed for the case of collinear kinematics. A complete polarization experiment allowing to reconstruct all of the four amplitudes describing this process is suggested. Furthermore, the spin observables of the inelastic charge-exchange reaction pd -> Delta^0(pp)(1S0) are analyzed in collinear kinematics within the single pN scattering mechanism involving the subprocess pn -> Delta^0p. The full set of spin observables related to the polarization of one or two initial particles and one final particle is obtained in terms of three invariant amplitudes of the reaction pd -> Delta (pp)(1S0) and the transition form factor d->(pp)(1S0). A complete polarization experiment for the reaction pd -> Delta^0(pp)(1S0) is suggested which allows one to determine three independent combinations of the four amplitudes of the elementary subprocess NN -> DeltaN.Comment: 12 pages, 1 figur