Commercial Bank Financing for Industrial Development

Has industrial development in South Dakota been hampered by financial constraints? Will the capital sufficient for future industrial financing needs be available? Focusing on commercial banks and their role in financing industrial development, the study which this bulletin reports specifically sought: 1 . to describe the structure, past, and probable future growth of manufacturing and processing industries in South Dakota. 2. to determine to what extent industrial firms are hampered by lack of funds for construction of new facilities, for expansion of present facilities, and for operating expenses; and to determine the basis of restriction. 3. to determine the present role of commercial banks in financing industrial development. 4. to determine attitudes that bankers have toward industrial development within their community and their attitudes and policies in financing this development. 5. to explore the potential and future role of the commercial banks in financing industrial development

Compartment Model for Controlling Infectious Livestock Disease: Cost-Effective Control Strategies for Johne's Disease In Dairy Herds

Replaced with revised version of paper 06/08/11.animal compartment model, dairy cattle disease, Johne’s disease, livestock disease control, Mycobacterium avium subspecies paratuberculosis, Farm Management, Livestock Production/Industries,

Economic Analysis of Johne's Disease Control Strategies in Dairy Herds

Infectious diseases play a critical role in determining the profitability of individual farms and maintaining the viability of livestock industries, international trade, and trade policies. Thus, it is critical to analyze the economic consequences of infectious diseases, and the effects of producer strategies to control or eliminate diseases in a cost efficient approach. Also, important is the goal to rally support for the development of public disease control programs. This study examined the long-term feasibility and effectiveness of various producer strategies to prevent and control Johne’s disease in dairy herds, an infectious and incurable disease which has significant economic repercussions for the dairy industry. There are few previous studies available on the economic aspects of Johne’s disease and there remains a knowledge gap with regard to the economics of the disease and the economic justification of the disease controls associated with the biological characteristics of the disease. This study contributes to this body of knowledge. We constructed an optimal control model integrating the biology of animals and disease into an economic framework to estimate the best control method in terms of maximizing an individual farm’s profit and minimizing disease elimination periods. Our results show that any Johne’s disease control method yields a higher net present value compared to no control. Implementing a single control strategy can control the disease, but a combination of control strategies in different categories is the most profitable and effective way to reduce the infection rate in a disease-infected herd. The results of the study are directly applicable to managing this disease on US dairy farms and contribute to controlling a high-priority pathogen in an important industry.Animal disease control, dairy herd model, Johne's disease, optimal control model, paratuberculosis, Agribusiness, Farm Management, Livestock Production/Industries, Research and Development/Tech Change/Emerging Technologies,

Economic Effects of a Potential Foodborne Disease: Potential Relationship between Mycobacterium Avium Subs. Paratuberculosis (MAP) in Dairy and Crohn’s in Humans

Welfare costs of a potential food shock were estimated by disseminating information to milk drinkers on the prevalence of Mycobacterium avium sub. paratuberculosis (MAP) in the U.S. milk supply, its potential linkage to Crohn’s disease in humans, and subsequent government intervention to minimize MAP in the milk supply. We found that 19.6% of milk consumers exposed to MAP information would stop milk consumption at current market prices, and that only 5% of those would return to their original milk consumption levels after the government intervention. Societal costs of the food shock after the intervention were estimated at $18.2 billion

CRISPR-enhanced human adipocyte \u27browning\u27 as cell therapy for metabolic disease [preprint]

Obesity and type 2 diabetes (T2D) are associated with poor tissue responses to insulin [1,2], disturbances in glucose and lipid fluxes [3-5] and comorbidities including steatohepatitis [6] and cardiovascular disease [7,8]. Despite extensive efforts at prevention and treatment [9,10], diabetes afflicts over 400 million people worldwide [11]. Whole body metabolism is regulated by adipose tissue depots [12-14], which include both lipid-storing white adipocytes and less abundant \u27brown\u27 and \u27brite/beige\u27 adipocytes that express thermogenic uncoupling protein UCP1 and secrete factors favorable to metabolic health [15-18]. Application of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing [19,20] to enhance \u27browning\u27 of white adipose tissue is an attractive therapeutic approach to T2D. However, the problems of cell-selective delivery, immunogenicity of CRISPR reagents and long term stability of the modified adipocytes are formidable. To overcome these issues, we developed methods that deliver complexes of SpyCas9 protein and sgRNA ex vivo to disrupt the thermogenesis suppressor gene NRIP1 [21,22] with near 100% efficiency in human or mouse adipocytes. NRIP1 gene disruption at discrete loci strongly ablated NRIP1 protein and upregulated expression of UCP1 and beneficial secreted factors, while residual Cas9 protein and sgRNA were rapidly degraded. Implantation of the CRISPR-enhanced human or mouse brown-like adipocytes into high fat diet fed mice decreased adiposity and liver triglycerides while enhancing glucose tolerance compared to mice implanted with unmodified adipocytes. These findings advance a therapeutic strategy to improve metabolic homeostasis through CRISPR-based genetic modification of human adipocytes without exposure of the recipient to immunogenic Cas9 or delivery vectors

Evaluation of the Influenza A Replicon for Transient Expression of Recombinant Proteins in Mammalian Cells

Recombinant protein expression in mammalian cells has become a very important technique over the last twenty years. It is mainly used for production of complex proteins for biopharmaceutical applications. Transient recombinant protein expression is a possible strategy to produce high quality material for preclinical trials within days. Viral replicon based expression systems have been established over the years and are ideal for transient protein expression. In this study we describe the evaluation of an influenza A replicon for the expression of recombinant proteins. We investigated transfection and expression levels in HEK-293 cells with EGFP and firefly luciferase as reporter proteins. Furthermore, we studied the influence of different influenza non-coding regions and temperature optima for protein expression as well. Additionally, we exploited the viral replication machinery for the expression of an antiviral protein, the human monoclonal anti-HIV-gp41 antibody 3D6. Finally we could demonstrate that the expression of a single secreted protein, an antibody light chain, by the influenza replicon, resulted in fivefold higher expression levels compared to the usually used CMV promoter based expression. We emphasize that the influenza A replicon system is feasible for high level expression of complex proteins in mammalian cells

GABAergic Neuron Deficit As An Idiopathic Generalized Epilepsy Mechanism: The Role Of BRD2 Haploinsufficiency In Juvenile Myoclonic Epilepsy

Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/− mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/− males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/− female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/− vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/− mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/− mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE

Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model

Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans