New fields on super Riemann surfaces

A new $(1,1)$-dimensional super vector bundle which exists on any super Riemann surface is described. Cross-sections of this bundle provide a new class of fields on a super Riemann surface which closely resemble holomorphic functions on a super Riemann surface, but which (in contrast to the case with holomorphic functions) form spaces which have a well defined dimension which does not change as odd moduli become non-zero.Comment: 12pp, kcl-th-94-

Metastability in Two Dimensions and the Effective Potential

We study analytically and numerically the decay of a metastable phase in (2+1)-dimensional classical scalar field theory coupled to a heat bath, which is equivalent to two-dimensional Euclidean quantum field theory at zero temperature. By a numerical simulation we obtain the nucleation barrier as a function of the parameters of the potential, and compare it to the theoretical prediction from the bounce (critical bubble) calculation. We find the nucleation barrier to be accurately predicted by theory using the bounce configuration obtained from the tree-level (``classical'') effective action. Within the range of parameters probed, we found that using the bounce derived from the one-loop effective action requires an unnaturally large prefactor to match the lattice results. Deviations from the tree-level prediction are seen in the regime where loop corrections would be expected to become important.Comment: 13pp, LaTex with Postscript figs, CLNS 93/1202, DART-HEP-93/0

Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA

Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA). During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG) cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS) biology. Keywords: nerve injury response; transcription; RNA epigenetics; antisense RNA; Egr2; myelination; YY1; neureguli

Ability of the National Surgical Quality Improvement Program Risk Calculator to Predict Complications Following Total Laryngectomy

Importance The accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator has been assessed in multiple surgical subspecialties; however, there have been no publications doing the same in the head and neck surgery literature. Objective To evaluate the accuracy of the calculator’s predictions in a single institution’s total laryngectomy (TL) population. Design, Setting, and Participants Total laryngectomies performed between 2013 and 2014 at a tertiary referral academic center were evaluated using the risk calculator. Predicted 30-day outcomes were compared with observed outcomes for return to operating room, surgical site infection, postoperative pneumonia, length of stay, and venous thromboembolism. Main Outcomes and Measures Comparison of the NSQIP risk calculator’s predicted postoperative complication rates and length of stay to what occurred in this patient cohort using percent error, Brier scores, area under the receiver operating characteristic curve, and Pearson correlation analysis. Results Of 49 patients undergoing TL, the mean (SD) age at operation was 59 (9.3) years, with 67% male. The risk calculator had limited efficacy predicting perioperative complications in this group of patients undergoing TL with or without free tissue reconstruction or preoperative chemoradiation or radiation therapy with a few exceptions. The calculator overestimated the occurrence of pneumonia by 165%, but underestimated surgical site infection by 7%, return to operating room by 24%, and length of stay by 13%. The calculator had good sensitivity and specificity of predicting surgical site infection for patients undergoing TL with free flap reconstruction (area under the curve, 0.83). For all other subgroups, however, the calculator had poor sensitivity and specificity for predicting complications. Conclusions and Relevance The risk calculator has limited utility for predicting perioperative complications in patients undergoing TL. This is likely due to the complexity of the treatment of patients with head and neck cancer and factors not taken into account when calculating a patient’s risk

Nanowired three-dimensional cardiac patches

Engineered cardiac patches for treating damaged heart tissues after a heart attack are normally produced by seeding heart cells within three-dimensional porous biomaterial scaffolds1, 2, 3. These biomaterials, which are usually made of either biological polymers such as alginate4 or synthetic polymers such as poly(lactic acid) (PLA)5, help cells organize into functioning tissues, but poor conductivity of these materials limits the ability of the patch to contract strongly as a unit6. Here, we show that incorporating gold nanowires within alginate scaffolds can bridge the electrically resistant pore walls of alginate and improve electrical communication between adjacent cardiac cells. Tissues grown on these composite matrices were thicker and better aligned than those grown on pristine alginate and when electrically stimulated, the cells in these tissues contracted synchronously. Furthermore, higher levels of the proteins involved in muscle contraction and electrical coupling are detected in the composite matrices. It is expected that the integration of conducting nanowires within three-dimensional scaffolds may improve the therapeutic value of current cardiac patches.National Institutes of Health (U.S.) (NIH, grant GM073626)National Institutes of Health (U.S.) (NIH, grant DE13023)National Institutes of Health (U.S.) (NIH, grant DE016516)American Heart Association (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award (no. F32GM096546)

Shear yielding of amorphous glassy solids: Effect of temperature and strain rate

We study shear yielding and steady state flow of glassy materials with molecular dynamics simulations of two standard models: amorphous polymers and bidisperse Lennard-Jones glasses. For a fixed strain rate, the maximum shear yield stress and the steady state flow stress in simple shear both drop linearly with increasing temperature. The dependence on strain rate can be described by a either a logarithm or a power-law added to a constant. In marked contrast to predictions of traditional thermal activation models, the rate dependence is nearly independent of temperature. The relation to more recent models of plastic deformation and glassy rheology is discussed, and the dynamics of particles and stress in small regions is examined in light of these findings

Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel

Differential expression of microRNAs (miRNAs) plays a role in many diseases, including cancer and cardiovascular diseases. Potentially, miRNAs could be targeted with miRNA-therapeutics. Sustained delivery of these therapeutics remains challenging. This study couples miR-mimics to PEG-peptide gold nanoparticles (AuNP) and loads these AuNP-miRNAs in an injectable, shear thinning, self-assembling polymer nanoparticle (PNP) hydrogel drug delivery platform to improve delivery. Spherical AuNPs coated with fluorescently labelled miR-214 are loaded into an HPMC-PEG-b-PLA PNP hydrogel. Release of AuNP/miRNAs is quantified, AuNP-miR-214 functionality is shown in vitro in HEK293 cells, and AuNP-miRNAs are tracked in a 3D bioprinted human model of calcific aortic valve disease (CAVD). Lastly, biodistribution of PNP-AuNP-miR-67 is assessed after subcutaneous injection in C57BL/6 mice. AuNP-miRNA release from the PNP hydrogel in vitro demonstrates a linear pattern over 5 days up to 20%. AuNP-miR-214 transfection in HEK293 results in 33% decrease of Luciferase reporter activity. In the CAVD model, AuNP-miR-214 are tracked into the cytoplasm of human aortic valve interstitial cells. Lastly, 11 days after subcutaneous injection, AuNP-miR-67 predominantly clears via the liver and kidneys, and fluorescence levels are again comparable to control animals. Thus, the PNP-AuNP-miRNA drug delivery platform provides linear release of functional miRNAs in vitro and has potential for in vivo applications.publishersversionpublishe

Radioluminescent nanoparticles for radiation-controlled release of drugs

The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO4 (CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30–40 fractions of 2–3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle (“PEG-PLA/CWO/PTX”) formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1 month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1 month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO4, or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols

Fluctuations and Bubble Dynamics in First-Order Phase Transitions

We numerically examine the effect of thermal fluctuations on a first-order phase transition in 2+1 dimensions. By focusing on the expansion of a single bubble we are able to calculate changes in the bubble wall's velocity as well as changes in its structure relative to the standard case where the bubble expands into a homogeneous background. Not only does the wall move faster, but the transition from the symmetric to the asymmetric phase is no longer smooth, even for a fairly strong transition. We discuss how these results affect the standard picture of electroweak baryogenesis.Comment: Latex, 30 pages, 11 ps figures, short discussion added in conclusions and minor clarifications, accepted to Phys Rev

Overestimating Resource Value and Its Effects on Fighting Decisions

Much work in behavioral ecology has shown that animals fight over resources such as food, and that they make strategic decisions about when to engage in such fights. Here, we examine the evolution of one, heretofore unexamined, component of that strategic decision about whether to fight for a resource. We present the results of a computer simulation that examined the evolution of over- or underestimating the value of a resource (food) as a function of an individual's current hunger level. In our model, animals fought for food when they perceived their current food level to be below the mean for the environment. We considered seven strategies for estimating food value: 1) always underestimate food value, 2) always overestimate food value, 3) never over- or underestimate food value, 4) overestimate food value when hungry, 5) underestimate food value when hungry, 6) overestimate food value when relatively satiated, and 7) underestimate food value when relatively satiated. We first competed all seven strategies against each other when they began at approximately equal frequencies. In such a competition, two strategies–“always overestimate food value,” and “overestimate food value when hungry”–were very successful. We next competed each of these strategies against the default strategy of “never over- or underestimate,” when the default strategy was set at 99% of the population. Again, the strategies of “always overestimate food value” and “overestimate food value when hungry” fared well. Our results suggest that overestimating food value when deciding whether to fight should be favored by natural selection