Blocking the path from vagueness to four dimensionalism

There is a general form of an argument which I call the 'argument from vagueness' which attempts to show that objects persist by perduring, via the claim that vagueness is never ontological in nature and thus that composition is unrestricted. I argue that even if we grant that vagueness is always the result of semantic indeterminacy rather than ontological vagueness, and thus also grant that composition is unrestricted, it does not follow that objects persist by perduring. Unrestricted mereological composition lacks the power to ensure that there exist instantaneous objects that wholly overlap persisting objects at times, and thus lacks the power to ensure that there exists anything that could be called a temporal part. Even if we grant that such instantaneous objects exist, however, I argue that it does not follow that objects perdure. To show this I briefly outline a coherent version of three dimensionalism that grants just such an assumption. Thus considerations pertaining to the nature of vagueness need not lead us inevitably to accept perdurantism.

Epitope-blocking enzyme-linked immunosorbent assay for detection of antibodies to Ross River virus in vertebrate sera

We describe the development of an epitope-blocking enzyme-linked immunosorbent assay (ELISA) for the sensitive and rapid detection of antibodies to Ross River virus (RRV) in human sera and known vertebrate host species. This ELISA provides an alternative method for the serodiagnosis of RRV infections.

Spontaneous and UV radiation-induced multiple metastatic melanomas in Cdk4(R24C/R24C)/TPras mice

Human melanoma susceptibility is often characterized by germ-line inactivating CDKN2A (INK4A/ARF) mutations, or mutations that activate CDK4 by preventing its binding to and inhibition by INK4A. We have previously shown that a single neonatal UV radiation (UVR) dose delivered to mice that carry melanocyte-specific activation of Hras (TPras) increases melanoma penetrance from 0% to 57%. Here, we report that activated Cdk4 cooperates with activated Hras to enhance susceptibility to melanoma in mice. Whereas UVR treatment failed to induce melanomas in Cdk4(R24C/R24C) mice, it greatly increased the penetrance and decreased the age of onset of melanoma development in Cdk4(R24C/R24C)/TPras animals compared with TPras alone. This increased penetrance was dependent on the threshold of Cdk4 activation as Cdk4(R24C/+)/TPras animals did not show an increase in UVR-induced melanoma penetrance compared with TPras alone. In addition, Cdk4(R24C/R24C)/TPras mice invariably developed multiple lesions, which occurred rarely in TPras mice. These results indicate that germ-line defects abrogating the pRb pathway may enhance UVR-induced melanoma. TPras and Cdk4(R24C/R24C)/TPras tumors were comparable histopathologically but the latter were larger and more aggressive and cultured cells derived from such melanomas were also larger and had higher levels of nuclear atypia. Moreover, the melanomas in Cdk4(R24C/R24C)/TPras mice, but not in TPras mice, readily metastasized to regional lymph nodes. Thus, it seems that in the mouse, Hras activation initiates UVR-induced melanoma development whereas the cell cycle defect introduced by mutant Cdk4 contributes to tumor progression, producing more aggressive, metastatic tumors.

theta-defensins prevent HIV-1 Env-mediated fusion by binding gp41 and blocking 6-helix bundle formation

Retrocyclin-1, a 0-defensin, protects target cells from human immunodeficiency virus, type 1 (HIV-1) by preventing viral entry. To delineate its mechanism, we conducted fusion assays between susceptible target cells and effector cells that expressed HIV-1 Env. Retrocyclin-1 (4 mu M) completely blocked fusion mediated by HIV-1 Envs that used CXCR4 or CCR5 but had little effect on cell fusion mediated by HIV-2 and simian immunodeficiency virus Envs. Retrocyclin-1 inhibited HIV-1 Env-mediated fusion without impairing the lateral mobility of CD4, and it inhibited the fusion of CD4-deficient cells with cells bearing CD4-independent HIV-1 Env. Thus, it could act without cross-linking membrane proteins or inhibiting gp120-CD4 interactions. Retrocyclin-1 acted late in the HIV-1 Env fusion cascade but prior to 6-helix bundle formation. Surface plasmon resonance experiments revealed that retrocyclin bound the ectodomain of gp41 with high affinity in a glycan-independent manner and that it bound selectively to the gp41 C-terminal heptad repeat. Native-PAGE, enzyme-linked immunosorbent assay, and CD spectroscopic analyses all revealed that retrocyclin-1 prevented 6-helix bundle formation. This mode of action, although novel for an innate effector molecule, resembles the mechanism of peptidic entry inhibitors based on portions of the gp41 sequence.

Investigations into the effect of LOS signal blocking on capacity of an indoor MIMO system

In indoor environments the properties of communication channel are affected by the presence of various objects which block the Line Of Sight signal propagation. For example, this occurs because of presence of movement of humans and furniture. In this paper, the effect of reflection and scattering due to the presence of such objects is studied with respect to the capacity of a multiple input multiple output (MIMO) wireless system. The carried out investigations are performed by applying a simple electromagnetic model, in which transmitting and receiving antennas of MIMO system, as well as signal blocking objects, are represented by wire dipoles. In order to provide a fair assessment, calculations of MIMO capacity are performed under both fixed transmitted power and fixed received power conditions.

Formalising progress properties of non-blocking programs

A non-blocking program is one that uses non-blocking primitives, such as load-linked/store-conditional and compare-and-swap, for synchronisation instead of locks so that no process is ever blocked. According to their progress properties, non-blocking programs may be classified as wait-free, lock-free or obstruction-free. However, a precise description of these properties does not exist and it is not unusual to find a definition that is ambiguous or even incorrect. We present a formal definition of the progress properties so that any confusion is removed. The formalisation also allows one to prove the widely believed presumption that wait-freedom is a special case of lock-freedom, which in turn is a special case of obstruction-freedom.

Implicit learning is not subject to blocking

Explicit (aware) learning has been shown to evidence certain characteristics, such as extinction, blocking, occasion setting, and reliance on context. These characteristics have not been assessed in implicit (unaware) learning. The current study investigated whether implicit learning is subject to blocking. Participants completed a cued reaction time task, where they watched rapid presentations of a random sequence of 8 pairs of shapes, and responded to two target shapes. One target was always preceded by a cue. The experimental group completed a pretraining phase where half the cue, one shape, was followed by the target. Both experimental and control groups completed a training phase where both elements of the cue, two shapes, were followed by the target. Both aware and unaware participants evidenced learning, whereby responding was faster for cued than uncued targets. Aware participants in the experimental group responded faster to targets preceded by the pretrained element than by the other element of the cue. Control and unaware experimental participants were faster to respond to targets preceded by either element of the cue. As blocking was only evident in aware participants, but implicit learning was observed in all participants, it is concluded that implicit learning is not subject to blocking.

Immunochemical detection of UV-induced DNA damage and repair

The application of an antiserum to ultraviolet radiation (UVR)-damaged DNA is presented. A novel experimental system was employed to ascertain the limits of detection for this antiserum. Using a DNA standard containing a known amount of dimer, the limits of detection were found to be 0.9 fmol of dimer. This was compared to a limit of 20-50 fmol dimer using gas chromatography-mass spectrometry (GC-MS). Induction of thymine dimers in DNA following UVR exposure, as assessed using this antiserum in an enzyme-linked immunosorbent assay (ELISA), was compared with GC-MS measurements. The ELISA method successfully demonstrated the induction of lesions in DNA irradiated either with UVC or UVB, although despite high sensitivity, no discernible binding was seen to UVA-irradiated DNA. The antiserum was also shown to be applicable to immunocytochemistry, localising damage in the nuclei of UVR exposed keratinocytes in culture. The ability of the antiserum to detect DNA damage in skin biopsies of individuals exposed to sub-erythemal doses of UVR was also demonstrated. Moreover, the subsequent removal of this damage, as evidenced by a reduction in antiserum staining, was noted in sections of biopsies taken in the hours following irradiation. © 2003 Elsevier B.V. All rights reserved.