Solvent Induced Disulfide Bond Formation in 2,5-dimercapto-1,3,4-thiadiazole

Disulfide bond formation is the decisive event in the protein folding to determine the conformation and stability of protein. To achieve this disulfide bond formation in vitro, we took 2,5-dimercapto-1,3,4-thiadiazole (DMcT) as a model compound. We found that disulfide bond formation takes place between two sulfhydryl groups of DMcT molecules in methanol. UV-Vis, FT-IR and mass spectroscopic as well as cyclic voltammetry were used to monitor the course of reaction. We proposed a mechanism for the solvent induced disulfide bond formation on the basis of the results we obtained

Privatization with Political Constraints: Auctions versus Private Negotiations

This paper investigates the design of privatization mechanisms in emerging market economies characterized by political constraints that limit the set of viable privatization mechanisms. Our objective is to explain the striking diversity of privatization mechanisms observed in practice and the frequent use of an apparently suboptimal privatization mechanism: private negotiations. We develop a simple model wherein privatization is to be carried out by a government agent who plays favorites among bidders and is potentially disciplined by forthcoming elections. We find that it is the degree of political constraints that determines which mechanism is more successful in raising funds. If the political environment is such that the privatization agent himself aims at raising the fair value for the company, then privatization auctions and private negotiations are equally successful in raising public revenues. If, however, political constraints distort the agent’s incentives, then one mechanism outperforms the other. In particular, if the distortion is moderate, then private negotiations can raise more value for a successful enterprise than privatization auctions. In this case the agent may play favorites among the bidders, but to the extent he cares about the price, he will use his bargaining power to negotiate his target price. If, however, the distortion is severe so that the agent lacks sufficient motivation to raise a fair price for the company, then privatization auctions will outperform private egotiations. Even though the agent may play favorites among the bidders, he would not put pressure on the bidders to raise the price during negotiations. In an auction, in contrast, the presence of other bidders, regardless how informed they are, induces competition and places a lower bound on the equilibrium winning bid. We also show that information disclosure laws may have negative welfare implications: they may help the privatization agent to collude with some of the bidders to the disadvantage of non-colluding bidders. Our theory provides further regulatory implications for privatization procedures in emerging market economies

Lattice Boltzmann Model for Axisymmetric Multiphase Flows

In this paper, a lattice Boltzmann (LB) model is presented for axisymmetric multiphase flows. Source terms are added to a two-dimensional standard lattice Boltzmann equation (LBE) for multiphase flows such that the emergent dynamics can be transformed into the axisymmetric cylindrical coordinate system. The source terms are temporally and spatially dependent and represent the axisymmetric contribution of the order parameter of fluid phases and inertial, viscous and surface tension forces. A model which is effectively explicit and second order is obtained. This is achieved by taking into account the discrete lattice effects in the Chapman-Enskog multiscale analysis, so that the macroscopic axisymmetric mass and momentum equations for multiphase flows are recovered self-consistently. The model is extended to incorporate reduced compressibility effects. Axisymmetric equilibrium drop formation and oscillations, breakup and formation of satellite droplets from viscous liquid cylindrical jets through Rayleigh capillary instability and drop collisions are presented. Comparisons of the computed results with available data show satisfactory agreement.Comment: 17 pages, 11 figures, to be published in Physical Review

The Galaxy Populations of X-Ray Detected, Poor Groups

(Abridged) We determine the quantitative morphology and star formation properties of galaxies in six nearby X-ray detected, poor groups using multi-object spectroscopy and wide-field R imaging. We measure structural parameters for each galaxy by fitting a PSF-convolved, two component model to their surface brightness profiles. To compare directly the samples, we fade, smooth, and rebin each galaxy image so that we effectively observe each galaxy at the same redshift (9000 km/s) and physical resolution (0.87h^(-1) kpc). We compare results for the groups to a sample of field galaxies. We find that: 1) Galaxies spanning a wide range in morphological type and luminosity are well-fit by a de Vaucouleurs bulge with exponential disk profile. 2) Morphologically classifying these nearby group galaxies by their bulge fraction (B/T) is fairly robust on average, even when their redshift has increased by up to a factor of four and the effective resolution of the images is degraded by up to a factor of five. 3) The fraction of bulge-dominated systems in these groups is higher than in the field (~50% vs. ~20%). 4) The fraction of bulge-dominated systems in groups decreases with increasing radius, similar to the morphology-radius (~density) relation observed in galaxy clusters. 5) Current star formation in group galaxies is correlated with significant morphological asymmetry for disk-dominated systems (B/T<0.4). 6) The group galaxies that are most disk-dominated (B/T<0.2) are less star forming and asymmetric on average than their counterparts in the field.Comment: Accepted for publication in the Astrophysical Journal (26 pages + 12 figures); Figs 1 & 2 also available at http://www.ucolick.org/~vy/astronomy/groups_figs.tar.g

A comparison of resting state functional magnetic resonance imaging to invasive electrocortical stimulation for sensorimotor mapping in pediatric patients

Localizing neurologic function within the brain remains a significant challenge in clinical neurosurgery. Invasive mapping with direct electrocortical stimulation currently is the clinical gold standard but is impractical in young or cognitively delayed patients who are unable to reliably perform tasks. Resting state functional magnetic resonance imaging non-invasively identifies resting state networks without the need for task performance, hence, is well suited to pediatric patients. We compared sensorimotor network localization by resting state fMRI to cortical stimulation sensory and motor mapping in 16 pediatric patients aged 3.1 to 18.6 years. All had medically refractory epilepsy that required invasive electrographic monitoring and stimulation mapping. The resting state fMRI data were analyzed using a previously trained machine learning classifier that has previously been evaluated in adults. We report comparable functional localization by resting state fMRI compared to stimulation mapping. These results provide strong evidence for the utility of resting state functional imaging in the localization of sensorimotor cortex across a wide range of pediatric patients

Should we tweet this? Generative response modeling for predicting reception of public health messaging on Twitter

The way people respond to messaging from public health organizations on social media can provide insight into public perceptions on critical health issues, especially during a global crisis such as COVID-19. It could be valuable for high-impact organizations such as the US Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) to understand how these perceptions impact reception of messaging on health policy recommendations. We collect two datasets of public health messages and their responses from Twitter relating to COVID-19 and Vaccines, and introduce a predictive method which can be used to explore the potential reception of such messages. Specifically, we harness a generative model (GPT-2) to directly predict probable future responses and demonstrate how it can be used to optimize expected reception of important health guidance. Finally, we introduce a novel evaluation scheme with extensive statistical testing which allows us to conclude that our models capture the semantics and sentiment found in actual public health responses.Comment: Accepted at ACM WebSci 202

Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.

One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells in vitro. GUCY2C CAR-T cells provided long-term protection against lung metastases of murine colorectal cancer cells engineered to express human GUCY2C in a syngeneic mouse model. GUCY2C murine CAR-T cells recognized and killed human colorectal cancer cells endogenously expressing GUCY2C, providing durable survival in a human xenograft model in immunodeficient mice. Thus, we have identified a human GUCY2C-specific CAR-T cell therapy approach that may be developed for the treatment of GUCY2C-expressing metastatic colorectal cancer

Short-time preparation and electrochemical properties of a single layer of tetraoctylammonium bromide capped Au nanoparticles on dithiol self-assembled monolayer-modified Au electrode

Short time immobilization of densely packed tetraoctylammonium bromide (TOAB) stabilized gold nanoparticles (AuNPs) were established on a Au electrode modified with a self-assembled monolayer (SAM) of 1,6-hexanedithiol (HDT) or 1,4-benzenedimethanethiol (BDMT). The quartz crystal microbalance experiment showed densely packed TOAB-AuNPs single layer formation on both SAMs was achieved within 20 min. AFM images demonstrated that the immobilized TOAB-AuNPs on the SAMs were densely packed and the AuNPs film thickness was 6-7 nm. The electronic communication between the immobilized AuNPs and the underlying bulk electrode was confirmed by cyclic voltammetry and electroreflectance spectroscopy. A reversible electron transfer reaction was observed for both [Fe(CN)6]4-/3- and [Ru(NH3)6]2+/3+ at TOAB-AuNPs immobilized on HDT (Au/HDT/AuNPs) and BDMT (Au/BDMT/AuNPs) modified electrodes. The electroreflectance spectra show a red-shifted strong positive-going plasmon resonance bands at 551 nm and 584 nm, respectively, for the Au/BDMT/AuNPs and Au/HDT/AuNPs electrodes. The observed reversible redox response for the solution redox species and red-shifted plasmon resonance bands for the immobilized AuNPs again indicated that the AuNPs were immobilized on the SAMs in a densely packed manner. An advantage of TOAB-AuNPs modified electrode prepared by short time immersion over citrate-stabilized AuNPs modified electrode was demonstrated by the enhanced oxidation of ascorbic acid (AA) at these electrodes. The oxidation of AA was shifted to 90 mV less positive potential with higher oxidation current at TOAB-AuNPs modified electrode when compared to citrate-stabilized AuNPs modified electrode

Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.

Background: The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8+, but not CD4+, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice. Here, the cancer vaccine Ad5-GUCY2C-PADRE was evaluated in a first-in-man phase I clinical study of patients with early-stage colorectal cancer to assess its safety and immunological efficacy. Methods: Ten patients with surgically-resected stage I or stage II (pN0) colon cancer received a single intramuscular injection of 1011 viral particles (vp) of Ad5-GUCY2C-PADRE. Safety assessment and immunomonitoring were carried out for 6 months following immunization. This trial employed continual monitoring of both efficacy and toxicity of subjects as joint primary outcomes. Results: All patients receiving Ad5-GUCY2C-PADRE completed the study and none developed adverse events greater than grade 1. Antibody responses to GUCY2C were detected in 10% of patients, while 40% exhibited GUCY2C-specific T-cell responses. GUCY2C-specific responses were exclusively CD8+ cytotoxic T cells, mimicking pre-clinical studies in mice in which GUCY2C-specific CD4+ T cells are eliminated by self-tolerance, while CD8+ T cells escape tolerance and mediate antitumor immunity. Moreover, pre-existing neutralizing antibodies (NAbs) to the Ad5 vector were associated with poor vaccine-induced responses, suggesting that Ad5 NAbs oppose GUCY2C immune responses to the vaccine in patients and supported by mouse studies. Conclusions: Split tolerance to GUCY2C in cancer patients can be exploited to safely generate antigen-specific cytotoxic CD8+, but not autoimmune CD4+, T cells by Ad5-GUCY2C-PADRE in the absence of pre-existing NAbs to the viral vector. TRIAL REGISTRATION: This trial (NCT01972737) was registered at ClinicalTrials.gov on October 30th, 2013. https://clinicaltrials.gov/ct2/show/NCT01972737