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.

Population genetic structure and Wolbachia infection in an endangered butterfly, Zizina emelina (Lepidoptera, Lycaenidae), in Japan.

Zizina emelina (de l'Orza) is listed on Japan's Red Data List as an endangered species because of loss of its principal food plant and habitat. We compared parts of the mitochondrial and nuclear genes of this species to investigate the level of genetic differentiation among the 14 extant populations. We also examined infection of the butterfly with the bacterium Wolbachia to clarify the bacterium's effects on the host population's genetic structure. Mitochondrial and nuclear DNA analyses revealed that haplotype composition differed significantly among most of the populations, and the fixation index F ST was positively correlated with geographic distance. In addition, we found three strains of Wolbachia, one of which was a male killer; these strains were prevalent in several populations. There was linkage between some host mitochondrial haplotypes and the three Wolbachia strains, although no significant differences were found in a comparison of host mitochondrial genetic diversity with nuclear genetic diversity in Wolbachia-infected or -uninfected populations. These genetic analyses and Wolbachia infection findings show that Z. emelina has little migratory activity and that little gene flow occurs among the current populations.

Prophylactic intra-arterial administration of fasudil hydrochloride for vasospasm following subarachnoid haemorrhage.

PURPOSE: We evaluated patients treated with prophylactic intra-arterial administration of fasudil hydrochloride (IAF) after subarachnoid haemorrhage (SAH). MATERIALS AND METHODS: Between August 1998 and December 2012, 92 patients with aneurysmal SAH were treated with IAF for angiographic vasospasm without ischemic symptoms after their follow-up angiography. Patients comprised 50 women and 42 men, aged 24-83 (mean 56.6) years. IAF consisted of 15 mg of fasudil hydrochloride dissolved in 20 ml physiological saline and injected through a catheter during approximately 15 min, after diagnostic angiography. The clinical outcome was evaluated using the Glasgow Outcome Scale (GOS) at discharge and ischemic lesions resulting from vasospasm were assessed on computed tomography (CT) scan at discharge. RESULTS: Forty-eight patients underwent surgical clipping and 44 patients underwent endovascular coiling. Angiographic improvement was observed in all patients (100 %). At discharge, 76 (83.0 %) of 92 patients showed good recovery on GOS. Nine patients developed progression of delayed ischemic neurological deficits (DIND) and three of these patients had ischemic lesions on CT scans. No patient had any significant changes in vital signs or any other adverse effects resulting from IAF. CONCLUSION: IAF therapy was safe and effective for patients with vasospasm following SAH. Prophylactic IAF therapy may prevent symptomatic vasospasm.

Predictive index for the onset of medication overuse headache in migraine patients.

Migraine patients are particularly prone to develop medication overuse headache (MOH). However, the risk factors for the transformation of migraine to MOH are still not clear. We investigated gene polymorphisms, personality traits, and characteristics of headache and lifestyle in 47 migraine patients (aged 36.4 ± 10.3) and 22 MOH patients (aged 39.6 ± 9.9) who progressed from migraine and made a scoring system for a predictive index (PI) of the onset of MOH in patients with migraine. By multivariate logistic stepwise regression analysis, type of migraine, regular and sufficient dietary intake, and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and dopamine D2 receptor (DRD2) C939T (rs6275) polymorphisms were selected as significant factors that contribute independently to the development from migraine to MOH (P < 0.05). The regression coefficients (ß) of these four selected factors were approximated and scored. The PI score in MOH patients (7.32 ± 1.60) was significantly higher than that in migraine patients (4.62 ± 1.83, P < 0.001). The proposed scoring system should in the future be the object of larger studies to confirm its validity.

Ultraviolet B irradiation of the mouse eye induces pigmentation of the skin more strongly than does stress loading, by increasing the levels of prohormone convertase 2 and α-melanocyte-stimulating hormone.

BACKGROUND: In previous studies, we made the unexpected finding that in mice, ultraviolet (UV)B irradiation of the eye increased the concentration of α-melanocyte-stimulating hormone (α-MSH) in plasma, and systemically stimulated epidermal melanocytes. AIMS: To compare the extent of the pigmentation induced by social and restraint stress (which activate the hippocampus-pituitary system) with that induced by UVB irradiation. METHODS: DBA/2 and sham-operated or hypophysectomized DBA/2 mice were subjected to local UVB exposure using a sunlamp directed at the eye, and two types of stress (social and restraint) were imposed. RESULTS: UVB irradiation of the eye or exposure to stress loading both increased the number of Dopa-positive melanocytes in the epidermis, and hypophysectomy strongly inhibited the UVB-induced and stress-induced stimulation of melanocytes. Irradiation of the eye caused a much greater increase in dopamine than did the stress load. Both UVB eye irradiation and stress increased the blood levels of α-MSH and adrenocorticotropic hormone (ACTH). In addition, the increase in plasma α-MSH was greater in animals subjected to UVB eye irradiation than in those subjected to stress loading, whereas the reverse occurred for plasma ACTH. UVB irradiation to the eye and stress loading increased the expression of prohormone convertase (PC)1/3 and PC2 in the pituitary gland. The increase in expression of pituitary PC2 was greater in animals subjected to UVB eye irradiation than to stress, whereas no difference was seen between the two groups for the increase in PC1/3. CONCLUSIONS: UVB eye irradiation exerts a stronger effect on pigmentation than stress loading, and is related to increased levels of α-MSH and PC2.

Alagille-like syndrome with surprising karyotype: a case report.

BACKGROUND: Chromosome 5p partial monosomy (5p-syndrome) and chromosome 6p partial trisomy are chromosomal abnormalities that result in a variety of symptoms, but liver dysfunction is not normally one of them. Alagille syndrome (OMIM #118450) is a multisystem disorder that is defined clinically by hepatic bile duct paucity and cholestasis, in association with cardiac, skeletal, and ophthalmologic manifestations, and characteristic facial features. Alagille syndrome is caused by mutations in JAG1 on chromosome 20 or NOTCH2 on chromosome 1. Here, we report a preterm infant with karyotype 46,XX,der(5)t(5,6)(p15.2;p22.3) and hepatic dysfunction, who was diagnosed as having incomplete Alagille syndrome. CASE PRESENTATION: The Japanese infant was diagnosed based on the cardiac abnormalities, ocular abnormalities, characteristic facial features, and liver pathological findings. Analysis of the JAG1 and NOTCH sequences failed to detect any mutations in these genes. CONCLUSIONS: These results suggest that, besides the genes that are known to be responsible for Alagille syndrome, other genetic mutations also may cause Alagille syndrome.

Negative predictors of clinical response to triptans in patients with migraine.

Moderate to severe migraine attacks are treated with triptans. However, about 25% of migraineurs fail to respond to triptans. We investigated the involvement of gene polymorphisms, personality traits and characteristics of headache, and made a scoring system for prediction of clinical response to triptans in patients with migraine. Gene polymorphisms including serotonin (5-HT)(1B) receptor G861C and dopamine receptor 2 (DRD2) C939T, personality traits and characteristics of headache were investigated in 46 consistent responders and 14 inconsistent responders to triptans. The multivariate stepwise logistic regression analysis revealed that age, periorbital/deep orbital pain and C/C genotype carrier at DRD2 C939T were significant factors that contributed independently to the negative response to triptans in patients with migraine. Their odds ratios were 6.329 (40-69 vs. 20-39 years, 95% CI 1.441-27.778), 6.772 (no vs. yes, periorbital/deep orbital pain, 95% CI 1.159-39.580) and 14.085 (non-C/C vs. C/C genotype at DRD2 C939T, 95% CI 1.253-166.667), respectively. The predictive index (PI) of clinical response to triptans in patients with migraine was calculated using these three factors. The score in inconsistent responders (1.6 ± 0.6) was significantly higher than that in consistent responders (0.8 ± 0.7, P < 0.001). Sensibility of low-score (RI = 0) group was 100%, and specificity of high-score (PI ≥ 2) group was 87%. The proposed scoring system should in the future be the object of larger studies to confirm its validity.

Partial response of angiosarcoma of the scalp to sorafenib: association with decreased expression of vascular endothelial growth factors and their receptors.

The prognosis of angiosarcoma remains very poor, even with combined, multimodal therapy. We report a case with partial response of angiosarcoma of the scalp to sorafenib, which is a new oral, molecular, targeted, multiple-kinase inhibitor. In addition, we confirmed, using immunohistochemistry, that sorafenib suppressed the expression of vascular endothelial growth factors and their receptors on the angiosarcoma tumour cells, and decreased cell numbers by inhibiting cellular proliferation.

Functions of chondroitin sulfate and heparan sulfate in the developing brain.

Chondroitin sulfate and heparan sulfate proteoglycans are major components of the cell surface and extracellular matrix in the brain. Both chondroitin sulfate and heparan sulfate are unbranched highly sulfated polysaccharides composed of repeating disaccharide units of glucuronic acid and N-acetylgalactosamine, and glucuronic acid and N-acetylglucosamine, respectively. During their biosynthesis in the Golgi apparatus, these glycosaminoglycans are highly modified by sulfation and C5 epimerization of glucuronic acid, leading to diverse heterogeneity in structure. Their structures are strictly regulated in a cell type-specific manner during development partly by the expression control of various glycosaminoglycan-modifying enzymes. It has been considered that specific combinations of glycosaminoglycan-modifying enzymes generate specific functional microdomains in the glycosaminoglycan chains, which bind selectively with various growth factors, morphogens, axon guidance molecules and extracellular matrix proteins. Recent studies have begun to reveal that the molecular interactions mediated by such glycosaminoglycan microdomains play critical roles in the various signaling pathways essential for the development of the brain.

Significance of glomerular activation of the alternative pathway and lectin pathway in lupus nephritis.

The objective of the present study was to elucidate the association between glomerular complement depositions belonging to the alternative (AP) and lectin (LP) pathways, and clinical findings of lupus nephritis (LN). Immunofluorescence (IF) was performed on 17 LN patients using antibodies against factor B, factor H, properdin, mannose-binding lectin (MBL) and L-ficolin. Compared with factor B/factor H negative patients (n = 9), positive patients (n = 8) showed longer duration of LN (p < 0.05) and more severe interstitial fibrosis (p < 0.05). Eleven patients had properdin deposition in glomeruli, and in three of them, with a duration of LN of less than 1 month, factor B was undetectable. Compared with properdin negative patients (n = 6), positive patients (n = 11) showed significantly higher urinary protein excretion (p < 0.01). MBL/L-ficolin positive patients (n = 11) also had significantly higher urinary protein excretion (p < 0.05) compared with negative patients (n = 6). An independent association was found between glomerular deposition of properdin and that of MBL/L-ficolin (p < 0.01) in addition to factor B/factor H. Traces of glomerular activation of AP and LP reflected the clinical status of LN. It appears that glomerular deposition of each complement component, especially properdin, may be an index of the histological activity of LN.

Immune responses to porphyromonas gingivalis infection suppress systemic inflammatory response in experimental murine model.

Periodontitis is a localized infectious disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), and the severity correlates to significance of immune responses. Recently, it has been reported that periodontitis is associated with the development of systemic disease such as diabetes and atherosclerosis because of increasing invasion of oral pathogens to the circulation. However, the association between local and systemic infectious responses is still unclear. In the present study, we examined the differences of biological responses in animals with or without bacterial infection. After Balb/c mice were infected subcutaneously with live P. gingivalis W83, serum, skin and liver were collected according to experimental protocol. The skin and liver tissues were observed pathologically by haematoxylin-eosin staining, and serum IL-6 levels were measured using ELISA method. Throughout the experimental period, conditions of the mice were observed continuously. As expected, severe infiltration of leukocytes were observed at inflamed skin corresponding to the number of bacterial challenges. Although no inflammatory appearance of skin was observed, serum IL-6 levels were increased dramatically (P <0.01, Student's t-test) and liver tissues were injured in the mice without bacterial challenge. Interestingly, although severe inflammatory appearance of the skin was observed, serum IL-6 levels were not increased and no inflammatory responses were observed in the liver of the 3-times bacterially challenged group. Importantly, immunoglobulin G against P. gingivalis W83 was detected in the blood of mice with 3-times bacterial challenge corresponding to improvement of weight loss and survival. In conclusion, although multiple infections develop severe localized inflammation, the immune system should be sufficient to protect the systemic inflammatory responses.

Prevention of retained fetal membranes and improvement in subsequent fertility with oxytocin administration in cows with assisted calving.

In dairy cows, the efficacy of oxytocin treatment for preventing retained fetal membranes (RFM) is controversial. The physiological condition of cows associated with the calving process may affect the action of oxytocin. This study aimed to elucidate the difference in the efficacy of exogenous oxytocin treatment immediately after calving among cows that received various obstetric interventions. The calving ease was recorded using a score of 1-5, and assisted birth was defined as a score of 2 or more. Cows that required calving assistance (assisted, n = 28) due to delayed calving progression had a prolonged time from calving to expulsion of the fetal membrane (P < 0.01), and impaired reproductive performance compared to cows that did not receive calving assistance (unassisted, n = 78). The effect of oxytocin treatment was determined using cows that did not expel their fetal membrane within 3 h after calving. Cows were randomly divided into the control (unassisted, n = 41; assisted, n = 22) or oxytocin group (unassisted, n = 33; assisted, n = 10). Oxytocin (50 IU) was administered intramuscularly to the cows in the oxytocin group between 3 and 6 h after calving, while no treatment was administered in the control group. In cows with assisted birth, oxytocin administration accelerated placental expulsion (P < 0.05) and improved several reproductive parameters, such as the number of services until conception (P < 0.05) and the calving to conception intervals (P < 0.05) compared to the control group. On the other hand, oxytocin administration slightly accelerated placental expulsion (P < 0.05), but failed to improve fertility in cows with unassisted birth. The results indicate that the action of oxytocin varies depending on the calving situation of the cows. Oxytocin administration during the early postpartum period could prevent RFM and improve the decline in reproductive performance associated with calving assistance.

Simulated and observed variability in ocean temperature and heat content.

Observations show both a pronounced increase in ocean heat content (OHC) over the second half of the 20th century and substantial OHC variability on interannual-to-decadal time scales. Although climate models are able to simulate overall changes in OHC, they are generally thought to underestimate the amplitude of OHC variability. Using simulations of 20th century climate performed with 13 numerical models, we demonstrate that the apparent discrepancy between modeled and observed variability is largely explained by accounting for changes in observational coverage and instrumentation and by including the effects of volcanic eruptions. Our work does not support the recent claim that the 0- to 700-m layer of the global ocean experienced a substantial OHC decrease over the 2003 to 2005 time period. We show that the 2003-2005 cooling is largely an artifact of a systematic change in the observing system, with the deployment of Argo floats reducing a warm bias in the original observing system.

Lymphatic vessel invasion detected by monoclonal antibody D2-40 as a predictor of lymph node metastasis in T1 colorectal cancer.

OBJECTIVE: When selecting patients who are at high risk for lymph node metastasis, the detection of lymphatic vessel invasion (LVI) is important. We investigated LVI detected by D2-40 staining as a predictor of lymph node metastasis in T1 colorectal cancer. MATERIALS AND METHODS: Clinicopathological factors including LVI were investigated in 136 patients who underwent colectomy with lymph node dissection for T1 colorectal cancer. We used immunostaining with monoclonal antibody D2-40 to detect LVI. RESULTS: Lymph node metastases were found in 18 patients (13.2%), and LVI were detected in 45 (33%); lymph node metastasis was more frequently observed in LVI-positive groups (13/45 vs 5/91, p < 0.001). Both univariate and multivariate analyses revealed that LVI detected by D2-40 and a poorly differentiated histology at the invasion front were independent risk factors of lymph node metastasis. CONCLUSION: LVI detected by D2-40 is important for the prediction of lymph node metastasis.

Bacterial community dynamics during reduction of odorous compounds in aerated pig manure slurry.

AIMS: To study the microbial community responsible for the reduction of the polluting load during aerobic digestion of pig slurry. METHODS AND RESULTS: We analysed bacterial succession by nonculture-based methods and determined the physicochemical parameters and polluting substances during 6 days of aerobic digestion. The bacterial subpopulations evolved by aeration, predominantly Bacillus spp., degraded organic matter and vigorously consumed oxygen, as indicated by low oxidation-reduction potential (ORP). In this phase, the volatile fatty acid (VFA) levels drastically decreased, and VFAs were almost depleted on day 4. Simultaneously, the ammonia concentration decreased to its lowest level on day 4; thereafter, it increased until the end of the process. After the decrease in the total organic carbon content in the supernatant of the decomposed slurry, the ORP increased (approximately 0 mV), and the microbial community showed an abundance of lineages belonging to the phylum Proteobacteria. CONCLUSIONS: Bacillus was the predominant member of the bacterial community driving the VFA-removal process. Their predominance was related to the presence of available carbon, including VFAs and changes in ORP. SIGNIFICANCE AND IMPACT OF THE STUDY: Information on the relationships among the involved microbes, polluting materials and physicochemical parameters will aid process design and retrofitting of the process.

Annular leucocytoclastic vasculitis.

Leucocytoclastic vasculitis (LV) is characterized by necrotizing inflammation around small blood vessels, composed mainly of neutrophils and their debris. The skin lesions of LV are polymorphous, but an annular variant is rare. Four previous reports have named this variant 'annular LV' (ALV) and in this paper, we report two additional cases. Patient 1 was a 80-year-old man, who presented with pruritic, erythematous target lesions on his legs, soles, abdomen and axillae; histological examination showed typical LV throughout the entire dermis. Oral prednisolone 15 mg daily rapidly resolved the patient's symptoms. Patient 2 was a 64-year-old man, who was referred to our hospital because of multiple purpuric target lesions on the buttocks, right thigh, lower legs, upper arms and forearms. Histopathology revealed LV throughout the entire dermis. Oral prednisolone 20 mg daily rapidly resolved the lesions. We categorized these cases morphologically as ALV and clinically as small-vessel vasculitis. ALV is not a distinct condition, but includes a broad range of small-vessel vasculitides.

Necrotizing fasciitis caused by Cryptococcus neoformans in a patient with pemphigus vegetans.

Cryptococcosis occurs most often in immunocompromised people. The cutaneous features of cryptococcosis include papules, pustules, nodules, subcutaneous swelling, abscesses, molluscum contagiosum-like or tumour-like lesions, cellulitis, blisters, ulcers and very rarely, necrotizing fasciitis (NF). NF is a destructive soft-tissue infection that is most typically caused by group A streptococci or by a combination of facultative and anaerobic bacteria. We present the case of a 55-year-old woman with pemphigus vegetans, who developed cryptococcal NF in the legs. She had been treated with immunosuppressants including plasmapheresis and pulse therapy with steroid and cyclophosphamide. Cryptococcal NF localized to the legs is very rare. Because diagnosis and treatment of cryptococcal infection is often delayed, clinicians should be aware of the possibility of cryptococcal infection when antibacterial therapy is not effective in an immunocompromised patient.

Local VEGF administration enhances healing of colonic anastomoses in a rabbit model.

BACKGROUND/AIMS: Many studies report the role of vascular endothelial growth factor (VEGF) in wound healing, but few describe local VEGF administration to the digestive tract. Leakage from colonic anastomoses, including those due to ischemia, represents a major complication causing increased mortality and morbidity. Angiogenesis is crucial to anastomotic healing and restoration of blood supply, and VEGF is a potent angiogenic factor showing improved healing in various models of reconstruction and anastomosis. Here, we examine the effects of local VEGF-A(165) administration on postoperative rabbit colon anastomosis. METHODS: Two colotomies per animal were made in the sinistral colon on opposite sides of the mesentery. Randomly assigned VEGF (10 microg/0.1 ml) or saline (0.1 ml) was injected into the muscularis propria on both sides of each colonic anastomosis before closing the access laparotomy using single-layer sutures. On postoperative days 3, 4 and 7, the bursting pressure of partially healed anastomoses was measured. On postoperative day 4, anastomotic tissues were examined for the following: hydroxyproline; histopathologically for inflammatory infiltrate and tissue organization and immunohistochemically for capillary proliferation and density; vessel density of midzone collaterals around anastomoses by microangiography. RESULTS: Compared to saline, VEGF administration significantly improved bursting pressure (p = 0.014, paired t test) and increased hydroxyproline (p = 0.027, paired t test) on postoperative day 4. Inflammatory cell infiltration and fibroblast proliferation were prominent, and submucosal capillary vascular counts were significantly higher for VEGF. CONCLUSIONS: Administration of VEGF to colonic anastomosis accelerates wound healing and strengthens the anastomosis by increased angiogenesis.

Clinical experience of using multidetector-row CT for the diagnosis of disorders in cattle.

To determine the clinical usefulness of multidetector-row CT for the diagnosis of disorders in cattle, images were obtained from 27 cattle, which were then subjected to postmortem and histopathological examinations. The cattle were divided into three categories of disorder: neurological (18 cases), skeletal (four cases) and other (five cases). In five cattle, which were suspected to have brain diseases, no abnormalities were identified by either CT or histopathological examination. Eight types of lesions were detected by CT in the cattle with neurological and vestibular disorders. The diseases diagnosed included hydrocephalus (three cases), intracranial arachnoid cysts (three cases), otitis media (five cases), cerebral abscess (one case), meningoencephalocele (one case), porencephaly (one case), bicephalus (one case) and rupture of the spinal cord (one case). Lesions were identified in all the cattle with skeletal disorders, including luxation (two cases), fracture (two cases), spondylosis (one case) and congenital disorders of the skeletal system (one case). Morphological disorders in the eyes (one case), nasal cavity (two cases), frontal sinuses (one case), thyroid glands (two cases), lung fields (two cases) and abdominal organs (two cases) were diagnosed by CT.