Fyodor Dostoevsky’s and Flannery O’Connor’s Use of the Grotesque: Irrational or Mysterious?

Both Fyodor Dostoevsky and Flannery O’Connor used the grotesque to portray their beliefs about human nature. Both believed that mystery is a crucial element of truth and humanity’s understanding is limited. Although they employed the grotesque differently, the similarities of their style stem from the similarities of their beliefs. O’Connor often referred to Dostoevsky’s artistry and his theology, and she was influenced by both. A comparison of Ivan Karamazov in Dostoevsky’s The Brothers Karamazov and Hazel Motes in O’Connor’s Wise Blood reveals the similarities in what each author believed about humanity’s capability to understand truth. What both authors believed about human nature, and the limitations of every aspect of humanity, particularly human reason, led to their use of the grotesque

A geometric and structural approach to the analysis and design of biological circuit dynamics: a theory tailored for synthetic biology

Much of the progress in developing our ability to successfully design genetic circuits with predictable dynamics has followed the strategy of molding biological systems to fit into conceptual frameworks used in other disciplines, most notably the engineering sciences. Because biological systems have fundamental differences from systems in these other disciplines, this approach is challenging and the insights obtained from such analyses are often not framed in a biologically-intuitive way. Here, we present a new theoretical framework for analyzing the dynamics of genetic circuits that is tailored towards the unique properties associated with biological systems and experiments. Our framework approximates a complex circuit as a set of simpler circuits, which the system can transition between by saturating its various internal components. These approximations are connected to the intrinsic structure of the system, so this representation allows the analysis of dynamics which emerge solely from the system's structure. Using our framework, we analyze the presence of structural bistability in a leaky autoactivation motif and the presence of structural oscillations in the Repressilator

Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis

Spontaneous intracellular calcium activity can be observed in a variety of cell types and is proposed to play critical roles in a variety of physiological processes. In particular, appropriate regulation of calcium activity patterns during embryogenesis is necessary for many aspects of vertebrate neural development, including proper neural tube closure, synaptogenesis, and neurotransmitter phenotype specification. While the observation that calcium activity patterns can differ in both frequency and amplitude suggests a compelling mechanism by which these fluxes might transmit encoded signals to downstream effectors and regulate gene expression, existing population-level approaches have lacked the precision necessary to further explore this possibility. Furthermore, these approaches limit studies of the role of cell-cell interactions by precluding the ability to assay the state of neuronal determination in the absence of cell-cell contact. Therefore, we have established an experimental workflow that pairs time-lapse calcium imaging of dissociated neuronal explants with a fluorescence in situ hybridization assay, allowing the unambiguous correlation of calcium activity pattern with molecular phenotype on a single-cell level. We were successfully able to use this approach to distinguish and characterize specific calcium activity patterns associated with differentiating neural cells and neural progenitor cells, respectively; beyond this, however, the experimental framework described in this article could be readily adapted to investigate correlations between any time-series activity profile and expression of a gene or genes of interest

Malaysian pharmacy educators’ view of the role of non-pharmacy trained educators in teaching pharmacy students

The common statement “…Pharmacy students should only be taught by pharmacists…” is a norm among many pharmacy educators in countries such as Malaysia. It is not, per se, a confronting statement but could indicate alarming attitudes not favorable to the current pharmacy education framework. Pharmacy education in the third millennium is transformed to contain and reflect on the innovations of the modernization era in which, globalization in health education, public health, development of the new facets of professionalization and professionalism, interprofessional and interdisciplinary teaching and learning activities are among the most talked about topics.1-6 Interestingly, these innovative ideas are the result of extremely cautious, vigilant, accurate, and continuous observations and contemplations which have undergone thorough examinations and experimentations before being presented as novice ideas and/or theories. For example, the notion of interdisciplinary learning dates back to late 1970s7 and today, there is concrete evidence of its effectiveness and usefulness in delivery of better health care.6,8 Hence, to contest such ideas and/or theories, one needs to be able to provide reliable evidence(s), as agreements or disagreements should be borne with a full sense of responsibility and accountability

Fabrication of a Horizontal and a Vertical Large Surface Area Nanogap Electrochemical Sensor

Nanogap sensors have a wide range of applications as they can provide accurate direct detection of biomolecules through impedimetric or amperometric signals. Signal response from nanogap sensors is dependent on both the electrode spacing and surface area. However, creating large surface area nanogap sensors presents several challenges during fabrication. We show two different approaches to achieve both horizontal and vertical coplanar nanogap geometries. In the first method we use electron-beam lithography (EBL) to pattern an 11 mm long serpentine nanogap (215 nm) between two electrodes. For the second method we use inductively-coupled plasma (ICP) reactive ion etching (RIE) to create a channel in a silicon substrate, optically pattern a buried 1.0 mm × 1.5 mm electrode before anodically bonding a second identical electrode, patterned on glass, directly above. The devices have a wide range of applicability in different sensing techniques with the large area nanogaps presenting advantages over other devices of the same family. As a case study we explore the detection of peptide nucleic acid (PNA)−DNA binding events using dielectric spectroscopy with the horizontal coplanar device

Thermal comfort, physiological responses and performance during exposure to a moderate temperature drift

The objective of this research was to study the effects of a moderate temperature drift on human thermal comfort, physiological responses, productivity and performance. A dynamic thermophysiological model was used to examine the possibility of simulating human thermal responses and thermal comfort under moderate transient conditions. To examine the influence of a moderate temperature ramp, a climate room set-up with experimental subjects was used. Eight subjects visited the climate room on two occasions: 1) exposure to a transient condition (a moderate temperature ramp) and 2) a steady temperature corresponding with a neutral thermal sensation (control situation). During the experiments both physiological responses and thermal sensation were measured. Productivity and performance were assessed with a ‘Remote Performance Measurement’ (RPM) method. Physiological and thermal sensation data indicate significant differences between the transient condition and the control situation. Productivity and performance tests show no significant changes between the two situations. Simulations obtained with the thermophysiological model were in good agreement with the measurements. Possible improvements of the performance and productivity tests and the thermophysiological model will be discussed

Genome engineering of isogenic human ES cells to model autism disorders.

Isogenic pluripotent stem cells are critical tools for studying human neurological diseases by allowing one to study the effects of a mutation in a fixed genetic background. Of particular interest are the spectrum of autism disorders, some of which are monogenic such as Timothy syndrome (TS); others are multigenic such as the microdeletion and microduplication syndromes of the 16p11.2 chromosomal locus. Here, we report engineered human embryonic stem cell (hESC) lines for modeling these two disorders using locus-specific endonucleases to increase the efficiency of homology-directed repair (HDR). We developed a system to: (1) computationally identify unique transcription activator-like effector nuclease (TALEN) binding sites in the genome using a new software program, TALENSeek, (2) assemble the TALEN genes by combining golden gate cloning with modified constructs from the FLASH protocol, and (3) test the TALEN pairs in an amplification-based HDR assay that is more sensitive than the typical non-homologous end joining assay. We applied these methods to identify, construct, and test TALENs that were used with HDR donors in hESCs to generate an isogenic TS cell line in a scarless manner and to model the 16p11.2 copy number disorder without modifying genomic loci with high sequence similarity