An analog-AI chip for energy-efficient speech recognition and transcription.

Models of artificial intelligence (AI) that have billions of parameters can achieve high accuracy across a range of tasks1,2, but they exacerbate the poor energy efficiency of conventional general-purpose processors, such as graphics processing units or central processing units. Analog in-memory computing (analog-AI)3-7 can provide better energy efficiency by performing matrix-vector multiplications in parallel on 'memory tiles'. However, analog-AI has yet to demonstrate software-equivalent (SWeq) accuracy on models that require many such tiles and efficient communication of neural-network activations between the tiles. Here we present an analog-AI chip that combines 35 million phase-change memory devices across 34 tiles, massively parallel inter-tile communication and analog, low-power peripheral circuitry that can achieve up to 12.4 tera-operations per second per watt (TOPS/W) chip-sustained performance. We demonstrate fully end-to-end SWeq accuracy for a small keyword-spotting network and near-SWeq accuracy on the much larger MLPerf8 recurrent neural-network transducer (RNNT), with more than 45 million weights mapped onto more than 140 million phase-change memory devices across five chips.

Interaction of GH polymorphism with body weight and endocrine functions in Japanese black calves.

We assessed the interaction of GH gene polymorphisms (AA, AB and BB genotypes) with body weight and measures of endocrine function in Japanese black calves at 10 months of age. The average body weight for the BB genotype (281+/-5 kg) was significantly lower (P=0.0017, ANOVA) than those for the AA (324+/-9 kg) and AB (317+/-7 kg) genotypes. Plasma concentrations of insulin and IGF-I were greater for the AA genotype than for the AB genotype, and AB and BB genotypes, respectively. There were significant differences in the triglyceride and cholesterol concentrations among the GH genotypes. The area under the basal GH concentration was significantly greater (P=0.0314) for the AA genotype than for the two other genotypes. The incremental area over the basal GH concentrations in response to intravenous GHRH injection (0.4 microg/kg BW) was significantly smaller (P=0.0005) for the BB genotype than for the two other genotypes. In addition, linear regression analysis between GH incremental area induced by GHRH and body weight demonstrated that there was a positive linear correlation (r=0.6496, P<0.002) for incremental areas less than 600 ng min/ml, but a negative correlation (r=0.6473, P<0.05) for incremental areas over 600 ng min/ml. These findings indicate that the GH genotypes of the animals could be associated with difference in the GH response in Japanese black cattle at 10 months of age. We also observed a relationship between genotype and animal performances, but other studies on more animals in different conditions must be realized to make a definite conclusion.

Ultra-high-angle double-crystal X-ray diffractometry (U-HADOX) for determining a change in the lattice spacing: theory.

Advantages of high-angle double-crystal X-ray diffractometry (HADOX) have been re-examined. It is found that, by extending the Bragg angle theta up to 89.99 degrees, the accuracy of a change in the lattice spacing to one part in 10(9)-10(10) can be attained in proportion to tan theta. In such a case, the dispersion-free condition is so serious that the spacing of the two crystals should be equal within one part in 10(6). Therefore, this method is appropriate for determining the thermal expansion coefficient in a limited temperature range. To cover a wide temperature range, the temperature of the reference crystal must be adjusted according to the temperature of the specimen crystal; the lattice spacing as a function of temperature can be determined by integrating the temperature derivative of the spacing.

Experimental study of critical exponents of electrical conductivity in a two-dimensional continuum percolation system

In this paper an experimental study is presented for critical exponents of electrical conductivity in an inverse Swiss-cheese model. Filled circles are drawn on random positions of square paper in drawing ink with an X-Y plotter, and electrical resistance between both opposite sides is measured automatically by the use of general purpose interface bus system. Electrical conductivity is obtained from the inverse of the electrical resistance. Electrical conductivity in a bond process is also measured with the same system. It is confirmed that the critical exponent of electrical conductivity of a continuum two-dimensional inverse Swiss-cheese model is different from that of a discrete one.

[Changes in proton magnetic resonance spectroscopy and Wechsler adult intelligence scale revised after clipping of unruptured aneurysms].

The purpose of this study is to evaluate the influence of surgery for unruptured aneurysms on neuropsychological status and cerebral metabolism. We studied 21 patients with unruptured aneurysms treated with direct surgery accompanied by craniotomy, rather than by the endovascular method. Patients were evaluated before and after surgery, using the Wechsler adult intelligence scale revised (WAIS-R) and proton magnetic resonance spectroscopy which measured the ratio of N-acetyl-aspartate to creatine (NAA/Cr). Although the results of WAIS-R (total IQ, verbal IQ and performance IQ) was not significantly different after surgery in any of the patients, the total IQ of the patients with anterior communicating artery aneurysms (AcoA) showed a significant decline compared with patients with other aneurysms after surgery. Five of eight AcoA patients showed a specific reduction in verbal IQ, suggesting deterioration of recent memory. The NAA/Cr remained within the normal range and was not significantly different before and after surgery. However, the NAA/Cr in the white matter of the frontal lobe of AcoA patients showed a significant reduction compared with that of non-AcoA patients. All three elderly patients older than 70 showed a reduction in NAA/Cr of more than one standard deviation from normal subjects in their frontal or parietal lobes. These results indicated that operation for unruptured aneurysms is reliable and well established but they also show that careful consideration should be given to possible deterioration in neuropsychological status and cerebral metabolism after operation in AcoA and elderly patients.

Neoadjuvant intra-arterial infusion chemotherapy combined with hormonal therapy for locally advanced breast cancer.

To determine the efficacy of combined neoadjuvant intra-arterial infusion chemotherapy and hormonal therapy for treating locally advanced breast cancer, we compared the outcomes of patients with or without this therapy, and also assessed histologic response. Ninety-four patients with locally advanced breast cancer (stage IIIa, 56; stage IIIb, 38). Nineteen stage IIIa and 17 stage IIIb patients received intra-arterial plus hormonal therapy while 37 stage IIIa and 21 stage IIIb patients with similar ages and follow-up durations did not. Treated patients received intra-arterial epirubicin plus oral medroxy-progesterone. Five-year disease-free survival rates were 77.5% for intra-arterially treated and 33.0% for other patients in stage IIIa, and 70.5% for intra-arterially treated and 38.1% for other patients in stage IIIb. Five-year overall survival rates were 94.4% for intra-arterially treated and 61.7% for other patients in stage IIIa, and 90.9% for intra-arterially treated and 56.3% for other patients in stage IIIb. Ten-year overall survival rates in stage IIIb were 90.9% for treated and 22.5% for other group patents. All differences were statistically significant (p<0.05). Good histologic response to intra-arterial therapy was seen in 75% of the primary tumors and 71% of involved lymph nodes. Neoadjuvant intra-arterial therapy with hormonal therapy yielded better survival rates than no intra-arterial therapy or our previous intra-arterial regimen.

Polymorphisms of HLA-DR and -DQ genes in Japanese patients with bullous pemphigoid.

Bullous pemphigoid (BP), an autoimmune skin disease of the elderly, is mediated by autoantibodies that bind to hemidesmosomes of epidermal basal cells. This study investigated BP-associated HLA-DR and -DQ genes among Japanese patients. We analyzed HLA-DR and -DQ genes among 23 Japanese BP patients based on the polymerase chain reaction-restriction fragment length polymorphism. Eighteen of these 23 patients (78%) carried at least one allele of HLA-DRB1*04 or DRB1*1101, with significant increases in HLA-DRB1*04 (*0403, *0406)/DQA1*0301/DQB1*0302 and DRB1*1101/DQA1*0505/DQB1*0302 haplotypes as well as the individual alleles DRB1*1101 and DQB1*0302 (corrected p < 0.05 for each comparison), when compared to control subjects. These data differ from the accepted DQB1*0301 (DQ7) association with the same disease among Caucasians. These findings indicate that different HLA class II haplotypes genetically influence susceptibility to BP among different ethnic groups. Our findings, together with previous reports on Caucasian patients with the pemphigoid group of bullous diseases, suggest that HLA-DRB1 molecules might participate in the regulation of autoimmune responses to BP antigens.

[Clinical study of selective intra-arterial infusion chemotherapy using trans-radial arterial approach in 4 cases of advanced breast cancer].

We administered neoadjuvant chemotherapy by a selective intra-arterial infusion method using a trans-radial approach in patients with advanced breast cancer (stage III and stage IV). The trans-radial approach uses the arterial flow, based on the Seldinger technique. In this method, the radial artery is cannulated, and epirubucin is infused into the artery that carries blood from the subclavical artery to the breast. We have used this method in 4 cases thus far. Two of the patients received a single intra-arterial infusion of epirubicin. The other 2 patients were catheterized before they received chemotherapy by intra-arterial infusion. This technique decreased the pain or discomfort caused by the catheterizations during chemotherapy in all 4 cases. However, the currently available catheters are not always able to approach the artery flowing into the breast, thus the protocol will need to be refined.

Osseous tissue reaction around hydroxyapatite block implanted into proximal metaphysis of tibia of rat with collagen-induced arthritis.

This study was conducted to investigate the influence of osteoporosis on new bone formation around a hydroxyapatite (HA) block implanted into the proximal metaphysis of the tibia of rats with collagen-induced arthritis (CIA). Ten rats were immunized with an emulsion of bovine type II collagen and Freund's complete adjuvant (arthritis group). Another 10 rats, which were not immunized were used as the control group. Seventeen days after immunization, HA block was implanted into the proximal metaphysis of the tibia. Four weeks after implantation, all rats were killed. The serum level of tetrate-resistant acid phosphatase (TRAP), bone mineral density (BMD) in the proximal metaphysis of the tibia and the affinity index in the arthritis group were 28.0+/-3.5 IU/ml, 130.3+/-28.7 mg/cm2 and 77.6+/-10.8%, respectively, and those in the control group were 24.6+/-5.5 IU/ml, 175.9+/-30.5 mg/cm2 and 56.3+/-14.8%. The serum level of TRAP was higher (P < 0.05) and BMD was lower (P < 0.005) in the arthritis group. The amount of new bone formation around the HA block was larger (affinity index, P < 0.05) in the arthritis group than in the control group. These findings suggest that bone formation around HA block might be enhanced even in conditions associated with highly activated bone resorption and bone formation, such as arthritis.

Intussusception due to vanishing colon cancer with metastasis of the regional lymph nodes: report of a case.

We present herein a case report of vanishing colon cancer with intussusception. A 70-year-old man with hematochezia was admitted to our hospital. Preoperative images showed ileus due to a colonic tumor. At operation, normograde intussusception without any tumor was recognized at the sigmoid colon. Interestingly, the regional lymph nodes were found to be invaded by tubular adenocarcinoma cells, thus suggesting that the colon cancer existed before the necrosis of the wall took place.

Neoadjuvant intraarterial high-dose chemotherapy and autologous peripheral blood stem cell transplantation for advanced breast cancer.

Eight locally advanced breast cancer patients were treated with neoadjuvant intraarterial high-dose chemotherapy (epirubicin) plus MPA combined with autologous PBSCT. All patients completed the scheduled treatment, and there were no toxic deaths. Patients were treated with an escalating dose of epirubicin (370-480 mg) and cyclophosphamide (0-6000 mg). The rate of clinical response was 100%. The rate of good histologic response was 87.5% in the main tumor and 75% in diseased lymph nodes. The 2-year survival rate was 100%. Six patients were disease-free at the time of writing. This treatment resulted in higher rates of clinical and histologic response when compared with standard-dose intraarterial chemotherapy.

Nipple discharge disorders: current diagnostic management and the role of fiber-ductoscopy.

Nipple discharge disorders is a field in which there has been both increasing awareness on the part of patients and advances in management. Today secretion from nipples can be classified according to its color, cellularity and biology. To be significant a discharge should be true, spontaneous, persistent and non-lactational. Moreover there are methods to differentiate patients who require surgical intervention from those who do not. Surgically significant nipple discharges are watery, serous (yellow), serosanguineous and bloody. Cytology smears of discharge material have helped to classify the cellular material, providing information about normality, atypia and malignancy and also about papillary formation of the exfoliated cells. Tests such as Hemoccult help to discover occult blood in the secreted fluid. Modern immunological tests can be performed on cytology smears where occurrence of high levels of carcinoembryonic antigen could indicate a latent malignancy. Galactography investigation is today the state-of-the-art approach to investigate patients with nipple discharge disorders and this examination can demonstrate the size, location and extent of an intraductal abnormality. Modern high-resolution ultrasound techniques are helpful in visualizing intraductal disorders and are becoming a good complementary approach if not an alternative to traditional radiology techniques. Recently even MR galactography has been shown to be of diagnostic value, but not as informative as regular galactography. The most sophisticated investigation method, which can also be used therapeutically, is fiber-ductoscopy of the concerned duct in a breast. This technique, although expensive and in its infancy, is a fascinating and promising approach for inspecting the intraductal lumina. In this article the background, current investigation methods and possibilities of the technique are described, as well as the most sophisticated ways to deal with nipple discharge disorders in human breasts.

Bullous pemphigoid associated with Shy-Drager syndrome.

We report a patient with Shy-Drager syndrome who developed multiple tense blisters mainly on the extremities. Circulating anti-basement membrane zone autoantibodies were detected by the indirect immunofluorescence method. Immunoblot analysis using normal human epidermal extracts demonstrated that this patient's serum reacted only with 230 kD bullous pemphigoid antigen (BPAG1). Concerning the pathoetiology of the association of bullous pemphigoid and Shy-Drager syndrome, we discuss a sequence similarity between BPAG1 and dystonin, a candidate gene for dystonia musculorum.

Pharmacokinetics of erythropoietin in genetically anemic mice.

We examined the pharmacokinetics of recombinant human erythropoietin (rh-EPO) in genetically anemic mice (W/Wv genotype) to clarify its disposition mechanism in hematopoietic injury such as occurs in aplastic anemia. After rh-EPO was administered to W/Wv and control (+/+ genotype) mice once a day for 1 week at different doses, both the hematocrit (Hct) and tissue uptake clearance (CLup) of 125I-rh-EPO by spleen and bone marrow in the femur were estimated on the eighth day. The hematocrit increased on eighth day, depending on the dose administered. Compared with +/+ mice 10 times more rh-EPO was needed in W/Wv mice to produce an almost equivalent pharmacological effect. In +/+ mice, the CLup of 125I-rh-EPO by spleen increased to 4-fold that of controls after treatment with rh-EPO, 4.8 microg/kg, whereas that by bone marrow remained unchanged, irrespective of the dose administered. On the other hand, the increase in both the Hct and CLup in spleen was minimal in W/Wv mice. The CLup by bone marrow and spleen in both types of mice showed saturation with similar Km values (389-619 pM), comparable with the dissociation constant of the EPO receptor. In addition, the Hct correlated with the sum of the CLup by bone marrow and spleen in both types of mice, and the correlation lines were superimposable. These results suggest that the pharmacological receptors govern the saturable tissue uptake not only in normal mice but also in those that are anemic.

Mechanism for the nonlinear pharmacokinetics of erythropoietin in rats.

The contribution of erythropoietin- (EPO) receptors in target tissues, such as bone marrow and spleen, to the nonlinear pharmacokinetics of recombinant human EPO (rh-EPO) was evaluated in rats. The total body clearance after i.v. administration of rh-EPO (0.2-5 microg/kg) decreased as the dose of rh-EPO increased, approaching a plateau at high doses. The uptake clearance of 125I-rh-EPO by the target tissues, bone marrow and spleen, exhibited clear saturation. The Km values ranged from 240 to 450 pM, which are comparable with the reported value for the dissociation constant of EPO binding to EPO-receptors (180 pM) in rat bone marrow cells. A single s.c. administration of a large dose of rh-EPO (1 microg/kg) caused a reduction in tissue uptake clearance of 125I-rh-EPO by bone marrow and spleen (down-regulation). Furthermore, repeated intravenous injection of rh-EPO caused up-regulation of the tissue uptake clearance of 125I-rh-EPO, especially by the spleen, in a dose-dependent manner. Hematopoietic parameters such as hematocrit and hemoglobin concentration were also increased by repeated rh-EPO treatment and significantly correlated with the sum of the tissue uptake clearances in bone marrow and spleen. These findings suggest that the pharmacological receptor could be an important factor in defining the nonlinear pharmacokinetics of rh-EPO.

Immunological response to repeated administration of recombinant human erythropoietin in rats: biphasic effect on its pharmacokinetics.

We studied changes in the pharmacokinetics of 125I-recombinant human erythropoietin (125I-rh-EPO) after repeated subcutaneous administration once a week for 4 weeks. The plasma level of trichloroacetic acid-precipitable radioactivity after the fourth administration of 125I-rh-EPO was minimal in 8 of 10 rats, whereas in the other two rats, the plasma level was almost the same or somewhat higher than that in control rats that had received the vehicle solution 3 times instead of the first three sequential administrations. Antibody against rh-EPO in serum was detected in all 10 rats receiving multiple administrations of 125I-rh-EPO. However, the binding capacity for 125I-rh-EPO in the latter two rats, assessed by an in vitro serum binding study, was lower than for the other eight rats, suggesting that the antibody level in these two was lower. The effect of intravenous preinjection of various volumes of anti-rh-EPO antiserum on the pharmacokinetics of 125I-rh-EPO was examined. The half-life in the beta-phase was prolonged at lower doses of antiserum. When the pretreatment dose of antiserum was further increased, the half-life in the beta-phase rather shortened and the total body clearance (CL(total) increased. These results suggest that repeated administration of rh-EPO induces the production of antibody against rh-EPO that affects the pharmacokinetics of rh-EPO in a biphasic manner; CL(total) was reduced when a small amount of antibody was produced, and CL(total) was increased when a large amount of antibody was produced.