Droplet-based digital antibiotic susceptibility screen reveals single-cell clonal heteroresistance in an isogenic bacterial population

Since antibiotic resistance is a major threat to global health, recent observations that the traditional test of minimum inhibitory concentration (MIC) is not informative enough to guide effective antibiotic treatment are alarming. Bacterial heteroresistance, in which seemingly susceptible isogenic bacterial populations contain resistant sub-populations, underlies much of this challenge. To close this gap, here we developed a droplet-based digital MIC screen that constitutes a practical analytical platform for quantifying the single-cell distribution of phenotypic responses to antibiotics, as well as for measuring inoculum effect with high accuracy. We found that antibiotic efficacy is determined by the amount of antibiotic used per bacterial colony forming unit (CFU), not by the absolute antibiotic concentration, as shown by the treatment of beta-lactamase-carrying Escherichia coli with cefotaxime. We also noted that cells exhibited a pronounced clustering phenotype when exposed to near-inhibitory amounts of cefotaxime. Overall, our method facilitates research into the interplay between heteroresistance and antibiotic efficacy, as well as research into the origin and stimulation of heterogeneity by exposure to antibiotics. Due to the absolute bacteria quantification in this digital assay, our method provides a platform for developing reference MIC assays that are robust against inoculum-density variations

Funnels in Energy Landscapes

Local minima and the saddle points separating them in the energy landscape are known to dominate the dynamics of biopolymer folding. Here we introduce a notion of a "folding funnel" that is concisely defined in terms of energy minima and saddle points, while at the same time conforming to a notion of a "folding funnel" as it is discussed in the protein folding literature.Comment: 6 pages, 3 figures, submitted to European Conference on Complex Systems 200

QAA subject benchmark statement architecture : version for consultation December 2019

The Statement is intended to guide lecturers and course leaders in the design of academic courses leading to qualifications in architecture, it will also be useful to those developing other related courses. Higher education providers may need to consider other reference points in addition to this Statement in designing, delivering and reviewing courses. These may include requirements set out by the Architects Registration Board (ARB), the Royal Institute of British Architects (RIBA) and the Institute for Apprenticeships and Technical Education (IfATE). Providers may also need to consider industry or employer expectations. Individual higher education providers will decide how they use this information. The broad subject of architecture is both academic and vocational. The bachelor's award for architecture is the first stage of the typical education of an architect. This is typically either a BSc or a BA degree. The second stage of academic qualification is a master's level degree, typically in the form of a two-year MArch, which is defined as an undergraduate master's award. Architecture qualifications typically require a total of 360 (Credit Accumulation and Transfer Scheme, or CATS) credits at bachelor's level and 240 (CATS) credits within a master's level degree. While this may equate to five years of 120 (CATS) credits each, higher education providers may construct alternatives to enable flexibility in student learning. This Statement seeks to encapsulate the nature of a rich and diverse academic discipline. It is not intended to prescribe a curriculum, but rather describes the broad intellectual territory within which individual higher education providers will locate their courses of study in architecture

Proteinlike behavior of a spin system near the transition between ferromagnet and spin glass

A simple spin system is studied as an analog for proteins. We investigate how the introduction of randomness and frustration into the system effects the designability and stability of ground state configurations. We observe that the spin system exhibits protein-like behavior in the vicinity of the transition between ferromagnet and spin glass. Our results illuminate some guiding principles in protein evolution.Comment: 12 pages, 4 figure

A Comparison of Selected Physical Fitness and Performance Variables between Division I and Division II Football Players

The purpose of this study was to compare select physical fitness and performance variables between Division I and Division II football players and determine if there is a significant difference in the performance variables of the athletes at these levels. The subjects included offensive and defensive starters, excluding kickers and punters, from 26 NCAA Division I teams and 23 NCAA Division II teams. Offensive players were divided into the following positions: quarterbacks, running backs, wide receivers, tight ends, and offensive line. The defensive players were divided into the following positions: defensive line, linebackers, and defensive backs. Division I athletes were superior in 58 of the 117 independent t-tests analyzed in this study (p\u3c.01). This study found Division II athletes were not superior in any of the t-tests. The greatest similarity between the two divisions was found in height and weight. Of the nine position groups compared for each of these variables, only two showed significant differences