Multiple M2 Research Articles

756 Effects of Bioengineered Allogeneic Cellular Constructs on Macrophage Phenotype in the Context of Burns

Abstract Introduction The persistent inflammatory and stress responses generate in burn patients have a strong effect on the immune system. Macrophages that are activated in response to burn injuries polarize towards an immunosuppressive phenotype commonly known as M2b. Furthermore, due to sepsis, the chronic exposure to the pro-inflammatory environment also leads to an exhausted macrophage phenotype. Together these effects compromise macrophage behavior that influences the healing outcome. In clinical trials, bioengineered allogeneic cellular constructs (BACCs) have shown potential in promoting healing in patients with deep partial thickness burns. However, the mechanism(s) behind these successful effects are not totally understood yet. For this reason, the aim of this study is to investigate how the crosstalk with the BACC influence different burn-related macrophage phenotype. Methods Primary human macrophages (N=4 healthy donors) were co-cultured with the BACC or collagen controls. Macrophages were isolated over 6 days of co-culture and their RNA was extracted for gene expression analysis, and conditioned media was collected to analyze the secretion of proteins. To assess phenotype changes, we performed gene set analysis using single sample gene set enrichment. To investigate changes in the phenotype of macrophages relevant to burn wounds macrophages were polarized to the immune suppressive M2b phenotype or LPS-exhausted phenotypes before co-culturing them with the BACC. Undifferentiated macrophages (M0) were used as controls. Results Gene expression analysis revealed a shift in undifferentiated macrophage phenotype towards an M2 phenotype by day 3 and 6 in co-culture as demonstrated by an increase in the expression of multiple M2 genes, including MRC1 and CCL18. Secretory analysis revealed a decrease in the secretory of inflammatory proteins, like interleukin 6. Conclusions Collectively these results demonstrate that BACCs promote the transition of macrophage phenotype towards a pro-reparative M2 phenotype which may contribute to the construct’s pro-healing capabilities. Applicability of Research to Practice This study provides insight into the mechanism by which BACCs promote healing in the burn wound environment.

The Effect of Psychological Intervention on the Visual Quality of Patients with a Diffractive Multifocal Intraocular Lens Implant.

This study aimed to investigate the effect of psychological intervention on the visual quality of patients with a diffractive multifocal intraocular lens implant and its possible mechanism. Eighty-nine patients undergoing age-related cataract surgery were enrolled in the study at the Affiliated Hospital of Southwest Medical University between December 2015 and July 2017. They were randomly divided into two groups: multiple focus M1 group (n = 45) and multiple focus M2 group (n = 40). The M1 group was only given routine preoperative health education, treatment, and evaluation, while the M2 group also received psychological intervention. After treatment, there was no statistical difference in the uncorrected distance and near visual acuity, corrected distance and near visual acuity, or the vision and near removal rate in either of the two groups (p > 0.05). However, postoperative glare was lower in the M2 group (p < 0.05), and patient satisfaction was higher in the M2 group (p < 0.05). The M2 group had a more obvious improvement in the Symptom Checklist-90 score (p < 0.05), the serum interleukin-6 (IL-6) was lower, and the serum brain-derived neurotrophic factor (BDNF) was higher in the M2 group (p < 0.05). In addition, serum IL-6 had a negative correlation with the depression score, and serum BDNF also showed a negative correlation with the anxiety score (p < 0.05). Psychological intervention improved the stress state of patients with age-related cataracts and diffractive multifocal intraocular lens implants, reduced the level of inflammatory factors in the body, improved the level of BDNF, reduced postoperative visual interference, and improved postoperative satisfaction.

Amantadine variant – aryl conjugates that inhibit multiple M2 mutant – amantadine resistant influenza a viruses

Influenza A viruses can cause a serious future threat due to frequent mutations. Amantadine and rimantadine drugs inhibit influenza A M2 wild-type (WT; bearing in the protein M2 proton channel serine at position-31) viruses by binding and blocking M2 WT channel-mediated proton current. The resistant to these drugs influenza A viruses bearing the S31N mutant in the M2 proton channel can be inhibited by amantadine – aryl conjugates, in which amantadine and an aryl group are linked through a methylene, which block M2 S31N channel-mediated proton current. However, the M2 amantadine/rimantadine resistant viruses bearing one of the four mutations L26F, V27A, A30T, G34E in residues that line the M2 channel pore pose an additional concern for public health.Here, we designed 33 compounds based on the structure of three previously published and potent amantadine-aryl conjugates against M2 S31N virus, by replacing amantadine with 16 amantadine variants. The compounds were tested against M2 WT and the five M2 amantadine resistant viruses aiming at identifying inhibitors against multiple M2 mutant – amantadine resistant viruses.We identified 16 compounds that inhibited in vitro two influenza A viruses with M2 WT or L26F channels. Additionally, compounds 21 or 32 or 33, which are conjugates of the rimantadine variant with CMe2 (instead of CHMe in rimantadine) or the diamantylamine or the 4-(1-adamantyl)benzenamine with the 2-hydroxy-4-methoxyphenyl aryl group, were in vitro inhibitors against three influenza A viruses with M2 WT or L26F or S31N, while compound 21 inhibited also in vitro the M2 G34E virus and compound 32 inhibited also in vitro the M2 A30T virus. Also, using electrophysiology, we showed that compound 21 was an efficient blocker of the M2 WT and M2 L26F channels, compound 32 blocked efficiently the M2 WT channel and compound 33 blocked the M2 WT, L26F and V27A channels. The drug metabolism and pharmacokinetics studies showed that these compounds need further optimization.

Trophoblast-derived IL-6 serves as an important factor for normal pregnancy by activating Stat3-mediated M2 macrophages polarization

Macrophages are major components of decidual microenvironment that play an important role in human implantation and placentation. Trophoblasts which migrate into the endometrium and interplay with decidual cells, have been reported to participate in the polarization of macrophages. However, the potential mechanisms of trophoblasts modulating M2 macrophages polarization still need further exploration. Herein, we used the co-cultured model to investigate the interaction between macrophages and trophoblasts. Our results illustrated that when co-cultured with trophoblasts, macrophages tended to polarize to M2-subtype, accompanied by increased expression of multiple M2 markers including CD206 and CCL18 mRNA expression and IL-10 and TGF-β protein level. Further experiments identified that trophoblast-derived IL-6, as the major contributor, promoted M2 macrophages polarization by activating Stat3 pathway. Moreover, activated M2 macrophages exerted a promoting role in the invasion and migration of trophoblasts in a feedback manner. Clinically, results from histology demonstrated that IL-6 expression in placental villous tissues was positive correlated with CD206-positive macrophage infiltration in decidua in normal pregnancy patients. Altogether, our findings indicate that trophoblasts induce M2 macrophages polarization via IL-6/Stat3 signal pathway, which in turn promote the invasion and migration of trophoblasts. These results provide insights into the crosstalk between macrophages and trophoblasts at maternal-fetal microenvironment in normal pregnancy.

SPI Implementation Based on M2e Microprocessor

Normally, the computer reads, writes and other control operations on the M2 board through the UART protocol. Our goal is to achieve control of the M2 board through the SPI protocol. The specific implementation is to use an M2 board (Master M2) as an intermediary to achieve control of the target M2 board (Slave M2). The communication between the user computer and the Master M2 still uses the UART protocol. The SPI protocol is used between the Master M2 and the Slave M2. The read/write and other operations of the Slave M2 board no longer need to occupy the UART resources of the user's computer, which eliminates the inconvenience of connecting two computers at the same time. In the case where data transmission is required for multiple M2 boards at the same time, a solution for improving efficiency and reducing cost is provided.

Phase, current, absorbance, and photoluminescence of double and triple metal ion-doped synthetic and salmon DNA thin films

We fabricated synthetic double-crossover (DX) DNA lattices and natural salmon DNA (SDNA) thin films, doped with 3 combinations of double divalent metal ions (M2+)-doped groups (Co2+–Ni2+, Cu2+–Co2+, and Cu2+–Ni2+) and single combination of a triple M2+-doped group (Cu2+–Ni2+–Co2+) at various concentrations of M2+ ([M2+]). We evaluated the optimum concentration of M2+ ([M2+]O) (the phase of M2+-doped DX DNA lattices changed from crystalline (up to ([M2+]O) to amorphous (above [M2+]O)) and measured the current, absorbance, and photoluminescent characteristics of multiple M2+-doped SDNA thin films. Phase transitions (visualized in phase diagrams theoretically as well as experimentally) from crystalline to amorphous for double (Co2+–Ni2+, Cu2+–Co2+, and Cu2+–Ni2+) and triple (Cu2+–Ni2+–Co2+) dopings occurred between 0.8 mM and 1.0 mM of Ni2+ at a fixed 0.5 mM of Co2+, between 0.6 mM and 0.8 mM of Co2+ at a fixed 3.0 mM of Cu2+, between 0.6 mM and 0.8 mM of Ni2+ at a fixed 3.0 mM of Cu2+, and between 0.6 mM and 0.8 mM of Co2+ at fixed 2.0 mM of Cu2+ and 0.8 mM of Ni2+, respectively. The overall behavior of the current and photoluminescence showed increments as increasing [M2+] up to [M2+]O, then decrements with further increasing [M2+]. On the other hand, absorbance at 260 nm showed the opposite behavior. Multiple M2+-doped DNA thin films can be used in specific devices and sensors with enhanced optoelectric characteristics and tunable multi-functionalities.

Evaluation of the prevalence of digital dermatitis and the effects on performance in beef feedlot cattle under organic trace mineral supplementation.

Bovine digital dermatitis (DD) is a contagious and multifactorial disease that leads to painful, ulcerative lesions of the skin near the heel-horn border of the foot, most commonly in dairy cattle. With regard to beef cattle, the pathogenesis and etiology of DD has not been widely reported or studied over the past several decades. A longitudinal field trial in a commercial feedlot was conducted to compare prevalence and effects of DD in beef steers provided a diet supplemented with a novel formulation of inorganic and organic trace mineral sources (OTM diet) compared to a diet provided with similar levels of trace minerals solely from inorganic sources (CON diet). A secondary objective was to evaluate the prevalence of DD and the potential effects on growth performance and carcass yield and quality. One thousand seventy-seven steers were assigned to 1 of the 2 treatment groups (CON diet or OTM diet) based on location of their home pens which were situated in 1 of 2 barns. All pens in the B barn (group B) were assigned to the OTM diet, and all pens in the A barn (group A) were assigned to the CON diet. The study was conducted in 2 phases: adaptation phase (AP) comprising the initial 60 d of feeding CON and OTM diets and postadaptation phase (PAP) which lasted until cattle were sent to harvest. In the AP, pens in group B had a greater proportion of steers (54.03%) with DD lesions compared to pens in group A (26.72%). During the PAP, the relative risk of observing an increased DD prevalence was significantly ( < 0.05) higher in CON group compared to OTM group. Growth performance, final live weight, and hot carcass weight were negatively impacted when steers were observed to have active DD lesions (M2 lesions) compared to steers with no M2 lesions over the study period. For ADG, a calculated loss per steer of 0.08 kg/d from type I (no M2 lesions) to type II (one M2 lesion; SE = 0.028; = 0.003) and loss of 0.14 kg/d from type I to type III (multiple M2 lesions; SE = 0.038; = 0.0003) were observed. A significant BW loss of approximately 10.06 kg (SE = 4.18; = 0.022) and a mean reduction of 5.5 kg per steer in HCW (SE = 2.74; = 0.043) were also found between type I and type II steers.

3-D printing seeks commercial markets

Companies that make three-dimensional printers are coming out with new products that they hope will jumpstart demand from the manufacturing sector. Although sales of consumer and desktop versions grew briskly last year, the same was not true for pricier machines geared to industry. At last week’s Additive Manufacturing Users Group conference, held in Chicago, start-up Carbon introduced the M2, which the firm says is a robust, industrial-grade machine with a higher capacity than its first model. Multiple M2 printers can be strung together and linked to a component that automatically washes and finishes the objects. Similarly, a new, larger printer from 3D Systems can produce plastic parts at 50 times the rate of its current systems, according to the company. It also includes a part-washing unit. 3D Systems was the first company to commercialize the popular stereolithography method of 3-D printing, which uses ultraviolet light to cure photosensitive polymers. The

Endovascular Therapy of M2 Occlusion in IMS III: Role of M2 Segment Definition and Location on Clinical and Revascularization Outcomes.

Uncertainty persists regarding the safety and efficacy of endovascular therapy of M2 occlusions following IV tPA. We reviewed the impact of revascularization on clinical outcomes in 83 patients with M2 occlusions in the Interventional Management of Stroke III trial according to specific M1-M2 segment anatomic features. Perfusion of any M2 branch distinguished M2-versus-M1 occlusion. Prespecified modified TICI and arterial occlusive lesion revascularization and clinical mRS 0-2 end points at 90 days for endovascular therapy-treated M2 occlusions were analyzed. Post hoc analyses of the relationship of outcomes to multiple baseline angiographic M2 and M1 subgroup characteristics were performed. Of 83 participants with M2 occlusion who underwent endovascular therapy, 41.0% achieved mRS 0-2 at 90 days, including 46.6% with modified TICI 2-3 reperfusion compared with 26.1% with modified TICI 0-1 reperfusion (risk difference, 20.6%; 95% CI, -1.4%-42.5%). mRS 0-2 outcome was associated with reperfusion for M2 trunk (n = 9) or M2 division (n = 42) occlusions, but not for M2 branch occlusions (n = 28). Of participants with trunk and division occlusions, 63.2% with modified TICI 2a and 42.9% with modified TICI 2b reperfusion achieved mRS 0-2 outcomes; mRS 0-2 outcomes for M2 trunk occlusions (33%) did not differ from distal (38.2%) and proximal (26.9%) M1 occlusions. mRS 0-2 at 90 days was dependent on reperfusion for M2 trunk but not for M2 branch occlusions. For M2 division occlusions, good outcome with modified TICI 2b reperfusion did not differ from that in modified TICI 2a. M2 segment definition and occlusion location may contribute to differences in revascularization and good outcome between Interventional Management of Stroke III and other endovascular therapy studies.

Influenza A M2 protein conformation depends on choice of model membrane.

While crystal and NMR structures exist of the influenza A M2 protein, there is disagreement between models. Depending on the requirements of the technique employed, M2 has been studied in a range of membrane mimetics including detergent micelles and membrane bilayers differing in lipid composition. The use of different model membranes complicates the integration of results from published studies necessary for an overall understanding of the M2 protein. Here we show using site-directed spin-label EPR spectroscopy (SDSL-EPR) that the conformations of M2 peptides in membrane bilayers are clearly influenced by the lipid composition of the bilayers. Altering the bilayer thickness or the lateral pressure profile within the bilayer membrane changes the M2 conformation observed. The multiple M2 peptide conformations observed here, and in other published studies, optimistically may be considered conformations that are sampled by the protein at various stages during influenza infectivity. However, care should be taken that the heterogeneity observed in published structures is not simply an artifact of the choice of the model membrane.

Survey of Human Antibody Responses to Influenza Virus Matrix Protein 2 by Use of a Sensitive Flow Cytometric Method

Conventional influenza vaccines are designed to elicit antibodies to strainspecific antigens, leaving a public health gap when novel viruses break out unexpectedly. As examples, strain-matched vaccine became available too late in the pandemic of 2009 to protect against the fall wave, and drift viruses are sometimes divergent enough to cause vaccine failure (eg, A/Sydney in 1997). Available vaccines are also inadequate to protect against various zoonotic strains, including avian influenza A(H5N1), influenza A(H7N7), and most recently influenza A(H7N9). For this reason, there is much interest in developing vaccines based on conserved influenza virus features that can provide protection regardless of strain. These are usually designed for influenza A virus, but such vaccines can also be made for influenza B virus. Universal influenza vaccines can induce immune protection dependent upon antibody or T-cell responses or both, and the target antigens explored have included nucleoprotein, matrix proteins (M1 and M2), the hemagglutinin (HA) stem, polymerase PB1, and other antigens, as reviewed previously [1]. M2, the focus of Zhong et al in the current issue of the Journal, has long been known as a target of antibodies that reduce viral replication and spread [2, 3]. Vaccines based on many forms of M2 (fusion proteins, M2 multiple antigenic peptides, peptide conjugates, and M2 expressed from viral vectors) provide protective immunity in animals [4–10], and some have been tested in humans. A clinical trial of recombinant M2 shows that this antigen is immunogenic when administered with adjuvant [11]. Human anti-M2 antibodies induced by natural infection have been reported, but data are scanty. Black et al reported that 6 of 17 pairs of acute-phase and convalescent-phase serum specimens showed increased anti-M2 activity by enzyme-linked immunosorbent assay (ELISA), while 12 of 17 convalescent-phase serum specimens demonstrated some signal by Western blot [12]. In a study by Feng et al, an increase in anti-M2 activity was found for 11 of 24 such serum pairs [13]. In that study, of the antibodies detectable by assay on cell surface tetrameric M2, only a minority also recognized M2e peptide. Thus, the majority of antibodies appeared to be conformational [13]. These antibodies may be biologically very important, so assays on native M2 are needed. However, measuring antibodies to native M2 has presented technical problems, with high background encountered in cell surface ELISA. To overcome these problems, Zhong et al developed a flow cytometric assay (M2-FCA) using a panel of 293FT transfected cell lines (M2-293FT) stably expressing full-length tetrameric forms of M2 from various viral strains [14]. With this sensitive assay, some mouse antibodies recognize strain-specific epitopes and some see epitopes cross-reactive among viral strains [14]. The present article uses the assay to analyze collections of human sera. Transfection efficiency and expression levels are normalized through the use of a positive human serum pool as a control. Unlike most serological assays in which a titer reflects the dilution at which a defined end point is reached, the unit of M2 antibody is defined for a single (1:40) dilution of serum. This allows large numbers of sera to be analyzed within a single run, but does not measure titers or other antibody properties revealed by dilution series. Results for healthy donors of different ages showed that antibodies to M2 were found in a higher percentage of, and at higher levels, in adults aged ≥40 years, compared with younger donors. If anti-M2 antibodies were present, they usually recognized both seasonal and swine-origin M2. Received 5 December 2013; accepted 5 December 2013. Correspondence: Suzanne Epstein, PhD, OCTGT, CBER, FDA, 1401 Rockville Pk, HFM-730, Rockville, MD 20852-1448 (suzanne.epstein@fda.hhs.gov). The Journal of Infectious Diseases Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/infdis/jit813

Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection

The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.

Fuzzy Kaluza–Klein induced M2ʼs from a single M5

We propose an algorithmic procedure of obtaining multiple M2 brane dynamics starting with an action of a single M5 brane. The procedure involves a novel Kaluza–Klein reduction. First, the M5 brane action is truncated to keep a few leading terms in the derivative expansion. Then 3 + 3 splitting of dimensions is carried out. With expansion in terms of the S 2 spherical harmonics, the fields are associated with SU ( N ) (or its infinite extension) gauge algebra. We present an elaborate reduction procedure that leads to ABJM theory when the fuzzy spherical harmonics are replaced by SU ( N ) gauge generators.

On the spectral properties of multi‐branes, M2 and M5 branes

AbstractIn this note we summarize some of the properties found in [1–3]. We characterize spectral properties of the quantum mechanical hamiltonian of theories with fermionic degrees of freedom beyond semiclassical approximation. We obtain a general class of bosonic polynomial potentials for which the Schröedinger operator has a discrete spectrum. This class includes all the scalar potentials in membrane, 5‐brane, p‐branes, multiple M2 branes, BLG and ABJM theories. We also give a sufficient condition for discreteness of the spectrum for supersymmmetric and non supersymmetric theories with a fermionic contribution. We characterize then the spectral properties of different theories: the BMN matrix model, the supermembrane with central charges and a bound state of N D2 with m D0. We show that, while the first two models have a purely discrete spectrum with finite multiplicity, the latter has a continuous spectrum starting from a constant given in terms of the monopole charge.

Open M2-branes with flux and the modified Basu–Harvey equation

The supersymmetric actions of closed multiple M2 branes with flux for the Bagger–Lambert (BL) and ABJM theories have been constructed recently by Lambert and Richmond (2009 J. High Energy Phys. JHEP10(2009)084). In this paper, we extend the construction to the case of open M2-branes with flux and derive the boundary conditions. This allows us to derive the modified Basu–Harvey equation in the presence of flux. As an example, we consider the Lorentzian BL model. A new feature of the fuzzy funnel solution describing a D2–D4 intersection is obtained as a result of the flux.

Spectral analysis of polynomial potentials and its relation with ABJ/M-type theories

We obtain a general class of polynomial potentials for which the Schrödinger operator has a discrete spectrum. This class includes all the scalar potentials in membrane, 5-brane, p-branes, multiple M2 branes, BLG and ABJM theories. We provide a proof of the discreteness of the spectrum of the associated Schrödinger operators. This is the first step in order to analyze BLG and ABJM supersymmetric theories from a non-perturbative point of view.

Identification of Hits as Matrix-2 Protein Inhibitors through the Focused Screening of a Small Primary Amine Library

Although amantadine derivatives are the only M2 drugs for influenza virus A, their use is limited in the U.S. because of drug resistance. Here we report the identification of multiple M2 inhibitors that were rapidly generated through focused screening of a small primary amine library that was designed using a scaffold-hopping strategy based on amantadine. These compounds are as active as amantadine and might be hits for further lead generation processes.

Dynamic, M2-Like Remodeling Phenotypes of CD11c+ Adipose Tissue Macrophages During High-Fat Diet–Induced Obesity in Mice

OBJECTIVETo identify, localize, and determine M1/M2 polarization of epidydimal adipose tissue (eAT) macrophages (Φs) during high-fat diet (HFD)-induced obesity.RESEARCH DESIGN AND METHODSMale C57BL/6 mice were fed an HFD (60% fat kcal) or low-fat diet (LFD) (10% fat kcal) for 8 or 12 weeks. eATMΦs (F4/80+ cells) were characterized by in vivo fluorescent labeling, immunohistochemistry, fluorescence-activated cell sorting, and quantitative PCR.RESULTSRecruited interstitial macrophage galactose-type C-type lectin (MGL)1+/CD11c− and crown-like structure–associated MGL1−/CD11c+ and MGL1med/CD11c+ eATMΦs were identified after 8 weeks of HFD. MGL1med/CD11c+ cells comprised ∼65% of CD11c+ eATMΦs. CD11c+ eATMΦs expressed a mixed M1/M2 profile, with some M1 transcripts upregulated (IL-12p40 and IL-1β), others downregulated (iNOS, caspase-1, MCP-1, and CD86), and multiple M2 and matrix remodeling transcripts upregulated (arginase-1, IL-1Ra, MMP-12, ADAM8, VEGF, and Clec-7a). At HFD week 12, each eATMΦ subtype displayed an enhanced M2 phenotype as compared with HFD week 8. CD11c+ subtypes downregulated IL-1β and genes mediating antigen presentation (I-a, CD80) and upregulated the M2 hallmark Ym-1 and genes promoting oxidative metabolism (PGC-1α) and adipogenesis (MMP-2). MGL1med/CD11c+ eATMΦs upregulated additional M2 genes (IL-13, SPHK1, CD163, LYVE-1, and PPAR-α). MGL1med/CD11c+ ATMΦs expressing elevated PGC-1α, PPAR-α, and Ym-1 transcripts were selectively enriched in eAT of obese mice fed pioglitazone for 6 days, confirming the M2 features of the MGL1med/CD11c+ eATMΦ transcriptional profile and implicating PPAR activation in its elicitation.CONCLUSIONSThese results 1) redefine the phenotypic potential of CD11c+ eATMΦs and 2) suggest previously unappreciated phenotypic and functional commonality between murine and human ATMΦs in the development of obesity and its complications.

Large-Nreduced models of supersymmetric quiver, Chern-Simons gauge theories and ABJM

Using the Eguchi-Kawai equivalence, we provide regularizations of supersymmetric quiver and Chern-Simons gauge theories which leave the supersymmetries unbroken. This allow us to study many interesting theories on a computer. As examples we construct large-$N$ reduced models of supersymmetric QCD with flavor and the ABJM model of multiple M2 branes.

Discovery of multiple lead compounds as M2 inhibitors through the focused screening of a small primary amine library.

AbstractThe discovery of new anti-influenza drugs is urgent, particularly considering the recent threat of swine flu. In this study, the influenza virus M2 protein was expressed in HEK293 cells and shown to have selective ion channel activity for monovalent ions. The anti-influenza virus drug amantadine hydrochloride significantly attenuated the inward current induced by hyperpolarization of HEK293 cell membranes. Although adamantine derivatives are the only M2 drugs for influenza virus A, their use is limited in the US due to drug resistance. Here we report the discovery of multiple M2 inhibitor lead compounds that were rapidly generated through focused screening of a small primary amine library. The screen was designed using a scaffold-hopping strategy based on amantadine. This study suggests that an antiviral compound directed against a conserved motif may be more useful than amantadine in inhibiting viral replication.