cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of membrane type-1 matrix metalloproteinase activity and intracellular localization in clinical thoracic aortic aneurysms.

Abstract Objective Membrane type-1 matrix metalloproteinase (MT1-MMP) is elevated during thoracic aortic aneurysm (TAA) development in mouse models, and plays an important role in the activation of matrix metalloproteinase (MMP)-2 and the release of matrix- bound transforming growth factor-β. In this study, we tested the hypothesis that MT1-MMP is subject to protein kinase C (PKC)–mediated regulation, which alters intracellular trafficking and activity with TAAs. Methods Levels of MMP-2, native and phosphorylated MT1-MMP, and PKC-δ were measured in aortic tissue from patients with small TAAs ( 6.5 cm; n = 8), and compared with values measured in normal controls (n = 8). Cellular localization of green fluorescent protein (GFP)-tagged MT1-MMP was assessed in aortic fibroblasts isolated from control and 4-week TAA mice. The effects of PKC-mediated phosphorylation on MT1-MMP cellular localization and function (active MMP-2 vs phospo-Smad2 abundance) were assessed after treatment with a PKC activator (phorbol-12-myristate-13-acetate [PMA], 100 nM) with and without a PKC-δ–specific inhibitor (rottlerin, 3 μM). Results Compared with controls, MT1-MMP abundance was increased in aortas from both TAA groups. Active MMP-2 was increased only in the large TAA group. The abundances of phosphorylated MT1-MMP and activated PKC-δ were enhanced in the small TAA group compared with the large TAA group. MT1-MMP was localized on the plasma membrane in aortic fibroblasts from control mice and in endosomes from TAA mice. Treatment with PMA induced MT1-MMP-GFP internalization, enhanced phospho-Smad2, and reduced MMP-2 activation, whereas rottlerin pretreatment inhibited these effects. Conclusions Phosphorylation of MT1-MMP mediates its activity through directing cellular localization, shifting its role from MMP-2 activation to intracellular signaling. Thus, targeted inhibition of MT1-MMP may have therapeutic relevance as an approach to attenuating TAA development.
Social Housing Landlords: North America

The social housing sector in North America complements the private housing market sector by serving households that do not have access to private market-rate housing. The overall social housing sector includes five distinct but overlapping domains: homeless shelter and service providers, group home and service providers for people with disabilities and specialised needs, elder housing, single-family housing and services to homeowners, and multifamily housing. The social housing sector in North America caters to about 5–10% of all households, but the nonprofit and cooperative housing segments are considerably smaller.
Migrant Informalities of Indian Steel Towns: Planning Lessons from Rourkela, Bhilai and Durgapur

This article examines the territorialization of migrant informality as a result of specific planning policies in Indian steel cities of Bhilai, Durgapur and Rourkela. Conceived of as ‘temples of mo...
Optimal thresholds for ischemic penumbra predicted by computed tomography perfusion in patients with acute ischemic stroke treated with mechanical thrombectomy.

Background and purpose Optimal thresholds for ischemic penumbra detected by CT perfusion (CTP) in patients with acute ischemic stroke (AIS) have not been elucidated. In this study we investigated optimal thresholds for salvageable ischemic penumbra and the risk of hemorrhagic transformation (HT). Methods A total of 156 consecutive patients with AIS treated with mechanical thrombectomy (MT) at our hospital were enrolled. Absolute (a) and relative (r) CTP parameters including cerebral blood flow (aCBF and rCBF), cerebral blood volume (aCBV and rCBV), and mean transit time (aMTT and rMTT) were evaluated for their value in detecting ischemic penumbra in each of seven arbitrary regions of interest defined by the major supplying blood vessel. Optimal thresholds were calculated by performing receiver operating characteristic curve analysis in 47 patients who achieved Thrombolysis In Cerebral Infarction (TICI) grade 3 recanalization. The risk of HT after MT was evaluated in 101 patients who achieved TICI grade 2b–3 recanalization. Results Absolute CTP parameters for distinguishing ischemic penumbra from ischemic core were as follows: aCBF, 27.8 mL/100 g/min (area under the curve 0.82); aCBV, 2.1 mL/100 g (0.75); and aMTT, 7.30 s (0.70). Relative CTP parameters were as follows: rCBF, 0.62 (0.81); rCBV, 0.83 (0.87); and rMTT, 1.61 (0.73). CBF was significantly lower in areas of HT than in areas of infarction (aCBF, p Conclusions CTP may be able to predict treatable ischemic penumbra and the risk of HT after MT in patients with AIS.
Asymmetric DNA methylation of CpG dyads is a feature of secondary DMRs associated with the Dlk1 / Gtl2 imprinting cluster in mouse

Differential DNA methylation plays a critical role in the regulation of imprinted genes. The differentially methylated state of the imprinting control region is inherited via the gametes at fertilization, and is stably maintained in somatic cells throughout development, influencing the expression of genes across the imprinting cluster. In contrast, DNA methylation patterns are more labile at secondary differentially methylated regions which are established at imprinted loci during post-implantation development. To investigate the nature of these more variably methylated secondary differentially methylated regions, we adopted a hairpin linker bisulfite mutagenesis approach to examine CpG dyad methylation at differentially methylated regions associated with the murine Dlk1/Gtl2 imprinting cluster on both complementary strands. We observed homomethylation at greater than 90% of the methylated CpG dyads at the IG-DMR, which serves as the imprinting control element. In contrast, homomethylation was only observed at 67–78% of the methylated CpG dyads at the secondary differentially methylated regions; the remaining 22–33% of methylated CpG dyads exhibited hemimethylation. We propose that this high degree of hemimethylation could explain the variability in DNA methylation patterns at secondary differentially methylated regions associated with imprinted loci. We further suggest that the presence of 5-hydroxymethylation at secondary differentially methylated regions may result in hemimethylation and methylation variability as a result of passive and/or active demethylation mechanisms.
Accident Experience with Trampolines

(1956). Accident Experience with Trampolines. Research Quarterly. American Association for Health, Physical Education and Recreation: Vol. 27, No. 4, pp. 452-455.
The 3.8 Å resolution cryo-EM structure of Zika virus

The recent rapid spread of Zika virus and its unexpected linkage to birth defects and an autoimmune-neurological syndrome has generated worldwide concern. Zika virus is a flavivirus like dengue, yellow fever and West Nile viruses. We present the 3.8A resolution structure of mature Zika virus determined by cryo-electron microscopy. The structure of Zika virus is similar to other known flavivirus structures except for the ~10 amino acids that surround the Asn154 glycosylation site found in each of the 180 envelope glycoproteins that make up the icosahedral shell. The carbohydrate moiety associated with this residue, recognizable in the cryo-EM electron density, may function as an attachment site of the virus to host cells. This region varies not only among Zika virus strains but also in other flaviviruses and suggests that changes in this region influence virus transmission and disease.
Plant Community Composition, Tree Physiology, and Bark-Beetle Mortality in Relation to Open and Enclosed Irrigation Channels: A Case Study Within a Wildland-Urban Interface Forest in Western Montana

Dry coniferous forests within the wildland–urban interface (WUI) in the northwestern US have experienced long-term drought and increasing bark-beetle infestations. An unexamined factor potentially ...
Anti-Viral Therapy, Epstein–Barr Virus, Autoimmunity, and Chaos (The Butterfly Effect)

Abstract Epstein–Barr virus (EBV) and related ubiquitous herpes viruses have been implicated as cofactors in common autoimmune diseases. Epidemiologic evidence suggests that multiple sclerosis and systemic lupus erythematosus do not occur in the absence of prior infection with EBV. EBV also is strongly suggested as a cofactor in rheumatoid arthritis and myasthenia gravis. However, the vast majority of adults are chronically infected with EBV but do not develop any autoimmune disease. In addition, EBV infects only a small percentage of lymphocytes and epithelial cells, whereas EBV-related autoimmune diseases target diverse organ systems. Thus, mystery remains why nearly universal exposure to EBV infection results in only a small population that develops autoimmune disease, with variable illnesses in variable organ systems. In this chapter we review the range of autoimmune syndromes associated with EBV and proposes that non-linear models also termed chaos theory, or the “butterfly effect”, are useful to model the onset and progression of these diseases. Non-linear or chaos theory-based models suggest that minor changes in viral replication and tissue tropism might have major effects on disease outcome from a single infectious agent such as EBV; therefore, anti-viral drugs, monoclonal antibodies, or vaccines could affect the course of the illness. Personalized combinations of existing anti-inflammatory and cytokine therapy, combined with anti-viral therapy and dietary modifications rather than monotherapy with any of these agents, could have disproportionate or unexpected beneficial effects in EBV-related autoimmune syndromes.
Storage effects on genomic DNA in rolled and mature coca leaves.

Rolled and mature leaf tissue was harvested from Erythroxylum coca var. coca Lam. (coca) to determine a method for storage that would maintain DNA with high quality and content up to 50 days. Harvesting coca leaf tissue under Andean field conditions often requires storage from 3 to 10 days before extraction where tissue integrity is lost. All samples of rolled and mature coca leaf tissue were harvested and separately stored fresh in RNAlater for 50 days at 4°, -20°, and 23°C, while similar samples were air-dried for 72 h at 23°C or ovendried for 72 h at 40°C after storage, before extraction. Triplicate samples of each tissue type were extracted for DNA at 10-day intervals and showed that DNA integrity and content were preserved in leaf tissue stored at 4° and -20°C for 50 days. Rolled and mature leaf tissue stored at 4°, -20°, and 23°C showed insignificant degradation of DNA after 10 days, and by day 50, only leaf tissue stored at 4° and -20°C had not significantly degraded. All air- and oven-dried leaf tissue extracts showed degradation upon drying (day 0) and continuous degradation up to day 50, despite storage conditions. Amplified fragment length polymorphism analysis of DNA from rolled and mature leaf tissue of coca stored at 4° and -20°C for 0, 10, and 50 days showed that DNA integrity and content were preserved. We recommend that freshly harvested rolled or mature coca leaf tissue be stored at 4°, -20°, and 23°C for 10 days after harvest, and if a longer storage is required, then store at 4° or -20°C.
Application of Transformations in Parametric Inference

The objective of the present paper is to provide a simple approach to statistical inference using the method of transformations of variables. We demonstrate performance of this powerful tool on exa...
Adiposity, Hepatic Triglyceride, and Carotid Intima Media Thickness During Behavioral Weight Loss Treatment in Antipsychotic-Treated Youth: A Randomized Pilot Study

Abstract Objectives: The purpose of this pilot study was to evaluate changes in adiposity, carotid intima media thickness (CIMT), and hepatic fat content measured via magnetic resonance imaging-est...
Foreword: Private, Environmental, Governance

This essay is the invited foreword to the 2017 J.B & Maurice C. Shapiro Environmental Law Symposium issue of the George Washington Journal of Energy and Environmental Law. The 2017 symposium was dedicated to the issue of private environmental governance. This essay recognizes the incredible growth of private environmental governance as an area of study in the legal academy. In addition to introducing the various contributions to the symposium issue, this essay proposes that rather than merely studying "private environmental governance" as an independent concept, scholars should look closely at the individual components, "private," "environmental," and "governance," to better understand the direction of the field and to give it a more complete theoretical grounding.
Design and Implementation of Knowledge Base for Runtime Management of Software Deﬁned Hardware

Runtime-reconfigurable software coupled with reconfigurable hardware is highly desirable as a means towards maximizing runtime efficiency without compromising programmability. Compilers for such software systems are extremely difficult to design as they must leverage different types of hardware at runtime. To address the need for static and dynamic compiler optimization of workflows matched to dynamically reconfigurable hardware, we propose a novel design of the central component of a dynamic software compiler for software defined hardware. Our comprehensive design focuses not just on static knowledge but also on semi-supervised extraction of knowledge from program executions and developing their performance models. Specifically, our novel dynamic and extensible knowledge base 1) continuously gathers knowledge during execution of workflows 2) identifies optimal implementations of workflows on optimal (available) hardware configurations. It plays a hub role in storing information from, and providing information to other components of the compiler, as well as the human analyst. Through a rich tripartite graph representation, the knowledge base captures and learns extensive information on decomposition and mapping of code steps to kernels and mapping of kernels to available hardware configurations. The knowledge base is implemented using the $C++$ Boost Library and is capable of quickly processing offline and online queries and updates. We show that our knowledge base can answer queries in $1 ms$ regardless of the number of workflows it stores. To the best of our knowledge, this is the first design of a dynamic and extensible knowledge base to support compilation of high-level languages to leverage arbitrary reconfigurable platforms.
Synthesis and Biological Activity of Tricyclic, Conformationally Restricted Analogs of Lipophilic Pyrido[2,3- d ]-Pyrimidine Antifolates

We have reported a series of phenyl substituted 2,4-diamino-5-methyl-6-anilinomethyl pyrido[2,3-d]pyrimidines as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii and Toxoplasma gondii 1,2 These are organisms which cause opportunistic infections in AIDS patients and are often fatal. Among the more potent and selective inhibitors of T. gondii DHFR which we have reported was compound 1, the N-10 methyl analog, which was 11 times as potent and 30 times as selective as trimetrexate (TMQ) 2 an FDA approved second line agent for P. carinii. Against P. carinii DHFR compound 1 was 3 times as potent and 8 times as selective as 2.
An unusual cause of chest pain in a 33 year old male: neurofibromatosis.

Abstract Chest pain in low risk patients is a common ED presentation. Rarely, these patients can have life-threatening conditions requiring timely diagnosis and intervention. There are currently standardized protocols for diagnosing cardiac ischemia, pulmonary embolus, and aortic dissection in low risk patients. Even more rare entities such as esophageal perforation, hemo/pneumothorax, and cardiac tamponade must also be kept in mind. We present the case of chest pain in a 33 year old male reporting no significant past medical history who developed spontaneous massive hemothorax while being evaluated in the ED. Subsequent investigation revealed that the patient had neurofibromatosis; the etiology of aneurysmal rupture in neurofibromatosis is discussed.
An Abstract on Evaluating the Use of Curated Digital Magazines in Marketing Courses: A Comparative Analysis

The rapid growth of mobile technologies has given rise to the emergence of applications (apps) that facilitate the creation and dissemination of online content for educational purposes. Some of these applications allow marketing educators to curate digital magazines that can extend student learning beyond the classroom. The use of curated digital magazines can help students better understand class-related topics by providing them with instant access to recent business content across different platforms (e.g., smartphones, tablets, laptops, and desktop computers). Marketing educators can curate their magazines by selecting business articles that expand the knowledge acquired in the classroom or clarify important class topics.
Age as a Predictor for Complications and Patient-reported Outcomes in Multilevel Transforaminal Lumbar Interbody Fusions: Analyses From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

STUDY DESIGN Retrospective review of a multi-institutional data registry. OBJECTIVE The authors sought to determine the association between age and complications & patient-reported outcomes (PRO) in patients undergoing multilevel transforaminal interbody lumbar fusion (MTLIF). SUMMARY OF BACKGROUND DATA Elderly patients undergoing MTLIF are considered high risk. However, data on complications and PRO are lacking. Additionally, safety of multilevel lumbar fusion in the elderly remains uncertain. METHODS Patients ≥50-year-old who underwent MTLIF for degenerative lumbar spine conditions were analyzed. Ninety-day complications and PROs (baseline, 90-d, 1-y, 2-y) were queried using the MSSIC database. PROs were measured by back & leg visual analog scale (VAS), Patient-reported Outcomes Measurement Information System (PROMIS), EuroQol-5D (EQ-5D), and North American Spine Society (NASS) Patient Satisfaction Index. Univariate analyses were used to compare among elderly and complication cohorts. Generalized estimating equation (GEE) was used to identify predictors of complications and PROs. RESULTS A total of 3120 patients analyzed with 961 (31%) ≥ 70-y-o and 2159 (69%) between 50-69. A higher proportion of elderly experienced postoperative complications (P = .003) including urinary retention (P = <.001) and urinary tract infection (P = .002). Multivariate analysis demonstrated that age was not independently associated with complications. Number of operative levels was associated with any (P = .001) and minor (P = .002) complication. Incurring a complication was independently associated with worse leg VAS and PROMIS scores (P = <.001). Preoperative independent ambulation was independently associated with improved PROMIS, and EQ5D (P = <.001). Within the elderly, preoperative independent ambulation and lower BMI were associated with improved PROMIS (P = <.001). Complications had no significant effect on PROs in the elderly. CONCLUSIONS Age was not associated with complications nor predictive of functional outcomes in patients who underwent MTLIF. Age alone, therefore, may not be an appropriate surrogate for risk. Furthermore, baseline preoperative independent ambulation was associated with better clinical outcomes and should be considered during preoperative surgical counseling.Level of Evidence: 3.
Herpes Simplex and Herpes Zoster

The viruses in the herpesvirus group include herpes simplex, varicella-zoster, Epstein Barr, and cytomegalovirus. This chapter addresses both herpes simplex and varicella-zoster viruses. Herpes simplex cutaneous lesions are caused by the herpes simplex virus. Herpes zoster and varicella are caused by the virus varicella-zoster.
Theresa M. Kelley, Clandestine Marriage: Botany and Romantic Culture and John Rignall and H. Gustav Klaus, with Valentine Cunningham, eds., Ecology and the Literature of the British Left: The Red and the Green

Review by Ben P. Robertson (Troy University) of Theresa M. Kelley, Clandestine Marriage: Botany and Romantic Culture . Baltimore: Johns Hopkins University Press, 2012. Pp. 342. $55. ISBN 9781421405179 and John Rignall and H. Gustav Klaus, with Valentine Cunningham, eds., Ecology and the Literature of the British Left: The Red and the Green . Farnham: Ashgate, 2012. Pp. 267. £60. ISBN 9781409418221.
Baiting Inside Attackers Using Decoy Documents

The insider threat remains one of the most vexing problems in computer security. A number of approaches have been proposed to detect nefarious insider actions including user modeling and profiling techniques, policy and access enforcement techniques, and misuse detection. In this work we propose trap-based defense mechanisms and a deployment platform for addressing the problem of insiders attempting to exfiltrate and use sensitive information. The goal is to confuse and confound an adversary requiring more effort to identify real information from bogus information and provide a means of detecting when an attempt to exploit sensitive information has occurred. “Decoy Documents” are automatically generated and stored on a file system by the D3 System with the aim of enticing a malicious user. We introduce and formalize a number of properties of decoys as a guide to design trap-based defenses to increase the likelihood of detecting an insider attack. The decoy documents contain several different types of bogus credentials that when used, trigger an alert. We also embed “stealthy beacons” inside the documents that cause a signal to be emitted to a server indicating when and where the particular decoy was opened. We evaluate decoy documents on honeypots penetrated by attackers demonstrating the feasibility of the method.
Dentinal dysplasia: Report of a case

Abstract We have described a case of dentinal dysplasia in a 29-year-old woman with ten remaining teeth exhibiting no color change, attrition, or dental caries and radiographically showing dwarfed, constricted roots with calcific masses in the pulp chamber. The family history was not complete, but the patient's three children were not affected. We believe that the case of calcified papilla reported by Stafne represents either a less severe manifestation of dental dysplasia or a very closely related malady.
Providing task isolation via TLB coloring

The translation look aside buffer (TLB) improves the performance of systems by caching the virtual page to physical frame mapping. But TLBs present a source of unpredictability for real-time systems. Standard heap allocated regions do not provide guarantees on the TLB set that will hold a particular page translation. This unpredictability can lead to TLB misses with a penalty of up to thousands of cycles and consequently intra- and inter-task interference resulting in loose bounds on the worst case execution time (WCET) and TLB-related preemption delay. In this work, we design and implement a new heap allocator that guarantees the TLB set, which will hold a particular page translation on a uniprocessor of a contemporary architecture. The allocator is based on the concept of page coloring, a software TLB partitioning method. Virtual pages are colored such that two pages of different color cannot map to the same TLB set. Our experimental evaluations confirm the unpredictability associated with the standard heap allocation. Using a set of synthetic and standard benchmarks, we show that our allocator provides task isolation for real-time tasks. To the best of our knowledge, such TLB isolation without special hardware support is unprecedented, increases TLB predictability and can facilitate WCET analysis.
Towards cost-sensitive assessment of intrusion response selection

In recent years, cost-sensitive intrusion response has gained significant interest mainly due to its emphasis on the balance between potential damage incurred by the intrusion and cost of the response. However, one of the challenges in applying this approach is defining consistent and adaptable measurements of these cost factors on the basis of requirements and policy of the system being protected against intrusions.In this paper we present a framework for the cost-sensitive selection of intrusion response. Specifically, we introduce a set of measurements that characterize potential costs associated with the intrusion handling process and propose evaluation method of intrusion response with respect to the risk of potential intrusion damage, effectiveness of response action and response cost for a system. We provide an implementation of the proposed solution as a plugin tool for Snort IDS and demonstrate its advantages on DARPA data set and real network traffic.
The transcriptional regulator, CosR, controls compatible solute biosynthesis and transport, motility and biofilm formation in Vibrio cholerae

Vibrio cholerae inhabits aquatic environments and colonizes the human digestive tract to cause the disease cholera. In these environments, V. cholerae copes with fluctuations in salinity and osmolarity by producing and transporting small, organic, highly soluble molecules called compatible solutes, which counteract extracellular osmotic pressure. Currently, it is unclear how V. cholerae regulates the expression of genes important for the biosynthesis or transport of compatible solutes in response to changing salinity or osmolarity conditions. Through a genome-wide transcriptional analysis of the salinity response of V. cholerae, we identified a transcriptional regulator we name CosR for compatible solute regulator. The expression of cosR is regulated by ionic strength and not osmolarity. A transcriptome analysis of a ΔcosR mutant revealed that CosR represses genes involved in ectoine biosynthesis and compatible solute transport in a salinity-dependent manner. When grown in salinities similar to estuarine environments, CosR activates biofilm formation and represses motility independently of its function as an ectoine regulator. This is the first study to characterize a compatible solute regulator in V. cholerae and couples the regulation of osmotic tolerance with biofilm formation and motility.
Scaffold informatics: multi-material strategies for tissue scaffolds

The dominant approach in 3D tissue engineering is to construct a scaffold of biocompatible material, to seed the scaffold with an appropriate cell type, to culture these cells in a bioreactor, and to implant the resulting tissue construct. Numerous individual materials have been investigated, but no single material has proven ideal for tissue culture. We advocate the use of multiple materials within a single scaffold. Such scaffolds would be produced using a 3D positioning system possessing multiple heads, capable of both fused deposition and droplet deposition of multiple materials. Our candidate materials for heterogenous deposition include poly-/spl epsiv/-caprolactone(PCL), alginate, fibrin, and chitosan. This paper discusses 1) the design of the hardware necessary to perform this operation, 2) the considerations in selecting candidate materials, and 3) the anticipated benefits to design and construction of tissue scaffolds.
Comparing Oil Spill Rates Using Different Data Sources1

ABSTRACT Different sources of data on past oil spill incidents contain different kinds of information about each incident and different degrees of accuracy. The appropriate data can be used to develop spill statistics and spill rate relationships. This paper examines data on reported oil spills that have occurred in the United States. Characteristics studied include the number of spills, spill sizes, spill sources, and the types of oil spilled. Studying characteristics of past spills can help government and industry to determine the scope of oil spill prevention policies and response planning methods. The main data sources used for this paper include the Oil Spill Intelligence Report's International Oil Spill Statistics annual summaries and the National Response Center online database. This report provides a discussion of the accuracy of information from sources of oil spill data, to help support the development of spill statistics and spill rate relationships.
Alemtuzumab and liver transplantation: a review.

Purpose of review Liver transplantation has always been fraught with conflict. The ongoing shortage of organs for transplantation has led to sicker recipients and the pressure to utilize more marginal grafts. At the same time, increasing public scrutiny and regulatory oversight have emphasized lower costs and better outcomes. This environment exaggerates the importance of the most fundamental conflict: that between preventing allograft rejection and avoiding the toxicities of immunosuppressive agents and the risks of infection. Resolving this struggle requires skillful balancing and a need to keep abreast of the latest developments. Alemtuzumab is a still-new agent with relatively little clinical experience that, therefore, deserves a review and an update of current knowledge in the setting of liver transplantation. Recent findings The use of alemtuzumab in liver transplant recipients has shown promise with little information to support concerns over significantly increased risks of infectious complications. However, there have been very few studies overall and fewer still in the last 2-3 years. Much of what is known must still be extrapolated from experience in kidney transplant recipients. Summary Alemtuzumab appears to be a drug with significant potential advantages for liver transplant recipients. Improved renal function may be the largest potential advantage. However, the advantages may be offset in some groups. Defining subgroups will be critical to the definition of the optimal role of alemtuzumab in liver transplant recipients.
Enabling Systems Biology Approaches Through Microfabricated Systems

With the experimental tools and knowledge that have accrued from a long history of reductionist biology, we can now start to put the pieces together and begin to understand how biological systems function as an integrated whole. Here, we describe how microfabricated tools have demonstrated promise in addressing experimental challenges in throughput, resolution and sensitivity to support systems-based approaches to biological understanding.
The photolysis of tryptophan with 337.1 nm laser radiation.

— Aqueous solutions of L-tryptophan were photolyzed by exposure to 337.1 nm radiation from a pulsed nitrogen laser. These data were compared with results for the 290 nm conventional-source photolysis of tryptophan. The progress of photolysis was monitored by fluorescence analysis of tryptophan. UV absorption spectroscopy, HPLC, TLC, and proton NMR spectroscopy. The loss of Trp was observed to be first order for 290 nm photolysis but of mixed order for 337.1 nm photolysis. Five photolysis products were detected by TLC analysis, including: N-formylkynurenine. kynurenine, tryptamine (detected after 290 nm photolysis but not 337.1 nm photolysis) and two unknown products. The tryptophan-containing peptides N-acetyl-tryptophanamide (NATA) and tryptophylglycine (Trp-Gly) were also observed to photolyze upon 337.1 nm laser radiation demonstrating that this phenomenon is not restricted to free tryptophan monomer. Since Trp is not ordinarily thought to absorb U V radiation at wavelengths as long as 337.1 nm. a number of experiments were performed in an effort to determine the mechanism of photolysis at this wavelength. Evidence is presented which indicates that the 337.1 nm laser photolysis of Trp does not result from two photon absorption, dielectric breakdown, or other laser-specific processes. Instead. it is concluded that this photolysis results either from a very weak absorption tail extending to 337.1 nm in tryptophan itself or from a reaction involving an impurity sensitizer which absorbs the 337.1 nm radiation. The sensitizing impurity. if present, could not. however, be removed by preparative HPLC and could not be detected by TLC or fluorescence analysis.
Accumulation of procollagen in the degenerative articular cartilage of dogs with osteoarthritis

Abstract Collagen metabolism was studied in degenerative articular cartilage of dogs with spontaneous, early onset osteoarthritis. A fraction of collagen which represented about 1.5.% of the total was extracted from cartilage samples with dilute phosphate buffer (pH 7.4) containing 0.2% sodium dodecyl sulfate. Agarose gel filtration in the presence of sodium dodecul sulfate revealed that extracts of degenerative cartilage had about 24% procollagen whereas extracts of normal samples had only 3%. The isolated procollagen fraction was rechromatographed on agarose columns in the presence of mercaptoethanol. This resulted in the identification of a collagen species which migrated between marker β and α collagen chains. The molecular weight of this collagen was estimated to be 150000. Based on incorporation of [14C]proline, its ratio of hydroxy[14C]proline to total 14C was 0.32. Procollagen was not found after limited pepsin digestion (pH 3,4°C, 16 h) of degenerative cartilage samples. Since the total collagen content (μg hydroxyproline/mg cartilage), hydroxy[14C]proline/mg cartilage, specific radioactivity of hydroxy[14C]proline (cpm/μg), in the whole cartilage, and the specific radioactivity of hydroxyproline in the extractable collagen fraction were similar for normal and degenerative cartilage we propose that procollagen accumulated in the degenerative cartilage due to a partial defect in conversion of procollagen to collagen.
The Role of Genetics in the Risk of Thromboembolism: Prothrombin 20210A and Oral Contraceptive Therapy

Purpose To provide an overview of the prothrombin 20210A mutation its effects on the incidence of venous thromboembolism (VTE) in users of oral contraceptive therapy (OCT) and screening recommendations for the primary care practice setting. Data sources Several databases including Medline Embase Biosis Cochrane Library and SciSearch were searched for articles published between 1996 and 2003. An integrative review of studies addressing prothrombin 20210A was done using available case-series and case-control studies. No randomized controlled trials on prothrombin 20210A were available in the literature from the years searched. Conclusions Prothrombin 20210A increases the risk of developing a VTE for those who carry the generic mutation. The presence of either concomitant circumstantial factors (e.g. surgery or immobilization) or a combination of genetic factors (e.g. factor V Leiden and prothrombin 20210A) raises the frequency of VTEs to an even greater extent. The risk increases exponentially in users of OCT. Screening guidelines for the use of OCT in prothrombin 20210A carriers remain unclear due to the paucity of empirical evidence related to the topic. (authors)
Incidentally detected misty mesentery on CT: risk of malignancy correlates with mesenteric lymph node size.

Objective To determine the natural history of incidentally detected misty mesentery on computed tomography (CT) and to correlate the risk of malignancy with size of mesenteric lymph nodes. Methods A retrospective review of all CT abdomen/pelvic examinations from January 1, 2004 through December 31, 2008 identified cases of misty mesentery. The largest mesenteric lymph node was measured, and additional areas of lymphadenopathy were identified. Follow-up was obtained by reviewing all subsequent CT examinations, clinical notes, and pathologic specimens. Patients were excluded if they had a known malignancy at the time of initial CT, CT or clinical history revealing a cause for the misty mesentery, or CT follow-up of less than 2 years. Results Thirty-seven patients with misty mesentery were included. The mean time from the original CT to the latest follow-up was 3.8 years. The largest lymph node measured less than 10 mm in 30 (81%) of 37 patients. All 30 patients demonstrated stable lymph node size, had no other regions with lymphadenopathy, and none developed malignancy. The largest lymph node was 10 mm or greater in 7 (19%) of 31 patients. Three of these patients developed non-Hodgkin lymphoma, 2 of which had other areas of lymphadenopathy. No cases of nonlymphomatous malignancy were identified. Conclusions The development of malignancy in patients with incidentally detected misty mesentery correlates with mesenteric lymph node size. Patients with misty mesentery and largest mesenteric lymph node less than 10 mm without additional areas of lymphadenopathy demonstrate a benign course, and no further follow-up may be necessary.
Effects of Operating Parameters on the Current Density Distribution in Proton Exchange Membrane Fuel Cells

During the operation of a proton exchange membrane (PEM) fuel cell, significant variation of the local current density could exist across the cell causing sharp temperature and stress gradients in certain points, and affecting the water management, all of which severely impact the cell performance and reliability. The variation of local current density is a critical issue in the performance of PEM fuel cell, and is influenced by the operating conditions. This article presents a model-assisted parametric design with the objective of determining the operating conditions which maximize the fuel cell performance while maintaining a level of uniformity in the current density distribution. A comprehensive two-dimensional model is adopted to simulate the species transport and electrochemical phenomena in a PEM fuel cell. Numerical simulations are performed for over a wide range of operating conditions to analyze the effects of various operating parameters on the variation of local current density of the fuel cell, and to develop design windows which serve as guideline in the design for maximum power density, minimum reactant stoichiometry, and uniform current density distribution.
G protein βγ subunits regulate cardiomyocyte hypertrophy through a perinuclear Golgi phosphatidylinositol 4-phosphate hydrolysis pathway

We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCe, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCe is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. Finally, blocking Gβγ at the Golgi or PM blocked ET-1-dependent cardiomyocyte hypertrophy. These data indicate that Gβγ regulation of the perinuclear Golgi PI4P pathway and a separate pathway at the PM is required for ET-1-stimulated hypertrophy, and the efficacy of Gβγ inhibition in preventing heart failure maybe due in part to its blocking both these pathways.
Distribution and diversity of soil protozoa in the McMurdo Dry Valleys of Antarctica

The polar desert soils of the McMurdo Dry Valley region support a limited water film community dominated by flagellates, amoebae, and nematodes. This study describes the protozoa and compares their distribution to nematodes. In 50 samples collected from 12 locations, rotifers and tardigrades were infrequent, and ciliates and testacea were rare. Soil protozoa occurred at all sites but the dominant nematode, Scottnema lindsayae (Timm 1971), did not, indicating soil habitat factors limiting nematode distribution are not limiting to protozoa. In contrast to the nematode species, which are all endemic to Antarctica, there were no endemic protozoan morphospecies found in our samples. The protozoan abundance was several orders of magnitude greater than that of the nematodes, and the species diversity was much greater. Most of the protozoa grew better at lower incubation temperatures. The ubiquitous distribution of protozoa suggests their importance in soil food webs and nutrient cycling in the dry valleys.
Maternal diet during pregnancy and unilateral retinoblastoma.

Purpose Previous studies have suggested a role for parental diet in childhood cancer prevention, but there are few studies of retinoblastoma. The aim of this study was to examine the relation between maternal diet and unilateral retinoblastoma.
Use of the valveless trocar system reduces carbon dioxide absorption during laparoscopy when compared with standard trocars.

Objectives To prospectively compare a novel type of valveless trocar that creates a curtain of pressurized carbon dioxide [CO2] gas (which maintains pneumoperitoneum at a lower gas flow rate) with standard trocars; to quantify the volume of CO2 used; and to characterize CO2 elimination during laparoscopic renal surgery. Methods A total of 51 patients undergoing laparoscopic renal surgery by a single surgeon were prospectively evaluated using either the valveless trocar (n = 26) or standard trocars (n = 25). Patient demographics, operative time, volume of CO2 gas consumed, CO2 elimination, perioperative parameters, and postoperative complications were recorded and analyzed. Results Both patient cohorts were comparable in their preoperative demographics, including body mass index, the number of patients with chronic obstructive pulmonary disease, and smoking history. Mean operative time was lower in the valveless trocar cohort (124.1 minutes) compared with the conventional trocar group (145.6 minutes), P = .047. Use of the valveless trocar was associated with a lower volume of intraoperative CO2 consumed (120.0 ± 82.8 vs 300.6 ± 191.5; P Conclusions Use of a valveless trocar significantly reduced CO2 consumption during transperitoneal laparoscopy. The valveless trocar also demonstrated significantly reduced CO2 elimination and absorption when compared with the standard trocar.
Failing to Communicate in an Educational Environment

Electronic communication tools can be empowering. They allow almost anyone to communicate easily with other groups or individuals, they are reasonably inexpensive--or even free--and they encourage traditional non-communicators to communicate. On the other hand, modern communication tools also allow people to carelessly share their opinions and thoughts and can be contradictory to the very objectives educators have for students.
The role of physical therapists in support of maxillofacial patients.

Abstract Each of the team members interested in head and neck cancer has a specialized frame of reference from which he appraises the needs and potentialities of the patient. The physical therapist can evaluate and treat losses of motion, imbalances of muscular activity, respiratory movements, and certain difficulties of mastication and deglutition. Each specialty can lend insight to the others to achieve a coordinated treatment program which, in turn, will improve the patient's image of himself and provide him with maximum functional independence.
Free Stochastic Measures via Noncrossing Partitions

Abstract We consider free multiple stochastic measures in the combinatorial framework of the lattice of all diagonals of an n -dimensional space. In this free case, one can restrict the analysis to only the noncrossing diagonals. We give definitions of what free multiple stochastic measures are, and calculate them for the free Poisson and free compound Poisson processes. We also derive general combinatorial Ito-type relationships between free stochastic measures of different orders. These allow us to calculate, for example, free Poisson–Charlier polynomials, which are the orthogonal polynomials with respect to the free Poisson measure.
Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas

Oncogenes involved in recurrent chromosomal translocations serve as diagnostic markers and therapeutic targets in hematopoietic tumors. In contrast to myeloid and B-cell neoplasms, translocations in peripheral T-cell lymphomas (PTCLs) are poorly understood. Here, we identified recurrent translocations involving the multiple myeloma oncogene-1/interferon regulatory factor-4 (IRF4) locus in PTCLs. IRF4 translocations exist in myeloma and some B-cell lymphomas, but have not been reported earlier in PTCLs. We studied 169 PTCLs using fluorescence in situ hybridization and identified 12 cases with IRF4 translocations. Two cases with t(6;14)(p25;q11.2) had translocations between IRF4 and the T-cell receptor-alpha (TCRA) locus. Both were cytotoxic PTCLs, unspecified (PTCL-Us) involving bone marrow and skin. In total, 8 of the remaining 10 cases were cutaneous anaplastic large-cell lymphomas (ALCLs) without TCRA rearrangements (57% of cutaneous ALCLs tested). These findings identified IRF4 translocations as a novel recurrent genetic abnormality in PTCLs. Cytotoxic PTCL-Us involving bone marrow and skin and containing IRF4/TCRA translocations might represent a distinct clinicopathologic entity. Translocations involving IRF4 but not TCRA appear to occur predominantly in cutaneous ALCLs. Detecting these translocations may be useful in lymphoma diagnosis. Further, due to its involvement in translocations, MUM1/IRF4 protein may play an important biologic role in some PTCLs, and might represent a possible therapeutic target.
Influence of the conformational state of polymethacrylic acid on the photophysical properties of pyrene in aqueous solution: a fluorescent probe and laser photolysis study

The excited state of pyrene observed in fluorescence and pulsed laser techniques is used to show that pyrene is solubilized in the polymer coil of aqueous solution of polymethacrylic acid (PMA) at pH 5, the pyrene is ejected into the aqueous phase of the system. In the presence of micellar solutions of surfactants increasing pH transports the pyrene from the polymer to the micellar aggregates. These fluorescence techniques are used to investigate the kinetics of expansion of the polymer coil. The system is suggested as a suitable model for the interaction of pyrene with biopolymers such as DNA.
Rocky Mountain “Spotless” and “Almost Spotless” Fever: A Wolf in Sheep's Clothing

In 10 (10.8%) of 93 laboratory-confirmed or probable cases of Rocky Mountain spotted fever seen at Duke University Medical Center from 1969 to 1991, illness without rash or fleeting or atypical skin eruptions were noted. Data from these 10 cases and 33 similar previously reported cases of Rocky Mountain "spotless" or "almost spotless" fever support the premise that human Rickettsia rickettsii infection has a broader spectrum than that indicated by its classic description. Sixty-one percent of patients with Rocky Mountain spotless or almost spotless fever have been men. Two-thirds have been black. Although in some cases the absence of rash may be due to the prompt institution of therapy with chloramphenicol or tetracycline, in others long delays in recognition of the disease and treatment occurred, resulting in the deaths of 53% of patients. On the basis of outcome in the cases reviewed, empirical administration of chloramphenicol or a tetracycline to selected patients is justifiable (including those patients with severe organ dysfunction), even if they have no rash, a transient rash, or a rash of unusual distribution. Indeed, without such therapy, patients with spotless or almost spotless fever may die. Recognizing such atypical cases is analogous to seeing a wolf in sheep's clothing--intuition, experience, knowledge, and a high index of suspicion are required.
Adenosine use during pregnancy

Adenosine is a naturally occurring endogenous nucleoside that suppresses atrioventricular nodal conduction time, terminates supraventricular tachycardia, and restores sinus rhythm. Its use has been reported in children and adults but not in pregnant patients. This case documents the successful termination of a supraventricular tachycardia in a 39-week pregnant hypotensive patient. Emergency physicians may wish to consider adenosine use in pregnant patients needing emergency therapy or when conventional therapy fails.