Semiconductor microlasers with intracavity microfluidics for biomedical analyses

Recently demonstrated microfluidic chips have the potential to be useful bioanalytical tools for DNA, protein, and cellular studies. To realize this potential, means for introducing fluids, separating their components, and detection must be integrated onto the chip. The authors have investigated semiconductor laser microcavity spectroscopy as a means for ultrasensitive detection of various fluids, cells, and particulates. Two methods for implementing this laser device are illustrated. A scanning method for reading the light signals from a static fluid in the microcavity is presented. The device has a microfabricated flow structure formed between two surfaces, a vertical cavity surface-emitting laser and a glass dielectric mirror. The resonance frequencies of this Fabry-Perot microcavity are very sensitive to the dielectric properties of the fluids confined inside the cavity. Further, the resonance linewidth or cavity Q is sensitive to the optical length of the cavity, light absorption, and light scattering from the fluid and the surfaces forming the cavity. If cells or particulates are present in the fluid they confine light transverse to the cavity length and develop additional sub-frequencies between the Fabry-Perot frequencies. Thus, the spectrum of light emitted from or transmitted through the cavity comprises a wealth of information about the cavity contents

Effect of the GaAsP shell on optical properties of self-catalyzed GaAs nanowires grown on silicon

We realize growth of self-catalyzed core-shell GaAs/GaAsP nanowires (NWs) on Si substrates using molecular-beam epitaxy. Transmission electron microscopy (TEM) of single GaAs/GaAsP NWs confirms their high crystal quality and shows domination of the zinc-blende phase. This is further confirmed in optics of single NWs, studied using cw and time-resolved photoluminescence (PL). A detailed comparison with uncapped GaAs NWs emphasizes the effect of the GaAsP capping in suppressing the non-radiative surface states: significant PL enhancement in the core-shell structures exceeding 2000 times at 10K is observed; in uncapped NWs PL is quenched at 60K whereas single core-shell GaAs/GaAsP NWs exhibit bright emission even at room temperature. From analysis of the PL temperature dependence in both types of NW we are able to determine the main carrier escape mechanisms leading to the PL quench

High EMSY expression defines a BRCA‐like subgroup of high‐grade serous ovarian carcinoma with prolonged survival and hypersensitivity to platinum

Background Approximately half of high‐grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination repair (HR) pathway defects, resulting in a distinct clinical phenotype comprising hypersensitivity to platinum, superior clinical outcome, and greater sensitivity to poly(adenosine diphosphate‐ribose) polymerase (PARP) inhibitors. EMSY, which is known to be amplified in breast and ovarian cancers, encodes a protein reported to bind and inactivate BRCA2. Thus, EMSY overexpression may mimic BRCA2 mutation, resulting in HR deficiency. However, to our knowledge, the phenotypic consequences of EMSY overexpression in HGSOC patients has not been explored. Methods Here we investigate the impact of EMSY expression on clinical outcome and sensitivity to platinum‐based chemotherapy using available data from transcriptomically characterized HGSOC cohorts. Results High EMSY expression was associated with better clinical outcome in a cohort of 265 patients with HGSOC from Edinburgh (overall survival multivariable hazard ratio, 0.58 [95% CI, 0.38‐0.88; P = .011] and progression‐free survival multivariable hazard ratio, 0.62 [95% CI, 0.40‐0.96; P = .030]). Superior outcome also was demonstrated in the Medical Research Council ICON7 clinical trial and multiple publicly available data sets. Patients within the Edinburgh cohort who had high EMSY expression were found to demonstrate greater rates of complete response to multiple platinum‐containing chemotherapy regimens (radiological complete response rate of 44.4% vs 12.5% at second exposure; P = .035) and corresponding prolonged time to disease progression (median, 151.5 days vs 60.5 days after third platinum exposure; P = .004). Conclusions Patients with HGSOCs demonstrating high EMSY expression appear to experience prolonged survival and greater platinum sensitivity, reminiscent of BRCA‐mutant cases. These data are consistent with the notion that EMSY overexpression may render HGSOCs HR deficient

Gene expression time delays & Turing pattern formation systems

The incorporation of time delays can greatly affect the behaviour of partial differential equations and dynamical systems. In addition, there is evidence that time delays in gene expression due to transcription and translation play an important role in the dynamics of cellular systems. In this paper, we investigate the effects of incorporating gene expression time delays into a one-dimensional putative reaction diffusion pattern formation mechanism on both stationary domains and domains with spatially uniform exponential growth. While oscillatory behaviour is rare, we find that the time taken to initiate and stabilise patterns increases dramatically as the time delay is increased. In addition, we observe that on rapidly growing domains the time delay can induce a failure of the Turing instability which cannot be predicted by a naive linear analysis of the underlying equations about the homogeneous steady state. The dramatic lag in the induction of patterning, or even its complete absence on occasions, highlights the importance of considering explicit gene expression time delays in models for cellular reaction diffusion patterning

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

Statistical Mechanics of Dilute Batch Minority Games with Random External Information

We study the dynamics and statics of a dilute batch minority game with random external information. We focus on the case in which the number of connections per agent is infinite in the thermodynamic limit. The dynamical scenario of ergodicity breaking in this model is different from the phase transition in the standard minority game and is characterised by the onset of long-term memory at finite integrated response. We demonstrate that finite memory appears at the AT-line obtained from the corresponding replica calculation, and compare the behaviour of the dilute model with the minority game with market impact correction, which is known to exhibit similar features.Comment: 22 pages, 6 figures, text modified, references updated and added, figure added, typos correcte

Quantum saturation and condensation of excitons in Cu2_2O: a theoretical study

Recent experiments on high density excitons in Cu$_2$O provide evidence for degenerate quantum statistics and Bose-Einstein condensation of this nearly ideal gas. We model the time dependence of this bosonic system including exciton decay mechanisms, energy exchange with phonons, and interconversion between ortho (triplet-state) and para (singlet-state) excitons, using parameters for the excitonic decay, the coupling to acoustic and low-lying optical phonons, Auger recombination, and ortho-para interconversion derived from experiment. The single adjustable parameter in our model is the optical-phonon cooling rate for Auger and laser-produced hot excitons. We show that the orthoexcitons move along the phase boundary without crossing it (i.e., exhibit a ``quantum saturation''), as a consequence of the balance of entropy changes due to cooling of excitons by phonons and heating by the non-radiative Auger two-exciton recombination process. The Auger annihilation rate for para-para collisions is much smaller than that for ortho-para and ortho-ortho collisions, explaining why, under the given experimental conditions, the paraexcitons condense while the orthoexcitons fail to do so.Comment: Revised to improve clarity and physical content 18 pages, revtex, figures available from G. Kavoulakis, Physics Department, University of Illinois, Urban

Modulation of Transmission Spectra of Anodized Alumina Membrane Distributed Bragg Reflector by Controlling Anodization Temperature

We have successfully prepared anodized alumina membrane distributed Bragg reflector (DBR) using electrochemical anodization method. The transmission peak of this distributed Bragg reflector could be easily and effectively modulated to cover almost any wavelength range of the whole visible spectrum by adjusting anodization temperature

Hemodynamic Effects of Anthrax Toxins in the Rabbit Model and the Cardiac Pathology Induced by Lethal Toxin

Anthrax lethal toxin (LeTx) and edema toxin (EdTx) have been shown to alter hemodynamics in the rodent model, while LeTx primarily is reported to induce extensive tissue pathology. However, the rodent model has limitations when used for comparison to higher organisms such as humans. The rabbit model, on the other hand, has gained recognition as a useful model for studying anthrax infection and its pathophysiological effects. In this study, we assessed the hemodynamic effects of lethal toxin (LeTx) and edema toxin (EdTx) in the rabbit model using physiologically relevant amounts of the toxins. Moreover, we further examine the pathological effects of LeTx on cardiac tissue. We intravenously injected Dutch-belted rabbits with either low-dose and high-dose recombinant LeTx or a single dose of EdTx. The animals’ heart rate and mean arterial pressure were continuously monitored via telemetry until either 48 or 72 h post-challenge. Additional animals challenged with LeTx were used for cardiac troponin I (cTnI) quantitation, cardiac histopathology, and echocardiography. LeTx depressed heart rate at the lower dose and mean arterial pressure (MAP) at the higher dose. EdTx, on the other hand, temporarily intensified heart rate while lowering MAP. Both doses of LeTx caused cardiac pathology with the higher dose having a more profound effect. Lastly, left-ventricular dilation due to LeTx was not apparent at the given time-points. Our study demonstrates the hemodynamic effects of anthrax toxins, as well as the pathological effects of LeTx on the heart in the rabbit model, and it provides further evidence for the toxins’ direct impact on the heart

Identification of CIITA Regulated Genetic Module Dedicated for Antigen Presentation

The class II trans-activator CIITA is a transcriptional co-activator required for the expression of Major Histocompatibility Complex (MHC) genes. Although the latter function is well established, the global target-gene specificity of CIITA had not been defined. We therefore generated a comprehensive list of its target genes by performing genome-wide scans employing four different approaches designed to identify promoters that are occupied by CIITA in two key antigen presenting cells, B cells and dendritic cells. Surprisingly, in addition to MHC genes, only nine new targets were identified and validated by extensive functional and expression analysis. Seven of these genes are known or likely to function in processes contributing to MHC-mediated antigen presentation. The remaining two are of unknown function. CIITA is thus uniquely dedicated for genes implicated in antigen presentation. The finding that CIITA regulates such a highly focused gene expression module sets it apart from all other transcription factors, for which large-scale binding-site mapping has indicated that they exert pleiotropic functions and regulate large numbers of genes