Molecular Dynamics Simulations of the O-glycosylated 21-residue MUC1 Peptides

The conformational propensities of the 21-residue peptide and its Oglycosylated analogs were studied by molecular dynamics (MD) simulations. This polypeptide motif comprises the tandem repeat of the human mucin (MUC1) protein core that is differently glycosylated in normal and cancer cells. To evaluate the structural effects of O-glycosylation on the polypeptide backbone, conformations of the nonglycosylated peptide and its glycosylated analogs were monitored during the 1 ns MD simulations. Radius gyration for whole peptide and its fragments, as well as root-mean-square-deviation between coordinate sets of the backbone atoms of starting structures and generated structures, were calculated. It was shown that O-glycosylation promotes and stabilizes the extended conformations of the whole peptide and its central PDTRP fragment. O-glycosylation of the specific Thr residues significantly affects the conformational distributions of the flanking Ser residues. It was also shown that Oglycosylation promoted backbone conformations of the immunodominant region PDTRP that were similar to the structural features of the peptides presented by the major histocompatability complex (MHC) to T-cell receptors Keywords: glycoprotein MUC1, glycopeptides, molecular dynamics, conformations

Dynamic multilateral markets

We study dynamic multilateral markets, in which players' payoffs result from intra-coalitional bargaining. The latter is modeled as the ultimatum game with exogenous (time-invariant) recognition probabilities and unanimity acceptance rule. Players in agreeing coalitions leave the market and are replaced by their replicas, which keeps the pool of market participants constant over time. In this infinite game, we establish payoff uniqueness of stationary equilibria and the emergence of endogenous cooperation structures when traders experience some degree of (heterogeneous) bargaining frictions. When we focus on market games with different player types, we derive, under mild conditions, an explicit formula for each type's equilibrium payoff as the market frictions vanish

Thermopower peak in phase transition region of (1-x)La2/3_{2/3}Ca1/3_{1/3}MnO3_{3}/xYSZ

The thermoelectric power (TEP) and the electrical resistivity of the intergranular magnetoresistance (IGMR) composite, (1-x)La$_{2/3}$Ca$_{1/3}$MnO$_{3}$/xYSZ (LCMO/YSZ) with x = 0, 0.75%, 1.25%, 4.5%, 13% 15% and 80% of the yttria-stabalized zirconia (YSZ), have been measured from 300 K down to 77 K. Pronounced TEP peak appears during the phase transition for the samples of x $>$ 0, while not observed for x = 0. We suggest that this is due to the magnetic structure variation induced by the lattice strain which is resulting from the LCMO/YSZ boundary layers. The transition width in temperature derived from $d\chi/dT$, with $\chi$ being the AC magnetic susceptibility, supports this interpretation.Comment: 4 pages, 4 eps figures, Latex, J. Appl. Phys 94, 7206 (2003

End of Life: A Family Narrative

This paper is based on ethnographic research that examines family reaction to an elderly husband and father's end of life. From a group of 30 families in our study (family defined as a widow aged 70 and over and two adult biological children between the ages of 40 and 60), we offer an extreme case example of family bereavement. We report our findings through the open-ended responses of a widow and two children who were interviewed ten months after the death of the husband and father. Three general themes emerged: (1) how the family imputes meaning to the end of life, (2) changes in the roles of family members, and (3) the family's ways of coping with the death, particularly through their belief system. A key finding is that the meaning family members find in their loved one's death is tied to the context of his death (how and where he died), their perception of his quality of life as a whole, and their philosophical, religious, and spiritual beliefs about life, death, and the afterlife that are already in place

Induced earthquake families reveal distinctive evolutionary patterns near disposal wells

The timing of events in seismic sequences can provide insights into the physical processes controlling fault slip. In southern Kansas, the rate of earthquakes rose rapidly starting in 2013 following expansion of energy production into the area, demanding the disposal of large volumes of wastewater into deep wells. Seismicity catalogs that are complete to low magnitudes can provide insights into the physical processes that induce seismicity near wastewater disposal. We develop a catalog of over 130,000 earthquakes recorded in southern Kansas from mid‐March 2014 through December 2017 by applying a matched filter algorithm to an original catalog of 5,831 template earthquakes. Detections have nearly identical waveforms to their associated template event and represent slip on nearly co‐located sections of a fault. We select template events with at least 100 associated detections and examine the characteristics of these prolific families of earthquakes. We find that families located close (<10 km) to areas with significant volumes of injected fluids have near‐Poissonian interevent times and the families remain active over longer durations. Families farther from high‐volume injection wells show strong clustering of interevent times and shorter sequence durations. We conclude that increasing pore fluid pressures from nearby disposal of large volumes of wastewater is the primary driver of these long duration episodes, with earthquake‐earthquake interactions driving sequences at greater distance from the wells

Shear flow effects on phase separation of entangled polymer blends

We introduce an entanglement model mixing rule for stress relaxation in a polymer blend to a modified Cahn-Hilliard equation of motion for concentration fluctuations in the presence of shear flow. Such an approach predicts both shear-induced mixing and demixing, depending on the relative relaxation times and plateau moduli of the two components

5-HT obesity medication efficacy via POMC activation is maintained during aging

Peer reviewedPublisher PD

Signaling about norms: socialization under strategic uncertainty

We consider a signaling model where adults possess information about the dominant social norm. Children want to conform to whatever norm is dominant but, lacking accurate information, take the observed behavior of their parent as representative. We show that this causes a signaling distortion in adult behavior, even in the absence of conflicts of interest. Parents adopt attitudes that encourage their children to behave in a socially safe way, i.e. the way that would be optimal under maximum uncertainty about the prevailing social norm. We discuss applications to sexual attitudes, collective reputation, and trust

Chaotic motion of space charge wavefronts in semiconductors under time-independent voltage bias

A standard drift-diffusion model of space charge wave propagation in semiconductors has been studied numerically and analytically under dc voltage bias. For sufficiently long samples, appropriate contact resistivity and applied voltage - such that the sample is biased in a regime of negative differential resistance - we find chaos in the propagation of nonlinear fronts (charge monopoles of alternating sign) of electric field. The chaos is always low-dimensional, but has a complex spatial structure; this behavior can be interpreted using a finite dimensional asymptotic model in which the front (charge monopole) positions and the electrical current are the only dynamical variables.Comment: 12 pages, 8 figure

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss