cssi/SciSciGPT-SciSciNet huggingface dataset:
Segmental Additive Tissue Engineering

Segmental bone defects caused by trauma and disease represent a major clinical problem worldwide. Current treatment options are limited and often associated with poor outcomes and severe complications. Bone engineering is a promising alternative solution, but a number of technical challenges must be addressed to allow for effective and reproducible construction of segmental grafts that meet the size and geometrical requirements needed for individual patients and routine clinical applications. It is important to devise engineering strategies and standard operating procedures that make it possible to scale up the size of bone-engineered grafts, minimize process and product variability, and facilitate technology transfer and implementation. To address these issues, we have combined traditional and modular tissue engineering approaches in a strategy referred to as Segmental Additive Tissue Engineering (SATE). To demonstrate this approach, a digital reconstruction of a rabbit femoral defect was partitioned transversally to the longitudinal axis into segments (modules) with discoidal geometry and defined thickness to enable protocol standardization and effective tissue formation in vitro. Bone grafts corresponding to each segment were then engineered using biomimetic scaffolds seeded with human induced pluripotent stem cell-derived mesodermal progenitors (iPSC-MPs) and a novel perfusion bioreactor with universal design. The SATE strategy enables the effective and reproducible engineering of segmental bone grafts for personalized skeletal reconstruction, and will facilitate technology transfer and implementation of a tissue engineering approach to segmental bone defect therapy.
On the classification and existence of structures in default logic

We investigate possible belief sets of an agent reasoning with defaults. Besides of Reiter's extensions which are based on a proof-theoretic paradigm (similar to Logic Programming), other structures for default theories, based on weaker or different methods of constructing belief sets are considered, in particular, weak extensions and minimal sets. The first of these concepts is known to be closely connected to autoepistemic expansions of Moore, the other to minimal stable autoepistemic theories containing the initial assumptions. We introduce the concept of ranking collection of defaults and investigate the properties of largest ranking subset of the family D, determined by W. We find a necessary and sufficient condition for a weak extension to be an extension in terms of ranking. We prove that for theories (D, W) without extension, the least fixed point of the associated operator (with weak extension or minimal set as a context) is an extension of suitably chosen (D',W) with D'\(\subseteq\)D. We investigate conditions for existence of extensions and introduce the notion of perfectly-ranked set of defaults and its variant of maximally perfectly-ranked set. Existence of such set of defaults turns out to be equivalent to existence of extension. Finally, we investigate convergence of algorithm for computing extension.
Low-dose pimozide augmentation of serotonin reuptake blockers in the treatment of trichotillomania.

Background There is some overlap in the phenomenology and treatment response of trichotillomania, Gilles de la Tourette's syndrome (TS), and obsessive compulsive disorder (OCD). Neuroleptics may play a role in the treatment of TS as well as refractory OCD, and the question arises whether this also holds for trichotillomania. Method Patients with trichotillomania were treated in open clinical practice with serotonin reuptake blockers. When symptom resolution was incomplete or symptom relapse occurred, low-dose pimozide was added. Results In six out of seven patients, the addition of pimozide to a serotonin reuptake blocker led to an improvement in hair pulling. In patients who were able to tolerate their medication, this response was sustained. Conclusion Augmentation of serotonergic agents with dopamine blockers may play a role in the treatment of trichotillomania. Further controlled trials of pimozide augmentation in trichotillomania are needed.
The Conceptual Status of DSM-5 Diagnoses

The history of the DSM process demonstrates the triumph of the biomedical model with DSM-III in 1980. That landmark document introduced a symptom-based, descriptive approach to diagnosis, with operational definitions of the diagnostic categories accomplished through the use of diagnostic criteria. The manual mostly achieved the desired goal of reliability in diagnostic across treatment and research settings. It was assumed that diagnostic validity, using the Robins/Guze criteria published 10 years before DSM-III, would follow for the DSM-III categories in the years following publication in 1980. The story of the ensuing decades is that of validity failure, with the unavoidable conclusion that the diagnostic categories do not represent real phenotypes. This chapter details the history of the failure to achieve Robins/Guze validity, the failed efforts of the DSM-5 Task Force and Work Groups to fill in the breach with a variety of measures, and, using analytic, philosophy of science tools—natural-kind analysis and complexity theory—what psychiatric nosology might look like in the future.
Questioning Style and Pimping in Clinical Education: A Quantitative Score Derived from a Survey of Internal Medicine Teaching Faculty.

AbstractConstruct: Pimping is a controversial pedagogical technique in medicine, and there is a tension between pimping being considered as “value adding” in some circumstances versus always unacceptable. Consequently, faculty differ in their attitudes toward pimping, and such differences may be measurable and used to inform future research regarding the impact of pimping on learner outcomes. Background: Despite renewed attention in medical education on creating a supportive learning environment, there is a dearth of prior research on pimping. We sought to characterize faculty who are more aggressive in their questioning style (i.e., those with a “pimper” phenotype) from those who are less threatening. Approach: This study was conducted between December 2015 and September 2016 at Johns Hopkins University. We created a 13-item questionnaire assessing faculty perceptions on pimping as a pedagogical technique. We surveyed all medicine faculty (n = 150) who had attended on inpatient teaching services at two u...
Abstract P113: Early Life Stress-Induced Increases in Urinary Aldosterone Precedes Renal Dysfunction and Hypertension in Male Mice Fed a High Fat Diet

We have previously shown that mice subjected to maternal separation and early weaning (MSEW), a model of early life stress, display exacerbated angiotensin II-dependent obesity-induced hypertension...
A Single Center Experience of Letermovir for the Prevention of CMV Infection in CMV-Seropositive Allogeneic Cell Transplant (Allo-HCT) Recipients

Introduction and Objectives Letermovir (LTV) is the first agent in the class of anti-CMV viral terminase inhibitors and was recently approved in the U.S. for the prevention of CMV infection in CMV-seropositive allo-HCT recipients. In the phase III study, use of LTV after transplant through day 100 resulted in significantly less CMV infections and decreased mortality at week 24 when compared to placebo. In March 2018, LTV was recommended for all CMV-seropositive allo-HCT recipients at our institution. We sought to evaluate the impact of this strategy on our patients. Methods We retrospectively evaluated all adult patients who had an allo-HCT and reached day 100 post-transplant from March – September 2018. Clinically significant CMV infection (CS-CMVi) was defined as CMV viremia or disease that resulted in initiation of anti-CMV therapy. All patients had twice-weekly CMV viral load monitoring. Patients were followed up to day 100 from HCT. Results A total of 74 patients underwent allo-HCT and reached day 100 post-transplant by end of September 2018. Fifty-three patients (72%) received LTV prophylaxis, and 21 patients (28%) did not. The most common reason for lack of LTV was insurance approval and financial issues (57%). The median age was 59 years (range: 45-66) in both groups, and 49% were male. Transplant types were similar between groups with the most common being from matched unrelated (46%) and matched related (31%) donors. The median time to engraftment was the same in both groups at 15 days (range: 12-19). Patients on LTV prophylaxis had less CS-CMVi than patients not on prophylaxis (21% vs. 52%, p = 0.01). Although not statistically significant, less patients on LTV prophylaxis had probable and proven CMV disease (LTV, 6% vs. no prophylaxis, 10%; p = 0.55), and less were hospitalized for treatment of CMV infections (LTV, 7% vs. no prophylaxis, 12%; p = 0.57). All-cause mortality at day 100 was numerically higher in the group without prophylaxis (no prophylaxis, 14% vs. LTV, 4%; p = 0.10). Conclusions This is the first ongoing study evaluating the impact of LTV for prevention of CMV infection. We found that LTV reduced the incidence of CS-CMVi including a trend towards decreased mortality. Given its demonstrated benefits, LTV should be considered in all CMV-seropositive allo-HCT recipients.
A review of the molecular design and biological activities of RXR agonists

An attractive approach to combat disease is to target theregulation of cell function. At the heart of this task are nuclear receptors (NRs); which control functions such as gene transcription. Arguably, the key player in this regulatory machinery is the retinoid X receptor (RXR). This NR associates with a third of the NRs found in humans. Scientists have hypothesized that controlling the activity of RXR is an attractive approach to control cellular functions that modulate diseases such as cancer, diabetes, Alzheimer's disease and Parkinson's disease. In this review, we will describe the key features of the RXR, present a historic perspective of the first RXR agonists, and discuss various templates that have been reported to activate RXR with a focus on their molecular structure, biological activity, and limitations. Finally, we will present an outlook of the field and future directions and considerations to synthesize or modulate RXR agonists to make these compounds a clinical reality.
A representationalist reading of Kantian intuitions

There are passages in Kant’s writings according to which empirical intuitions have to be (a) singular, (b) object-dependent, and (c) immediate. It has also been argued that empirical intuitions (d) are not truth-apt, and (e) need to provide the subject with a proof of the possibility of the cognized object. Having relied on one or another of the a-e constraints, the naive realist readers of Kant have argued that it is not possible for empirical intuitions to be representations. Instead they have argued for a relationalist reading of empirical intuitions in terms of an acquaintance relation between the subject and the intuited object. For the sake of argument, I will grant the naive realist reader of Kant that empirical intuitions should satisfy all the (a)–(e) constraints. Nevertheless, by incorporating these constraints, one by one, into a representationalist theory of empirical intuitions, I will show that not only doesn’t a naive realist reading of empirical intuitions follow, but also that the naive realist has hastily overlooked a range of perfectly representationalist readings of intuitions available to Kant and his representationalist allies. On the positive side, I will argue that there is an extra constraint on intuitions—i.e., that givenness does not require presence to consciousness—that directly goes against any naive realist account of intuitions.
Structural Mapping of Beans (Cowpea) Marketers in Imo State, Nigeria

Agriculture has been the backbone in the growth and development of many developing countries.
Cooperative Target Tracking in Elliptical Formation

This paper presents cooperative tracking of a moving target using a group of mobile robots in an elliptical formation. This result is obtained based on the balanced circular formation obtained earlier, by further applying a similarity transformation. Orientation of the elliptical formation can be specified by a design parameter. Since our control law to each agent was designed as the summation of two control components (i.e., tracking and formation), only the formation control component needs to be modified. The extension to elliptical formation is achieved for both single-integrator and double-integrator robot models. For the communication topology, the cyclic pursuit strategy is used. The effectiveness of the proposed schemes is demonstrated by simulation examples.
High-K+ causes inner hair cell ribbon synapse degeneration

Abstract Recent studies demonstrated that inner hair cell (IHC) ribbon synapses, the first-synapse in the mammal auditory system, could be degenerated by noise and aging, leading to hidden hearing loss (HHL) and eventually other hearing disorders. However, the underlying mechanism remains unclear. Here, we report that elevation of extracellular K+ could induce IHC ribbon degeneration. Similar to noise-exposure, the degeneration was dose-dependent and only occurred in IHCs. Blockage of Ca2+-dependent K+ (BK) channels attenuated the degeneration. However, application of the IHC ribbon synapse neurotransmitter glutamate and glutamate receptor (GluR) agonists only caused ribbon swelling but not degeneration; GluR antagonist also had no effect on the regeneration, suggesting that glutamate-excitotoxicity is not a mechanism for ribbon degeneration in IHCs. These data reveal a new presynaptic mechanism for IHC synapse degeneration and HHL, and also suggest that the BK channel is a potential target for prevention and treatment of this common cochlear synaptopathy.
Perforin Is Dispensable for Anti-CD19 CAR-T Cell Cytotoxicity but Contributes to CAR-T Cell Contraction and Regulates Host Inflammatory Response

Abstract Background: Chimeric antigen receptor transduced T cell (CAR-T) therapy against B-cell malignancies is highly effective, but is frequently associated with cytokine release syndrome (CRS). In severe cases, CRS can be associated with a prolonged life-threatening systemic inflammatory response mimicking manifestations of hemophagocytic lymphohistiocytosis (HLH). Primary HLH occurs among individuals harboring genetic defects in granule-mediated cytotoxicity pathway, such as perforin gene mutations. In a murine primary HLH model, IFNγ derived from antigen-specific CD8+ T cells is implicated as a major mediator of HLH pathology. We explored the role of granule-mediated cytotoxicity and IFNγ in CAR-T response and toxicity, using an established syngeneic murine model of anti-CD19-CAR-T therapy against B-cell malignancy. Methods: Splenic T cells derived from perforin knockout (Prf-/-), wild-type (WT), and IFNγ adenylate-uridylate-rich element-deleted (ARE-/-: a strain with stable IFNγ mRNA transcript) mice on the B6 background were transduced with second-generation murine anti-CD19 CAR (ScFV-CD28-CD3z). In in vivo experiments, mice received cyclophosphamide (200 mg/kg) intraperitoneally 24 hours prior to CAR-T adoptive transfer as lymphodepletion. Results: Both WT and Prf-/- T cells were successfully transduced with a mean transduction efficiency of 80%, and resulted in similar immunophenotypic composition (CD8/CD4, TCM/TEM) at baseline. Compared to WT CAR-T, Prf-/- CAR-T produced a higher amount of IFNγ when co-cultured with CD19+ leukemia (12-hour coculture supernatant IFNγ, WT 7822 pg/mL vs. Prf-/- 14743 pg/mL, p Conclusion: Collectively, these data suggest that perforin is dispensable in murine CD19-CAR-T cytotoxic activity, but contributes to CAR-T contraction, and possibly to the regulation of a secondary inflammatory response. We hypothesize that IFNγ may be the major mediator of the observed differences. Experiments are underway to further elucidate the interplay of perforin and INFγ in CAR-mediated cytotoxicity and to determine whether targeting IFNγ may be a therapeutic option in HLH-like CAR toxicity. Download : Download high-res image (76KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.
Financial Education and Asset Accumulation of Older Workers

This paper presents an exploratory analysis of the impact associated with Financial Education on workers' decisions regarding their accumulation of assets & composition of asset portfolios. As part of the analysis I use all six waves of the Health Retirement Study (HRS), a nationally representative longitudinal panel data of older workers that began in 1992 and followed every two years, to quantify the effect (if any) from attending financial education by workers on rates of asset accumulation. Cross-sectional evidence coupled with results obtained from structural econometric model of asset choice I report a statistical and economically meaningful impact of financial education on workers' investment decisions. This would suggest debate on the reform of Social Security such as the proposed creation of self-directed individual savings accounts need be joined by calls for some form of financial education for current and future cohort of workers as they transition to retirement.
Bullying victimization and delinquent involvement: An application of general strain theory

Abstract Bullying victimization is linked to numerous undesirable outcomes which are likely to affect victims over the life course. The current study incorporates data from the National Longitudinal Survey of Youth (1997) and draws from Agnew’s General Strain Theory to estimate the effects of bullying victimization on depressive symptoms and delinquency. Results suggest repeated bullying victimization increases depressive symptoms in adolescence for both males and females (ages 12–16). The results also indicate that it is problematic to assess delinquent outcomes for bullying victimization independent of mediating mental health factors, namely depressive symptoms. Additionally, depressive symptoms mediate the bullying victimization and delinquent relationship for females but not males. A discussion pertaining to relevant policy implications and future research investigating the delinquent outcomes of bullying victimization is provided.
Introduction to the Special Issue: Mechanisms of Variation in Reading Comprehension: Processes and Products

This introduction to the special issue entitled “Mechanisms of Variation in Reading Comprehension: Processes and Products” defines what is referred to as the process and product of reading comprehe...
The Last Journey. I. An Extreme-Scale Simulation on the Mira Supercomputer

The Last Journey is a large-volume, gravity-only, cosmological N-body simulation evolving more than 1.24 trillion particles in a periodic box with a side-length of 5.025Gpc. It was implemented using the HACC simulation and analysis framework on the BG/Q system, Mira. The cosmological parameters are chosen to be consistent with the results from the Planck satellite. A range of analysis tools have been run in situ to enable a diverse set of science projects, and at the same time, to keep the resulting data amount manageable. Analysis outputs have been generated starting at redshift z~10 to allow for construction of synthetic galaxy catalogs using a semi-analytic modeling approach in post-processing. As part of our in situ analysis pipeline we employ a new method for tracking halo sub-structures, introducing the concept of subhalo cores. The production of multi-wavelength synthetic sky maps is facilitated by generating particle lightcones in situ, also beginning at z~10. We provide an overview of the simulation set-up and the generated data products; a first set of analysis results is presented. A subset of the data is publicly available.
Gastrointestinal, Hepatobiliary, and Pancreatic Tumors

The concepts of “personalized medicine” and “genomic medicine” raise an emerging medical discipline that incorporates molecular genetic testing into clinical care of various diseases for diagnostic and therapeutic decision-making. The field of personalized cancer therapy is rapidly growing with dramatic changes of conventional clinical management and dynamic development of new therapeutic strategies for cancers in the gastrointestinal (GI) system. A proper selection of “targeting” or “tailored” anticancer therapies relies on the information supplied by molecular genetic analysis. Also molecular findings are often and tremendously helpful in resolving the challenges of achieving accurate diagnoses solely based on evaluation and other traditional methods. New tumor classification adopting molecular and genomic alterations will profoundly and comprehensively alter the current understanding of GI neoplastic diseases and their clinical diagnosis, prognosis, and management. Overall, molecular genetic pathology plays an integral role in the clinical diagnosis and treatment of GI tumors. This chapter reviews molecular knowledge and practice widely used in the clinical management of gastrointestinal tract, hepatocytic, and pancreatic neoplasms.
Unifying the data center caching layer: feasible? profitable?

Data centers today host large numbers of workloads and many of these workloads consume significant storage resources. Given the long history of successes in storage caching, it is only natural such successes bear fruit in modern data centers, at scale. This paper presents CaaS, a generalized caching service for cloud data centers. Departing from existing application, storage, or data-type specific caches, CaaS unifies and abstracts data center caching resources making these available to any workload and for any data type. Also departing from past caching practices, CaaS is fault-tolerant allowing it to cache writes without risk of data loss. We expect that systems such as CaaS will help bridge the gap between heterogeneous and distributed cache resources and data-intensive applications in a data center.
Determining the risk of driver-at-fault events associated with common distraction types using naturalistic driving data.

Abstract Introduction: Studies thus far have focused on automobile accidents that involve driver distraction. However, it is hard to discern whether distraction played a role if fault designation is missing because an accident could be caused by an unexpected external event over which the driver has no control. This study seeks to determine the effect of distraction in driver-at-fault events. Method: Two generalized linear mixed models, one with at-fault safety critical events (SCE) and the other with all-cause SCEs as the outcomes, were developed to compare the odds associated with common distraction types using data from the SHRP2 naturalistic driving study. Results: Adjusting for environment and driver variation, 6 of 10 common distraction types significantly increased the risk of at-fault SCEs by 20-1330%. The three most hazardous sources of distraction were handling in-cabin objects (OR = 14.3), mobile device use (OR = 2.4), and external distraction (OR = 1.8). Mobile device use and external distraction were also among the most commonly occurring distraction types (10.1% and 11.0%, respectively). Conclusions: Focusing on at-fault events improves our understanding of the role of distraction in potentially avoidable automobile accidents. The in-cabin distraction that requires eye-hand coordination presents the most danger to drivers’ ability in maintaining fault-free, safe driving. Practical Applications: The high risk of at-fault SCEs associated with in-cabin distraction should motivate the smart design of the interior and in-vehicle information system that requires less visual attention and manual effort.
Self-Transcendence: Moving from Spiritual Disequilibrium to Well-Being Across the Cancer Trajectory.

Abstract Objectives To synthesize research results on self-transcendence among people affected by cancer and their caregivers to inform oncology nursing practices that promote well-being across the cancer trajectory. Self-transcendence is an inherent capacity to expand self-boundaries beyond the person's usual form to create something meaningful, whether it is a new purpose, perspective, situation, or artifact that fosters well-being. Data Sources Peer-reviewed, research-based publications, and peer-reviewed theoretical publications were used. Conclusion Research results are consistent with Reed's self-transcendence theory that proposes self-transcendence as a healing process for application in nursing practice. Self-transcendence facilitates well-being through the creative experiences afforded by expanding self-boundaries intrapersonally, interpersonally, and transpersonally. Nurses may use this knowledge in various practices that support well-being among people who have cancer and their families. Implications for Nursing Practice Five comprehensive practice implications to support self-transcendence and foster well-being in individuals affected by cancer and their caregivers were synthesized from the research-based literature and aligned with Reed's self-transcendence theory.
Executive Functioning and Emotion Regulation in Children with and without ADHD.

Difficulties with emotion regulation affect the majority of youth with attention-deficit/hyperactivity disorder (ADHD) and predict greater functional impairment than ADHD symptoms alone. Deficits in executive functioning are also present for most children with ADHD, and have been linked with emotion regulation difficulties in both clinical and neurotypical populations throughout development. The current study was the first to assess all three core executive functions (working memory, inhibitory control, set shifting) simultaneously in a clinically-diverse sample of children with and without ADHD and common comorbidities and investigate the extent to which they uniquely predict emotion dysregulation. A sample of 151 children ages 8–13 years (M = 10.36, SD = 1.52; 52 girls; 70.2% White/Non-Hispanic) were assessed using a criterion battery of executive functioning tasks, teacher-reported ADHD symptoms, and parent-reported emotion regulation. Results of the bias-corrected, bootstrapped conditional effects path model revealed that better-developed working memory predicted better emotion regulation (β = 0.23) and fewer ADHD symptoms (β = -0.21 to -0.37), that ADHD symptoms (β = -0.18 to -0.20) independently predicted emotion dysregulation, and that working memory exerted indirect effects on emotion regulation through both inattention and hyperactivity/impulsivity (β = 0.04–0.07). Sensitivity analyses indicated that these effects were generally robust to control for age, sex, executive function interrelations, and inclusion/exclusion of children with co-occurring ASD. These findings underscore the importance of working memory (relative to inhibitory control and set shifting) and its relations with ADHD symptoms for understanding children’s emotion regulation skills, and may help explain the limited efficacy of first-line ADHD treatments, which do not target working memory, for improving emotion regulation skills.
Theridion echinatum Gao & Li, 2014, a junior synonym of Theridion zonulatum Thorell, 1890 (Araneae, Theridiidae) with comments on its web architecture.

The spider genus Theridion was established by Walckenaer in 1805 with Theridion pictum (Walckenaer, 1802) as the type species. It is the most ‘species rich’ theridiid genus comprising 584 described species and 6 subspecies (World Spider Catalog 2015). Theridion zonulatum Thorell, 1890, ‘the zebra theridiid spider’, which is known only by the female, was described from Sumatra. Gao & Li (2014) described Theridion echinatum from the Yunnan Province in China based only on male specimens. During our surveys of Indian spiders, we came across a matching-pair of male and female theridiid spiders from the Kerala region in India. Our female spiders appeared to belong to T. zonulatum , while male spiders shared the features of T. echinatum . This led us to the conclusion that both T. zonulatum and T. echinatum are conspecific. In the present paper, we synonymise T. echinatum with T. zonulatum . The web architecture of T. zonulatum is also described.
Optimization of a-SiGe based triple, tandem and single-junction solar cells

Recent research activities at the University of Toledo (UT) in the fabrication of high-efficiency triple, tandem and single-junction solar cells, all employing high-quality a-SiGe cells, are reviewed in this paper. Incorporating various improvements in device fabrication, the UT group fabricated 1) triple-junction a-Si/a-SiGe/a-SiGe solar cells with 12.5% initial efficiency and 10.7% stable efficiency, tandem-junction a-Si/a-SiGe solar cells with 12.9% initial efficiency, and single-junction a-SiGe solar cells with 12.5-13% initial efficiency and 10.5% stable efficiency. This review also highlights recent UT work on the nanocrystalline silicon p-layer and light-assisted electrochemical shunt passivation process.
Ageing. New mice for old questions.

Although mutations have been identified that cause premature ageing in humans, it remains unclear exactly how we age and which genes are involved. A group of Japanese geneticists have discovered a new gene in mice called klotho that suppresses characteristics of ageing. Mice carrying a mutation in this gene develop diseases similar to ageing-related disorders in humans such as arteriosclerosis (hardening of the arteries), osteoporosis (brittle bones) and cataracts.The klotho protein is novel (bearing no resemblance to proteins encoded by premature ageing genes) and may be involved in cell signalling or remodelling of the extracellular matrix.
Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport.

We have previously reported a topological model of the electrogenic Na+–HCO3− cotransporter (NBC1) in which the cotransporter spans the plasma membrane 10 times with N- and C-termini localized intracellularly. An analysis of conserved amino acid residues among members of the SLC4 superfamily in both the transmembrane segments (TMs) and intracellular/extracellular loops (ILs/ELs) provided the basis for the mutagenesis approach taken in the present study to determine amino acids involved in NBC1-mediated ion transport. Using large-scale mutagenesis, acidic and basic amino acids putatively involved in ion transport mediated by the predominant variant of NBC1 expressed in the kidney (kNBC1) were mutated to neutral and/or oppositely charged amino acids. All mutant kNBC1 cotransporters were expressed in HEK-293T cells and the Na+-dependent base flux of the mutants was determined using intracellular pH measurements with 2′,7′-bis-(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Critical glutamate, aspartate, lysine, arginine and histidine residues in ILs/ELs and TMs were detected that were essential for kNBC1-mediated Na+-dependent base transport. In addition, critical phenylalanine, serine, tyrosine, threonine and alanine residues in TMs and ILs/ELs were detected. Furthermore, several amino acid residues in ILs/ELs and TMs were shown to be essential for membrane targeting. The data demonstrate asymmetry of distribution of kNBC1 charged amino acids involved in ion recognition in putative outward-facing and inward-facing conformations. A model summarizing key amino acid residues involved in kNBC1-mediated ion transport is presented.
Raman Scattering Measurements of Vibrational Relaxation in Expanding Nitrogen

Spontaneous Raman scattering spectroscopy is used to study vibrational relaxation behavior in a nonequilibrium expansion. A sample of vibrationally excited, undissociated N2 is produced in a reflected shock tunnel and rapidly expanded through a two-dimensional nozzle. The flow characteristics of the short-lived steady expansion are confirmed by comparing holographic interferometry measurements directly to 2-D flowfleld calculations. The vibrationally relaxing gas is probed on the axis of the nozzle by a single 250 mJ pulse from a 248 nm KrF excimer laser. The Raman scattered light is dispersed and detected by an intensified CCD array. Analysis of the Raman spectra shows that the relative populations of the first few vibrational levels do not deviate significantly from a Boltzmann distribution. Pointwise measurements of the vibrational energy are reported for corrected area expansion ratios of up to 5.5 for stagnation conditions of 102 atm, 2800 K and 102 atm, 5600 K. Good agreement is found between the measured vibrational state distributions and detailed numerical simulations based on the Landau-Teller model and on an anharmonic oscillator model. Relaxation times are deduced by comparison to the Landau-Teller solutions and found to be within the uncertainty of Millikan and White’s correlation for vibrational relaxation under shock heating conditions.
Raising the antioxidant levels within mouse muscle fibres does not affect contraction-induced injury

A protocol of 75 lengthening contractions (LCP) administered to skeletal muscles of mice causes an initial force deficit owing to the mechanical disruption of sarcomeres and a reduction in calcium release from the sarcoplasmic reticulum. During the 3 days following the LCP, a ‘sealing off process’ and inflammatory response occurs. The reactive oxygen species (ROS) released by invading inflammatory cells produce a secondary force deficit that is more severe than the initial deficit. The timing of the infiltration of inflammatory cells and increase in force deficit relative to the sealing off process is not well documented. We tested the null hypothesis that following a lifetime of overexpression of the genes for the intracellular antioxidants manganese superoxide dismutase, copper zinc superoxide dismutase or catalase in transgenic mice, the force deficits 3 days following the administration of a 75 LCP to in situ extensor digitorum longus muscles are not different from those of wild-type mice. Following the LCP, the force deficits ranged from 39 to 59% for the muscles of transgenic mice that overexpressed the genes for intracellular antioxidants and were not different from the force deficit of 44% observed for muscles of wild-type mice. The results provide evidence that the ROS damage does not occur within the cytosol of the injured fibres. Apparently, the hypercontraction of sarcomeres and accumulation of vesicles seal off and protect the intact portions of damaged fibres, such that the ROS damage and repair occurs in the milieu of the necrotic segments that are continuous with the extracellular matrix.
Alcohol, host defence and society

Impaired health caused by alcohol abuse has been known throughout recorded history. Over the past century, alcohol abuse has been clearly linked to host susceptibility to infectious disease, particularly bacterial pneumonia. Recently, both acute and chronic alcohol intake have been shown to result in specific defects in innate and adaptive immunity; these could, in principle, be subjected to specific modulation to overcome the immunosuppressive effects of the most commonly abused substance in the Western world.
Pulmonary Vascular Disease Related to Hemodynamic Stress in the Pulmonary Circulation

Hemodynamic stress in the pulmonary vessel is directly linked to the development of vascular remodeling and dysfunction, ultimately leading to pulmonary hypertension. Recently, some advances have been made in our molecular understanding of the exogenous upstream stimuli that initiate hemodynamic pertubations as well as the downstream vasoactive effectors that control these responses. However, much still remains unknown regarding how these complex signaling pathways connect in order to result in these characteristic pathophysiological changes. This chapter will describe our current understanding of and needed areas of research into the clinical, physiological, and molecular changes associated with pressure/volume overload in the pulmonary circulation. © 2011 American Physiological Society. Compr Physiol 1:123-139, 2011.
Stability of cancer chemotherapeutic agents in a totally implanted drug delivery system

The stability and compatibility of serveral chemotherapeutic agents with an implantable infusion device were evaluated. The totally implantable drug delivery system can be placed subcutaneously in an ambulatory patient to permit the regional administration of antineoplastic drugs. The in vitro method of assessing the stability of three chemotherapeutic agents with the pumping device involved placing the pumps, filled with cytarabine, dichloromethotrexate, and vinblastine, in a 37 degree C water bath with mild agitation. Control solutions placed in amber vials were maintained under simulated physiological conditions. Samples (1 ml) were removed periodically, frozen at -20 degrees C and later toward and batch assayed by high pressure liquid chromatography to determine drug concentrations. An in vivo assessment of the stability of floxuridine was also conducted in five patients receiving intra-arterial hepatic infusions by the device. The concentrations placed in the pump were compared with the contractions removed at the time of refill. Cytarabine and dichloromethotrexate showed no appreciable drug decomposition in the control vials or the pump over the 15-day and 28-day study periods, respectively. Vinblastine underwent a 48% and 20% drugs loss in the pump and control, respectively, during a 14-day period. In the vivo assessment of floxuridine, less than 5% drug degradation was found for infusion times ranging from four to 12 days. Cytarabine, dichloromethothrexate, and floxuridine were stable and compatible with the implantable infusion evice, and vinblastine was found to be unstable. The compatibility of all agents with the infusion device should be evaluated before clinical application.
Electron Exciter Speeds Associated with Interplanetary Type III Solar Radio Bursts

This article provides a comprehensive quantitative investigation of the kinematics of the electron exciters associated with interplanetary type III solar radio bursts. Detailed multispacecraft analyses of the radio and plasma wave data from the widely separated Wind and STEREO spacecraft are provided for five interplanetary type III bursts that illustrate different aspects of the problems involved in establishing the electron exciter speeds. The exciter kinematics are determined from the observed frequency drift and in-situ radiation characteristics for each type III burst. The analysis assumes propagation of the electron exciters along a Parker spiral, with origin at the associated solar active region, and curvature determined by the measured solar wind speed. The analyses take fully into account the appropriate light-propagation-time corrections from the radio source to the observing spacecraft as the exciters propagate along the Parker spiral path. For the five in-situ type III bursts analyzed in detail here, we found that their initial exciter speeds, near the Sun, ranged from $0.2c$ to $0.38c$ , where $c$ is the speed of light. This is significantly higher than the exciter speeds derived from other recent analyses. The results presented here further suggest that the type III electron exciters normally decelerate as they propagate through the interplanetary medium. We argue based on the observations by the widely separated spacecraft that the initial part of the type III radiation usually occurs at the fundamental of the plasma frequency. Finally, we compare the results for the exciter speeds to all previous determinations and provide quantitative arguments to explain the differences.
Differentiation of earthquakes and underground nuclear explosions on the basis of amplitude characteristics

The particle velocity ratios of the maximum shear-surface waves to maximum compressional waves were determined for a large number of earthquakes recorded over a wide geographic range. These results are compared with similar types of data for underground nuclear detonations recorded in the United States. It was found that this technique could be used as a diagnostic aid in distinguishing between these two types of sources at distances less than 1000 km.
Aryl Halide Radical Clocks as Probes of Stannylene/Aryl Halide C–H Activation Rates

Using the radical cyclization induced by the reaction of (1) with 1-(but-3-en-1-yloxy)-2-iodobenzene, we have determined the rate of allylic and propargylic C–H activation to be 1.1 ± 0.2 × 108 M−1 s−1. The rate of oxidative addition of aryl halide with 1 was estimated to be 107–108 M−1 s−1. The radical cyclization involving 1 and 1-(allyloxy)-2-iodobenzene proceeds quantitatively, indicating that the rate of cyclization (9.6 × 109 s−1) is faster than the rate of hydrocarbon/alkene/alkyne C–H abstraction.
Synthesis of aromatic polymers by the reaction between monomers containing biphenylene and acetylene groups

The thermal reaction of a bis(biphenylene) monomer, N,N′-bis(biphenylene-2-yl)-4,4′-hexafluoroisopropylidenediphthalimide (3), with either of two diacetylenic monomers, bis(4-ethynylphenyl) ether (4) or bis[4-(phenylethynyl)phenyl] ether (5), gave polymers that contain phenanthrene units as a result of the reaction of the biphenylene groups with the acetylene groups. The reaction could be carried out in solution or in the melt, and in the latter case, reaction exotherms were found at 367°C and 386°C, respectively, for 4 and 5. Polymer 6, obtained from the melt reaction of 3 with 5, is insoluble in all solvents and thermally stable, showing no weight loss in air up to 480°C and in argon up to 500°C.
Can utilizing social media and visual programming increase retention of minorities in programming classes

This paper discusses how Social Digital Literacy is being used in CS1 to teach critical and computational thinking by delivering content to students through the use of social media. Social Digital Literacy (SDL) is the way in which people use social media to enhance their social network, effectively increase their knowledge base, while communicating clearly and professionally through the use of social media. The increased popularity of social media amongst college students makes it an opportune time to consider a new form of literacy based on how technology is used by students, the devices that students interact with on a daily bases and the mainstream acceptance of social media in daily life. In order to retain students in computing classes, students are taught in an efficacious manner how to capitalize on the technology that they use on a daily basis. By increasing their SDL proficiency to become a more informed student, a well versed employee and consciously aware of what they post to social media. The expectation is that the approach being used can be implemented in any introductory programming course.
Cell Surface Coatings and Membrane Potentials of Malignant and Nonmalignant Cells

A positive surface potential indicating a cell coating is common to malignant cells, lymphocytes, and normal and malignant trophoblastic cells. This characteristic was not generally found for other normal cell types tested by microelectrode penetration.
Advances and controversies in neonatal ICU platelet transfusion practice.

Platelet transfusions are the principal means of treating thrombocytopenia in neonatal ICUs (NICUs). More than 95% percent of the platelet transfusions given to NICU patients are given prophylactically, with the supposition that this reduces the risk for a serious hemorrhage. Unfortunately, this common use of platelet transfusions in the NICU lacks a substantial evidence base. This review focuses on the issue of prophylactic platelet transfusion practice in the NICU and evaluates the rationale, benefits, risks, and the studies needed to improve this important aspect of neonatology practice.
Integration of manufacturing system design and quality management

Manufacturing system design and product quality are tightly coupled. Although extensive research and practice have been devoted to designing manufacturing systems and to improving product quality i...
Quantum control: Engineering a revolution

Rapidly changing noise impedes high-fidelity quantum control. An engineering framework for predicting and mitigating such dynamics has now been validated, revealing physical insights into the time evolution of quantum states.
The independent effects of hyperventilation, tolazoline, and dopamine on infants with persistent pulmonary hypertension.

We studied the separate and combined effects of hyperventilation and administration of dopamine and tolazoline in five infants with pulmonary hypertension managed with indwelling pulmonary artery catheters. In five infants the right-to-left shunt reversed during ventilator-induced respiratory alkalosis (pH>7.6). Response to drugs was variable and unpredictable. One infant could be oxygenated at normal pH during combined dopamine and tolazoline infusion. Other infants showed no response to drugs, or became worse during infusion. The ratio of pulmonary artery to systemic artery pressure averaged 1.14 with standard therapy, but decreased to 0.98 following respiratory alkalosis alone, to 0.87 following drug infusions, and to 0.70 following the combination of alkalosis and drug infusion. These changes were significant by analysis of variance at P P P
Oscilloscope Waveform Digitizer

The instrument presented utilizes an oscilloscope, television camera and control logic to digitize high speed transient or repetitive waveforms displayed on the CRT of an oscilloscope. It allows visual study of signals which would normally be degraded by the cabling used to carry the signal from the source to a remote oscilloscope. The instrument is placed near the source where digital conversion of the waveform takes place. The digital data is stored in local memory and is transmitted to a computer for manipulation and presentation. This allows long term study of transient waveforms. The unit extends the analog to digital conversion speed to 20 samples in 20 ns. Assuming 5 samples per cycle, this would correspond to digitizing transients in the 200 MHz frequency range.
Polarization and depolarization in PSG films

The temperature dependence of the polarization in thin phosphosilicate glass (PSG) films is characterized by an activation energy ΔH = (0.39 + 0.039Et) eV, whereas the decay mechanism has an activation energy of 0.5eV. The flatband voltage shift due to PSG polarization was linear with applied fields as large as 5.5 × 106V ċ cm-1. The effective time constants for the polarization and depolarization are distinctly different. Polarization occurs an order of magnitude faster than depolarization. A physical model has been postulated to explain the observed effects.
Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells.

Fibronectin (Fn) forms a fibrillar network that controls cell behavior in both physiological and diseased conditions including cancer. Indeed, breast cancer-associated stromal cells not only increase the quantity of deposited Fn but also modify its conformation. However, (i) the interplay between mechanical and conformational properties of early tumor-associated Fn networks and (ii) its effect on tumor vascularization remain unclear. Here, we first used the Surface Forces Apparatus to reveal that 3T3-L1 preadipocytes exposed to tumor-secreted factors generate a stiffer Fn matrix relative to control cells. We then show that this early matrix stiffening correlates with increased molecular unfolding in Fn fibers, as determined by Forster Resonance Energy Transfer. Finally, we assessed the resulting changes in adhesion and proangiogenic factor (VEGF) secretion of newly seeded 3T3-L1s, and we examined altered integrin specificity as a potential mechanism of modified cell–matrix interactions through integrin blockers. Our data indicate that tumor-conditioned Fn decreases adhesion while enhancing VEGF secretion by preadipocytes, and that an integrin switch is responsible for such changes. Collectively, our findings suggest that simultaneous stiffening and unfolding of initially deposited tumor-conditioned Fn alters both adhesion and proangiogenic behavior of surrounding stromal cells, likely promoting vascularization and growth of the breast tumor. This work enhances our knowledge of cell – Fn matrix interactions that may be exploited for other biomaterials-based applications, including advanced tissue engineering approaches.