cssi/SciSciGPT-SciSciNet huggingface dataset:
Didox, a unique ribonucleotide reductase inhibitor and free radical scavenger, can protect against doxorubicin caused cardiotoxicity with enhanced antitumor activity

2125 Doxorubicin (DOX) is the lead member of the class of anthracyclines having antitumor activity against hematological and solid cancers, and plays a prominent role in breast cancer therapy. Long term cardiomyopathy hinders clinical use of anthracyclines. The total dosage of Doxorubicin in treatment protocols is limited because of this concern. The prevailing thesis is that Doxorubicin injures the heart by generating damaging free radicals through iron-catalyzed redox cycling. Didox is a unique ribonucleotide reductase (RR) inhibitor possessing free radical scavenging and iron chelating properties while exhibiting anti-cancer activity on its own. Therefore Didox was tested to see if it could decrease DOX toxicity without reducing its anticancer activity. The cardioprotective effects of Didox were assessed, both acutely and chronically in the rat, using a Langendorff model of heart perfusion. Cardiac function, as measured by Rate Pressure Product (RPP), was decreased 40% by DOX alone, but was ameliorated with Didox infusion. Free radical presence, as measured by EPR spin trapping, showed that Didox treatment decreased the DOX-induced DMPO-OH signal intensity by greater than 80%. These results indicate that Didox offers cardioprotection against DOX mediated injury through its ability to scavenge free radicals. Chronic DOX toxicity studies were performed by weekly single dose i.v. injections of DOX or DOX + Didox. The progression of cardiomyopathy was monitored using echocardiography. After 8 weeks of treatment, DOX treated animals demonstrated marked cardiomyopathy as evidenced by fractional shortening. The animals were then sacrificed and the cardioprotective effects of Didox assessed by measuring functional and histological parameters. Chronic administration of DOX resulted in greater than 50% decrease in left ventricular function as measured by RPP, but Didox offered more than 40% restoration. Also, we examined the effect of Didox and the classical RR inhibitor, hydroxyurea, as well as Zinecard, the iron chelator used clinically, to protect against cardiotoxicity in the mammary (16/c) mouse tumor model singly and in combination with DOX. Both DOX and the RR inhibitors had antitumor activity when used alone producing a modest increase in survival over the untreated group. However, when DOX was combined with the RR inhibitors there was a significant (greater than additive) enhancement of the antitumor activity. These results further support our premise that a free radical scavenger can be used in conjunction with DOX and not impede its antitumor activity, and Didox may even enhance it. Therefore Didox has the potential to be a valuable addition to combination cancer treatment protocols that contain an anthracycline such as DOX.
A source-attractor approach to network detection of radiation sources

Radiation source detection using a network of detectors is an active field of research for homeland security and defense applications. We propose Source-attractor Radiation Detection (SRD) method to aggregate measurements from a network of detectors for radiation source detection. SRD method models a potential radiation source as a “magnet”-like attractor that pulls in pre-computed virtual points from the detector locations. A detection decision is made if a sufficient level of attraction, quantified by the increase in the clustering of the shifted virtual points, is observed. Compared with traditional methods, SRD has the following advantages: i) it does not require an accurate estimate of the source location from limited and noise-corrupted sensor readings, unlike the localization-based methods, and ii) its virtual point shifting and clustering calculation involve simple arithmetic operations based on the number of detectors, avoiding the high computational complexity of grid-based likelihood estimation methods. We evaluate its detection performance using canonical datasets from Domestic Nuclear Detection Office's (DNDO) Intelligence Radiation Sensors Systems (IRSS) tests. SRD achieves both lower false alarm rate and false negative rate compared to three existing algorithms for network source detection.
Parental Involvement During the College Transition: A Review and Suggestion for its Conceptual Definition

The transition to college is a salient ecological shift in emerging adults’ lives that has important implications for renegotiating parental involvement as youth gain independence while navigating the world of higher education. However, the construct of parental involvement itself lacks clear characterization in literatures spanning higher education and developmental psychology, which is of significant concern given the universality of parental programming across college campuses nationwide. Therefore, the current article aimed to review and integrate theoretical and empirical literatures across higher education and developmental psychology to suggest a definition of parental involvement that is appropriate for the developmental period of emerging adulthood and the context of the college transition. We define parental involvement as a multidimensional construct composed of parental support giving, parent-student contact, and parental academic engagement, and provide a unified theoretical perspective on how changes in parental involvement are inherently linked to emerging adults’ development of self-sufficiency via integration into the autonomy-supportive context of college. We conclude with a brief review of research linking parental involvement and student outcomes, with a focus on identifying key limitations to formulate practical suggestions for future work, notably the need to consistently adhere to a clear and appropriate definition of parental involvement.
Does having a strong commitment matter in building sustainable networks

Unpredicted disasters obstruct the operation of a well-functioning network, but such a network should be resistant to the challenges of such disasters to provide successful responses. This study aims to investigate the effect of a strong commitment driven by drills on building sustainable emergency management networks during disasters. The logic of collaboration risk is embedded in the collective action dilemma; therefore, building a strong commitment is important. On the basis of an Emergency Medicine survey done in 2012 and 2013 in the Southeastern Economic Regions of Korea, the relation between strong commitment and network arrangements was examined using the Logistic Regression Quadratic Assignment Procedure analysis. The results of this study show that higher levels of strong commitment driven by exercises are more likely to result in sustainable ties. This implies that beyond the interest of creating planning networks, the means of reinforcing the degree of commitment among members of networks, such as drills, must be developed.
Nuclear Export Inhibition Enhances HLH-30/TFEB Activity, Autophagy, and Lifespan

Summary Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi screen in C. elegans and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via xpo-1 silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models. Selective XPO1 inhibitors recapitulated the effect on autophagy and lifespan observed by silencing xpo-1 and protected ALS-afflicted flies from neurodegeneration. XPO1 inhibition in HeLa cells enhanced TFEB nuclear localization, autophagy, and lysosome biogenesis without affecting mTOR activity, revealing a conserved regulatory mechanism for HLH-30/TFEB. Altogether, our study demonstrates that altering the nuclear export of HLH-30/TFEB can regulate autophagy and establishes the rationale of targeting XPO1 to stimulate autophagy in order to prevent neurodegeneration.
Computational imaging in complex media (Conference Presentation)

Computational imaging is a new frontier of imaging technology that overcomes fundamental limitations of conventional systems by jointly designing optics, devices, signal processing, and algorithms. In this talk, I will first present recent advancements in high-throughput computational microscopy based on coded illumination and nonlinear phase retrieval, which enables wide field-of-view and high-resolution Gigapixel and 3D phase microscopy capability. Next, I will present a new neural network inspired framework for solving inverse scattering problems using recursive models to enable recovery of multiple scattering information in large-scale complex media. Such computational imaging approach creates significant new capabilities by integrating hardware and computation at the system level. It promises wide applications, such as biomedicine, metrology, and remote sensing.
Microvascular Endothelial Function and Neurocognition Among Adults With Major Depressive Disorder.

Background Cardiovascular risk factors (CVRFs) and endothelial dysfunction have been associated independently with poorer neurocognition in middle-aged adults, particularly on tests of frontal lobe function. However, to our knowledge, no studies have examined markers of microvascular dysfunction on neurocognition or the potential interaction between macro- and microvascular biomarkers on neurocognition in middle-aged and older adults with major depressive disorder (MDD). Methods Participants included 202 adults with MDD who were not receiving mental health treatment. Microvascular endothelial function was assessed using a noninvasive marker of forearm reactive hyperemia velocity while macrovascular endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery. CVRFs were assessed using the Framingham Stroke Risk Profile and fasting lipid levels. A standardized neurocognitive assessment battery was used to assess three cognitive domains: executive function, working memory, and verbal memory. Results Greater microvascular dysfunction was associated with poorer neurocognition across all three domains. Microvascular function continued to predict verbal memory performance after accounting for background factors and CVRFs. Macro- and microvascular function interacted to predict working memory performance (F = 4.511, 178, p = 0.035), with a similar nonsignificant association for executive function (F = 2.731, 178, p = 0.095), with moderate associations observed between microvascular function and neurocognition in the presence of preserved FMD (r61 = 0.40, p = 0.001), but not when FMD was impaired (r63 = −0.05, p = 0.675). Conclusion Greater microvascular dysfunction is associated with poorer neurocognition among middle-aged and older adults. This association was strongest in participants with preserved macrovascular function.
Impact Response of an Adhesively Bonded Lap Joint

Failure of adhesively bonded joints is often dictated by the stresses developed within the adhesive layer, which are difficult to measure experimentally. While solutions, including closed-form solutions, exist for static cases, even numerical solutions are not easily obtainable for dynamic cases where the bonded layers are dissimilar in material and/or geometry. In this paper, we present a method to determine the dynamic stresses in the adhesive and adherends of adhesively bonded lap joints subjected to arbitrary dynamic end loads. In the formulation the adherends are treated as orthotropic plates while the adhesive layer is approximated as a tension-shear spring. The equations of motion result in a complex system of fourteen (14) partial differential equations in time and space. The equations are solved numerically using the Finite Difference Method (FDM). First, special cases where known solutions exist are solved to verify both the formulation and the numerical approach. Next, the problem of a lap joint subject to a remote, transmitted impact is considered and results are obtained. The planar distribution of stresses within the adhesive layer shows areas of dynamic stress concentration which may act as crack nucleation sites.Copyright © 2014 by ASME
Extracellular Vimentin/VWF (von Willebrand Factor) Interaction Contributes to VWF String Formation and Stroke Pathology

Background and Purpose- VWF (von Willebrand factor) strings mediate spontaneous platelet adhesion in the vascular lumen, which may lead to microthrombi formation and contribute to stroke pathology. However, the mechanism of VWF string attachment at the endothelial surface is unknown. We tested the novel hypothesis that VWF strings are tethered to the endothelial surface through an interaction between extracellular vimentin and the A2 domain of VWF. We further explored the translational value of blocking this interaction in a model of ischemic stroke. Methods- Human endothelial cells and pressurized cerebral arteries were stimulated with histamine to elicit VWF string formation. Recombinant proteins and antibodies were used to block VWF string formation. Mice underwent transient middle cerebral artery occlusion with reperfusion. Just before recanalization, mice were given either vehicle or A2 protein (recombinant VWF A2 domain) to disrupt the vimentin/VWF interaction. Laser speckle contrast imaging was used to monitor cortical perfusion. Results- Pressurized cerebral arteries produced VWF strings following histamine stimulation, which were reduced in arteries from Vim KO (vimentin knockout) mice. VWF string formation was significantly reduced in endothelial cells incubated with A2 protein or antivimentin antibodies. Lastly, A2 protein treatment significantly improved cortical reperfusion after middle cerebral artery occlusion. Conclusions- We provide the first direct evidence of cerebral VWF strings and demonstrate that extracellular vimentin significantly contributes to VWF string formation via A2 domain binding. Lastly, we show that pharmacologically targeting the vimentin/VWF interaction through the A2 domain can promote improved reperfusion after ischemic stroke. Together, these studies demonstrate the critical role of VWF strings in stroke pathology and offer new therapeutic targets for treatment of ischemic stroke.
A Professionalism and Mentoring Curriculum for Pathology Residents in Training

Professionalism is a core Accreditation Council for Graduate Medical Education competency. The Mentoring and Professionalism in Training Program was developed to promote humanism in health-care professionals in our health system. A modified version was implemented in the pathology residency program for professionalism competency. Twenty-one trainees were divided into 3 groups, with a facilitator who was a graduate of the system Mentoring and Professionalism in Training Program. Five sessions included topics on appreciative inquiry, active role modeling, conflict resolution, team building, feedback, mindfulness, and physician well-being. Participants completed pre- and postsurveys. Qualitative responses were very positive, for example, one participant felt the sessions helped "understand intricacies of workplace relationships and ways of effective, respectful, communication." The Mentoring and Professionalism in Training is a curriculum that teaches team building, conflict resolution, and feedback along with strategies to balance well-being with professional commitments and growth. It is an effective educational tool that can satisfy the Accreditation Council for Graduate Medical Education professionalism curriculum.
An altimeter height extraction technique for dynamically changing rivers of South and South-East Asia

Abstract A new approach is proposed in this study to maximize the skill of satellite altimeter-derived heights by utilizing river extent information from additional sensors. We apply this approach for JASON-3 nadir altimeter. First, locations were identified in South and South East Asia region as potential candidates for this approach based on river extent. Information on river extent composed of river width and course (i.e., path) from visible (Landsat) and Synthetic Aperture Radar (SAR) platform (Sentinel-1). The extent-based approach was applied to filter out non-water radar returns in two methods: 1) River Mask (RM) based K-means (KM) clustering (hence, RM + KM) and 2) K-means clustering embedded with River Mask (RM) (hence, KMRM). Both methods were validated over 12 locations with long records of in-situ height observations and with distinct river characteristics. The maximum benefit observed in utilizing dynamic river mask is during low flow season when the probability of non-water radar signal contamination is highest. For highly varying seasonal widths, satellite imagery on river conditions, as an ensemble of techniques, yields heights with higher accuracy. An average RMSE improvement of 40% in 8 out of 12 stations is observed. Overall, at least one of the two dynamic mask-based techniques studied consistently outperformed the conventional technique of altimeter height extraction based on a fixed river mask. Information on river mask or extent can play an important role in highly meandering rivers as the deviation between actual satellite altimeter passes and nominal passes can be considered during the extraction of heights. Compared to visible (Landsat) imagery, SAR was found to be much more effective at improving altimeter height extraction because of the all-weather capability during frequently cloudy conditions. The practicality of the river mask-based approach for altimeter height extraction needs to be carefully considered by the operational end user based on available computational resources and the latency that can be afforded. An ensemble of morphology based techniques using SAR imagery is likely the future of satellite altimeter-based river height extraction in South and South-East Asia where rivers are increasingly impacted by human regulation, encroachment and seasonality.
Gemini: A Distributed Crash Recovery Protocol for Persistent Caches

Gemini is a distributed crash recovery protocol for persistent caches. When a cache instance fails, Gemini assigns other cache instances to process its reads and writes. Once the failed instance recovers, Gemini starts to recover its persistent content while using it to process reads and writes immediately. Gemini does so while guaranteeing read-after-write consistency. It also transfers the working set of the application to the recovering instance to maximize its cache hit ratio. Our evaluation shows that Gemini restores hit ratio two orders of magnitude faster than a volatile cache. Working set transfer is particularly effective with workloads that exhibit an evolving access pattern.
Resources for the Family Caregiver: A Review of the Family Caregiver Alliance and the AARP Caregiving Resource Center

The rate of family caregiving is steadily increasing as baby boomers retire and their loved ones step into the role as family caregiver. Whether caregiving is a sudden or anticipated role, caregive...
Information Communications Technology Support to Reconstruction and Development: Some Observations from Afghanistan

Abstract : Recent United States (US) government experiences with failed-state interventions suggests that telecommunications (telecoms) and information technology (IT) reconstruction initiatives continue to suffer from a lack of adequate understanding of the affected nation information culture and telecoms and IT business cultures. A coherent telecoms and IT-related civil-military strategy and plan for intervening nations and responding international organizations (IO) and non-governmental organizations (NGO) is lacking as well and there are no agreed mechanisms and procedures to enable effective civil-military coordination and information sharing among participants and with the affected nation. National Defense University, Center for Technology and National Security Policy studies suggest that information and IT can significantly increase the likelihood of success in failed-state interventions and subsequent reconstruction if they are engaged from the outset as part of an overall strategy and plan that coordinates the actions of outside interveners and focuses on generating effective results for the affected nation. This paper examines Afghanistan telecoms and IT as a case study of its use as an enabler of sector reconstruction. Some of the successes and related coordination and information sharing challenges encountered by the multinational civil-military responders and affected nation telecoms and IT organizations are illuminated as well.
Application of Nontarget High Resolution Mass Spectrometry Data to Quantitative Source Apportionment

High resolution mass spectrometry (HRMS) analyses provide expansive chemical characterizations of environmental samples. To date, most research efforts have developed tools to expedite labor- and time-intensive contaminant identification efforts. However, even without chemical identity, the richness of nontarget HRMS data sets represents a significant opportunity to chemically differentiate samples and delineate source contributions. To develop this potential, we evaluated the use of unidentified HRMS detections to define sample uniqueness and provide additional statistical resolution for quantitative source apportionment, overcoming a critical limitation of existing approaches based on targeted contaminants. By creating a series of sample mixtures that mimic pollution sources in a representative watershed, we assessed the fidelity of HRMS source fingerprints during dilution and mixing. This approach isolated 8-447 nontarget compounds per sample for source apportionment and yielded accurate source concentration estimates (between 0.82 and 1.4-fold of actual values), even in multisource systems with <1% source contributions. Furthermore, we mined the nontarget data to identify five source-specific chemical end-members amenable to apportionment. While additional development studies are needed to fully evaluate the myriad factors affecting method accuracy and capabilities, this study provides a conceptual foundation for novel applications of nontarget HRMS data to confidently distinguish and quantify source impacts in complex systems.
Readability of online dengue materials: The need for accessible information as part of infectious disease prevention and control efforts

Abstract Background Dengue is the fastest spreading viral infection. A number of epidemics have occurred in subtropical and tropical regions of the United States. A future expansion and intensification of dengue has been predicted, partly due to changing environmental conditions. In the absence of treatment, prevention and control are vital to addressing this vector-borne disease. Health education and community engagement are a key part of such efforts. Given that the majority of Americans search for health information online, ensuring the readability of web-based dengue information is an important consideration for health officials. To date, there is a dearth of information on this topic. Methods To address this gap, "Dengue fever" was searched using Google Chrome to generate a sample of 100 websites. Using Readable.io, the readability of these 100 sites was then determined using five different tests. The data were analyzed using SPSS. Results The results indicate that the vast majority of online materials on dengue are written at a level far beyond what is recommended. Three of the five tests did not find any of the sampled sites to be appropriate in terms of readability. In general, the websites analyzed tended to be written at a level beyond the 10th grade. Conclusion These findings have important implications for future dengue outbreaks in the United States.
EarSense: earphones as a teeth activity sensor

This paper finds that actions of the teeth, namely tapping and sliding, produce vibrations in the jaw and skull. These vibrations are strong enough to propagate to the edge of the face and produce vibratory signals at an earphone. By re-tasking the earphone speaker as an input transducer - a software modification in the sound card - we are able to sense teeth-related gestures across various models of ear/headphones. In fact, by analyzing the signals at the two earphones, we show the feasibility of also localizing teeth gestures, resulting in a human-to-machine interface. Challenges range from coping with weak signals, distortions due to different teeth compositions, lack of timing resolution, spectral dispersion, etc. We address these problems with a sequence of sensing techniques, resulting in the ability to detect 6 distinct gestures in real-time. Results from 18 volunteers exhibit robustness, even though our system - EarSense - does not depend on per-user training. Importantly, EarSense also remains robust in the presence of concurrent user activities, like walking, nodding, cooking and cycling. Our ongoing work is focused on detecting teeth gestures even while music is being played in the earphone; once that problem is solved, we believe EarSense could be even more compelling.
Exploring moderators of mirror exposure on pre- to post changes in body image outcomes: Systematic review and meta-analysis.

Mirror exposure (ME) is embedded within cognitive behavioral treatment of body image concern (BIC), and existing literature demonstrates its potential value as a BIC intervention. The purpose of th...
Distinct Age-Related Epigenetic Signatures in CD4 and CD8 T Cells.

Healthy immune aging is in part determined by how well the sizes of naive T cell compartments are being maintained with advancing age. Throughout adult life, replenishment largely derives from homeostatic proliferation of existing naive and memory T cell populations. However, while the subpopulation composition of CD4 T cells is relatively stable, the CD8 T cell compartment undergoes more drastic changes with loss of naive CD8 T cells and accumulation of effector T cells, suggesting that CD4 T cells are more resilient to resist age-associated changes. To determine the epigenetic basis for these differences in behaviors, we compared chromatin accessibility maps of CD4 and CD8 T cell subsets from young and old individuals and related the results to the expressed transcriptome. The dominant age-associated signatures resembled hallmarks of differentiation, which were more pronounced for CD8 naive and memory than the corresponding CD4 T cell subsets, indicating that CD8 T cells are less able to keep cellular quiescence upon homeostatic proliferation. In parallel, CD8 T cells from old adults, irrespective of their differentiation state, displayed greater reduced accessibility to genes of basic cell biological function, including genes encoding ribosomal proteins. One possible mechanism is the reduced expression of the transcription factors YY1 and NRF1. Our data suggest that chromatin accessibility signatures can be identified that distinguish CD4 and CD8 T cells from old adults and that may confer the higher resilience of CD4 T cells to aging.
Understanding Participant Needs for Engagement and Attitudes towards Passive Sensing in Remote Digital Health Studies

Digital psychiatry is a rapidly growing area of research. Mobile assessment, including passive sensing, could improve research into human behavior and may afford opportunities for rapid treatment delivery. However, retention is poor in remote studies of depressed populations in which frequent assessment and passive monitoring are required. To improve engagement and understanding participant needs overall, we conducted semi-structured interviews with 20 people representative of a depressed population in a major metropolitan area. These interviews elicited feedback on strategies for long-term remote research engagement and attitudes towards passive data collection. Our results found participants were uncomfortable sharing vocal samples, need researchers to take a more active role in supporting their understanding of passive data collection, and wanted more transparency on how data were to be used in research. Despite these findings, participants trusted researchers with the collection of passive data. They further indicated that long term study retention could be improved with feedback and return of information based on the collected data. We suggest that researchers consider a more educational consent process, giving participants a choice about the types of data they share in the design of digital health apps, and consider supporting feedback in the design to improve engagement.
Alcohol-related cirrhosis is associated with high coronary artery calcium scores in patients undergoing evaluation for orthotopic liver transplantation.

BACKGROUND AND AIMS Coronary artery disease is a major cause of morbidity and mortality in liver transplant patients. Coronary artery calcium (CAC) score has been used to evaluate the risk of CAD in non-cirrhotic patients. However, its significance in cirrhotic patients is unknown. This study aimed to identify factors associated with elevated CAC scores in patients with end-stage liver disease undergoing liver transplant evaluation. METHODS We retrospectively reviewed all patients who underwent liver transplantation evaluation and had coronary CT scan between January 2015 and December 2018. Patients with prior history of CAD were excluded. CAC score was calculated based on the method described by Agatston. RESULTS Sixty-two patients were included. 37.1% had alcohol-related liver disease and 27.4% had NASH cirrhosis. Mean CAC score was 261.1 ± SD, 463.84. Alcohol-related liver disease, male gender, and hypertension were significantly associated with CAC score >100 and only alcohol-related liver disease was associated with CAC score >300. In logistic regression, patients with alcohol-related liver disease had more than sixfold increase in risk of having CAC scores >100 and 300 (OR 6.14, and 6.70, respectively). CONCLUSION Alcohol-related liver disease, male gender, and hypertension were significantly associated with an increased CAC score >100. However, alcohol-related liver disease was the only factor associated with CAC score >300.
The Role of Exosomes in Lysosomal Storage Disorders

Exosomes, small membrane-bound organelles formed from endosomal membranes, represent a heterogenous source of biological and pathological biomarkers capturing the metabolic status of a cell. Exosomal cargo, including lipids, proteins, mRNAs, and miRNAs, can either act as inter-cellular messengers or are shuttled for autophagic/lysosomal degradation. Most cell types in the central nervous system (CNS) release exosomes, which serve as long and short distance communicators between neurons, astrocytes, oligodendrocytes, and microglia. Lysosomal storage disorders are diseases characterized by the accumulation of partially or undigested cellular waste. The exosomal content in these diseases is intrinsic to each individual disorder. Emerging research indicates that lysosomal dysfunction enhances exocytosis, and hence, in lysosomal disorders, exosomal secretion may play a role in disease pathogenesis. Furthermore, the unique properties of exosomes and their ability to carry cargo between adjacent cells and organs, and across the blood–brain barrier, make them attractive candidates for use as therapeutic delivery vehicles. Thus, understanding exosomal content and function may have utility in the treatment of specific lysosomal storage disorders. Since lysosomal dysfunction and the deficiency of at least one lysosomal enzyme, glucocerebrosidase, is associated with the development of parkinsonism, the study and use of exosomes may contribute to an improved understanding of Parkinson disease, potentially leading to new therapeutics.
Characterizing the Magnitude of and Risk Factors for Functional Limb Lengthening in Patients Undergoing Primary Total Knee Arthroplasty

Background: There is little data on the magnitude and factors for functional leg lengthening after primary total knee arthroplasty (TKA). Questions/Purpose: We sought to determine the incidence of ...
Daily transient coating of the intestine leads to weight loss and improved glucose tolerance

The worsening obesity epidemic has driven a parallel increase in incidence of type-2 diabetes (T2D) found in 13% of the adult US population. Roux-en-Y gastric bypass surgery (RYGB) is the golden standard surgical treatment for obesity-related T2D. However, over 70% of T2D patient do not meet the NIH criteria for surgery, and many that do, are reluctant to consider such an invasive intervention. Mechanisms behind the antidiabetic effect of RYGB are not clearly understood, but isolation of proximal bowel from nutrient exposure plays a critical role. In this study, we tested the impact of daily administration of an oral gut coating agent, LuCI (Luminal Coating of the Intestine), in controlling weight and insulin resistance. LuCI is not systemically absorbed and provides a transient coating of the proximal intestines and excludes the coated bowel from nutrient contact, thus mimicking the effects of RYGB. We demonstrate that LuCI results in weight loss and improved insulin sensitivity in a rat DIO model. LuCI also appears to replicate hormonal changes seen after RYGB, by increasing post-prandial GLP-1 and GIP levels. LuCI has the potential to replicate the metabolic benefit of surgery and be a novel therapeutic strategy for obesity associated T2D.
Deficiency of AMPKα1 Exacerbates Intestinal Injury and Remote Acute Lung Injury in Mesenteric Ischemia and Reperfusion in Mice

Mesenteric ischemia and reperfusion (I/R) injury can ensue from a variety of vascular diseases and represents a major cause of morbidity and mortality in intensive care units. It causes an inflammatory response associated with local gut dysfunction and remote organ injury. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of metabolic homeostasis. The catalytic α1 subunit is highly expressed in the intestine and vascular system. In loss-of-function studies, we investigated the biological role of AMPKα1 in affecting the gastrointestinal barrier function. Male knock-out (KO) mice with a systemic deficiency of AMPKα1 and wild-type (WT) mice were subjected to a 30 min occlusion of the superior mesenteric artery. Four hours after reperfusion, AMPKα1 KO mice exhibited exaggerated histological gut injury and impairment of intestinal permeability associated with marked tissue lipid peroxidation and a lower apical expression of the junction proteins occludin and E-cadherin when compared to WT mice. Lung injury with neutrophil sequestration was higher in AMPKα1 KO mice than WT mice and paralleled with higher plasma levels of syndecan-1, a biomarker of endothelial injury. Thus, the data demonstrate that AMPKα1 is an important requisite for epithelial and endothelial integrity and has a protective role in remote organ injury after acute ischemic events.
Prognosis of Chronic Pancreatitis

Prognosis in chronic pancreatitis must be viewed as guarded. In one series of 50 patients who were followed closely for periods up to 19 years, mortality was 56%.1 More than half of the deaths were caused directly by alcohol. These included cirrhosis of the liver and a variety of pancreatic complications (including abscess, pseudocyst, and hemorrhagic necrosis). Other causes of death in chronic pancreatitis include general debilitation, varieties of infections including pneumonia and tuberculosis, narcotic addiction, and prolonged hypoglycemia caused by inappropriately large amounts of insulin.
Observations on the rare earths—LXVII: Some observations on the absorption spectra of non-aqueous solutions of some acetylacetone chelates☆

Abstract Measurements of the absorption spectra of solutions of acetylacetonates of certain of the tripositive rare-earth metal ions in various non-aqueous solvents yield alterations in absorption intensitiess and resolutions of principal bands which support the view that the natures of these bands are determined by electrical fields imposed upont the 4 f electrons by the anionic-type groups. For each species studied, only certain absorption bands are affected. The effects upon these bands are dependent upon the solvent used, but bear no simple relationship to dielectric constant. The absorption spectra of such solutions are in accord with Beer's law. Cryoscopic measurements show the solutes to be monomolecular in benzene and in carbon tetrachloride.
VX-166, a novel potent small molecule caspase inhibitor, as a promising new treatment for sepsis

Lymphocyte apoptosis has been identified as an important factor contributing to both the onset of sepsis and to the progression into septic shock and multiple organ failure. Antiapoptotic therapy through caspase inhibition therefore offers a novel and promising approach to the treatment or prevention of sepsis. Significantly, administration of caspase inhibitors has already been shown to be beneficial in animal models of the disease. We have designed VX-166, a novel broad caspase inhibitor that has an advantageous pharmacokinetic and toxicity profile and should be suitable for use in man. The present study was performed to evaluate VX-166 as a therapeutic agent for the treatment of sepsis.
Chapter 5 Functional Modulators Linking Inflow with Outflow of Aqueous Humor

Publisher Summary The gene expression program of the human ocular ciliary epithelium (CE) indicates that this tissue is the source of multiple neuroendocrine factors found in the aqueous humor (AqH). In particular, the biosynthesis of enzymes involved in the processing and maturation of neuropeptides, vasoactive peptides, prostaglandins, steroid hormones, and retinoids suggests that they are likely functional components of multiple local interactive and metabolic endocrine loops. The diversity of biological activities assigned to regulatory peptides identified in the AqH predicts that they are engaged in neuroendocrine circuitries, including inflow and outflow of AqH, immune homeostasis, and circadian rhythms. Emerging evidence demonstrates that the trabecular meshwork (TM) cells, the main cell type of the conventional AqH outflow pathway, express receptors for many of the endocrine factors secreted by the CE. Therefore, the CE should be considered a multifunctional and interactive tissue with the avascular tissues of the anterior segment such as the cornea, the lens, and the TM. This chapter discusses the molecular and physiological basis of a potential local neuroendocrine circuitry mechanism linking inflow with outflow of AqH.
Physical Processes That Control Strong Ground Motion

This chapter reviews the main characteristics of strong earthquake ground motion and the main physical processes that control these motions. Strong motions are characterized by peak amplitudes and by their spectra. Empirical upper limits and median values are identified. The mathematical basis for a physics-based prediction of strong motion is the representation theorem, which shows how source models and wave-propagation effects combine to generate strong ground motions. The properties of source models are described. The major wave-propagation effects are cataloged and described. Models that implement this physics-based approach are successful in generating realistic synthetics with approximately the correct amplitudes.
Is There a Government Role in Methanol Market Development

Given that a transportation fuel transition away from oil will occur, this paper explores fuel selection and government involvement. Arguments are made for choosing a petroleum replacement now, establishing methanol as the fuel of choice, planning for the transition and involving government in market readiness. Mandatory introduction of methanol compatible fuel vehicles and a national fuel distribution system, so that the marketplace can accommodate methanol when it is economically viable, is proposed. The cost of this approach is comparable to that of other energy activities designed to deal with transportation's oil dependence.
Toward a More Musical Foghorn

Ten college students gave preference judgments for 4 pure tones (120, 300, 500, and 835 IIz) and 11 tone composites constructed from combinations of the pure tones. Equal aversion (tolerance) levels were also measured for the four pure tones and for five of the composites. Sensation-level measures were employed to express aversion thresholds in order to take account of the differential sensitivity of the human ear at different frequencies. Certain operational conclusions were suggested for the design of acoustic navigation aids. The higher frequency pure tones and composites were generally more preferred, and were also tolerated at higher sensation levels. The 120-IIz pure tone was a highly non-preferred signal. The presence of a 120-Hz component in any composite lowered both the preference value and the maintained sensation level. In the case of the moderately preferred 500-Hz pure tone, adding other more-preferred, pure-tone components increased the preference for the signal.
Detection and classification of North Atlantic right whales in the bay of fundy using independent component analysis

A novel method of detection and classification for marine mammals is presented which uses techniques from independent component analysis to solve the blind source separation problem for North Atlantic right whales (Eubalaena glacialis). Using the fundamentally non-Gaussian nature of marine mammal vocalizations and data collected on multiple hydrophones, we are able to separate right whale source spectra, up to an unknown scale, from ambient noise. This technique assumes that the array data is a linear combination of non-Gaussian source signals but does not require specific knowledge of the array geometry. A detection algorithm which separates right whale vocalizations from ambient background using a Kolmogorov-Smirnov test statistic is presented and tested on data collected in the Bay of Fundy. The performance of the detector was found to be such that it was possible to achieve a probability of detection of about three-fourths with a false alarm probability of about one-third. Independent component analysis was found to provide little improvement over standard principle component analysis, which was used as preprocessing step.
Central chemosensitivity, sleep, and wakefulness

Central chemoreceptors are widespread within the brainstem. This conclusion is based on in vitro evidence of neurons from many locations that are responsive to pH changes and on in vivo evidence of respiratory responses to focal acidification at these same locations. Why are there so many chemoreceptor sites? As one possibility we hypothesize that function at different sites varies with arousal state. In unanesthetized rats, we produce focal acidification at single sites with microdialysis (probe tip = 1 mm×240 μm diameter) using artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis, measured at the region of the retrotrapezoid nucleus (RTN) in unanesthetized rats, is approximately equivalent to that observed with end-tidal PCO2 = 7–8 mmHg above the eupneic value. Focal acidification of the retrotrapezoid nucleus (RTN) increased ventilation by 24% only in wakefulness via an increase in tidal volume [1]. In the medullary raphe, the excitatory effect of such focal acidification was observed only in sleep (defined by EEG and EMG criteria); ventilation and frequency increased by 15–20% in NREM sleep and frequency by 15% in REM sleep. There was no effect in wakefulness [2]. In our most recent study, focal acidification of nucleus tractus solitarius (NTS) increased ventilation by up to 20% in both wakefulness and NREM sleep due to an effect on both tidal volume and frequency. The increase in ventilation is greater with focal acidification in the caudal part of NTS at the level of the area postrema. Acidification of more rostral parts of the NTS produced variable results. The medullary raphe contributes to chemoreception in sleep, the RTN in wakefulness, and the cNTS in both sleep and wakefulness. Central chemoreceptors at these three different locations do appear to vary in effectiveness with arousal state. The response at each site is only a fraction of the response attributable to all sites being stimulated at the same intensity. Hypocapnia resulting from single site stimulation can lower the contribution of other sites minimizing the apparent effectiveness of single site stimulation.
Impact of collection container material and holding times on sample integrity for mercury and methylmercury in water

Mercury (Hg) and methylmercury (MeHg) concentrations in streamwater can vary on short timescales (hourly or less) during storm flow and on a diel cycle; the frequency and timing of sampling required to accurately characterize these dynamics may be difficult to accomplish manually. Automated sampling can assist in sample collection; however use has been limited for Hg and MeHg analysis due to stability concerns of trace concentrations during extended storage times. We examined the viability of using automated samplers with disposable low-density polyethylene (LDPE) sample bags to collect industrially contaminated streamwater for unfiltered and filtered Hg and MeHg analysis. Specifically we investigated the effect of holding times ranging from hours to days on streamwater collected during baseflow and storm flow. Unfiltered and filtered Hg and MeHg concentrations decreased with increases in time prior to sample processing; holding times of 24 hours or less resulted in concentration changes (mean 11 7% different) similar to variability in duplicates collected manually during analogous field conditions (mean 7 10% different). Comparisons of samples collected with manual and automated techniques throughout a year for a wide range of stream conditions were also found to be similar to differences observed between duplicate grab samples. These results demonstratemore » automated sampling into LDPE bags with holding times of 24 hours or less can be effectively used to collect streamwater for Hg and MeHg analysis, and encourage the testing of these materials and methods for implementation in other aqueous systems where high-frequency sampling is warranted.« less
Gas Filled Photonic Crystal Fiber Lasers

The recent demonstration of lasing based on population inversion in gas filled photonic crystal fibers opens up new wavelength regions for fiber lasers. The gaseous active medium mitigates some of the power limiting factors of lasers based on solid core fibers.
Subjective versus objective: classifying analytical models for productive heterogeneous performance prediction

Heterogeneous analytical models are valuable tools that facilitate optimal application tuning via runtime prediction; however, they require several man-hours of effort to understand and employ for meaningful performance prediction. Consequently, developers face the challenge of selecting adequate performance models that best fit their design goals and level of system knowledge. In this research, we present a classification that enables users to select a set of easy-to-use and reliable analytical models for quality performance prediction. These models, which target the general-purpose graphical processing unit (GPGPU)-based systems, are categorized into two primary analytical classes: subjective-analytical and objective-analytical. The subjective-analytical models predict the computation and communication components of an application by describing the system using minimum qualitative relations among the system parameters; whereas the objective-analytical models predict these components by measuring pertinent hardware events using micro-benchmarks. We categorize, enhance, and characterize the existing analytical models for GPGPU computations, network-level, and inter-connect communications to facilitate fast and reliable application performance prediction. We also explore a suitable combination of the aforementioned analytical classes, the hybrid approach, for high-quality performance prediction and report prediction accuracy up to 95 % for several tested GPGPU cluster configurations. The research aims to ultimately provide a collection of easy-to-select analytical models that promote straightforward and accurate performance prediction prior to large-scale implementation.