370 research outputs found
Passive water control at the surface of a superhydrophobic lichen
Some lichens have a super-hydrophobic upper surface, which repels water drops, keeping the surface dry but probably preventing water uptake. Spore ejection requires water and is most efficient just after rainfall. This study was carried out to investigate how super-hydrophobic lichens manage water uptake and repellence at their fruiting bodies, or podetia. Drops of water were placed onto separate podetia of Cladonia chlorophaea and observed using optical microscopy and cryo-scanning-electron microscopy (cryo-SEM) techniques to determine the structure of podetia and to visualise their interaction with water droplets. SEM and optical microscopy studies revealed that the surface of the podetia was constructed in a three-level structural hierarchy. By cryo-SEM of water-glycerol droplets placed on the upper part of the podetium, pinning of the droplet to specific, hydrophilic spots (pycnidia/apothecia) was observed. The results suggest a mechanism for water uptake, which is highly sophisticated, using surface wettability to generate a passive response to different types of precipitation in a manner similar to the Namib Desert beetle. This mechanism is likely to be found in other organisms as it offers passive but selective water control
The dynamic mass spectrometry probe (DMSP) - Advanced process analytics for therapeutic cell manufacturing, health monitoring and biomarker discovery
Spatially and temporally resolved in situ monitoring of biochemical cell culture environments, e.g., in application to therapeutic cell bioreactors, is of critical importance for facilitating the development of new and reliable quality control methodologies for cell therapies. Identifying and monitoring secreted biomolecular critical quality attributes (CQAs) to enable online feedback control will enable large scale, cost-effective manufacturing of therapeutic cells. These CQA biomarkers have varying concentrations within a bioreactor, both in time and space. Current methods for monitoring these diverse biomolecules are generally ex-situ, time consuming, destructive, provide bulk measurements, or lack the ability to reveal the complete secretome/metabolome composition. The Dynamic Mass Spectrometry Probe (DMSP) synergistically incorporates a sampling interface for localized intake of a small fluid volume of the cellular content, a micro-fabricated mass exchanger for sample conditioning and inline separation, and an integrated electrospray ionization (ESI) emitter for softly ionizing (i.e. preserved biochemical structure) extracted biomolecules for mass spectrometry (MS). ESI-MS via DMSP treatment enables both biomarker discovery and transient (~1 min) analysis of biochemical information indicative of cell health and potency. DMSP is manufactured using advanced batch microfabrication techniques, which minimize dead volume (~20 nL) and ensure repeatable operation and precise geometry of each device. DMSP treatment removes 99% of compounds that interfere with mass spectrometry analysis, such as inorganic salts, while retaining biomolecules of interest within the sample for ESI-MS analysis. DMSP has demonstrated the ability to substantially increase signal to noise ratio in MS detection of biomolecules, and to further enhance sensitivity for probing lower biomarker concentrations via introduction of ESI-MS enhancing molecules (i.e. proton donating chemicals, protein denaturing solvents, and supercharging agents) into the sample within the integrated mass exchanger. To exemplify the DMSP’s unique capabilities, Fig. 1 demonstrates detection of multiple low-concentration protein biomarkers sampled from a biochemically-complex cell media solution serving as a proxy to samples taken directly from cell growth bioreactors [1].
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Network conduciveness with application to the graph-coloring and independent-set optimization transitions
We introduce the notion of a network's conduciveness, a probabilistically
interpretable measure of how the network's structure allows it to be conducive
to roaming agents, in certain conditions, from one portion of the network to
another. We exemplify its use through an application to the two problems in
combinatorial optimization that, given an undirected graph, ask that its
so-called chromatic and independence numbers be found. Though NP-hard, when
solved on sequences of expanding random graphs there appear marked transitions
at which optimal solutions can be obtained substantially more easily than right
before them. We demonstrate that these phenomena can be understood by resorting
to the network that represents the solution space of the problems for each
graph and examining its conduciveness between the non-optimal solutions and the
optimal ones. At the said transitions, this network becomes strikingly more
conducive in the direction of the optimal solutions than it was just before
them, while at the same time becoming less conducive in the opposite direction.
We believe that, besides becoming useful also in other areas in which network
theory has a role to play, network conduciveness may become instrumental in
helping clarify further issues related to NP-hardness that remain poorly
understood
Iterative focused screening with biological fingerprints identifies selective Asc-1 inhibitors distinct from traditional high throughput screening
N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer’s disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine–serine–cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs. To identify novel Asc-1 inhibitors, two different screening approaches were performed with whole-cell amino acid uptake in heterologous cells stably expressing human Asc-1: (1) a high-throughput screen (HTS) of 3 M compounds measuring 35S l-cysteine uptake into cells attached to scintillation proximity assay beads in a 1536 well format and (2) an iterative focused screen (IFS) of a 45 000 compound diversity set using a 3H d-serine uptake assay with a liquid scintillation plate reader in a 384 well format. Critically important for both screening approaches was the implementation of counter screens to remove nonspecific inhibitors of radioactive amino acid uptake. Furthermore, a 15 000 compound expansion step incorporating both on- and off-target data into chemical and biological fingerprint-based models for selection of additional hits enabled the identification of novel Asc-1-selective chemical matter from the IFS that was not identified in the full-collection HTS
Polynomial iterative algorithms for coloring and analyzing random graphs
We study the graph coloring problem over random graphs of finite average
connectivity . Given a number of available colors, we find that graphs
with low connectivity admit almost always a proper coloring whereas graphs with
high connectivity are uncolorable. Depending on , we find the precise value
of the critical average connectivity . Moreover, we show that below
there exist a clustering phase in which ground states
spontaneously divide into an exponential number of clusters. Furthermore, we
extended our considerations to the case of single instances showing consistent
results. This lead us to propose a new algorithm able to color in polynomial
time random graphs in the hard but colorable region, i.e when .Comment: 23 pages, 10 eps figure
Prioritizing Residents\u27 Needs: On the Creation of a Residents as Teachers and Leaders Program
Introduction: Residents are responsible for the majority of medical student teaching and directly supervise, instruct, and evaluate students. Many organizations now recommend that residency training programs include venues specifically designed to develop resident teaching skills. [See PDF for abstract]
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Experimental Evolution of Extreme Resistance to Ionizing Radiation in Escherichia coli after 50 Cycles of Selection.
In previous work (D. R. Harris et al., J Bacteriol 191:5240-5252, 2009, https://doi.org/10.1128/JB.00502-09; B. T. Byrne et al., Elife 3:e01322, 2014, https://doi.org/10.7554/eLife.01322), we demonstrated that Escherichia coli could acquire substantial levels of resistance to ionizing radiation (IR) via directed evolution. Major phenotypic contributions involved adaptation of organic systems for DNA repair. We have now undertaken an extended effort to generate E. coli populations that are as resistant to IR as Deinococcus radiodurans After an initial 50 cycles of selection using high-energy electron beam IR, four replicate populations exhibit major increases in IR resistance but have not yet reached IR resistance equivalent to D. radiodurans Regular deep sequencing reveals complex evolutionary patterns with abundant clonal interference. Prominent IR resistance mechanisms involve novel adaptations to DNA repair systems and alterations in RNA polymerase. Adaptation is highly specialized to resist IR exposure, since isolates from the evolved populations exhibit highly variable patterns of resistance to other forms of DNA damage. Sequenced isolates from the populations possess between 184 and 280 mutations. IR resistance in one isolate, IR9-50-1, is derived largely from four novel mutations affecting DNA and RNA metabolism: RecD A90E, RecN K429Q, and RpoB S72N/RpoC K1172I. Additional mechanisms of IR resistance are evident.IMPORTANCE Some bacterial species exhibit astonishing resistance to ionizing radiation, with Deinococcus radiodurans being the archetype. As natural IR sources rarely exceed mGy levels, the capacity of Deinococcus to survive 5,000 Gy has been attributed to desiccation resistance. To understand the molecular basis of true extreme IR resistance, we are using experimental evolution to generate strains of Escherichia coli with IR resistance levels comparable to Deinococcus Experimental evolution has previously generated moderate radioresistance for multiple bacterial species. However, these efforts could not take advantage of modern genomic sequencing technologies. In this report, we examine four replicate bacterial populations after 50 selection cycles. Genomic sequencing allows us to follow the genesis of mutations in populations throughout selection. Novel mutations affecting genes encoding DNA repair proteins and RNA polymerase enhance radioresistance. However, more contributors are apparent
Recognizing Treelike k-Dissimilarities
A k-dissimilarity D on a finite set X, |X| >= k, is a map from the set of
size k subsets of X to the real numbers. Such maps naturally arise from
edge-weighted trees T with leaf-set X: Given a subset Y of X of size k, D(Y) is
defined to be the total length of the smallest subtree of T with leaf-set Y .
In case k = 2, it is well-known that 2-dissimilarities arising in this way can
be characterized by the so-called "4-point condition". However, in case k > 2
Pachter and Speyer recently posed the following question: Given an arbitrary
k-dissimilarity, how do we test whether this map comes from a tree? In this
paper, we provide an answer to this question, showing that for k >= 3 a
k-dissimilarity on a set X arises from a tree if and only if its restriction to
every 2k-element subset of X arises from some tree, and that 2k is the least
possible subset size to ensure that this is the case. As a corollary, we show
that there exists a polynomial-time algorithm to determine when a
k-dissimilarity arises from a tree. We also give a 6-point condition for
determining when a 3-dissimilarity arises from a tree, that is similar to the
aforementioned 4-point condition.Comment: 18 pages, 4 figure
Causal Set Dynamics: A Toy Model
We construct a quantum measure on the power set of non-cyclic oriented graphs
of N points, drawing inspiration from 1-dimensional directed percolation.
Quantum interference patterns lead to properties which do not appear to have
any analogue in classical percolation. Most notably, instead of the single
phase transition of classical percolation, the quantum model displays two
distinct crossover points. Between these two points, spacetime questions such
as "does the network percolate" have no definite or probabilistic answer.Comment: 28 pages incl. 5 figure
Pre-service Teachers as Curriculum Makers: What Could Social Justice Look Like in a Middle School Curriculum?
In this article, we answer the questions 1) What could social justice look like in the middle school curriculum; 2) How do we help young adolescents recognize and repudiate racism and other forms of social injustice; and 3) What are some lessons learned from a middle level teacher preparation with a focus on social justice ? By presenting three examples of social justice curriculum created by pre-service teachers in their teacher leadership education course, we argue for spaces that allow pre-service teachers to be curriculum-makers if we are truly seeking social justice educators in schools. We conclude, through the perspective of the pre-service teachers, effective practices they believe should be a part of teacher preparation that focus on social justice education
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