An extremely energetic cosmic ray observed by a surface detector array.

Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle's energy as [Formula: see text] (~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.

Assessment of feline hospitalization environment using a one-way mirror.

A separate, cat-specific hospitalization room away from dogs is recommended to reduce stress in cats; however, this can be difficult for some hospitals to provide. In such cases, measures are undertaken to reduce the cat's stress by providing a place to hide. However, inability to observe the cat's condition may be an obstacle to providing veterinary care. The use of a one-way mirror to create a sheltered environment while allowing observation of the cats was assessed. Five healthy cats were assessed using the Cat Stress Score (CSS) while in a cage with either a transparent panel or a one-way mirror. No significant differences in the CSS between the transparent panel and one-way mirror were observed. Variations in the CSS scores depended on the cat's personality, with friendlier and more sociable cats showing a lower CSS with the one-way mirror. A one-way mirror may be useful to reduce stress in hospitalized cats.

Metal doped polyaniline as neuromorphic circuit elements for in-materia computing.

Polyaniline-based atomic switches are material building blocks whose nanoscale structure and resultant neuromorphic character provide a new physical substrate for the development next-generation, nanoarchitectonic-enabled computing systems. Metal ion-doped devices consisting of a Ag/metal ion doped polyaniline/Pt sandwich structure were fabricated using an in situ wet process. The devices exhibited repeatable resistive switching between high (ON) and low (OFF) conductance states in both Ag+ and Cu2+ ion-doped devices. The threshold voltage for switching was>0.8 V and average ON/OFF conductance ratios (30 cycles for 3 samples) were 13 and 16 for Ag+ and Cu2+ devices, respectively. The ON state duration was determined by the decay to an OFF state after pulsed voltages of differing amplitude and frequency. The switching behaviour is analagous to short-term (STM) and long-term (LTM) memories of biological synapses. Memristive behaviour and evidence of quantized conductance were also observed and interpreted in terms of metal filament formation bridging the metal doped polymer layer. The successful realization of these properties within physical material systems indicate polyaniline frameworks as suitable neuromorphic substrates for in materia computing.

High-resolution, high-throughput HLA genotyping by next-generation sequencing.

The human leukocyte antigen (HLA) class I and class II loci are the most polymorphic genes in the human genome. Hematopoietic stem cell transplantation requires allele-level HLA typing at multiple loci to select the best matched unrelated donors for recipient patients. In current methods for HLA typing, both alleles of a heterozygote are amplified and typed or sequenced simultaneously, often making it difficult to unambiguously determine the sequence of the two alleles. Next-generation sequencing methods clonally propagate in parallel millions of single DNA molecules, which are then also sequenced in parallel. Recently, the read lengths obtainable by one such next-generation sequencing method (454 Life Sciences, Inc.) have increased to >250 nucleotides. These clonal read lengths make possible setting the phase of the linked polymorphisms within an exon and thus the unambiguous determination of the sequence of each HLA allele. Here we demonstrate this capacity as well as show that the throughput of the system is sufficiently high to enable a complete, 7-locus HLA class I and II typing for 24 or 48 individual DNAs in a single GS FLX sequencing run. Highly multiplexed amplicon sequencing is facilitated by the use of sample-specific internal sequence tags (multiplex identification tags or MIDs) in the primers that allow pooling of samples yet maintain the ability to assign sequences to specific individuals. We have incorporated an HLA typing software application developed by Conexio Genomics (Freemantle, Australia) that assigns HLA genotypes for these 7 loci (HLA-A, -B, -C, DRB1, DQA1, DQB1, DPB1), as well as for DRB3, DRB4, and DRB5 from 454 sequence data. The potential of this HLA sequencing system to analyze chimeric mixtures is demonstrated here by the detection of a rare HLA-B allele in a mixture of two homozygous cell lines (1/100), as well as by the detection of the rare nontransmitted maternal allele present in the blood of a severe combined immunodeficiency disease syndrome (SCIDS) patient.

Neonatal pseudo-Bartter syndrome due to maternal eating disorder.

A total of 4 of 153 low birth weight infants at our hospital were found to have pseudo-Bartter syndrome in 2005 and 2006. The neonates (two of whom were twins; light for gestational age 2, appropriate for gestational age 1 and small for gestational age 1) showed symptoms of apnea and/or poor feeding or patent ductus arteriosus, which disappeared by day 4. Hypokalemia, hypochloremia and metabolic alkalosis normalized by day 8. The mothers had repeatedly rushed to the restroom after eating while in hospital, and were lighter at delivery than before pregnancy; however, vomiting was not observed. The mothers had several stress factors related to pregnancy, and all recovered from the eating disorder after delivery. Urinary Cl/creatinine (mequiv. mg(-1)) and serum Mg in the infants were <0.1 and 1.6 to 2.3 mg per 100 ml, respectively. Eating disorder during pregnancy may have caused Bartter-like syndrome and weight loss, and led to the same syndrome and intrauterine growth retardation in the offspring. Therefore, a hidden maternal eating disorder may underlie neonatal pseudo-Bartter syndrome.

Plasma angiotensin II concentrations in the early neonatal period.

BACKGROUND: There have been only a few reports on the renin-angiotensin system in low birthweight infants; in particular, plasma angiotensin II concentrations have not been studied. AIM: To investigate plasma angiotensin II concentrations in early neonatal infants including low birthweight infants. METHODS: Forty six patients were studied, of whom 14 weighed not less than 2500 g (normal birth weight), 16 weighed less than 2500 g but not less than 1500 g (moderately low birth weight), and 16 weighed less than 1500 g (very low birth weight). Blood samples were collected twice, on day 0 and day 7. Angiotensin II concentration was assayed using an enzyme immunoassay kit with a microplate. RESULTS: Geometric means of angiotensin II concentrations on day 7 were 19 pg/ml in the normal birthweight group, 28 pg/ml in the moderately low birthweight group, and 76 pg/ml in the very low birthweight group. The concentrations on day 7 in the very low birthweight group were significantly higher than those in the normal birthweight and moderately low birthweight groups (p = 0.005, p = 0.031). There were significant correlations between angiotensin II concentration on day 7 and gestational age (r(s) = -0.4, p = 0.007) and birth weight (r(s) = -0.36, p = 0.016). CONCLUSIONS: Specific physiological conditions associated with a very low birth weight are thought to be responsible for the increased concentration of angiotensin II on day 7. It is necessary to measure angiotensin II concentration for a longer period after birth and study the factors that could influence it.

Epidemiological and outcome characteristics of major burns in Tokyo.

The Tokyo Burn Unit Association (TBUA) was established in 1983 funded by the Tokyo Metropolitan Government, and is organized by 13 burn units in Tokyo. TBUA covers more than 90% of severe burn patients occurring in Tokyo, and all of the cases are registered according to the burn injury registration format. The purpose of this study is to analyze the registered data and to elucidate epidemiological and outcome characteristics of major burn injuries in Tokyo. The total of 6988 hospitalized patients had data for epidemiological analysis, and 6401 patients had complete data for outcome analysis as well, and were included in this study. The characteristic profiles for the analysis included age, sex, cause of burns, inhalation injury, %BSA, burn index (BI), length of burn unit stay, and outcome, and were analyzed by age groups. The mean age of the patients was 40.4 years, and 63% of them were male. It was noteworthy that 25% of the total patients were elderly patients over 60 years of age. Flame was the most common cause making up 45.6% followed by scalding (32.0%). The overall mortality rate was 15.4%. Inhalation injury was accompanied in 27.3% of burn patients. The mortality rate was 34.6% with inhalation injury, and 8.2% without inhalation injury. Causes of death showed that multiple organ failure made up 36.9% of total mortality, followed by sepsis 25.2 and shock 19.0%. The burn size (%BSA and BI) and inhalation injury were the factors for high mortality rate in all age groups whereas age was a predictor for high mortality in the patients older than 16 years of age. Gender was not a factor for high mortality in any age group. The mortality rate showed mildly decreasing tendency since 1995 for which implementation of skin bank was thought to be responsible.

Quantification of human mitochondrial DNA in a real time PCR.

Recently, a moderately priced machine for real-time quantitative PCR has become available, the Perkin Elmer 5700. The rapid and quantitative assay of mitochondrial DNA (mtDNA) copy number is potentially useful in a variety of molecular, evolutionary and forensic fields. Using this new tool, we have evaluated the precision and reliability of the real time PCR to quantify undeleted mitochondrial genome copy number, and to determine the frequency of an age-associated deletion of 4977 base pairs in length, in 42 human iliopsoas muscle DNA samples from persons of known age. We have evaluated the accuracy with which age can be predicted, knowing only the frequency of this common 4977 bp deletion, and derived a statistical formula which describes the confidence with which the 4977 bp frequency predicts age. The results indicate that the mutation frequency could be used to distinguish between tissue from young and old individuals. However in this data set, while there was considerable agreement of 4977 bp frequency among replicates from the same individual sample, there was substantial diversity of mean mutation frequency between individuals of the same or similar ages. The simplest interpretation of these results is that there are biological modifiers of 4977 bp frequency that are age-independent, which are potentially interesting but may limit the usefulness of this deletion frequency alone as a "molecular forensic clock."

In silico mapping of complex disease-related traits in mice.

Experimental murine genetic models of complex human disease show great potential for understanding human disease pathogenesis. To reduce the time required for analysis of such models from many months down to milliseconds, a computational method for predicting chromosomal regions regulating phenotypic traits and a murine database of single nucleotide polymorphisms were developed. After entry of phenotypic information obtained from inbred mouse strains, the phenotypic and genotypic information is analyzed in silico to predict the chromosomal regions regulating the phenotypic trait.

Constituents of crinoidea. 2. Isolation and structure of the novel type gangliosides from the feather star Comanthus japonica.

Two novel type gangliosides CJP2 and CJP3 have been obtained from the feather star Comanthus japonica. On the basis of methylation linkage analysis combined with ammonolysis and other chemical and spectroscopic evidence, the chemical structures of CJP2 and CJP3 were determined to be alpha-9-O-Me-NeuGc-(2-->3)-inositolphosphoceramide and alpha-9-O-Me-NeuGc-(2-->11)-alpha-9-O-Me-NeuGc-(2-->3)-inositolphosphoceramide, respectively. These gangliosides are unique in that they are inositolphosphoceramide derivatives possessing sialic acid; such gangliosides have not previously been identified. The presence of 9-O-methyl-N-glycolyl-neuraminosyl residues is also unique in naturally occurring gangliosides.

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease.

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.

Constituents of holothuroidea. 10. Isolation and structure of a biologically active ganglioside molecular species from the sea cucumber Holothuria leucospilota.

Three ganglioside molecular species, HLG-1 (1), HLG-2 (2), and HLG-3 (3) have been obtained from the lipid fraction of the chloroform/methanol extract of the sea cucumber Holothuria leucospilota. The structures of these gangliosides have been determined, on the basis of chemical and spectroscopic evidence, as 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (1), 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->4)-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (2) and 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-neuraminosyl)-(2-->4)-(N-aetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moieties were composed of heterogeneous phytosphingosine, sphingosine and 2-hydroxy fatty acid units. Compounds 2 and 3 represent new ganglioside molecular species. These three ganglioside molecular species showed neuritogenic activity toward the rat pheochromocytoma cell line, PC-12 cell, in the presence of NGF (nerve growth factor).

A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan.

BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.

Constituents of ophiuroidea. 1. Isolation and structure of three ganglioside molecular species from the brittle star Ophiocoma scolopendrina.

Three ganglioside molecular species, OSG-0 (1), OSG-1 (2), and OSG-2 (3) have been obtained from the polar lipid fraction of the chloroform/methanol extract of the brittle star Ophiocoma scolopendrina. The structures of these gangliosides have been determined on the basis of chemical and spectroscopic evidence as 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (1), 1-O-[8-O-sulfo-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyll-ceramide (2) and 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->8)-(N-acetyl- and N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moieties were composed of heterogeneous unsubstituted fatty acid, 2-hydroxy fatty acid and phytosphingosine units. Compounds 2 and 3 represent new ganglioside molecular species.

Transcriptional analysis of multiple sclerosis brain lesions reveals a complex pattern of cytokine expression.

Multiple sclerosis (MS) is a common and severe neurological disorder associated with an autoimmune response directed against myelin components within the CNS. Lymphocyte activation, extravasation, and recruitment, as well as effector function, involves the turning on and off of a number of genes, thus triggering specific transcriptional pathways. The characterization of the transcriptome in MS lesions should provide a better understanding of the mechanisms that generate and sustain the pathogenic immune response in this disease. Here we performed transcriptional profiling of 56 relevant genes in brain specimens from eight MS patients and eight normal controls by kinetic RT-PCR. Results showed a high transcriptional activity for the gene coding for myelin basic protein (MBP); however, it was not differentially expressed in MS samples, suggesting that remyelination is an active process also in the noninflammatory brain. CD4 and HLA-DRalpha transcripts were dramatically increased in MS as compared with controls. This reveals a robust MHC class II up-regulation and suggests that Ag is being presented locally to activated T cells. Although analysis of cytokine and cytokine receptor genes expression showed predominantly increased levels of several Th1 molecules (TGF-ss, RANTES, and macrophage-inflammatory protein (MIP)-1alpha) in MS samples, some Th2 genes (IL-3, IL-5, and IL-6/IL-6R) were found to be up-regulated as well. Similarly, both proinflammatory type (CCR1, CCR5) and immunomodulatory type (CCR4, CCR8) chemokine receptors were differentially expressed in the MS brain. Overall, our data suggest a complex regulation of the inflammatory response in human autoimmune demyelination.

Preoperative diagnosis of ileal lipoma by endoscopic ultrasonography probe.

The occurrence of tumor in the small intestine is relatively rare. It has been demonstrated that lipoma of the ileum is a cause of intussusception. We report a 59-year-old man admitted to our hospital for lower abdominal pain. Diagnosis of intussusception was made by abdominal x-ray and ultrasonography. Enema contrast studies revealed ileocolic intussusception. Colonoscopy revealed a tumor with an submucosal tumor (SMT)-like head and coil-spring appearance in the ascending colon. Endoscopic ultrasonography (EUS) revealed a hyperechoic submucosal lesion with features compatible with lipoma. Subsequently, this was confirmed histopathologically after resection. To our knowledge, this is the first report of preoperative diagnosis of ileal lipoma by EUS.

Sedative activity of two flavonol glycosides isolated from the flowers of Albizzia julibrissin Durazz.

The flowers of Albizzia julibrissin are used as a sedative in oriental traditional medicine. The phytochemical study of this plant allowed the isolation of two flavonol glycosides, quercitrin (1) and isoquercitrin (2). The sedative activity of these compounds was evaluated, and both compounds 1 and 2 increased pentobarbital-induced sleeping time in dose-dependent manner in mice. These results support the use of the flowers of this plant as a sedative agent.

Rotundines A-C, three novel sesquiterpene alkaloids from Cyperus rotundus.

Rotundines A (1), B (2), and C (3), three novel sesquiterpene alkaloids with an unprecedented carbon skeleton, were isolated from the rhizomes of Cyperus rotundus. The structures of 1-3 were elucidated by spectral and chemical methods.

Cytotoxic lavandulyl flavanones from Sophora flavescens.

Two new lavandulylated flavanones, (2S)-2'-methoxykurarinone (1) and (-)-kurarinone (2), were isolated from the root of Sophora flavescens, together with two known lavandulyl flavanones, sophoraflavanone G (3) and leachianone A (4), and two known isoflavonoids, formononetin and l-maakiain. The structures of 1 and 2 were determined on the basis of optical rotation and spectral evidence and by comparison with known compounds. Compounds 1-4 exhibited cytotoxic activity against human myeloid leukemia HL-60 cells.