PhD by Published Work: is it time to clarify and tighten-up the ground rules?

The Doctor of Philosophy (PhD) by Published Work (PhD by PW) is gaining impetus as a format of doctoral output both nationally and abroad (Smith, 2015). Indeed, doing a PhD by PW makes perfect sense, particularly for many staff who have come into Higher Education to teach from other professions where “having a doctorate” has not traditionally been part of their professional culture, e.g. in nursing, social work, law or teaching. Frick (2019) is also optimistic about its popularity and expansion, and has recently explored whether this PhD route can act as a real panacea to the ills of high traditional doctoral dropout rates and slow doctoral completions. The PhD by PW is a great route for people who might have atypical career pathways into academia; or who have struggled with the financial and work/life juggling act of committing to the traditional PhD, including many NTFs. It is an inclusive route, enabling candidates to build incrementally on existing achievements – thus benefitting and giving opportunities to those who have taken a career break or for those with caring responsibilities (Lee, 2010; Smith, 2015)

Antikaon production in nucleon-nucleon reactions near threshold

The antikaon production cross section from nucleon-nucleon reactions near threshold is studied in a meson exchange model. We include both pion and kaon exchange, but neglect the interference between the amplitudes. In case of pion exchange the antikaon production cross section can be expressed in terms of the antikaon production cross section from a pion-nucleon interaction, which we take from the experimental data if available. Otherwise, a $K^*$-resonance exchange model is introduced to relate the different reaction cross sections. In case of kaon exchange the antikaon production cross section is related to the elastic $KN$ and $\bar KN$ cross sections, which are again taken from experimental measurements. We find that the one-meson exchange model gives a satisfactory fit to the available data for the $NN\to NNK\bar K$ cross section at high energies. We compare our predictions for the cross section near threshold with an earlier empirical parameterization and that from phase space models.Comment: 16 pages, LaTeX, 5 postscript figures included, submitted to Z. Phys.

Comparison of human uterine cervical electrical impedance measurements derived using two tetrapolar probes of different sizes

BACKGROUND We sought to compare uterine cervical electrical impedance spectroscopy measurements employing two probes of different sizes, and to employ a finite element model to predict and compare the fraction of electrical current derived from subepithelial stromal tissue. METHODS Cervical impedance was measured in 12 subjects during early pregnancy using 2 different sizes of the probes on each subject. RESULTS Mean cervical resistivity was significantly higher (5.4 vs. 2.8 Ωm; p < 0.001) with the smaller probe in the frequency rage of 4–819 kHz. There was no difference in the short-term intra-observer variability between the two probes. The cervical impedance measurements derived in vivo followed the pattern predicted by the finite element model. CONCLUSION Inter-electrode distance on the probes for measuring cervical impedance influences the tissue resistivity values obtained. Determining the appropriate probe size is necessary when conducting clinical studies of resistivity of the cervix and other human tissues

Clostridium perfringens Epsilon Toxin Compromises the Blood-Brain Barrier in a Humanized Zebrafish Model

This is the final version. Available on open access from Elsevier vis the DOI in this recordClostridium perfringens epsilon toxin (ETX) is hypothesized to mediate blood-brain barrier (BBB) permeability by binding to the myelin and lymphocyte protein (MAL) on the luminal surface of endothelial cells (ECs). However, the kinetics of this interaction and a general understanding of ETX's behavior in a live organism have yet to be appreciated. Here we investigate ETX binding and BBB breakdown in living Danio rerio (zebrafish). Wild-type zebrafish ECs do not bind ETX. When zebrafish ECs are engineered to express human MAL (hMAL), proETX binding occurs in a time-dependent manner. Injection of activated toxin in hMAL zebrafish initiates BBB leakage, hMAL downregulation, blood vessel stenosis, perivascular edema, and blood stasis. We propose a kinetic model of MAL-dependent ETX binding and neurovascular pathology. By generating a humanized zebrafish BBB model, this study contributes to our understanding of ETX-induced BBB permeability and strengthens the proposal that MAL is the ETX receptor.National Institute of Neurological Disorders and StrokeWilma S. and Laurence A. Tisch Foundatio

A Conserved Ribosomal Protein Has Entirely Dissimilar Structures in Different Organisms

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. Ribosomes from different species can markedly differ in their composition by including dozens of ribosomal proteins that are unique to specific lineages but absent in others. However, it remains unknown how ribosomes acquire new proteins throughout evolution. Here, to help answer this question, we describe the evolution of the ribosomal protein msL1/msL2 that was recently found in ribosomes from the parasitic microorganism clade, microsporidia. We show that this protein has a conserved location in the ribosome but entirely dissimilar structures in different organisms: in each of the analyzed species, msL1/msL2 exhibits an altered secondary structure, an inverted orientation of the N-termini and C-termini on the ribosomal binding surface, and a completely transformed 3D fold. We then show that this fold switching is likely caused by changes in the ribosomal msL1/msL2-binding site, specifically, by variations in rRNA. These observations allow us to infer an evolutionary scenario in which a small, positively charged, de novo-born unfolded protein was first captured by rRNA to become part of the ribosome and subsequently underwent complete fold switching to optimize its binding to its evolving ribosomal binding site. Overall, our work provides a striking example of how a protein can switch its fold in the context of a complex biological assembly, while retaining its specificity for its molecular partner. This finding will help us better understand the origin and evolution of new protein components of complex molecular assemblies-thereby enhancing our ability to engineer biological molecules, identify protein homologs, and peer into the history of life on Earth

Electrophoresis- and FRET-Based Measures of Serpin Polymerization

Many serpinopathies, including alpha-1 antitrypsin (A1AT) deficiency, are associated with the formation of unbranched polymer chains of mutant serpins. In vivo, this deficiency is the result of mutations that cause kinetic or thermodynamic destabilization of the molecule. However, polymerization can also be induced in vitro from mutant or wild-type serpins under destabilizing conditions. The characteristics of the resulting polymers are dependent upon induction conditions. Due to their relationship to disease, serpin polymers, mainly those formed from A1AT, have been widely studied. Here, we describe Förster resonance energy transfer (FRET) and gel-based approaches for their characterization

Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats

Rationale Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Objectives Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. Methods The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. Results We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. Conclusions These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control

Beyond Logarithmic Corrections to Cardy Formula

As shown by Cardy modular invariance of the partition function of a given unitary non-singular 2d CFT with left and right central charges c_L and c_R, implies that the density of states in a microcanonical ensemble, at excitations Delta and Delta-bar and in the saddle point approximation, is \rho_0(\Delta,\bar\Delta;c_L, c_R)=c_L c_R \exp(2\pi\sqrt{{c_L\Delta}/{6}})\exp(2\pi\sqrt{{c_R\bar\Delta}/{6}}). In this paper, we extend Cardy's analysis and show that in the saddle point approximation and up to contributions which are exponentially suppressed compared to the leading Cardy's result, the density of states takes the form \rho(\Delta,\bar\Delta; c_L,c_R)= f(c_L\Delta) f(c_R\bar\Delta)\rho_0(\Delta,\bar\Delta; c_L, c_R), for a function f(x) which we specify. In particular, we show that (i) \rho (\Delta,\bar\Delta; c_L, c_R) is the product of contributions of left and right movers and hence, to this approximation, the partition function of any modular invariant, non-singular unitary 2d CFT is holomorphically factorizable and (ii) \rho(\Delta,\bar\Delta; c_L, c_R)/(c_Lc_R) is only a function of $c_R\bar\Delta$ and $c_L\Delta$. In addition, treating \rho(\Delta,\bar\Delta; c_L, c_R) as the density of states of a microcanonical ensemble, we compute the entropy of the system in the canonical counterpart and show that the function f(x) is such that the canonical entropy, up to exponentially suppressed contributions, is simply given by the Cardy's result \ln\rho_0(\Delta,\bar\Delta; c_L, c_R).Comment: 30 pages, no figures; v2: minor improvements, one reference added, v3: minor corrections to match the published versio

What limits supercurrents in high temperature superconductors? A microscopic model of cuprate grain boundaries

The interface properties of high-temperature cuprate superconductors have been of interest for many years, and play an essential role in Josephson junctions, superconducting cables, and microwave electronics. In particular, the maximum critical current achievable in high-Tc wires and tapes is well known to be limited by the presence of grain boundaries, regions of mismatch between crystallites with misoriented crystalline axes. In studies of single, artificially fabricated grain boundaries the striking observation has been made that the critical current Jc of a grain boundary junction depends exponentially on the misorientation angle. Until now microscopic understanding of this apparently universal behavior has been lacking. We present here the results of a microscopic evaluation based on a construction of fully 3D YBCO grain boundaries by molecular dynamics. With these structures, we calculate an effective tight-binding Hamiltonian for the d-wave superconductor with a grain boundary. The critical current is then shown to follow an exponential suppression with grain boundary angle. We identify the buildup of charge inhomogeneities as the dominant mechanism for the suppression of the supercurrent.Comment: 28 pages, 12 figure

Adaptive Filtering Enhances Information Transmission in Visual Cortex

Sensory neuroscience seeks to understand how the brain encodes natural environments. However, neural coding has largely been studied using simplified stimuli. In order to assess whether the brain's coding strategy depend on the stimulus ensemble, we apply a new information-theoretic method that allows unbiased calculation of neural filters (receptive fields) from responses to natural scenes or other complex signals with strong multipoint correlations. In the cat primary visual cortex we compare responses to natural inputs with those to noise inputs matched for luminance and contrast. We find that neural filters adaptively change with the input ensemble so as to increase the information carried by the neural response about the filtered stimulus. Adaptation affects the spatial frequency composition of the filter, enhancing sensitivity to under-represented frequencies in agreement with optimal encoding arguments. Adaptation occurs over 40 s to many minutes, longer than most previously reported forms of adaptation.Comment: 20 pages, 11 figures, includes supplementary informatio