Macrofossils and biostratigraphy of the Bakken Formation (Devonian and Mississippian) in western North Dakota

The Bakken Formation, up to 145 feet thick in North Dakota, is a subsurface formation in the Williston Basin that typically consists of two black shale members separated by a middle member of predominantly gray siltstone or silty limestone up to 85 feet thick. Well over 500 macrofossils representing more than 50 taxa were collected from cores of 40 wells. Brachiopods, the most common fossil, represent 17 genera, 1 of which have not been previously reported from the Bakken. Nonbrachiopod fossils of this study, mostly not previously reported from the Bakken, are a hylothyrid, a conulariid, a syringoporid coral, several genera of gastropods and pelecypods, straight and coiled cephalopods, a trilobite, a conchostracan, a shrimp-like organism, pelmatozoan columns, fish fragments, trace fossils, and Foerstia sp. and other plants. Fossils not treated herein are foraminiferids, ostracods conodonts, and palynomorphs. The macrofossils of the Bakken occur mostly within five stratigraphic intervals; each interval contains a different assemblage and appears to represent a geographic extension of a previously known fauna. The basal few feet of the lower shale member locally contains a benthic rhynchonellid fauna that appears similar to fossils from near the base of Devonian black shales in the eastern United States. Foerstia sp., found in the basal 20 to 30 percent of the lower shale member in one core, appears to mark a widespread time-stratigraphic interval of Late Devonian age. The conchostracan Cyzicus (Lioestheria sp. is prolific in the upper few inches of the lower shale near the center of the basin; it is concentrated at a similar interval in correlatives of the Bakken that crop out in the Western Interior. The other fossiliferous intervals of the Bakken occur in the middle member and are found in association with lithologies that are used here to divide the middle member into three stratigraphic units: units 1, 2, and 3. The lowest of these, unit 1, up to about 30 feet thick, contains a Syringothyris brachiopod assemblage similar to that of the Louisiana Limestone of latest Devonian age in the upper Mississippi Valley and in siltstones of Bakken correlatives in the western United States, also of latest Devonian age. Unit 2 is up to about 35 feet thick and is poorly fossiliferous. Blade-like leaves are abundant in the basal few feet of unit 2 near the center of the basin, and correlate with similar “leaves” that are locally abundant at the base of the Mississippian type section in Illinois. This correlation, together with the correlation of the brachiopods in units 1 and 3, suggest an early Mississippian age for unit 2. The base of unit 2, a poorly defined contact, thus appears to mark the base of the Mississippian in North Dakota. Unit 3 of the Bakken, about 5 feet thick, contains brachiopods that correlate with those of the McCraney Limestone in the type Mississippian section and the Spirifer marionensis assemblage of the Exshaw Formation in Alberta, both of early, but not earliest, Kinderhookian age; this may be the first correlation made between the McCraney and Exshaw. Macrofossils in the upper shale member are generally small, thin-shelled, and rare; no fossiliferous intervals or age-diagnostic fossils were found in this member. The lower Bakken shale appears to have been deposited in a deepened sea during a period of worldwide rise in sea level. Unit 1 of the middle member was deposited during a major regression and units 2 and 3 are transgressive, shallow-water deposits. The upper Bakken shale was deposited during a major, worldwide rise in sea level

Estimating the Impact of Food and Drug Administration Regulation of Cigarette Package Warning Labels and the Potential Added Impact of Plain Packaging: Evidence From Experimental Auctions Among Adult Smokers

Objective: To estimate differences in demand for cigarette packages with different packaging and health warning label formats. Methods: Adult smokers (n=404) in four states participated in experimental auctions. Participants bid on two of four experimental conditions, each involving a different health warning label format but with the same warning message: 1. text on 50% of pack side; 2. text on 50% of the pack front and back; 3. text with a graphic picture on 50% of the pack front and back; and 4. same as previous format, but without brand imagery. Results: Mean bids decreased across conditions (1. $3.52; 2.$3.43; 3. $3.11; 4.$2.93). Bivariate and multivariate random effects models indicated that there was no statistically significant difference in demand for packs with either of the two text only warnings; however, demand was significantly lower for both packs with prominent pictorial warnings, with the lowest demand associated with the plain, unbranded pack. Conclusions: Results suggest that prominent health warnings with graphic pictures will reduce demand for cigarettes. Regulators should not only consider this type of warning label, but also plain packaging policies for tobacco products.experimental auctions, cigarette labels, grotesque images, Food Consumption/Nutrition/Food Safety, Health Economics and Policy, C93,

Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease

X-linked severe immunodeficiency disease (SCID-X1) is an inherited, rare, and life-threating disease. The genetic origin is a defect in the interleukin 2 receptor γ chain (IL2RG) gene and patients are classically characterized by absence of T and NK cells, as well as presence of partially-functional B cells. Without any treatment the disease is usually lethal during the first year of life. The treatment of choice for these patients is hematopoietic stem cell transplantation, with an excellent survival rate (>90%) if an HLA-matched sibling donor is available. However, when alternative donors are used, the success and survival rates are often lower. Gene therapy has been developed as an alternative treatment initially using γ-retroviral vectors to correct the defective γ chain in the absence of pre-conditioning treatment. The results were highly promising in SCID-X1 infants, showing long-term T-cell recovery and clinical benefit, although NK and B cell recovery was less robust. However, some infants developed T-cell acute lymphoblastic leukemia after the gene therapy, due to vector-mediated insertional mutagenesis. Consequently, considerable efforts have been made to develop safer vectors. The most recent clinical trials using lentiviral vectors together with a low-dose pre-conditioning regimen have demonstrated excellent sustained T cell recovery, but also B and NK cells, in both children and adults. This review provides an overview about the different gene therapy approaches used over the last 20 years to treat SCID-X1 patients, particularly focusing on lymphoid immune reconstitution, as well as the developments that have improved the process and outcomes

Lentiviral vector transduction of spermatozoa as a tool for the study of early development

Spermatozoa and lentiviruses are two of nature’s most efficient gene delivery vehicles. Both can be genetically modified and used independently for the generation of transgenic animals or gene transfer/therapy of inherited disorders. Here we show that mature spermatozoa can be directly transduced with various pseudotyped lentiviral vectors and used in in vitro fertilisation studies. Lentiviral vectors encoding Green Fluorescent Protein (GFP) were shown to be efficiently processed and expressed in sperm. When these transduced sperm were used in in vitro fertilisation studies, GFP expression was observed in arising blastocysts. This simple technique of directly transducing spermatozoa has potential to be a powerful tool for the study of early and pre-implantation development and could be used as a technique in transgenic development and vertical viral transmission studies

Actual and Predicted Behavior of Large Metal Culverts

The stability of large metal culverts depends on the performance of the backfill around the pipe, which must be considered as a part of the structure when evaluating its safety. A simplified method to evaluate the current stability of such a structure on the basis of the structure\u27s shape is derived. Useful when limited amount of information is available, this method provides an economical procedure for: (1) evaluating the condition of the existing backfill and its capability to provide a safe support for the structure; (2) predicting final movements and determining if additional investigations are necessary to establish the safety of the structure; and (3) determining if measured deflections are in agreement with those predicted and, if not, determining if the safety of the structure is endangered by phenomena other than the expected behavior of surrounding soil (e.g. voids near pipe, soil erosion, non-symmetric loadings)

Integrase-deficient lentiviral vectors mediate efficient gene transfer to human vascular smooth muscle cells with minimal genotoxic risk

We have previously shown that injury-induced neointima formation was rescued by adenoviral-Nogo-B gene delivery. Integrase-competent lentiviral vectors (ICLV) are efficient at gene delivery to vascular cells but present a risk of insertional mutagenesis. Conversely, integrase-deficient lentiviral vectors (IDLV) offer additional benefits through reduced mutagenesis risk, but this has not been evaluated in the context of vascular gene transfer. Here, we have investigated the performance and genetic safety of both counterparts in primary human vascular smooth muscle cells (VSMC) and compared gene transfer efficiency and assessed the genotoxic potential of ICLVs and IDLVs based on their integration frequency and insertional profile in the human genome. Expression of enhanced green fluorescent protein (eGFP) mediated by IDLVs (IDLV-eGFP) demonstrated efficient transgene expression in VSMCs. IDLV gene transfer of Nogo-B mediated efficient overexpression of Nogo-B in VSMCs, leading to phenotypic effects on VSMC migration and proliferation, similar to its ICLV version and unlike its eGFP control and uninfected VSMCs. Large-scale integration site analyses in VSMCs indicated that IDLV-mediated gene transfer gave rise to a very low frequency of genomic integration compared to ICLVs, revealing a close-to-random genomic distribution in VSMCs. This study demonstrates for the first time the potential of IDLVs for safe and efficient vascular gene transfer

Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency

Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8 + T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8 + lymphoblasts had reduced interferon-γ secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL

Microbial Diversity Aboard Spacecraft: Evaluation of the International Space Station

An evaluation of the microbial flora from air, water, and surface samples provided a baseline of microbial diversity onboard the International Space Station (ISS) to gain insight into bacterial and fungal contamination during the initial stages of construction and habitation. Using 16S genetic sequencing and rep-PeR, 63 bacterial strains were isolated for identification and fingerprinted for microbial tracking. The use of these molecular tools allowed for the identification of bacteria not previously identified using automated biochemical analysis and provided a clear indication of the source of several ISS contaminants. Fungal and bacterial data acquired during monitoring do not suggest there is a current microbial hazard to the spacecraft, nor does any trend indicate a potential health risk. Previous spacecraft environmental analysis indicated that microbial contamination will increase with time and require continued surveillance