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Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Zratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10−21s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z= 8 and N= 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called ‘doubly magic’ nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N= 20 shell structure.

Nuclear magic numbers correspond to fully occupied energy shells of protons or neutrons inside atomic nuclei. Doubly magic nuclei, with magic numbers for both protons and neutrons, are spherical and extremely rare across the nuclear landscape. Although the sequence of magic numbers is well established for stable nuclei, experimental evidence has revealed modifications for nuclei with a large asymmetry between proton and neutron numbers. Here we provide a spectroscopic study of the doubly magic nucleus 78Ni, which contains fourteen neutrons more than the heaviest stable nickel isotope. We provide direct evidence of its doubly magic nature, which is also predicted by ab initio calculations based on chiral effective-field theory interactions and the quasi-particle random-phase approximation. Our results also indicate the breakdown of the neutron magic number 50 and proton magic number 28 beyond this stronghold, caused by a competing deformed structure. State-of-the-art phenomenological shell-model calculations reproduce this shape coexistence, predicting a rapid transition from spherical to deformed ground states, with 78Ni as the turning point. A spectroscopic study of 78Ni confirms its doubly magic nature and reveals it as a stronghold beyond which the magic numbers 28 and 50 break down because of competing deformation.

In the Longyearbyen CO2laboratory project, it is planned to inject carbon dioxide into a Triassic–Jurassic fractured sandstone–shale succession (Kapp Toscana Group) at a depth of 700–1000 m below the local settlement. The targeted storage sandstones offer moderate secondary porosity and low permeability (unconventional reservoir), whereas water injection tests evidence good lateral fluid flow facilitated by extensive fracturing. Therefore, a detailed investigation of fracture sets/discontinuities and their characteristics have been undertaken, concentrating on the upper reservoir interval (670–706 m). Datasets include drill cores and well logs, and observations of outcrops, that mainly show fracturing but also some disaggregation deformation bands in the sandstones. The fracture distribution has a lithostratigraphical relationship, and can be subdivided into: (A) massive to laminated shaly intervals, offering abundant lower-angle shear fractures; (B) massive to thin-bedded, heterogeneous, mixed silty–shaly intervals, with a predominance of non-systematic, pervasive bed-confined fractures; and (C) massive to laminated, medium- to thick-bedded, fine- to coarse-grained sandstones with a lower frequency of mostly steep fractures. These domains represent pseudo-geomechanical units characterized by specific fracture sets and fracture intensity, with indicated relationships between the bed thickness and fracture intensity, and with domains separated along bedding interfaces. We discuss the impact of these lithostructural domains on the fluid flow pathways in the heterolithic storage unit.

Background & Objective: The factor VIII (FVIII) B domain shares very little amino acid homology with other known proteins and is not directly necessary for procoagulant activity. Despite this, missense mutations within the B domain have been reported in patients with hemophilia A. Given that the B domain is dispensable for secretion and function of FVIII, we hypothesized that these mutations should not be causative of hemophilia A in these patients. Methods: Plasmid vectors containing B domain missense mutations that were reported to be associated with moderate/severe hemophilia A (T751S, D826E, V993L, H1047Y, T1353A, N1441K, L1462P, E1579D, A1591S, P1641L and S1669L) were analyzed for their effect on synthesis and secretion compared with FVIII wild‐type (WT) following transient transfection into COS‐1 and CHO cells in vitro. Further, H1047Y, N1441K and E1579D mutants were expressed in vivoin a hemophilia A mouse model by hydrodynamic tail‐vein injection. Results: FVIII activity and antigen levels for all mutants expressed into the conditioned media of COS‐1 and CHO cells were similar to FVIII WT. Also, plasma expression of these mutants was similar to FVIII WT in hemophilia A mice. An in vivotail clip bleeding assay also demonstrated that blood loss from hemophilia A mice expressing FVIII WT, H1047Y, N1441K and E1579D was similar. Conclusions: We conclude that most missense mutations within the FVIII B domain would be unlikely to lead to severe hemophilia A and that the majority of such missense mutations represent polymorphisms or non‐pathologic mutations.

Pilocytic astrocytomas are classified as WHO grade I gliomas that occur predominantly in children and young adults. Reports of the tumors in elderly adults are extremely rare. We describe two cases of pilocytic astrocytoma in elderly adults, a 68-year-old man and a 71-year-old woman. Brain computed tomography (CT) and magnetic resonance imaging (MRI) revealed well-circumscribed lesions associated with contrast enhancement and minimal surrounding edema. Pathological studies revealed findings consistent with pilocytic astrocytomas. Although these tumors are rarely found in elderly adults, pilocytic astrocytomas should be considered in the differential diagnosis if the radiographic features of the tumors are characteristic of pilocytic astrocytomas.

The ansa cervicalis(AC) is part of the cervical plexus and is formed by the ventral rami of spinal nerves C1-C3. It is usually formed by two roots that run parallel to each other and then form a loop anterior to the internal jugular vein. Herein, we report a rare case where the AC was found deep to the internal carotid artery and common carotid artery and had sympathetic contributions.

In order to estimate work of external force per unit area to infiltrate molten aluminum into bundle of two types of carbon fibers which were PAN (polyacrylonitrile) based and pitch based, wettability of graphite by molten pure aluminum and aluminum – 2.0, 2.9 and 9.1 mass % magnesium alloy was measured using sessile drop method. Basal plane and prismatic plane exist on the surface in the case of PAN and pitch based fibers, respectively. The wettability was examined in the atmosphere of Ar + 3 vol. % H2 at 1189 K. Both the contact angle and the surface tension were estimated using Young-Laplace equation. The surface tension decreased form 1.0 N/m at 0 mass % Mg to 0.7 mass % Mg at 9.1 mass % Mg. The contact angle between molten aluminum and basal plane or prismatic plane of graphite was 127º or 148º respectively. In the case of basal plane, the contact angle increased with increasing magnesium content. In the case of prismatic plane, whereas, the contact angle decreased from 155º at 2.0 mass % Mg to 125º at 2.9 mass % Mg. The work of external force for infiltration was calculated using Young’s equation. In the case of basal plane, the work was constant at 0.6 J/m2 regardless of magnesium content. In the case of prismatic plane, the work decreased with increasing magnesium content. It was found that the influence of magnesium content on the work would be different between using PAN-based carbon fiber and using pitch-based carbon fiber.

The stabilization of proteins due to cavity-filling mutations are thought to be attributable to removal of hydrophobic residues from solvent exposure in denatured (D) state and formation of close packing in native (N) state. However, it is still unclear which contribution is dominant to stabilize proteins, because experiments can probe only the free energy difference between the two states (N and D). To address this question, we carried out molecular dynamics simulations, circular dichroism (CD) measurements, and X-ray crystallographic experiments on the cavity-filling mutations of the DNA-binding domain of the Myb transcriptional regulator. The cavity size was altered by systematic natural and nonnatural amino acid substitutions at a fixed site. The stability free energy change (ΔΔG(N→D;W→M)) and the cavity-size change (ΔV) calculated for the mutations agreed with the experimental data observed by urea-titration/CD measurements and crystallographic structure analysis, respectively. We found that the experimental ΔΔG values correlate well with the calculated native-state free energy change due to mutations ΔG(N;W→M) and with ΔV (their correlation coefficients are larger than 0.9) but not with the denatured-state ΔG(D;W→M). These results demonstrated that the decrease in cavity size increases the protein stability by lowering the free energy of native state for this protein. We discussed physicochemical meanings of our calculation results for ΔG(N;W→M) and ΔG(D;W→M).

Abstract: Spindle cell hemangioendothelioma occurring in skeletal muscle is extremely rare. No reported studies have performed an imaging evaluation of intramuscular spindle cell hemangioendothelioma. We report on such a tumor arising in an unusual site, the right extensor digiti minimi, in a 46-year-old woman. An en bloc resection was performed and the patient has been disease free for 8 years. Radiologic imaging in the present case showed similar findings to those described in intramuscular hemangioma.

An in vitro processing system of mouse rRNA was achieved using an RNA polymerase I‐specific transcription system, (S100) and recombinant plasmids consisting of mouse rRNA gene (rDNA) segments containing the transcription initiation and 5′‐terminal region of 18S (or 41S) rRNA. Pulse‐chase experiments showed that a specific processing occurred with transcripts of the plasmid DNAs when the direction of transcription was the correct orientation relative to the 18S rRNA coding sequence, but not with transcripts of the DNA templates in which this coding sequence was in the opposite orientation. From the S1 nuclease protection analyses, we concluded that there are several steps of endonucleolytic cleavage including one 105 nucleotides upstream from the 5′ end of 18S rRNA. Intermediates cleaved at this site were identified in in vivo processing of rRNA. This result indicates that endonucleolytic cleavage takes place 105 nucleotides upstream from the 5′ terminus of 18S rRNA prior to the formation of mature 18S rRNA. Trimming or cleavage of the 105 nucleotides may be involved in the formation of the 5′ terminus of mature 18S rRNA.

We report a patient with refractory anemia with excess blasts who showed a lineage-unrestricted hematologic response to granulocyte colony-stimulating factor (G-CSF). After 17 months of a stable disease state, the patient developed pneumonia, progression of cytopenia, and reduced cellularity and blast mass in the bone marrow. He was given G-CSF to overcome the pneumonia. Not only the neutrophil count, but also the platelet count increased soon after initiation of the G-CSF therapy; both counts became normal on the fifth day of the G-CSF therapy. Additionally, the anemia improved gradually. The neutrophil and platelet counts were maintained in the normal range for 3 months after cessation of the G-CSF. In vitro studies showed that G-CSF alone stimulated megakaryocyte colony formation from bone marrow mononuclear cells (BMMNC), and accessory cells in the BMMNC were necessary for expression of this G-CSF-induced in vitro megakaryocytopoiesis. These results suggest that, in coordination with accessory cells, G-CSF stimulated megakaryocytopoiesis in the patient. This case provides valuable information for understanding the mechanisms of a lineage-unrestricted hematologic response to G-CSF, which is very rarely observed in MDS.

A magnetic determination of the dipole moment of the Pfirsch-Schluter current in a finite beta stellarator/heliotron plasma is described. The rotating cosine saddle diagnostic coils and the poloidal flux loops are used to identify the dipole current in a finite beta toroidal plasma. A typical dipole moment of the toroidal current in the standard Heliotron E configuration is 0.6 kA m, when the volume averaged beta is 0.50% at a magnetic field of 0.94 T. The measured equilibrium dipole current is practically proportional to the diamagnetic volume average beta available up to 0.95%. The observed dipole moment of the Pfirsch-Schluter current is compared with a magnetohydrodynamic (MHD) calculation for a finite beta stellarator plasma

We performed curettage and bone grafting of amyloid cysts of the femoral neck in five patients on long-term haemodialysis. All had had hip pain on weight-bearing. The duration of haemodialysis before the operation averaged 15 years and the average age of the patients was 53 years. All the large cystic lesions were located in the anterosuperior quadrant of the femoral neck. At operation, they were found to consist of fibrous tissue containing amyloid deposits. Postoperatively, all five patients had painless hips and the grafts had incorporated into the bone defects.

The rate of blood flow in free bone grafts in rabbits was monitored for 8 weeks after transplantation using the hydrogen washout technique. Blood flow was present at 2 weeks in both autografts and allografts, although the rate was significantly lower in the allograft compared to the autograft. Autografts showed a rapid increase from 2 to 3 weeks and a maximum flow 4 weeks after transplantation, whereas in allografts the rate of increase was slower. This study has demonstrated that the hydrogen washout technique is a useful method of monitoring blood flow and can be applied to clinical investigations.

A technique of oblique tibial osteotomy is described which is effective in correcting varus and medial rotational deformities in young children. The oblique cut in one plane corrects both elements of the deformity at the same time. We have used the method on both legs in four children and satisfactory results were obtained.

Factor IX BMNagoya (IX Nagoya) is a natural mutant of factor IX responsible for severe hemophilia B. A patient with this mutant is characterized by a markedly prolonged ox brain prothrombin time. IX Nagoya was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that treatment of IX Nagoya with factor XIa/Ca2+resulted in cleavage only at the Arg145-Ala146bond. Reversed-phase high performance liquid chromatography of a trypsin digest of IX Nagoya showed an aberrant peptide, which was further digested with proteinase Asp-N. Primary structure analysis of one of the Asp-N peptides revealed that Arg180is replaced by Trp. An essentially complete (99%) amino acid sequence of IX Nagoya was obtained by sequencing fragments derived from a lysyl endopeptidase digest in which no other substitutions in the catalytic triad or substrate binding site were found. We also found that IX Nagoya is activated by α-chymotrypsin or rat mast cell chymase by monitoring the rate of factor X activation using a fluorogenic peptide substrate in the presence of factor VIII, phospholipids, and Ca2+. These results indicate that the substitution of Arg180by Trp impairs the cleavage by factor XIa required for activation of this zymogen and that the substitution causes hemophilia BM.

A prospective study was performed on 62 hands in 45 consecutive patients on chrome dialysis carpal tunnel syndrome developed within an average of 116 months after formation of the arterio-venous fistula. We measured the intra-carpal canal pressure by the wick catheter technique and performed neurography. At operation, a markedly thickened transverse carpal ligament was usually found. A pneumatic tourniquet was applied in all except three cases, whose functioning fistulae were made of implants, but no complications such as obturation of the fistulae occurred. Thirty-three (76.7%) of 43 cases had good results. Full recovery of sensibility was obtained in all hands in which symptoms had been present for less than two years. There was no benefit from operation in two patients (4.7%), both of whom had symptoms for more than two years.

Summary Anti-thoracic duct lymphocyte globulin (ALG) therapy is effective in patients with aplastic anemia. We examined the effect of ALG on human megakaryocyte progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) in vitro. Normal human bone marrow mononuclear cells (MNC) were cultured in plasma clots with varying concentrations of ALG or non-immunized horse IgG. After 12 days of culture, significant megakaryocyte colony formation was observed in cultures containing ALG but not in cultures containing non-immunized horse IgG. The peak stimulatory effect seemed to occur with 10–25µg/ml of ALG. When marrow MNC, depleted of adherent and T cells, were cultured in plasma clots with ALG, its stimulatory effect on megakaryocytopoiesis decreased markedly. Finally, it was demonstrated that ALG stimulated marrow MNC to produce a factor stimulatory for CFU-Meg. The in vitro megakaryocytopoietic stimulatory effect of ALG may be related to its clinical efficacy in some patients with aplastic anemia.

We have reviewed 83 patients who had undergone canal-expansive laminoplasty for the treatment of cervical myelopathy between 1982 and 1991. The procedures used for laminoplasty were a Z-plasty in 35 patients, unilateral laminoplasty in 19, and sagittal splitting of the spinous processes in 29. At an average follow-up of more than two years and five months, there were no significant differences in clinical results among the three operations, and excellent or good results were obtained in more than 70% of the patients. However, Z-plasty was the least preferable because this procedure had the longest operating time and the greatest intraoperative blood loss. The sagittal splitting procedure is recommended in routine laminoplasty in order to avoid complications at the site of osteotomy, and to allow simultaneous posterior fusion to be easily performed.

In this paper, a de-NOx system, that complies with the envirorunental regulation and at the same time saves the operation cost, is introduced. The paper consists of two parts, i.e., the modeling of the NOx producing process and the design of the de-NOx control system.

The blood supply to the central third of the Achilles tendon was studied in adult rabbits using the hydrogen washout technique before and after soft tissue dissection including paratenon. The soft tissue dissection caused a decrease of the blood flow rate in the Achilles tendon by approximately 35 per cent. These results may indicate that the central third of the tendon with a paratenon receives its blood supply from the extrinsic vascular system by approximately 35 per cent and from the intrinsic vascular system by approximately 65 per cent.

The principal determinant of the pyrimidine preference by the c-Myb DNA-binding domain at the initial base of the consensus sequence was investigated by mutation of both the protein and the DNA base pairs, with analysis by a filter binding assay. Amino acid residue 187 was revealed to interact with the pyrimidine base position, as estimated from our previous complex structure. Unexpectedly, since the pyrimidine preference is retained even in the Gly187 mutant, the principal origin of the base specificity should not occur via the direct-readout mechanism, but by an indirect-readout mechanism, namely in the intrinsic "bendability" of the pyrimidine-purine step of the DNA duplex. A significant but rather small positive base pair roll is detectable in the conformation of DNA in complex with the c-Myb DNA-binding domain. Following the conventional chemical rules of the direct-readout mechanism, amino acid mutagenesis at position 187 yielded several new base preferences for the protein.

Rat liver 60 S ribosomal subunits were modified with 2-iminothiolane. After treatment with hydrogen peroxide, the cross-linked proteins were extracted and then separated into 24 fractions by chromatography on carboxymethylcellulose. Each protein fraction was then analyzed by diagonal polyacrylamide-sodium dodecyl sulfate gel electrophoresis (Sommer, A., and Traut, R.R. (1974) Proc. Natl. Acad. Sci. U. S. A. 71, 3946-3950). The pieces of gel containing cross-linked protein spots that were shifted from the diagonal line were labeled with 125I. The labeled protein was extracted from the gel and identified by three kinds of two-dimensional gel electrophoresis, followed by autoradiography. Fifty-three cross-linked protein pairs involving 35 protein species containing two acidic proteins were identified. From these and previous results, a preliminary model of the protein topography of the 60 S ribosomal subunit was constructed and discussed in relation to other functional data on 60 S ribosomal proteins.

Neighboring proteins in rat liver 60 S ribosomal subunits were investigated by two kinds of cross-linking techniques: treatment of 60 S subunits with 1) hydrogen peroxide, which promotes the formation of protein-protein disulfide linkages and 2) a disulfide-bridged bifunctional reagent dithiobis(succinimidyl propionate). The cross-linked protein complexes formed were separated by two-dimensional polyacrylamide gel electrophoresis in a basic-sodium dodecyl sulfate gel system under nonreducing conditions. Each complex in the gel was labeled with 125I and extracted under reducing conditions. The protein components of the complex were analyzed by two kinds of two-dimensional polyacrylamide gel electrophoresis, followed by autoradiography. Closely neighboring pairs disulfide-linked by hydrogen peroxide were identified as L4-L6, L4-L29, L6-L29, L18a-L29, and L29-L32; more distant pairs cross-linked with dithiobis(succinimidyl propionate) were identified as L3-L5, L3-L24, L3-L37a, L4-L14, L4-L18a, L5-L10, L5-L11, L7/L7a-L27, L7/L7a-L36, L13-L35, and L13a-L14.

We found a new thrombophilic tendency in a family with protein S deficiency. The propositus, a 38-year-old Japanese man, is an offspring of consanguineous marriage and suffered from recurrent episodes of thromboembolism. Hemostatic studies, including platelet counts, platelet aggregation, assays of coagulation factors, and plasminogen activity were all within normal limits. The levels of antithrombin III, alpha 2-macroglobulin, protein C, and protein C inhibitor were also normal. However, functional protein S activity in plasma was markedly decreased (9%) in the propositus. The family study revealed that the reduced levels of functional protein S, less than 5% to 29% of normal (normal range: mean +/- 2 SD of 15 normal adults were 44 to 180%), were found in 11 members of this family over three generations. Six of 11 members had severe protein S deficiency (less than 5%), whereas five had partial deficiency. Four of eight adults with protein S deficiency had recurrent episodes of thrombosis. Immunologic levels of protein S antigen were variable in this family and did not correlate closely with the functional levels. These results suggest that the recurrent thrombotic disease in this family appears to be associated with an inherited deficiency of functional protein S.

A monoclonal antibody to human antihemophilic factor (AHF, factor VIII) was derived from BALB/c mouse spleen cells fused with P3x63Ag8 mouse plasmacytoma cells. This antibody, harvested from culture medium or ascites fluid, reacted with purified AHF and with plasmas with normal subjects or classic hemophiliacs, as measured by enzyme-linked immunosorbent assay (ELISA), but not with plasmas from patients with severe von Willebrand's disease. The antibody possessed only IgG, heavy chains and kappa light chains. It blocked ristocetin-induced platelet agglutination and, to a lesser degree, platelet retention by glass bead columns, but it did not inhibit the procoagulant activity of AHF significantly. An amount of rabbit antiserum against AHF that provided equivalent inhibition of ristocetin-induced platelet agglutination inhibited glass bead retention much more effectively than the mouse monoclonal antibody. This difference was exaggerated in studies of the corresponding Fab fragments. These data suggest that the site or sites on the AHF complex molecule that are associated with ristocetin-induced platelet agglutination differ quantitatively or qualitatively from those associated with enhancement of platelet retention by glass beads. ELISA titers of immunoreactive AHF, using the monoclonal antibody, were closely correlated to those using rabbit antiserum against AHF in normal, hemophilic, and most von Willebrand's disease plasma.