3,528 research outputs found

    First-place finish : imparting fine surface finishes when micromilling

    Get PDF
    There are several key milling practices that help impart fine surface finishes in micromilling. They include running at ultrahigh spindle speeds, carefully monitoring chip load, employing climb milling when possible and using CAM software to develop toolpaths that enhance surface finishes. There are also promising developments that can improve surface finishes in areas as diverse as using atomized cutting fluids and milling ultrafine-grain workpieces

    Characterization of the PCMBS-dependent modification of KCa3.1 channel gating.

    Get PDF
    Intermediate conductance, calcium-activated potassium channels are gated by the binding of intracellular Ca(2+) to calmodulin, a Ca(2+)-binding protein that is constitutively associated with the C terminus of the channel. Although previous studies indicated that the pore-lining residues along the C-terminal portion of S6 contribute to the activation mechanism, little is known about whether the nonluminal face of S6 contributes to this process. Here we demonstrate that the sulfhydral reagent, parachloromercuribenze sulfonate (PCMBS), modifies an endogenous cysteine residue predicted to have a nonluminal orientation (Cys(276)) along the sixth transmembrane segment (S6). Modification of Cys(276) manipulates the steady-state and kinetic behavior of the channel by shifting the gating equilibrium toward the open state, resulting in a left shift in apparent Ca(2+) affinity and a slowing in the deactivation process. Using a six-state gating scheme, our analysis shows that PCMBS slows the transition between the open state back to the third closed state. Interpreting this result in the context of the steady-state and kinetic data suggests that PCMBS functions to shift the gating equilibrium toward the open state by disrupting channel closing. In an attempt to understand whether the nonluminal face of S6 participates in the activation mechanism, we conducted a partial tryptophan scan of this region. Substituting a tryptophan for Leu(281) recapitulated the effect on the steady-state and kinetic behavior observed with PCMBS. Considering the predicted nonluminal orientation of Cys(276) and Leu(281), a simple physical interpretation of these results is that the nonluminal face of S6 forms a critical interaction surface mediating the transition into the closed conformation, suggesting the nonluminal C-terminal portion of S6 is allosterically coupled to the activation gate

    英語で伝える科学 第1回

    Get PDF
    Sharing Science - Writing Outside of Professional Journal

    Where is pain in the brain?

    Get PDF
    Key argues that fish cannot experience pain based on (1) brain imaging in humans, (2) consequences of lesions and (3) direct brain stimulation. Imaging indeed shows that pain-relevant signals reach the cortex, but not that they underlie the subjective experience of pain. Lesions and stimulation data are more to the point, but Key paints an idiosyncratic and misleading picture of their effects. S1 and S2 ablation does not eliminate evoked or spontaneous pain, although there may be up- or down-modulation. Likewise, stimulation of pain-associated cortical areas rarely induces pain, and pain almost never occurs at the onset of epileptic seizures. In contrast, cortical lesions and activation do have striking and reliable effects on visual, auditory, smell and touch perception. Overall, the case for the cerebral cortex being an essential substrate for pain experience in humans is too equivocal a starting point for ruling out the possibility of pain experience in fish

    On becoming a cancer biologist

    Get PDF
    I am not a cancer biologist but I am becoming one. Becoming is a process, a transformation. Taking what was and using it as the foundation for what is or what will be

    MicroRNAs, Cellular Behavior, and Endometrial Cancer

    Get PDF
    Endometrial cancer is the most common gynecological cancer and the fourth most common cancer in women worldwide. In spite of its’ relative importance to overall morbidity among women, molecular research in endometrial cancers lags far behind other cancers such as breast and colorectal. Nowhere is this more true than in research in the newly emergent field of post-transcriptional gene regulation by small, regulatory RNAs, primarily microRNAs (miRNAs). Here, structure, biogenesis, and mode of action of miRNAs is presented along with a brief overview of the role of miRNAs in carcinogenesis and a review of the few miRNA studies in endometrial cancer carried out to date
    corecore