Synergistic effect of factor VII gene polymorphisms causing mild factor VII deficiency in a case of severe factor X deficiency.

PubMed

Deshpande, Rutuja; Ghosh, Kanjaksha; Shetty, Shrimati

2017-01-01

Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation.

Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER).

PubMed

Napolitano, Mariasanta; Giansily-Blaizot, Muriel; Dolce, Alberto; Schved, Jean F; Auerswald, Guenter; Ingerslev, Jørgen; Bjerre, Jens; Altisent, Carmen; Charoenkwan, Pimlak; Michaels, Lisa; Chuansumrit, Ampaiwan; Di Minno, Giovanni; Caliskan, Umran; Mariani, Guglielmo

2013-04-01

Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (<1-45 years of age, 21 female). Severest phenotypes (central nervous system, gastrointestinal, joint bleeding episodes) were highly prevalent. Twenty-one patients received recombinant activated factor VII (24 courses), four received plasma-derived factor VII, and ten received fresh frozen plasma. Prophylactic schedules clustered into "frequent" courses (three times weekly, n=23) and "infrequent" courses (≤ 2 times weekly, n=15). Excluding courses for menorrhagia, "frequent" and "infrequent" courses produced 18/23 (78%) and 5/12 (41%) "excellent" outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on "frequent" administrations (three times weekly) and a 90 μg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency.

Use of recombinant factor VII for tooth extractions in a patient with severe congenital factor VII deficiency: a case report.

PubMed

Weinstock, Robert J; Onyejiuwa, Andrew; Shnayder, Garry; Clarkson, Earl I

2015-04-01

Patients with factor VII deficiency have an increased risk of prolonged perioperative hemorrhage. In this article, the authors present a case of severe factor VII deficiency in a patient who required tooth extraction. A 44-year-old woman with severe congenital factor VII deficiency sought care for a symptomatic, carious, and nonrestorable maxillary right second molar that required extraction. The authors obtained hematologic consultation, and the patient underwent the extraction under general anesthesia in the inpatient setting. Perioperative management included performing relevant laboratory studies, preoperative recombinant factor VII infusion, and postoperative intravenous aminocaproic acid administration. No hemorrhagic complications occurred throughout the perioperative course. The degree of factor VII deficiency correlates poorly with bleeding risk. Perioperative management is variable, requiring preoperative consultation with a hematologist. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

Recombinant activated factor VII in cardiac surgery: single-center experience.

PubMed

Singh, Sarvesh Pal; Chauhan, Sandeep; Choudhury, Minati; Malik, Vishwas; Choudhary, Shiv Kumar

2014-02-01

The widespread off-label use of recombinant activated factor VII for the control of refractory postoperative hemorrhage continues despite a warning from the Food and Drug Administration. Although effective in reducing the need for transfusion of blood and blood products, safety concerns still prevail. To compare the dosing and efficacy of recombinant activated factor VII between pediatric and adult patients, and in the operating room and intensive care unit. The records of 69 patients (33 children and 36 adults) who underwent cardiovascular surgery and received recombinant activated factor VII were reviewed retrospectively. The dose of recombinant activated factor VII, mediastinal drainage, use of blood and blood products, incidence of thrombosis, and 28-day mortality were studied. the efficacy of recombinant activated factor VII was comparable in adults and children, despite the lower dose in adults. Prophylactic use of recombinant activated factor VII decreased the incidence of mediastinal exploration and the duration of intensive care unit stay. A 4.3% incidence of thrombotic complications was observed in this study. The efficacious dose of recombinant activated factor VII is much less in adults compared to children. Prophylactic use of recombinant activated factor VII decreases the dose required, the incidence of mediastinal exploration, and intensive care unit stay, with no survival benefit.

[Coagulation factor VII levels in uremic patients and theirs influence factors].

PubMed

Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

2004-12-01

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

Monthly haemostatic factor variability in women and men.

PubMed

Hill, Alison M; Stewart, Paul W; Fung, Mark K; Kris-Etherton, Penny M; Ginsberg, Henry N; Tracy, Russell P; Pearson, Thomas A; Lefevre, Michael; Reed, Roberta G; Elmer, Patricia J; Holleran, Stephen; Ershow, Abby G

2014-01-01

Hormonal status influences haemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1. We studied 103 subjects (39 premenopausal women, 18 postmenopausal women and 46 men) during three, randomized, 8-week energy- and nutrient-controlled experimental diets in the Dietary Effects on Lipids and Thrombogenic Activity (DELTA) Study. Fasting blood samples were collected weekly during the last 4 weeks of each diet period, and haemostatic factors were quantified. Two linear mixed-effects models were used for fibrinogen, factor VII and PAI-1: one to estimate and compare group-specific components of variance, and the other to estimate additional fixed effects representing cyclical functions of day of menstrual cycle in premenopausal women. Systematic cyclical variation with day of menstrual cycle was observed for fibrinogen (P < 0.0001), factor VII (P = 0.0012) and PAI-1 (P = 0.0024) in premenopausal women. However, the amplitude of cycling was small relative to the total magnitude of intra-individual variability. In addition, the intra-individual variance and corresponding coefficient of variation observed in premenopausal women did not differ from postmenopausal women and men. The variability in haemostatic factors in premenopausal women is no greater than for postmenopausal women or men. Consequently, premenopausal women can be included in studies investigating haemostatic factor responses without controlling for stage of menstrual cycle. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Enhanced functional recombinant factor VII production by HEK 293 cells stably transfected with VKORC1 where the gamma-carboxylase inhibitor calumenin is stably suppressed by shRNA transfection.

PubMed

Wajih, Nadeem; Owen, John; Wallin, Reidar

2008-01-01

Recombinant members of the vitamin K-dependent protein family (factors IX and VII and protein C) have become important pharmaceuticals in treatment of bleeding disorders and sepsis. However, because the in vivo gamma-carboxylation system in stable cell lines used for transfection has a limited capacity of post translational gamma-carboxylation, the recovery of fully gamma-carboxylated and functional proteins is low. In this work we have engineered recombinant factor VII producing HEK 293 cells to stably overexpress VKORC1, the reduced vitamin K gamma-carboxylase cofactor and in addition stably silenced the gamma-carboxylase inhibitory protein calumenin. Stable cell lines transfected with only a factor VII cDNA had a 9% production of functional recombinant factor VII. On the other hand, these recombinant factor VII producing cells when engineered to overexpress VKORC1 and having calumenin stably suppressed more than 80% by shRNA expression, produced 68% functional factor VII. The technology presented should be applicable to all vertebrae members of the vitamin K-dependent protein family and should lower the production cost of the clinically used factors VII, IX and protein C.

46 CFR 134.170 - Operating manual.

Code of Federal Regulations, 2010 CFR

2010-10-01

...; (iii) Wave height; (iv) Wave period; (v) Wind; (vi) Current; (vii) Temperatures; and (viii) Other environmental factors. (4) The heaviest loads allowable on deck. (5) Information on the use of any special cross... (vii) Access to different compartments and decks. (12) A list of shutdown locations for emergencies and...

Enhanced Functional Recombinant Factor VII Production by HEK 293 Cells Stably Transfected with VKORC1 where the Gamma-Carboxylase Inhibitor Calumenin is Stably Suppressed by shRNA Transfection

PubMed Central

Wajih, Nadeem; Owen, John; Wallin, Reidar

2008-01-01

Introduction Recombinant members of the vitamin K-dependent protein family (factors IX and VII and protein C) have become important pharmaceuticals in treatment of bleeding disorders and sepsis. However, because the in vivo γ-carboxylation system in stable cell lines used for transfection has a limited capacity of post translational γ carboxylation, the recovery of fully γ-carboxylated and functional proteins is low. Materials and Methods In this work we have engineered recombinant factor VII producing HEK 293 cells to stably overexpress VKORC1, the reduced vitamin K γ-carboxylase cofactor and in addition stably silenced the γ-carboxylase inhibitory protein calumenin. Results and Conclusions Stable cell lines transfected with only a factor VII cDNA had a 9% production of functional recombinant factor VII. On the other hand, these recombinant factor VII producing cells when engineered to overexpress VKORC1 and having calumenin stably suppressed more than 80% by shRNA expression, produced 68% functional factor VII. The technology presented should be applicable to all vertebrae members of the vitamin K-dependent protein family and should lower the production cost of the clinically used factors VII, IX and protein C. PMID:18177690

Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

PubMed

Koizume, Shiro; Miyagi, Yohei

2015-01-01

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

Effects of the Application of the New Nuclear Data Library ENDF/B to the Criticality Analysis of AP1000

NASA Astrophysics Data System (ADS)

Kuntoro, Iman; Sembiring, T. M.; Susilo, Jati; Deswandri; Sunaryo, G. R.

2018-02-01

Calculations of criticality of the AP1000 core due to the use of new edition of nuclear data library namely ENDF/B-VII and ENDF/B-VII.1 have been done. This work is aimed to know the accuracy of ENDF/B-VII.1 compared to ENDF/B-VII and ENDF/B-VI.8. in determining the criticality parameter of AP1000. Analysis ws imposed to core at cold zero power (CZP) conditions. The calculations have been carried out by means of MCNP computer code for 3 dimension geometry. The results show that criticality parameter namely effective multiplication factor of the AP1000 core are higher than that ones resulted from ENDF/B-VI.8 with relative differences of 0.39% for application of ENDF/B-VII and of 0.34% for application of ENDF/B-VII.1.

Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

PubMed

Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas

2015-05-15

Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. Copyright © 2015 John Wiley & Sons, Ltd.

Acquired factor VII deficiency associated with acute myeloid leukemia.

PubMed

Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

2015-04-01

Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

Management of Surgical Third Lower Molar Extraction and Postoperative Progress in Patients With Factor VII Deficiency: A Clinical Protocol and Focus on This Rare Pathologic Entity.

PubMed

Passarelli, Pier Carmine; Pasquantonio, Guido; D'Addona, Antonio

2017-10-01

The purpose of the present study was to analyze the management of surgical third molar extraction and postoperative progress in patients with a diagnosis of factor VII deficiency. Close collaboration between the oral-maxillofacial surgeon and hematologist will allow the team to categorize the risk and operate safely, thereby minimizing the incidence and severity of intraoperative and postoperative complications. The present retrospective study included 7 patients with factor VII deficiency who had undergone third lower molar surgery. Their factor VII deficiency ranged from 10.5 to 21.0%. Recombinant activated factor VII (rFVIIa) (coagulation factor VIIa [recombinant]; NovoSeven RT; Novo Nordisk, Bagsvaerd, Denmark) was transfused intravenously in a single dose of 25 μg/kg body weight, 30 minutes before surgical extractions. After the surgery, betamethasone, an analgesic, and an ice pack were administered. Pretreatment with recombinant activated factor VII resulted in excellent hemostasis. No hemorrhagic complications and no postoperative major bleeding were observed. The extraction of the third lower molar appears to be a safe procedure for patients with factor VII deficiency when appropriate prophylaxis with rFVIIa is used. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassay.

PubMed

Amano, Satoshi; Ogura, Yuki; Akutsu, Nobuko; Nishiyama, Toshio

2007-02-01

Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor-beta1 (TGF-beta1). The synthesis of type VII collagen was elevated by TGF-beta1, platelet-derived growth factor, tumor necrosis factor-alpha, and interleukin-1beta, but not by TGF-alpha. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level.

Interrelation between factor VII, prekallikrein, and hyperfibrinolysis in advanced cirrhosis.

PubMed Central

Violi, F; Alessandri, C; Ferro, D; Saliola, M; Cordova, C; Musca, A; Balsano, F

1989-01-01

Factor VII and prekallikrein activities were studied in 37 patients with liver cirrhosis who were in a decompensated state. Sixteen of them died 30-70 days after admission; 21 survived and were discharged after 30-80 days. Seven who died and six survivors had signs of hyperfibrinolysis: factor VII activity differentiated the two groups independently of the presence of hyperfibrinolysis. The presence of hyperfibrinolysis significantly reduced prekallikrein activity, which did not differentiate clearly survivors from non-survivors. Long term follow up of survivors showed a good correlation between factor VII and prekallikrein activities with long term survival. Hyperfibrinolysis seemed to influence the clinical course of patients: 87% of patients with hyperfibrinolysis who died had fatal haemorrhagic episodes. Low factor VII activity may be a precursor of terminal liver insufficiency. PMID:2613916

What Are Rare Clotting Factor Deficiencies?

MedlinePlus

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven®)

PubMed Central

Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

2013-01-01

This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. Case report A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. Conclusion This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of severe side effects. PMID:23516010

Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven(®)).

PubMed

Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

2013-01-01

This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of severe side effects.

What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

MedlinePlus

... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

Effects of Recombinant Activated Factor VII in Traumatic Nonsurgical Intracranial Hemorrhage

DTIC Science & Technology

2006-09-01

with inhibitors to factors VIII and IX, and it is ap- proved in Europe for the treatment of patients with acquired hemophilia, congenital FVII deficiency...GARY P. WRATTEN SURGICAL SYMPOSIUM Effects of Recombinant Activated Factor VII in Traumatic Nonsurgical Intracranial Hemorrhage Christopher E. White...OBJECTIVE: To determine whether treatment with recombi- nant activated factor VII (rFVIIa) will prevent progression of bleeding in nonsurgical

Warfarin dose requirement in Turkish patients: the influences of patient characteristics and polymorphisms in CYP2C9, VKORC1 and factor VII.

PubMed

Yildirim, E; Erol, K; Birdane, A

2014-01-01

To determine the contribution of cytochrome P4502C9 (CYP2C9), vitamin K epoxide reductase (VKORC1) and factor VII genotypes, age, body mass index (BMI), international normalized ratio (INR) and other individual patient characteristics on warfarin dose requirements in an adult Turkish population. Blood samples were collected from 101 Turkish patients. Genetic analyses for CYP2C9*2 and *3, VKORC1 -1639 G>A and factor VII -401 G>T polymorphisms were performed. Age, INR, BMI values and other individual patient characteristics were also recorded. The mean daily warfarin dosage was significantly higher in patients with the CYP2C9*1/*1 genotype than in the CYP2C9*2/*2 and CYP2C9*1/*3 groups (p ≤ 0.05). With respect to the VKORC1 -1639 G>A polymorphism, the mean warfarin daily dose requirement was higher in the wild type group compared to the heterozygous group (p≤0.001). The mean daily dose requirement for patients with the GG form of factor VII was significantly higher than that of patients with the TT genotype (p ≤ 0.05). Age, gender, BMI, INR had no statistically significant correlation with warfarin dose (p ≥ 0.05). Polymorphisms in CYP2C9, VKORC1 and factor VII did partially affect daily warfarin dose requirements, while age, gender, BMI and INR do not. However, further case-control studies with a larger study size and different genetic loci are needed to confirm our study.

Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology.

PubMed

Pfeiffer, Caroline; Mathieu-Dupas, Eve; Logghe, Pauline; Lissalde-Lavigne, Géraldine; Balicchi, Julien; Caliskan, Umran; Valentin, Thomas; Laune, Daniel; Molina, Franck; Schved, Jean François; Giansily-Blaizot, Muriel

2016-05-01

While the immune response to hemophilic factors in hemophilia has been widely studied, little is known about the development of anti-Factor VII (FVII) antibodies in FVII deficiency. We developed a robust technique based on the x-MAP technology to detect the presence of antibodies against FVII and characterize their isotype and validated this method using blood samples from 100 patients with FVII deficiency (median FVII clotting activity [FVII:C]: 6%) and 95 healthy controls. Anti-FVII antibodies were detected in patients but also in some controls, although the concentration of total immunoglobulin G (IgGt) and IgG1 and IgG4 subclasses was significantly different between groups. The IgG1 subclass concentrations remained significantly different also when only untreated patients were compared with controls. This difference could partially be related to the F7 genotype, particularly in patients harboring the p.Arg139Gln mutation. This x-MAP-based method might be useful for assessing the immunogenicity of novel FVII compounds and of activated FVII (FVIIa) concentrates. Further prospective studies are needed to better understand the clinical relevance of these antibodies in the management of patients with FVII deficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

PubMed

Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2012-03-01

Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

PubMed

Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

2017-06-01

During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation of systemic coagulation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With Adverse Outcomes

DTIC Science & Technology

2010-07-01

using the FVII coagulant activity (FVII:C) assay, a one- stage assay using thromboplastin tissue factor , which quantifies FVII clotting activity in...and the resultant production of dysfunctional factors II, VII, and X. This study focused on PT specifically because this measure examines the TF...ORIGINAL ARTICLE Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With

Coagulation factor VII is regulated by androgen receptor in breast cancer.

PubMed

Naderi, Ali

2015-02-01

Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Case report: a 70-year-old man with undiagnosed factor VII deficiency presented with acute ischemic stroke.

PubMed

Ip, Hing-Lung; Chan, Anne Yin-Yan; Ng, Kit-Chung; Soo, Yannie Oi-Yan; Wong, Lawrence Ka-Sing

2013-11-01

Factor VII deficiency is an uncommon coagulation disorder that patient usually presents with bleeding diathesis, but thrombotic event has been reported. We report a case of unusual clinical presentation in a patient with undiagnosed factor VII deficiency who presented with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

PubMed

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-03-28

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

PubMed Central

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-01-01

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency. PMID:28350321

Serendipitous Discovery of Factor VII Deficiency and the Ensuing Dilemma.

PubMed

Umakanthan, Jayadev M; Dhakal, Prajwal; Gundabolu, Krishna; Koepsell, Scott A; Baljevic, Muhamed

2018-03-01

Congenital factor VII deficiency is a challenging disorder to manage, as it is associated with varied genotypes that do not clinically correlate with a bleeding phenotype. Individuals with severe factor VII deficiency (FVII: c <1%) might be asymptomatic, while patients with moderate deficiency (FVII: c level >5%) may experience severe hemorrhages. In modern medicine, due to extensive routine pre-operative laboratory testing, clinically asymptomatic patients without any bleeding history might be incidentally discovered, raising clinical dilemmas. Careful consideration of bleeding versus thrombosis risk has to be made in such cases, especially in the elderly. Clinical history of no prior bleeding complications may be a reassuring factor. Minimal required replacement dosing of recombinant activated factor VII can be given peri-operatively in such situations, with close monitoring.

The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

PubMed

Quek, S C; Low, P S; Saha, N; Heng, C K

2006-11-01

Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study.

PubMed

Hoffmann, Till; Assmann, Alexander; Dierksen, Angelika; Roussel, Elisabeth; Ullrich, Sebastian; Lichtenberg, Artur; Albert, Alexander; Sixt, Stephan

2018-04-18

Although off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. This prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan-Meier estimates. There was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P < .001). The key results were confirmed after adjustment by propensity score-based analyses. When combined with early and specific restoration of hemostatic reserves after cardiac surgery, very low-dose recombinant activated factor VII treatment of refractory bleeding is effective and not associated with any apparent increase in adverse events. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

PubMed

Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

2017-02-01

Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

In vitro effects of recombinant activated factor VII on thrombin generation and coagulation following inhibition of platelet procoagulant activity by prasugrel.

PubMed

Mazzeffi, Michael; Szlam, Fania; Jakubowski, Joseph A; Tanaka, Kenichi A; Sugidachi, Atsuhiro; Levy, Jerrold H

2013-07-01

Prasugrel is a thienopyridyl P2Y12 antagonist with potent antiplatelet effects. At present, little is known about its effects on thrombin generation or what strategies may emergently reverse its anticoagulant effects. In the current study we evaluated whether recombinant activated factor VII may reverse prasugrel induced effects and increase thrombin generation in an in vitro model. The effect of prasugrel active metabolite, PAM (R-138727), was evaluated on platelet aggregation, thrombin generation, and rotational thromboelastometry parameters using blood from 20 healthy volunteers. Additionally, we evaluated the effects of adenosine diphosphate (ADP) and recombinant activated factor VII on restoring these parameters towards baseline values. PAM reduced maximum platelet aggregation and led to platelet disaggregation. It also decreased peak thrombin, increased lag time, and increased time to peak thrombin. Treatment with recombinant activated factor VII restored all three parameters of thrombin generation towards baseline. ADP decreased lag time and time to peak thrombin, but had no effect on peak thrombin. When recombinant activated factor VII and ADP were combined they had a greater effect on thrombin parameters than either drug alone. PAM also increased thromboelastometric clotting time and clot formation time, but had no effect on maximum clot firmness. Treatment with either recombinant activated factor VII or ADP restored these values towards baseline. Recombinant activated factor VII restores thrombin generation in the presence of PAM. In patients taking prasugrel with life-threatening refractory bleeding it has the potential to be a useful therapeutic approach. Additional clinical studies are needed to validate our findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

PubMed

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-12-15

Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

The Plant Cysteine Oxidases from Arabidopsis thaliana are kinetically tailored to act as oxygen sensors.

PubMed

White, Mark D; Kamps, Jos J A G; East, Samuel; Taylor Kearney, Leah J; Flashman, Emily

2018-05-30

Group VII Ethylene Response Factors (ERF-VIIs) regulate transcriptional adaptation to flooding-induced hypoxia in plants. ERF-VII stability is controlled in an O 2 -dependent manner by the Cys/Arg branch of the N-end rule pathway, whereby oxidation of a conserved N-terminal cysteine residue initiates target degradation. This oxidation is catalyzed by Plant Cysteine Oxidases (PCOs) which use O 2 as co-substrate to generate Cys-sulfinic acid. The PCOs directly link O2 availability to ERF-VII stability and anaerobic adaptation leading to the suggestion that they act as plant O 2 sensors. However, their ability to respond to fluctuations in O 2 concentration has not been established. Here, we investigated the steady-state kinetics of Arabidopsis thaliana PCOs 1-5 to ascertain whether their activities are sensitive to O 2 levels. We found that the most catalytically competent isoform is AtPCO4, in terms of both responding to O 2 , and oxidizing At RAP2.2 and 2.12, two of the primary hypoxic response activating ERF-VIIs; these data suggest that AtPCO4 plays a central role in ERF-VII regulation. Furthermore, we found that AtPCO activity is susceptible to decreases in pH and that the hypoxia-inducible AtPCOs 1/2 and the non-inducible AtPCOs 4/5 have discrete AtERF-VII substrate preferences. Pertinently, the AtPCOs had K m app (O 2 ) values in a physiologically relevant range, which should enable them to sensitively react to changes in O 2 availability. This work validates an O 2 -sensing role for the PCOs and suggests that differences in expression pattern, ERF-VII selectivity and catalytic capability may enable the different isoforms to have distinct biological functions. Individual PCOs could therefore be targeted to manipulate ERF-VII levels and improve stress tolerance in plants. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Similarities and discrepancies in homozygous factor VII defects due to mutations in the region of residues Met298 to Cys310 (exon 8) in the catalytic domain of factor VII.

PubMed

Girolami, A; Berti de Marinis, G; Bonamigo, E; Vettore, S

2011-06-01

Patients with the Arg304Gln mutation in factor VII Padua (FVII Padua) show discrepant activity levels that depend on the thromboplastin used in the assay system. This report investigates the possibility that residues close to Arg304 (exon 8) show the same discrepant behavior. All available homozygous patients with a mutation in a 13-residue region (preceding and following Arg304) have been evaluated. Only the Arg304Trp mutation showed a discrepancy similar to that shown by the Arg304Gln mutation. Other homozygotes failed to show differences, despite their all being positive for cross-reacting material. Another FVII amino acid residue involved in tissue factor binding and activation is Arg79 (exon 4). No comparison could be carried out because no homozygotes for deficiency in this region have ever been described. The relationship between these 2 residues involved in tissue factor binding and activation has not yet been completely clarified; however, Arg residues 79 and 304 are the only 2 residues definitely shown thus far to be involved in this important function.

The preparation and structure of salty ice VII under pressure

NASA Astrophysics Data System (ADS)

Klotz, Stefan; Bove, Livia E.; Strässle, Thierry; Hansen, Thomas C.; Saitta, Antonino M.

2009-05-01

It is widely accepted that ice, no matter what phase, is unable to incorporate large amounts of salt into its structure. This conclusion is based on the observation that on freezing of salt water, ice expels the salt almost entirely as brine. Here, we show that this behaviour is not an intrinsic physico-chemical property of ice phases. We demonstrate by neutron diffraction that substantial amounts of dissolved LiCl can be built homogeneously into the ice VII structure if it is produced by recrystallization of its glassy (amorphous) state under pressure. Such `alloyed' ice VII has significantly different structural properties compared with pure ice VII, such as an 8% larger unit cell volume, 5 times larger displacement factors, an absence of a transition to an ordered ice VIII structure and plasticity. Our study suggests that there could be a whole new class of `salty' high-pressure ice forms.

The preparation and structure of salty ice VII under pressure.

PubMed

Klotz, Stefan; Bove, Livia E; Strässle, Thierry; Hansen, Thomas C; Saitta, Antonino M

2009-05-01

It is widely accepted that ice, no matter what phase, is unable to incorporate large amounts of salt into its structure. This conclusion is based on the observation that on freezing of salt water, ice expels the salt almost entirely as brine. Here, we show that this behaviour is not an intrinsic physico-chemical property of ice phases. We demonstrate by neutron diffraction that substantial amounts of dissolved LiCl can be built homogeneously into the ice VII structure if it is produced by recrystallization of its glassy (amorphous) state under pressure. Such 'alloyed' ice VII has significantly different structural properties compared with pure ice VII, such as an 8% larger unit cell volume, 5 times larger displacement factors, an absence of a transition to an ordered ice VIII structure and plasticity. Our study suggests that there could be a whole new class of 'salty' high-pressure ice forms.

Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

PubMed

Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

2017-10-01

The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

The Effect of Recombinant Activated Factor VII on Mortality in Combat-Related Casualties With Severe Trauma and Massive Transfusion

DTIC Science & Technology

2008-02-01

The Effect of Recombinant Activated Factor VII on Mortality in Combat-Related Casualties With Severe Trauma and Massive Transfusion Philip C...REPORT TYPE 3. DATES COVERED 00-00-2007 to 00-00-2007 4. TITLE AND SUBTITLE The Effect of Recombinant Activated Factor VII on Mortality in Combat...Boffard study,17 the effect of rFVIIa on 24-hour blood product ad- ministration was only determined for patients who lived for at least 24 hours

Double heterozygous mutations Gln100Leu and His348Gln of the F7 gene in a patient with factor VII deficiency.

PubMed

Li, Min; Zheng, Fangxiu; Jin, Yanhui; Wang, Mingshan; Zhu, Liqing; Yang, Lihong

2013-03-01

A 25-year-old Chinese woman who had a history of easy bruising was admitted to hospital due to uncontrolled epistaxis. She showed factor VII activity level of 2% and factor VII antigen level of 4% of the normal value. We detected a novel missense mutation g.8355 A>T (p.Gln100Leu) in the second epidermal growth factor-like (EGF) domain and a g.11482 T>G (p.His348Gln) in the catalytic domain. Although the Gln100 residue is close to the junction of EGF-2 domain with the serine protease domain, we infer that the substitution of polar negatively charged Gln residue at the position 100 with introduction of nonpolar Leu residue may be likely to perturb proper folding, resulting in decreasing factor VII activity.

Factor VII deficiency: a single-center experience.

PubMed

Salcioglu, Zafer; Akcay, Arzu; Sen, Hulya Sayilan; Aydogan, Gonul; Akici, Ferhan; Tugcu, Deniz; Ayaz, Nuray Aktay; Baslar, Zafer

2012-11-01

Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.

Life-threatening bleeding in a case of autoantibody-induced factor VII deficiency.

PubMed

Okajima, K; Ishii, M

1999-02-01

A male patient presented with life-threatening bleeding induced by autoantibody-induced factor VII (F.VII) deficiency. This patient had macroscopic hematuria, skin ecchymosis, gastrointestinal bleeding, and a neck hematoma that was causing disturbed respiration. He developed acute renal failure and acute hepatic failure, probably due to obstruction of the ureters and the biliary tract, respectively. Although activated partial thromboplastin time was normal, prothrombin time (PT) was remarkably prolonged at 71.8 seconds compared to 14.0 seconds in a normal control. Both the immunoreactive level of F.VII antigen and the F.VII activity of the patient's plasma samples were < 1.0% of normal. Although an equal part of normal plasma was added to the patient's plasma, PT was not corrected. The patient's plasma inhibited F.VII activity. These findings suggested the presence of a plasma inhibitor for F.VII. After administration of large doses of methylprednisolone, PT was gradually shortened and plasma levels of F.VII increased over time. Bleeding, acute renal failure, and acute hepatic failure improved markedly following the steroid treatment. These observations suggest that life-threatening bleeding can be induced by autoantibody-induced F.VII deficiency and that immunosuppressive therapy using large doses of steroid can be successful in inhibiting the production of the autoantibody.

Molecular cloning, characterization and expression analysis of coagulation factor VII gene in grass carp (Ctenopharyngodon idella).

PubMed

Liu, Qiaolin; Xu, Baohong; Xiao, Tiaoyi; Su, Jianming; Zhong, Lei

2013-08-01

Coagulation factor VII has been studied in several species but, to date, not in grass carp (Ctenopharyngodon idella), a commercially important freshwater fish found in China. In this study, the full-length cDNA of grass carp coagulation factor VII (GcCFVII) was cloned using a RACE-Ready cDNA Kit, grass carp were challenged with a hemorrhagic virus, and temporal expression profiles of GcCFVII in the thymus, gills, liver, spleen, and head kidney were examined at 0 h, 24 h, 48 h, 72 h, 96 h, and 138 h using fluorescence quantitative PCR. The results showed the 1480 bp GcCFVII to contain three conservative motifs: Gla, EGF-CA, and Tryp-SPc, similar to other species. Phylogenetic analysis showed the evolution of GcCFVII gene to be consistent with the evolution of the species. After viral challenge, GcCFVII expression in five tissues of grass carp showed different patterns of fluctuation. These results provide a solid basis for further investigation of GcCFVII and its relationship with grass carp hemorrhage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids.

PubMed

Tholstrup, T; Marckmann, P; Jespersen, J; Sandström, B

1994-02-01

The effect of fats high in individual, prevalent saturated dietary fatty acids on lipoproteins and hemostatic variables in young healthy subjects was evaluated in a randomized strictly controlled metabolic feeding study. Three experimental diets: shea butter (S; 42% stearic acid), palm oil (P; 43% palmitic palmitic acid), and palm-kernel oil with high-oleic sunflower oil (ML; 10% myristic acid, 30% lauric acid) were served to 15 men for 3 wk each, separated by washout periods. Diet S compared with diet P resulted in significant reduction in plasma cholesterol (22%) LDL cholesterol (26%), apolipoprotein B (18%), HDL cholesterol (12%), apolipoprotein A-I (13%), and a 13% lower factor VII coagulant activity (P = 0.001). Similar differences were observed between diets S and ML. In conclusion, intake of shea butter high in stearic acid favorably affects blood lipids and factor VII coagulant activity in young men, compared with fats high in saturated fatty acids with 12-16 carbons.

A rare combination: congenital factor VII deficiency with Chiari malformation.

PubMed

Bay, Ali; Aktekin, Elif; Erkutlu, Ibrahim

2015-12-01

Congenital factor (VII) deficiency is a rare bleeding disorder. We present a patient with congenital FVII deficiency and congenital hydrocephalus who underwent a ventriculoperitoneal shunt operation and needed no prophylaxis after the procedure.

Prophylactic Level VII Nodal Dissection as a Prognostic Factor in Papillary Thyroid Carcinoma: a Pilot Study of 27 Patients.

PubMed

Fayek, Ihab Samy

2015-01-01

Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value<0.001), extrathyroidal extension (p-value<0.001), level VI positive ((p-value<0.001) and level VII positive ((p-value<0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.

Evaluation of off-label recombinant activated factor VII for multiple indications in children.

PubMed

Reiter, Pamela D; Valuck, Robert J; Taylor, Ruston S

2007-07-01

Despite a paucity of safety and efficacy data, the use of recombinant activated factor VII in children for off-label indications has now surpassed its use in hemophilia. A retrospective chart review was conducted of 46 subjects (age, 6.7 +/- 6 years; weight, 26 +/- 20 kg) who received recombinant activated factor VII for nonhemophiliac indications between January 1, 2004, and September 1, 2005. Indications for use included prevention (n = 6) or treatment (n = 40) of bleeding due to general surgery, hepatic failure, gastrointestinal bleeding, severe traumatic brain injury, bone marrow transplant, cardiac, acetaminophen overdose, and multiorgan system failure. Decreases in prothrombin time, partial thromboplastin time, and international normalized ratio were observed. No inappropriate thrombotic events were noted. Administration of recombinant activated factor VII was associated with a reduction in coagulation markers without obvious adverse thrombotic events at cost of $4189 per dose. These findings should be confirmed in a prospective trial.

Influence of stearic acid on postprandial lipemia and hemostatic function.

PubMed

Sanders, Thomas A B; Berry, Sarah E E

2005-12-01

It has been suggested that fats rich in stearic acid may result in exaggerated postprandial lipemia and have adverse effects on hemostatic function. The effects of test meals containing different saturated and monounsaturated FA were compared in healthy subjects in a series of studies to investigate this hypothesis. Stearic acid, when present as cocoa butter, resulted in similar postprandial lipemia and factor VII activation compared with a meal containing high-oleic sunflower oil. Stearic acid when presented as shea butter or as randomized stearate-rich TAG resulted in decreased postprandial lipemia and decreased postprandial activation of factor VII. Stearic acid-rich test meals did not result in impaired fibrinolytic activity compared with either a low-fat meal or a meal high in oleate. The difference in responses between the different stearic acid-rich fats appears to be due to varying solid fat contents of the fats at 37 degrees C.

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency.

PubMed

Jones, Kareen L; Greenberg, Robert S; Ahn, Edward S; Kudchadkar, Sapna R

2016-01-01

Congenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss. A two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa. Important considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period. A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Isolated acquired factor VII deficiency: review of the literature.

PubMed

Mulliez, Sylvie M N; Devreese, Katrien M J

2016-04-01

Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

PubMed

Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

2012-05-01

Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore unlikely that its use would be of clinical importance.

Cost effectiveness of recombinant activated factor VII for the control of bleeding in patients with severe blunt trauma injuries in the United Kingdom.

PubMed

Morris, S; Ridley, S; Munro, V; Christensen, M C

2007-01-01

The aim of this study was to assess the lifetime cost effectiveness of recombinant activated factor VII vs placebo as adjunctive therapy for control of bleeding in patients with severe blunt trauma in the UK. We developed a cost-effectiveness model based on patient level data from a 30-day international, randomised, placebo-controlled Phase II trial. The data were supplemented with secondary data from UK sources to estimate lifetime costs and benefits. The model produced a baseline estimate of the incremental cost per life year gained with recombinant activated factor VII relative to placebo of 12 613 UK pounds. The incremental cost per quality adjusted life year gained was 18 825 UK pounds. These estimates are sensitive to the choice of discount rate and health state utility values used. Preliminary results suggest that relative to placebo, recombinant activated factor VII may be a cost-effective therapy to the UK National Health Service.

Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy.

PubMed

Duanmu, J; Cheng, J; Xu, J; Booth, C J; Hu, Z

2011-04-26

The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR. The TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume. To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model. We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers.

30 CFR 750.12 - Permit applications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 779; (vii) Part 780; (viii) Part 783; (ix) Part 784; and (x) Part 785; (2) The following provisions of... consider the following factors as well as other relevant factors in determining the significance of a... significant deterioration limitations, or other Federal laws for air quality protection. (vii) A description...

77 FR 61753 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-11

..., Inc.; Astria Semiconductor Holdings, Inc.; FormFactor, Inc. 20121365 G ABRY Partners VII, L.P.; Source.... 20121303 G Wind Point Partners L.P.; Mistral Equity Partners, LP; Wind Point Partners VII-A, L.P. 20121307... Dillard. 20121364 G Apollo Investment Fund VII, L.P.; Jimmy Sanders Incorporated; Apollo Investment Fund...

Factors Influencing Title VII Bilingual Program Institutionalization.

ERIC Educational Resources Information Center

Lewis, Gerald R.; And Others

1985-01-01

This study of the primary restraining and driving forces that influence Title VII bilingual education programs found the external environment, the local community, to be the main factor influencing institutionalization and self-renewal. The internal environment--the local school, and the local school's organization or central office, school board,…

Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

PubMed

Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

2016-03-01

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

42 CFR 57.1507 - Limitations applicable to loan guarantee.

Code of Federal Regulations, 2010 CFR

2010-10-01

... factors consistent with the purpose of part B of title VII of the Act and this subpart. (3) In determining... under part B of title VII of the Act or any other law of the United States, or to the total of such... part B of title VII of the Act. In making such determinations, the Secretary will in each case consider...

29 CFR 825.107 - Successor in interest coverage.

Code of Federal Regulations, 2010 CFR

2010-07-01

... because it is a “successor in interest” to a covered employer, the factors used under Title VII of the... VII, whether the successor has notice of the employee's claim is not a consideration. Notice may be relevant, however, in determining successor liability for violations of the predecessor. The factors to be...

Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation.

PubMed

Chiu, Bill; Melin-Aldana, Hector; Superina, Riccardo A

2007-10-01

A 3-year-old girl developed extrahepatic portal vein obstruction (EHPVO) after a liver transplant. She had sequelae of portal hypertension that required another transplantation. The circumstances allowed for comparison of liver-dependent coagulation factor production between the second donor liver and the explanted liver with EHPVO. Liver samples from the explanted first graft and the second transplant were obtained. Fresh tissue was used to perform reverse transcription-polymerase chain reaction with primers against factors V, VII, as well as VIII, protein C, and paraffin-embedded sections for hepatocyte proliferation using Ki-67 antibody as well as for apoptosis using TUNEL assay. The transcription of factor VII and that of protein C were decreased in the explant as compared with the newly transplanted liver (factor VII, 77% of the donor; protein C, 88% of the donor). The transcription of factor V and that of factor VIII were unchanged. The explant had a greater percentage of proliferating hepatocytes than the new organ (0.85% +/- 0.75% vs 0.11% +/- 0.21%). The percentage of apoptotic cells was similar between the 2 livers (0.09% +/- 0.13% vs 0.09% +/- 0.13%). Idiopathic EHPVO is associated with a reduction in liver-dependent coagulation factor transcription and an increase in hepatocyte proliferation. Portal blood flow deprivation alters hepatic homeostasis and initiates mechanisms that attempt to restore liver-dependent coagulation factors.

Lack of bleeding in patients with severe factor VII deficiency.

PubMed

Barnett, J Mark; Demel, Kurt C; Mega, Anthony E; Butera, James N; Sweeney, Joseph D

2005-02-01

Factor VII deficiency, although rare, is now recognized as the most common autosomal recessive inherited factor deficiency. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk. The general recommendation for surgery is to achieve a FVII level in excess of 15% (0.15 1U/mL). We present three cases of severe factor VII deficiency, each of whom appeared hemostatically competent based on clinical history. Subject 1 is a 33 year-old African-American female with a baseline FVII of <1%, who had a fractured tibia requiring open reduction with internal fixation without any FVII replacement and subsequently underwent successful laparoscopic knee surgery with a factor VII level measured at 6%. Subject 2 is a 58 year-old African-American female with a factor VII level of 9% who underwent an elective left total hip replacement without any factor replacement and had no excessive bleeding, but who sustained a pulmonary embolism postoperatively. Subject 3 is a 19-year-old African-American male with a baseline FVII of 1% with a history of active participation in football without noticeable injury and who underwent an emergent appendectomy without bleeding. These three cases represent individuals with the severe form of FVII deficiency who did not exhibit excessive bleeding when challenged with surgical procedures. The clinical history would appear the most valuable tool in predicting the likelihood of bleeding in these patients, and we suggest that the presumption that all patients with severe FVII deficiency should receive replacement therapy before surgical procedures may not be valid in all cases. Copyright 2005 Wiley-Liss, Inc.

The mannose 6-phosphate-binding sites of M6P/IGF2R determine its capacity to suppress matrix invasion by squamous cell carcinoma cells

PubMed Central

Probst, Olivia C.; Karayel, Evren; Schida, Nicole; Nimmerfall, Elisabeth; Hehenberger, Elisabeth; Puxbaum, Verena; Mach, Lukas

2013-01-01

The M6P (mannose 6-phosphate)/IGF2R (insulin-like growth factor II receptor) interacts with a variety of factors that impinge on tumour invasion and metastasis. It has been shown that expression of wild-type M6P/IGF2R reduces the tumorigenic and invasive properties of receptor-deficient SCC-VII squamous cell carcinoma cells. We have now used mutant forms of M6P/IGF2R to assess the relevance of the different ligand-binding sites of the receptor for its biological activities in this cellular system. The results of the present study demonstrate that M6P/IGF2R does not require a functional binding site for insulin-like growth factor II for inhibition of anchorage-independent growth and matrix invasion by SCC-VII cells. In contrast, the simultaneous mutation of both M6P-binding sites is sufficient to impair all cellular functions of the receptor tested. These findings highlight that the interaction between M6P/IGF2R and M6P-modified ligands is not only important for intracellular accumulation of lysosomal enzymes and formation of dense lysosomes, but is also crucial for the ability of the receptor to suppress SCC-VII growth and invasion. The present study also shows that some of the biological activities of M6P/IGF2R in SCC-VII cells strongly depend on a functional M6P-binding site within domain 3, thus providing further evidence for the non-redundant cellular functions of the individual carbohydrate-binding domains of the receptor. PMID:23347038

Stability of prothrombin and factor VII in freeze-dried plasma

PubMed Central

Brozović, M.; Gurd, L. J.; Robertson, I.; Bangham, D. R.

1971-01-01

The stability of prothrombin and factor VII was studied using accelerated degradation tests in three preparations of freeze-dried pooled normal plasmas. In a previous report (Brozović, Gurd, Robertson, and Bangham, 1971) factor X was shown to be relatively unstable in these preparations of freeze-dried plasma: it was calculated that up to 8% of the original factor X activity would be lost after 10 years at −20°C, up to 54% at 4°C, and up to 90% at room temperature. The losses of factor VII activity were estimated to be negligible at −20°C, between 2 and 18% at 4°C, and between 20 and 70% of the original activity at 20°C, after 10 years of storage. Prothrombin was found to be less stable than factor VII: the expected loss in 10 years at −20°C may be up to 4%, at 4°C up to 30%, and at 20°C up to 83% of the initial activity. These findings indicate that in freeze-dried plasma prothrombin as well as factor X may be insufficiently stable for plasma to serve as long-term reference material for the standardization of the one-stage prothrombin time. Moreover, the loss of prothrombin and factor X in freeze-dried plasma stored at 4°C may be so high that when it is required to preserve these factors it may be necessary to store freeze-dried plasma at lower temperatures. PMID:5130534

Coagulation factor VII variants resistant to inhibitory antibodies.

PubMed

Branchini, Alessio; Baroni, Marcello; Pfeiffer, Caroline; Batorova, Angelika; Giansily-Blaizot, Muriel; Schved, Jean F; Mariani, Guglielmo; Bernardi, Francesco; Pinotti, Mirko

2014-11-01

Replacement therapy is currently used to prevent and treat bleeding episodes in coagulation factor deficiencies. However, structural differences between the endogenous and therapeutic proteins might increase the risk for immune complications. This study was aimed at identifying factor (F)VII variants resistant to inhibitory antibodies developed after treatment with recombinant activated factor VII (rFVIIa) in a FVII-deficient patient homozygous for the p.A354V-p.P464Hfs mutation, which predicts trace levels of an elongated FVII variant in plasma. We performed fluorescent bead-based binding, ELISA-based competition as well as fluorogenic functional (activated FX and thrombin generation) assays in plasma and with recombinant proteins. We found that antibodies displayed higher affinity for the active than for the zymogen FVII (half-maximal binding at 0.54 ± 0.04 and 0.78 ± 0.07 BU/ml, respectively), and inhibited the coagulation initiation phase with a second-order kinetics. Isotypic analysis showed a polyclonal response with a large predominance of IgG1. We hypothesised that structural differences in the carboxyl-terminus between the inherited FVII and the therapeutic molecules contributed to the immune response. Intriguingly, a naturally-occurring, poorly secreted and 5-residue truncated FVII (FVII-462X) escaped inhibition. Among a series of truncated rFVII molecules, we identified a well-secreted and catalytically competent variant (rFVII-464X) with reduced binding to antibodies (half-maximal binding at 0.198 ± 0.003 BU/ml) as compared to the rFVII-wt (0.032 ± 0.002 BU/ml), which led to a 40-time reduced inhibition in activated FX generation assays. Taken together our results provide a paradigmatic example of mutation-related inhibitory antibodies, strongly support the FVII carboxyl-terminus as their main target and identify inhibitor-resistant FVII variants.

Altered lumbar spine structure, biochemistry and biomechanical properties in a canine model of mucopolysaccharidosis type VII

PubMed Central

Smith, Lachlan J; Martin, John T; Szczesny, Spencer E; Ponder, Katherine P; Haskins, Mark E; Elliott, Dawn M

2010-01-01

Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disorder characterized by a deficiency in β-glucuronidase activity, leading to systemic accumulation of poorly degraded glycosaminoglycans (GAG). Along with other morbidities, MPS VII is associated with paediatric spinal deformity. The objective of this study was to examine potential associations between abnormal lumbar spine matrix structure and composition in MPS VII, and spine segment and tissue-level mechanical properties, using a naturally occurring canine model with a similar clinical phenotype to the human form of the disorder. Segments from juvenile MPS VII and unaffected dogs were allocated to: radiography, gross morphology, histology, biochemistry, and mechanical testing. MPS VII spines had radiolucent lesions in the vertebral body epiphyses. Histologically, this corresponded to a GAG-rich cartilaginous region in place of bone, and elevated GAG staining was seen in the annulus fibrosus. Biochemically, MPS VII samples had elevated GAG in the outer annulus fibrosus and epiphyses, low calcium in the epiphyses, and high water content in all regions except the nucleus pulposus. MPS VII spine segments had higher range of motion and lower stiffness than controls. Endplate indentation stiffness and failure loads were significantly lower in MPS VII samples, while annulus fibrosus tensile mechanical properties were normal. Vertebral body lesions in MPS VII spines suggest a failure to convert cartilage to bone during development. Low stiffness in these regions likely contributes to mechanical weakness in motion segments and is a potential factor in the progression of spinal deformity. PMID:19918911

Recombinant activated factor VII for bleeding in patients without inherited bleeding disorders.

PubMed

Selin, S; Tejani, A

2006-03-01

(1) Recombinant activated factor VII (rFVIIa) is licensed in Canada for the prevention and treatment of bleeding in hemophiliacs, but it is increasingly used to control bleeding in non-hemophilic patients during surgery, or during treatment for severe trauma or intracerebral hemorrhage (ICH). (2) In one clinical trial, there was a significant reduction in mortality among patients with ICH treated with rFVIIa. In another trial, administration of rFVIIa significantly reduced the number of trauma patients needing massive blood transfusions although there was no significant difference in mortality. (3) Adequately powered randomized controlled trials are needed to clarify the efficacy and safety of rFVIIa for non-bleeding disorder indications. Phase III trials in ICH and trauma are underway. (4) There is potential for non-hemophilic use, particularly if clinical efficacy and cost effectiveness are established.

The safety and efficacy of the administration of recombinant activated factor VII in major surgery and trauma patients.

PubMed

Wilson, Stephen J; Bellamy, Mark C; Giannoudis, Peter V

2005-05-01

Recombinant activated Factor VII (rFVIIa) has been successfully used in the treatment of haemophilia A and B with associated inhibitors for some years. Activated Factor VII binds to activated platelets independently of tissue factor. The resulting stimulation of an exaggerated early thrombin burst at sites of vascular injury makes it an attractive potential treatment for massive, uncontrolled bleeding associated with surgery and trauma. This article describes the evidence relating to surgery and trauma. The lack of large, controlled trials of rFVIIa means that a definitive recommendation regarding its use cannot be made at present. However, in the context of clearly defined protocols and balanced treatment strategies, rFVIIa may have a role in traumatic bleeding. Large scale, randomised controlled trials in trauma are required, as is further work on the safety profile of rFVIIa with an independent international safety monitoring committee.

Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery.

PubMed

Harper, Patrick C; Smith, Mark M; Brinkman, Nathan J; Passe, Melissa A; Schroeder, Darrell R; Said, Sameh M; Nuttall, Gregory A; Oliver, William C; Barbara, David W

2018-02-01

To compare outcomes following inactive prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac surgery. Retrospective propensity-matched analysis. Academic tertiary-care center. Patients undergoing cardiac surgery requiring cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC. Outcomes following intraoperative administration of rFVIIa (263) or factor IX complex (72) as rescue therapy to treat bleeding. In the 24 hours after surgery, propensity-matched patients receiving PCC versus rFVIIa had significantly less chest tube outputs (median difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion rates (26% v 49%, p = 0.027). There were no significant differences between propensity-matched groups in postoperative stroke, deep venous thrombosis, pulmonary embolism, myocardial infarction, or intracardiac thrombus. Postoperative dialysis was significantly less likely in patients administered PCC versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7). No significant difference in 30-day mortality in patients receiving PCC versus rFVIIa was present following propensity matching. Use of rFVIIa versus inactive PCCs was significantly associated with renal failure requiring dialysis and increased postoperative bleeding and transfusions. Copyright © 2018 Elsevier Inc. All rights reserved.

Experimental evidence for competitive growth advantage of genotype VII over VI: implications for foot-and-mouth disease virus serotype A genotype turnover in nature.

PubMed

Mohapatra, J K; Subramaniam, S; Singh, N K; Sanyal, A; Pattnaik, B

2012-04-01

In India, systematic genotype replacement has been observed for serotype A foot-and-mouth disease virus. After a decade of co-circulation of genotypes VI and VII, genotype VII emerged as the single dominant genotype since 2001. To derive possible explanations for such epochal evolution dynamics, in vitro intergenotype growth competition experiments involving both co- and superinfection regimes were conducted. Coinfection of BHK-21 cells demonstrated abrupt loss in the genotype VI viral load with commensurate increase in the load of genotype VII as measured by the genotype differentiating ELISA, RT-PCR and real-time RT-PCR. The superinfection dynamics was shaped by temporal spacing of infection, where the invading genotype VII took more number of passages than coinfection to eventually overtake the resident genotype VI. It was speculated that such superior replicative fitness of genotype VII could have been a possible factor for the ultimate dominance of genotype VII in nature. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fish as bioreactors: transgene expression of human coagulation factor VII in fish embryos.

PubMed

Hwang, Gyulin; Müller, Ferenc; Rahman, M Aziz; Williams, Darren W; Murdock, Paul J; Pasi, K John; Goldspink, Geoffrey; Farahmand, Hamid; Maclean, Norman

2004-01-01

A plasmid containing human coagulation factor VII (hFVII) complementary DNA regulated by a cytomegalovirus promoter was microinjected into fertilized eggs of zebrafish, African catfish, and tilapia. The active form of hFVll was detected in the fish embryos by various assays. This positive expression of human therapeutic protein in fish embryos demonstrates the possibility of exploitation of transgenic fish as bioreactors.

Remarks on KERMA Factors in ACE files

NASA Astrophysics Data System (ADS)

Konno, C.; Ochiai, K.; Takakura, K.; Sato, S.

2014-04-01

Some neutron KERMA factors in ACE files are negative and extremely large if nuclear data libraries do not keep energy-balance. The status of neutron KERMA factors in the official ACE file of ENDF/B-VII.1 is examined. As a result, it is found out that neutron KERMA factors of nuclei more than 200 in ENDF/B-VII.1 have some problems. Effects of the inadequate KERMA factor are also investigated, which are large for neutron heat while those are small for total (neutron + gamma) heat. Users who use only neutron KERMA factors should check if the factors are adequate or not before they use the factors.

High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

PubMed

Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

2016-01-01

Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

Impact of nuclear data on sodium-cooled fast reactor calculations

NASA Astrophysics Data System (ADS)

Aures, Alexander; Bostelmann, Friederike; Zwermann, Winfried; Velkov, Kiril

2016-03-01

Neutron transport and depletion calculations are performed in combination with various nuclear data libraries in order to assess the impact of nuclear data on safety-relevant parameters of sodium-cooled fast reactors. These calculations are supplemented by systematic uncertainty analyses with respect to nuclear data. Analysed quantities are the multiplication factor and nuclide densities as a function of burn-up and the Doppler and Na-void reactivity coefficients at begin of cycle. While ENDF/B-VII.0 / -VII.1 yield rather consistent results, larger discrepancies are observed between the JEFF libraries. While the newest evaluation, JEFF-3.2, agrees with the ENDF/B-VII libraries, the JEFF-3.1.2 library yields significant larger multiplication factors.

Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

PubMed

Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

2018-06-16

Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be the most consistent and strongest staining biomarkers in diseased mice. This mouse appears to mimic human corneal disease. It is an appropriate model for testing of therapeutics to treat EB ocular disease. Copyright © 2018. Published by Elsevier Ltd.

Specific DNA binding of a potential transcriptional regulator, inosine 5'-monophosphate dehydrogenase-related protein VII, to the promoter region of a methyl coenzyme m reductase I-encoding operon retrieved from Methanothermobacter thermautotrophicus strain DeltaH.

PubMed

Shinzato, Naoya; Enoki, Miho; Sato, Hiroaki; Nakamura, Kohei; Matsui, Toru; Kamagata, Yoichi

2008-10-01

Two methyl coenzyme M reductases (MCRs) encoded by the mcr and mrt operons of the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus DeltaH are expressed in response to H(2) availability. In the present study, cis elements and trans-acting factors responsible for the gene expression of MCRs were investigated by using electrophoretic mobility shift assay (EMSA) and affinity particle purification. A survey of their operator regions by EMSA with protein extracts from mrt-expressing cultures restricted them to 46- and 41-bp-long mcr and mrt upstream regions, respectively. Affinity particle purification of DNA-binding proteins conjugated with putative operator regions resulted in the retrieval of a protein attributed to IMP dehydrogenase-related protein VII (IMPDH VII). IMPDH VII is predicted to have a winged helix-turn-helix DNA-binding motif and two cystathionine beta-synthase domains, and it has been suspected to be an energy-sensing module. EMSA with oligonucleotide probes with unusual sequences showed that the binding site of IMPDH VII mostly overlaps the factor B-responsible element-TATA box of the mcr operon. The results presented here suggest that IMPDH VII encoded by MTH126 is a plausible candidate for the transcriptional regulator of the mcr operon in this methanogen.

Management of factor VII-deficient patients undergoing joint surgeries--preliminary results of locally developed treatment regimen.

PubMed

Windyga, J; Zbikowski, P; Ambroziak, P; Baran, B; Kotela, I; Stefanska-Windyga, E

2013-01-01

Inherited factor VII (FVII) deficiency is a rare coagulation disorder with variable haemorrhagic manifestations. In severely affected cases spontaneous haemarthroses leading to advanced arthropathy have been observed. Such cases may require surgery. Therapeutic options for bleeding prevention in FVII deficient patients undergoing surgery comprise various FVII preparations but the use of recombinant activated factor VII (rFVIIa) seems to be the treatment of choice. To present the outcome of orthopaedic surgery under haemostatic coverage of rFVIIa administered according to the locally established treatment regimen in five adult patients with FVII baseline plasma levels below 10 IU dL(-1). Two patients required total hip replacement (THR); three had various arthroscopic procedures. Recombinant activated factor VII was administered every 8 h on day of surgery (D0) followed by every 12-24 h for the subsequent 9-14 days, depending on the type of surgery. Factor VII plasma coagulation activity (FVII:C) was determined daily with no predefined therapeutic target levels. Doses of rFVIIa on D0 ranged from 18 to 37 μg kg(-1) b.w. and on the subsequent days--from 13 to 30 μg kg(-1) b.w. Total rFVIIa dose per procedure ranged from 16 to 37.5 mg, and the total number of doses per procedure was 16-31. None of our patients developed excessive bleeding including those in whom FVII:C trough levels returned nearly to the baseline level on the first post-op day. Preliminary results demonstrate that rFVIIa administered according to our treatment regimen is an effective and safe haemostatic agent for hypoproconvertinaemia patients undergoing orthopaedic surgery. © 2012 Blackwell Publishing Ltd.

Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.

PubMed

Biedermann, J S; van den Besselaar, A M H P; de Maat, M P M; Leebeek, F W G; Kruip, M J H A

2017-03-01

Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL -1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL -1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences regarding FVII sensitivity exist between various thromboplastins used for VKA monitoring. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Therefore, thromboplastin choice may affect FVII-mediated INR stability. © 2017 International Society on Thrombosis and Haemostasis.

High Dose, Prolonged Epsilon Aminocaproic Acid Infusion, and Recombinant Factor VII for Massive Postoperative Retroperitoneal Hemorrhage following Splenectomy.

PubMed

Lee, Alex T; Barnes, Christopher R; Jain, Shweta; Pauldine, Ronald

2016-01-01

The antifibrinolytic agent ε -aminocaproic acid is used to decrease procedural blood loss in a variety of high risk surgeries. The utility of recombinant factor VII administration in massive hemorrhage has also been reported in a variety of settings, though the impact in a surgical context remains unclear. We describe the case of a patient who underwent massive open splenectomy and developed diffuse retroperitoneal bleeding on postoperative day one. Massive transfusion was initiated, but attempts to control hemorrhage with surgical and interventional radiology approaches were unsuccessful, as was recombinant factor VII administration. Commencement of a high dose aminocaproic acid infusion was followed by a prominent rise in fibrinogen levels and stabilization of the hemorrhage. Indications, dosages, and adverse effects of ε -aminocaproic acid as described in the literature are reviewed.

High Dose, Prolonged Epsilon Aminocaproic Acid Infusion, and Recombinant Factor VII for Massive Postoperative Retroperitoneal Hemorrhage following Splenectomy

PubMed Central

Barnes, Christopher R.; Jain, Shweta; Pauldine, Ronald

2016-01-01

The antifibrinolytic agent ε-aminocaproic acid is used to decrease procedural blood loss in a variety of high risk surgeries. The utility of recombinant factor VII administration in massive hemorrhage has also been reported in a variety of settings, though the impact in a surgical context remains unclear. We describe the case of a patient who underwent massive open splenectomy and developed diffuse retroperitoneal bleeding on postoperative day one. Massive transfusion was initiated, but attempts to control hemorrhage with surgical and interventional radiology approaches were unsuccessful, as was recombinant factor VII administration. Commencement of a high dose aminocaproic acid infusion was followed by a prominent rise in fibrinogen levels and stabilization of the hemorrhage. Indications, dosages, and adverse effects of ε-aminocaproic acid as described in the literature are reviewed. PMID:27957347

Recombinant factor VIIa (eptacog alfa): a review of its use in congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders.

PubMed

Croom, Katherine F; McCormack, Paul L

2008-01-01

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is structurally similar to human plasma-derived coagulation factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa interacts with thrombin-activated platelets to produce a thrombin burst leading to accelerated fibrin clot formation localized to the site of vascular injury. It is approved in many countries for use as an intravenous hemostatic agent in patients with congenital hemophilia with inhibitors, and also for acquired hemophilia, factor VII deficiency, and Glanzmann thrombasthenia in some countries. Studies have shown it to be effective and generally well tolerated when used intravenously to treat bleeding episodes or provide hemostatic cover during surgery in patients with congenital hemophilia with inhibitors, acquired hemophilia, factor VII deficiency or Glanzmann thrombasthenia. Based on available data, its efficacy in terms of patient-assessed response may be similar to that of activated prothrombin complex concentrate (aPCC), but treatment with a single 270 microg/kg dose of recombinant factor VIIa might reduce the need for rescue therapy compared with aPCC. Recombinant factor VIIa is not immunogenic in patients with hemophilia, does not produce an anamnestic response in hemophilia patients with inhibitors, and has very low thrombogenicity. It is recommended in guidelines as the treatment of choice for bleeds in patients with hemophilia B with high-responding inhibitors and for patients with factor VII deficiency, and is also a first-line therapeutic option for high-responder hemophilia A patients with inhibitors and those with acquired hemophilia. Cost data from pharmacoeconomic analyses support its use in hemophilia patients with inhibitors. Thus, recombinant factor VIIa is a valuable treatment option for patients with these rare, but potentially serious, bleeding disorders.

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

PubMed

Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

2009-03-01

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

PubMed

Giansily-Blaizot, Muriel; Aguilar-Martinez, Patricia; Briquel, Marie-Elisabeth; d'Oiron, Roseline; De Maistre, Emmanuel; Epelbaum, Serge; Schved, Jean-François

2003-02-01

Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.

Title VII and the Male/Female Earnings Gap: An Economic Analysis.

ERIC Educational Resources Information Center

Beller, Andrea

1978-01-01

After controlling statistically for the effects of other factors that affect earnings, it was found that enforcement of sex discrimination charges under Title VII increased the relative demand for women and thus decreased the male/female earnings differential between 1967 and 1974. (Author)

15 CFR 400.24 - Application for zone.

Code of Federal Regulations, 2010 CFR

2010-01-01

...; (vii) If part of a port facility, a summary of port and transportation services and facilities; if not... from those firms that are considered prime prospects; and (vii) A description of proposed manufacturing and processing operations, if applicable, with information covering the factors described in § 400.31...

Factor VII Tokushima: the first case of factor VII Cys22Gly with the development of myocardial infarction in the proband receiving recombinant factor VIIa replacement therapy.

PubMed

Shigekiyo, Toshio; Sekimoto, Etsuko; Shibata, Hironobu; Ozaki, Shuji; Okumura, Takanobu; Fujinaga, Hiroyuki; Shibata, Hiroshi; Aihara, Ken-ichi; Akaike, Masashi

2015-12-01

An 81-year-old man was referred to our department because of suspected factor VII (FVII) deficiency. His FVII activity was under 1%, whereas the FVII activity levels of his son and granddaughter were 65 and 109%, respectively. The nucleotide at position 3886 of his FVII gene was homozygous for G. A single T to G substitution results in the replacement of wild-type Cys at residue 22 by Gly. His son was heterozygous for G and T at position 3886, whereas his granddaughter was homozygous for wild-type T. These results suggest that he was homozygous for FVII Cys22Gly. He underwent radiofrequency ablation (RFA) for hepatocellular carcinoma, receiving 20 μg/kg of recombinant FVIIa prior to RFA and 10 μg/kg of recombinant FVIIa twice after RFA. He showed no bleeding tendency; however, a myocardial infarction was diagnosed and percutaneous coronary intervention was performed.

Cerebral Venous Sinus Thrombosis in a Patient with Undiagnosed Factor VII Deficiency.

PubMed

Qadir, Hira; Rashid, Anila; Adil, Salman Naseem

2017-09-01

Factor VII (FVII) deficiency is one of the rare inherited bleeding disorders. Thrombosis has been occasionally described in inherited FVII deficiency. Here, we report a young female with undiagnosed FVII deficiency who presented with cerebral venous sinus thrombosis (CVST). Oral contraceptive pill was found to be prothrombotic risk factor. The CVSToccurred in spite of the congenital FVII deficiency indicating that no definitive antithrombotic protection is assured by this defect. Low molecular weight heparin and anti-Xa assay were found to be safe choice of anticoagulation and monitoring, respectively, in this patient.

What a Decade of Experiments Reveals about Factors that Influence the Sense of Presence: Latest Findings

DTIC Science & Technology

2007-05-01

Paper presented at VII Encontro Portugues de Computacao Grafica, Eurographics, Monte de Caparica, Portugal, February. Slater, M., Usoh, M., and Steed...window? An experimental comparison of immersive and non-immersive walkthroughs. Paper presented at VII Encontro Portugues de Computacao Grafica

Factors Effecting on Study Habits

ERIC Educational Resources Information Center

Khan, Zebun Nisa

2016-01-01

The present study was undertaken with the objectives to find out the impact of Socio-economic Status as well as sex differences on study habits of class VII students (100) of Government Colleges of Amroha District. The effects of two independent variables on study habits of the aforementioned students were assessed by using two Psychological tests…

Beneficial nutritional properties of olive oil: implications for postprandial lipoproteins and factor VII.

PubMed

Williams, C M

2001-08-01

Previous research concerning protective cardiovascular properties of olive oil has focussed on the beneficial consequences on blood cholesterol levels of substituting dietary saturated fatty acids with oleic acid. Despite evidence implicating raised circulating triglycerides in the postprandial state in the pathogenesis of atherosclerosis and thrombosis, little research had been conducted to investigate effects of monounsaturated fatty acids on postprandial events. In a case control study of southern (n = 30) versus northern European (n = 30) men, significant differences in postprandial triglyceride and apolipoprotein (apo) B-48 response were observed, with evidence of attenuated and potentially beneficial responses in the Southern Europeans. In a randomised controlled study manufactured foods typical of the Northern European food culture, were used to deliver diets rich in either saturated or monounsaturated fatty acids (from olive oil). During the period of the olive oil enriched diet, LDL-cholesterol levels were 15% lower (p < 0.001) than during the saturated fat diet. Postprandial triglyceride response was shifted towards the profile seen in southern European men and the postprandial activation of factor VII, as well as the production of factor VII antigen, was reduced on the olive oil diet. The study demonstrated significant improvements in biomarkers for cardiovascular disease in subjects osed to high olive oil diets (Southern Europeans) or transferred to such diets in the short term (Northern European volunteers). The study produced novel findings with respect to potential mechanisms by which diets high in monounsaturated fatty acids (MUFA) can reduce population risk of cardiovascular disease.

A Method for Visualization of Incoming Adenovirus Chromatin Complexes in Fixed and Living Cells

PubMed Central

Komatsu, Tetsuro; Dacheux, Denis; Kreppel, Florian; Nagata, Kyosuke; Wodrich, Harald

2015-01-01

Inside the adenovirus virion, the genome forms a chromatin-like structure with viral basic core proteins. Core protein VII is the major DNA binding protein and was shown to remain associated with viral genomes upon virus entry even after nuclear delivery. It has been suggested that protein VII plays a regulatory role in viral gene expression and is a functional component of viral chromatin complexes in host cells. As such, protein VII could be used as a maker to track adenoviral chromatin complexes in vivo. In this study, we characterize a new monoclonal antibody against protein VII that stains incoming viral chromatin complexes following nuclear import. Furthermore, we describe the development of a novel imaging system that uses Template Activating Factor-I (TAF-I/SET), a cellular chromatin protein tightly bound to protein VII upon infection. This setup allows us not only to rapidly visualize protein VII foci in fixed cells but also to monitor their movement in living cells. These powerful tools can provide novel insights into the spatio-temporal regulation of incoming adenoviral chromatin complexes. PMID:26332038

Intravenous rFVIIa Administered for Hemorrhage Control in Hypothermic Coagulopathic Swine with Grade V Liver Injuries

DTIC Science & Technology

2001-04-01

Hendriks H, Meijer K, Hagenaars A, et al. Recombinant factor VIIa (rFVIIa, NovoSeven) decreases blood loss and blood product requirements during...and John R. Hess, MD, MPH Background: Intravenous adminis- tration of recombinant activated human clotting factor VII (rFVIIa) has been used...onds, fibrinogen was 91 6 20 mg/dL, and platelets were 221 6 57 3 105/mL, with no differences between groups (p > 0.05). Clotting factor levels

Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae: production of O-fucosylated epidermal growth factor domains.

PubMed

Chigira, Yuko; Oka, Takuji; Okajima, Tetsuya; Jigami, Yoshifumi

2008-04-01

Development of a heterologous system for the production of homogeneous sugar structures has the potential to elucidate structure-function relationships of glycoproteins. In the current study, we used an artificial O-glycosylation pathway to produce an O-fucosylated epidermal growth factor (EGF) domain in Saccharomyces cerevisiae. The in vivo O-fucosylation system was constructed via expression of genes that encode protein O-fucosyltransferase 1 and the EGF domain, along with genes whose protein products convert cytoplasmic GDP-mannose to GDP-fucose. This system allowed identification of an endogenous ability of S. cerevisiae to transport GDP-fucose. Moreover, expression of EGF domain mutants in this system revealed the different contribution of three disulfide bonds to in vivo O-fucosylation. In addition, lectin blotting revealed differences in the ability of fucose-specific lectin to bind the O-fucosylated structure of EGF domains from human factors VII and IX. Further introduction of the human fringe gene into yeast equipped with the in vivo O-fucosylation system facilitated the addition of N-acetylglucosamine to the EGF domain from factor IX but not from factor VII. The results suggest that engineering of an O-fucosylation system in yeast provides a powerful tool for producing proteins with homogenous carbohydrate chains. Such proteins can be used for the analysis of substrate specificity and the production of antibodies that recognize O-glycosylated EGF domains.

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

PubMed Central

Kim, Mi Eun; Jung, Inae; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

2017-01-01

The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics. PMID:29104209

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo.

PubMed

Kim, Mi Eun; Jung, Inae; Lee, Jong Suk; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

2017-11-01

The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos , cox-2 , il-1β , tnf-α , and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

The Back Pay Remedy in Title VII Class Actions: Problems of Procedure

ERIC Educational Resources Information Center

Edwards, Charles A.

1974-01-01

The class action for back pay has developed as a significant factor in employment discrimination litigation under Title VII of the Civil Rights Act of 1964. Problems of demonstrating each class member's entitlement are examined and a bifurcated trial procedure is proposed as a method for handling such cases. (JT)

Implementation Practices of Bilingual Education Programs.

ERIC Educational Resources Information Center

Ortiz, Flora Ida

The ethnographic study investigated the implementation practices of a bilingual education program. A school site containing factors which were determined to be prevalent across Title VII programs was selected from over 300 Title VII sites. In addition, the school also contained a local student population, i.e., no one was bused from elsewhere; two…

Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

PubMed

Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

1999-04-01

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

Onset of ice VII phase during ps laser pulse propagation through liquid water

NASA Astrophysics Data System (ADS)

Kumar, V. Rakesh; Kiran, P. Prem

2017-01-01

Water dominantly present in liquid state on earth gets transformed to crystalline polymorphs under different dynamic loading conditions. Out of different crystalline phases discovered till date, ice VII is observed to be stable over wide pressure (2-63 GPa) and temperature (>273 K) ranges. The formation of ice VII crystalline structure has been vastly reported during high pressure static compression using diamond anvil cell and propagation of high energy (>50 mJ/pulse) nanosecond laser pulse induced dynamic high pressures through liquid water. We present the onset of ice VII phase at low threshold of 2 mJ/pulse during 30 ps (532 nm, 10 Hz) laser pulse induced shock propagating through liquid water. Role of input pulse energy on the evolution of Stoke's and anti-Stoke's Raman shift of the dominant A1g mode of ice VII, filamentation, free-electrons, plasma shielding is presented. The H-bond network rearrangement, electron ion energy transfer time coinciding with the excitation pulse duration supported by the filamentation and plasma shielding of the ps laser pulses reduced the threshold of ice VII structure formation. Filamentation and the plasma shielding have shown the localized creation and sustenance of ice VII structure in liquid water over 3 mm length and 50 μm area of cross-section.

A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

PubMed

Coleman, Lewis S

2007-01-01

A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

[Administration of activated recombinant factor VII (novo seven) for the control of massive bleeding in gynecology].

PubMed

Tanchev, S; Pandurski, F; Georgiev, A; Gesheva, Iu; Platikanov, V; Dinov, P

2004-01-01

We report our clinical opinion for recombinant activated factor VII (NovoSeven, Novo Nordisk, Copenhagen, Denmark) administration in gynecology patients with massive haemorrhage. 3 women with gynecology deseases and severe bleeding in recieved NovoSeven in bolus IV. The blood loss and laboratory changes in hematology and haemostasis parameters are monitored. The bleeding was ceased in all cases. Decrease in values of Hb, Er and PTT was noted. The use of recombinant factor VIIA in gynecology patients with severe bleeding is effective and safe enough and could be an alternative to the extreme surgical procedures.

The Crystal Structure of a hCA VII Variant Provides Insights into the Molecular Determinants Responsible for Its Catalytic Behavior.

PubMed

Buonanno, Martina; Di Fiore, Anna; Langella, Emma; D'Ambrosio, Katia; Supuran, Claudiu T; Monti, Simona Maria; De Simone, Giuseppina

2018-05-24

Although important progress has been achieved in understanding the catalytic mechanism of Carbonic Anhydrases, a detailed picture of all factors influencing the catalytic efficiency of the various human isoforms is still missing. In this paper we report a detailed structural study and theoretical pKa calculations on a hCA VII variant. The obtained data were compared with those already known for another thoroughly investigated cytosolic isoform, hCA II. Our structural studies show that in hCA VII the network of ordered water molecules, which connects the zinc bound solvent molecule to the proton shuttle His64, is altered compared to hCA II, causing a reduction of the catalytic efficiency. Theoretical calculations suggest that changes in solvent network are related to the difference in pKa of the proton shuttle in the two enzymes. The residue that plays a major role in determining the diverse pKa values of the proton shuttle is the one in position four, namely His for hCA II and Gly for hCA VII. This residue is located on the protein surface, outside of the active site cavity. These findings are in agreement with our previous studies that highlighted the importance of histidines on the protein surface of hCA II (among which His4) as crucial residues for the high catalytic efficiency of this isoform.

Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency.

PubMed

Borhany, M; Boijout, H; Pellequer, J-L; Shamsi, T; Moulis, G; Aguilar-Martinez, P; Schved, J-F; Giansily-Blaizot, M

2013-11-01

Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series. © 2013 John Wiley & Sons Ltd.

[Our experience with recombinant activated factor VII (NovoSeven) in the high risk cardiosurgical patients with bleeding complication].

PubMed

Miskolczi, Szabolcs; Vaszily, Miklós; Papp, Csaba; Péterffy, Arpád

2008-01-01

Haemorrhagic complications significantly increase mortality and cost of treatment in cardiac surgery. A few years ago recombinant activated factor VII has been introduced to decrease such complications. In our department recombinant activated factor VII has been used in 11 patients between 2004 and 2007. Nine of them underwent a combined (simultaneous CABG and valve replacement) high risk surgery with long aortic cross clamp time and long extracorporeal circulation time. One patient underwent a repeat coronary artery bypass operation and one was operated for aortic dissection. The average dose given was 6.5 mg (2.4-9.6 mg). The average amount of bleeding without NovoSeven given was 5440 ml, however it was only 987 ml when NovoSeven was used. Nine of the patients were completely recovered and discharged from hospital, but two of them died in the postoperative period for delayed use of the recombinant factor VII-a and for severe co-morbidities (bowel ischaemia, cirrhosis of the liver). NovoSeven given in the proper time and dose significantly reduces bleeding following cardiac surgery, even if it cannot be stopped surgically. Using recombinant factor VIIa can save life in case of severe non-surgical diffuse bleeding or in case of suture insufficiency caused by friable soft tissues following high risk combined surgery with extremely long aortic cross clamp time and extracorporeal circulation time. Significant delay in the use of NovoSeven should be avoided because the temporary reduction of bleeding usually does not change fatal outcome.

Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients.

PubMed

van Geffen, Mark; Mathijssen, Natascha C J; Holme, Pål A; Laros-van Gorkom, Britta A P; van Kraaij, Marian G J; Masereeuw, Roselinde; Peyvandi, Flora; van Heerde, Waander L

2013-07-01

Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Onset of ice VII phase during ps laser pulse propagation through liquid water

NASA Astrophysics Data System (ADS)

Paturi, Prem Kiran; Vaddapally, Rakesh Kumar; Acrhem Team

2015-06-01

Water dominantly present in liquid state on earth gets transformed to crystalline polymorphs under different dynamic loading conditions. Out of 15 different crystalline phases discovered till date, ice VII is observed to be stable over wide pressure (2-63 GPa) and temperature (>273 K) ranges. We present the onset of ice VII phase at low threshold of 2 mJ/pulse during 30 ps (532 nm, 10 Hz) laser pulse induced shock propagating through liquid water. Role of input pulse energy on the evolution of Stoke's and anti-Stoke's Raman shift of the dominant A1g mode of ice VII, filamentation, free-electrons, plasma shielding is presented. The H-bond network rearrangement, electron ion energy transfer time coinciding with the excitation pulse duration supported by the filamentation and plasma shielding of the ps laser pulses reduced the threshold of ice VII structure formation. Filamentation and the plasma shielding have shown the localized creation and sustenance of ice VII structure in liquid water over 3 mm length and 50 μm area of cross-section. The work is supported by Defence Research and Developement Organization, India through Grants-in-Aid Program.

Biological and Phylogenetic Characterization of a Genotype VII Newcastle Disease Virus from Venezuela: Efficacy of Field Vaccination

PubMed Central

Perozo, Francisco; Marcano, Rosmar

2012-01-01

Here we report the biological and molecular characterization of a virulent genotype VII Newcastle disease virus (NDV) circulating in Venezuela and the assessment of the vaccination efficacy under field conditions compared to controlled rearing conditions. Biological pathotyping showed a mean embryo dead time of 50 h and an intracerebral pathogenicity index of 1.86. Sequence-based phylogenetic analysis demonstrated that the virus belongs to genotype VII in class II (a genotype often found in Asia and Africa), representing the first report of the presence of this genotype in the continent of South America. A vaccine-challenge trial in commercial broilers reared in fields or in a experimental setting included dual (live/killed) priming of 1-day-old chicks plus two live NDV and infectious bursal disease virus (IBDV) field vaccinations at days 7 and 17, followed by a very stringent genotype VII NDV challenge at day 28. Serology for NDV and IBDV, bursal integrity, and protection against NDV lethal challenge were assessed. At 28 days, field vaccinates showed significantly lower NDV (1,356 versus 2,384) and higher IBD (7,295 versus 1,489) enzyme-linked immunosorbent assay (ELISA) antibody titers than the experimentally reared birds. A lower bursal size and bursa-body weight ratio (P < 0.05) and higher bursa lesion score were also detected in the field set. Only 57.1% of field vaccinates survived the lethal challenge, differing (P < 0.05) from 90.5% survival in the experimental farm. Overall, results confirmed the presence of the genotype VII viruses in South America and suggest that field-associated factors such as immunosuppression compromise the efficacy of the vaccination protocols implemented. PMID:22238433

Reduction and removal of heptavalent technetium from solution by Escherichia coli.

PubMed

Lloyd, J R; Cole, J A; Macaskie, L E

1997-03-01

Anaerobic, but not aerobic, cultures of Escherichia coli accumulated Tc(VII) and reduced it to a black insoluble precipitate. Tc was the predominant element detected when the precipitate was analyzed by proton-induced X-ray emission. Electron microscopy in combination with energy-dispersive X-ray analysis showed that the site of Tc deposition was intracellular. It is proposed that Tc precipitation was a result of enzymatically mediated reduction of Tc(VII) to an insoluble oxide. Formate was an effective electron donor for Tc(VII) reduction which could be replaced by pyruvate, glucose, or glycerol but not by acetate, lactate, succinate, or ethanol. Mutants defective in the synthesis of the transcription factor FNR, in molybdenum cofactor (molybdopterin guanine dinucleotide [MGD]) synthesis, or in formate dehydrogenase H synthesis were all defective in Tc(VII) reduction, implicating a role for the formate hydrogenlyase complex in Tc(VII) reduction. The following observations confirmed that the hydrogenase III (Hyc) component of formate hydrogenlyase in both essential and sufficient for Tc(VII) reduction: (i) dihydrogen could replace formate as an effective electron donor for Tc(VII) reduction by wild-type bacteria and mutants defective in MGD synthesis; (ii) the inability of fnr mutants to reduce Tc(VII) can be suppressed phenotypically by growth with 250 microM Ni2+ and formate; (iii) Tc(VII) reduction is defective in a hyc mutant; (iv) the ability to reduce Tc(VII) was repressed during anaerobic growth in the presence of nitrate, but this repression was counteracted by the addition of formate to the growth medium; (v) H2, but not formate, was an effective electron donor for a Sel- mutant which is unable to incorporate selenocysteine into any of the three known formate dehydrogenases of E. coli. This appears to be the first report of Hyc functioning as an H2-oxidizing hydrogenase or as a dissimilatory metal ion reductase in enteric bacteria.

Factor VII deficiency

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer.

PubMed

Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E

2017-01-03

Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.

Where Are the Baryons? III. Nonequilibrium Effects and Observables

NASA Astrophysics Data System (ADS)

Cen, Renyue; Fang, Taotao

2006-10-01

A significant fraction (40%-50%) of baryons at the present epoch are predicted to be shock-heated to the warm-hot intergalactic medium (WHIM) by our previous numerical simulations. Here we recompute the evolution of the WHIM with several major improvements: (1) galactic superwind feedback processes from galaxy and star formation are explicitly included; (2) major metal species (O V to O IX) are computed explicitly in a nonequilibrium way; and (3) mass and spatial dynamic ranges are larger by factors of 8 and 2, respectively, than in our previous simulations. We find the following: (1) Nonequilibrium calculations produce significantly different results than do ionization equilibrium calculations. (2) The abundance of O VI absorption lines based on nonequilibrium simulations with galactic superwinds is in remarkably good agreement with the latest observations, strongly validating our model, while the predicted abundances for O VII and O VIII absorption lines appear to be lower than the still very uncertain observations. The expected abundances for O VI (as well as Lyα), O VII, and O VIII absorption systems are in the range 50-100 per unit redshift at equivalent width EW=1 km s-1, decreasing to 10-20 per unit redshift at EW=10 km s-1, to one to three lines for O VII and O VIII and negligible for O VI at EW>100 km s-1. (3) Emission lines, primarily O VI and Lyα in the UV and O VII and O VIII in soft X-rays, are potentially observable by future missions, and different lines provide complementary probes of the WHIM in the temperature-density-metallicity phase space. The number of emission lines per unit redshift that may be detectable by planned UV and soft X-ray missions are of order 0.1-1.

Prehospital Blood Transfusion in the En Route Management of Severe Combat Trauma: A Matched Cohort Study

DTIC Science & Technology

2014-09-01

routine use of tranexamic acid and decreased recombinant activated factor VII use repre- sent the effects of opposing trends in the evidence base for...Respiratory rate 19 (15Y24) 20 (16Y26) 0.173** Heart rate 92 (74Y115) 105 (82Y128) 0.041** Tranexamic acid 22 (22.6) 0 (0) U/T Recombinant activated factor VII...Military Applica- tion of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study. Arch Surg. 2012;147(2):113Y119. 6. Penn-Barwell JG

Federal Programs Supporting Educational Change, Vol. VII: Factors Affecting Implementation and Continuation.

ERIC Educational Resources Information Center

Berman, Paul; And Others

This report is one of three volumes that describe the second phase of a study that examined the implementation of four federal change agent programs related to education. Phase 2 of the study focused on what happens to local projects in the two largest change agent programs--ESEA Title III and ESEA Title VII--when federal funding stops. This…

Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

PubMed

Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

2011-10-01

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

Postprandial changes in platelet function and coagulation factors after high-fat meals with different fatty acid compositions.

PubMed

Freese, R; Mutanen, M

1995-09-01

To compare the postprandial effects of three oils differing in their fatty acid composition on platelet aggregation and coagulation. The oils studied were low-erucic acid rapeseed oil (RO, oleic acid 54% of fatty acids), sunflower oil (SO, linoleic acid 64% of fatty acids) and butter oil (BO, saturated fatty acids 62% of fatty acids). The postprandial effects of three fat-loads were followed for 5 h. Division of Nutrition, University of Helsinki. Twelve healthy female subjects (aged 23-38 years) were recruited among university students and employees. Postprandial lipaemia was induced by high-fat meals containing fat (RO, SO or BO) 1 g/kg of body weight, skim-milk powder, sugar, strawberries, and water. Each subject ingested each meal in three separate mornings after an overnight fast. The order of the meals was randomised. Blood samples were taken before and 1, 2.5, and 5 h after the test meal. All three test meals similarly affected platelet aggregation in platelet-rich plasma. Aggregation induced by collagen (0.6, 1 and 2.5 micrograms/ml) decreased during the 5-h period after the meals (P = 0.000). ADP-induced aggregation did not change during the follow-up period after any meal (P = 0.105-0.483). All fat loads increased factor VII coagulant activity (F VII:C) (P = 0.000), but in plasma fibrinogen concentration (P = 0.155) or antithrombin III activity (P = 0.278) no postprandial changes were found. These results show that high-fat meals have acute effects on platelet function and F VII:C in healthy women and that these effects are not mediated through the fatty acid composition of the meals.

The Story of Serum Prothrombin Conversion Accelerator, Proconvertin, Stable Factor, Cothromboplastin, Prothrombin Accelerator or Autoprothrombin I, and Their Subsequent Merging into Factor VII.

PubMed

Girolami, Antonio; Cosi, Elisabetta; Santarossa, Claudia; Ferrari, Silvia; Luigia Randi, Maria

2015-06-01

Factor VII (FVII) deficiency is one of the two congenital coagulation disorders that was not discovered by the description of a new bleeding patient whose clotting pattern did not fit the blood coagulation knowledge of the time (the other is factor XIII deficiency). The existence of an additional factor capable of accelerating the conversion of prothrombin into thrombin was suspected before 1951, the year in which the first family with FVII deficiency was discovered. As several investigators were involved in the discovery of FVII deficiency from both sides of the Atlantic, several different names were tentatively suggested to define this entity, namely stable factor (in contrast with labile factor or FV), cothromboplastin, proconvertin, serum prothrombin conversion accelerator, prothrombin acceleration, and autoprothrombin I. The last term was proposed by those who denied the existence of this new entity, which was instead considered to be a derivate of prothrombin activation, namely autoprothrombin. The description of several families, from all over the world, of the same defect, however clearly demonstrated the singularity of the condition. Factor VII was then proposed to define this protein. In subsequent years, several variants were described with peculiar reactivity toward tissue thromboplastins of different origin. Molecular biology techniques demonstrated several gene mutations, usually missense mutations, often involving exon 8 of the FVII gene. Later studies dealt with the relation of FVII with tissue factor and activated FVII (FVIIa). The evaluation of circulating FVIIa was made possible by the use of a truncated form of tissue factor, which is only sensitive to FVIIa present in the circulation. The development of FVII concentrates, both plasma derived and recombinant, has facilitated therapeutic management of FVII-deficient patients. The use of FVIIa concentrates was noted to be associated with the occasional occurrence of thrombotic events, mainly venous. Total or partial liver transplants have been performed with success in these patients and have "cured" their deficiencies. Prenatal diagnosis has also been performed and recent research involves the development of inhibitors of FVII + tissue factor complex or of FVIIa. This approach, if successful, could provide another antithrombotic therapeutics tool. The story of FVII well summarizes the efforts of both theoretical and clinical approaches in the characterization of a coagulation disorder, that is, among the rare bleeding conditions, most frequently encountered in clinical practice. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Factor VII and protein C are phosphatidic acid-binding proteins.

PubMed

Tavoosi, Narjes; Smith, Stephanie A; Davis-Harrison, Rebecca L; Morrissey, James H

2013-08-20

Seven proteins in the human blood clotting cascade bind, via their GLA (γ-carboxyglutamate-rich) domains, to membranes containing exposed phosphatidylserine (PS), although with membrane binding affinities that vary by 3 orders of magnitude. Here we employed nanodiscs of defined phospholipid composition to quantify the phospholipid binding specificities of these seven clotting proteins. All bound preferentially to nanobilayers in which PS headgroups contained l-serine versus d-serine. Surprisingly, however, nanobilayers containing phosphatidic acid (PA) bound substantially more of two of these proteins, factor VIIa and activated protein C, than did equivalent bilayers containing PS. Consistent with this finding, liposomes containing PA supported higher proteolytic activity by factor VIIa and activated protein C toward their natural substrates (factors X and Va, respectively) than did PS-containing liposomes. Moreover, treating activated human platelets with phospholipase D enhanced the rates of factor X activation by factor VIIa in the presence of soluble tissue factor. We hypothesize that factor VII and protein C bind preferentially to the monoester phosphate of PA because of its accessibility and higher negative charge compared with the diester phosphates of most other phospholipids. We further found that phosphatidylinositol 4-phosphate, which contains a monoester phosphate attached to its myo-inositol headgroup, also supported enhanced enzymatic activity of factor VIIa and activated protein C. We conclude that factor VII and protein C bind preferentially to monoester phosphates, which may have implications for the function of these proteases in vivo.

Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity.

PubMed

Erem, Cihangir

2006-03-01

Various abnormalities of coagulation and fibrinolysis occur in patients with thyroid diseases, and may range from subclinical laboratory abnormalities to clinically significant disorders of coagulation and, rarely, major haemorrhage or thromboembolism. The influence of subclinical hypothyroidism (SHypo) on haemostasis is controversial, both hypercoagulable and hypocoagulable states have been reported. A hypercoagulable state might be a risk factor for thromboembolic disease in SHypo. On the other hand, subclinical hyperthyroidism (SCHyper) is associated with enhanced cardiovascular risk. In the English literature, there are no studies on changes in coagulation and fibriolytic status in subjects with SCHyper. Therefore, the aim of the present study was to investigate the markers of endogenous coagulation and fibrinolysis, and to evaluate the relationships between serum lipid profile and thyroid hormones and these haemostatic parameters in subclinical thyroid patients. Various haemostatic parameters were investigated in 30 patients with SHypo and 20 patients with SCHyper and compared to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these haemostatic parameters were examined. Compared with the control subjects, only FX activity was significantly increased in patients with SCHyper (P < 0.01). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in patients with SHypo compared with the control group (P < 0.001 and P < 0.01, respectively). TC levels were significantly higher in patients with SCHyper than in controls (P < 0.05). No differences could be found in coagulation/fibrinolysis parameters between subclinical hypothyroid patients and control subjects. In patients with SCHyper, serum TSH level was positively correlated with FX activity (r: 0.58, P < 0.01) and inversely correlated with PAI-1 (r: -0.55. P < 0.05). Serum TG levels were inversely correlated with plasma activities of factors V, VII, VIII, IX, X and vWF (r: -0.83, P < 0.001; r: -0.68, P < 0.05; r: -0.61, P < 0.05; r: -0.77, P < 0.01; r: -0.63, P < 0.05; r: -0.60, P < 0.05, respectively). Serum TC levels were positively correlated with plasma fibrinogen levels (r: 0.72, P < 0.05). Serum HDL-C levels were positively correlated with protein S activity (r: 0.68, P < 0.05) and negatively correlated with F VII activity (r: -0.69, P < 0.05). Also, in patients with SHypo, serum TG levels were positively correlated with serum TSH levels (r: 0.42, P < 0.05), plasma activities of factors V, VII and X (r: 0.42, P < 0.05; r: 0.54, P < 0.01; r: 0.57, P < 0.01, respectively) and negatively correlated with plasma fibrinogen levels (r: -0.41, P < 0.05). Serum TC levels were positively correlated with factors V and X (r: 0.42, P < 0.05; r: 0.58, P < 0.01, respectively) and negatively correlated with t-PA Ag levels (r: -0.44, P < 0.05). Serum HDL-C levels were inversely correlated with F VII activity (r: -0.48, P < 0.05). Some differences were found in the haemostatic parameters and lipid profile between the subclinical thyroid patients and healthy controls. Increased factor X activity in patients with subclinical hyperthyroidism represent a potential hypercoagulable state, which might augment the already existing risk for atheroscleroic complications. Also, subclinical hypothyroid patients exhibit a more atherogenic lipid profile compared with healthy individuals. Therefore, subclinical hypothyroidism is also associated with an increased risk of cardiovascular disease. However, thyroid hormones may play a role at different levels of the complex haemostatic system in subclinical thyroid disease.

26 CFR 25.2522(c)-3T - Transfers not exclusively for charitable, etc., purposes in the case of gifts made after July 31...

Code of Federal Regulations, 2010 CFR

2010-04-01

...) and (c)(2)(vii)(a) of this section that guaranteed annuity interests or unitrust interests... uses an individual other than one permitted in paragraphs (c)(2)(vi)(a) and (c)(2)(vii)(a) of this... of years is determined by taking the factor for valuing the annuity or unitrust interest for the...

Modified Filamentous Bacteriophage as a Scaffold for Carbon Nanofiber.

PubMed

Szot-Karpińska, Katarzyna; Golec, Piotr; Leśniewski, Adam; Pałys, Barbara; Marken, Frank; Niedziółka-Jönsson, Joanna; Węgrzyn, Grzegorz; Łoś, Marcin

2016-12-21

With the advent of nanotechnology, carbon nanomaterials such as carbon nanofibers (CNF) have aroused substantial interest in various research fields, including energy storage and sensing. Further improvement of their properties might be achieved via the application of viral particles such as bacteriophages. In this report, we present a filamentous M13 bacteriophage with a point mutation in gene VII (pVII-mutant-M13) that selectively binds to the carbon nanofibers to form 3D structures. The phage-display technique was utilized for the selection of the pVII-mutant-M13 phage from the phage display peptide library. The properties of this phage make it a prospective candidate for a scaffold material for CNFs. The results for binding of CNF by mutant phage were compared with those for maternal bacteriophage (pVII-M13). The efficiency of binding between pVII-mutant-M13 and CNF is about 2 orders of magnitude higher compared to that of the pVII-M13. Binding affinity between pVII-mutant-M13 and CNF was also characterized using atomic force microscopy, scanning electron microscopy, and transmission electron microscopy, which confirmed the specificity of the interaction of the phage pVII-mutant-M13 and the CNF; the binding occurs via the phage's ending, where the mutated pVII protein is located. No similar behavior has been observed for other carbon nanomaterials such as graphite, reduced graphene oxide, single-walled carbon nanotubes, and multiwalled carbon nanotubes. Infrared spectra confirmed differences in the interaction with CNF between the pVII-mutant-M13 and the pVII-M13. Basing on conducted research, we hypothesize that the interactions are noncovalent in nature, with π-π interactions playing the dominant role. Herein, the new bioconjugate material is introduced.

A comparison between recombinant activated factor VII (Aryoseven) and Novoseven in patients with congenital factor VII deficiency.

PubMed

Faranoush, M; Abolghasemi, Hassan; Toogeh, Gh; Karimi, M; Eshghi, P; Managhchi, M; Hoorfar, H; Dehdezi, B Keikhaei; Mehrvar, A; Khoeiny, B; Kamyar, K; Heshmat, R; Baghaeipour, M R; Mirbehbahani, N B; Fayazfar, R; Ahmadinejad, M; Naderi, M

2015-11-01

In order to establish the efficacy and biosimilar nature of AryoSeven to NovoSeven in the treatment of congenital factor VII (FVII) deficiency, patients received either agent at 30 μg/kg, intravenously per week for 4 weeks, in a randomized fashion. The primary aim was to compare FVII:coagulation activity (FVII:C), 20 minutes after recombinant activated FVII (rFVIIa) injection, in the 2 groups. A secondary measure was self-reported bleeding. The median interquartile baseline range of the plasma level of activated FVII (FVIIa) activity in the 2 groups was 1.6 (1.1-14.0) IU/dL and 5.0 (1.1-25.5) IU/dL. All patients achieved levels of FVIIa (FVII:C) >30 IU/dL, 20 minutes after the injection of rFVIIa. Bleeding was similar between the 2 groups, with a comparable decrease in severity and frequency compared to the last month prior to treatment. AryoSeven is similar to NovoSeven in increasing postinjection FVIIa activity as well as in clinical safety and efficacy. © The Author(s) 2014.

A review of recombinant factor VII for refractory bleeding in nonhemophilic trauma patients.

PubMed

Barletta, Jeffrey F; Ahrens, Christine L; Tyburski, James G; Wilson, Robert F

2005-03-01

Recombinant factor VII (rFVII) is an attractive agent to control refractory, coagulopathic bleeding in patients following major surgery. The purpose of this review is to evaluate the published experiences of rFVII in adult, nonhemophilic, surgical and trauma patients. A computerized literature search was conducted to identify articles pertaining to rFVII use for refractory bleeding in adult, nonhemophilic, surgical patients. The selected articles were reviewed and the applicable data was analyzed. A total of 117 patients were found in 8 case series and 24 case reports. Overall, rFVII was effective in restoring hemostasis in 99/117 (85%) patients with 76/99 (77%) surviving to hospital discharge. In trauma patients, hemostasis was achieved in 20/26 (77%) patients and 17/20 (85%) survived. There were 5 (4%) thromboembolic events observed in the 117 cases and much disparity was noted with the initial dose. Severe acidosis affected the activity of rFVII. Recombinant factor VII is an effective therapeutic agent for achieving hemostasis in nonhemophilic surgical patients. Published clinical experiences, however, are limited to small case series and case reports.

Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/db mice.

PubMed

Mihara, Masatomo; Aihara, Ken-ichi; Ikeda, Yasumasa; Yoshida, Sumiko; Kinouchi, Mizuho; Kurahashi, Kiyoe; Fujinaka, Yuichi; Akaike, Masashi; Matsumoto, Toshio

2010-02-01

The binding of thrombin to its receptor stimulates inflammatory cytokines including IL-6 and monocyte chemoattractant protein-1 (MCP-1); both are associated with the development of insulin resistance. Because increased adiposity enhanced the expression of coagulation factor VII that stimulates the coagulation pathway in adipose tissue, we tested whether the inhibition of thrombin action ameliorates insulin resistance in obese diabetic (Lpr(-/-):db/db) mice. The 4-wk administration of argatroban, a selective thrombin inhibitor, reduced fasting plasma glucose and ameliorated insulin resistance in these mice. It also reduced adipocyte size and macrophage infiltration into adipose tissue. The aberrant gene expression of MCP-1, IL-6, adiponectin, and factor VII and suppressed insulin receptor substrate-1-Akt signaling in adipose tissue of db/db mice were reversed by argatroban treatment. These results demonstrate that increased adiposity enhances the production of thrombin in adipose tissue by stimulating factor VII expression and suggest that increased thrombin activity in adipose tissue plays an important role in the development of insulin resistance via enhancing MCP-1 production, leading to macrophage infiltration and insulin receptor substrate-1-Akt pathway inactivation.

Safety update on the use of recombinant activated factor VII in approved indications.

PubMed

Neufeld, Ellis J; Négrier, Claude; Arkhammar, Per; Benchikh el Fegoun, Soraya; Simonsen, Mette Duelund; Rosholm, Anders; Seremetis, Stephanie

2015-06-01

This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. No confirmed cases of neutralising antibodies against rFVIIa have been reported in patients with congenital haemophilia, acquired haemophilia or Glanzmann's thrombasthenia. The favourable safety profile of rFVIIa can be attributed to the recombinant nature of rFVIIa and its localised mechanism of action at the site of vascular injury. Recombinant FVIIa activates factor X directly on the surface of activated platelets, which are present only at the site of injury, meaning that systemic activation of coagulation is avoided and the risk of thrombotic events (TEs) thus reduced. Nonetheless, close monitoring for signs and symptoms of TE is warranted in all patients treated with any pro-haemostatic agent, including rFVIIa, especially the elderly and any other patients with concomitant conditions and/or predisposing risk factors to thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential regulation and impact of fucosyltransferase VII and core 2 β1,6-N-acetyl-glycosaminyltransferase for generation of E-selectin and P-selectin ligands in murine CD4+ T cells

PubMed Central

Schroeter, Micha F; Ratsch, Boris A; Lehmann, Jeanette; Baumgrass, Ria; Hamann, Alf; Syrbe, Uta

2012-01-01

Ligands for E-selectin and P-selectin (E-lig and P-lig) are induced on CD4+ T cells upon differentiation into effector T cells. Glycosyltransferases, especially α 1,3-fucosyltransferase VII (FucT-VII) and core 2 β1,6-N-acetyl-glycosaminyltransferase I (C2GlcNAcT-I), are critical for their synthesis. We here analysed the signals that control the expression of E-lig, P-lig and mRNA coding for FucT-VII and C2GlcNAcT-I. In line with previous reports, we found that P-lig expression correlates with the regulation of C2GlcNAcT-I, whereas E-lig expression can occur at low levels of C2GlcNAcT-I mRNA but requires high FucT-VII mRNA expression. Interestingly, the two enzymes are regulated by different signals. Activation-induced C2GlcNAcT-I up-regulation under permissive (T helper type 1) conditions was strongly reduced by cyclosporin A (CsA), suggesting the involvement of T-cell receptor-dependent, calcineurin/NFAT-dependent signals in combination with interleukin-12 (IL-12) -mediated signals in the regulation of C2GlcNAcT-I. In contrast, expression of FucT-VII mRNA was not significantly inhibited by CsA. Interleukin-4 inhibited the expression of FucT-VII but IL-2 and IL-7 were found to support induction of FucT-VII and E-lig. E-selectin, P-selectin and their ligands initially appeared to have rather overlapping functions. These findings however, unravel striking differences in the regulation of E-lig and P-lig expression, dictated by the dominance of FucT-VII and C2GlcNAcT-I, respectively, and their dependency on signals from either promiscuous or homeostatic cytokines (FucT-VII) or a strong T-cell receptor signal in combination with inflammatory cytokines in case of C2GlcNAcT-I. PMID:23039181

Oxidation of Microcystins by Permanganate: pH and Temperature-Dependent Kinetics, Effect of DOM Characteristics, and Oxidation Mechanism Revisited.

PubMed

Kim, Min Sik; Lee, Hye-Jin; Lee, Ki-Myeong; Seo, Jiwon; Lee, Changha

2018-05-23

Oxidative degradation of six representative microcystins (MCs) (MC-RR, -LR, -YR, -LF, -LW and -LA) by potassium permanganate (KMnO4; Mn(VII)) was investigated, focusing on the temperature- and pH-dependent reaction kinetics, the effect of dissolved organic matter (DOM), and the oxidation mechanisms. Second-order rate constants for the reactions of the six MCs with Mn(VII) (kMn(VII),MC) were determined to be 160.4-520.1 M-1 s-1 (MC-RR > -LR  -YR > -LF  -LW > -LA) at pH 7.2 and 21°C. The kMn(VII),MC values exhibited activation energies ranging from 15.1 to 22.4 kJ mol-1. With increasing pH from 2 to 11, the kMn(VII),MC values decreased until pH 5, and plateaued over the pH range of 5-11, except for that of MC-YR (which increased at pH > 8). Species-specific second-order rate constants were calculated using predicted pKa values of MCs. The oxidation of MCs in natural waters was accurately predicted by the kinetic model using kMn(VII),MC and Mn(VII) exposure ([Mn(VII)]dt) values. Among different characteristics of DOM in natural waters, UV254, SUVA254, and the abundance of humic-like substances characterized by fluorescence spectroscopy exhibited good correlation with [Mn(VII)]dt. A thorough product study of MC-LR oxidation by Mn(VII) was performed using liquid chromatography-mass spectrometry.

Blister-inducing antibodies target multiple epitopes on collagen VII in mice

PubMed Central

Csorba, Kinga; Chiriac, Mircea Teodor; Florea, Florina; Ghinia, Miruna Georgiana; Licarete, Emilia; Rados, Andreea; Sas, Alexandra; Vuta, Vlad; Sitaru, Cassian

2014-01-01

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease of mucous membranes and the skin caused by autoantibodies against collagen VII. In silico and wet laboratory epitope mapping studies revealed numerous distinct epitopes recognized by EBA patients' autoantibodies within the non-collagenous (NC)1 and NC2 domains of collagen VII. However, the distribution of pathogenic epitopes on collagen VII has not yet been described. In this study, we therefore performed an in vivo functional epitope mapping of pathogenic autoantibodies in experimental EBA. Animals (n = 10/group) immunized against fragments of the NC1 and NC2 domains of collagen VII or injected with antibodies generated against the same fragments developed to different extent experimental EBA. Our results demonstrate that antibodies targeting multiple, distinct epitopes distributed over the entire NC1, but not NC2 domain of collagen VII induce blistering skin disease in vivo. Our present findings have crucial implications for the development of antigen-specific B- and T cell-targeted therapies in EBA. PMID:25091020

Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.

PubMed

Napolitano, M; Di Minno, M N D; Batorova, A; Dolce, A; Giansily-Blaizot, M; Ingerslev, J; Schved, J-F; Auerswald, G; Kenet, G; Karimi, M; Shamsi, T; Ruiz de Sáez, A; Dolatkhah, R; Chuansumrit, A; Bertrand, M A; Mariani, G

2016-09-01

A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 μg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 μg kg(-1) (divided as three doses). Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies. © 2016 John Wiley & Sons Ltd.

Recombinant activated factor VII in cardiac surgery: a systematic review.

PubMed

Warren, Oliver; Mandal, Kaushik; Hadjianastassiou, Vassilis; Knowlton, Lisa; Panesar, Sukhmeet; John, Kokotsakis; Darzi, Ara; Athanasiou, Thanos

2007-02-01

Postoperative hemorrhage is a common complication in cardiac surgery, and it is associated with a considerable increase in morbidity, mortality, and cost. Recombinant activated factor VII (rFVIIa) is an emerging hemostatic agent, increasingly used in cardiac surgery. This article systematically reviews the evidence regarding the efficacy, safety, and cost of rFVIIa in this setting. Although definitive evidence from randomized controlled trials is lacking, the use of rFVIIa in patients experiencing refractory postoperative hemorrhage seems promising and relatively safe. However further research is required to definitively establish its clinical utility in the postoperative cardiac patient.

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin...

Expanding the versatility of phage display II: improved affinity selection of folded domains on protein VII and IX of the filamentous phage.

PubMed

Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

2011-02-24

Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before.

Investigating the air oxidation of V(II) ions in a vanadium redox flow battery

NASA Astrophysics Data System (ADS)

Ngamsai, Kittima; Arpornwichanop, Amornchai

2015-11-01

The air oxidation of vanadium (V(II)) ions in a negative electrolyte reservoir is a major side reaction in a vanadium redox flow battery (VRB), which leads to electrolyte imbalance and self-discharge of the system during long-term operation. In this study, an 80% charged negative electrolyte solution is employed to investigate the mechanism and influential factors of the reaction in a negative-electrolyte reservoir. The results show that the air oxidation of V(II) ions occurs at the air-electrolyte solution interface area and leads to a concentration gradient of vanadium ions in the electrolyte solution and to the diffusion of V(II) and V(III) ions. The effect of the ratio of the electrolyte volume to the air-electrolyte solution interface area and the concentrations of vanadium and sulfuric acid in an electrolyte solution is investigated. A higher ratio of electrolyte volume to the air-electrolyte solution interface area results in a slower oxidation reaction rate. The high concentrations of vanadium and sulfuric acid solution also retard the air oxidation of V(II) ions. This information can be utilized to design an appropriate electrolyte reservoir for the VRB system and to prepare suitable ingredients for the electrolyte solution.

Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature.

PubMed

Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup; Philips, Malou; Dalhoff, Kim; Bendtsen, Flemming

2009-01-01

The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences the accuracy of the plasma PT assay. The accuracy of Nycotest PT was studied using plasma added NAC in vitro and plasma from subjects infused with NAC. The latter results were compared with those obtained by analysis of PT by CoaguChek S. Therapeutic NAC concentrations added to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures <24 degrees C. Activity lost at 37 degrees C could partly be recovered by subsequent incubation at 5 or 20 degrees C. Incubation at 37 degrees C prior to assay led to a significant additional depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored below 24 degrees C. This was supported by similarity of results obtained by analysis of appropriately stored plasma and simultaneously drawn blood by CoaguChek S. Residual reactive NAC does not interfere with the accuracy of the PT assay of plasma stored below 24 degrees C, but NAC-induced loss in activity at 37 degrees C may be partly recovered during subsequent storage below 24 degrees C.

[Haplotype Analysis of Coagulation Factor VII Gene in a Patient with Congenital Coagulation Factor VII Deficiency with Heterozygous p.Arg337Cys Mutation and o.Aro413Gin Polymorphism..

PubMed

Suzuki, Keijiro; Yoshioka, Tomoko; Obara, Takehiro; Suwabe, Akira

2016-05-01

Congenital coagulation factor VII (FVII) deficiency is a rare hemorrhagic disease with an autosomal reces- sive inheritance pattern. We analyzed coagulation factor VII gene (F7) of a patient with FVII deficiency and used expression studies to investigate the effect of a missense mutation on FVII secretion. The proband, a 69-year-old Japanese woman, had a history of postpartum bleeding and excessive bleeding after dental extrac- tion. She was found to have mildly increased PT-INR (1.17) before an ophthalmic operation. FVII activity and antigen were reduced (29.0% and 32.8%). Suspecting that the proband was FVII deficient, we analyzed F7 of the patient. Sequence analysis revealed that the patient was heterozygous for a point mutation (p.Arg337Cys) in the catalytic domain and polymorphisms: the decanucleotide insertion at the promoter re- gion, dimorphism (c.525C >T) in exon 5, and p.Arg413Gln in exon 8. Haplotype analysis clarified that p.Arg337Cys was located on the p.Arg413 allele (Ml allele). The other allele had the p.Arg413Gln polymor- phism(M2 allele) which is known to produce less FVII. Expression studies revealed that p.Arg337Cys causes impairment of FVII secretion. Insufficient secretion of FVII arising from both the p.Arg337Cys/M1 allele and the p.Arg337/M2 allele might lower the FVII level of this patient(<50%). The FVII level in a heterozygous FVII deficient patient might be influenced by F7 polymorphisms on the normal allele. There- fore, genetic analyses are important for the diagnosis of heterozygous FVII deficiency.

The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Sanzari, Jenine K.; Kennedy, Ann R.

2013-01-01

Purpose To determine whether proton radiation affects coagulation. Material and methods Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3–7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved. Results HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0. Conclusions PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy. PMID:22221163

Successful synthesis of active human coagulation factor VII by co-expression of mammalian gamma-glutamyl carboxylase and modification of vit.K cycle in Drosophila Schneider S2 cells.

PubMed

Nagahashi, Kotomi; Umemura, Kazuo; Kanayama, Naohiro; Iwaki, Takayuki

2017-04-01

Mammalian gamma-glutamyl carboxylase and reduced vitamin K are indispensable for synthesis of mature mammalian vitamin K dependent proteins including some of blood coagulation factors (factors II, VII, IX, and X). It was well known that Drosophila melanogaster expressed gamma-glutamyl carboxylase and possessed a vit.K cycle although native substrates for them have not been identified yet. Despite the potential capability of gamma carboxylation in D. melanogaster derived cells such as S2 cells, Drosophila gamma-glutamyl carboxylase failed to gamma carboxylate a peptide fused to the human coagulation factor IX propeptide. Thus, it had been believed that the Drosophila system was not adequate to synthesize mammalian vit.K dependent proteins. Indeed, we previously attempted to synthesize biologically active factor VII in S2 cells although we were not able to obtain it. However, recently, a successful transient expression of biologically active human factor IX from S2 cells was reported. In the present study, several expression vectors which enable expressing mammalian GGCX, VKORC1, and/or PDIA2 along with F7 were developed. S2 cells transfected with pMKA85, pMAK86, and pMAK219 successfully synthesized active FVII. Thus, mammalian GGCX was indispensable to synthesize active FVII while mammalian VKORC1 and PDIA2 were not critical but supportive factors for S2 cells.

Multicomutation flow system for manganese speciation by solid phase extraction and flame atomic absorption spectrometry

NASA Astrophysics Data System (ADS)

Tobiasz, Anna; Sołtys, Monika; Kurys, Ewa; Domagała, Karolina; Dudek-Adamska, Danuta; Walas, Stanisław

2017-08-01

In the paper an application of solid phase extraction technique for speciation analysis of manganese in water samples with the use of flame atomic absorption spectrometry is presented. Two types of sorbents, activated silica gel and Dowex 1 × 4, were used respectively for simultaneously Mn2 + and MnO42 - retention and preconcentration. The whole procedure was realized in multicomutation flow system. Different conditions like: type and concentration of eluent, sample pH and loading time were tested during the study. Under appropriate conditions, it was possible to obtained enrichment factors of 20 and 16 for Mn(II) and Mn(VII), respectively. Precision of the procedure was close to 4% (measured as relative standard deviation), whereas the detection limit (3σ) was 1.4 μg·L- 1 for Mn(II) and 4.8 μg·L- 1 for Mn(VII).

Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population.

PubMed

Barillari, Giovanni; Fabbro, Elisabetta; Pasca, Samantha; Bigotto, Enrico

2009-06-01

Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P < 0.05) for tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein, factor VII and factor XI; conversely for factor VIII, factor IX, factor XII, antithrombin III and fibrinogen, the results gave a difference statistically significant (P < 0.01). In patients with DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.

Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

PubMed Central

Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

2011-01-01

Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

Quantitative proteomics identify an association between extracellular matrix degradation and immunopathology of genotype VII Newcastle disease virus in the spleen in chickens.

PubMed

Hu, Zenglei; Gu, Han; Hu, Jiao; Hu, Shunlin; Wang, Xiaoquan; Liu, Xiaowen; Jiao, Xinan; Liu, Xiufan

2018-06-15

Pathogenesis of genotype VII Newcastle disease virus (NDV) is characterized with remarkable immunopathology in the spleen in chickens. However, the mechanism for this unique pathological phenotype is not fully understood. Previous transcriptomics data showed that genotype VII NDV JS5/05 caused a greater downregulation of extracellular matrix (ECM) genes than genotype IV virus Herts/33 in the spleen. In this study, the role of ECM in pathology of genotype VII NDV was investigated using quantitative proteomics. Pathology studies showed that JS5/05 caused severe immunopathology characterized with remarkable necrosis in the spleen, whereas Herts/33 only induced mild pathological changes. The ECM was firstly enriched from the spleens and ECM proteins of different categories were identified by LC-MS/MS. Quantitative proteomic analysis showed that JS5/05 caused a significant disruption of ECM integrity and molecular composition compared to Herts/33. Particularly, JS5/05 induced a more remarkable collagen breakdown in the spleen compared to Herts/33. Moreover, matrix metalloproteinase (MMP)-13 and -14 were significantly upregulated by JS5/05 infection. KEGG pathway analysis suggested that differential regulation of ECM proteins by JS5/05 and Herts/33 may impact pathology through different pathways. Therefore, our results suggested that MMP upregulation and consequent ECM degradation contribute to immunopathology of genotype VII NDV in the spleen. Pathogenesis of genotype VII NDV is characterized with severe immunopathology in the spleen in chickens. Elucidating the mechanism of this pathology phenotype is critical to understand pathogenesis of genotype VII NDV. Here, we present the proteomic data of an important non-cellular compartment, the extracellular matrix (ECM), in the spleen from chickens infected with genotype VII and IV NDVs. Our results suggest that significant upregulation of matrix metalloproteinases by genotype VII NDV and consequent disruption of ECM integrity and composition may be associated with immunopathology in the spleen. Moreover, ECM degradation, represented by collagen breakdown, is an important pathology event in the process of genotype VII NDV infection. Our study for the first time presents evidence of ECM regulation by NDV and adds ECM remodeling as a new manifestation for NDV pathology. Our findings also deepen the understanding of NDV pathogenesis. Copyright © 2018. Published by Elsevier B.V.

Purification and Autoactivation Method for Recombinant Coagulation Factor VII.

PubMed

Granovski, Vladimir; Freitas, Marcela C C; Abreu-Neto, Mario Soares; Covas, Dimas T

2018-01-01

Recombinant coagulation factor VII is a very important and complex protein employed for treatment of hemophiliac patients (hemophilia A/B) who develop inhibitors antibodies to conventional treatments (FVIII and FIX). The rFVII is a glycosylated molecule and circulates in plasma as zymogen of 50 kDa. When activated the molecule is cleaved to 20-30 kDa and has a half-life of about 3 h, needing to be processed fast and efficiently until freeze-drying. Here, we describe a very simple and fast purification sequence for rFVII using affinity FVII Select resin and a dialysis system that can be easily scaled up.

Primary prophylaxis for children with severe congenital factor VII deficiency - Clinical and laboratory assessment.

PubMed

Kuperman, A A; Barg, A A; Fruchtman, Y; Shaoul, E; Rosenberg, N; Kenet, G; Livnat, T

2017-09-01

Severe congenital factor VII (FVII) deficiency is a rare bleeding disorder. Prophylaxis with replacement therapy has been suggested to patients, yet the most beneficial dosing regimens and therapy intervals are still to be defined. Due to the lack of evidence-based data, we hereby present our experience with long-term administration and monitoring primary prophylaxis in children with severe FVII deficiency and an extremely high bleeding risk. Four children with familial FVII deficiency, treated by prophylactic recombinant activated factor VII (rFVIIa), 15-30μg/kg/dose, given 2-3 times weekly since infancy, are discussed. Clinical follow up and monitoring laboratory assays, including thrombin generation, measured at various time points after prophylactic rFVIIa administration are presented. Among our treated patients neither FVII activity nor thrombin generation parameters (both already declined 24h post rFVIIa administration) were able to predict the impact of prophylaxis, and could not be used as surrogate markers in order to assess the most beneficial treatment frequency. However, the long clinical follow-up and comprehensive laboratory assessment performed, have shown that early primary prophylaxis as administered in our cohort was safe and effective. Copyright © 2016 Elsevier Inc. All rights reserved.

Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging.

PubMed

Liu, Heng; Chen, Xiao; Xue, Wei; Chu, Chengchao; Liu, Yu; Tong, Haipeng; Du, Xuesong; Xie, Tian; Liu, Gang; Zhang, Weiguo

The highly infiltrative and invasive nature of glioma cells often leads to blurred tumor margins, resulting in incomplete tumor resection and tumor recurrence. Accurate detection and precise delineation of glioma help in preoperative delineation, surgical planning and survival prediction. In this study, recombinant epidermal growth factor-like domain-1, derived from human coagulation factor VII, was conjugated to iron oxide nanoparticles (IONPs) for targeted glioma magnetic resonance (MR) imaging. The synthesized EGF1-EGFP-IONPs exhibited excellent targeting ability toward tissue factor (TF)-positive U87MG cells and human umbilical vein endothelial cells in vitro, and demonstrated persistent and efficient MR contrast enhancement up to 12 h for preclinical glioma models with high targeting specificity in vivo. They hold great potential for clinical translation and developing targeted theranostics against brain glioma.

Dynamic expression of transcription factor Brn3b during mouse cranial nerve development

PubMed Central

Sajgo, Szilard; Ali, Seid; Popescu, Octavian; Badea, Tudor Constantin

2015-01-01

During development transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. Such a combinatorial code has been proposed for the differentiation of projection neurons of the somatic and visceral components of cranial nerves. It is possible that individual neuronal cell types are not specified by unique transcription factors, but rather emerge through the intersection of their expression domains. Brn3a, Brn3b and Brn3c, in combination with each other and/or transcription factors of other families, can define subgroups of Retinal Ganglion Cells (RGC), Spiral and Vestibular Ganglia, inner ear and vestibular hair cell neurons in the vestibuloacoustic system, and groups of somatosensory neurons in the Dorsal Root Ganglia (DRG). In the present study we investigated the expression and potential role of the Brn3b transcription factor in cranial nerves and associated nuclei of the brainstem. We report the dynamic expression of Brn3b in the somatosensory component of cranial nerves II, V, VII and VIII and visceromotor nuclei of nerves VII, IX, X, as well as other brainstem nuclei during different stages of development into adult stage. We find that genetically identified Brn3bKO RGC axons show correct but delayed pathfinding during the early stages of embryonic development. However loss of Brn3b does not affect the anatomy of the other cranial nerves normally expressing this transcription factor. PMID:26356988

Human Cells as Platform to Produce Gamma-Carboxylated Proteins.

PubMed

de Sousa Bomfim, Aline; de Freitas, Marcela Cristina Corrêa; Covas, Dimas Tadeu; de Sousa Russo, Elisa Maria

2018-01-01

The gamma-carboxylated proteins belong to a family of proteins that depend on vitamin K for normal biosynthesis. The major representative gamma-carboxylated proteins are the coagulation system proteins, for example, factor VII, factor IX, factor X, prothrombin, and proteins C, S, and Z. These molecules have harbored posttranslational modifications, such as glycosylation and gamma-carboxylation, and for this reason they need to be produced in mammalian cell lines. Human cells lines have emerged as the most promising alternative to the production of gamma-carboxylated proteins. In this chapter, the methods to generate human cells as a platform to produce gamma-carboxylated proteins, for example the coagulation factors VII and IX, are presented. From the cell line modification up to the vitamin K adaptation of the produced cells is described in the protocols presented in this chapter.

Absence of in vitro Procoagulant Activity in Immunoglobulin Preparations due to Activated Coagulation Factors

PubMed Central

Oviedo, Adriana E.; Bernardi, María E.; Guglielmone, Hugo A.; Vitali, María S.

2015-01-01

Summary Background Immunoglobulin (IG) products, including intravenous (IVIG) or subcutaneous (SCIG) immunoglobulins are considered safe and effective for medical therapy; however, a sudden and unexpected increase in thromboembolic events (TE) after administration of certain batches of IVIG products has been attributed to the presence of activated coagulation factors, mainly factor XIa. Our aims were to examine the presence of enduring procoagulant activity during the manufacturing process of IGs, with special focus on monitoring factor XIa, and to evaluate the presence of in vitro procoagulant activity attributed to coagulation factors in different lots of IVIG and SCIG. Methods Samples of different steps of IG purification, 19 lots of IVIG and 9 of SCIG were analyzed and compared with 1 commercial preparation of IVIG and 2 of SCIG, respectively. Factors II, VII, IX, XI and XIa and non-activated partial thromboplastin time (NAPTT) were assayed. Results The levels of factors II, VII, IX, X and XI were non-quantifiable once fraction II had been re-dissolved and in all analyzed lots of IVIG and SCIG. The level of factor XIa at that point was under the detection limits of the assay, and NAPTT yielded values greater than the control during the purification process. In SCIG, we detected higher concentrations of factor XIa in the commercial products, which reached values up to 5 times higher than the average amounts found in the 9 batches produced by UNC-Hemoderivados. Factor XIa in commercial IVIG reached levels slightly higher than those of the 19 batches produced by UNC-Hemoderivados. Conclusion IVIG and SCIG manufactured by UNC-Hemoderivados showed a lack of thrombogenic potential, as demonstrated not only by the laboratory data obtained in this study but also by the absence of any reports of TE registered by the post marketing pharmacovigilance department. PMID:26733772

Strategic Petroleum Reserve Plan. Distribution Plan for the Strategic Petroleum Reserve. Amendment No. 3. Energy Action DOE No. 5

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

Purpose of this Strategic Petroleum Reserve (SPR) Plan Amendment is to provide a Distribution Plan, setting forth the method of drawdown and distribution of the Reserve. Chapter VII of the SPR Plan contained a Distribution Plan which identified and discussed the major objectives, criteria and other factors that will be considered in developing the detailed plan. This Amendment replaces Chapter VII of the SPR Plan in its entirety.

Speciation analysis of Mn(II)/Mn(VII) using Fe3O4@ionic liquids-β-cyclodextrin polymer magnetic solid phase extraction coupled with ICP-OES.

PubMed

Chen, Songqing; Qin, Xingxiu; Gu, Weixi; Zhu, Xiashi

2016-12-01

Ionic liquids-β-cyclodextrin polymer (ILs-β-CDCP) was attached on Fe 3 O 4 nanoparticles to prepare magnetic solid phase extraction agent (Fe 3 O 4 @ILs-β-CDCP). The properties and morphology of Fe 3 O 4 @ILs-β-CDCP were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction(XRD), size distribution and magnetic analysis. A new method of magnetic solid phase extraction (MSPE) coupled to ICP-OES for the speciation of Mn(II)/Mn(VII) in water samples was established. The results showed that Mn(VII) and total manganese [Mn(II)+Mn(VII)] were quantitatively extracted after adjusting aqueous sample solution to pH 6.0 and 10.0, respectively. Mn(II) was calculated by subtraction of Mn(VII) from total manganese. Fe 3 O 4 @ILs-β-CDCP showed a higher adsorption capacity toward Mn(II) and Mn(VII). Several factors, such as the pH value, extraction temperature and sample volume, were optimized to achieve the best extraction efficiency. Moreover, the adsorption ability of Fe 3 O 4 @ILs-β-CDCP would not be significantly lower after reusing of 10 times. The accuracy of the developed method was confirmed by analyzing certified reference materials (GSB 07-1189-2000), and by spiking spring water, city water and lake water samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunomodulatory activity of various fractions derived from Physalis angulata L extract.

PubMed

Lin, Y S; Chiang, H C; Kan, W S; Hone, E; Shih, S J; Won, M H

1992-01-01

The immunomodulatory effects of Physalis angulata L. extract fraction VII (PA-VII), PA-VII-A, PA-VII-B and PA-VII-C were investigated in this study. The results showed that PA-VII and PA-VII-C strongly enhanced blastogenesis response, PA-VII-B had moderate activity, and PA-VII-A exerted only slight effect on cell proliferation. A synergistic effect was observed when the suboptimal dosage of phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was added to the culture. Furthermore, PA-VII and PA-VII-C possessed stimulatory activity on B cells and less effect on T cells. The antibody responses were also augmented by PA-VII, PA-VII-B and PA-VII-C, but not by PA-VII-A. The enhancement of antibody response could be observed both in BALB/c and C3H/HeJ mice.

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

PubMed

Isbister, Geoffrey K; Maduwage, Kalana; Scorgie, Fiona E; Shahmy, Seyed; Mohamed, Fahim; Abeysinghe, Chandana; Karunathilake, Harendra; O'Leary, Margaret A; Gnanathasan, Christeine A; Lincz, Lisa F

2015-01-01

Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming. In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y) and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13), associated with low fibrinogen [median,<0.01 g/L; IQR: <0.01-0.9 g/L), low factor V levels [median,<5%; IQR: <5-4%], low factor VIII levels [median,40%; IQR: 12-79%] and low factor X levels [median, 48%; IQR: 29-67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48 h post-antivenom. The median INR remained >3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec) at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis). Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

Energy levels and radiative rates for transitions in Fe V, Co VI and Ni VII

NASA Astrophysics Data System (ADS)

Aggarwal, K. M.; Bogdanovich, P.; Keenan, F. P.; Kisielius, R.

2017-03-01

Energy levels, Landé g-factors and radiative lifetimes are reported for the lowest 182 levels of the 3d4, 3d34s and 3d34p configurations of Fe V, Co VI and Ni VII. Additionally, radiative rates (A-values) have been calculated for the E1, E2 and M1 transitions among these levels. The calculations have been performed in a quasi-relativistic approach (QR) with a very large configuration interaction (CI) wavefunction expansion, which has been found to be necessary for these ions. Our calculated energies for all ions are in excellent agreement with the available measurements, for most levels. Discrepancies among various calculations for the radiative rates of E1 transitions in Fe V are up to a factor of two for stronger transitions (f ≥ 0.1), and larger (over an order of magnitude) for weaker ones. The reasons for these discrepancies have been discussed and mainly are due to the differing amount of CI and methodologies adopted. However, there are no appreciable discrepancies in similar data for M1 and E2 transitions, or the g-factors for the levels of Fe V, the only ion for which comparisons are feasible.

Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

PubMed

Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

2010-11-01

Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated factor X in the presence of tissue factor and activated factor VII.

Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report.

PubMed

Sheth, Sujit; Soff, Gerald; Mitchell, Beau; Green, David; Kaicker, Shipra; Fireman, Fernando; Tugal, Oya; Guarini, Ludovico; Giardina, Patricia; Aledort, Louis

2012-02-01

While isolated factor VII (FVII) deficiency is being more frequently diagnosed owing to improved preoperative screening procedures, there is no specific guideline for perioperative management of such patients. To complicate the issue, FVII activity levels seem to correlate less well with the risk of hemorrhage than the patient's past and family bleeding history do. We have devised expert consensus recommendations for managing such patients perioperatively, taking into consideration the personal and family bleeding history, the FVII activity level and the inherent bleeding risk of the procedure itself. We hope that clinicians will find this a useful tool in the decision-making process, thereby limiting the use of recombinant factor VIIa to those who need it most, and preventing possible thrombotic complications in those without a strong indication for its use.

Mechanism of action of recombinant activated factor VII: an update.

PubMed

Hedner, Ulla

2006-01-01

Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.

Expanding the Versatility of Phage Display II: Improved Affinity Selection of Folded Domains on Protein VII and IX of the Filamentous Phage

PubMed Central

Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

2011-01-01

Background Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Methodology/Principal Findings Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Conclusions/Significance Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before. PMID:21390283

Factor VII assay performance: an analysis of the North American Specialized Coagulation Laboratory Association proficiency testing results.

PubMed

Zantek, N D; Hsu, P; Refaai, M A; Ledford-Kraemer, M; Meijer, P; Van Cott, E M

2013-06-01

The performance of factor VII (FVII) assays currently used by clinical laboratories was examined in North American Specialized Coagulation Laboratory Association (NASCOLA) proficiency tests. Data from 12 surveys conducted between 2008 and 2010, involving 20 unique specimens plus four repeat-tested specimens, were analyzed. The number of laboratories per survey was 49-54 with a total of 1224 responses. Numerous reagent/instrument combinations were used. For FVII > 80 or <40 U/dL, 99.5% of results (859/863) were correctly classified by laboratories as normal/abnormal. Classification of specimens with 40-73 U/dL FVII was heterogeneous. Interlaboratory precision was better for normal specimens (coefficient of variation (CV) 10.7%) than for FVII<20 U/dL (CV 33.1%), with a mean CV of 17.2% per specimen. Intralaboratory precision for repeated specimens demonstrated no significant difference between the paired survey results (mean absolute difference 2.5-5.0 U/dL). For specimens with FVII >50 U/dL, among commonly used methods, one thromboplastin and one calibrator produced results 5-6 U/dL higher and another thromboplastin and calibrator produced results 5-6 U/dL lower than all other methods, and human thromboplastin differed from rabbit by +7.6 U/dL. Preliminary evidence suggests these differences could be due to the calibrator. For FVII <50 U/dL, differences among the commonly used reagents and calibrators were generally not significant. © 2013 Blackwell Publishing Ltd.

The Tenth Circuit View of Title VII Discovery--EEOC v. University of New Mexico, 504 F. 2d 1296 (10th Cir. 1974); Rich v. Martin Marietta Corp., 522 F. 2d 353 (10th Cir. 1975)

ERIC Educational Resources Information Center

Hoeltgen, Kristine A.

1976-01-01

In both these cases the Tenth Circuit continued the trend begun in earlier Title VII cases of giving a liberal interpretation to the scope of discovery. In these decisions the court began to speak more particularly of the factors to be considered in acting on motions to compel discovery. (Author/LBH)

Use of recombinant activated factor VII for reduction of perioperative blood loss during elective surgical correction of spine deformity in a Jehovah's Witness. Case report.

PubMed

Kącka, Katarzyna; Kącki, Wojciech; Merak, Joanna; Błęka, Adam

2010-01-01

Planned surgical procedures at patients who refuse allogenic blood transfusion because of religious convictions are important problem, not only medical but also ethical and juristical. At the study authors report the successful use of activated recombinant factor VII (rFVIIa) for the reduction of perioperative blood loss in four years old child - Jehovah's Witness, who had planned Torode kyphectomy. Applied perioperative management together with preparing to surgery with erythropoietin allowed for reduction of blood loss and avoiding of blood transfusion. Authors state, that appropriate perioperative proceeding makes a possibility of safe surgical procedures also at patients who refuse the transfusion.

[Significance of vitamin K (VK) administration in patients under chemotherapy during postoperative fasting period].

PubMed

Ojiro, M; Takenoshita, M; Toshinaga, T; Shimazu, H

1992-01-01

Recently coagulopathy caused by vitamin K (VK) deficiency following antibiotic therapy in malnourished patients has been reported. We studied on the same problem particularly in patients under chemotherapy during postoperative fasting period. For this purpose, prothrombin time (PT), vitamin K-dependent coagulation factors (Factor II (F-II), VII (F-VII) and protein C), PIVKA-II (PK-II) and plasma level of VK in two groups of patients with or without VK administration were measured in esophageal cancer patients. In the group with VK, VK2 were given intravenously everyday. In the group without VK, PT prolonged and F-II decreased from the seventh postoperative day, especially on the 14th day significantly. Although F-VII and protein C decreased on the first day and returned subsequently on the seventh day, no significance was observed between two groups. PK-II increased clearly in the group without VK from the seventh day, whereas no significant changes were observed in the group with VK. The plasma level of VK1 decreased in both groups, but VK2, especially MK-4, was high in the group with VK.

[Hereditary heterozygous factor VII deficiency in patients undergoing surgery : Clinical relevance].

PubMed

Woehrle, D; Martinez, M; Bolliger, D

2016-10-01

A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients. In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015. In addition, by searching the literature, we identified publications reporting patients with FVII deficiency undergoing surgical procedures without perioperative substitution. We identified 22 patients undergoing 46 surgical procedures, resulting in a prevalence of 1:1500-2000. Coagulation factor concentrates were administered during the perioperative period in 15 procedures (33 %), whereas in the other 31 procedures (66 %), FVII deficiency was not substituted. No postoperative bleeding or thromboembolic events were reported. In addition, we found no differences in pre- and postoperative hemoglobin and coagulation parameters, with the exception of an improved postoperative INR value in the substituted group. In the literature review, we identified five publications, including 125 patients with FVII deficiency, undergoing 213 surgical procedures with no perioperative substitution. Preoperative substitution using coagulation factor concentrates does not seem to be mandatory in patients with an FVII level ≥15 %. For decision-making on preoperative substitution, patient history of an increased tendency to bleed may be more important than the FVII level or increased INR value.

Radiographic evaluation of bones and joints in mucopolysaccharidosis I and VII dogs after neonatal gene therapy.

PubMed

Herati, Ramin Sedaghat; Knox, Van W; O'Donnell, Patricia; D'Angelo, Marina; Haskins, Mark E; Ponder, Katherine P

2008-11-01

Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the glycosaminoglycan-degrading lysosomal enzymes alpha-L-iduronidase and beta-glucuronidase, respectively, and result in abnormal bones and joints. Here, the severity of skeletal disease in MPS I and MPS VII dogs and the effects of neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal, respectively, and bone dysplasia and articular erosions, and joint subluxation were severe. Previously, we reported that neonatal intravenous injection of a retroviral vector (RV) with the appropriate gene resulted in expression in liver and blood cells, and high serum enzyme activity. In this study, we demonstrate that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of normal, respectively, and there were partial improvements of qualitative abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and 96% of normal, respectively) were not significantly different from normal dogs. Qualitative changes in MPS I bones and joints were generally modest and were partially improved with RV treatment, although cervical spine disease was severe and was difficult to correct with gene therapy in both models. The greater severity of skeletal disease in MPS VII than in MPS I dogs may reflect accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does not prevent, skeletal disease in MPS I and MPS VII dogs.

Ischemic stroke in a patient with moderate to severe inherited factor VII deficiency.

PubMed

Reddy, Manasa; Tawfik, Bernard; Gavva, Chakri; Yates, Sean; De Simone, Nicole; Hofmann, Sandra L; Rambally, Siayareh; Sarode, Ravi

2016-12-01

Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

10 CFR 430.62 - Submission of data.

Code of Federal Regulations, 2010 CFR

2010-01-01

... energy factor expressed in cycles per kilowatt-hour. (vii) Faucets, the maximum water use in gpm (L/min... seasonal energy efficiency ratio and heating seasonal performance factor. For central air conditioning heat pumps whose seasonal energy efficiency ratio and heating seasonal performance factor are based on an...

The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo[1,2-a]pyridine derivatives.

PubMed

El-Sayed, Wael M; Hussin, Warda A; Al-Faiyz, Yasair S; Ismail, Mohamed A

2013-09-05

The antimutagenic activity of eight novel imidazo[1,2-a]pyridine derivatives (I-VIII) against sodium azide (NaN3) and benzo[a]pyrene (B[a]P) was evaluated using the Salmonella reverse mutation assay. At non-toxic concentrations (12.5-50 µM), imidazopyridines I, II, III, and V with a terminal imidazopyridine group were mutagenic, while derivatives VII and VIII with a central imidazopyridine group were not mutagenic. Compounds IV, VII, and VIII exerted a moderate antimutagenic activity against NaN3 under pre-exposure conditions, and a strong activity (>40%) against B[a]P in the presence of S9 under both pre- and co-exposure conditions and mostly independent on the dose. Imidazopyridines possibly inhibited the microsomal-dependent activation of B[a]P. The demethylated derivative VII was the most active antimutagen. All imidazopyridines had a low to moderate antioxidant activity. The antibacterial activity of imidazopyridines was sporadic and moderate probably due to the failure of bacteria to convert imidazopyridines into active metabolites. The position of imidazopyridine was a pivotal factor in the mutagenic/antimutagenic activity. The strong antimutagenic compounds were dicationic planar compounds with a centered imidazo[1,2-a]pyridine spacer. With LD50 of 60 mg/kg in mice for both derivatives VII and VIII, it is safe to investigate the anticancer activity of these derivatives in animal models. © 2013 Elsevier B.V. All rights reserved.

VizieR Online Data Catalog: Ba V, Ba VI, and Ba VII oscillator strengths (Rauch+, 2014)

NASA Astrophysics Data System (ADS)

Rauch, T.; Werner, K.; Quinet, P.; Kruk, J. W.

2014-04-01

table1.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba V. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. table2.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba VI. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. table3.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba VII. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. (3 data files).

The use of recombinant factor VIIa (NovoSeven) for treatment of active or impending bleeding in brain injury: broadening the indications.

PubMed

Yusim, Yakov; Perel, Azriel; Berkenstadt, Haim; Attia, Moshe; Knoller, Nachshon; Sidi, Avner

2006-11-01

We report three patients with severe traumatic brain injury, both open and closed, who were treated with recombinant activated factor VII. This treatment was given in a desperate, last-ditch effort to save the life of patient 1, as a preventive or early treatment of a developing hematoma in patient 2, and as treatment of a threatening hematoma in patient 3. One of the three patients survived. During the past few years we have broadened the indications for recombinant activated factor VII and started using it as a preventive measure rather than as a "last line of defense." However, the potential complications of disseminated intravascular coagulation and thrombotic events, as well as the cost-effectiveness in view of the available evidence-based medicine, should be considered.

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

PubMed

Günther, A; Mosavi, P; Ruppert, C; Heinemann, S; Temmesfeld, B; Velcovsky, H G; Morr, H; Grimminger, F; Walmrath, D; Seeger, W

2000-06-01

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

PubMed

Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

2009-11-14

To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (P<0.05) during the regeneration phase compared with D0. Among these 5 factors, factor IX and factor XI showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in plasma activity for both factors were consistent with our RT-PCR findings. In contrast, the plasma activities of the other coagulation factors (fibrinogen, factors V, VII, XIII, and VWF) were not significantly reduced, despite the reduction in the liver mRNA levels. Unlike the other factors, FX showed a temporal increase in its plasma activity, with significant increases (P<0.05) detected at D1. Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions.

Chronic dietary fat intake modifies the postprandial response of hemostatic markers to a single fatty test meal.

PubMed

Delgado-Lista, Javier; Lopez-Miranda, Jose; Cortés, Begoña; Perez-Martinez, Pablo; Lozano, Aquiles; Gomez-Luna, Rafael; Gomez, Purificacion; Gomez, Maria Jose; Criado, Juan; Fuentes, Francisco; Perez-Jimenez, Francisco

2008-02-01

Hemostasis is the result of a complex equilibrium between coagulation and fibrinolysis, and the influence of different dietary models on this equilibrium is not entirely known. The objective was to compare the effects of the chronic intake of different dietary models on postprandial hemostasis. In a randomized crossover design, 20 healthy men consumed for 28 d each diets rich in monounsaturated fatty acids (MUFAs), saturated fatty acids (SFAs), and carbohydrates plus n-3 fatty acids (CHO/N3). Fasting and postprandial hemostatic factors (factor VII coagulant activity, plasminogen activator inhibitor-1, tissue-type plasminogen activator, d-dimer, and thromboxane B(2)) were measured; meal tests for the postprandial measures were based on butter, virgin olive oil, and walnuts for the SFA, MUFA, and CHO/N3 diets, respectively. There were no differences in the fasting variables after the dietary periods. After the 3 fatty meals were consumed, we observed an increase in thromboxane B(2) and d-dimer and a reduction in tissue plasminogen activator, irrespective of the dietary model. The MUFA or CHO/N3 meals lowered postprandial concentrations of factor VII coagulant activity, although the reduction was greater after the MUFA-enriched meal. The concentration of plasminogen activator inhibitor-1 was greater after the SFA meal than after the other 2 meals. The administration of a fatty meal induces a postprandial procoagulant tendency, irrespective of the type of fat consumed. However, the use of a dietary model rich in SFA creates a more procoagulant environment than does a model that includes MUFA or CHO/N3 as the source of fatty acids.

48 CFR 42.1104 - Surveillance requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... following factors: (i) Contract requirements for reporting production progress and performance. (ii) The... contractor's financial capability. (vii) Any supplementary written instructions from the contracting office...

Optimization of Lyophilized Plasma for Use in Combat Casualties

DTIC Science & Technology

2013-01-21

SD. (Fib: fibrinogen, FII: Factor II, FV: Factor V, FVII : Factor VII, FVIII: Factor VIII, FIX: Factor IX, FX: Factor X, FXI: Factor XI, FXII...coagulation factor activity. Twenty swine were anesthetized and subjected to a validated model of polytrauma and hemorrhagic shock. They were...to assess inflammatory markers. Major Findings: 50%LP had higher electrolyte concentrations, osmolarity, and increased coagulation factor activity

Radiographic Evaluation of Bones and Joints in Mucopolysaccharidosis I and VII Dogs After Neonatal Gene Therapy

PubMed Central

Herati, Ramin Sedaghat; Knox, Van W.; O’Donnell, Patricia; D’Angelo, Marina; Haskins, Mark E.; Ponder, Katherine P.

2009-01-01

Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the glycosaminoglycan-degrading lysosomal enzymes α-L-iduronidase and β-glucuronidase, respectively, and result in abnormal bones and joints. Here, the severity of skeletal disease in MPS I and MPS VII dogs and the effects of neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal, respectively, and bone dysplasia and articular erosions, and joint subluxation were severe. Previously, we reported that neonatal intravenous injection of a retroviral vector (RV) with the appropriate gene resulted in expression in liver and blood cells, and high serum enzyme activity. In this study, we demonstrate that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of normal, respectively, and there were partial improvements of qualitative abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and 96% of normal, respectively) were not significantly different from normal dogs. Qualitative changes in MPS I bones and joints were generally modest and were partially improved with RV treatment, although cervical spine disease was severe and was difficult to correct with gene therapy in both models. The greater severity of skeletal disease in MPS VII than in MPS I dogs may reflect accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does not prevent, skeletal disease in MPS I and MPS VII dogs. PMID:18707908

Proposed re-evaluation of the 154Eu thermal ( n, γ) capture cross-section based on spent fuel benchmarking studies

DOE PAGES

Skutnik, Steven E.

2016-09-22

154Eu is a nuclide of considerable importance to both non-destructive measurements of used nuclear fuel assembly burnup as well as for calculating the radiation source term for used fuel storage and transportation. But, recent evidence from code validation studies of spent fuel benchmarks have revealed evidence of a systemic bias in predicted 154Eu inventories when using ENDF/B-VII.0 and ENDF/B-VII.1 nuclear data libraries, wherein Eu-154 is consistently over-predicted on the order of 10% or more. Further, this bias is found to correlate with sample burnup, resulting in a larger departure from experimental measurements for higher sample burnups. Here, the bias in Eu-154 is characterized across eleven spent fuel destructive assay benchmarks from five different assemblies. Based on these studies, possible amendments to the ENDF/B-VII.0 and VII.1 evaluations of the 154Eu (n,γ) 155Eu are explored. By amending the location of the first resolved resonance for the 154Eu radiative capture cross-section (centered at 0.195 eV in ENDF/B-VII.0 and VII.1) to 0.188 eV and adjusting the neutron capture width proportional tomore » $$\\sqrt1/E$$, the amended cross-section evaluation was found to reduce the bias in predicted 154Eu inventories by approximately 5–7%. And while the amended capture cross-section still results in a residual over-prediction of 154Eu (ranging from 2% to 9%), the effect is substantially attenuated compared with the nominal ENDF/B-VII.0 and VII.1 evaluations.« less

Clinical course of sly syndrome (mucopolysaccharidosis type VII)

PubMed Central

Montaño, Adriana M; Lock-Hock, Ngu; Steiner, Robert D; Graham, Brett H; Szlago, Marina; Greenstein, Robert; Pineda, Mercedes; Gonzalez-Meneses, Antonio; Çoker, Mahmut; Bartholomew, Dennis; Sands, Mark S; Wang, Raymond; Giugliani, Roberto; Macaya, Alfons; Pastores, Gregory; Ketko, Anastasia K; Ezgü, Fatih; Tanaka, Akemi; Arash, Laila; Beck, Michael; Falk, Rena E; Bhattacharya, Kaustuv; Franco, José; White, Klane K; Mitchell, Grant A; Cimbalistiene, Loreta; Holtz, Max; Sly, William S

2016-01-01

Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients’ phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. Methods We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. Results We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. Conclusions MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy. PMID:26908836

Proposed re-evaluation of the 154Eu thermal ( n, γ) capture cross-section based on spent fuel benchmarking studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skutnik, Steven E.

154Eu is a nuclide of considerable importance to both non-destructive measurements of used nuclear fuel assembly burnup as well as for calculating the radiation source term for used fuel storage and transportation. But, recent evidence from code validation studies of spent fuel benchmarks have revealed evidence of a systemic bias in predicted 154Eu inventories when using ENDF/B-VII.0 and ENDF/B-VII.1 nuclear data libraries, wherein Eu-154 is consistently over-predicted on the order of 10% or more. Further, this bias is found to correlate with sample burnup, resulting in a larger departure from experimental measurements for higher sample burnups. Here, the bias in Eu-154 is characterized across eleven spent fuel destructive assay benchmarks from five different assemblies. Based on these studies, possible amendments to the ENDF/B-VII.0 and VII.1 evaluations of the 154Eu (n,γ) 155Eu are explored. By amending the location of the first resolved resonance for the 154Eu radiative capture cross-section (centered at 0.195 eV in ENDF/B-VII.0 and VII.1) to 0.188 eV and adjusting the neutron capture width proportional tomore » $$\\sqrt1/E$$, the amended cross-section evaluation was found to reduce the bias in predicted 154Eu inventories by approximately 5–7%. And while the amended capture cross-section still results in a residual over-prediction of 154Eu (ranging from 2% to 9%), the effect is substantially attenuated compared with the nominal ENDF/B-VII.0 and VII.1 evaluations.« less

78 FR 24293 - Pilot Program on NAFTA Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Part 385, Appendix B, Section VII. Parts of the FMCSRs and HMRs having similar characteristics are combined together into six regulatory areas called ``factors.'' The regulatory factors are intended to evaluate the adequacy of a carrier's management controls. M. Passed Phase 1, Factor 1: A ``yes'' in this...

76 FR 56868 - Pilot Project on NAFTA Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... part 385, Appendix B, Section VII. Parts of the FMCSRs and HMRs having similar characteristics are combined together into six regulatory areas called ``factors.'' The regulatory factors are intended to evaluate the adequacy of a carrier's management controls. L. Passed Phase 1, Factor 1: A ``yes'' in this...

77 FR 12356 - Pilot Program on NAFTA Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... part 385, Appendix B, Section VII. Parts of the FMCSRs and HMRs having similar characteristics are combined together into six regulatory areas called ``factors.'' The regulatory factors are intended to evaluate the adequacy of a carrier's management controls. M. Passed Phase 1, Factor 1: A ``yes'' in this...

A new manufacturing process to remove thrombogenic factors (II, VII, IX, X, and XI) from intravenous immunoglobulin gamma preparations.

PubMed

Park, Dong Hwarn; Kang, Gil Bu; Kang, Dae Eun; Hong, Jeung Woon; Lee, Min Gyu; Kim, Ki Yong; Han, Jeung Whan

2017-01-01

Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products. Here, we used a chromatographic process using a new resin that binds with high capacity to IgG and removes procoagulant activities. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: <1.56 mIU/mL, chromogenic FXIa assay: <0.16 mIU/mL, non-activated partial thromboplastin time (NaPTT): >250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a concentration 32.5 times higher than the concentration in normal specimens, the procoagulant activities were below the detection limit (<0.31 ng/mL). These results demonstrate the ability of our manufacturing process to remove procoagulant activities to below the detection limit (except by NaPTT), suggesting a reduced risk of thromboembolic events that maybe potentially caused by our IVIG preparation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Two-incision laparoscopic appendectomy for a severe hemophilia A child patient with coagulation factor VII deficiency: Case report and review of literature.

PubMed

He, Jin Peng; Feng, Jie Xiong

2017-10-01

The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. The patient had an uneventful recovery. It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment.

Kinetic modeling sheds light on the mode of action of recombinant factor VIIa on thrombin generation.

PubMed

Mitrophanov, Alexander Y; Reifman, Jaques

2011-10-01

The therapeutic potential of a hemostatic agent can be assessed by investigating its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa)--a promising hemostasis-inducing biologic--experimental studies addressing its effects on thrombin generation yielded disparate results. To elucidate the inherent ability of rFVIIa to modulate thrombin production, it is necessary to identify rFVIIa-induced effects that are compatible with the available biochemical knowledge about thrombin generation mechanisms. The existing body of knowledge about coagulation biochemistry can be rigorously represented by a computational model that incorporates the known reactions and parameter values constituting the biochemical network. We used a thoroughly validated numerical model to generate activated factor VII (FVIIa) titration curves in the cases of normal blood composition, hemophilia A and B blood, blood lacking factor VII, blood lacking tissue factor pathway inhibitor, and diluted blood. We utilized the generated curves to perform systematic fold-change analyses for five quantitative parameters characterizing thrombin accumulation. The largest fold changes induced by increasing FVIIa concentration were observed for clotting time, thrombin peak time, and maximum slope of the thrombin curve. By contrast, thrombin peak height was much less affected by FVIIa titrations, and the area under the thrombin curve stayed practically unchanged. Comparisons with experimental data demonstrated that the computationally derived patterns can be observed in vitro. rFVIIa modulates thrombin generation primarily by accelerating the process, without significantly affecting the total amount of generated thrombin. Copyright © 2011 Elsevier Ltd. All rights reserved.

7 CFR 4279.30 - Lenders' functions and responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... sound lending practices, (v) Supervising construction (vi) Distribution of loan funds, (vii) Servicing... the loan processing phase. The lender must analyze all credit factors associated with each proposed loan and apply its professional judgment to determine that the credit factors, considered in...

Evidence of a Structural Defect in Ice VII and the Side Chain Dependent Response of Small Model Peptides to Increased Pressure

PubMed Central

Scott, J. Nathan; Vanderkooi, Jane M.

2014-01-01

The effect of high pressure on the OH stretch of dilute HOD in D2O was examined using high pressure FTIR. It was found that at pressures directly above the ice VI to ice VII transition, ice VII displays a splitting in the OH absorption indicative of differing hydrogen bonding environments. This result is contrary to published structures of ice VII in which each OH oscillator should experience an identical electronic environment. The anomalous band was found to decrease in absorbance and finally disappear at ~43.0 kbar. In addition, the pressure response of the amide I′ and II′ bands of three small model peptides was examined. Analysis of these bands’ response to increased pressure indicates significant side chain dependence of their structural rearrangement, which may play a role in the composition of full length proteins of barophilic organisms. PMID:21740637

The effectivenes of science domain-based science learning integrated with local potency

NASA Astrophysics Data System (ADS)

Kurniawati, Arifah Putri; Prasetyo, Zuhdan Kun; Wilujeng, Insih; Suryadarma, I. Gusti Putu

2017-08-01

This research aimed to determine the significant effect of science domain-based science learning integrated with local potency toward science process skills. The research method used was a quasi-experimental design with nonequivalent control group design. The population of this research was all students of class VII SMP Negeri 1 Muntilan. The sample of this research was selected through cluster random sampling, namely class VII B as an experiment class (24 students) and class VII C as a control class (24 students). This research used a test instrument that was adapted from Agus Dwianto's research. The aspect of science process skills in this research was observation, classification, interpretation and communication. The analysis of data used the one factor anova at 0,05 significance level and normalized gain score. The significance level result of science process skills with one factor anova is 0,000. It shows that the significance level < alpha (0,05). It means that there was significant effect of science domain-based science learning integrated with local potency toward science learning process skills. The results of analysis show that the normalized gain score are 0,29 (low category) in control class and 0,67 (medium category) in experiment class.

Management of Labour and Delivery in a Patient With Acquired Factor VII Deficiency With Inhibitor: A Case Report.

PubMed

Matei, Anca; Dolan, Sean; Andrews, James; Rivard, Georges-Étienne

2016-02-01

Acquired factor VII (FVII) deficiency with inhibitor increases the risk of hemorrhage during pregnancy. However, there are no published reports guiding its management in the peripartum period. A 24-year-old woman with inhibitory antibodies to FVII delivered at 34 weeks of gestation. The patient was administered recombinant factor VIIa (rFVIIa) and tranexamic acid. There were no bleeding-related complications; however, the FVII level was supratherapeutic. The patient returned during a second pregnancy. A reduced dose of rFVIIa was administered. The delivery was complicated by postpartum hemorrhage, which resolved with the addition of uterotonic agents. Recombinant FVIIa and tranexamic acid offer an effective peripartum treatment in women with inhibitory antibody to FVII. Further research should delineate the optimal time of administration. Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Inhibitor development after liver transplantation in congenital factor VII deficiency.

PubMed

See, W-S Q; Chang, K-O; Cheuk, D K-L; Leung, Y-Y R; Chan, G C-F; Chan, S-C; Ha, S-Y

2016-09-01

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement. © 2016 John Wiley & Sons Ltd.

Pathogenetic role of Factor VII deficiency and thrombosis in cross-reactive material positive patients.

PubMed

Girolami, A; Sambado, L; Bonamigo, E; Ferrari, S; Lombardi, A M

2013-12-01

Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.

Evaluation of the 235U prompt fission neutron spectrum including a detailed analysis of experimental data and improved model information

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neudecker, Denise; Talou, Patrick; Kahler, Albert Comstock III

We present an evaluation of the 235U prompt fission neutron spectrum (PFNS) induced by thermal to 20-MeV neutrons. Experimental data and associated covariances were analyzed in detail. The incident energy dependence of the PFNS was modeled with an extended Los Alamos model combined with the Hauser-Feshbach and the exciton models. These models describe prompt fission, pre-fission compound nucleus and pre-equilibrium neutron emissions. The evaluated PFNS agree well with the experimental data included in this evaluation, preliminary data of the LANL and LLNL Chi-Nu measurement and recent evaluations by Capote et al. and Rising et al. However, they are softer thanmore » the ENDF/B-VII.1 (VII.1) and JENDL-4.0 PFNS for incident neutron energies up to 2 MeV. Simulated effective multiplication factors k eff of the Godiva and Flattop-25 critical assemblies are further from the measured k eff if the current data are used within VII.1 compared to using only VII.1 data. However, if this work is used with ENDF/B-VIII.0β2 data, simulated values of k eff agree well with the measured ones.« less

Evaluation of the 235U prompt fission neutron spectrum including a detailed analysis of experimental data and improved model information

DOE PAGES

Neudecker, Denise; Talou, Patrick; Kahler, Albert Comstock III; ...

2017-09-13

We present an evaluation of the 235U prompt fission neutron spectrum (PFNS) induced by thermal to 20-MeV neutrons. Experimental data and associated covariances were analyzed in detail. The incident energy dependence of the PFNS was modeled with an extended Los Alamos model combined with the Hauser-Feshbach and the exciton models. These models describe prompt fission, pre-fission compound nucleus and pre-equilibrium neutron emissions. The evaluated PFNS agree well with the experimental data included in this evaluation, preliminary data of the LANL and LLNL Chi-Nu measurement and recent evaluations by Capote et al. and Rising et al. However, they are softer thanmore » the ENDF/B-VII.1 (VII.1) and JENDL-4.0 PFNS for incident neutron energies up to 2 MeV. Simulated effective multiplication factors k eff of the Godiva and Flattop-25 critical assemblies are further from the measured k eff if the current data are used within VII.1 compared to using only VII.1 data. However, if this work is used with ENDF/B-VIII.0β2 data, simulated values of k eff agree well with the measured ones.« less

Evaluation of the 235U prompt fission neutron spectrum including a detailed analysis of experimental data and improved model information

NASA Astrophysics Data System (ADS)

Neudecker, Denise; Talou, Patrick; Kahler, Albert C.; White, Morgan C.; Kawano, Toshihiko

2017-09-01

We present an evaluation of the 235U prompt fission neutron spectrum (PFNS) induced by thermal to 20-MeV neutrons. Experimental data and associated covariances were analyzed in detail. The incident energy dependence of the PFNS was modeled with an extended Los Alamos model combined with the Hauser-Feshbach and the exciton models. These models describe prompt fission, pre-fission compound nucleus and pre-equilibrium neutron emissions. The evaluated PFNS agree well with the experimental data included in this evaluation, preliminary data of the LANL and LLNL Chi-Nu measurement and recent evaluations by Capote et al. and Rising et al. However, they are softer than the ENDF/B-VII.1 (VII.1) and JENDL-4.0 PFNS for incident neutron energies up to 2 MeV. Simulated effective multiplication factors keff of the Godiva and Flattop-25 critical assemblies are further from the measured keff if the current data are used within VII.1 compared to using only VII.1 data. However, if this work is used with ENDF/B-VIII.0β2 data, simulated values of keff agree well with the measured ones.

Platelet Glycoprotein lb-1X and Malignancy

DTIC Science & Technology

2011-09-01

Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci...JM, Hakim J, de Prost D. Vascular endothelial growth factor production by fibroblasts in response to factor VIIa binding to tissue factor involves...interactions in vitro. (14) The extrinsic pathway of coagulation triggered by factor VII ( FVII ) and tissue factor can be activated in cancer patients. (15

76 FR 56272 - Pilot Project on NAFTA Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... controls. A list of acute and critical regulations is included in 49 CFR part 385, Appendix B, Section VII... areas called ``factors.'' The regulatory factors are intended to evaluate the adequacy of a carrier's management controls. L. Passed Phase 1, Factor 1: A ``yes'' in this column indicates the carrier has...

In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

PubMed

Augustsson, Cecilia; Persson, Egon

2014-11-13

Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

29 CFR 1608.1 - Statement of purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... upon the principles of title VII. Any uncertainty as to the meaning and application of title VII in... Commission believes that it is now necessary to clarify and harmonize the principles of title VII in order to... who comply with the principles of title VII. (b) Purposes of title VII. Congress enacted title VII in...

42 CFR 66.206 - Grant awards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... other pertinent factors: (i) The scientific, technical, or educational merit of the proposed program...; (vii) The reasonableness of the proposed budget in relation to the proposed program; and (viii) The... of such awards will be made after consideration of such factors as the grantee's progress and...

40 CFR 194.44 - Engineered barriers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... compliance assessment; (vi) Public comments requesting specific engineered barriers; (vii) The increased or..., after consideration of one or more of the factors in paragraph (c)(1) of this section, the Department... without evaluating the remaining factors in paragraph (c)(1) of this section, then any compliance...

25 CFR 700.833 - Civil penalty amounts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... factors. (i) Agreement by the person being assessed a civil penalty to return to the Federal Land Manager...) Demonstration of hardship or inability to pay, provided that this factor shall only be considered when the... under the circumstances. (vii) Determination of other mitigating circumstances appropriate to...

42 CFR 136.351 - Application and selection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... factors: (1) The extent of the unmet health care needs of the urban Indians in the urban center involved..., in the urban center. Factors to be considered in determining relative accessibility include: (i...; (vi) Technical barriers created by State and local health agencies; (vii) Availability of...

Recombinant activated factor VII: 30 years of research and innovation.

PubMed

Hedner, Ulla

2015-06-01

Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital haemophilia and inhibitors. The story of its development began in the 1970s, when FVIIa was identified as one of the activated coagulation factors that has minimal potential for inducing thromboembolic side-effects. Extensive research over the last 30 years has greatly increased our knowledge of the characteristics of FVII, its activation, and the mechanisms by which rFVIIa restores haemostasis. In haemophilia, the haemostatic effect of rFVIIa is mediated via binding to thrombin-activated platelets at the site of injury, thereby enhancing thrombin generation also in the absence of factor (F) VIII or FIX. The mechanism of action of rFVIIa has also allowed its successful use in other clinical scenarios characterised by impaired thrombin generation, and its licensed uses have now been extended to acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety and Equality at Odds: OSHA and Title VII Clash over Health Hazards in the Workplace.

ERIC Educational Resources Information Center

Crowell, Donald R.; Copus, David A.

1978-01-01

Discusses the legal problems presented by job health hazards which have a different effect on men and women. Where methods of eliminating or minimizing exposure, as required by the Occupational Safety and Health Act, affect only one sex, the provisions of Title VII of the Civil Rights Act may be violated. (MF)

36 CFR 907.12 - Preparation of an environmental assessment.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Energy requirements and conservation; (vi) Solid waste; (vii) Transportation; (viii) Community facilities and services; (ix) Social and economic; (x) Historic and aesthetic; and (xi) Other relevant factors...

The role of recombinant activated factor VII in the haematological management of elective orthopaedic surgery in haemophilia A patients with inhibitors

PubMed Central

Castaman, Giancarlo

2017-01-01

The clinical profile and expectations of haemophilic patients with inhibitors have changed over the last three decades, mainly because of the prolongation of life-expectancy, often resulting in an increase of the orthopaedic burden. Recombinant activated factor VII (rFVIIa) is the most frequently used bypassing agent in haemophilia patients with inhibitors during elective orthopaedic surgery. For nearly 30 years, rFVIIa has been successfully used to control haemostasis in several major and minor surgical procedures. Clinical trials, case series, reports and surveys were progressively aimed at optimising rFVIIa usage in very demanding conditions managed in highly specialised centres. Recommendations from consensus opinions and guidelines have been provided on the basis of this clinical experience. PMID:28686157

Japanese family with congenital factor VII deficiency.

PubMed

Sakakibara, Kanae; Okayama, Yoshiki; Fukushima, Kenji; Kaji, Shunsaku; Muraoka, Michiko; Arao, Yujiro; Shimada, Akira

2015-10-01

Congenital factor VII (FVII) deficiency is a rare bleeding disorder with autosomal recessive inheritance. The present female patient was diagnosed with congenital FVII deficiency because of low hepaplastin test (HPT), although vitamin K was given. Heterozygous p.A191T mutation was detected in the peripheral blood, and the same mutation was also found in the mother and sister. To the best of our knowledge, this is the fourth reported case of p.A191T mutation of FVII in the literature and the first to be reported in Japan. FVII coagulation activity (FVII:C) in asymptomatic heterozygous carriers is mildly reduced. Therefore, some patients may not be accurately diagnosed with congenital FVII deficiency. In infants with low HPT without vitamin K deficiency, congenital FVII deficiency should be considered. © 2015 Japan Pediatric Society.

Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation.

PubMed

Mariani, Guglielmo; Napolitano, Mariasanta; Dolce, Alberto; Pérez Garrido, Rosario; Batorova, Angelika; Karimi, Mehran; Platokouki, Helen; Auerswald, Günter; Bertrand, Anne-Marie; Di Minno, Giovanni; Schved, Jean F; Bjerre, Jens; Ingerslev, Jorgen; Sørensen, Benny; Ruiz-Saez, Arlette

2013-02-01

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

Photosynthetic pigments of oceanic Chlorophyta belonging to prasinophytes clade VII.

PubMed

Lopes Dos Santos, Adriana; Gourvil, Priscillia; Rodríguez, Francisco; Garrido, José Luis; Vaulot, Daniel

2016-02-01

The ecological importance and diversity of pico/nanoplanktonic algae remains poorly studied in marine waters, in part because many are tiny and without distinctive morphological features. Amongst green algae, Mamiellophyceae such as Micromonas or Bathycoccus are dominant in coastal waters while prasinophytes clade VII, yet not formerly described, appear to be major players in open oceanic waters. The pigment composition of 14 strains representative of different subclades of clade VII was analyzed using a method that improves the separation of loroxanthin and neoxanthin. All the prasinophytes clade VII analyzed here showed a pigment composition similar to that previously reported for RCC287 corresponding to pigment group prasino-2A. However, we detected in addition astaxanthin for which it is the first report in prasinophytes. Among the strains analyzed, the pigment signature is qualitatively similar within subclades A and B. By contrast, RCC3402 from subclade C (Picocystis) lacks loroxanthin, astaxanthin, and antheraxanthin but contains alloxanthin, diatoxanthin, and monadoxanthin that are usually found in diatoms or cryptophytes. For subclades A and B, loroxanthin was lowest at highest light irradiance suggesting a light-harvesting role of this pigment in clade VII as in Tetraselmis. © 2015 Phycological Society of America.

Pulp response to high fluoride releasing glass ionomer, silver diamine fluoride, and calcium hydroxide used for indirect pulp treatment: An in-vivo comparative study

PubMed Central

Korwar, Atish; Sharma, Sidhartha; Logani, Ajay; Shah, Naseem

2015-01-01

Aims and Objectives: The study aims at determining pulp response of two high fluoride releasing materials silver diamine fluoride (SDF) and Type VII glass ionomer cement (GIC) when used as indirect pulp treatment (IPT) materials. Materials and Methods: Deep Class V cavities were made on four first premolars indicated for extraction for orthodontic reasons. SDF, Type VII GIC, and calcium hydroxide base are given in three premolars, and one is kept control. Premolars were extracted 6 weeks after the procedure and subjected to histopathological examination to determine the pulp response. The results were analyzed using Chi-square test. Results: No inflammatory changes were observed in any of the groups. Significantly more number of specimens in SDF and Type VII GIC groups showed tertiary dentin deposition (TDD) when compared to control group. No significant difference was seen in TDD when intergroup comparison was made. Odontoblasts were seen as short cuboidal cells with dense basophilic nucleus in SDF and Type VII GIC group. Conclusion: The study demonstrated TDD inducing ability of SDF and Type VII GIC and also established the biocompatibility when used as IPT materials. PMID:26321822

Optimization Issues with Complex Rotorcraft Comprehensive Analysis

NASA Technical Reports Server (NTRS)

Walsh, Joanne L.; Young, Katherine C.; Tarzanin, Frank J.; Hirsh, Joel E.; Young, Darrell K.

1998-01-01

This paper investigates the use of the general purpose automatic differentiation (AD) tool called Automatic Differentiation of FORTRAN (ADIFOR) as a means of generating sensitivity derivatives for use in Boeing Helicopter's proprietary comprehensive rotor analysis code (VII). ADIFOR transforms an existing computer program into a new program that performs a sensitivity analysis in addition to the original analysis. In this study both the pros (exact derivatives, no step-size problems) and cons (more CPU, more memory) of ADIFOR are discussed. The size (based on the number of lines) of the VII code after ADIFOR processing increased by 70 percent and resulted in substantial computer memory requirements at execution. The ADIFOR derivatives took about 75 percent longer to compute than the finite-difference derivatives. However, the ADIFOR derivatives are exact and are not functions of step-size. The VII sensitivity derivatives generated by ADIFOR are compared with finite-difference derivatives. The ADIFOR and finite-difference derivatives are used in three optimization schemes to solve a low vibration rotor design problem.

Photometric and spectral evolution of the symbiotic eclipsing variable V1329 Cygni at a late stage of its nova-like outburst

NASA Astrophysics Data System (ADS)

Arkhipova, V. P.; Esipov, V. F.; Ikonnikova, N. P.; Komissarova, G. V.

2015-03-01

The photoelectric UBV observations of the peculiar symbiotic star V1329 Cyg performed at the Crimean Station of the SAI-MSU during 245 nights over the period 2003-2014 are presented. The star's light curves since 1973 from the Crimean observations are shown. The brightness decline after its outburst over the last 40 years was . The phase color curves at phases 0.2 and 0.8 have maxima. Their qualitative interpretation in terms of the model of interacting winds in symbiotic binary star systems is proposed. The orbital period of the binary system has been redetermined. The spectroscopic observations at the 125-cm telescope of the Crimean Station from 1994 to 2014 have confirmed the change in the system's emission spectrum with orbital phase. The HI, He I, and Fe II line fluxes clearly trace the orbital motion. The Balmer hydrogen lines as well as the continuum at λ6000 and the V-band flux change by a factor of ˜3.5 from minimum to maximum light. The neutral helium lines change by a factor of 5. The high-excitation He II, [FeVII], [Ca VII] lines and the Raman O VI λ6825 line have shown changes in the fluxes by a factor of ˜2-3 weakly correlating with the orbital phase. The equivalent widths of the HI and He I lines are maximal at the star's maximum light and have distinct minima at phases 0.2 and 0.8, while the equivalent widths of the He II, [FeVII], and [CaVII] lines are minimal in the range of phases 0.2-0.8. The question about the location of the permitted and forbidden line emission zones in the binary system V1329 Cyg is discussed. The evolution of the emission spectrum for V1329 Cyg from 1980 to 2014 has been studied on the basis of new and archival data. A gradual decrease in the absolute fluxes of the nebular emission lines has been detected. The [O III] and [Fe VII] lines have weakened significantly. However, the [Fe X] λ6375 Å line has appeared and gradually strengthened, suggesting an increase in the degree of gas ionization in the line formation zone.

36 CFR 296.16 - Civil penalty amounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... remit the penalty may be based upon any of the following factors: (i) Agreement by the person being... factor shall only be considered when the person being assessed a civil penalty has not been found to have... constitute excessive punishment under the circumstances; (vii) Determination of other mitigating...

Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII.

PubMed

Inturi, Raviteja; Mun, Kwangchol; Singethan, Katrin; Schreiner, Sabrina; Punga, Tanel

2018-02-01

Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections. IMPORTANCE Human adenoviruses (HAdVs) are common pathogens causing a wide range of diseases. To achieve pathogenicity, HAdVs have to counteract a variety of host cell antiviral defense systems, which would otherwise hamper virus replication. In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and MKRN1 proteins may prime MKRN1 for proteasomal degradation, because the MKRN1 protein is efficiently degraded during the late phase of HAdV-C5 infection. Since MKRN1 protein accumulation is also reduced in measles virus- and vesicular stomatitis virus-infected cells, our results signify the general strategy of viruses to target MKRN1. Copyright © 2018 American Society for Microbiology.

a New ENDF/B-VII.0 Based Multigroup Cross-Section Library for Reactor Dosimetry

NASA Astrophysics Data System (ADS)

Alpan, F. A.; Anderson, S. L.

2009-08-01

The latest of the ENDF/B libraries, ENDF/B-VII.0 was released in December 2006. In this paper, the ENDF/B-VII.O evaluations were used in generating a new coupled neutron/gamma multigroup library having the same group structure of VITAMIN-B6, i.e., the 199-neutron, 42-gamma group library. The new library was generated utilizing NJOY99.259 for pre-processing and the AMPX modules for post-processing of cross sections. An ENDF/B-VI.3 based VITAMIN-B6-like library was also generated. The fine-group libraries and the ENDF/B-VI.3 based 47-neutron, 20-gamma group BUGLE-96 library were used with the discrete ordinates code DORT to obtain a three-dimensional synthesized flux distribution from r, r-θ, and r-z models for a standard Westinghouse 3-loop design reactor. Reaction rates were calculated for ex-vessel neutron dosimetry containing 63Cu(n,α)60Co, 46Ti(n,p)46Sc, 54Fe(n,P)54Mn, 58Ni(n,P)58Co, 238U(n,f)137Cs, 237Np(n,f)137Cs, and 59Co(n,γ)60Co (bare and cadmium covered) reactions. Results were compared to measurements. In comparing the 199-neutron, 42-gamma group ENDF/B-VI.3 and ENDF/B-VII.O libraries, it was observed that the ENDF/B-VI.3 based library results were in better agreement with measurements. There is a maximum difference of 7% (for the 63Cu(n,α)60Co reaction rate calculation) between ENDF/B-VI.3 and ENDF/B-VII.O. Differences between ENDF/B-VI.3 and ENDF/B-VII.O libraries are due to 16O, 1H, 90Zr, 91Zr, 92Zr, 238U, and 239Pu evaluations. Both ENDF/B-VI.3 and ENDF/B-VII.O library calculated reaction rates are within 20% of measurement and meet the criterion specified in the U. S. Nuclear Regulatory Commission Regulatory Guide 1.190, "Calculational and Dosimetry Methods for Determining Pressure Vessel Neutron Fluence."

Youth Suicidal Behavior

MedlinePlus

... ii Risk Factors* Mental illness Substance abuse iv Firearms in the household vi Previous suicide attempts viii ... connectedness iii Safe schools v Reduced access to firearms vii Academic achievement ix Self-esteem xi Talking ...

Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

PubMed

Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

2005-04-26

Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

PubMed

Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

2012-01-01

Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

Two-incision laparoscopic appendectomy for a severe hemophilia A child patient with coagulation factor VII deficiency

PubMed Central

He, Jin Peng; Feng, Jie Xiong

2017-01-01

Abstract Rationale: The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. Patient concerns: An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. Diagnoses: He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. Interventions: Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. Outcomes: The patient had an uneventful recovery. Lessons: It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment. PMID:29019885

Upregulation of the Coagulation Factor VII Gene during Glucose Deprivation Is Mediated by Activating Transcription Factor 4

PubMed Central

Cronin, Katherine R.; Mangan, Thomas P.; Carew, Josephine A.

2012-01-01

Background Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Methodology/Principal Findings Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/− SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/−15% to 188+/−27% and 100+/−8.8% to 176.3+/−17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Conclusions/Significance Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress. PMID:22848420

Use of global assays to understand clinical phenotype in congenital factor VII deficiency.

PubMed

Greene, L A; Goldenberg, N A; Simpson, M L; Villalobos-Menuey, E; Bombardier, C; Acharya, S S; Santiago-Borrero, P J; Cambara, A; DiMichele, D M

2013-09-01

Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy. Global assays of coagulation and fibrinolysis may better characterize overall haemostatic balance and aid in haemorrhagic risk assessment. We evaluated the ability of novel global assays to better understand clinical bleeding severity in congenital FVII deficiency. Subjects underwent central determination of factor VII activity (FVII:C) as well as clot formation and lysis (CloFAL) and simultaneous thrombin and plasmin generation (STP) global assay analysis. A bleeding score was assigned to each subject through medical chart review. Global assay parameters were analysed with respect to bleeding score and FVII:C. Subgroup analyses were performed on paediatric subjects and subjects with FVII ≥ 1 IU dL(-1). CloFAL fibrinolytic index (FI2 ) inversely correlated with FVII:C while CloFAL maximum amplitude (MA) and STP maximum velocity of thrombin generation (VT max) varied directly with FVII:C. CloFAL FI2 directly correlated with bleeding score among subjects in both the total cohort and paediatric subcohort, but not among subjects with FVII ≥ 1 IU dL(-1) . Among subjects with FVII ≥ 1 IU dL(-1), STP time to maximum velocity of thrombin generation and time to maximum velocity of plasmin generation inversely correlated with bleeding score. These preliminary findings suggest a novel potential link between a hyperfibrinolytic state in bleeding severity and congenital FVII deficiency, an observation that should be further explored. © 2013 John Wiley & Sons Ltd.

77 FR 40938 - Pilot Program on NAFTA Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-11

... regulations is included in 49 CFR part 385, Appendix B, Section VII. Parts of the FMCSRs and HMRs having similar characteristics are combined together into six regulatory areas called ``factors.'' The regulatory factors are intended to evaluate the adequacy of a carrier's management controls. M. Passed Phase 1...

32 CFR 229.16 - Civil penalty amounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and/or a proposal to mitigate or remit the penalty may be based upon any of the following factors: (i... or inability to pay, provided that this factor shall only be considered when the person being...) Determination that the proposed penalty would constitute excessive punishment under the circumstances; (vii...

75 FR 66829 - Determination of Foreign Exchange Swaps and Forwards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

... Commodity Exchange Act (``CEA''), as amended by Title VII of the Dodd-Frank Wall Street Reform and Consumer... the application of the factors that the Secretary must consider in making a determination regarding... Treasury must consider the following factors: \\7\\ Notwithstanding any such determination by the Secretary...

40 CFR 86.1806-04 - On-board diagnostics.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 2002). (vii) As an alternative to the above standards, heavy-duty vehicles may conform to the... standards shall utilize multiplicative factors from the California vehicle type (i.e. LEV II, ULEV II... standards shall utilize the Tier 2 Bin 4 emission standards and the CARB ULEV II multiplicative factors to...

18 CFR 1312.16 - Civil penalty amounts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to mitigate or remit the penalty may be based upon any of the following factors: (i) Agreement by the... to pay, provided that this factor shall only be considered when the person being assessed a civil...) Determination that the proposed penalty would constitute excessive punishment under the circumstances; (vii...

Screening Study on Feasibility of Standards of Performance ...

EPA Pesticide Factsheets

... VII ittttl w.xi Itl lln-.virc li .-illy Im 61,1, | ell to I III' ptl.rv'NS wt'l^lil | I linll.1l I"lis il|'|>l I- ^O f.'thl*' I,i fi,,,-l, M M.tir,-.-: ... 3 Industrial Factors K. Factor K is the ...

48 CFR 315.204-5 - Part IV-Representations and instructions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... as using too few.) (3) Examples of topics that form a basis for evaluation factors. Typical examples of topics that form a basis for the development of evaluation factors are listed in the following... special research, test, and other equipment or facilities. (vii) Managerial capability (ability to achieve...

48 CFR 315.204-5 - Part IV-Representations and instructions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... as using too few.) (3) Examples of topics that form a basis for evaluation factors. Typical examples of topics that form a basis for the development of evaluation factors are listed in the following... special research, test, and other equipment or facilities. (vii) Managerial capability (ability to achieve...

48 CFR 315.204-5 - Part IV-Representations and instructions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... as using too few.) (3) Examples of topics that form a basis for evaluation factors. Typical examples of topics that form a basis for the development of evaluation factors are listed in the following... special research, test, and other equipment or facilities. (vii) Managerial capability (ability to achieve...

Biased Gs versus Gq proteins and β-arrestin signaling in the NK1 receptor determined by interactions in the water hydrogen bond network.

PubMed

Valentin-Hansen, Louise; Frimurer, Thomas M; Mokrosinski, Jacek; Holliday, Nicholas D; Schwartz, Thue W

2015-10-02

X-ray structures, molecular dynamics simulations, and mutational analysis have previously indicated that an extended water hydrogen bond network between trans-membranes I-III, VI, and VII constitutes an allosteric interface essential for stabilizing different active and inactive helical constellations during the seven-trans-membrane receptor activation. The neurokinin-1 receptor signals efficiently through Gq, Gs, and β-arrestin when stimulated by substance P, but it lacks any sign of constitutive activity. In the water hydrogen bond network the neurokinin-1 has a unique Glu residue instead of the highly conserved AspII:10 (2.50). Here, we find that this GluII:10 occupies the space of a putative allosteric modulating Na(+) ion and makes direct inter-helical interactions in particular with SerIII:15 (3.39) and AsnVII:16 (7.49) of the NPXXY motif. Mutational changes in the interface between GluII:10 and AsnVII:16 created receptors that selectively signaled through the following: 1) Gq only; 2) β-arrestin only; and 3) Gq and β-arrestin but not through Gs. Interestingly, increased constitutive Gs but not Gq signaling was observed by Ala substitution of four out of the six core polar residues of the network, in particular SerIII:15. Three residues were essential for all three signaling pathways, i.e. the water-gating micro-switch residues TrpVI:13 (6.48) of the CWXP motif and TyrVII:20 (7.53) of the NPXXY motif plus the totally conserved AsnI:18 (1.50) stabilizing the kink in trans-membrane VII. It is concluded that the interface between position II:10 (2.50), III:15 (3.39), and VII:16 (7.49) in the center of the water hydrogen bond network constitutes a focal point for fine-tuning seven trans-membrane receptor conformations activating different signal transduction pathways. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Hypoxia induces cancer-associated cAMP/PKA signalling through HIF-mediated transcriptional control of adenylyl cyclases VI and VII.

PubMed

Simko, Veronika; Iuliano, Filippo; Sevcikova, Andrea; Labudova, Martina; Barathova, Monika; Radvak, Peter; Pastorekova, Silvia; Pastorek, Jaromir; Csaderova, Lucia

2017-08-31

Hypoxia is a phenomenon often arising in solid tumours, linked to aggressive malignancy, bad prognosis and resistance to therapy. Hypoxia-inducible factor-1 has been identified as a key mediator of cell and tissue adaptation to hypoxic conditions through transcriptional activation of many genes involved in glucose metabolism and other cancer-related processes, such as angiogenesis, cell survival and cell invasion. Cyclic adenosine 3'5'-monophosphate is one of the most ancient and evolutionarily conserved signalling molecules and the cAMP/PKA signalling pathway plays an important role in cellular adaptation to hypoxia. We have investigated possible new mechanisms behind hypoxic activation of the cAMP/PKA pathway. For the first time, we have shown that hypoxia induces transcriptional up-regulation of the system of adenylyl cyclases, enzymes responsible for cAMP production, in a panel of carcinoma cell lines of various origin. Our data prove functional relevance of the hypoxic increase of adenylyl cyclases VI and VII at least partially mediated by HIF-1 transcription factor. We have identified adenylyl cyclase VI and VII isoforms as mediators of cellular response to hypoxia, which led to the elevation of cAMP levels and enhanced PKA activity, with an impact on cell migration and pH regulation.

40 CFR 60.2635 - What are the operator training and qualification requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Combustion controls and monitoring. (v) Operation of air pollution control equipment and factors affecting... devices. (vii) Actions to correct malfunctions or conditions that may lead to malfunction. (viii) Bottom...

Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

PubMed

Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

2016-06-01

Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa.

A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

PubMed

Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

2012-12-01

Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

[Molecular genetic analysis for a pedigree with severe hereditary coagulation factor VII deficiency].

PubMed

Ding, Qiu-lan; Wang, Hong-li; Wang, Xue-feng; Wang, Ming-shan; Fu, Qi-hua; Wu, Wen-man; Hu, Yi-qun; Wang, Zhen-yi

2003-10-01

To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree. The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production. Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation. Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.

Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

PubMed

Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

1998-04-15

The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

Characterisation of clotting factors, anticoagulant protein activities and viscoelastic analysis in healthy donkeys.

PubMed

Perez-Ecija, A; Mendoza, F J

2017-11-01

Studies have demonstrated differences in commonly measured haemostatic parameters between donkeys and horses. Whether clotting factors, anticoagulant protein activities and thromboelastography parameters also differ between species is still unknown. To characterise haemostatic parameters in healthy donkeys and to compare these with those in horses. Cross-sectional study. Clotting factors (V, VII, VIII, IX, X, XI and XII), and antithrombin III, Protein C and Protein S activities were measured in 80 healthy Andalusian and crossbred donkeys and 40 healthy Andalusian crossbred horses with assays based on human deficient plasmas. Thromboelastography was performed in 34 donkeys using a coagulation and platelet function analyser. Donkeys had shorter activated partial thromboplastin time (mean ± s.d. 33.4 ± 5.2 s vs. 38.8 ± 4.2 s; P<0.001) and higher Factor VII (1825 ± 206 vs. 1513 ± 174; P<0.001), IX (142 ± 41 vs. 114 ± 28; P<0.05) and XI (59.4 ± 14.0 vs. 27.2 ± 6.3; P<0.001) activities, whereas horses showed higher Factor X (130 ± 32 vs. 145 ± 23; P>0.05) and XII (96 ± 21 vs. 108 ± 15; P<0.001) activities. Antithrombin III (204 ± 26 vs. 174 ± 29; P<0.001), Protein C (33.16 ± 10.0 vs. 7.57 ± 1.70; P<0.001) and Protein S (median [interquartile range]: 7.8 [5.8-9.3] vs. 6.2 [5.2-7.0]; P<0.001) activities were higher in donkeys. Activated clot time (175 [159-189]), time to peak (6.5 [5.8-7.8]) and clot formation rate (26.9 [16.9-36.4]) in donkeys were shorter than reported values in horses. Haemostatic pathways could not be fully evaluated in donkeys because some tests are unavailable. Certain fibrinolytic parameters (plasmin, plasminogen, etc.) have not been characterised in donkeys and this may have affected our results. The haemostatic system in donkeys differs from that in horses and extrapolation of reference values between these species is not appropriate. © 2017 EVJ Ltd.

19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 3 2014-04-01 2014-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 3 2011-04-01 2011-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 3 2013-04-01 2013-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 3 2012-04-01 2012-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

Speciation of Mn(II), Mn(VII) and total manganese in water and food samples by coprecipitation-atomic absorption spectrometry combination.

PubMed

Citak, Demirhan; Tuzen, Mustafa; Soylak, Mustafa

2010-01-15

A speciation procedure based on the coprecipitation of manganese(II) with zirconium(IV) hydroxide has been developed for the investigation of levels of manganese species. The determination of manganese levels was performed by flame atomic absorption spectrometry (FAAS). Total manganese was determined after the reduction of Mn(VII) to Mn(II) by ascorbic acid. The analytical parameters including pH, amount of zirconium(IV), sample volume, etc., were investigated for the quantitative recoveries of manganese(II). The effects of matrix ions were also examined. The recoveries for manganese(II) were in the range of 95-98%. Preconcentration factor was calculated as 50. The detection limit for the analyte ions based on 3 sigma (n=21) was 0.75 microg L(-1) for Mn(II). The relative standard deviation was found to be lower than 7%. The validation of the presented procedure was performed by analysis of certified reference material having different matrices, NIST SRM 1515 (Apple Leaves) and NIST SRM 1568a (Rice Flour). The procedure was successfully applied to natural waters and food samples.

Measurement and Analysis of Neutron Leakage Spectra from Pb and LBE Cylinders with D-T Neutrons

NASA Astrophysics Data System (ADS)

Chen, Size; Gan, Leting; Li, Taosheng; Han, Yuncheng; Liu, Chao; Jiang, Jieqiong; Wu, Yican

2017-09-01

For validating the current evaluated neutron data libraries, neutron leakage spectra from lead and lead bismuth eutectic (LBE) cylinders have been measured using an intense D-T pulsed neutron source with time-of-flight (TOF) method by Institute of Nuclear Energy Safety Technology (INEST), Chinese Academy of Sciences (CAS). The measured leakage spectra have been compared with the calculated ones using Super Monte Carlo Simulation Program for Nuclear and Radiation Process (SuperMC) with the evaluated pointwise data of lead and bismuth processed from ENDF/B-VII.1, JEFF-3.1 and JENDL-4.0 libraries. This work shows that calculations of the three libraries are all generally consistent with the lead experimental result. For LBE experiment, the JEFF-3.1 and JENDL-4.0 calculations both agree well with the measurement. However, the result of ENDF/B-VII.1 fails to fit with the measured data, especially in the energy range of 5.5 and 7 MeV with difference more than 80%. Through sensitivity analysis with partial cross sections of 209Bi in ENDF/B-VII.1 and JEFF, the difference between the measurement and the ENDF/B-VII.1 calculation in LBE experiment is found due to the neutron data of 209Bi.

[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog].

PubMed

Lutze, G; Römhild, W; Elwert, J; Leppelt, J; Kutschmann, K

2003-01-01

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

49 CFR Appendix A to Part 385 - Explanation of Safety Audit Evaluation Criteria

Code of Federal Regulations, 2010 CFR

2010-10-01

... safety management controls in place, is included in Appendix B, VII. List of Acute and Critical... having similar characteristics are combined together into six regulatory areas called “factors.” The regulatory factors, evaluated on the basis of the adequacy of the carrier's safety management controls, are...

78 FR 23557 - Fipronil; Receipt of Application for Emergency Exemptions, Solicitation of Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-19

... your concerns and suggest alternatives. vii. Explain your views as clearly as possible, avoiding the... population who, as a result of their location, cultural practices, or other factors, may have atypical or... that an emergency situation exists based upon three factors: A severe increase in cabbage maggot...

40 CFR 35.4065 - How can my group get more than $50,000?

Code of Federal Regulations, 2010 CFR

2010-07-01

... ten factors below must occur: (i) A Remedial Investigation/Feasibility Study (“RI/FS”) costing more...” (ESD); (vii) A legislative or regulatory change results in new site information after EPA awards the... the community require many meetings, copies, etc.; and (x) Any other factor that, in EPA's judgment...

Structural Equation Analysis of the Wechsler Adult Intelligence Scale-Revised in a Normal Elderly Sample.

ERIC Educational Resources Information Center

Burton, D. Bradley; And Others

1994-01-01

A maximum-likelihood confirmatory factor analysis was performed by applying LISREL VII to the Wechsler Adult Intelligence Scale-Revised results of a normal elderly sample of 225 adults. Results indicate that a three-factor model fits best across all sample combinations. A mild gender effect is discussed. (SLD)

39 CFR 255.8 - Access to postal facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... with the National Historic Preservation Act of 1966, 16 U.S.C. 470 et seq.; (vii) The availability of other options to foster service accessibility; and (viii) Any other factor that is relevant and...

12 CFR 202.1 - Authority, scope and purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... regulation is issued by the Board of Governors of the Federal Reserve System pursuant to title VII (Equal... prohibits creditor practices that discriminate on the basis of any of these factors. The regulation also...

40 CFR 86.001-25 - Maintenance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... used to determine exhaust, evaporative or refueling emission deterioration factors, as appropriate, is.... (b)(3)(vi)(E)-(b)(3)(vi)(J) [Reserved]. For guidance see § 86.098-25. (b)(3)(vii)-(b)(6)(i)(E...

Longitudinal association of hemostatic factors with risk for cancers of the breast, colorectum, and lung among postmenopausal women.

PubMed

Kabat, Geoffrey C; Salazar, Christian R; Zaslavsky, Oleg; Lane, Dorothy S; Rohan, Thomas E

2016-09-01

The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.

Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes

PubMed Central

Dayal, Jasbani H. S.; Cole, Clare L.; Pourreyron, Celine; Watt, Stephen A.; Lim, Yok Zuan; Salas-Alanis, Julio C.; Murrell, Dedee F.; McGrath, John A.; Stieger, Bruno; Jahoda, Colin; Leigh, Irene M.; South, Andrew P.

2014-01-01

ABSTRACT Type VII collagen is the main component of anchoring fibrils, structures that are integral to basement membrane homeostasis in skin. Mutations in the gene encoding type VII collagen COL7A1 cause recessive dystrophic epidermolysis bullosa (RDEB) an inherited skin blistering condition complicated by frequent aggressive cutaneous squamous cell carcinoma (cSCC). OATP1B3, which is encoded by the gene SLCO1B3, is a member of the OATP (organic anion transporting polypeptide) superfamily responsible for transporting a wide range of endogenous and xenobiotic compounds. OATP1B3 expression is limited to the liver in healthy tissues, but is frequently detected in multiple cancer types and is reported to be associated with differing clinical outcome. The mechanism and functional significance of tumour-specific expression of OATP1B3 has yet to be determined. Here, we identify SLCO1B3 expression in tumour keratinocytes isolated from RDEB and UV-induced cSCC and demonstrate that SLCO1B3 expression and promoter activity are modulated by type VII collagen. We show that reduction of SLCO1B3 expression upon expression of full-length type VII collagen in RDEB cSCC coincides with acquisition of front-to-rear polarity and increased organisation of 3D spheroid cultures. In addition, we show that type VII collagen positively regulates the abundance of markers implicated in cellular polarity, namely ELMO2, PAR3, E-cadherin, B-catenin, ITGA6 and Ln332. PMID:24357722

Dissimilar behavior of technetium and rhenium in borosilicatewaste glass as determined by X-ray absorption spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lukens, Wayne W.; McKeown, David A.; Buechele, Andrew C.

2006-11-09

Technetium-99 is an abundant, long-lived (t1/2 = 213,000 yr)fission product that creates challenges for the safe, long-term disposalof nuclear waste. While 99Tc receives attention largely due to its highenvironmental mobility, it also causes problems during its incorporationinto nuclear waste glass due to the volatility of Tc(VII) compounds. Thisvolatility decreases the amount of 99Tc stabilized in the waste glass andcauses contamination of the waste glass melter and off-gas system. Theapproach to decrease the volatility of 99Tc that has received the mostattention is reduction of the volatile Tc(VII) species to less volatileTc(IV) species in the glass melt. On engineering scale experiments,rhenium ismore » often used as a non-radioactive surrogate for 99Tc to avoidthe radioactive contamination problems caused by volatile 99Tc compounds.However, Re(VII) is more stable towards reduction than Tc(VII), so morereducing conditions would be required in the glass melt to produceRe(IV). To better understand the redox behavior of Tc and Re in nuclearwaste glass, a series of glasses were prepared under different redoxconditions. The speciation of Tc and Re in the resulting glasses wasdetermined by X-ray absorption fine structure spectroscopy. Surprisingly,Re and Tc do not behave similarly in the glass melt. Although Tc(0),Tc(IV), and Tc(VII) were observed in these samples, only Re(0) andRe(VII) were found. In no case was Re(IV) (or Re(VI))observed.« less

Thromboelastography to Direct the Administration of Recombinant Activated Factor VII in a Child with Traumatic Injury Requiring Massive Transfusion

DTIC Science & Technology

2009-01-01

in a child with hemophilia and high titer inhibitors to factor VIII: A case report and brief review. J Extra Cor- por Technol 2006; 38:254–259 16...J Trauma 1969; 9:939–965 20. Sorensen B, Ingerslev J: Thromboelastogra- phy and recombinant factor VIIa- hemophilia and beyond. Semin Hematol 2004; 41

Production of coagulation factor VII in human cell lines Sk-Hep-1 and HKB-11.

PubMed

Corrêa de Freitas, Marcela Cristina; Bomfim, Aline de Sousa; Mizukami, Amanda; Picanço-Castro, Virgínia; Swiech, Kamilla; Covas, Dimas Tadeu

2017-09-01

Recombinant factor VII (rFVII) is the main therapeutic choice for hemophilia patients who have developed inhibitory antibodies against conventional treatments (FVIII and FIX). Because of the post-translational modifications, rFVII needs to be produced in mammalian cell lines. In this study, for the first time, we have shown efficient rFVII production in HepG2, Sk-Hep-1, and HKB-11 cell lines. Experiments in static conditions for a period of 96 h showed that HepG2-FVII produced the highest amounts of rhFVII, with an average of 1843 ng/mL. Sk-hep-1-FVII cells reached a maximum protein production of 1432 ng/mL and HKB-11-FVII cells reached 1468 ng/mL. Sk-Hep-1-rFVII and HKB-11-rFVII were selected for the first step of scale-up. Over 10 days of spinner flask culture, HKB-11 and SK-Hep-1 cells showed a cumulative production of rFVII of 152 μg and 202.6 μg in 50 mL, respectively. Thus, these human cell lines can be used for an efficient production of recombinant FVII. With more investment in basic research, human cell lines can be optimized for the commercial production of different bio therapeutic proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy and safety of recombinant activated factor vii in major surgical procedures: systematic review and meta-analysis of randomized clinical trials.

PubMed

Ranucci, Marco; Isgrò, Giuseppe; Soro, Giorgio; Conti, Daniela; De Toffol, Barbara

2008-03-01

To investigate the efficacy and safety of recombinant activated factor VII (rFVIIa) treatment in patients undergoing major surgical procedures. Relevant studies were searched in BioMedCentral, CENTRAL, PubMed, and PubMed Central. Only randomized controlled trials on humans undergoing major surgery were included. Efficacy was determined as the rate of patients receiving allogeneic packed red blood cells; safety was assessed in terms of thromboembolic complications and mortality rate. We followed the Cochrane Collaboration method for data extraction and internal validity procedures, as well as the Quality of Reporting of Meta-analyses statement. Seven randomized controlled trials met the inclusion criteria. Treatment with rFVIIa is associated with a reduced risk of receiving allogeneic packed red blood cells (odds ratio, 0.29; 95% confidence interval, 0.10-0.80). In a subgroup analysis, only patients receiving at least 50 mug/kg of rFVIIa had a significant benefit (odds ratio, 0.43; 95% confidence interval, 0.23-0.78). No differences in thromboembolic complications and mortality rates were observed. Treatment with rFVIIa is effective in reducing the rate of patients undergoing transfusion with allogeneic packed red blood cells. However, the cost-benefit ratio is favorable only in patients who need a huge number of packed red blood cell units. No safety concerns arise from the present study.

40 CFR 721.10133 - 2-Propenoic acid, 2-methyl, 2-hydroxyethyl ester, homopolymer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for Occupational Safety and Health (NIOSH) assigned protection factor (APF) of at least 1,000. A NIOSH... percent), (f), (g)(1)(vii), and (g)(2)(iv). (iii) Industrial, commercial, and consumer activities...

46 CFR 4.05-2 - Incidents involving foreign tank vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... discharge, resulting from damage to the vessel or its equipment. The factors you must consider to determine...; (vi) The nature of damage to the vessel; and (vii) Failure or breakdown aboard the vessel, its...

77 FR 47116 - Manufacturer of Controlled Substances; Notice of Registration; Penick Corporation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... Ecgonine (9180) II Hydrocodone (9193) VII Morphine (9300) II Oripavine (9330) II Thebaine (9333) II... has considered the factors in 21 U.S.C. 823(a) and determined that the registration of Penick...

29 CFR 1608.11 - Limitations on the application of these guidelines.

Code of Federal Regulations, 2010 CFR

2010-07-01

... AFFIRMATIVE ACTION APPROPRIATE UNDER TITLE VII OF THE CIVIL RIGHTS ACT OF 1964, AS AMENDED § 1608.11... such factors as progress in correcting the conditions disclosed by the self analysis. The currency of...

Star formation and abundances in the nearby irregular galaxy VII ZW 403

NASA Astrophysics Data System (ADS)

Tully, R. B.; Boesgaard, A. M.; Dyck, H. M.; Schempp, W. V.

1981-05-01

Photometry in J, H, and K bands reveals that there is an unresolved source of infrared emission associated with the brightest H II region in VII Zw 403, and the colors suggest the presence of a substantial number of K and M supergiants in addition to the hot O stars that must be present to account for the ionized gas. Spectrophotometry of this emission region indicates that reddening is substantial, and that the interpretation of the observed Balmer decrement in terms of reddening is not straightforward. The primary nucleosynthesis products O, S, and Ne are underabundant compared with the sun by a factor of 15; N is underabundant compared with the sun by a factor of 160; and the helium abundance suggests that either there could have been only a small number of star formation episodes or the galaxy is younger than the time scale of the process that deposits N in the interstellar medium.

Health economic review of recombinant activated factor VII for treatment of bleeding episodes in hemophilia patients with inhibitors.

PubMed

Stephens, Jennifer M; Joshi, Ashish V; Sumner, Michael; Botteman, Marc F

2007-06-01

Severe hemophilia with inhibitors is a rare disease with substantial clinical, humanistic and economic consequences. This review provides an overview of the role of recombinant activated factor VII (rFVIIa) versus plasma-derived bypassing agents for hemophilia with inhibitors and summarizes the 13 formal economic analyses (6 burden of illness and 7 comparative studies) that have been published in this indication. The findings suggest that the economic impact of rFVIIa has occurred primarily during hospitalization to manage major bleeding episodes and to allow for elective orthopedic surgeries that would not have been attempted prior to rFVIIa. Comparative analyses for on-demand treatment suggest that the total cost of treating a bleeding episode with rFVIIa may be lower than with plasma-based agents due to faster bleeding resolution, higher initial efficacy rates and avoidance of second and third lines of treatment.

Type VII Collagen Expression in the Human Vitreoretinal Interface, Corpora Amylacea and Inner Retinal Layers

PubMed Central

Wullink, Bart; Pas, Hendri H.; Van der Worp, Roelofje J.; Kuijer, Roel; Los, Leonoor I.

2015-01-01

Type VII collagen, as a major component of anchoring fibrils found at basement membrane zones, is crucial in anchoring epithelial tissue layers to their underlying stroma. Recently, type VII collagen was discovered in the inner human retina by means of immunohistochemistry, while proteomic investigations demonstrated type VII collagen at the vitreoretinal interface of chicken. Because of its potential anchoring function at the vitreoretinal interface, we further assessed the presence of type VII collagen at this site. We evaluated the vitreoretinal interface of human donor eyes by means of immunohistochemistry, confocal microscopy, immunoelectron microscopy, and Western blotting. Firstly, type VII collagen was detected alongside vitreous fibers6 at the vitreoretinal interface. Because of its known anchoring function, it is likely that type VII collagen is involved in vitreoretinal attachment. Secondly, type VII collagen was found within cytoplasmic vesicles of inner retinal cells. These cells resided most frequently in the ganglion cell layer and inner plexiform layer. Thirdly, type VII collagen was found in astrocytic cytoplasmic inclusions, known as corpora amylacea. The intraretinal presence of type VII collagen was confirmed by Western blotting of homogenized retinal preparations. These data add to the understanding of vitreoretinal attachment, which is important for a better comprehension of common vitreoretinal attachment pathologies. PMID:26709927

SLY1 and Syntaxin 18 specify a distinct pathway for procollagen VII export from the endoplasmic reticulum

PubMed Central

Nogueira, Cristina; Erlmann, Patrik; Villeneuve, Julien; Santos, António JM; Martínez-Alonso, Emma; Martínez-Menárguez, José Ángel; Malhotra, Vivek

2014-01-01

TANGO1 binds and exports Procollagen VII from the endoplasmic reticulum (ER). In this study, we report a connection between the cytoplasmic domain of TANGO1 and SLY1, a protein that is required for membrane fusion. Knockdown of SLY1 by siRNA arrested Procollagen VII in the ER without affecting the recruitment of COPII components, general protein secretion, and retrograde transport of the KDEL-containing protein BIP, and ERGIC53. SLY1 is known to interact with the ER-specific SNARE proteins Syntaxin 17 and 18, however only Syntaxin 18 was required for Procollagen VII export. Neither SLY1 nor Syntaxin 18 was required for the export of the equally bulky Procollagen I from the ER. Altogether, these findings reveal the sorting of bulky collagen family members by TANGO1 at the ER and highlight the existence of different export pathways for secretory cargoes one of which is mediated by the specific SNARE complex containing SLY1 and Syntaxin 18. DOI: http://dx.doi.org/10.7554/eLife.02784.001 PMID:24842878

Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy

PubMed Central

Bornert, Olivier; Kühl, Tobias; Bremer, Jeroen; van den Akker, Peter C; Pasmooij, Anna MG; Nyström, Alexander

2016-01-01

Genetically evoked deficiency of collagen VII causes dystrophic epidermolysis bullosa (DEB)—a debilitating disease characterized by chronic skin fragility and progressive fibrosis. Removal of exons carrying frame-disrupting mutations can reinstate protein expression in genetic diseases. The therapeutic potential of this approach is critically dependent on gene, protein, and disease intrinsic factors. Naturally occurring exon skipping in COL7A1, translating collagen VII, suggests that skipping of exons containing disease-causing mutations may be feasible for the treatment of DEB. However, despite a primarily in-frame arrangement of exons in the COL7A1 gene, no general conclusion of the aptitude of exon skipping for DEB can be drawn, since regulation of collagen VII functionality is complex involving folding, intra- and intermolecular interactions. To directly address this, we deleted two conceptually important exons located at both ends of COL7A1, exon 13, containing recurrent mutations, and exon 105, predicted to impact folding. The resulting recombinantly expressed proteins showed conserved functionality in biochemical and in vitro assays. Injected into DEB mice, the proteins promoted skin stability. By demonstrating functionality of internally deleted collagen VII variants, our study provides support of targeted exon deletion or skipping as a potential therapy to treat a large number of individuals with DEB. PMID:27157667

24 CFR 1000.162 - How will a recipient know that non-dwelling structures assisted under the IHBG program meet the...

Code of Federal Regulations, 2010 CFR

2010-04-01

..., design, features, amenities, performance or other factors. The standards for such structures must be able to support the reasonableness and necessity for these factors and to clearly identify the affordable... change; (vi) Cultural relevance of design; (vii) Size and scope supported by population and need; (viii...

50 CFR 23.70 - How can I trade internationally in American alligator and other crocodilian skins, parts, and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... requirements for skins and parts. (vii) Habitat evaluation. (viii) Information on nuisance alligator management... or hatchlings is allowed, what factors are used to set harvest levels, and whether any alligators are... allowed, what factors are used to set harvest levels, and whether any alligators are returned to the wild...

Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

PubMed Central

Altman, Raul; Scazziota, Alejandra Silvia; Herrera, Maria de Lourdes; Gonzalez, Claudio

2006-01-01

Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG) in vitro. Methods and results TG was quantified by time parameters: lag time (LT) and time to peak (TTP), and by amount of TG: peak of TG (PTG) and area under thrombin formation curve after 35 minutes (AUC→35min) in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT) technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA), ADP, and collagen (Col). In addition, the effects of recombinant activated FVII (rFVIIa) alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p < 0.05) and PTG and AUC→35min were significantly increased (p < 0.05) in platelet rich plasma activated with AA, ADP, Col, and rFVIIa compared to non-activated platelet rich plasma from normal subjects (p = 0.01). Furthermore platelet rich plasma activated by the combined effects of rFVIIa plus AA, ADP or Col had significantly reduced LT and TTP and increased AUC→35min (but not PTG) when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis. PMID:16630353

Effects of exposure to factor concentrates containing donations from identified AIDS patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jason, J.; Holman, R.C.; Dixon, G.

1986-10-03

The authors recipients of eight lots of factors VII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV), T-cell subset numbers, T-helper to T-suppressor ratios, or immunogloubulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normalmore » range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rats of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposed within this population.« less

New Nipponentomon species from northern Asia (Protura: Acerentomata, Nipponentomidae).

PubMed

Bu, Yun; Wu, Dong Hui; Shrubovych, Julia; Yin, Wen Ying

2013-01-01

Nipponentomnon imadatei sp. nov. from Northeast China and Nippon entomon taiga sp. nov. from Siberia, Russia are described. Nipponentornon heterothrixi Yin & Xie is redescribed based on type materials and lectotype and paralectotypes are designed for the species. Nipponentonon bidentatumn and N. nippon are reported for the first time from China. Nipponentornon imnadatei sp. nov. is characterized by a short labrum, absence of seta Pla on tergite VII and presence of three A-setae on sternites IV-VI. It is similar to N. jaceki from the Russian Far East, but differs in the shape of the comb, shape of setaβ1 on the foretarsus, length of sensillum e on the foretarsus, and in chaetotaxy on tergite I and sternites IV-VI. Nipponentomnon taiga sp. nov. is characterized by a short labrum, presence of seta P2a' on nota, seta P0a on tergite I, seta Pla on tergites I-VII, and absence of seta P3a on tergites II-VII. It is similar to N. heterothrixi, but differs in absence of seta d6 on the head, shape of accessory setae on tergites VI and VII, long and setiform setaβ1, and shorter sensilla c, e, g, a' and c' on the foretarsus than in sensilla in N. heterothrixi and in the porotaxy. A key for the world species of the genus is provided and the porotaxy of five species is reported in detail.

Analysis of 238Pu and 56Fe Evaluated Data for Use in MYRRHA

NASA Astrophysics Data System (ADS)

Díez, C. J.; Cabellos, O.; Martínez, J. S.; Stankovskiy, A.; Van den Eynde, G.; Schillebeeckx, P.; Heyse, J.

2014-04-01

A sensitivity analysis on the multiplication factor, keff, to the cross section data has been carried out for the MYRRHA critical configuration in order to show the most relevant reactions. With these results, a further analysis on the 238Pu and 56Fe cross sections has been performed, comparing the evaluations provided in the JEFF-3.1.2 and ENDF/B-VII.1 libraries for these nuclides. Then, the effect in MYRRHA of the differences between evaluations are analysed, presenting the source of the differences. With these results, recommendations for the 56Fe and 238Pu evaluations are suggested. These calculations have been performed with SCALE6.1 and MCNPX-2.7e.

40 CFR Appendix Vii to Part 600 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false [Reserved] VII Appendix VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES Appendix VII to Part 600 [Reserved] ...

40 CFR Appendix Vii to Part 600 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false [Reserved] VII Appendix VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES Appendix VII to Part 600 [Reserved] ...

40 CFR Appendix Vii to Part 600 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false [Reserved] VII Appendix VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES Appendix VII to Part 600 [Reserved] ...

42 CFR 57.2003 - Determinations of increased enrollment solely for the program.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Other Federal programs, such as those set forth in title VII and VIII of the Public Health Service Act... unusual factors, such as: (1) An institution having been newly established or (2) an institution...

Phenotypic Characterization of Mice Carrying Homozygous Deletion of KLF11, a Gene in Which Mutations Cause Human Neonatal and MODY VII Diabetes

PubMed Central

Mathison, Angela; Escande, Carlos; Calvo, Ezequiel; Seo, Seungmae; White, Thomas; Salmonson, Ann; Faubion, William A.; Buttar, Navtej; Iovanna, Juan; Lomberk, Gwen; Chini, Eduardo N.

2015-01-01

We have previously shown that amino acid changes in the human Kruppel-Like Factor (KLF) 11 protein is associated with the development of maturity onset diabetes of the young VII, whereas complete inactivation of this pathway by the −331 human insulin mutation causes neonatal diabetes mellitus. Here, we report that Klf11−/− mice have decreased circulating insulin levels, alterations in the control of blood glucose and body weight, as well as serum dyslipidemia, but do not develop diabetes. Functional assays using ex vivo liver tissue sections demonstrate that Klf11−/− mice display increased insulin sensitivity. Genome-wide experiments validated by pathway-specific quantitative PCR arrays reveal that the Klf11−/− phenotype associates to alterations in the regulation of gene networks involved in lipid metabolism, in particular those regulated by peroxisome proliferator-activated receptor-γ. Combined, these results demonstrate that the major phenotype given by the whole-body deletion of Klf11 in mouse is not diabetes but increased insulin sensitivity, likely due to altered transcriptional regulation in target tissues. The absence of diabetes in the Klf11−/− mouse either indicates an interspecies difference for the role of this transcription factor in metabolic homeostasis between mouse and humans, or potentially highlights the fact that other molecular factors can compensate for its absence. Nevertheless, the data of this study, gathered at the whole-organism level, further support a role for KLF11 in metabolic processes like insulin sensitivity, which regulation is critical in several forms of diabetes. PMID:26248217

Kinetic Modeling Sheds Light on the Mode of Action of Recombinant Factor VIIa on Thrombin Generation

DTIC Science & Technology

2011-01-01

Regular Article Kinetic modeling sheds light on the mode of action of recombinant factor VIIa on thrombin generation Alexander Y. Mitrophanov...its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa) ― a promising hemostasis-inducing...modulate thrombin production , it is necessary to identify rFVIIa-induced effects that are compatible with the available biochemical knowledge about

Defense Analysis: The Decision Process

DTIC Science & Technology

1985-07-01

problems ot resource allocation. Includes chapters on tormulating the problem, the research ettort, evaluation ot alternatives, interpretations of...Economics and Decision Making. He is a graduate of Colgate University (BA, Psychology) and received his Masters degree at the Naval Post Graduate School...Analysis 62 ’, ’The Steps irn Subject iye Aiuslysis 66 " Identify the Factors 66 Discusss the Factors 67 Evaluate Each Factor 67 Summa r y 68 Chapter VII

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

The effects of a low-dose monophasic preparation of levonorgestrel and ethinyl estradiol on coagulation and other hemostatic factors.

PubMed

Archer, D F; Mammen, E F; Grubb, G S

1999-11-01

This study was undertaken to evaluate the effects on hemostatic factors of a low-dose preparation of levonorgestrel and ethinyl estradiol in a 12-cycle study. Thirty healthy women began taking 100 microg levonorgestrel and 20 microg ethinyl estradiol on the first day of the menstrual cycle, continued to take the preparation for the next 21 days, and then took placebo for 7 days. Mean changes in prothrombin time, partial thromboplastin time, and levels of factors VII and X, antithrombin, plasminogen, fibrinogen, protein S, thrombin-antithrombin complexes, and D-dimer were analyzed at baseline and at cycles 3, 6, and 12 with paired Student t tests. Factor X, plasminogen antigen and activity, and D-dimer levels were significantly increased (P

Retention of fissure sealants in young permanent molars affected by dental fluorosis: a 12-month clinical study.

PubMed

Hasanuddin, S; Reddy, E R; Manjula, M; Srilaxmi, N; Rani, S T; Rajesh, A

2014-10-01

To evaluate and compare retention and caries occurance following placement of Clinpro and FUJI VII fissure sealants, by two different techniques simultaneously in unsealed, contralateral young permanent molars of 7- to 10-year-old children affected by mild to moderate dental fluorosis at various recall intervals of 1 week, 1, 3, 6 and 12 months. 80 schoolchildren with mild to moderate dental fluorosis were assigned to Group A and Group B with 40 children in each group. In Group A Clinpro fissure sealant and in Group B Fuji VII fissure sealant was used. In both the groups fissure sealants were applied by conventional fissure sealant technique (CST) on one side and enameloplasty sealant technique (EST) on the other side of the same arch. The applied fissure sealants were evaluated clinically for retention and caries incidence. Clinpro fissure sealant showed a retention rate of 95% when compared with Fuji VII (57.5%) at the end of 12 months, which was statistically significant. Regarding techniques, EST showed better results than CST in both the groups. Comparison of groups with respect to retention and techniques at different time periods was performed using Mann-Whitney U test (p < 0.05). Comparison of different time periods with respect to retention and technique in all the groups was performed using Wilcoxon matched pairs test by ranks (p < 0.05). Clinpro fissure sealant showed better retention at all treatment intervals, when compared with Fuji VII. Further follow-up is required to study the efficacy of the fissure sealant placement techniques.

Intelsat VII program and the future

NASA Astrophysics Data System (ADS)

Madon, P. J.; Sachdev, D. K.

The evolution of the Intelsat VII spacecraft is discussed. The role of competitive procurement process in this evolution is addressed, and the overall system-level features of the spacecraft are reviewed. The time frame for the five Intelsat VII missions is summarized, and follow-up projects to Intelsat VII are discussed.

Recombinant Factor VIIa Reduces Rebleed Hemorrhage Volume in a Swine Aortotomy Model: A Randomized Double-Blinded Study

DTIC Science & Technology

2008-06-01

Bpops,[ a dose of 90 Hg kgj1 will produce serum concentrations of factor VII high enough to reduce hemorrhage by accelerating thrombin production and...interaction is species-specific, and human FVII seems to have only between 5% and 50% activity when exposed to porcine tissue factor (15). The results...Copyright @ 200 by the Shock Society. Unauthorized reproduction of this article is prohibited.8 RECOMBINANT FACTOR VIIA REDUCES REBLEED HEMORRHAGE

Computational Analysis of the Effects of Reduced Temperature on Thrombin Generation: The Contributions of Hypothermia to Coagulopathy

DTIC Science & Technology

2013-09-01

reactions characterize the interactions of factor VII ( FVII ) and factor VIIa (FVIIa) and their complexes with TF and other clotting factors . These...patients), is one of the major factors contributing to coagulopathy of trauma.1–3 Heavy bleeding may result in a decreased blood volume and...tri- phosphate synthesis.4 Transfusion of blood products and resuscitation fluids, which are stored at low temperatures or even in a frozen state

Why Johnny Can Read...But Doesn't

ERIC Educational Resources Information Center

Landy, Sarah

1977-01-01

The article analyzes characteristics of readers vs. non-readers and environmental factors which influence reading patterns among Grade VII (age 12-13) students. The study is based on 573 students and includes data on frequency of reading and book subject preferences. (JAB)

Syndromes, disorders and maternal risk factors associated with neural tube defects (VII).

PubMed

Chen, Chih-Ping

2008-09-01

Neural tube defects (NTDs) may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome), Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher- Zweymller syndrome, parietal foramina (cranium bifidum), Apert syndrome, craniomicromelic syndrome, XXagonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Enhancement of students’ creative thinking skills on mixture separation topic using project based student worksheet

NASA Astrophysics Data System (ADS)

Nurisalfah, R.; Fadiawati, N.; Jalmo, T.

2018-05-01

The aim of this study is to describe the effectiveness of project based student worksheet in improving students' creative thinking skills. The research method is using quasi experiment with the matching only pre-test post-test control group design. The population in this research is all students of class VII SMP N 2 Belitang Madang Raya with class VII1 as control class and class VII4 as experiment class. The sample of this research is obtaining by purposive sampling technique. The effectiveness of project based student worksheet is based on significant post-test differences between the control class and the experiment class as well as the effect size. The results show that the using of project based student worksheet is effective in improving students' creative thinking skills on mixture separation topic.

Congenital Factor VII Deficiency in Children at Tertiary Health Care Facility in Pakistan.

PubMed

Alam, Muhammad Matloob; Moiz, Bushra; Rehman, Karim Abdur; Jethwani, Priyanka; Fadoo, Zehra

2015-10-01

This study presents the demographics, clinical spectrum, and outcome of patients with congenital factor VII (FVII) deficiency at a tertiary care center over a period of 12 years. Of the 49 patients, 27 (55%) patients were males. Consanguinity was found in 92% of the patients. The median age of symptom onset was 2.4 (interquartile range [IQR]: 1.1-6.5) years with a median age of 5.8 (IQR: 3.1-10) years at diagnosis. Life-threatening complications like intracranial bleeding (ICB) and intra-abdominal bleeding (IAB) were observed in 8 (16.4%) patients. We found that 11 (55%) of the 20 patients with FVII coagulant activity (FVIIc) <1% were either asymptomatic or showed mild phenotype. In contrast, 9 (53%) of the 17 patients with FVIIc >5% were affected by severe symptoms. Age <1 year was the only identified risk factor associated with development of life-threatening bleeding episodes (P = .042; odds ratio 6.46). Overall, 4 (8.2%) died as a consequence of ICB (3 patients) and IAB (1 patient). © The Author(s) 2013.

77 FR 5396 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-03

... Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION: Final... rule, extends its existing recordkeeping requirements under title VII of the Civil Rights Act of 1964 (Title VII) and the Americans with Disabilities Act (ADA) to entities covered by title II of the Genetic...

76 FR 31892 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION: Notice...'' or ``Commission'') proposes to extend its existing recordkeeping requirements under title VII of the Civil Rights Act of 1964 (Title VII) and the Americans with Disabilities Act (ADA) to entities covered...

Congenital factor XI and factor VII deficiencies assure an apparent opposite protection against arterial or venous thrombosis: An intriguing observation.

PubMed

Girolami, A; Peroni, E; Girolami, B; Ferrari, S; Lombardi, A M

2016-09-01

To investigate the prevalence and type of thrombotic events reported in patients with congenital factor XI (FXI) or factor VII (FVII) deficiency. Data on all patients with congenital FXI or FVII deficiency and a thrombotic event were gathered by means of a time unlimited PubMed search carried out in June 2014 and in February 2015. Appropriate keywords including the medical subject headings were used in both instances. Side tables were also consulted and cross-checking of the references was carried out to avoid omissions. The thrombosis event had to be proven by objective methods. Forty-three patients with FXI deficiency had arterial thrombosis and only eight had venous thrombosis. On the contrary, only five patients with FVII deficiency had arterial thrombosis whereas 31 patients had venous thrombosis. The arterial/venous ratios were 5.37 and 0.17 for FXI or FVII, respectively. Arterial thrombosis is frequent in FXI deficiency whereas venous thrombosis is rare. The reverse is true for FVII deficiency. The significance of these findings is discussed especially in view of the recent use of synthetic anti-FXI compounds in the prophylaxis of post-orthopedic surgery of venous thrombosis complications.

An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

PubMed

Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

2016-06-24

Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

External female genitalia of six species of the genus Meccus (Hemiptera: Reduviidae: Triatominae).

PubMed

Rivas, Nancy; Sánchez-Cordero, Victor; Camacho, Alejandro D; Alejandre-Aguilar, Ricardo

2017-12-01

Triatomine classification is based on morphological characteristics. Studies have been conducted to improve their identification by observing many characteristics. However, there are problems of differentiating among highly interrelated species and new criteria are required. The purpose of this study was to determine the morphological differences in the external female genitalia of M. pallidipennis, M. longipennis, M. picturatus, M. bassolsae, M. mazzottii, and M. phyllosomus in order to distinguish among species using scanning electron microscopy. Observations were made of the dorsal, posterior, lateral, and ventral views of the female external genitalia for each species. In the six species we studied, relevant differences were observed in the dorsal view of the X segment, as well as the IX, VIII, and VII tergites. In the posterior and lateral view, the most visible differences were registered in the gonocoxite size of the segments VIII, IX, and X. Finally, in the ventral view of the VII sternite, differences among species were observed in the size of the inflection in the top and upper corner. Our results show that it was possible to differentiate among the triatominae species for each of the four views by using a scanning electron microscope to analyze morphological characteristics of the VII, VIII, IX, and X abdomen segments. © 2017 The Society for Vector Ecology.

Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran.

PubMed

Dorgalaleh, Akbar; Alavi, Sayed Ezatolla Rafiee; Tabibian, Shadi; Soori, Shahrzad; Moradi, Es'hagh; Bamedi, Taregh; Asadi, Mansour; Jalalvand, Masumeh; Shamsizadeh, Morteza

2017-05-01

Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs. In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs. For this study, all relevant publications were searched in Medlin until 2015. Iran has the highest global incidence of factor XIII deficiency. Factor VII deficiency also is common in Iran, while factor II deficiency, with a prevalence of 1 per ∼3 million, is the rarest form of RBDs. Factor activity is available for all RBDs except for factor XIII deficiency, in which clot solubility remains as a diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few recurrent, common mutations only in patients with factor XIII deficiency, and considerable novel mutations in other RBDs. Clinical manifestations of these patients are variable and patients with factor XIII, factor X and factor VII more commonly presented severe life-threatening bleeding, while patients with combined factor V and factor VIII presented a milder phenotype. Plasma-derived products are the most common therapeutic choice in Iran, used prophylactically or on-demand for the management of these patients. Since Iran has a high rate of RBDs with life-threatening bleeding, molecular studies can be used for carrier detection and, therefore, prevention of the further expansion of these disorders and their fatal consequence.

A core viral protein binds host nucleosomes to sequester immune danger signals

PubMed Central

Avgousti, Daphne C.; Herrmann, Christin; Kulej, Katarzyna; Pancholi, Neha J.; Sekulic, Nikolina; Petrescu, Joana; Molden, Rosalynn C.; Blumenthal, Daniel; Paris, Andrew J.; Reyes, Emigdio D.; Ostapchuk, Philomena; Hearing, Patrick; Seeholzer, Steven H.; Worthen, G. Scott; Black, Ben E.; Garcia, Benjamin A.; Weitzman, Matthew D.

2016-01-01

Viral proteins mimic host protein structure and function to redirect cellular processes and subvert innate defenses1. Small basic proteins compact and regulate both viral and cellular DNA genomes. Nucleosomes are the repeating units of cellular chromatin and play an important role in innate immune responses2. Viral encoded core basic proteins compact viral genomes but their impact on host chromatin structure and function remains unexplored. Adenoviruses encode a highly basic protein called protein VII that resembles cellular histones3. Although protein VII binds viral DNA and is incorporated with viral genomes into virus particles4,5, it is unknown whether protein VII impacts cellular chromatin. Our observation that protein VII alters cellular chromatin led us to hypothesize that this impacts antiviral responses during adenovirus infection. We found that protein VII forms complexes with nucleosomes and limits DNA accessibility. We identified post-translational modifications on protein VII that are responsible for chromatin localization. Furthermore, proteomic analysis demonstrated that protein VII is sufficient to alter protein composition of host chromatin. We found that protein VII is necessary and sufficient for retention in chromatin of members of the high-mobility group protein B family (HMGB1, HMGB2, and HMGB3). HMGB1 is actively released in response to inflammatory stimuli and functions as a danger signal to activate immune responses6,7. We showed that protein VII can directly bind HMGB1 in vitro and further demonstrated that protein VII expression in mouse lungs is sufficient to decrease inflammation-induced HMGB1 content and neutrophil recruitment in the bronchoalveolar lavage fluid. Together our in vitro and in vivo results show that protein VII sequesters HMGB1 and can prevent its release. This study uncovers a viral strategy in which nucleosome binding is exploited to control extracellular immune signaling. PMID:27362237

A molecular dynamic investigation for shock induced phase transition of water

NASA Astrophysics Data System (ADS)

Mitra, Nilanjan; Neogi, Anupam

2015-06-01

Atomistic equilibrium molecular dynamics (EMD) was carried out to investigate shock induced phase transition of bulk liquid water. Multi-scale shock technique (MSST) was utilized to investigate low (US = 2 . 5km /s) to strong (US = 6 . 5km /s) intensity shock response on an extended flexible three point model up to 100 ns. The thermodynamic pathway of phase transition from liquid water to ice VII was investigated using temporal variation of thermodynamic state variables, power spectrum analyses of O-H bond vibration along with temporal evolution of pair correlation function between O-O, O-H and H-H atoms. Static structure factor along with pair-distribution function extended up to 20 Å was calculated and compared against the ideal ice VII to get information regarding long range ordering. Bragg reflection at different crystal planes were evaluated to investigate percentage of crystallinity of the shocked sample. Specific questions answered in this work involves: What is the exact time frame after the passage of shock at certain intensity in which nucleation of solid phase can be observed? Is it a complete or partial phase transition? Are external nucleators essential for this transformation? What is the percentage of crystallinity of the nucleated phase?

Spall behavior of cast iron with varying microstructures

NASA Astrophysics Data System (ADS)

Plume, Gifford; Rousseau, Carl-Ernst

2014-07-01

The spall strength of cast iron with varying microstructures has been investigated using plate impact at moderate speed. Stress history measurements were made with manganin stress gauges embedded between the back face of the specimen and a low impedance polycarbonate backing. Five separate cast irons were tested. Four of these consisted of gray cast iron with graphite in flake form, with three classified as Type VII A2 and the fourth containing a bimodal distribution of Types VII A4 and VII D8. The fifth casting consisted of ductile cast iron with graphite in nodular form, classified as Type I, size class 5. The spall strength for the Type VII A2 gray cast irons varied between 40 and 370 MPa, and that of the additional gray cast iron, between 410 and 490 MPa. The spall strength of the ductile cast iron fell within the range of 0.94-1.2 GPa. It is shown that the spall strength is linked to the damage level at the spall plane, where an increased level of tensile stress is required to generate higher levels of damage. Post mortem analysis was performed on the recovered samples, revealing the graphite phase to be the primary factor governing the spall fracture of cast irons, where crack nucleation is directly correlated to the debonding of graphite from the metal matrix. The average length of graphite found within a casting is linked to the material's strength, where strength increases as a function of decreasing length. The morphology and mean free path of graphite precipitates further govern the subsequent coalescence of initiated cracks to form a complete fracture plane. In cases where graphite spacing is large, increased energy level is required to complete the fracture process. A secondary factor governing the spall fracture of cast irons has also been linked to the microstructure of the metal matrix, with pearlite yielding higher spall strengths than free ferrite.

76 FR 52656 - Lock+Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On August 4, 2011, Lock+Hydro Friends Fund VII, filed an... Friends Fund VII, 5090 Richmond Avenue 390, Houston, TX 77056; phone (877) 556- 6566 x709. FERC Contact...

76 FR 79065 - Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... DEPARTMENT OF LABOR Equal Employment Opportunity Commission 29 CFR Part 1602 Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA CFR Correction In Title 29 of the Code of Federal... title VII or section 107 of the ADA'' and add in their place the words ``section 709(c) of title VII...

15 CFR 990.55 - Restoration selection-developing restoration plans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OIL... involvement of the responsible parties in the assessment; and (vii) A description of monitoring for.... (3) The monitoring component to the Draft Restoration Plan should address such factors as duration...

76 FR 66914 - Amendment of Limitation of Duty- and Quota-Free Imports of Apparel Articles Assembled in...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-28

... eligible fabrics, fabric components, or components knit-to-shape. Title VII of the Tax Relief and Health... Clothing (ATC), and the conversion factors for units of measure into square meter equivalents used by the...

10 CFR 431.422 - Prescriptions of a rule.

Code of Federal Regulations, 2010 CFR

2010-01-01

... costs, benefits, burdens, and reliability of alternative approaches to energy savings or production... factors including: The extent to which the State regulation will increase manufacturing or distribution...)(vii) of this section, and shall be available for public review, except for confidential or proprietary...

The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort.

PubMed

Rabelo, F Y; Jardim, L L; Landau, M B; Gadelha, T; Corrêa, M F B; Pereira, I F M; Rezende, S M

2015-09-01

Inherited factor VII (FVII) deficiency is the most common among the rare bleeding disorders. It is transmitted as an autosomal recessive inheritance, due to mutations in the FVII gene (F7). Molecular studies of FVII deficiency are rare in non-Caucasian populations. The aim of the study was to evaluate the molecular basis behind low levels of FVII activity (FVII:C) levels in a cohort of Brazilian patients. A total of 34 patients with low FVII levels were clinically evaluated and submitted to laboratory tests, among these, prothrombin time and FVII:C, with different thromboplastins. All exons and intron/exon boundaries of F7 were amplified and sequenced. A total of 14 genetic alterations were identified, of which six were described previously, c.1091G>A, c.1151C>T, c.-323_-313insCCTATATCCT, c.285G>A, c.525C>T, c.1238G>A and eight (54.0%) and eight were new, c.128G>A, c.252C>T, c.348G>A, c.417G>A, c.426G>A, c.745_747delGTG, c.843G>A and c.805+52C>T. In addition to the mutation c.1091G>A, known as FVII Padua, the mutation c.1151C>T also presented discrepant FVII:C levels when tested with human and rabbit brain thromboplastin. There was no association between phenotype and genotype. Most of the identified genetic alterations found were polymorphisms. Low levels of FVII:C in this population were mostly related to polymorphisms in F7 and associated with a mild clinical phenotype. Mutation c.1151C>T was associated with discrepant levels of FVII:C using different thromboplastins, such as reported with FVII Padua. © 2015 John Wiley & Sons Ltd.

Differences in N-glycosylation of recombinant human coagulation factor VII derived from BHK, CHO, and HEK293 cells.

PubMed

Böhm, Ernst; Seyfried, Birgit K; Dockal, Michael; Graninger, Michael; Hasslacher, Meinhard; Neurath, Marianne; Konetschny, Christian; Matthiessen, Peter; Mitterer, Artur; Scheiflinger, Friedrich

2015-09-18

BACKGROUND & Recombinant factor VII (rFVII), the precursor molecule for recombinant activated FVII (rFVIIa), is, due to its need for complex post translational modifications, produced in mammalian cells. To evaluate the suitability of a human cell line in order to produce rFVII with post-translational modifications as close as possible to pdFVII, we compared the biochemical properties of rFVII synthesized in human embryonic kidney-derived (HEK)293 cells (HEK293rFVII) with those of rFVII expressed in Chinese hamster ovary (CHO, CHOrFVII) and baby hamster kidney (BHK, BHKrFVII) cells, and also with those of plasma derived FVII (pdFVII), using various analytical methods. rFVII was purified from selected production clones derived from BHK, CHO, and HEK293 cells after stable transfection, and rFVII isolates were analyzed for protein activity, impurities and post-translational modifications. RESULTS & The analytical results showed no apparent gross differences between the various FVII proteins, except in their N-linked glycosylation pattern. Most N-glycans found on rFVII produced in HEK293 cells were not detected on rFVII from CHO and BHK cells, or, somewhat unexpectedly, on pdFVII; all other protein features were similar. HEK293rFVII glycans were mainly characterized by a higher structural variety and a lower degree of terminal sialylation, and a high amount of terminal N-acetyl galactosamines (GalNAc). All HEK293rFVII oligosaccharides contained one or more fucoses (Fuc), as well as hybrid and high mannose (Man) structures. From all rFVII isolates investigated, CHOrFVII contained the highest degree of sialylation and no terminal GalNAc, and CHO cells were therefore assumed to be the best option for the production of rFVII.

Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis

PubMed Central

Muders, Thomas; Theuerkauf, Nils; Spitzhüttl, Juliane; Schellhaas, Torsten; Schewe, Jens-Christian; Guenther, Ulf; Wrigge, Hermann; Putensen, Christian

2017-01-01

Background Despite being still invasive and challenging, technical improvement has resulted in broader and more frequent application of extracorporeal membrane oxygenation (ECMO), to prevent hypoxemia and to reduce invasiveness of mechanical ventilation (MV). Heparin-coated ECMO-circuits are currently standard of care, in addition to heparin based anticoagulation (AC) regimen guided by activated clotting time (ACT) or activated partial thromboplastin time (aPTT). Despite these advances, a reliable prediction of hemorrhage is difficult and the risk of hemorrhagic complication remains unfortunately high. We hypothesized, that there are coagulation parameters that are indices for a higher risk of hemorrhage under veno-venous (VV)-ECMO therapy. Methods Data from 36 patients with severe respiratory failure treated with VV-ECMO at a University Hospital intensive care unit (ICU) were analyzed retrospectively. Patients were separated into two groups based on severity of hemorrhagic complications and transfusion requirements. The following data were collected: demographics, hemodynamic data, coagulation samples, transfusion requirements, change of ECMO-circuit during treatment and adverse effects, including hemorrhage and thrombosis. Results In this study 74 hemorrhagic events were observed, one third of which were severe. Patients suffering from severe hemorrhage had a lower survival rate on VV-ECMO (43% vs. 91%; P=0.002) and in ICU (36% vs. 86%; P=0.002). SAPS II, factor VII and X were different between mild and severe hemorrhage group. Conclusions Severe hemorrhage under VV-ECMO is associated with higher mortality. Only factor VII and X differed between groups. Further clinical studies are required to determine the timing of initiation and targets for AC therapies during VV-ECMO. PMID:29312706

Recombinant activated factor VII: its mechanism of action and role in the control of hemorrhage.

PubMed

Allen, Geoffrey A; Hoffman, Maureane; Roberts, Harold R; Monroe, Dougald M

2002-12-01

Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa may also have indications for the treatment of bleeding in patients with other hemostatic disorders, including qualitative and quantitative platelet defects, factor deficiencies other than hemophilia, and in otherwise healthy patients with uncontrollable hemorrhage following surgery or trauma. We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings. A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage. Findings from our group and others have demonstrated that rFVIIa is able to directly activate factor X and increase thrombin production on the surface of activated platelets in the absence of factor VIII or IX, as well as to improve thrombin generation in thrombocytopenia, and to yield a fibrin dot more resistant to fibrinolysis in vitro. Through these primary mechanisms, we believe that rFVIIa may be able to compensate for a variety of defects in hemostasis and merits further investigation as a general therapeutic for uncontrollable hemorrhage.

Effects of porosity distribution and porosity volume fraction on the electromechanical properties of 3-3 piezoelectric foams

NASA Astrophysics Data System (ADS)

Nguyen, B. V.; Challagulla, K. S.; Venkatesh, T. A.; Hadjiloizi, D. A.; Georgiades, A. V.

2016-12-01

Unit-cell based finite element models are developed to completely characterize the role of porosity distribution and porosity volume fraction in determining the elastic, dielectric and piezoelectric properties as well as relevant figures of merit of 3-3 type piezoelectric foam structures. Eight classes of foam structures which represent structures with different types and degrees of uniformity of porosity distribution are identified; a Base structure (Class I), two H-type foam structures (Classes II, and III), a Cross-type foam structure (Class IV) and four Line-type foam structures (Classes V, VI, VII, and VIII). Three geometric factors that influence the electromechanical properties are identified: (i) the number of pores per face, pore size and the distance between the pores; (ii) pore orientation with respect to poling direction; (iii) the overall symmetry of the pore distribution with respect to the center of the face of the unit cell. To assess the suitability of these structures for such applications as hydrophones, bone implants, medical imaging and diagnostic devices, five figures of merit are determined via the developed finite element model; the piezoelectric coupling constant (K t ), the acoustic impedance (Z), the piezoelectric charge coefficient (d h ), the hydrostatic voltage coefficient (g h ), and the hydrostatic figure of merit (d h g h ). At high material volume fractions, foams with non-uniform Line-type porosity (Classes V and VII) where the pores are preferentially distributed perpendicular to poling direction, are found to exhibit the best combination of desirable piezoelectric figures of merit. For example, at about 50% volume fraction, the d h , g h , and d h g h figures of merit are 55%, 1600% and 2500% higher, respectively, for Classes V and VII of Line-like foam structures compared with the Base structure.

Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine

DTIC Science & Technology

2012-12-15

and its correction (or normalization of pH) has been suggested before clinical use of rFVIIa [21, 22]. FVII is one of the many coagulation factors ...A or B (deficient in Factor VIII and Factor IX). Mice lacking FVII die in-utero or soon after birth due to vascular and hemostatic defects [23...the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is not known if acidosis induced by hemorrhagic shock or infusion of

Phenotypic and genotypic characterization of four factor VII deficiency patients from central China.

PubMed

Liu, Hui; Wang, Hua-Fang; Cheng, Zhi-peng; Wang, Qing-yun; Hu, Bei; Zeng, Wei; Wu, Ying-ying; Guo, Tao; Tang, Liang; Hu, Yu

2015-06-01

Hereditary coagulation factor VII deficiency (FVIID) is a rare autosomal, recessive inherited hemorrhagic disorder related to a variety of mutations or polymorphisms throughout the factor VII (FVII) gene (F7). The aims of this study were to characterize the molecular defect of the F7 gene in four unrelated patients with FVIID and to find the genotype-phenotype correlation. All nine exons, exon-intron boundaries, and 5' and 3'-untranslated regions of the F7 gene were amplified by PCR and the purified PCR products were sequenced directly. Suspected mutations were confirmed by another PCR and sequencing of the opposite strand. Family studies were also performed. A total of five unique lesions were identified, including three missense mutations (c.384A>G, c.839A>C, c.1163T>G, predicting p.Tyr128Cys, p.Glu280Ala and p.Phe388Cys substitution, respectively) and two splice junction mutations (c.572-1G>A, c.681+1G>T), among which two (p.Glu280Ala, p.Phe388Cys) were novel. A previously reported mutation p.Tyr128Cys was seen in the homozygous state in two unrelated patients. The other two cases were both compound heterozygotes of a missense mutation and a splicing site mutation. Multiple sequence alignment using DNAMAN analysis showed that all the missense mutations were found in residues that highly conserved across species and vitamin K-dependent serine proteases. Online software Polyphen and SIFT were used to confirm the pathogenic of the missense mutation. p.Tyr128Cys seems to be a hotspot of the F7 gene in ethnic Han Chinese population.

Overexpression of Grain Amaranth (Amaranthus hypochondriacus) AhERF or AhDOF Transcription Factors in Arabidopsis thaliana Increases Water Deficit- and Salt-Stress Tolerance, Respectively, via Contrasting Stress-Amelioration Mechanisms

PubMed Central

Massange-Sánchez, Julio A.; Palmeros-Suárez, Paola A.; Espitia-Rangel, Eduardo; Rodríguez-Arévalo, Isaac; Sánchez-Segura, Lino; Martínez-Gallardo, Norma A.; Alatorre-Cobos, Fulgencio; Tiessen, Axel; Délano-Frier, John P.

2016-01-01

Two grain amaranth transcription factor (TF) genes were overexpressed in Arabidopsis plants. The first, coding for a group VII ethylene response factor TF (i.e., AhERF-VII) conferred tolerance to water-deficit stress (WS) in transgenic Arabidopsis without affecting vegetative or reproductive growth. A significantly lower water-loss rate in detached leaves coupled to a reduced stomatal opening in leaves of plants subjected to WS was associated with this trait. WS tolerance was also associated with an increased antioxidant enzyme activity and the accumulation of putative stress-related secondary metabolites. However, microarray and GO data did not indicate an obvious correlation between WS tolerance, stomatal closure, and abscisic acid (ABA)-related signaling. This scenario suggested that stomatal closure during WS in these plants involved ABA-independent mechanisms, possibly involving reactive oxygen species (ROS). WS tolerance may have also involved other protective processes, such as those employed for methyl glyoxal detoxification. The second, coding for a class A and cluster I DNA binding with one finger TF (i.e., AhDof-AI) provided salt-stress (SS) tolerance with no evident fitness penalties. The lack of an obvious development-related phenotype contrasted with microarray and GO data showing an enrichment of categories and genes related to developmental processes, particularly flowering. SS tolerance also correlated with increased superoxide dismutase activity but not with augmented stomatal closure. Additionally, microarray and GO data indicated that, contrary to AhERF-VII, SS tolerance conferred by AhDof-AI in Arabidopsis involved ABA-dependent and ABA-independent stress amelioration mechanisms. PMID:27749893

Compound heterozygous mutations (p.Leu13Pro and p.Tyr294*) associated with factor VII deficiency cause impaired secretion through ineffective translocation and extensive intracellular degradation of factor VII.

PubMed

Suzuki, Keijiro; Sugawara, Takeshi; Ishida, Yoji; Suwabe, Akira

2013-02-01

Congenital coagulation factor VII (FVII) deficiency is a rare coagulation disease. We investigated the molecular mechanisms of this FVII deficiency in a patient with compound heterozygous mutations. A 22-year-old Japanese female was diagnosed with asymptomatic FVII deficiency. The FVII activity and antigen were greatly reduced (activity, 13.0%; antigen, 10.8%). We analyzed the F7 gene of this patient and characterized mutant FVII proteins using in vitro expression studies. Sequence analysis revealed that the patient was compound heterozygous with a point mutation (p.Leu13Pro) in the central hydrophobic core of the signal peptides and a novel non-sense mutation (p.Tyr294*) in the catalytic domain. Expression studies revealed that mutant FVII with p.Leu13Pro (FVII13P) showed less accumulation in the cells (17.5%) and less secretion into the medium (64.8%) than wild type showed. Truncated FVII resulting from p.Tyr294* (FVII294X) was also decreased in the cells (32.0%), but was not secreted into the medium. Pulse-chase experiments revealed that both mutants were extensively degraded intracellularly compared to wild type. The majority of FVII13P cannot translocate into endoplasmic reticulum (ER). However, a small amount of FVII13P was processed normally with post-translational modifications and was secreted into the medium. The fact that FVII294X was observed only in ER suggests that it is retained in ER. Proteasome apparently plays a central role in these degradations. These findings demonstrate that both mutant FVIIs impaired secretion through ineffective translocation to and retention in ER with extensive intracellular degradation, resulting in an insufficient phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

Using a minigene approach to characterize a novel splice site mutation in human F7 gene causing inherited factor VII deficiency in a Chinese pedigree.

PubMed

Yu, T; Wang, X; Ding, Q; Fu, Q; Dai, J; Lu, Y; Xi, X; Wang, H

2009-11-01

Factor VII deficiency which transmitted as an autosomal recessive disorder is a rare haemorrhagic condition. The aim of this study was to identify the molecular genetic defect and determine its functional consequences in a Chinese pedigree with FVII deficiency. The proband was diagnosed as inherited coagulation FVII deficiency by reduced plasma levels of FVII activity (4.4%) and antigen (38.5%). All nine exons and their flanking sequence of F7 gene were amplified by polymerase chain reaction (PCR) for the proband and the PCR products were directly sequenced. The compound heterozygous mutations of F7 (NM_000131.3) c.572-1G>A and F7 (NM_000131.3) c.1165T>G; p.Cys389Gly were identified in the proband's F7 gene. To investigate the splicing patterns associated with F7 c.572-1G>A, ectopic transcripts in leucocytes of the proband were analyzed. F7 minigenes, spanning from intron 4 to intron 7 and carrying either an A or a G at position -1 of intron 5, were constructed and transiently transfected into human embryonic kidney (HEK) 293T cells, followed by RT-PCR analysis. The aberrant transcripts from the F7 c.572-1G>A mutant allele were not detected by ectopic transcription study. Sequencing of the RT-PCR products from the mutant transfectant demonstrated the production of an erroneously spliced mRNA with exon 6 skipping, whereas a normal splicing occurred in the wide type transfectant. The aberrant mRNA produced from the F7 c.572-1G>A mutant allele is responsible for the factor VII deficiency in this pedigree.

[Prophylactic use of a recombinant activated factor VII in delivery haemorrhage by caesarean in a woman with major factor VII deficiency: a case report].

PubMed

Comes, Jean-François; Devignes, Jean; Thiebaugeorges, Olivier; Briquel, Marie-Elisabeth; Lecompte, Thomas

2011-01-01

Taking in charge the delivery of pregnant women with inherited major deficiency of factor VII (FVII) is poorly reported in literature. We report here the haemorrhagic prophylaxis of delivery by recombinant activated FVII (rFVIIa) in a 27-year-old women, gravida 1, para 0, with major deficiency FVII by missense mutation (p.Arg337Cys). Her parents, first germen, presented a FVII deficiency. She has four brothers and three sisters, of which only one brother has major FVII deficiency with hemorrhagic diathesis in childhood (hematochezia). At her birth, because of dystocia, a right sterno-cleido-mastoid muscle hematoma and left clavicle fracture occurred. The FVII concentration was 0.08 U/mL. At the age of fifteen, a surgery of appendicitis was performed with substitution by FVII from plasma donors without any haemorrhagic complication. Because of anatomic specificity (bifid uterus and vagina), caesarean was planned. After reviewing of the literature, caesarean was performed at 38th week of gestation with haemorrhagic prophylaxis consisting in administration of rFVIIa (eptacog alfa) at a dose of 20 μg/kg, 30 min before surgery, then every 3 h during 48 h. No haemorrhagic complication occurred. Thrombosis prophylaxis was ensured by enoxaparin (4000 UI a day subcutaneously started 6 h after surgery for 5 days). Clinical examination of the newborn was normal. In future, modalities of taking in charge have to be evaluated by prospective studies involving a sufficiently numerous group of woman with FVII major deficiency, or by retrospective studies with the means of national or European registers.

Type VII Collagen is Enriched in the Enamel Organic Matrix Associated with the Dentin-Enamel Junction of Mature Human Teeth

PubMed Central

McGuire, Jacob D.; Walker, Mary P.; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P.

2014-01-01

The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of the enamel organic matrix at the dentin-enamel junction (DEJ) of mature human teeth. Immunofluorescent confocal microscopy of demineralized tooth sections localized type VII collagen to the organic matrix surrounding individual enamel rods near the DEJ. Morphologically, immunoreactive type VII collagen helical-bundles resembled the gnarled-pattern of enamel rods detected by Coomassie Blue staining. Western blotting of whole crown or enamel matrix extracts also identified characteristic Mr=280 and 230 kDa type VII dimeric forms, which resolved into 75 and 25 kDa bands upon reduction. As expected, the collagenous domain of type VII collagen was resistant to pepsin digestion, but was susceptible to purified bacterial collagenase. These results demonstrate the inner enamel organic matrix in mature teeth contains macromolecular type VII collagen. Based on its physical association with the DEJ and its well-appreciated capacity to complex with other collagens, we hypothesize that enamel embedded type VII collagen fibrils may contribute not only to the structural resilience of enamel, but may also play a role in bonding enamel to dentin. PMID:24594343

Learning from history: the legacy of Title VII in academic family medicine.

PubMed

Newton, Warren; Arndt, Jane E

2008-11-01

The current renaissance of interest in primary care could benefit from reviewing the history of federal investment in academic family medicine. The authors review 30 years of experience with the Title VII, Section 747 Training in Primary Care Medicine and Dentistry (Title VII) grant program, addressing three questions: (1) What Title VII grant programs were available to family medicine, and what were their goals? (2) How did Title VII change the discipline? and (3) What impact did Title VII family medicine programs have outside the discipline?Title VII grant programs evolved from broad support for the new discipline of family medicine to a sharper focus on specific national workforce objectives such as improving care for underserved and vulnerable populations and increasing diversity in the health professions. Grant programs were instrumental in establishing family medicine in nearly all medical schools and in supporting the educational underpinnings of the field. Title VII grants helped enhance the social capital of the discipline. Outside family medicine, Title VII fostered the development of innovative ambulatory education, institutional initiatives focusing on underserved and vulnerable populations, and primary care research capacity. Adverse effects include relative inattention to clinical and research missions in family medicine academic units and, institutionally, the development of medical education initiatives without core institutional support, which has put innovation and extension of education to communities at risk as grant funding has decreased. Reinvestment in academic family medicine can yield substantial benefits for family medicine and help reorient academic health centers. This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs.

Clinical evaluation of glass ionomer for pit and fissure sealing of fully erupted molars.

PubMed

Sly, Edith G; Kaplan, Andrea E; Missana, Liliana

2010-01-01

The aim of this study was to evaluate the clinical behavior of two conventional glass ionomers used for pit and fissure sealing in terms of retention, marginal adaptation, caries recurrence and cracking. Eighty-three fully erupted first permanent molars were sealed, in a group of children aged 5 to 8 years. A double-blind, single operator, paired design was used. Materials applied were Fuji IX and VII. Retention (R), presence of caries (PC), marginal discoloration (MD), marginal adaptation (MA) and cracking (C) were evaluated at 6 and 12 months using Ryge's criteria. Data registered 6 months after treatment were: Fuji IX: R: Alpha 37, Bravo 2, Charlie: 4; PC: Alpha 43, Bravo: 0; MA: Alpha 38, Bravo: 1; MD: Alpha 39, Bravo: 0, Charlie: 0; C: Alpha 39, Bravo: 0. Fuji VII: R: Alpha 29, Bravo 4, Charlie: 7; PC: Alpha 40, Bravo: 0; MA: Alpha: 34, Bravo: 0; MD: Alpha: 34, Bravo: 0, Charlie: 0; C: Alpha 33, Bravo: 0. Results after one year were: Fuji IX: R: Alpha 33, Bravo: 3, Charlie: 9; PC: Alpha 44, Bravo: 1; MA: Alpha 33, Bravo: 1; MD: Alpha: 34, Bravo: 0, Charlie: 0; C: Alpha: 34, Bravo: 0. Fuji VII: R: Alpha 22, Bravo 4, Charlie: 13, PC: Alpha 40, Bravo: 0; MA: Alpha 23, Bravo: 1; MD: Alpha 23, Bravo: 1, Charlie: 0; C: Alpha 23, Bravo: 1. Statistical analysis using Fisher test showed no significant difference (p > 0.05) for R, and MA. For PC, MD and C, values are not reported because both materials showed the same results. The second control showed no significant difference (p > 0.05) for R, MA, PC, MD and C. Results suggest no difference between Fuji IX and Fuji VII as sealants in fully erupted permanent molars.

Structural incorporation of MgCl2 into ice VII at room temperature

NASA Astrophysics Data System (ADS)

Watanabe, Mao; Komatsu, Kazuki; Noritake, Fumiya; Kagi, Hiroyuki

2017-05-01

Raman spectra and X-ray diffraction patterns were obtained from 1:100 and 1:200 \\text{MgCl}2:\\text{H}2\\text{O} solutions (in molar ratio) at pressures up to 6 GPa using diamond anvil cells (DACs) and compared with those of pure water. The O-H stretching band from ice VII crystallized from the 1:200 solution was approximately 10 cm-1 higher than that of pure ice VII. The phase boundaries between ice VII and VIII crystallized from the MgCl2 solutions at 4 GPa were 2 K lower than those of pure ice VII and VIII. These observations indicate that ice VII incorporates MgCl2 into its structure. The unit cell volumes of ice VII crystallized from pure water and the two solutions coincided with each other within the experimental error, and salt incorporation was not detectable from the cell volume. Possible configurations of ion substitution and excess volume of ice VIII were simulated on the basis of density functional theory (DFT) calculations.

Influence of the hydrogen bond quantum nature in liquid water and heavy water on stimulated Raman scattering

NASA Astrophysics Data System (ADS)

Li, Fabing; Li, Zhanlong; Li, Shuo; Fang, Wenhui; Sun, Chenglin; Men, Zhiwei

2018-06-01

Stimulated Raman scattering (SRS) of liquid water and heavy water have been investigated using Nd:YAG laser. The SRS spectra of liquid heavy water indicate that ice-VII and ice-VIII structures are formed by shock-induced compression (SIC) in forward and backward directions, respectively. Simultaneously, the SRS spectra reveal of liquid water that only ice-VII structure is formed in the backward direction. The difference in ice structures formed by SIC in liquid water and heavy water could be attributed to the effect of the hydrogen bond quantum nature with H+. SRS spectra of 2 M NaOH water solution with ice-VII and ice-VIII structures have been successfully obtained in forward and backward, respectively, as OH- greatly reduce the quantum nature of hydrogen bonds by neutralizing H+ in water. The hydrogen bond quantum nature is important for understanding isotope calibration test structure and isotopic effect.

The Politics of Affirmative Action.

ERIC Educational Resources Information Center

Walters, David

1982-01-01

Reviews legislation and labor policies which have discriminated historically against Blacks as a class and explains how Title VII of the Civil Rights Act of 1964 was intended to redress such generalized discrimination. Discusses political and economic factors that jeopardize already insufficient efforts to enforce equal employment opportunities…

Attrition of Hmong Students in Teacher Education Programs.

ERIC Educational Resources Information Center

Root, Steven; Rudawski, Anthony; Taylor, Matthew; Rochon, Ronald

2003-01-01

A descriptive study addressed student attrition in two Title VII Bilingual Education Career Ladder Programs for Hmong paraprofessionals and traditional-age college students working toward teacher certification in Wisconsin. Surveys showed that dropouts were disproportionately male and nontraditional students; factors included financial problems,…

ADVISORY ON UPDATED METHODOLOGY FOR ESTIMATING CANCER RISKS FROM EXPOSURE TO IONIZING RADIATION

EPA Science Inventory

The National Academy of Sciences (NAS) published the Biological Effects of Ionizing Radiation (BEIR) committee's report (BEIR VII) on risks from ionizing radiation exposures in 2006. The Committee analyzed the most recent epidemiology from the important exposed cohorts and factor...

Crew factors in flight operations VII : psychophysiological responses to overnight cargo operations

DOT National Transportation Integrated Search

1996-02-01

To document the psychophysiological effects of flying overnight cargo operations, 41 B-727 crew members (average age 38 yr) were monitored before, during, and after one of two typical 8-day trip patterns. During daytime layovers, the average sleep ep...

48 CFR 13.106-3 - Award and documentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Supporting the award decision if other than price-related factors were considered in selecting the supplier...) Comparison of the proposed price with prices found reasonable on previous purchases; (iii) Current price... being purchased; (vi) Comparison to an independent Government estimate; or (vii) Any other reasonable...

Chronic sleep deprivation markedly reduces coagulation factor VII expression

PubMed Central

Pinotti, Mirko; Bertolucci, Cristiano; Frigato, Elena; Branchini, Alessio; Cavallari, Nicola; Baba, Kenkichi; Contreras-Alcantara, Susana; Ehlen, J. Christopher; Bernardi, Francesco; Paul, Ketema N.; Tosini, Gianluca

2010-01-01

Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (−30.5%) the thrombin generation potential in plasma evaluated upon extrinsic (TF/FVIIa pathway) but not intrinsic activation of coagulation. This variation was consistent with a decrease (−49.8%) in the plasma activity levels of factor VII (FVII), the crucial physiologicalal trigger of coagulation, which was even more pronounced at the liver mRNA level (−85.7%). The recovery in normal sleep conditions for three days completely restored thrombin generation and FVII activity in plasma. For the first time, we demonstrate that chronic sleep deprivation on its own reduces, in a reversible manner, the FVII expression levels, thus influencing the TF/FVIIa activation pathway efficiency. PMID:20418241

The effect of recombinant activated factor VII in the treatment of intracerebral hemorrhage on health plan budgets.

PubMed

Earnshaw, Stephanie R; Wilson, Michele R; Joshi, Ashish V

2006-11-01

Treating patients with intracerebral hemorrhage (ICH) using recombinant activated factor VII (rFVIla) has been found to improve survival and functional outcome. To examine how the introduction of rFVIla 80 microg/kg as a treatment for ICH affects the budget of a health plan, a decision-analysis model was developed which considered both short-term hospitalization costs and long-term management of disability. Assuming a health plan enrollment of 1 million members and initial rFVIla uptake of 50% in appropriate patients, the annual health plan cost may be expected to increase by dollar 64,781 (dollar 0.005 per-member per-month). With a 5% increase in uptake each year, the annual health plan's cost may decrease compared with the current budget within three years. The implications for this sample health plan's budget are modest in the first year, and a reduction in costs is expected within three years owing to improved functional outcomes of patients.

20 CFR 1002.198 - What efforts must the employer make to help the employee become qualified for the reemployment...

Code of Federal Regulations, 2010 CFR

2010-04-01

... position does not make him or her unqualified. (2) Whether a task is essential depends on several factors, and these factors include but are not limited to: (i) The employer's judgment as to which functions... experience of past incumbents in the job; and/or (vii) The current work experience of incumbents in similar...

Evolving Service Roles in Presence Missions,

DTIC Science & Technology

1995-08-01

Service chronology of discrete presence incidents for the period from the beginning of the end of the Cold War (1983) through late 1994. Six detailed...Discussion Vi-8 VI VII. OBSERVATIONS AND RECOMMENDATIONS VII-1 A. Observations VII-1 B. Recommendations VII-2 APPENDICES A. Chronology of...great value in improving understanding between nations, it also seems extremely unlikely that such activities could substitute for well- trained

Effect of Recombinant FVIIA in Hypothermic, Coagulopathic Pigs with Liver Injuries

DTIC Science & Technology

2005-04-01

1󈨊 190 210 230 250 Time (min) United States Army Institute of Surgical Research 33 FIG 5A. Activated Factor FVII (FVIIa) in pig plasma--as measured by...8217X18)F 18) Pre-Dilution Basal Post-Dilution Basal Experimental stage with reference to liver injury FIG 5B. Activated Factor FVII (rFVIIa...the drug, rcombinant activated Factor VII (rFVIIa) on survival, survival time, blood loss, and disseminated intravascular coagulation (DIC) in

Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs

PubMed Central

Peck, Sun H.; O'Donnell, Philip J.M.; Kang, Jennifer L.; Malhotra, Neil R.; Dodge, George R.; Pacifici, Maurizio; Shore, Eileen M.; Haskins, Mark E.; Smith, Lachlan J.

2015-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients. PMID:26422116

Aromaticity Parameters in Asphalt Binders Calculated From Profile Fitting X-ray Line Spectra Using Pearson VII and Pseudo-Voigt Functions

NASA Astrophysics Data System (ADS)

Shirokoff, J.; Lewis, J. Courtenay

2010-10-01

The aromaticity and crystallite parameters in asphalt binders are calculated from data obtained after profile fitting x-ray line spectra using Pearson VII and pseudo-Voigt functions. The results are presented and discussed in terms of the peak profile fit parameters used, peak deconvolution procedure, and differences in calculated values that can arise owing to peak shape and additional peaks present in the pattern. These results have implications concerning the evaluation and performance of asphalt binders used in highways and road applications.

Type VII collagen is enriched in the enamel organic matrix associated with the dentin-enamel junction of mature human teeth.

PubMed

McGuire, Jacob D; Walker, Mary P; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P

2014-06-01

The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of the enamel organic matrix at the dentin-enamel junction (DEJ) of mature human teeth. Immunofluorescent confocal microscopy of demineralized tooth sections localized type VII collagen to the organic matrix surrounding individual enamel rods near the DEJ. Morphologically, immunoreactive type VII collagen helical-bundles resembled the gnarled-pattern of enamel rods detected by Coomassie Blue staining. Western blotting of whole crown or enamel matrix extracts also identified characteristic Mr=280 and 230 kDa type VII dimeric forms, which resolved into 75 and 25 kDa bands upon reduction. As expected, the collagenous domain of type VII collagen was resistant to pepsin digestion, but was susceptible to purified bacterial collagenase. These results demonstrate the inner enamel organic matrix in mature teeth contains macromolecular type VII collagen. Based on its physical association with the DEJ and its well-appreciated capacity to complex with other collagens, we hypothesize that enamel embedded type VII collagen fibrils may contribute not only to the structural resilience of enamel, but may also play a role in bonding enamel to dentin. Copyright © 2014 Elsevier Inc. All rights reserved.

Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII

PubMed Central

Smith, Lachlan J; Baldo, Guilherme; Wu, Susan; Liu, Yuli; Whyte, Michael P; Giugliani, Roberto; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

2012-01-01

Mucopolysaccharidosis type VII (MPS VII) is characterized by deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan and dermatan sulfate glycosaminoglycans (GAGs), and multisystemic disease. MPS VII patients can develop kypho-scoliotic deformity and spinal cord compression due to disease of intervertebral discs, vertebral bodies, and associated tissues. We have previously demonstrated in MPS VII dogs that intervertebral discs degenerate, vertebral bodies have irregular surfaces, and vertebral body epiphyses have reduced calcification, but the pathophysiological mechanisms underlying these changes are unclear. We hypothesized that some of these manifestations could be due to upregulation of destructive proteases, possibly via the binding of GAGs to Toll-like receptor 4 (TLR4), as has been proposed for other tissues in MPS models. In this study, the annulus fibrosus of the intervertebral disc of 6 month-old MPS VII dogs had cathepsin B and K activities that were 117- and 2-fold normal, respectively, which were associated with elevations in mRNA levels for cathepsins as well as TLR4. The epiphyses of MPS VII dogs had a marked elevation in mRNA for the cartilage-associated gene collagen II, consistent with a developmental delay in the conversion of the cartilage to bone in this region. A spine from a human patient with MPS VII exhibited similar increased cartilage in the vertebral bodies adjacent to the end plates, disorganization of the intervertebral discs, and irregular vertebral end plate morphology. These data suggest that the pathogenesis of destructive changes in the spine in MPS VII may involve upregulation of cathepsins. Inhibition of destructive proteases, such as cathepsins, might reduce spine disease in patients with MPS VII or related disorders. PMID:22513347

Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients

PubMed Central

Woodley, David T.; Cogan, Jon; Hou, Yingping; Lyu, Chao; Marinkovich, M. Peter; Keene, Douglas

2017-01-01

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. METHODS. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. RESULTS. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti–type VII collagen autoantibodies in patients’ blood or skin. CONCLUSION. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. TRIAL REGISTRATION. ClinicalTrials.gov NCT02698735. FUNDING. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH, and VA Merit Award. PMID:28691931

An evaluation of microleakage of various glass ionomer based restorative materials in deciduous and permanent teeth: An in vitro study

PubMed Central

Singla, Teena; Pandit, I.K.; Srivastava, Nikhil; Gugnani, Neeraj; Gupta, Monika

2011-01-01

Aim To evaluate the microleakage of recently available glass ionomer based restorative materials (GC Fuji IX GP, GC Fuji VII, and Dyract) and compare their microleakage with the previously existing glass ionomer restorative materials (GC Fuji II LC) in primary and permanent teeth. Method One hundred and fifty (75 + 75) non-carious deciduous and permanent teeth were restored with glass ionomer based restorative materials after making class I cavities. Samples were subjected to thermocycling after storing in distilled water for 24 h. Two coats of nail polish were applied 1 mm short of restorative margins and samples sectioned buccolingually after storing in methylene blue dye for 24 h. Microleakage was assessed using stereomicroscope. Result Significant differences (P < 0.05) were found when inter group comparisons were done. Except when GC Fuji VII (Group III) was compared with GC Fuji II LC (Group II) and Dyract (Group IV), non-significant differences (P > 0.05) were observed. It was found that there was no statistically significant difference when the means of microleakage of primary teeth were compared with those of permanent teeth. Conclusions GC Fuji IX GP showed maximum microleakage and GC Fuji VII showed least microleakage. PMID:23960526

40 CFR 63.1367 - Recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...), records of consumption, production, and the rolling average values of the HAP and VOC factors. (3) For... Standards for Hazardous Air Pollutants for Pesticide Active Ingredient Production § 63.1367 Recordkeeping...)(i) through (vii) of this section to document that HAP emissions or HAP loadings (for wastewater) are...

(99)Tc(VII) Retardation, Reduction, and Redox Rate Scaling in Naturally Reduced Sediments.

PubMed

Liu, Yuanyuan; Liu, Chongxuan; Kukkadapu, Ravi K; McKinley, James P; Zachara, John; Plymale, Andrew E; Miller, Micah D; Varga, Tamas; Resch, Charles T

2015-11-17

An experimental and modeling study was conducted to investigate pertechnetate (Tc(VII)O4(-)) retardation, reduction, and rate scaling in three sediments from Ringold formation at U.S. Department of Energy's Hanford site, where (99)Tc is a major contaminant in groundwater. Tc(VII) was reduced in all the sediments in both batch reactors and diffusion columns, with a faster rate in a sediment containing a higher concentration of HCl-extractable Fe(II). Tc(VII) migration in the diffusion columns was reductively retarded with retardation degrees correlated with Tc(VII) reduction rates. The reduction rates were faster in the diffusion columns than those in the batch reactors, apparently influenced by the spatial distribution of redox-reactive minerals along transport paths that supplied Tc(VII). X-ray computed tomography and autoradiography were performed to identify the spatial locations of Tc(VII) reduction and transport paths in the sediments, and results generally confirmed the newly found behavior of reaction rate changes from batch to column. The results from this study implied that Tc(VII) migration can be reductively retarded at Hanford site with a retardation degree dependent on reactive Fe(II) content and its distribution in sediments. This study also demonstrated that an effective reaction rate may be faster in transport systems than that in well-mixed reactors.

A Novel GUSB Mutation in Brazilian Terriers with Severe Skeletal Abnormalities Defines the Disease as Mucopolysaccharidosis VII

PubMed Central

Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Kallio, Heli; Snellman, Marjatta; Sainio, Kirsi; Lohi, Hannes

2012-01-01

Hundreds of different human skeletal disorders have been characterized at molecular level and a growing number of resembling dysplasias with orthologous genetic defects are being reported in dogs. This study describes a novel genetic defect in the Brazilian Terrier breed causing a congenital skeletal dysplasia. Affected puppies presented severe skeletal deformities observable within the first month of life. Clinical characterization using radiographic and histological methods identified delayed ossification and spondyloepiphyseal dysplasia. Pedigree analysis suggested an autosomal recessive disorder, and we performed a genome-wide association study to map the disease locus using Illumina’s 22K SNP chip arrays in seven cases and eleven controls. A single association was observed near the centromeric end of chromosome 6 with a genome-wide significance after permutation (pgenome  = 0.033). The affected dogs shared a 13-Mb homozygous region including over 200 genes. A targeted next-generation sequencing of the entire locus revealed a fully segregating missense mutation (c.866C>T) causing a pathogenic p.P289L change in a conserved functional domain of β-glucuronidase (GUSB). The mutation was confirmed in a population of 202 Brazilian terriers (p = 7,71×10−29). GUSB defects cause mucopolysaccharidosis VII (MPS VII) in several species and define the skeletal syndrome in Brazilian Terriers. Our results provide new information about the correlation of the GUSB genotype to phenotype and establish a novel canine model for MPS VII. Currently, MPS VII lacks an efficient treatment and this model could be utilized for the development and validation of therapeutic methods for better treatment of MPS VII patients. Finally, since almost one third of the Brazilian terrier population carries the mutation, breeders will benefit from a genetic test to eradicate the detrimental disease from the breed. PMID:22815736

Production of MPS VII mouse (Gustm(hE540A·mE536A)Sly) doubly tolerant to human and mouse β-glucuronidase

PubMed Central

Tomatsu, Shunji; Orii, Koji O.; Vogler, Carole; Grubb, Jeffrey H.; Snella, Elizabeth M.; Gutierrez, Monica; Dieter, Tatiana; Holden, Christopher C.; Sukegawa, Kazuko; Orii, Tadao; Kondo, Naomi; Sly, William S.

2006-01-01

Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an autosomal recessive lysosomal storage disease caused by β-glucuronidase (GUS) deficiency. A naturally occurring mouse model of that disease has been very useful for studying experimental approaches to therapy. However, immune responses can complicate evaluation of the long-term benefits of enzyme replacement or gene therapy delivered to adult MPS VII mice. To make this model useful for studying the long-term effectiveness and side effects of experimental therapies delivered to adult mice, we developed a new MPS VII mouse model, which is tolerant to both human and murine GUS. To achieve this, we used homologous recombination to introduce simultaneously a human cDNA transgene expressing inactive human GUS into intron 9 of the murine Gus gene and a targeted active site mutation (E536A) into the adjacent exon 10. When the heterozygote products of germline transmission were bred to homozygosity, the homozygous mice expressed no GUS enzyme activity but expressed inactive human GUS protein highly and were tolerant to immune challenge with human enzyme. Expression of the mutant murine Gus gene was reduced to about 10% of normal levels, but the inactive murine GUS enzyme also conferred tolerance to murine GUS. This MPS VII mouse model should be useful to evaluate therapeutic responses in adult mice receiving repetitive doses of enzyme or mice receiving gene therapy as adults. Heterozygotes expressed only 9.5–26% of wild-type levels of murine GUS instead of the expected 50%, indicating a dominant-negative effect of the mutant enzyme monomers on the activity of GUS tetramers in different tissues. Corrective gene therapy in this model should provide high enough levels of expression of normal GUS monomers to overcome the dominant negative effect of mutant monomers on newly synthesized GUS tetramers in most tissues. PMID:12700165

Heptavalent Actinide Tetroxides NpO 4 – and PuO 4 –: Oxidation of Pu(V) to Pu(VII) by Adding an Electron to PuO 4

DOE PAGES

Gibson, John K.; de Jong, Wibe A.; Dau, Phuong D.; ...

2017-11-14

The highest known actinide oxidation states are Np(VII) and Pu(VII), both of which have been identified in solution and solid compounds. Recently a molecular Np(VII) complex, NpO 3(NO 3) 2-, was prepared and characterized in the gas phase. In accord with the lower stability of heptavalent Pu, no Pu(VII) molecular species has been identified. Reported here are the gas-phase syntheses and characterizations of NpO 4 - and PuO 4 -. Reactivity studies and density functional theory computations indicate the heptavalent metal oxidation state in both. This is the first instance of Pu(VII) in the absence of stabilizing effects due tomore » condensed phase solvation or crystal fields. Here, the results indicate that addition of an electron to neutral PuO 4, which has a computed electron affinity of 2.56 eV, counterintuitively results in oxidation of Pu(V) to Pu(VII), concomitant with superoxide reduction.« less

Heptavalent Actinide Tetroxides NpO 4 – and PuO 4 –: Oxidation of Pu(V) to Pu(VII) by Adding an Electron to PuO 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gibson, John K.; de Jong, Wibe A.; Dau, Phuong D.

The highest known actinide oxidation states are Np(VII) and Pu(VII), both of which have been identified in solution and solid compounds. Recently a molecular Np(VII) complex, NpO 3(NO 3) 2-, was prepared and characterized in the gas phase. In accord with the lower stability of heptavalent Pu, no Pu(VII) molecular species has been identified. Reported here are the gas-phase syntheses and characterizations of NpO 4 - and PuO 4 -. Reactivity studies and density functional theory computations indicate the heptavalent metal oxidation state in both. This is the first instance of Pu(VII) in the absence of stabilizing effects due tomore » condensed phase solvation or crystal fields. Here, the results indicate that addition of an electron to neutral PuO 4, which has a computed electron affinity of 2.56 eV, counterintuitively results in oxidation of Pu(V) to Pu(VII), concomitant with superoxide reduction.« less

Synergetic Action of Domain II and IV Underlies Persistent Current Generation in Nav1.3 as revealed by a tarantula toxin

PubMed Central

Tang, Cheng; Zhou, Xi; Zhang, Yunxiao; xiao, Zhaohua; Hu, Zhaotun; Zhang, Changxin; Huang, Ying; Chen, Bo; Liu, Zhonghua; Liang, Songping

2015-01-01

The persistent current (INaP) through voltage-gated sodium channels enhances neuronal excitability by causing prolonged depolarization of membranes. Nav1.3 intrinsically generates a small INaP, although the mechanism underlying its generation remains unclear. In this study, the involvement of the four domains of Nav1.3 in INaP generation was investigated using the tarantula toxin α-hexatoxin-MrVII (RTX-VII). RTX-VII activated Nav1.3 and induced a large INaP. A pre-activated state binding model was proposed to explain the kinetics of toxin-channel interaction. Of the four domains of Nav1.3, both domain II and IV might play important roles in the toxin-induced INaP. Domain IV constructed the binding site for RTX-VII, while domain II might not participate in interacting with RTX-VII but could determine the efficacy of RTX-VII. Our results based on the use of RTX-VII as a probe suggest that domain II and IV cooperatively contribute to the generation of INaP in Nav1.3. PMID:25784299

Antimicrobial peptide scolopendrasin VII, derived from the centipede Scolopendra subspinipes mutilans, stimulates macrophage chemotaxis via formyl peptide receptor 1

PubMed Central

Park, Yoo Jung; Lee, Ha Young; Jung, Young Su; Park, Joon Seong; Hwang, Jae Sam; Bae, Yoe-Sik

2015-01-01

In this study, we report that one of the antimicrobial peptides scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates actin polymerization and the subsequent chemotactic migration of macrophages through the activation of ERK and protein kinase B (Akt) activity. The scolopendrasin VII-induced chemotactic migration of macrophages is inhibited by the formyl peptide receptor 1 (FPR1) antagonist cyclosporine H. We also found that scolopendrasin VII stimulate the chemotactic migration of FPR1-transfected RBL-2H3 cells, but not that of vector-transfected cells; moreover, scolopendrasin VII directly binds to FPR1. Our findings therefore suggest that the antimicrobial peptide scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates macrophages, resulting in chemotactic migration via FPR1 signaling, and the peptide can be useful in the study of FPR1-related biological responses. [BMB Reports 2015; 48(8): 479-484] PMID:26129676

U.S. Army Medical Department Journal, July-September 2004

DTIC Science & Technology

2004-09-01

on the surface of intestinal, lung, and brain cells. The TF protein then converts FVII into an activated form. Activated factor VII then combines...and FIX, which limits generation of thrombin. Platelets are able to increase production of thrombin when increased FVIIa is present. Normally FVII ...hemorrhage in severe neonatal FVII deficiency. Hemophilia. 2000; 6: 50-54. 12. Gilchrist J. Use of recombinant factor VIIa to treat a severe

Sequence and Expression Analyses of Ethylene Response Factors Highly Expressed in Latex Cells from Hevea brasiliensis

PubMed Central

Piyatrakul, Piyanuch; Yang, Meng; Putranto, Riza-Arief; Pirrello, Julien; Dessailly, Florence; Hu, Songnian; Summo, Marilyne; Theeravatanasuk, Kannikar; Leclercq, Julie; Kuswanhadi; Montoro, Pascal

2014-01-01

The AP2/ERF superfamily encodes transcription factors that play a key role in plant development and responses to abiotic and biotic stress. In Hevea brasiliensis, ERF genes have been identified by RNA sequencing. This study set out to validate the number of HbERF genes, and identify ERF genes involved in the regulation of latex cell metabolism. A comprehensive Hevea transcriptome was improved using additional RNA reads from reproductive tissues. Newly assembled contigs were annotated in the Gene Ontology database and were assigned to 3 main categories. The AP2/ERF superfamily is the third most represented compared with other transcription factor families. A comparison with genomic scaffolds led to an estimation of 114 AP2/ERF genes and 1 soloist in Hevea brasiliensis. Based on a phylogenetic analysis, functions were predicted for 26 HbERF genes. A relative transcript abundance analysis was performed by real-time RT-PCR in various tissues. Transcripts of ERFs from group I and VIII were very abundant in all tissues while those of group VII were highly accumulated in latex cells. Seven of the thirty-five ERF expression marker genes were highly expressed in latex. Subcellular localization and transactivation analyses suggested that HbERF-VII candidate genes encoded functional transcription factors. PMID:24971876

Sequence and expression analyses of ethylene response factors highly expressed in latex cells from Hevea brasiliensis.

PubMed

Piyatrakul, Piyanuch; Yang, Meng; Putranto, Riza-Arief; Pirrello, Julien; Dessailly, Florence; Hu, Songnian; Summo, Marilyne; Theeravatanasuk, Kannikar; Leclercq, Julie; Kuswanhadi; Montoro, Pascal

2014-01-01

The AP2/ERF superfamily encodes transcription factors that play a key role in plant development and responses to abiotic and biotic stress. In Hevea brasiliensis, ERF genes have been identified by RNA sequencing. This study set out to validate the number of HbERF genes, and identify ERF genes involved in the regulation of latex cell metabolism. A comprehensive Hevea transcriptome was improved using additional RNA reads from reproductive tissues. Newly assembled contigs were annotated in the Gene Ontology database and were assigned to 3 main categories. The AP2/ERF superfamily is the third most represented compared with other transcription factor families. A comparison with genomic scaffolds led to an estimation of 114 AP2/ERF genes and 1 soloist in Hevea brasiliensis. Based on a phylogenetic analysis, functions were predicted for 26 HbERF genes. A relative transcript abundance analysis was performed by real-time RT-PCR in various tissues. Transcripts of ERFs from group I and VIII were very abundant in all tissues while those of group VII were highly accumulated in latex cells. Seven of the thirty-five ERF expression marker genes were highly expressed in latex. Subcellular localization and transactivation analyses suggested that HbERF-VII candidate genes encoded functional transcription factors.

Determinants of drug costs in hopitalised patients with haemophilia: impact of recombinant activated factor VII.

PubMed

Galanaud, Jean Philippe; Pelletier-Fleury, Nathalie; Logerot-Lebrun, Hélène; Lambert, Thierry

2003-01-01

To analyse the determinants of anti-haemophilic drug costs in hospitalised patients with haemophilia and to estimate the impact of recombinant activated factor VII (rFVIIa) therapy on this expenditure. The perspective of the study was from the viewpoint of the hospital. A prospective study was carried out. All patients with haemophilia who were hospitalised in 1999 in Bicêtre public hospital, Paris, France were included in the cohort. For each of the 96 patients (154 hospital stays), we estimated the costs of anti-haemophilic drugs (coagulation concentrates) used. Costs were then stratified by different variables (severity of the disease, presence of a circulating inhibitor to coagulation factors, etc.) and a multivariate model was developed to determine the relationship between these variables and total anti-haemophilic drug costs, while controlling for potential confounders. Our study revealed: (i) the independent role of the five following variables in contributing to high anti-haemophilic drug expenditure: presence of a circulating inhibitor to coagulation factors, odds ratio (OR) = 16.9 (95% CI: 4.3-66); severity of the disease (factor VIII or factor IX < or =0.01 IU/mL), OR = 3.7 (95% CI: 1.6-8.6); length of hospital stay >4 days, OR = 8 (95% CI: 2.2-29.4); age >18 years old, OR = 6.2 (95% CI: 1.6-24.5); and surgical reasons for hospitalisation (whether surgery was haemophilia related [OR = 35.7 (95% CI: 7.3-175)] or not [OR = 5.4 (95% CI: 1.3-22.5)]); (ii) the large share that rFVIIa represented in this expenditure on medicines: rFVIIa was used in 20.1% of hospital stays and accounted for 56.2% of the total anti-haemophilic drug costs, which were estimated at 4,384,732 Euros (2000 values). Our data underline the heavy cost of the treatment of haemophilic patients with an inhibitor to coagulation factors. But, to the question of whether the high expenditure linked to rFVIIa utilisation will be balanced out by later benefits, it is not yet possible to reply with any certainty; further cost-benefit evaluation should be carried out.

Effect of neonatal gene therapy on lumbar spine disease in mucopolysaccharidosis VII dogs

PubMed Central

Smith, Lachlan J; Martin, John T; O'Donnell, Patricia; Wang, Ping; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

2012-01-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan, and dermatan sulfate glycosaminoglycans in various tissues including those of the spine. Associated spine disease can be due to abnormalities in the vertebrae, the intervertebral discs, or other spine tissues. The goal of this study was to determine if neonatal gene therapy could prevent lumbar spine disease in MPS VII dogs. MPS VII dogs were injected intravenously with a retroviral vector (RV) expressing canine GUSB at 2 to 3 days after birth, which resulted in transduction of hepatocytes that secreted GUSB into blood. Expression was stable for up to 11 years, and mean survival was increased from 0.4 years in untreated dogs to 6.1 years in treated dogs. Despite a profound positive clinical effect, 6-month-old RV-treated MPS VII dogs still had hypoplastic ventral epiphyses with reduced calcification in the lumbar spine, which resulted in a reduced stiffness and increased range of motion that was not improved relative to untreated MPS VII dogs. At six to 11 years of age, ventral vertebrae remained hypoplastic in RV-treated MPS VII dogs, and there was desiccation of the nucleus pulposus in some discs. Histochemical staining demonstrated that discs did not have detectable GUSB activity despite high serum GUSB activity, which is likely due to poor diffusion into this relatively avascular structure. Thus, neonatal gene therapy cannot prevent lumbar spine disease in MPS VII dogs, which predicts that enzyme replacement therapy (ERT) will similarly be relatively ineffective even if started at birth. PMID:22510705

[Establishment of nude mouse model with ovarian carcinomaand the effect of Paris Phyllin VII combined with silica nano complex on the inhibition and the antioxidant ability of ovarian carcinoma in nude mice].

PubMed

Chen, Jun; Wang, Bihang; Zhang, Jialing; Yang, Ruiqi; Fan, Limei

2015-08-04

To establish the research model of ovarian carcinoma in nude mice, and to explore the effect of Paris Phyllin VII combined with silica nano complex on the inhibition and the antioxidant ability of ovarian carcinoma in nude mice. Nude mice models with ovarian carcinoma were established by axillary subcutaneous inoculation of human SKOV3/DDP resistant ovarian cancer cell 200 µl and were used in the experiment. Treating the nude mice with Paris Phyllin VII combined with silica nano complex by gavage for 15 days to observe the weight change of the nude mice, tumor inhibition effect and changes of serum antioxidant capacity. Compared with the negative control group, tumor inhibition rate increased significantly in Paris Phyllin VII combined with silica nano complex treatment group, and was higher than that in both Paris Phyllin VII treatment only and silica nano composites treatment only group. The serum superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) level of Paris Phyllin VII combined with silica nano complex treatment group was significantly higher than that of control group, Paris Phyllin VII treatment only and silica nano composites treatment only group. The serum malonaldehyde (MDA) level of Paris Phyllin VII combined with silica nano complex treatment group was significantly lower than that of the negative control group. Paris Phyllin VII combined with silica nano complex treatment can inhibit the ovarian carcinoma in nude mice, which may mediate by the enhancement of antioxidant capability in nude mice with ovarian cancer.

Effects of In Vitro Hemodilution, Hypothermia and rFVIIa Addition on Coagulation in Human Blood

DTIC Science & Technology

2012-03-30

primary fluids used by many trauma units and the US Army for pre-hospital resuscitation [17]. HX, a hetastarch-based product in a balanced electro...and has been associated with dilution of coagulation factors and hypothermia. Recombinant activated Factor VII (rFVIIa) has been used, often as a...of rFVIIa results in an enhancement of thrombin generation on the platelet surface at the site of injury independent of the presence of Factor VIII

A Search for Factors Causing Training Costs to Rise by Examining the U. S. Navy’s AT, AW, and AX Ratings during their First Enlistment Period

DTIC Science & Technology

1986-09-01

HYPOTHESIS TEST .................... 20 III. TIME TO GET RATED TWO FACTOR ANOVA RESULTS ......... 23 IV. TIME TO GET RATED TUKEY’S PAIRED COvfl’PARISON... TEST RESULTS A ............................................ 24 V. TIME TO GET RATED TUKEY’S PAIRED COMPARISON TEST RESULTS B...25 VI. SINGLE FACTOR ANOVA HYPOTHESIS TEST #I............... 27 VII. AT: TIME TO GET RATED ANOVA TEST RESULTS ............. 30

Influence of blood lipids on global coagulation test results.

PubMed

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung

2015-01-01

High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

Influence of Blood Lipids on Global Coagulation Test Results

PubMed Central

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon

2015-01-01

Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). Results The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. Conclusion High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels. PMID:25553275

30 CFR 250.916 - What are the CVA's primary duties during the design phase?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Stress analyses; (vi) Material designations; (vii) Soil and foundation conditions; (viii) Safety factors... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Platforms and... pipeline risers, and riser tensioning systems; (ii) Turrets and turret-and-hull interfaces; (iii...

Early Science with the Large Millimeter Telescope: discovery of the 12CO(1-0) emission line in the ring galaxy VIIZw466

NASA Astrophysics Data System (ADS)

Wong, O. Ivy; Vega, O.; Sánchez-Argüelles, D.; Narayanan, G.; Wall, W. F.; Zwaan, M. A.; Rosa González, D.; Zeballos, M.; Bekki, K.; Mayya, Y. D.; Montaña, A.; Chung, A.

2017-04-01

We report an early science discovery of the 12CO(1-0) emission line in the collisional ring galaxy VII Zw466, using the Redshift Search Receiver instrument on the Large Millimeter Telescope Alfonso Serrano. The apparent molecular-to-atomic gas ratio either places the interstellar medium (ISM) of VII Zw466 in the H I-dominated regime or implies a large quantity of CO-dark molecular gas, given its high star formation rate. The molecular gas densities and star formation rate densities of VII Zw466 are consistent with the standard Kennicutt-Schmidt star formation law even though we find this galaxy to be H2-deficient. The choice of CO-to-H2 conversion factors cannot explain the apparent H2 deficiency in its entirety. Hence, we find that the collisional ring galaxy, VII Zw466, is either largely deficient in both H2 and H I or contains a large mass of CO-dark gas. A low molecular gas fraction could be due to the enhancement of feedback processes from previous episodes of star formation as a result of the star-forming ISM being confined to the ring. We conclude that collisional ring galaxy formation is an extreme form of galaxy interaction that triggers a strong galactic-wide burst of star formation that may provide immediate negative feedback towards subsequent episodes of star formation - resulting in a short-lived star formation history or, at least, the appearance of a molecular gas deficit.

Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

PubMed

de Moerloose, P; Schved, J-F; Nugent, D

2016-07-01

Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

Gene disruption reveals a dispensable role for plasmepsin VII in the Plasmodium berghei life cycle.

PubMed

Mastan, Babu S; Kumari, Anchala; Gupta, Dinesh; Mishra, Satish; Kumar, Kota Arun

2014-06-01

Plasmepsins (PM), aspartic proteases of Plasmodium, comprises a family of ten proteins that perform critical functions in Plasmodium life cycle. Except VII and VIII, functions of the remaining plasmepsin members have been well characterized. Here, we have generated a mutant parasite lacking PM VII in Plasmodium berghei using reverse genetics approach. Systematic comparison of growth kinetics and infection in both mosquito and vertebrate host revealed that PM VII depleted mutants exhibited no defects in development and progressed normally throughout the parasite life cycle. These studies suggest a dispensable role for PM VII in Plasmodium berghei life cycle. Copyright © 2014 Elsevier B.V. All rights reserved.

National Waterways Study. Waterway Science and Technology.

DTIC Science & Technology

1981-08-01

Revetments 278 VII-A Split Hull Type Trailing Suction Hopper Dredge 304 VII-B Drag Heads 306 VII-C Overflow Systems 307 VII-D Trailing Suction Hopper... head reversals are possible. Poor approach conditions currently exist at some locks which could have been mitigated if modern, improved design...of ti,.c that a navigable pass section can be used. Navigation dams must be designed to pass high flows and floods with minor swell head and without in

Improving the Timeliness of Equal Employment Opportunity Complaint Processing in Department of Defense

DTIC Science & Technology

2015-01-01

1964 (Title VII) and the Pregnancy Discrimination Act amendment to Title VII, the Equal Pay Act of 1963, the Age Discrimi- nation in Employment Act of...Act of 1964 (Title VII) and the Pregnancy Discrimination Act amendment to Title VII, the Equal Pay Act of 1963, the Age Discrimination in...EEO programs uti - lize training on the EEO complaint process and framing of claims and that they use more-structured investigation requests

Active site mutant transgene confers tolerance to human β-glucuronidase without affecting the phenotype of MPS VII mice

PubMed Central

Sly, William S.; Vogler, Carole; Grubb, Jeffrey H.; Zhou, Mi; Jiang, Jinxing; Zhou, Xiao Yan; Tomatsu, Shunji; Bi, Yanhua; Snella, Elizabeth M.

2001-01-01

Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an autosomal recessive lysosomal storage disorder due to an inherited deficiency of β-glucuronidase. A naturally occurring mouse model for this disease was discovered at The Jackson Laboratory and shown to be due to homozygosity for a 1-bp deletion in exon 10 of the gus gene. The murine model MPS VII (gusmps/mps) has been very well characterized and used extensively to evaluate experimental strategies for lysosomal storage diseases, including bone marrow transplantation, enzyme replacement therapy, and gene therapy. To enhance the value of this model for enzyme and gene therapy, we produced a transgenic mouse expressing the human β-glucuronidase cDNA with an amino acid substitution at the active site nucleophile (E540A) and bred it onto the MPS VII (gusmps/mps) background. We demonstrate here that the mutant mice bearing the active site mutant human transgene retain the clinical, morphological, biochemical, and histopathological characteristics of the original MPS VII (gusmps/mps) mouse. However, they are now tolerant to immune challenge with human β-glucuronidase. This “tolerant MPS VII mouse model” should be useful for preclinical trials evaluating the effectiveness of enzyme and/or gene therapy with the human gene products likely to be administered to human patients with MPS VII. PMID:11226217

Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII.

PubMed

Sleeper, M M; Fornasari, B; Ellinwood, N M; Weil, M A; Melniczek, J; O'Malley, T M; Sammarco, C D; Xu, L; Ponder, K P; Haskins, M E

2004-08-17

Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease caused by deficient beta-glucuronidase (GUSB) activity resulting in defective catabolism of glycosaminoglycans (GAGs). Cardiac disease is a major cause of death in MPS VII because of accumulation of GAGs in cardiovascular cells. Manifestations include cardiomyopathy, mitral and aortic valve thickening, and aortic root dilation and may cause death in the early months of life or may be compatible with a fairly normal lifespan. We previously reported that neonatal administration of a retroviral vector (RV) resulted in transduction of hepatocytes, which secreted GUSB into the blood and could be taken up by cells throughout the body. The goal of this study was to evaluate the effect on cardiac disease. Six MPS VII dogs were treated intravenously with an RV-expressing canine GUSB. Echocardiographic parameters, cardiovascular lesions, and biochemical parameters of these dogs were compared with those of normal and untreated MPS VII dogs. RV-treated dogs were markedly improved compared with untreated MPS VII dogs. Most RV-treated MPS VII dogs had mild or moderate mitral regurgitation at 4 to 5 months after birth, which improved or disappeared when evaluated at 9 to 11 and at 24 months. Similarly, mitral valve thickening present early in some animals disappeared over time, whereas aortic dilation and aortic valve thickening were absent at all times. Both myocardium and aorta had significant levels of GUSB and reduction in GAGs.

29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

Code of Federal Regulations, 2014 CFR

2014-07-01

... GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The employee coverage of the prohibitions against discrimination based on sex contained in title VII is...

Weather applications and products enabled through vehicle infrastructure integration (VII) : feasibility and concept development study

DOT National Transportation Integrated Search

2007-01-01

Vehicle Infrastructure Integration (VII) involves the two-way wireless transmission of data from vehicle-to-vehicle and vehicle-to-infrastructure utilizing Dedicated Short Range Communications (DSRC). VII will enable the development of weather-relate...

Vehicle infrastructure integration proof of concept : technical description--vehicle : final report

DOT National Transportation Integrated Search

2009-05-19

This report provides the technical description of the VII system developed for the Cooperative Agreement VII Program between the USDOT and the VII Consortium. The basic architectural elements are summarized and detailed descriptions of the hardware a...

Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.

PubMed

Olson, N C; Raffield, L M; Lange, L A; Lange, E M; Longstreth, W T; Chauhan, G; Debette, S; Seshadri, S; Reiner, A P; Tracy, R P

2018-01-01

Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). Objective Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke and mortality. Patients/Methods We measured FVIIa and FVIIa-AT in 3486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n = 2410) and examined associations of FVII phenotypes with incident cardiovascular disease. Results In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa, β = -25.9 mU mL -1 per minor allele; FVIIa-AT, β = -26.6 pm per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa, β = 7.8 mU mL -1 per minor allele; FVIIa-AT, β = 9.9 per minor allele). Adjusted for risk factors, a one standard deviation higher FVIIa was associated with increased risk of ischemic stroke (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all causes (HR, 1.08; 95% CI, 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR, 0.69; 95% CI, 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. Conclusions The results support the importance of the F7 and PROCR loci in variation in circulating FVIIa and FVIIa-AT. The findings suggest FVIIa is a risk factor for ischemic stroke in older adults, whereas higher FVIIa-AT may reflect mortality risk. © 2017 International Society on Thrombosis and Haemostasis.

Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

PubMed Central

Ruusuvuori, Eva; Huebner, Antje K; Kirilkin, Ilya; Yukin, Alexey Y; Blaesse, Peter; Helmy, Mohamed; Jung Kang, Hyo; El Muayed, Malek; Christopher Hennings, J; Voipio, Juha; Šestan, Nenad; Hübner, Christian A; Kaila, Kai

2013-01-01

Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation during intense GABAA-receptor activation. P13–14 CA VII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13–P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CA VII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS. PMID:23881097

The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol.

PubMed

Takahashi, N; Yoshizaki, T; Hiranaka, N; Kumano, O; Suzuki, T; Akanuma, M; Yui, T; Kanazawa, K; Yoshida, M; Naito, S; Fujiya, M; Kohgo, Y; Ieko, M

2015-05-01

A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear. We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation. C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays. The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes. Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.

Pathogenesis of aortic dilatation in mucopolysaccharidosis VII mice may involve complement activation

PubMed Central

Baldo, Guilherme; Wu, Susan; Howe, Ruth A.; Ramamoothy, Meera; Knutsen, Russell H.; Fang, Jiali; Mecham, Robert P.; Liu, Yuli; Wu, Xiaobo; Atkinson, John P.; Ponder, Katherine P.

2012-01-01

Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme β-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation, which is associated with upregulation of the elastases cathepsin S (CtsS) and matrix metalloproteinase 12 (MMP12). To test the role of these enzymes, MPS VII mice were crossed with mice deficient in CtsS or MMP12, and the effect upon aortic dilatation was determined. CtsS deficiency did not protect against aortic dilatation in MPS VII mice, but also failed to prevent an upregulation of cathepsin enzyme activity. Further analysis with substrates and inhibitors specific for particular cathepsins suggests that this enzyme activity was due to CtsB, which could contribute to elastin fragmentation. Similarly, MMP12 deficiency and deficiency of both MMP12 and CtsS could not prevent aortic dilatation in MPS VII mice. Microarray and reverse-transcriptase real-time PCR were performed to look for upregulation of other elastases. This demonstrated that mRNA for complement component D was elevated in MPS VII mice, while immunostaining demonstrated high levels of complement component C3 on surfaces within the aortic media. Finally, we demonstrate that neonatal intravenous injection of a retroviral vector encoding β-glucuronidase reduced aortic dilatation. We conclude that neither CtsS nor MMP12 are necessary for elastin fragmentation in MPS VII mouse aorta, and propose that CtsB and/or complement component D may be involved. Complement may be activated by the GAGs that accumulate, and may play a role in signal transduction pathways that upregulate elastases. PMID:21944884

Effect of neonatal gene therapy on lumbar spine disease in mucopolysaccharidosis VII dogs.

PubMed

Smith, Lachlan J; Martin, John T; O'Donnell, Patricia; Wang, Ping; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

2012-09-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan, and dermatan sulfate glycosaminoglycans in various tissues including those of the spine. Associated spine disease can be due to abnormalities in the vertebrae, the intervertebral disks, or other spine tissues. The goal of this study was to determine if neonatal gene therapy could prevent lumbar spine disease in MPS VII dogs. MPS VII dogs were injected intravenously with a retroviral vector (RV) expressing canine GUSB at 2 to 3 days after birth, which resulted in transduction of hepatocytes that secreted GUSB into blood. Expression was stable for up to 11 years, and mean survival was increased from 0.4 years in untreated dogs to 6.1 years in treated dogs. Despite a profound positive clinical effect, 6-month-old RV-treated MPS VII dogs still had hypoplastic ventral epiphyses with reduced calcification in the lumbar spine, which resulted in a reduced stiffness and increased range of motion that were not improved relative to untreated MPS VII dogs. At six to 11 years of age, ventral vertebrae remained hypoplastic in RV-treated MPS VII dogs, and there was desiccation of the nucleus pulposus in some disks. Histochemical staining demonstrated that disks did not have detectable GUSB activity despite high serum GUSB activity, which is likely due to poor diffusion into this relatively avascular structure. Thus, neonatal gene therapy cannot prevent lumbar spine disease in MPS VII dogs, which predicts that enzyme replacement therapy (ERT) will similarly be relatively ineffective even if started at birth. Copyright © 2012 Elsevier Inc. All rights reserved.

The Effect of Neonatal Gene Therapy with a Gamma Retroviral Vector on Cardiac Valve Disease in Mucopolysaccharidosis VII Dogs after a Decade

PubMed Central

Bigg, Paul W.; Sleeper, Meg M.; O’Donnell, Patricia A.; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve thickening scores of 2.3±0.7, 2.3±0.6, 1.8±0.5, and 1.6±0.7, respectively, which were higher than the values of 0.6±0.1, 0.1±0.4, 0.3±0.8, and 0.1±0.4, respectively, in treated MPS VII dogs. Treated MPS VII dogs maintained low aortic regurgitation and aortic valve thickening scores for their lifetime. Although mitral regurgitation and mitral valve thickening scores increased to 2.0 at ≥8 years of age in the treated MPS VII dogs, older normal dogs from the colony had similar scores, making it difficult to assess mitral valve disease. Older treated dogs had calcification within the mitral and aortic valve annulus, while GUSB staining demonstrated enzyme activity within the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac valve disease in MPS VII dogs for up to 11 years, and propose that neonatal initiation of ERT should have a similar effect. PMID:23860311

The effect of neonatal gene therapy with a gamma retroviral vector on cardiac valve disease in mucopolysaccharidosis VII dogs after a decade.

PubMed

Bigg, Paul W; Sleeper, Meg M; O'Donnell, Patricia A; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

2013-11-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into the blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve thickening scores of 2.3 ± 0.7, 2.3 ± 0.6, 1.8 ± 0.5, and 1.6 ± 0.7, respectively, which were higher than the values of 0.6 ± 0.1, 0.1 ± 0.4, 0.3 ± 0.8, and 0.1 ± 0.4, respectively, in treated MPS VII dogs. Treated MPS VII dogs maintained low aortic regurgitation and aortic valve thickening scores in their lifetime. Although mitral regurgitation and mitral valve thickening scores increased to 2.0 at ≥ 8 years of age in the treated MPS VII dogs, older normal dogs from the colony had similar scores, making it difficult to assess mitral valve disease. Older treated dogs had calcification within the mitral and the aortic valve annulus, while GUSB staining demonstrated enzyme activity within the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac valve disease in MPS VII dogs for up to 11 years, and propose that neonatal initiation of ERT should have a similar effect. © 2013.

Nonredundant functions of Arabidopsis LecRK-V.2 and LecRK-VII.1 in controlling stomatal immunity and jasmonate-mediated stomatal closure.

PubMed

Yekondi, Shweta; Liang, Fu-Chun; Okuma, Eiji; Radziejwoski, Amandine; Mai, Hsien-Wei; Swain, Swadhin; Singh, Prashant; Gauthier, Mathieu; Chien, Hsiao-Chiao; Murata, Yoshiyuki; Zimmerli, Laurent

2018-04-01

Stomatal immunity restricts bacterial entry to leaves through the recognition of microbe-associated molecular patterns (MAMPs) by pattern-recognition receptors (PRRs) and downstream abscisic acid and salicylic acid signaling. Through a reverse genetics approach, we characterized the function of the L-type lectin receptor kinase-V.2 (LecRK-V.2) and -VII.1 (LecRK-VII.1). Analyses of interactions with the PRR FLAGELLIN SENSING2 (FLS2) were performed by co-immunoprecipitation and bimolecular fluorescence complementation and whole-cell patch-clamp analyses were used to evaluate guard cell Ca 2+ -permeable cation channels. The Arabidopsis thaliana LecRK-V.2 and LecRK-VII.1 and notably their kinase activities were required for full activation of stomatal immunity. Knockout lecrk-V.2 and lecrk-VII.1 mutants were hyper-susceptible to Pseudomonas syringae infection and showed defective stomatal closure in response to bacteria or to the MAMPs flagellin and EF-Tu. By contrast, Arabidopsis over-expressing LecRK-V.2 or LecRK-VII.1 demonstrated a potentiated stomatal immunity. LecRK-V.2 and LecRK-VII.1 are shown to be part of the FLS2 PRR complex. In addition, LecRK-V.2 and LecRK-VII.1 were critical for methyl jasmonate (MeJA)-mediated stomatal closure, notably for MeJA-induced activation of guard cell Ca 2+ -permeable cation channels. This study highlights the role of LecRK-V.2 and LecRK-VII.1 in stomatal immunity at the FLS2 PRR complex and in MeJA-mediated stomatal closure. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Cost-Effectiveness Analysis of Biogeneric Recombinant Activated Factor VII (AryoSeven™) and Activated Prothrombin Complex Concentrates (FEIBA™) to Treat Hemophilia A Patients with Inhibitors in Iran.

PubMed

Golestani, Mina; Eshghi, Peyman; Rasekh, Hamid Reza; Cheraghali, Abdoll Majid; Salamzadeh, Jamshid; Naderi, Majid; Managhchi, Mohammad Reza; Hoorfar, Hamid; Toogeh, Gholam Reza; Imani, Ali; Khodayari, Mohammad Taghi; Habibpanah, Behnaz; Hantooshzadeh, Razieh

2016-01-01

Nowadays, bypassing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCC) are used to treat bleeding episodes in the Hemophilia patients with inhibitors. AryoSeven® is an Iranian biogeneric rFVIIa with homogeneity of efficacy and the nature to NovoSeven in a comparative trial. The current clinical trial aimed to evaluate the cost-effectiveness of FEIBA and AryoSeven® by Decision Analytic Model according to the Iranian healthcare system. An open label, multi-center, cross-over clinical trial was designed. Patients were categorized into 3 groups based on their prior tendency to one or none of the products. To determine the premium therapeutic strategy, the Incremental cost-effectiveness ratio (ICER) was calculated. Protocol F led to more treatment success in group F than the other groups (P= 0.03). Also, there was a significant statistical difference between the mean of effectiveness scores in the groups using protocol F (P = 0.01). The effectiveness of protocol F and A were 89% and 72%, respectively. ICER cost US$ to manage an episode of bleeding to get one more unit of effectiveness using FEIBA VS. AryoSeven. Although the results showed that AryoSeven was more cost-effective compared to FEIBA, the two strategies were undominated. In other words, both medicines can be applied in the first line of the treatment if the cost of FEIBA was reduced. The present clinical trial was registered at IRCT website, under ID No.2013020612380N1.

Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation.

PubMed

Hollis, Allison L; Lowery, Ashleigh V; Pajoumand, Mehrnaz; Pham, Si M; Slejko, Julia F; Tanaka, Kenichi A; Mazzeffi, Michael

2016-01-01

Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.

Effect of temporary cements on the shear bond strength of luting cements

PubMed Central

FIORI-JÚNIOR, Marco; MATSUMOTO, Wilson; SILVA, Raquel Assed Bezerra; PORTO-NETO, Sizenando Toledo; SILVA, Jaciara Miranda Gomes

2010-01-01

Objective The purpose of this study was to evaluate, by shear bond strength (SBS) testing, the influence of different types of temporary cements on the final cementation using conventional and self-etching resin-based luting cements. Material and Methods Forty human teeth divided in two halves were assigned to 8 groups (n=10): I and V (no temporary cementation); II and VI: Ca(OH)2-based cement; III and VII: zinc oxide (ZO)based cement; IV and VIII: ZO-eugenol (ZOE)-based cement. Final cementation was done with RelyX ARC cement (groups I to IV) and RelyX Unicem cement (groups V to VIII). Data were analyzed statistically by ANOVA and Tukey's test at 5% significance level. Results Means were (MPa): I - 3.80 (±1.481); II - 5.24 (±2.297); III - 6.98 (±1.885); IV - 6.54 (±1.459); V - 5.22 (±2.465); VI - 4.48 (±1.705); VII - 6.29 (±2.280); VIII - 2.47 (±2.076). Comparison of the groups that had the same temporary cementation (Groups II and VI; III and VII; IV and VIII) showed statistically significant difference (p<0.001) only between Groups IV and VIII, in which ZOE-based cements were used. The use of either Ca(OH)2 based (Groups II and VI) or ZO-based (Groups III and VII) cements showed no statistically significant difference (p>0.05) for the different luting cements (RelyXTM ARC and RelyXTM Unicem). The groups that had no temporary cementation (Groups I and V) did not differ significantly from each other either (p>0.05). Conclusion When temporary cementation was done with ZO- or ZOE-based cements and final cementation was done with RelyX ARC, there was an increase in the SBS compared to the control. In the groups cemented with RelyX Unicem, however, the use of a ZOE-based temporary cement affected negatively the SBS of the luting agent used for final cementation. PMID:20379679

40 CFR Appendixes I-Vii to Part 85 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

40 CFR Appendixes I-Vii to Part 85 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

40 CFR Appendixes I-Vii to Part 85 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

40 CFR Appendixes I-Vii to Part 85 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 19 2013-07-01 2013-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

40 CFR Appendixes I-Vii to Part 85 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 19 2014-07-01 2014-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

Adenovirus core protein VII contains distinct sequences that mediate targeting to the nucleus and nucleolus, and colocalization with human chromosomes.

PubMed

Lee, Tim W R; Blair, G Eric; Matthews, David A

2003-12-01

During adenovirus infection, following capsid dissociation, core protein VII enters the host cell nucleus complexed with adenovirus DNA. In order to determine whether protein VII may have an active role in this nuclear import, regions of the preVII gene were amplified by PCR, and further oligonucleotide mutants were designed with site-directed mutation of codons for the basic amino acids arginine and lysine. Fragments were cloned into a mammalian expression plasmid to express the peptides as N-terminal fusions to enhanced green fluorescent protein. Results demonstrate that preVII protein contains both nuclear and nucleolar targeting sequences. Such signals may be important in the delivery of adenovirus DNA to the host cell nucleus during adenovirus infection. Furthermore, the data suggest that protein VII may bind to human chromosomes by means of two distinct domains, one sharing homology with the N-terminal regulatory tail of histone H3.

Clustering of haemostatic variables and the effect of high cashew and walnut diets on these variables in metabolic syndrome patients.

PubMed

Pieters, Marlien; Oosthuizen, Welma; Jerling, Johann C; Loots, Du Toit; Mukuddem-Petersen, Janine; Hanekom, Susanna M

2005-09-01

We investigated the effect of a high walnut and cashew diet on haemostatic variables in people with the metabolic syndrome. Factor analysis was used to determine how the haemostatic variables cluster with other components of the metabolic syndrome and multiple regression to determine possible predictors. This randomized, control, parallel, controlled-feeding trial included 68 subjects who complied with the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a 3-week run-in following the control diet, subjects were divided into three groups receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks. The nut intervention had no significant effect on von Willebrand factor antigen, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1 activity, tissue plasminogen activator activity or thrombin activatable fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass-correlates and acute phase response factors, and factor VII coagulant activity clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen activator activity, plasminogen activator inhibitor 1 activity and von Willebrand factor antigen clustered into a separate endothelial function factor. HDL-C and markers of obesity were the strongest predictors of the haemostatic variables. We conclude that high walnut and cashew diets did not influence haemostatic factors in this group of metabolic syndrome subjects. The HDL-C increase and weight loss may be the main focus of dietary intervention for the metabolic syndrome. Furthermore, diet composition may have only limited effects if weight loss is not achieved.

The Effect of Neonatal Gene Therapy on Skeletal Manifestations in Mucopolysaccharidosis VII Dogs after a Decade

PubMed Central

Xing, Elizabeth M.; Knox, Van W.; O'Donnell, Patricia A.; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. PMID:23628461

Oxidation of phenolic endocrine disrupting chemicals by potassium permanganate in synthetic and real waters.

PubMed

Jiang, Jin; Pang, Su-Yan; Ma, Jun; Liu, Huiling

2012-02-07

In this study, five selected environmentally relevant phenolic endocrine disrupting chemicals (EDCs), estrone, 17β-estradiol, estriol, 17α-ethinylestradiol, and 4-n-nonylphenol, were shown to exhibit similarly appreciable reactivity toward potassium permanganate [Mn(VII)] with a second-order rate constant at near neutral pH comparable to those of ferrate(VI) and chlorine but much lower than that of ozone. In comparison with these oxidants, however, Mn(VII) was much more effective for the oxidative removal of these EDCs in real waters, mainly due to the relatively high stability of Mn(VII) therein. Mn(VII) concentrations at low micromolar range were determined by an ABTS [2,2-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid diammonium] spectrophotometric method based on the stoichiometric reaction of Mn(VII) with ABTS [Mn(VII) + 5ABTS → Mn(II) + 5ABTS(•+)] forming a stable green radical cation (ABTS(•+)). Identification of oxidation products suggested the initial attack of Mn(VII) at the hydroxyl group in the aromatic ring of EDCs, leading to a series of quinone-like and ring-opening products. The background matrices of real waters as well as selected model ligands including phosphate, pyrophosphate, NTA, and humic acid were found to accelerate the oxidation dynamics of these EDCs by Mn(VII). This was explained by the effect of in situ formed dissolved Mn(III), which could readily oxidize these EDCs but would disproportionate spontaneously without stabilizing agents.

40 CFR Appendixes Vi-Vii to Part 600 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false [Reserved] VI Appendixes VI-VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Appendixes VI-VII to Part 600 [Reserved] ...

40 CFR Appendixes Vi-Vii to Part 600 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false [Reserved] VI Appendixes VI-VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Appendixes VI-VII to Part 600 [Reserved] ...

29 CFR 1604.4 - Discrimination against married women.

Code of Federal Regulations, 2014 CFR

2014-07-01

... DISCRIMINATION BECAUSE OF SEX § 1604.4 Discrimination against married women. (a) The Commission has determined... applicable to married men is a discrimination based on sex prohibited by title VII of the Civil Rights Act... married females, for so long as sex is a factor in the application of the rule, such application involves...

Comparison of Employer Factors in Disability and Other Employment Discrimination Charges

ERIC Educational Resources Information Center

Nazarov, Zafar E.; von Schrader, Sarah

2014-01-01

Purpose: We explore whether certain employer characteristics predict Americans with Disabilities Act (ADA) charges and whether the same characteristics predict receipt of the Age Discrimination in Employment Act and Title VII of the Civil Rights Act charges. Method: We estimate a set of multivariate regressions using the ordinary least squares…

Federal Programs Supporting Educational Change, Vol. 2: Factors Affecting Change Agent Projects.

ERIC Educational Resources Information Center

Berman, Paul; Pauly, Edward W.

This second volume in the change-agent series reports the interim results of an exploratory statistical analysis of a survey of a nationwide sample of 293 change-agent projects funded by four federal demonstration programs--Elementary Secondary Education Act (ESEA) Title III, Innovative Projects; ESEA Title VII, Bilingual Projects; Vocational…

77 FR 59610 - Flonicamid; Applications To Add New Food Uses on Previously Registered Pesticide Products

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... entities may include, but are not limited to: Crop production (NAICS code 111). Animal production (NAICS... to illustrate your concerns and suggest alternatives. vii. Explain your views as clearly as possible... factors, may have atypical or disproportionately high and adverse human health impacts or environmental...

7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Debentures and/or TCs. (iv) Arranging for the production of Offering Circulars, certificates, and such other... to determine those factors that will minimize or reduce the cost of funding Debentures. (iii) Monitor... the Secretary; (vii) Remain custodian of such other documentation as the Secretary shall direct by...

13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... periodic sales of Debentures and/or TCs. (iv) Arranging for the production of Offering Circulars... financial markets to determine those factors that will minimize or reduce the cost of funding Debentures... SBA; (vii) Remain custodian of such other documentation as SBA shall direct by written instructions...

13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Participating Securities and/or TCs. (iv) Arranging for the production of the Offering Circular, certificates... markets to determine those factors that will minimize or reduce the cost of funding Debentures or... instructions from SBA; (vii) Remain custodian of such other documentation as SBA shall direct by written...

76 FR 12693 - Notice of an Opportunity To Serve on the Innovation Advisory Board Advising the Department of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... experts, and State and local government officials active in technology-based economic development. DATES...) Barriers to competitiveness in newly emerging business or technology sectors, factors influencing... development and evolution of start-ups, firms, and industries. (vii) The effects of domestic and international...

20 CFR 416.929 - How we evaluate symptoms, including pain.

Code of Federal Regulations, 2012 CFR

2012-04-01

...), and (5), and (d). These include statements or reports from you, your treating or nontreating source... expected to produce your symptoms, such as pain. Your symptoms, such as pain, fatigue, shortness of breath..., standing for 15 to 20 minutes every hour, sleeping on a board, etc.); and (vii) Other factors concerning...

20 CFR 416.929 - How we evaluate symptoms, including pain.

Code of Federal Regulations, 2013 CFR

2013-04-01

...), and (5), and (d). These include statements or reports from you, your treating or nontreating source... expected to produce your symptoms, such as pain. Your symptoms, such as pain, fatigue, shortness of breath..., standing for 15 to 20 minutes every hour, sleeping on a board, etc.); and (vii) Other factors concerning...

20 CFR 416.929 - How we evaluate symptoms, including pain.

Code of Federal Regulations, 2014 CFR

2014-04-01

...), and (5), and (d). These include statements or reports from you, your treating or nontreating source... expected to produce your symptoms, such as pain. Your symptoms, such as pain, fatigue, shortness of breath..., standing for 15 to 20 minutes every hour, sleeping on a board, etc.); and (vii) Other factors concerning...

11p15 duplication and 13q34 deletion with Beckwith-Wiedemann syndrome and factor VII deficiency.

PubMed

Jurkiewicz, Dorota; Kugaudo, Monika; Tańska, Anna; Wawrzkiewicz-Witkowska, Angelika; Tomaszewska, Agnieszka; Kucharczyk, Marzena; Cieślikowska, Agata; Ciara, Elżbieta; Krajewska-Walasek, Małgorzata

2015-06-01

Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith-Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation-sensitive multiplex ligation-dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay. © 2015 Japan Pediatric Society.

[The role of recombinant activated factor VII in neuro- surgical and neurocritical patients].

PubMed

Rama-Maceiras, P; Ingelmo-Ingelmo, I; Fábregas-Juliá, N; Hernández-Palazón, J

2011-06-01

Central nervous system haemorrhage is a severe pathology, as a small amount of bleeding inside the brain can result in devastating consequences. Haemostatic agents might decrease the consequences of intra- cranial bleeding, whichever spontaneous, traumatic, or anticoagulation treatment etiology. Proacogulant recombinant activated factor VII (rFVIIa) has been given after central nervous system bleeding, with an off-label indication. In this update, we go over the drug mechanism of action, its role in the treatment of central nervous system haemorrhage and the published evidences regarding this subject. We carried out a literature review concerning the treatment with rFVIIa in central nervous system haemorrhage, neurocritical pathologies and neurosurgical procedures, searching in MEDLINE and in clinical trials registry: http://clinicaltrials.gov (last review September 2010), as well as performing a manual analysis of collected articles, looking for aditional references. The results of randomized clinical trials do not support the systematic administration of rFVIIa for spontaneous intracranial cerebral haemorrhage. In other central nervous system related haemorrhages, the current available data consist on retrospective studies, expert opinion or isolated case reports.

Comparison of student's learning achievement through realistic mathematics education (RME) approach and problem solving approach on grade VII

NASA Astrophysics Data System (ADS)

Ilyas, Muhammad; Salwah

2017-02-01

The type of this research was experiment. The purpose of this study was to determine the difference and the quality of student's learning achievement between students who obtained learning through Realistic Mathematics Education (RME) approach and students who obtained learning through problem solving approach. This study was a quasi-experimental research with non-equivalent experiment group design. The population of this study was all students of grade VII in one of junior high school in Palopo, in the second semester of academic year 2015/2016. Two classes were selected purposively as sample of research that was: year VII-5 as many as 28 students were selected as experiment group I and VII-6 as many as 23 students were selected as experiment group II. Treatment that used in the experiment group I was learning by RME Approach, whereas in the experiment group II by problem solving approach. Technique of data collection in this study gave pretest and posttest to students. The analysis used in this research was an analysis of descriptive statistics and analysis of inferential statistics using t-test. Based on the analysis of descriptive statistics, it can be concluded that the average score of students' mathematics learning after taught using problem solving approach was similar to the average results of students' mathematics learning after taught using realistic mathematics education (RME) approach, which are both at the high category. In addition, It can also be concluded that; (1) there was no difference in the results of students' mathematics learning taught using realistic mathematics education (RME) approach and students who taught using problem solving approach, (2) quality of learning achievement of students who received RME approach and problem solving approach learning was same, which was at the high category.

Role of Pilus Proteins in Adherence and Invasion of Streptococcus agalactiae to the Lung and Cervical Epithelial Cells*

PubMed Central

Sharma, Puja; Lata, Hem; Arya, Deepak Kumar; Kashyap, Arun Kumar; Kumar, Hemant; Dua, Meenakshi; Ali, Arif; Johri, Atul Kumar

2013-01-01

Streptococcus agalactiae, or group B Streptococcus (GBS), is an important opportunistic pathogen that causes pneumonia, sepsis, and meningitis in neonates and severe diseases in immunocompromised adults. We have performed comparative genomics of prevalent GBS serotypes of Indian origin (i.e. Ia, III, V, and VII). Pilus-proteins were commonly found up-regulated, and their expression was studied by using antiserum for GBS80 (backbone protein of pilus island-I), GBS67 (ancillary protein of PI-2a), and SAN1518 (backbone protein of PI-2b) by whole cell and Western blot analysis. To check the role of pilus proteins in adherence and invasion, an inhibition assay was performed. Comparative immunoblotting experiments revealed that expression of pili proteins does not differ in geographically different selected serotypes, Ia and V, of India and the United States. In the case of A549 cells, we found that GBS VII invasion and adherence was inhibited by pilus protein-specific antiserum SAN1518 significantly (p < 0.001) by 88.5 and 91%, respectively. We found that mutant strains, deficient in the pilus proteins (Δgbs80 and Δsan1518) exhibit a significant decrease in adherence in the case of type Ia, III, and VII. In the case of type VII, we have found a 95% reduction in invasion when Δsan1518 was used with A549 cells. Because the pilus proteins were identified previously as vaccine candidates against GBS serotypes of developed countries, we also found their role in the attachment and invasion of GBS of Indian origin. Thus, the present work supports the idea of making a more effective pilus protein-based vaccine that can be used universally. PMID:23209289

LEA Title VII Program Evaluations. Panel Presentations.

ERIC Educational Resources Information Center

Balu, Raj

These panel presentations focus on LEA Title VII Program Evaluations. Raj Balu, an administrator of bilingual programs in Chicago presents information regarding the bilingual education program in the Chicago public schools, as well as information on Title VII programs and what kind of evaluation is being done. Jesus Salazar, who is currently…

32 CFR 2003.7 - Support Staff (Article VII).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Support Staff (Article VII). 2003.7 Section 2003... (ISCAP) BYLAWS, RULES, AND APPEAL PROCEDURES Bylaws § 2003.7 Support Staff (Article VII). The staff of..., provides program and administrative support for the Panel. The Executive Secretary supervises the staff in...

32 CFR 2003.7 - Support Staff (Article VII).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Support Staff (Article VII). 2003.7 Section 2003... (ISCAP) BYLAWS, RULES, AND APPEAL PROCEDURES Bylaws § 2003.7 Support Staff (Article VII). The staff of..., provides program and administrative support for the Panel. The Executive Secretary supervises the staff in...

Adenovirus Core Protein VII Downregulates the DNA Damage Response on the Host Genome

PubMed Central

Avgousti, Daphne C.; Della Fera, Ashley N.; Otter, Clayton J.; Herrmann, Christin; Pancholi, Neha J.

2017-01-01

ABSTRACT Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein VII, a virally encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by the cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome. Here we show that protein VII at cellular chromatin results in a significant decrease in accumulation of phosphorylated H2AX (γH2AX) following irradiation, indicating that protein VII inhibits DDR signaling. The oncoprotein SET was recently suggested to modulate the DDR by affecting access of repair proteins to chromatin. Since protein VII binds SET, we investigated a role for SET in DDR inhibition by protein VII. We show that knockdown of SET partially rescues the protein VII-induced decrease in γH2AX accumulation on the host genome, suggesting that SET is required for inhibition. Finally, we show that knockdown of SET also allows ATM to localize to incoming viral genomes bound by protein VII during infection with a mutant lacking early region E4. Together, our data suggest that the protein VII-SET interaction contributes to DDR evasion by adenovirus. Our results provide an additional example of a strategy used by adenovirus to abrogate the host DDR and show how viruses can modify cellular processes through manipulation of host chromatin. IMPORTANCE The DNA damage response (DDR) is a cellular network that is crucial for maintaining genome integrity. DNA viruses replicating in the nucleus challenge the resident genome and must overcome cellular responses, including the DDR. Adenoviruses are prevalent human pathogens that can cause a multitude of diseases, such as respiratory infections and conjunctivitis. Here we describe how a small adenovirus core protein that localizes to host chromatin during infection can globally downregulate the DDR. Our study focuses on key players in the damage signaling pathway and highlights how viral manipulation of chromatin may influence access of DDR proteins to the host genome. PMID:28794020

Properties of synaptic transmission from the reticular formation dorsal to the facial nucleus to trigeminal motoneurons during early postnatal development in rats.

PubMed

Gemba-Nishimura, A; Inoue, T; Nakamura, S; Nakayama, K; Mochizuki, A; Shintani, S; Yoshimura, S

2010-03-31

We previously reported that electrical stimulation of the reticular formation dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at short latencies and that RdVII neurons were antidromically activated by stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory premotor neurons targeting the MoV are likely located in the RdVII. We thus examined the properties of synaptic transmission from the RdVII to jaw-closing and jaw-opening motoneurons in horizontal brainstem preparations from developing rats using voltage-sensitive dye, patch-clamp recordings and laser photostimulation. Electrical stimulation of the RdVII evoked optical responses in the MoV. Combined bath application of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV) reduced these optical responses, and addition of the glycine receptor antagonist strychnine and the GABA(A) receptor antagonist bicuculline further reduced the remaining responses. Electrical stimulation of the RdVII evoked postsynaptic currents (PSCs) in all 19 masseter motoneurons tested in postnatal day (P)1-4 rats, and application of CNQX and the NMDA receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced the PSC amplitudes by more than 50%. In the presence of CNQX and CPP, the GABA(A) receptor antagonist SR95531 further reduced PSC amplitude, and addition of strychnine abolished the remaining PSCs. Photostimulation of the RdVII with caged glutamate also evoked PSCs in masseter motoneurons of P3-4 rats. In P8-11 rats, electrical stimulation of the RdVII also evoked PSCs in all 14 masseter motoneurons tested, and the effects of the antagonists on the PSCs were similar to those in P1-4 rats. On the other hand, RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested. These results suggest that both neonatal and juvenile jaw-closing motoneurons receive strong synaptic inputs from the RdVII through activation of glutamate, glycine and GABA(A) receptors, whereas inputs from the RdVII to jaw-opening motoneurons seem to be weak. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Coincidences between O VI and O VII Lines: Insights from High-resolution Simulations of the Warm-hot Intergalactic Medium

NASA Astrophysics Data System (ADS)

Cen, Renyue

2012-07-01

With high-resolution (0.46 h -1 kpc), large-scale, adaptive mesh-refinement Eulerian cosmological hydrodynamic simulations we compute properties of O VI and O VII absorbers from the warm-hot intergalactic medium (WHIM) at z = 0. Our new simulations are in broad agreement with previous simulations with ~40% of the intergalactic medium being in the WHIM. Our simulations are in agreement with observed properties of O VI absorbers with respect to the line incidence rate and Doppler-width-column-density relation. It is found that the amount of gas in the WHIM below and above 106 K is roughly equal. Strong O VI absorbers are found to be predominantly collisionally ionized. It is found that (61%, 57%, 39%) of O VI absorbers of log N(O VI) cm2 = (12.5-13, 13-14, > 14) have T < 105 K. Cross correlations between galaxies and strong [N(O VI) > 1014 cm-2] O VI absorbers on ~100-300 kpc scales are suggested as a potential differentiator between collisional ionization and photoionization models. Quantitative prediction is made for the presence of broad and shallow O VI lines that are largely missed by current observations but will be detectable by Cosmic Origins Spectrograph observations. The reported 3σ upper limit on the mean column density of coincidental O VII lines at the location of detected O VI lines by Yao et al. is above our predicted value by a factor of 2.5-4. The claimed observational detection of O VII lines by Nicastro et al., if true, is 2σ above what our simulations predict.

Cetuximab in treatment of metastatic colorectal cancer: final survival analyses and extended RAS data from the NORDIC-VII study.

PubMed

Guren, Tormod Kyrre; Thomsen, Maria; Kure, Elin H; Sorbye, Halfdan; Glimelius, Bengt; Pfeiffer, Per; Österlund, Pia; Sigurdsson, Fridbjörn; Lothe, Inger Marie Bowitz; Dalsgaard, Astrid Marie; Skovlund, Eva; Christoffersen, Thoralf; Tveit, Kjell Magne

2017-05-09

The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis. A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations. Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy. Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.

Protein Replacement Therapy and Gene Transfer in Canine Models of Hemophilia A, Hemophilia B, von Willebrand Disease, and Factor VII Deficiency

PubMed Central

Nichols, Timothy C.; Dillow, Aaron M.; Franck, Helen W.G.; Merricks, Elizabeth P.; Raymer, Robin A.; Bellinger, Dwight A.; Arruda, Valder R.; High, Katherine A.

2011-01-01

Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders. PMID:19293459

Nuclear data libraries assessment for modelling a small fluoride salt-cooled, high-temperature reactor

NASA Astrophysics Data System (ADS)

Mohamed, Hassan; Lindley, Benjamin; Parks, Geoffrey

2017-01-01

Nuclear data consists of measured or evaluated probabilities of various fundamental physical interactions involving the nuclei of atoms and their properties. Most fluoride salt-cooled high-temperature reactor (FHR) studies that were reviewed do not give detailed information on the data libraries used in their assessments. Therefore, the main objective of this data libraries comparison study is to investigate whether there are any significant discrepancies between main data libraries, namely ENDF/B-VII, JEFF-3.1 and JEF-2.2. Knowing the discrepancies, especially its magnitude, is important and relevant for readers as to whether further cautions are necessary for any future verification or validation processes when modelling an FHR. The study is performed using AMEC's reactor physics software tool, WIMS. The WIMS calculation is simply a 2-D infinite lattice of fuel assembly calculation. The comparison between the data libraries in terms of infinite multiplication factor, kinf and pin power map are presented. Results show that the discrepancy between JEFF-3.1 and ENDF/B-VII libraries is reasonably small but increases as the fuel depletes due to the data libraries uncertainties that are accumulated at each burnup step. Additionally, there are large discrepancies between JEF-2.2 and ENDF/B-VII because of the inadequacy of the JEF-2.2 library.

CONSULTATION ON UPDATED METHODOLOGY FOR ...

EPA Pesticide Factsheets

The National Academy of Sciences (NAS) expects to publish the Biological Effects of Ionizing Radiation (BEIR) committee's report (BEIR VII) on risks from ionizing radiation exposures in calendar year 2005. The committee is expected to have analyzed the most recent epidemiology from the important exposed cohorts and to have factored in any changes resulting from the updated analysis of dosimetry for the Japanese atomic bomb survivors. To the extent practical, the Committee will also consider any relevant radiobiological data, including those from the Department of Energy's low dose effects research program. Based on their evaluation of relevant information, the Committee is then expected to propose a set of models for estimating risks from low-dose ionizing radiation. ORIA will review the BEIR VII report and consider revisions to the Agency's methodology for estimating cancer risks from exposure to ionizing radiation in light of this report and other relevant information. This will be the subject of the Consultation. This project supports a major risk management initiative to improve the basis on which radiation risk decisions are made. This project, funded by several Federal Agencies, reflects an attempt to characterize risks where there are substantial uncertainties. The outcome will improve our ability to assess risks well into the future and will strengthen EPAs overall capability for assessing and managing radiation risks. the BEIR VII report is funde

Lentiviral-mediated gene therapy results in sustained expression of β-glucuronidase for up to 12 months in the gus(mps/mps) and up to 18 months in the gus(tm(L175F)Sly) mouse models of mucopolysaccharidosis type VII.

PubMed

Derrick-Roberts, Ainslie L K; Pyragius, Carmen E; Kaidonis, Xenia M; Jackson, Matilda R; Anson, Donald S; Byers, Sharon

2014-09-01

A number of mucopolysaccharidosis type VII (MPS VII) mouse models with different levels of residual enzyme activity have been created replicating the range of clinical phenotypes observed in human MPS VII patients. In this study, a lentivirus encoding murine β-glucuronidase was administered intravenously at birth to both the severe (Gus(mps/mps) strain) and attenuated (Gus(tm(L175F)Sly) strain) mouse models of MPS VII. Circulating enzyme levels were normalized in the Gus(mps/mps) mice and were 3.5-fold higher than normal in the Gus(tm(L175F)Sly) mouse 12 and 18 months after administration. Tissue β-glucuronidase activity increased over untreated levels in all tissues evaluated in both strains at 12 months, and the elevated level was maintained in Gus(tm(L175F)Sly) tissues at 18 months. These elevated enzyme levels reduced glycosaminoglycan storage in the liver, spleen, kidney, and heart in both models. Bone mineral volume decreased toward normal in both models after 12 months of therapy and after 18 months in the Gus(tm(L175F)Sly) mouse. Open-field exploration was improved in 18-month-old treated Gus(tm(L175F)Sly) mice, while spatial learning improved in both 12- and 18-month-old treated Gus(tm(L175F)Sly) mice. Overall, neonatal administration of lentiviral gene therapy resulted in sustained enzyme expression for up to 18 months in murine models of MPS VII. Significant improvements in biochemistry and enzymology as well as functional improvement of bone and behavior deficits in the Gus(tm(L175F)Sly) model were observed. Therapy significantly increased the lifespan of Gus(mps/mps) mice, with 12 months being the longest reported lentiviral treatment for this strain. It is important to assess the long-term outcome on enzyme levels and effect on pathology for lentiviral gene therapy to be a potential therapy for MPS patients.

The effect of neonatal gene therapy on skeletal manifestations in mucopolysaccharidosis VII dogs after a decade.

PubMed

Xing, Elizabeth M; Knox, Van W; O'Donnell, Patricia A; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

2013-06-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. Copyright © 2013 Elsevier Inc. All rights reserved.

Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs.

PubMed

Bigg, Paul W; Baldo, Guilherme; Sleeper, Meg M; O'Donnell, Patricia A; Bai, Hanqing; Rokkam, Venkata R P; Liu, Yuli; Wu, Susan; Giugliani, Roberto; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

2013-11-01

Mucopolysaccharidosis VII (MPS VII) is due to the deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiovascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues. © 2013.

Pathogenesis of Mitral Valve Disease in Mucopolysaccharidosis VII Dogs

PubMed Central

Bigg, Paul W.; Baldo, Guilherme; Sleeper, Meg M.; O'Donnell, Patricia A.; Bai, Hanqing; Rokkam, Venkata R.P.; Liu, Yuli; Wu, Susan; Giugliani, Roberto; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiavascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues. PMID:23856419

29 CFR 1910.16 - Longshoring and marine terminals.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Ionizing radiation. Subpart Z, § 1910.1096; (vi) Noise. Subpart G, § 1910.95; (vii) Nonionizing radiation. Subpart G, § 1910.97; Note to paragraph (a)(2)(vii): Exposures to nonionizing radiation emissions from.... Subpart Z, § 1910.1200; (vii) Ionizing radiation. Subpart Z, § 1910.1096; (viii) Noise. Subpart G, § 1910...

48 CFR 952.227-14 - Rights in data-general. (DOE coverage-alternates VI and VII)

Code of Federal Regulations, 2012 CFR

2012-10-01

.... (DOE coverage-alternates VI and VII) 952.227-14 Section 952.227-14 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.227-14 Rights in data-general. (DOE coverage—alternates VI and VII) Alternate VI...

48 CFR 952.227-14 - Rights in data-general. (DOE coverage-alternates VI and VII)

Code of Federal Regulations, 2014 CFR

2014-10-01

.... (DOE coverage-alternates VI and VII) 952.227-14 Section 952.227-14 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.227-14 Rights in data-general. (DOE coverage—alternates VI and VII) Alternate VI...

48 CFR 952.227-14 - Rights in data-general. (DOE coverage-alternates VI and VII)

Code of Federal Regulations, 2013 CFR

2013-10-01

.... (DOE coverage-alternates VI and VII) 952.227-14 Section 952.227-14 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.227-14 Rights in data-general. (DOE coverage—alternates VI and VII) Alternate VI...

77 FR 14516 - Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14339-000] Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On December 22, 2011, Lock+ Hydro Friends Fund VII filed...

76 FR 24471 - Qualified Hydro 26, LLC; Lock+ Hydro Friends Fund VII; Western Minnesota Municipal Power Agency...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-02

...; 14113-000] Qualified Hydro 26, LLC; Lock+ Hydro Friends Fund VII; Western Minnesota Municipal Power... Hydro), Lock+ Hydro Friends Fund VII (Hydro Friends) and Western Minnesota Municipal Power Agency (WMMPA... 02114; (978) 283-2822. Hydro Friends' proposed Lock and Dam 11 Hydropower Project No. 14112 would...

76 FR 57013 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... EQUAL EMPLOYMENT OPPORTUNITY COMMISSION 29 CFR Part 1602 RIN 3046-AA89 Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION... under title VII, the ADA, and GINA. (76 FR 31892, June 2, 2011). No requests to present oral testimony...

Contribution of tertiary amino groups to Re(VII) biosorption on modified corn stalk: competitiveness and regularity.

PubMed

Lou, Zhenning; Zhao, Ziyi; Li, Yexia; Shan, Weijun; Xiong, Ying; Fang, Dawei; Yue, Shuang; Zang, Shuliang

2013-04-01

The effects of basic strength and steric hindrance of gels modified by dimethylamine, diethylamine, di-n-octylamine and di-2-ethylhexylamine, respectively, on rhenium (Re(VII)) adsorption capacity and selectivity were discussed. By comparing with the adsorption of other coexisting metals, such as Mo(VI), Cu(II), Pb(II), Fe(III), Zn(II), Mn(VII) and Ni(II), the gel modified by di-n-octylamine (DNOA-OCS) showed a high affinity for Re(VII) at higher hydrochloric acid concentration (C(H)(+)≥1.0 mol L(-1)), and the maximum adsorption capacity was 98.69 mg g(-1). This article not only described the adsorption behavior but also suggested isotherms, kinetics and thermodynamics of Re(VII) onto the DNOA-OCS gel in an aqueous medium using several models. Further study on adsorption of rhenium in a fixed-bed column packed with the DNOA-OCS gel under continuous and recirculating modes could confirm that the corn stalk gel modified by di-n-octylamine could be used as the adsorbent of Re(VII) from Mo-containing wastewater. Copyright © 2013 Elsevier Ltd. All rights reserved.

Demonstration of resonant photopumping of Mo VII by Mo XII for a VUV laser near 600 {Angstrom}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ilcisin, K.J.; Aumayr, F.; Schwob, J.L.

1993-09-01

We present data of experiments on the resonant photopumping of Mo VII by Mo XII as a method of generating a coherent VUV source near 600 {angstrom}. The experiment is based on a scheme proposed by Feldman and Reader in which the 4p{sup 6} -- 4p{sup 5}6s transition in Mo VII in resonantly photopumped by the 5s {sup 2}S{sub 1/2} -- 4p {sup 2}P{sub 1/2} transition in Mo XII. Results of the laser produced plasma experiments show the successful enhancement of the population of the Mo VII 4p{sup 5}6s upper lasing level when pumped by an adjacent Mo VII plasma.more » No enhancement was seen in a control experiment where the Mo VII plasma was pumped by a Zr X plasma. Improvements of the intensity of the Mo XII pump source, achieved using an additional pump laser, lead to the generation of a population inversion for the VUV transition.« less

Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential.

PubMed

Anand, Sanjeev K; Gaba, Amit; Singh, Jaswant; Tikoo, Suresh K

2014-02-01

Viruses modulate the functions of mitochondria by translocating viral proteins to the mitochondria. Subcellular fractionation and sensitivity to proteinase K/Triton X-100 treatment of mitochondrial fractions of bovine adenovirus (BAdV)-3-infected/transfected cells suggested that core protein pVII localizes to the mitochondria and contains a functional mitochondrial localization signal. Moreover, mitochondrial localization of BAdV-3 pVII appears to help in the retention of mitochondrial Ca(2+), inducing a significant increase in the levels of ATP and maintaining the mitochondrial membrane potential (MMP) in transfected cells. In contrast, mitochondrial localization of BAdV-3 pVII has no significant effect on the levels of cytoplasmic Ca(2+) and reactive oxygen species production in the transfected cells. Consistent with these results, expression of pVII in transfected cells treated with staurosporine decreased significantly the activation of caspase-3. Our results suggested that BAdV-3 pVII localizes to mitochondria, and interferes with apoptosis by inhibiting loss of the MMP and by increasing mitochondrial Ca(2+) and ATP production.

Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines.

PubMed

Witter, Lauren E; Gruber, Erika J; Lean, Fabian Z X; Stokol, Tracy

2017-01-01

OBJECTIVE To evaluate expression of procoagulant tissue factor (TF) by canine hemangiosarcoma cells in vitro. SAMPLES 4 canine hemangiosarcoma cell lines (SB-HSA [mouse-passaged cutaneous tumor], Emma [primary metastatic brain tumor], and Frog and Dal-1 [primary splenic tumors]) and 1 nonneoplastic canine endothelial cell line (CnAoEC). PROCEDURES TF mRNA and TF antigen expression were evaluated by quantitative real-time PCR assay and flow cytometry, respectively. Thrombin generation was measured in canine plasma and in coagulation factor-replete or specific coagulation factor-deficient human plasma by calibrated automated thrombography. Corn trypsin inhibitor and annexin V were used to examine contributions of contact activation and membrane-bound phosphatidylserine, respectively, to thrombin generation. RESULTS All cell lines expressed TF mRNA and antigen, with significantly greater expression of both products in SB-HSA and Emma cells than in CnAoEC. A greater percentage of SB-HSA cells expressed TF antigen, compared with other hemangiosarcoma cell lines. All hemangiosarcoma cell lines generated significantly more thrombin than did CnAoEC in canine or factor-replete human plasma. Thrombin generation induced by SB-HSA cells was significantly lower in factor VII-deficient plasma than in factor-replete plasma and was abolished in factor X-deficient plasma; residual thrombin generation in factor VII-deficient plasma was abolished by incubation of cells with annexin V. Thrombin generation by SB-HSA cells was unaffected by the addition of corn trypsin inhibitor. CONCLUSIONS AND CLINICAL RELEVANCE Hemangiosarcoma cell lines expressed procoagulant TF in vitro. Further research is needed to determine whether TF can be used as a biomarker for hemostatic dysfunction in dogs with hemangiosarcoma.

Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus.

PubMed

Watson, G L; Sayles, J N; Chen, C; Elliger, S S; Elliger, C A; Raju, N R; Kurtzman, G J; Podsakoff, G M

1998-12-01

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a genetic deficiency of beta-glucuronidase (GUS). We used a recombinant adeno-associated virus vector (AAV-GUS) to deliver GUS cDNA to MPS VII mice. The route of vector administration had a dramatic effect on the extent and distribution of GUS activity. Intramuscular injection of AAV-GUS resulted in high, localized production of GUS, while intravenous administration produced low GUS activity in several tissues. This latter treatment of MPS VII mice reduced glycosaminoglycan levels in the liver to normal and reduced storage granules dramatically. We show that a single administration of AAV-GUS can provide sustained expression of GUS in a variety of cell types and is sufficient to reverse the disease phenotype at least in the liver.

Anatomic Variability of the Upper Mediastinal Lymph Node Level VII.

PubMed

Hartl, Dana M; Breuskin, Ingrid; Mirghani, Haïtham; Berdelou, Amandine; Déandréis, Désirée; Pottier, Edwige; Borget, Isabelle; Schlumberger, Martin; Leboulleux, Sophie

2016-08-01

Lymph node level VII, between the sternal notch and the innominate artery, is a frequent site of lymph node metastases in thyroid cancer. The objective of this study was to determine the cranial-caudal dimensions of level VII in patients undergoing central neck dissection for thyroid cancer and its accessibility through a neck incision only. Consecutive patients undergoing central neck dissection for thyroid cancer, with no previous neck dissection, mediastinal or thoracic surgery. The innominate artery was identified and the distance between the sternal notch and the upper border of the artery was measured to the nearest .5 mm. The sizes of level VII were compared with respect to age, sex, height, body mass index, type of neck dissection (therapeutic or prophylactic), and the incidence of previous thyroidectomy. One-hundred-one consecutive patients (65 women, 36 men, mean age 44 years (range 15-87) underwent prophylactic (n = 55) or therapeutic (n = 46) bilateral central compartment neck dissection. Level VII was accessible via the horizontal neck incision in all cases. Sizes of level VII ranged from 6 cm above the sternal notch to 35 mm below the sternal notch, with a mean distance of 3.5 mm below the sternal notch. The innominate artery was at the level of the sternal notch in 29 patients, and cranial to the sternal notch in 20 cases. No statistical relationship with age, sex, therapeutic/prophylactic neck dissection, previous surgery, body mass index or height was found. The maximal distance below the sternal notch was 35 mm. Level VII did not exist in 49 % of patients, and was less than 25 mm caudal to the sternal notch in 95 % of cases. Distinguishing level VII from level VI in thyroid cancer surgery may not be pertinent, due to the ease of access via a classic horizontal neck incision and the small sizes of level VII in the majority of patients.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.

PubMed

Ordookhani, Arash; Burman, Kenneth D

2017-04-01

There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders

PubMed Central

Ordookhani, Arash; Burman, Kenneth D.

2017-01-01

Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Results Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Conclusions Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted. PMID:29026409

A product Pearson-type VII density distribution

NASA Astrophysics Data System (ADS)

Nadarajah, Saralees; Kotz, Samuel

2008-01-01

The Pearson-type VII distributions (containing the Student's t distributions) are becoming increasing prominent and are being considered as competitors to the normal distribution. Motivated by real examples in decision sciences, Bayesian statistics, probability theory and Physics, a new Pearson-type VII distribution is introduced by taking the product of two Pearson-type VII pdfs. Various structural properties of this distribution are derived, including its cdf, moments, mean deviation about the mean, mean deviation about the median, entropy, asymptotic distribution of the extreme order statistics, maximum likelihood estimates and the Fisher information matrix. Finally, an application to a Bayesian testing problem is illustrated.

The effects of recombinant activated factor VII dose on the incidence of thromboembolic events in patients with coagulopathic bleeding.

PubMed

Bucklin, Mason H; Acquisto, Nicole M; Nelson, Catherine

2014-05-01

Previous studies have suggested the used of off-label recombinant factor VII (rFVIIa) increases the risk of thromboembolic events, but the effect of the dose of rFVIIa is not well described in the literature. All adult patients that received off-label rFVIIa from 2005-2012 were included in this single-center, retrospective cohort study. The primary endpoint was the incidence of a thromboembolic event in the low dose (<50 mcg/kg) compared to the high dose (≥50 mcg/kg) cohort. Secondary endpoints compared time to thromboembolic event, incidence of arterial compared to venous events, and mortality. There were 152 patients that received rFVIIa during the study period with 66 in the low dose cohort and 86 in the high dose cohort. Mean total dose of rFVIIa was 30.2 mcg/kg (SD ± 9.5 mcg/kg) in the low dose and 99.8 mcg/kg (SD ± 64.7 mcg/kg) in the high dose cohort (p=0.0001). The overall incidence of thromboembolic events was 12.5%. There were 12 (14%) events in the low dose cohort and seven (10.6%) in the high dose cohort, RR=0.76 (95% CI 0.31-1.82). There were no differences in any of the secondary outcomes. A higher incidence of thromboembolic events in cardiothoracic surgery (20.8%) and penetrating trauma patients (21.4%) was seen compared to the remaining cohort (6.7%). No significant difference in the incidence of thromboembolic events was seen between low dose versus high dose rFVIIa over a seven year period at our institution. However, due to the relatively low overall incidence and a small sample size, type II error may be present. Copyright © 2014 Elsevier Ltd. All rights reserved.

Economic analysis of recombinant activated factor VII versus plasma-derived activated prothrombin complex concentrate in mild to moderate bleeds: haemophilia registry data from the Czech Republic.

PubMed

Salaj, Peter; Penka, Miroslav; Smejkal, Petr; Geierova, Vera; Ovesná, Petra; Brabec, Petr; Cetkovsky, Petr; Kubes, Radovan; Mesterton, Johan; Lindgren, Peter

2012-05-01

Several studies suggest that recombinant activated factor VII (rFVIIa) is more cost-effective than plasma-derived activated prothrombin complex concentrate (pd-aPCC) in haemophilia with inhibitors. However, most do not consider differences between treated patients. This study compared the pharmacoeconomics of rFVIIa versus pd-aPCC treatment of mild to moderate bleeds in inhibitor patients, taking co-variables into account. The HemoRec and HemIS registries capture exhaustive bleeding data in inhibitor patients in the Czech Republic. For each bleed, patient and bleed characteristics, treatment outcomes and bypassing agent use were retrospectively analysed, and direct costs of care per bleed calculated. Generalised Linear Model regression methods with cluster effect were employed to account for the possibility of several bleedings from the same patient. There were 108 and 53 mild to moderate bleeds in the rFVIIa and pd-aPCC groups, respectively. Although re-bleeding rates were similar in both groups, deeper analyses revealed significant differences in time to bleed resolution: 93.8% of bleeds treated with rFVIIa were resolved within ≤ 12 h, versus 60.4% with pd-aPCC (P < 0.001). Mean total cost/bleed was lower with rFVIIa (336,852 [median, 290,696] CZK; €12,760 [11,011]) than pd-aPCC (522,768 [341,310] CZK; €19,802 [12,928]) (P = 0.002). Results were maintained after controlling for potential co-variables (bleed nature, time to treatment, target joints). The lower total treatment costs per bleed with rFVIIa than pd-aPCC suggest that first-line rFVIIa is more cost-effective than pd-aPCC in mild to moderate bleeds. Time to bleed resolution was also significantly shorter with rFVIIa. These results were maintained when controlled for potential confounders. Copyright © 2012 Elsevier Ltd. All rights reserved.

In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

DTIC Science & Technology

2007-11-01

purified soy phosphatides in ellagic acid (Actin FS Activated PTT Reagent, Dade Behring, Marburg, Germany) was added to plasma samples in a 1:1 volume...acetylsali- cylic acid or any other nonsteroidal anti-inflammatory drugs for the 7 days before blood sampling. A smooth cubital venipuncture was

76 FR 54493 - Furfuryl Alcohol From China; Institution of a Five-Year Review Concerning the Antidumping Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... the use, cost, or availability of major inputs into production); and factors related to the ability to... constitutes a major proportion of the total domestic production of the product. In its original determination... products which the Commission conducts under Title VII of the Act, or in internal audits and investigations...

75 FR 23303 - Chlorinated Isocyanurates From China and Spain

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

... output of the Domestic Like Product constitutes a major proportion of the total domestic production of... Commission conducts under Title VII of the Act, or in internal audits and investigations relating to the... various factors specified in section 752(a) of the Act (19 U.S.C. 1675a(a)) including the likely volume of...

16 CFR 305.8 - Submission of data.

Code of Federal Regulations, 2010 CFR

2010-01-01

... input voltage and frequency; (vi) Ballast efficacy factor; and (vii) Type (F40T12, F96T12 or F96T12HO..., heat pumps, furnaces, ceiling fans, and pool heaters) for each basic model in current production..., for each basic model in current production: the brand name; the model numbers for each basic model...

College and Adult Reading VII: The Seventh Yearbook of the North Central Reading Association.

ERIC Educational Resources Information Center

Wark, David M., Ed.

Spanning the annual meetings of the North Central Reading Association from 1971 to 1974, this yearbook presents papers dealing with programs and centers, materials and techniques, a new research field, and in honor of Roger S. Pepper. Papers include: "Attitudinal Factors among Marginal Admission Students" (Roger S. Pepper and John A. Drexler,…

77 FR 24436 - Approval and Promulgation of Air Quality Implementation Plans; Wisconsin; Milwaukee-Racine...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

.... How did EPA address missing data? V. Proposed Action VI. What is the effect of this action? VII.... ** Indicates incomplete data due to monitor shut down. IV. How did EPA address missing data? Appendix N of 40... in Milwaukee, where there are missing or incomplete data due to monitor shutdown or other factors...

In Vivo Bleeding Time and In Vitro Thrombelastography Measurements are Better Indicators of Dilutional Hypothermic Coagulopathy Than Prothrombin Time

DTIC Science & Technology

2007-06-01

of increased bruising, hematomas, and oozing from the recent surgical sites, or in massive hemorrhage from silent, pre-existing lesions such as peptic ... ulcers . Severe reduction of the vitamin K-dependent coagulation factors II, VII, IX, and X prolongs both PT and aPTT tests. Treatment with sodium

40 CFR 86.117-96 - Evaporative emission enclosure calibrations.

Code of Federal Regulations, 2014 CFR

2014-07-01

...), as measured in paragraph (b)(1) of this section. (v) r=FID response factor to methanol. (vi) PB = Barometric pressure, in. Hg. (kPa). (vii) T=Enclosure ambient temperature, R(K). (viii) i=Indicates initial reading. (ix) f=Indicates final reading. (x)(A) k=3.05. (B) For SI units, k=17.60. (xi) MHC, out = mass of...

40 CFR 86.117-96 - Evaporative emission enclosure calibrations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... this section. (v) r=FID response factor to methanol. (vi) PB=Barometric pressure, in. Hg. (kPa). (vii) T=Enclosure ambient temperature, R(K). (viii) i=Indicates initial reading. (ix) f=Indicates final reading. (x)(A) k=3.05. (B) For SI units, k=17.60. (xi) MHC, out=mass of hydrocarbon exiting the enclosure...

40 CFR 86.117-96 - Evaporative emission enclosure calibrations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... this section. (v) r=FID response factor to methanol. (vi) PB=Barometric pressure, in. Hg. (kPa). (vii) T=Enclosure ambient temperature, R(K). (viii) i=Indicates initial reading. (ix) f=Indicates final reading. (x)(A) k=3.05. (B) For SI units, k=17.60. (xi) MHC, out=mass of hydrocarbon exiting the enclosure...

29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 4 2012-07-01 2012-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 4 2013-07-01 2013-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 4 2011-07-01 2011-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

Turning Back the Title VII Clock: The Resegregation of the American Work Force through Validity Generalization.

ERIC Educational Resources Information Center

Goldstein, Barry L.; Patterson, Patrick O.

1988-01-01

Refers to Title VII of the Civil Rights Act of 1964 and the Supreme Court's disparate impact interpretation of Title VII in Griggs versus Duke Power Company. Contends that attacks on the Griggs decision are legally unsound and that claims made by advocates of validity generalization are scientifically unsupported. (Author/NB)

40 CFR Appendix Vii to Part 86 - Standard Bench Cycle (SBC)

Code of Federal Regulations, 2012 CFR

2012-07-01

.... VII Appendix VII to Part 86—Standard Bench Cycle (SBC) 1. The standard bench aging durability procedures [Ref. § 86.1823-08(d)] consist of aging a catalyst-oxygen-sensor system on an aging bench which follows the standard bench cycle (SBC) described in this appendix. 2. The SBC requires use of an aging...

40 CFR Appendix Vii to Part 86 - Standard Bench Cycle (SBC)

Code of Federal Regulations, 2013 CFR

2013-07-01

.... VII Appendix VII to Part 86—Standard Bench Cycle (SBC) 1. The standard bench aging durability procedures [Ref. § 86.1823-08(d)] consist of aging a catalyst-oxygen-sensor system on an aging bench which follows the standard bench cycle (SBC) described in this appendix. 2. The SBC requires use of an aging...

Title VII Sexual Harassment Guidelines and Educational Employment [and] What Can Students Do About Sex Discrimination?

ERIC Educational Resources Information Center

Howard, Susan; And Others

Guidelines concerning sexual harassment of employees at educational institutions under Title VII of the Civil Rights Act of 1964 are considered. November 1980 final interpretive guidelines issued by the Equal Employment Opportunity Commission state that Title VII prohibits sexual harassment of employees, that employers are responsible for the…

Survey of Land-Grant Colleges and Universities. Bulletin, 1930, No. 9. Volume II. [Part VII - Index

ERIC Educational Resources Information Center

Office of Education, United States Department of the Interior, 1930

1930-01-01

The attached document covers the concluding sections of the second volume of the Survey of Land-Grant Colleges and Universities: Part VII through the index. Part VII, Extension services, is divided into the following sections: (1) Introduction; (2) Position and objectives of Smith-Lever cooperative extension; (3) Administrative organization of…

75 FR 67416 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-02

... Clerical and Grammatical Corrections to Chapter VII, Section 1 (Exercise of Options Contracts) of the... (``BOX'') to make a clerical correction to Chapter VII, Section 1 (Exercise of Options Contracts) of the... Exchange is proposing to make a clerical correction to the rule text of Chapter VII, Section 1 (Exercise of...

Underuse of Title VII Funding for Indian Education in Arizona, Nevada, and Utah

ERIC Educational Resources Information Center

West Comprehensive Center at WestEd, 2015

2015-01-01

Title VII provides funding for the education of American Indian/Alaska Native students based on a formula grant available to school districts, charter schools, and local education agencies (LEAs). This report explores why some eligible schools and districts do not apply for federal Title VII, potentially resulting in American Indian/Alaska Native…

78 FR 34545 - Prohibition Against Federal Assistance to Swaps Entities (Regulation KK)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-10

...) only, call (202) 263- 4869. SUPPLEMENTARY INFORMATION: Section 716 of Title VII of the Dodd-Frank Wall... agencies to enforce compliance with laws such as Title VII of the Dodd-Frank Act against uninsured U.S... 716 and Title VII of the Dodd-Frank Act generally are intended to reduce systemic risks from...

20 CFR Appendix Vii to Subpart C... - “Old-Law” Contribution and Benefit Base

Code of Federal Regulations, 2010 CFR

2010-04-01

... Appendix VII to Subpart C of Part 404 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Computing Primary Insurance Amounts Pt. 404, Subpt. C, App. VII... Security Act without the enactment of the 1977 amendments. Year Amount 1979 $18,900 1980 20,400 1981 22,200...

Managing Information Technology: Facing the Issues. Track VII: Applications and Technology Issues.

ERIC Educational Resources Information Center

CAUSE, Boulder, CO.

Eight papers making up Track VII of the 1989 conference of the Professional Association for the Management of Information Technology in Higher Education (known as CAUSE, an acronym of the association's former name) are presented in this document. The focus of Track VII is on applications and technology issues, and the papers include: "The…

Heptavalent Neptunium in a Gas-Phase Complex: (Np VIIO 3 +)(NO 3 –) 2

DOE PAGES

Dau, Phuong D.; Maurice, Remi; Renault, Eric; ...

2016-09-15

A central goal of chemistry is to achieve ultimate oxidation states, including in gas-phase complexes with no condensed phase perturbations. In the case of the actinide elements, the highest established oxidation states are labile Pu(VII) and somewhat more stable Np(VII). We have synthesized and characterized gas-phase AnO 3(NO 3) 2- complexes for An = U, Np, and Pu by endothermic NO 2 elimination from AnO 2(NO 3) 3-. It was previously demonstrated that the PuO 3+ core of PuO 3(NO 3) 2- has a Pu—O• radical bond such that the oxidation state is Pu(VI); it follows that in UO 3(NOmore » 3) 2- it is the stable U(VI) oxidation state. On the basis of the relatively more facile synthesis of NpO 3(NO 3) 2-, a Np(VII) oxidation state is inferred. This interpretation is substantiated by reactivity of the three complexes: NO 2 spontaneously adds to UO 3(NO 3) 2- and PuO 3(NO 3) 2- but not to NpO 3(NO 3) 2-. This unreactive character is attributed to a Np(VII)O 3+ core with three stable Np=O bonds, this in contrast to reactive U—O• and Pu—O• radical bonds. The computed structures and reaction energies for the three AnO 3(NO 3) 2- support the conclusion that the oxidation states are U(VI), Np(VII), and Pu(VI). These results establish the extreme Np(VII) oxidation state in a gas-phase complex, and demonstrate the inherently greater stability of Np(VII) versus Pu(VII).« less

Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse

PubMed Central

Giusti, Delphine; Gatouillat, Grégory; Le Jan, Sébastien; Plée, Julie; Bernard, Philippe; Antonicelli, Frank; Pham, Bach-Nga

2018-01-01

Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P < 0.01), independently of mucosal involvement. Those 10 relapsing BP patients were also characterized by a sustained high concentration of anti-BP180 AAb, whereas the serum anti-BP230 AAb concentrations did not vary in BP patients with relapse according to the presence of anti-type VII collagen AAbs. Thus, our study showed that anti-type VII collagen along with anti-BP180 AAbs detection stratified BP patients at time of relapse, illustrating a still dysregulated immune response that could reflect a potential epitope spreading mechanism in those BP patients. PMID:29619029

The adenovirus major core protein VII is dispensable for virion assembly but is essential for lytic infection

PubMed Central

Suomalainen, Maarit; Zheng, Yueting; Boucke, Karin

2017-01-01

The Adenovirus (Ad) genome within the capsid is tightly associated with a virus-encoded, histone-like core protein—protein VII. Two other Ad core proteins, V and X/μ, also are located within the virion and are loosely associated with viral DNA. Core protein VII remains associated with the Ad genome during the early phase of infection. It is not known if naked Ad DNA is packaged into the capsid, as with dsDNA bacteriophage and herpesviruses, followed by the encapsidation of viral core proteins, or if a unique packaging mechanism exists with Ad where a DNA-protein complex is simultaneously packaged into the virion. The latter model would require an entirely new molecular mechanism for packaging compared to known viral packaging motors. We characterized a virus with a conditional knockout of core protein VII. Remarkably, virus particles were assembled efficiently in the absence of protein VII. No changes in protein composition were evident with VII−virus particles, including the abundance of core protein V, but changes in the proteolytic processing of some capsid proteins were evident. Virus particles that lack protein VII enter the cell, but incoming virions did not escape efficiently from endosomes. This greatly diminished all subsequent aspects of the infectious cycle. These results reveal that the Ad major core protein VII is not required to condense viral DNA within the capsid, but rather plays an unexpected role during virus maturation and the early stages of infection. These results establish a new paradigm pertaining to the Ad assembly mechanism and reveal a new and important role of protein VII in early stages of infection. PMID:28628648

Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference.

PubMed

Temperini, Claudia; Cecchi, Alessandro; Scozzafava, Andrea; Supuran, Claudiu T

2009-02-01

Thiazide and high ceiling diuretics were recently shown to inhibit all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1) with a very different profile as compared to classical inhibitors, such as acetazolamide, methazolamide, and ethoxzolamide. Some of these structurally related compounds have a very different behavior against the widespread isozyme CA II, with chlorthalidone, trichloromethiazide, and furosemide being efficient inhibitors against CA II (K(I)s of 65-138 nM), whereas indapamide is a much weaker one (K(I) of 2520 nM). Furthermore, some of these diuretics are quite efficient (low nanomolar) inhibitors of other isoforms, for example, chlorthalidone against hCA VB, VII, IX, and XIII; indapamide against CA VII, IX, XII, and XIII, trichloromethiazide against CA VII and IX, and furosemide against CA I and XIV. Examining the four X-ray crystal structures of their CA II adducts, we observed several (2-3) active site water molecules interacting with the chlorthalidone, trichloromethiazide, and furosemide scaffolds which may be responsible for this important difference of activity. Indeed, indapamide bound to CA II has no interactions with active site water molecules. Chlorthalidone bound within the CA II active site is in an enolic (lactimic) tautomeric form, with the enolic OH also participating in two strong hydrogen bonds with Asn67 and a water molecule. The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications.

In vitro microleakage of glass-ionomer composite resin hybrid materials.

PubMed

Rodrigues, J A; De Magalhães, C S; Serra, M C; Rodrigues Júnior, A L

1999-01-01

The purpose of this study was to evaluate the microleakage of six glass-ionomer composite resin hybrid materials compared with a glass-ionomer cement and a composite resin. Standardized class 5 dentin cavities were prepared on root surfaces of 240 extracted human teeth that were randomly assigned to eight groups and restored using the following restorative systems: (I) Vitremer, (II) Compoglass, (III) Photac-Fil Aplicap, (IV) Variglass, (V) Dyract, (VI) Fuji II LC, (VII) Ketac-Fil Aplicap, and (VIII) Z100. The teeth were thermocycled, placed in a 2% methylene blue solution, and sectioned with diamond disks. Dye penetration was scored on a scale of 0-3. Results showed no significant differences among groups VIII, IV, I, V, VI, III, and II. There were also no significant differences among groups VI, III, II, and VII.

Analysis of Expandability and Modifiability of Computer Configuration Concepts for ATC. Volume I. Distributed Concept.

DTIC Science & Technology

1979-11-01

C-9 TRANSITION CONFIGURATION ........................... C-29 i r Fvii LIST OF TABLES Table Page 2.1-1 PARAMETERS DESCRIBING ATC OPERATION - BASELINE...buffer load from each sensor. Medium Storage (Buffer space for data in and out is largest factor .) II P=K +KR Processing. Where R is the number of... factors to the data from the next scan VII Provides support service Operational Role VIII Dependence Requires data from Preliminary Processing and Target

Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

PubMed

Heinz, Stefan; Braspenning, Joris

2015-01-01

An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

Awareness of dysgeusia and gustatory tests in patients undergoing chemotherapy for breast cancer.

PubMed

Kuba, Sayaka; Fujiyama, Rie; Yamanouchi, Kosho; Morita, Michi; Sakimura, Chika; Hatachi, Toshiko; Matsumoto, Megumi; Yano, Hiroshi; Takatsuki, Mitsuhisa; Hayashida, Naomi; Nagayasu, Takeshi; Eguchi, Susumu

2018-05-12

We analyzed the prevalence of gustatory test abnormalities in breast cancer (BC) patients undergoing chemotherapy. We enrolled 43 BC patients undergoing chemotherapy and 38 BC patients who had never undergone chemotherapy (control group). Two gustatory tests were conducted: an instillation method examining the threshold for four basic taste stimuli and an electrogustometry method measuring the threshold for perception with electric stimulation at the front two-thirds of the tongue (cranial nerve VII) and at the back third of the tongue (cranial nerve IX). The results of the two gustatory tests and clinicopathological factors were compared between the chemotherapy and control groups and between patients with and without awareness of dysgeusia in the chemotherapy group. In the chemotherapy group, 19 (44%) patients were aware of dysgeusia and 8 (19%) had hypogeusia using the instillation method. Although more patients had parageusia in the chemotherapy than control group, no significant differences in the results of the two gustatory tests were observed. Patients with dysgeusia awareness had a higher threshold at cranial nerve IX using the electrogustometry method than those without dysgeusia awareness; no significant differences in hypogeusia were observed using the instillation method. In fact, 74% (14/19) of patients with dysgeusia awareness could identify the four tastes accurately using the instillation method. Similar results were observed for the instillation and electrogustometry methods at cranial nerve VII. While approximately half of the chemotherapy patients were aware of dysgeusia, 81% (35/43) of them could accurately identify the four basic tastes using the instillation method.

Observation of Solar Wind Charge Exchange Emission From Exospheric Material in and Outside Earth's Magnetosheath 2008 September 25

NASA Technical Reports Server (NTRS)

Snowden, S. L.; Collier, M. R.; Cravens, T.; Kuntz, K. D.; Lepri, S. T.; Robertson, I.; Tomas, L.

2009-01-01

A long XMM-Newton exposure is used to observe solar wind charge exchange (SWCX) emission from exospheric material in and outside Earth's magnetosheath. The light curve of the O vii (0.5-0.62 keV) band is compared with a model for the expected emission, and while the emission is faint and the light curve has considerable scatter, the correlation is significant to better than 99.9%. This result demonstrates the validity of the geocoronal SWCX emission model for predicting a contribution to astrophysical observations to a scale factor of order unity (1.5). In addition, an average value of the SWCX O vii emission from the magnetosheath over the observation of 2.6 +/- 0.5 LU is derived. The results also demonstrate the potential utility of using X-ray observations to study global phenomena of the magnetosheath which currently are only investigated using in situ measurements.

A search for the millimetre lines of HCN in Comets Wilson 1987 VII and Machholz 1988 XV

NASA Astrophysics Data System (ADS)

Crouvisier, J.; Despois, D.; Bockelee-Morvan, D.; Gerard, E.; Paubert, G.; Johansson, L. E. B.; Ekelund, L.; Winnberg, A.; Ge, W.; Irvine, W. M.; Kinzel, W. M.; Schloerb, F. P.

1990-08-01

The J(1-0) lines of HCN at 89 GHz were searched for in Comet Wilson 1987 VII, with the FCRAO, the SEST and the IRAM radio telescopes between February and June 1987. There was no firm detection, but significant upper limits were obtained, which put severe constraints on the HCN production rate in that comet. A direct comparison with the observations of P/Halley suggests that the HCN abundance relative to water might be smaller in Comet Wilson by at least a factor of two. The J(1-0) and J(3-2) lines of HCN at 89 and 266 GHz were searched for in Comet Machholz 1988 XV when it was close to perihelion at 0.17 AU from the sun. There was no detection. At that moment, the comet was probably no longer active.

A comparison of the C III, O V, F VI, and Ne VII Delta n = 0 (2-2) line emissions from a laboratory plasma with theoretical predictions and astrophysical observations

NASA Technical Reports Server (NTRS)

Finkenthal, M.; Yu, . L.; Lippmann, S.; Huang, L. K.; Moos, H. W.; Stratton, B. C.; Bhatia, A. K.

1987-01-01

Spectra of the Delta n = 0 (2-2) transitions of Be I-like ions, C III, O V, F VI, and Ne VII emitted from the TEXT tokamak, were measured with photometrically calibrated instrumentation and compared to the predictions of several models which differ in their treatment of electron impact excitation, using either the distorted wave or R-matrix approach. It was found that the ions from C III to Ne VII were located near the edge of the plasma, at densities between 10 to the 12th and 13th/cu cm. The experimental line ratios were compared with several sets of computations. Agreement is obtained between the experimental data and computations by using the R-matrix technique. This leads to the conclusion that the effect resonances must be included in collision strength calculations, particularly at low nuclear charge. The results show that the line ratios studied may be used with confidence as electron density diagnostics for laboratory or astrophysical plasmas.

8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

Code of Federal Regulations, 2012 CFR

2012-01-01

... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

Code of Federal Regulations, 2013 CFR

2013-01-01

... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

Code of Federal Regulations, 2010 CFR

2010-01-01

... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

Code of Federal Regulations, 2014 CFR

2014-01-01

... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

Code of Federal Regulations, 2011 CFR

2011-01-01

... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

20 CFR Appendix Vii to Subpart C... - “Old-Law” Contribution and Benefit Base

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false âOld-Lawâ Contribution and Benefit Base VII... Appendix VII to Subpart C of Part 404—“Old-Law” Contribution and Benefit Base Explanation: We use these... appendix IV). This is the contribution and benefit base that would have been effective under the Social...