Scalable processors in the billion-transistor era: IRAM

Members of the University of California, Berkeley, argue that the memory system will be the greatest inhibitor of performance gains in future architectures. Thus, they propose the intelligent RAM or IRAM. This approach greatly increases the on-chip memory capacity by using DRAM technology instead of much less dense SRAM memory cells. The resultant on-chip memory capacity coupled with the high bandwidths available on chip should allow cost-effective vector processors to reach performance levels much higher than those of traditional architectures. Although vector processors require explicit compilation, the authors claim that vector compilation technology is mature (having been used for decades in supercomputers), and furthermore, that future workloads will contain more heavily vectorizable components     

Potassium transport across rabbit descending colon in vitro: evidence for single-file diffusion through a paracellular pathway

The results of previous studies indicate that the bidirectional fluxes of K across short-circuited rabbit descending colon are attributable to passive diffusion through paracellular pathways and that this route is ten times more permeable to K than to Na and Cl. However, transepithelial diffusion potentials in the presence of large transepithelial Na and K concentration differences are much lower than those predicted by the "constant field equation" and appear to be inconsistent with this high K selectivity. The results of the present studies, designed to resolve this apparent contradiction, indicate that: (a) The ratios of the bidirectional transepithelial fluxes of K determined over a wide range of combined chemical and electrical potential differences conform reasonably well with those predicted by the Ussing flux-ratio equation. (b) The permeability coefficient of K (PK), determined from the net fluxes in the presence of concentration differences and from unidirectional fluxes under short-circuit conditions, decreases with increasing K concentration; in the presence of low K concentrations, PK is approximately ten-times PNa, but it approaches PNa in the presence of high K concentrations. PNa is not affected under these conditions. These results provide an explanation for the failure to observe large transepithelial diffusion potentials in the presence of large transepithelial Na and K concentration differences. In addition, these results are consistent with the notion that K diffuses across this preparation through two parallel pathways, one that does not discriminate among K, Na and Cl (a "free-solution" shunt) and another that is highly K selective and involves an interaction with one, or at most two, sites along the route.     

Mechanical ventilation: past and present

BACKGROUND: Early stages of cutaneous T-cell lymphoma (CTCL) may be difficult to distinguish from benign inflammatory dermatoses by routine histologic examination. OBJECTIVE: Our purpose was to determine whether clonal rearrangements of the T-cell receptor (TCR) gamma gene by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE) could be detected in the early stages of CTCL and to correlate these findings with conventional histopathology. METHODS: A total of 39 specimens from 12 patients with CTCL were obtained. The slides were evaluated independently by three dermatopathologists, and categorized into three groups: nondiagnostic, suggestive of CTCL, and diagnostic of CTCL. Of the 39 specimens, 33 were tested by PCR/DGGE by means of GC-clamped primers for clonal rearrangement of the TCR gamma gene. RESULTS: The histologic evaluation of the 12 cases showed a significant variation among the three dermatopathologists. The correlation of PCR/DGGE with routine histology was as follows: Clonal TCR gamma gene rearrangements were demonstrated in 73% of the specimens nondiagnostic for CTCL, 71% of those suggestive of CTCL, and 74% of those diagnostic of CTCL. CONCLUSION: Clonal TCR gamma gene rearrangements may be detected in patients with early CTCL, even when the histologic findings are not unequivocally diagnostic. In patients with multiple biopsy specimens, identical clones were demonstrated in all rearranged samples, indicating the same neoplastic clone was present in the earliest stages of disease.     

Lost and found half a century later: Letters by Freud and Einstein.

The author offers a letter that she had written as a student to 100 scientists and philosophers in 1932 to elucidate the process that occurred when these individuals had their most productive thought. 41 of the 100 responded; the correspondence received from Einstein and Freud are reproduced. In 1947, the letters were lost, apparently left on a commuter train. The author describes the process which led to the rediscovery of these important missives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of process parameter changes on the composition of magnetron sputtered and evaporated TiN and AlN films measured by UHV in-situ techniques

TiN and AlN films are deposited on HSS steel substrates in an ultrahigh vacuum magnetron system equipped with in-situ Auger electron spectroscopy (AES) and mass spectrometric sensors for plasma diagnostics. The composition of TiN_x coatings is measured by AES as a function of the N₂ pressure, the bias voltage, and the d.c. power. The flux of ionic particles impinging on the substrate surface and their energies are determined by a quadruple mass analyzer mounted behind a hole in the substrate. In addition, the reactivity of neutral nitrogen molecules in a reactive evaporation process is measured by a quartz crystal microbalance.     

Update on the antitrust ghost in the standard-setting machine [patents]

This article presents Richard Stern's Micro Law paper in the May-June 2005 issue of IEEE Micro, by two lawyers involved in presenting Hewlett-Packard's RAND proposal to the IEEE PatCom recently. The paper captured the essence of a long-running obstacle to addressing the anticompetitive patent "hold-up" that undermines the open-standards objectives of standards developing organizations (SDOs). That obstacle is the misconceived fear of antitrust liability if an SDO allows any consideration of license intentions beyond vague or vacuous commitments to reasonable and nondiscriminatory (RAND) licensing during the course of a standard-setting process.     

Phase I trial of the thioether phospholipid analogue BM 41.440 in cancer patients

The online version of the original article can be found at     

Phase I trial of the thioether phospholipid analogue BM 41.440 in cancer patients

BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is a new thioether phospholipid, which has been shown to possess antineoplastic, antimetastatic, anti-invasive and immunomodulating properties in serveral tumor models. The mechanism whereby this compound exerts its direct antineoplastic effect is thought to be related to specific interference with the normal phospholipid metabolism, preferentially of neoplastic cells. BM 41.440 was evaluated in a multicenter phase I study in patients (pts) with refractory cancers. In phase I A, 34 pts were orally treated with doses ranging from 0.5 to 7.0 mg/kg body weight (bw). Three different formulations were tested. The maximum-tolerated dose (MTD) was ca. 5 mg/kg bw. The limiting side effects were nausea and vomiting. There was no evidence for systemic toxicities like myelosuppression, nephro-, neuro-, hepatotoxicity or hematological side effects. The current phase I B is designed to determine the MTD of BM 41.440 administered orally on a daily schedule for at least eight weeks. So far, 19 pts have entered this trial at dose levels ranging from 1.0 to 5.0 mg/kg bw/day. Some pts receiving 1.0 and 2.5 mg/kg bw/day, respectively, have been treated, up to now, for more than nine months. Clinical progress was followed with at-least-weekly blood counts, chemistry profiles, urine analysis, liver function tests and recordings of side effects. Tumor parameters were evaluated at eight-week intervals. In parallel, pharmacokinetic investigations were performed in some pts in phase I A and IB. First results on tolerability and therapeutic efficacy of the long-term BM 41.440 treatment are reported in this intermediate evaluation.     

MATE1 Deficiency Exacerbates Dofetilide-Induced Proarrhythmia

Dofetilide is a rapid delayed rectifier potassium current inhibitor widely used to prevent the recurrence of atrial fibrillation and flutter. The clinical use of this drug is associated with increases in QTc interval, which predispose patients to ventricular cardiac arrhythmias. The mechanisms involved in the disposition of dofetilide, including its movement in and out of cardiomyocytes, remain unknown. Using a xenobiotic transporter screen, we identified MATE1 (SLC47A1) as a transporter of dofetilide and found that genetic knockout or pharmacological inhibition of MATE1 in mice was associated with enhanced retention of dofetilide in cardiomyocytes and increased QTc prolongation. The urinary excretion of dofetilide was also dependent on the MATE1 genotype, and we found that this transport mechanism provides a mechanistic basis for previously recorded drug-drug interactions of dofetilide with various contraindicated drugs, including bictegravir, cimetidine, ketoconazole, and verapamil. The translational significance of these observations was examined with a physiologically-based pharmacokinetic model that adequately predicted the drug-drug interaction liabilities in humans. These findings support the thesis that MATE1 serves a conserved cardioprotective role by restricting excessive cellular accumulation and warrant caution against the concurrent administration of potent MATE1 inhibitors and cardiotoxic substrates with a narrow therapeutic window.