Desalination and Reuse of High-Salinity Shale Gas Produced Water: Drivers, Technologies, and Future Directions

In the rapidly developing shale gas industry, managing produced water is a major challenge for maintaining the profitability of shale gas extraction while protecting public health and the environment. We review the current state of practice for produced water management across the United States and discuss the interrelated regulatory, infrastructure, and economic drivers for produced water reuse. Within this framework, we examine the Marcellus shale play, a region in the eastern United States where produced water is currently reused without desalination. In the Marcellus region, and in other shale plays worldwide with similar constraints, contraction of current reuse opportunities within the shale gas industry and growing restrictions on produced water disposal will provide strong incentives for produced water desalination for reuse outside the industry. The most challenging scenarios for the selection of desalination for reuse over other management strategies will be those involving high-salinity produced water, which must be desalinated with thermal separation processes. We explore desalination technologies for treatment of high-salinity shale gas produced water, and we critically review mechanical vapor compression (MVC), membrane distillation (MD), and forward osmosis (FO) as the technologies best suited for desalination of high-salinity produced water for reuse outside the shale gas industry. The advantages and challenges of applying MVC, MD, and FO technologies to produced water desalination are discussed, and directions for future research and development are identified. We find that desalination for reuse of produced water is technically feasible and can be economically relevant. However, because produced water management is primarily an economic decision, expanding desalination for reuse is dependent on process and material improvements to reduce capital and operating costs

The LKB1 Tumor Suppressor as a Biomarker in Mouse and Human Tissues

Germline mutations in the LKB1 gene (also known as STK11) cause the Peutz-Jeghers Syndrome, and somatic loss of LKB1 has emerged as causal event in a wide range of human malignancies, including melanoma, lung cancer, and cervical cancer. The LKB1 protein is a serine-threonine kinase that phosphorylates AMP-activated protein kinase (AMPK) and other downstream targets. Conditional knockout studies in mouse models have consistently shown that LKB1 loss promotes a highly-metastatic phenotype in diverse tissues, and human studies have demonstrated a strong association between LKB1 inactivation and tumor recurrence. Furthermore, LKB1 deficiency confers sensitivity to distinct classes of anticancer drugs. The ability to reliably identify LKB1-deficient tumors is thus likely to have important prognostic and predictive implications. Previous research studies have employed polyclonal antibodies with limited success, and there is no widely-employed immunohistochemical assay for LKB1. Here we report an assay based on a rabbit monoclonal antibody that can reliably detect endogenous LKB1 protein (and its absence) in mouse and human formalin-fixed, paraffin-embedded tissues. LKB1 protein levels determined through this assay correlated strongly with AMPK phosphorylation both in mouse and human tumors, and with mRNA levels in human tumors. Our studies fully validate this immunohistochemical assay for LKB1 in paraffin-embedded formalin tissue sections. This assay should be broadly useful for research studies employing mouse models and also for the development of human tissue-based assays for LKB1 in diverse clinical settings

Architecture and Advanced Electronics Pathways Toward Highly Adaptive Energy- Efficient Computing

With the explosion of the number of compute nodes, the bottleneck of future computing systems lies in the network architecture connecting the nodes. Addressing the bottleneck requires replacing current backplane-based network topologies. We propose to revolutionize computing electronics by realizing embedded optical waveguides for onboard networking and wireless chip-to-chip links at 200-GHz carrier frequency connecting neighboring boards in a rack. The control of novel rate-adaptive optical and mm-wave transceivers needs tight interlinking with the system software for runtime resource management

Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model

Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16LUC), which faithfully reports expression of p16INK4a, a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16+/LUC mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic mice. Expression of p16INK4a with aging did not predict cancer development, suggesting that the accumulation of senescent cells is not a principal determinant of cancer-related death. In 14 of 14 tested tumor models, expression of p16LUC was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities. Activation of p16INK4a was noted in the emerging neoplasm and surrounding stromal cells. This work suggests that p16INK4a activation is a characteristic of all emerging cancers, making the p16LUC allele a sensitive, unbiased reporter of neoplastic transformation

El espacio como instrumento de formación. Arquitectura como estrategia educativa aplicado a un Jardín Infantil

Artículo de GradoEl proyecto se desarrolla como ejercicio académico en un contexto real donde se propone adoptar y entender la transformación de la idea de diseño en las instalaciones educacionales en el país con base en la petición que la secretaria de educación le hizo a el Arq. Frank Locker, donde el arquitecto debe establecer criterios de diseño en búsqueda de cambiar la forma de aprender, todo esto basado en la relación entre el tipo de educación y la arquitectura como lugar de aprendizaje, enfocado en lo que la educación Colombiana busca.1. Resumen 2. Abstract 3. Contenido 4. Introducción 5. Hipótesis 6. Objetivo General 7. Objetivos Específicos 8. Marco teórico 9. Metodología 10. Resultados 11. La relación entre equipamiento y la transformación de espacio público en un entorno urbano no consolidado 12. Espacio para la enseñanza 13. Disposición de elementos estructurales para mayor eficiencia formal y sismo resistente 14. Discusión basada en comparación con particularidades similares 15. Conclusión 16. ReferenciasPregradoArquitect

Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model

Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16LUC), which faithfully reports expression of p16INK4a, a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16+/LUC mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic mice. Expression of p16INK4a with aging did not predict cancer development, suggesting that the accumulation of senescent cells is not a principal determinant of cancer-related death. In 14 of 14 tested tumor models, expression of p16LUC was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities. Activation of p16INK4a was noted in the emerging neoplasm and surrounding stromal cells. This work suggests that p16INK4a activation is a characteristic of all emerging cancers, making the p16LUC allele a sensitive, unbiased reporter of neoplastic transformation

Immunological assays for chemokine detection in in-vitro culture of CNS cells

Herein we review the various methods currently in use for determining the expression of chemokines by CNS cells in vitro. Chemokine detection assays are used in conjuction with one another to provide a comprehensive, biologically relevant assessment of the chemokines which is necessary for correct data interpretation of a specific observed biological effect. The methods described include bioassays for soluble chemokine receptors, RNA extraction, RT-PCR, Real - time quantitative PCR, gene array analysis, northern blot analysis, Ribonuclease Protection assay, Flow cytometry, ELISPOT, western blot analysis, and ELISA. No single method of analysis meets the criteria for a comprehensive, biologically relevant assessment of the chemokines, therefore more than one assay might be necessary for correct data interpretation, a choice that is based on development of a scientific rationale for the method with emphasis on the reliability and relevance of the method

Locally Administrated Perindopril Improves Healing in an Ovariectomized Rat Tibial Osteotomy Model

Angiotensin-converting enzyme inhibitors are widely prescribed to regulate blood pressure. High doses of orally administered perindopril have previously been shown to improve fracture healing in a mouse femur fracture model. In this study, perindopril was administered directly to the fracture area with the goal of stimulating fracture repair. Three months after being ovariectomized (OVX), tibial fractures were produced in Sprague–Dawley rats and subsequently stabilized with intramedullary wires. Perindopril (0.4 mg/kg/day) was injected locally at the fractured site for a treatment period of 7 days. Vehicle reagent was used as a control. Callus quality was evaluated at 2 and 4 weeks post-fracture. Compared with the vehicle group, perindopril treatment significantly increased bone formation, increased biomechanical strength, and improved microstructural parameters of the callus. Newly woven bone was arranged more tightly and regularly at 4 weeks post-fracture. The ultimate load increased by 66.1 and 76.9% (p<0.01), and the bone volume over total volume (BV/TV) increased by 29.9% and 24.3% (p<0.01) at 2 and 4 weeks post-fracture, respectively. These findings suggest that local treatment with perindopril could promote fracture healing in ovariectomized rats

GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis under physiological and pathological conditions. Anti-VEGF therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. We have reported previously the development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti-angiogenic activity <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>In the current study, we utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested alone or in combination with doxorubicin for <it>in vivo </it>efficacy in the MMTV-PyMT transgenic model of breast cancer.</p> <p>Results</p> <p>The derivative GU81 has increased <it>in vitro </it>efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 alone) had no effect on tumor weight, histology, tumor fat content, or tumor growth index. However, GU81 is able to significantly to reduce total vascular area as a single agent. GU81 used in combination with doxorubicin significantly reduced tumor weight and growth index compared to all other treatment groups. Furthermore, treatment with combination therapy significantly arrested tumor progression at the premalignant stage, resulting in increased tumor fat content. Interestingly, treatment with GU81 alone increased tumor-VEGF levels and macrophage infiltration, an effect that was abrogated when used in combination with doxorubicin.</p> <p>Conclusion</p> <p>This study demonstrates the VEGFR2 antagonist peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous murine MMTV-PyMT breast tumors.</p

Somatic LKB1 Mutations Promote Cervical Cancer Progression

Human Papilloma Virus (HPV) is the etiologic agent for cervical cancer. Yet, infection with HPV is not sufficient to cause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrent genetic alterations have been identified in cervical cancers. Thus, the pressing question as to the biological basis of cervical cancer progression has remained unresolved, hampering the development of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor. Approximately one-half of tumors with mutations harbored single nucleotide substitutions or microdeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplex ligation probe amplification (MLPA). Biallelic mutations were identified in most cervical cancer cell lines; HeLa, the first human cell line, harbors a homozygous 25 kb deletion that occurred in vivo. LKB1 inactivation in primary tumors was associated with accelerated disease progression. Median survival was only 13 months for patients with LKB1-deficient tumors, but >100 months for patients with LKB1-wild type tumors (P = 0.015, log rank test; hazard ratio = 0.25, 95% CI = 0.083 to 0.77). LKB1 is thus a major cervical tumor suppressor, demonstrating that acquired genetic alterations drive progression of HPV-induced dysplasias to invasive, lethal cancers. Furthermore, LKB1 status can be exploited clinically to predict disease recurrence