Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide

Background: The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial KATP channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic KATP channels less than does Glib. We examined the effects of Glim on IP and on the protection afforded by diazoxide (Diaz), an opener of mitochondrial KATP channels. Methods and results: Rat hearts were Langendorff-perfused, subjected to 35 minutes of regional ischemia and 120 minutes of reperfusion, and assigned to 1 of the following treatment groups: (1) control; (2) IP of 2x 5 minutes each of global ischemia before lethal ischemia; or pretreatment with (3) 30 µmol/L Diaz, (4) 10 µmol/L Glim, (5) 10 µmol/L Glib, (6) IP+Glim, (7) IP+Glib, (8) Diaz+Glim, or (9) Diaz+Glib. IP limited infarct size (18.5±1% vs 43.7±3% in control, P<0.01) as did Diaz (22.2±4.7%, P<0.01). The protective actions of IP or Diaz were not abolished by Glim (18.5±3% in IP+Glim, 22.3±3% in Diaz+Glim; P<0.01 vs control). However, Glib abolished the infarct-limiting effects of IP and Diaz. Patch-clamp studies in isolated rat ventricular myocytes confirmed that both Glim and Glib (each at 1 µmol/L) blocked sarcolemmal KATP currents. However, in isolated cardiac mitochondria, Glim (10 µmol/L) failed to block the effects of KATP opening by GTP, in contrast to the blockade caused by Glib. Conclusions: Although it blocks sarcolemmal currents in rat cardiac myocytes, Glim does not block the beneficial effects of mitochondrial KATP channel opening in the isolated rat heart. These data may have significant implications for the treatment of type 2 diabetes in patients with ongoing ischemic heart disease

Partitions with Prescribed Hook Differences

We investigate partition identities related to off-diagonal hook differences. Our results generalize previous extensions of the Rogers—Ramanujan identities. The identity of the related polynomials with constructs in statistical mechanics is discussed

Extended scaling relations for planar lattice models

It is widely believed that the critical properties of several planar lattice models, like the Eight Vertex or the Ashkin-Teller models, are well described by an effective Quantum Field Theory obtained as formal scaling limit. On the basis of this assumption several extended scaling relations among their indices were conjectured. We prove the validity of some of them, among which the ones by Kadanoff, [K], and by Luther and Peschel, [LP].Comment: 32 pages, 7 fi

Mean Field Theory of Sandpile Avalanches: from the Intermittent to the Continuous Flow Regime

We model the dynamics of avalanches in granular assemblies in partly filled rotating cylinders using a mean-field approach. We show that, upon varying the cylinder angular velocity $\omega$, the system undergoes a hysteresis cycle between an intermittent and a continuous flow regimes. In the intermittent flow regime, and approaching the transition, the avalanche duration exhibits critical slowing down with a temporal power-law divergence. Upon adding a white noise term, and close to the transition, the distribution of avalanche durations is also a power-law. The hysteresis, as well as the statistics of avalanche durations, are in good qualitative agreement with recent experiments in partly filled rotating cylinders.Comment: 4 pages, RevTeX 3.0, postscript figures 1, 3 and 4 appended

Exact solution of the six-vertex model with domain wall boundary condition. Critical line between ferroelectric and disordered phases

This is a continuation of the papers [4] of Bleher and Fokin and [5] of Bleher and Liechty, in which the large $n$ asymptotics is obtained for the partition function $Z_n$ of the six-vertex model with domain wall boundary conditions in the disordered and ferroelectric phases, respectively. In the present paper we obtain the large $n$ asymptotics of $Z_n$ on the critical line between these two phases.Comment: 22 pages, 6 figures, to appear in the Journal of Statistical Physic

Oncolytic Viruses: Do They Have a Role in Anti-Cancer Therapy?

Oncolytic viruses are replication competent, tumor selective and lyse cancer cells. Their potential for anti-cancer therapy is based upon the concept that selective intratumoral replication will produce a potent anti-tumor effect and possibly bystander or remote cell killing, whilst minimizing normal tissue toxicity. Viruses may be naturally oncolytic or be engineered for oncolytic activity, and possess a host of different mechanisms to provide tumor selectivity. Clinical use of live replicating viruses is associated with a unique set of safety issues. Clinical experience has so far provided evidence of limited efficacy and a favourable toxicity profile. The interaction with the host immune system is complex. An anti-viral immune response may limit efficacy by rapidly clearing the virus. However, virally-induced cell lysis releases tumor associated antigens in a ‘dangerous’ context, and limited evidence suggests that this can lead to the generation of a specific anti-tumor immune response. Combination therapy with chemotherapy or radiotherapy represents a promising avenue for ongoing translation of oncolytic viruses into clinical practice. Obstacles to therapy include highly effective non-specific host mechanisms to clear virus following systemic delivery, immune-mediated clearance, and intratumoral barriers limiting virus spread. A number of novel strategies are now under investigation to overcome these barriers. This review provides an overview of the potential role of oncolytic viruses, highlighting recent progress towards developing effective therapy and asks if they are a realistic therapeutic option at this stage

Properties of layer-by-layer vector stochastic models of force fluctuations in granular materials

We attempt to describe the stress distributions of granular packings using lattice-based layer-by-layer stochastic models that satisfy the constraints of force and torque balance and non-tensile forces at each site. The inherent asymmetry in the layer-by-layer approach appears to lead to an asymmetric force distribution, in disagreement with both experiments and general symmetry considerations. The vertical force component probability distribution is robust and in agreement with predictions of the scalar q model while the distribution of horizontal force components is qualitatively different and depends on the details of implementation.Comment: 18 pages, 12 figures (with subfigures), 1 table. Uses revtex, epsfig,subfigure, and cite. Submitted to PRE. Plots have been bitmapped. High-resolution version is available. Email [email protected] or download from http://rainbow.uchicago.edu/~mbnguyen/research/vm.htm

The arctic curve of the domain-wall six-vertex model

The problem of the form of the `arctic' curve of the six-vertex model with domain wall boundary conditions in its disordered regime is addressed. It is well-known that in the scaling limit the model exhibits phase-separation, with regions of order and disorder sharply separated by a smooth curve, called the arctic curve. To find this curve, we study a multiple integral representation for the emptiness formation probability, a correlation function devised to detect spatial transition from order to disorder. We conjecture that the arctic curve, for arbitrary choice of the vertex weights, can be characterized by the condition of condensation of almost all roots of the corresponding saddle-point equations at the same, known, value. In explicit calculations we restrict to the disordered regime for which we have been able to compute the scaling limit of certain generating function entering the saddle-point equations. The arctic curve is obtained in parametric form and appears to be a non-algebraic curve in general; it turns into an algebraic one in the so-called root-of-unity cases. The arctic curve is also discussed in application to the limit shape of $q$-enumerated (with $0<q\leq 4$) large alternating sign matrices. In particular, as $q\to 0$ the limit shape tends to a nontrivial limiting curve, given by a relatively simple equation.Comment: 39 pages, 2 figures; minor correction

The influence of photoperiod on the reproductive physiology of the greater red musk shrew: Crocidura flavescens

Photoperiodism involves the use of both absolute measures of day length and the direction in which day length is changing as a cue for regulating seasonal changes in physiology and behaviour so that birth and lactation coincide with optimal resource availability, increasing offspring survival. Induced ovulation and opportunistic breeding is often found in species that are predominantly solitary and territorial. In this study, the photoperiodic reproductive responses of male greater red musk shrews (Crocidura flavescens (I. Geoffroy Saint-Hilaire, 1827)) were investigated in the laboratory. The presence of spermatozoa regardless of the light cycle, suggest that although the shrews are photoresponsive, they may be capable of breeding throughout the year. Significantly greater testicular volume and eminiferous tubule diameter following exposure to a short day-light cycle suggests that these animals may have breeding peaks that correspond to short days. The presence of epidermal spines on the penis indicates that the shrew is likely also an induced ovulator. Flexible breeding patterns combined with induced ovulation affords this solitary species the greatest chance of reproductive success

Depositional setting, provenance and tectonic-volcanic setting of Eocene-Recent deep-sea sediments of the oceanic Izu-Bonin forearc, NW Pacific (IODP Expedition 352)

New biostratigraphical, geochemical, and magnetic evidence is synthesized with IODP Expedition 352 shipboard results to understand the sedimentary and tectono-magmatic development of the Izu–Bonin outer forearc region. The oceanic basement of the Izu–Bonin forearc was created by supra-subduction zone seafloor spreading during early Eocene (c. 50–51 Ma). Seafloor spreading created an irregular seafloor topography on which talus locally accumulated. Oxide-rich sediments accumulated above the igneous basement by mixing of hydrothermal and pelagic sediment. Basaltic volcanism was followed by a hiatus of up to 15 million years as a result of topographic isolation or sediment bypassing. Variably tuffaceous deep-sea sediments were deposited during Oligocene to early Miocene and from mid-Miocene to Pleistocene. The sediments ponded into extensional fault-controlled basins, whereas condensed sediments accumulated on a local basement high. Oligocene nannofossil ooze accumulated together with felsic tuff that was mainly derived from the nearby Izu–Bonin arc. Accumulation of radiolarian-bearing mud, silty clay, and hydrogenous metal oxides beneath the carbonate compensation depth (CCD) characterized the early Miocene, followed by middle Miocene–Pleistocene increased carbonate preservation, deepened CCD and tephra input from both the oceanic Izu–Bonin arc and the continental margin Honshu arc. The Izu–Bonin forearc basement formed in a near-equatorial setting, with late Mesozoic arc remnants to the west. Subduction-initiation magmatism is likely to have taken place near a pre-existing continent–oceanic crust boundary. The Izu–Bonin arc migrated northward and clockwise to collide with Honshu by early Miocene, strongly influencing regional sedimentation