cssi/SciSciGPT-SciSciNet huggingface dataset:
In Chronic Myeloid Leukemia (CML) Patients with Complete Cytogenetic Response to Imatinib, BCR-ABL Kinase Domain Mutations Are Relatively Rare and Not Consistently Associated with Subsequent Relapse.

Background: Imatinib mesylate (IM) induces complete cytogenetic remission (CCR) in 82% of newly diagnosed patients with CML in chronic phase. Most of these patients display minimal residual disease by nested RT-PCR for BCR-ABL . A previous study suggested that kinase domain (KD) mutations in BCR-ABL may be responsible for disease persistence in a significant percentage (9/13) of CCR patients (Chu et al. Blood, 2005). As the relapse rate in this small cohort was high, we decided to investigate the incidence of KD mutants in a more representative group of patients with stable CCR. Methods: We performed nested RT-PCR for BCR-ABL in 72 CCR patients, using 2 sets of primers spanning the breakpoint and entire kinase domain, with ABL as a control gene. Mutation analysis was performed with direct sequencing and denaturing-HPLC of BCR-ABL amplicons. Median time on IM in these patients was 32 months (range, 8–65). In case of wild-type sequence, PCR products were subcloned and a median of 16 individual clones (range, 11–20) sequenced. Results : Amplification was successful in 42/72 patients (58%). We detected 11 different point mutations in 9/42 (21%), of which 3 were novel (C305S, T212R, N231D). The remaining 8 mutants are known to be IM-resistant. C305S was found only by analysis of subclones, while all other mutations were detected upon initial analysis. 5/9 patients with a mutation had a corresponding rise in BCR-ABL transcripts by qRT-PCR. In the other 4, low or undetectable levels of BCR-ABL were maintained. For 2 of these, follow-up mutation analysis detected wild-type BCR-ABL , indicating a decrease of the mutant clone below the detection threshold. For patient 5, with G250E, an initial rise in BCR-ABL was followed by a continual decrease and stable CCR. Although most of the mutants detected were expected to lead to hematologic relapse, at a median follow-up of 12 months, this occurred in only one case. Conclusions : KD mutations were detected in a modest proportion of CCR patients (12% of all patients and 21% of BCR-ABL -positive patients). The relatively high rate of PCR negativity may be due to the long amplicons (1.4kb). Our data imply that, in the majority of patients, disease persistence must be mediated by mechanisms other than KD mutations. In addition, some mutants failed to persist upon follow-up analysis, suggesting that the mutations occurred in transiently amplifying cells that are not capable of prolonged survival.
Does a future-oriented temporal perspective relate to body mass index, eating, and exercise? A meta-analysis.

Abstract Objective The present study aimed to quantify the magnitude of the association between future temporal perspective and Body Mass Index (BMI), diet, and exercise, respectively, and to clarify whether subjective future-focus scales or delay-discounting tasks are a more robust predictor of health behaviors. Methods A systematic search was conducted for studies that included a dispositional measure of future temporal perspective and a measure of BMI, eating, and/or exercise behavior. Effect sizes for BMI, eating, and exercise were calculated using a random-effects model. Results The aggregate effect sizes for BMI ( r = 0.14, k = 36, 95% CI = 0.10 - 0.18, p r = 0.16, k = 18, 95% CI = 0.12–0.21, p r = 0.12, k = 18, 95% CI = 0.09–0.14, p Conclusions Although small in magnitude, the association between temporal perspective and health outcomes is comparable to other individual differences, such as personality and temperament. Future research is needed to examine how increasing the value placed on future outcomes can be integrated into long-term health behavior change interventions.
Quality Indicators for Reviews of Research in Special Education.

ABSTRACTReviews of research in special education have a unique place in the scientific literature, with the potential to inform a broad audience about the effectiveness and acceptability of assessment and intervention strategies for a heterogeneous group of children and youth. Results from reviews are useful to school leaders, practitioners, parents, policymakers, grant funders, researchers, journal editors, and reviewers. Despite an international movement toward the implementation of evidence-based practices, which includes quality indicators for reviews of research, the field of special education has not yet embraced its own set of review indicators. In this manuscript, we make the case for and propose a set of quality indicators for special education, with the goal of making all reviews in the field trustworthy, transparent, and systematic. Attaining a high level of quality in research reviews will then help researchers guide consumers to select the most effective interventions for youth with disabilities.
Novel Carrier Doping Mechanism for Transparent Conductor: Electron Donation from Embedded Ag Nanoparticles to the Oxide Matrix

A trade-off between the carrier concentration and carrier mobility is an inherent problem of traditional transparent conducting oxide (TCO) films. In this study, we demonstrate that the electron concentration of TCO films can be increased without deteriorating the carrier mobility by embedding Ag nanoparticles (NPs) into Al-doped ZnO (AZO) films. An increment of Ag NP content up to 0.7 vol % in the AZO causes the electron concentration rising to 4 × 1020 cm–3. A dependence of the conductivity on temperature suggests that the energy barrier for the electron donation from Ag NPs at room temperature is similar to the Schottky barrier height at the Ag–AZO interface. In spite of an increase in the electron concentration, embedded Ag NPs do not compromise the carrier mobility at room temperature. This is evidence showing that this electron donation mechanism by Ag NPs is different from impurity doping, which produces both electrons and ionized scattering centers. Instead, an increase in the Fermi energy level o...
A Flexible Passive Space Array with Springs (II)

A passive space communicator in synchronous orbit will consist of small aluminum beads chained together and aligned vertically by the Earth’s gravity-gradient. The analysis for small deviations from vertical uses a continuous chain model, and pitch and roll frequencies and mode-shapes are described. Damping of the lowest-order, otherwise rigid and undamped, modes can be obtained by inserting springs between the end portions and the main portion of the chain. The roll damping depends on tuning the springs so that energy is transferred out of roll. The effect of detuning on roll damping time is investigated.
Eye health knowledge and eye health information exposure among hispanic/latino individuals results from the hispanic community health study/ study of latinos

Importance Routine eye care is important to maintaining eye health and preventing visual impairment. However, poor knowledge of ocular risk factors and disease as well as minimal exposure to eye health information may compromise adherence to eye care recommendations. Studies have shown that Hispanic/Latino people have poor eye care utilization, but little is known about their knowledge of eye health and exposure to eye health information. Objective To examine factors associated with more eye health knowledge and greater exposure to eye health information among Hispanic/Latino people. Design, Setting, and Participants This was a cross-sectional ocular study of 1235 participants living in the Miami, Florida, site of the Hispanic Community Health Study/Study of Latinos, a multisite epidemiologic study of disease prevalence and development among Hispanic/Latino people. Data were collected from October 1, 2011, through September 30, 2013, and data analyses were conducted between May 28, 2014, and March 18, 2015. Descriptive and multivariable regression analyses were performed for 3 ocular health care outcomes. Regression models were built sequentially, with variables conceptually grouped according to Andersen’s Behavioral Model of Health Services Use and Behavioral Model for Vulnerable Populations. Main Outcomes and Measures Ability to identify 8 factors on a general eye health knowledge scale and number of eye health information sources seen or heard about in the past 12 months. Results Of the 1235 participants, 748 (73.4%) self-identified as being of Cuban descent and 407 (19.2%) self-identified as being from Central or South America, 478 (46.7%) were women and 757 (53.3%) were men, and the mean (SD) age was 53.6 (8.1) years. Participants with at least a high school degree or general educational development certificate had greater eye health knowledge (incidence rate ratio [IRR], 1.08; 95% CI, 1.01-1.15 and IRR, 1.11; 95% CI, 1.04-1.17, respectively) as did those with a higher mental health score on the Short Form 12-Item, version 2, Health Survey (IRR, 1.03; 95% CI, 1.01-1.04). Those with educational attainment beyond a high school degree or a general educational development certificate (IRR, 1.29; 95% CI, 1.07-1.54), those who were 60 years or older (IRR, 1.32; 95% CI, 1.06-1.63), and those with a household income in US dollars of $20 001 to $40 000 (IRR, 1.23; 95% CI, 1.05-1.44) or greater than $40 000 (IRR, 1.25; 95% CI, 0.98-1.59) were more likely to be exposed to at least 5 sources of eye health information in the past 12 months. Conclusions and Relevance Among Hispanic/Latino people, age, educational level, income, and mental health may be important correlates of eye disease knowledge and eye health information exposure. These findings might be used to support the development of targeted interventions designed to improve eye health in this population.
Parametric Study of Trade-Offs in the Hybrid Transport Theory MAVRIC Methodology for Shielding and Dosimetry Analyses

New computational methods in dose assessment and shielding calculations have drastically increased possible accuracy and resolution of the solution, while also increasing both memory demand and run...
A CS1-NKG2D Bispecific Antibody Collectively Activates Cytolytic Immune Cells against Multiple Myeloma

Multiple myeloma (MM) is an incurable hematologic malignancy of plasma cells, with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single-chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb). Although NKG2D is a potent activation receptor ubiquitously expressed on mostly cytolytic immune cells including NK cells, CD8+ T cells, γδ T cells, and NKT cells, the CS1 tumor-associated antigen on MM represents a promising target. CS1-NKG2D biAb engaged human MM cell lines and NKG2D+ immune cells, forming immune synapses. In effector cells, CS1-NKG2D biAb triggered the phosphorylation of AKT, a downstream protein kinase of the activated NKG2D-DAP10 complex. The EC50 values of CS1-NKG2D biAb for CS1high and for CS1low MM cell lines with effector PBMCs were 10-12 and 10-9 mol/L, respectively. CS1-NKG2D biAb acted through multiple types of immune cells, and this induced cytotoxicity was both CS1- and NKG2D-specific. In vivo, survival was significantly prolonged using CS1-NKG2D biAb in a xenograft NOD-SCIDIL2γc-/- (NSG) mouse model engrafted with both human PBMCs and MM cell lines. Collectively, we demonstrated that the CS1-NKG2D biAb facilitated an enhanced immune synapse between CS1+ MM cells and NKG2D+ cytolytic innate and antigen-specific effector cells, which, in turn, activated these immune cells for improved clearance of MM. Cancer Immunol Res; 6(7); 776-87. ©2018 AACR.
Renal Sodium-Glucose Transporter-2 Inhibitors as Antidiabetic Agents

Abstract Type 2 diabetes mellitus is reaching epidemic proportions worldwide. Intensive glycemic control is necessary to prevent macrovascular and microvascular complications associated with diabetes. Yet, despite the availability of a number of therapeutic options, optimal control of blood glucose in diabetics remains a challenge. Also, currently available antidiabetic medications can cause adverse effects, such as hyperglycemia, weight gain, and fluid retention, often limiting their use. Glycemic control is difficult to attain, even with a combination of multiple oral agents, and with insulin added. These concerns underscore the need to develop new and better-tolerated therapeutic agents for glycemic control. In this context, the sodium-glucose cotransporter-2 (SGLT2) responsible for renal glucose reabsorption provides an attractive target for therapeutic intervention to regulate blood sugar levels. Unlike conventional diabetes therapies, SGLT2 inhibitors are effective without progressive loss of activity, and in subjects with varying degrees of insulin resistance and β-cell function. This has led to the development and recent Food and Drug Administration approvals of a novel class of drugs (“glifozins”), which include dapagliflozin (Farxiga), canagliflozin (Invokana), and empagliflozin (Jardiance). Today these drugs are also being investigated for potential therapeutic value in treating cardiovascular diseases. This chapter gives a brief overview of SGLT2 inhibitors and discusses the potential of harnessing plant-based molecules for their effectiveness in inhibiting SGLT2.
The Evolutionary Genetics of Xiphophorus

Fishes of the genus Xiphophorus, the platyfish and swordtails, are common inhabitants of the streams and rivers of Central America. The 15 species described occupy a variety of habitats, ranging widely through the Atlantic drainage from northeastern Mexico, south-east through Guatemala, Honduras and Belize. Like most other members of the family Poeciliidae, Xiphophorus species are internally fertilizing and ovoviviparous (Rosen and Bailey, 1963). Females can store sperm and produce broods for several months after a successful mating.
Feed Ingredients | Feed Supplements: Ruminally Protected Amino Acids

Ruminally protected amino acids are free amino acids that have been coated or encapsulated with materials that allow for a significant portion of the amino acid to escape ruminal degradation but be released in the abomasum or small intestine. Derivatives and analogues of amino acids have also been evaluated as protected amino acids. Indeed, some have been identified that are more resistant to ruminal degradation, or have greater absorption from the rumen, than the free amino acid. Commercial products are presently limited to rumen-protected methionine, rumen-protected lysine, and the isopropyl ester of methionine hydroxy analogue. As nutritional supplements, they are used to correct lysine and methionine deficiencies in digestible protein and reduce the amounts of rumen-undegradable protein that must be fed to provide a given supply of absorbed lysine and methionine. Protected amino acids are taking on added importance in dairy cattle nutrition to achieve improved amino acid balance, support more efficient milk production, and minimize wasting of nitrogenous compounds.
Value-Based Radiology in Abdominal and Pelvic Imaging

In this chapter, five cases are presented to illustrate the central role of radiologists in patient care. These cases illustrate the incredible value that the radiologists can bring to the table, and the input of radiologists in promoting evidence-based guidelines in the management of patients. Clinical algorithms in determining when an abdominopelvic CT examination is indicated for blunt abdominopelvic trauma are discussed. A case in the workup of incidentalomas shows the potential for high-value care radiologists can offer to patients, a case illustrating the radiologist ability to influence medical versus surgical management of appendicitis in the era where imaging diagnosis has arguably trumped over clinical diagnosis of appendicitis. Cases discussing the central role of radiologists in diagnosing renal colic and colonic diverticulitis, and the potential for radiologists to act as patients advocate to minimize unnecessary radiation exposure associated with CT scans, are also discussed.
Predictors and Clinical Outcomes of Vasoplegia in Patients Bridged to Heart Transplantation with Continuous Flow Left Ventricular Assist Devices

Purpose Vasoplegia has been implicated in adverse outcomes after heart transplantation (HT). Although left ventricular assist device (LVAD) is associated with increased risk of vasoplegia, pre-operative predictors of vasoplegia in this population and its impact on survival after HT are unknown. In this study, we sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with continuous flow LVAD. Methods We retrospectively analyzed 94 patients who underwent HT after bridging with LVAD between July, 2008 and June, 2018 at a large institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours post HT for >24 hours to maintain a mean arterial pressure >70 mm Hg. Logistic regression was used to examine predictors of vasoplegia and the association with survival was examined using Cox proportional hazard regression. Results Overall, 44 (46.8%) patients with LVAD developed vasoplegia after HT. Patients with and without vasoplegia had similar pre-operative LVAD, echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older, had longer LVAD support, higher pre-operative creatinine, cardiopulmonary bypass time (CBT), and Charlson comorbidity index, and had higher rates of hypothyroidism and sustained ventricular tachycardia (VT) (all p Conclusion Longer LVAD support, impaired renal function, sustained VT, and prolonged intra-operative CBT are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with poor prognosis; hence, detailed assessment of these predictors can be clinically important.
Forensic analysis of Microsoft Skype for Business

Abstract We present three case studies to illustrate a methodology for conducting forensics investigation on Microsoft Skype for Business. The proposed methodology helps to retrieve information on chat and audio communications made by any account who accessed the PC, to retrieve IP addresses and communication routes for all the participants of a call, and to retrieve forensics evidence to identify the end-user devices of a VoIP call by analyzing the CODECs exchanged by the clients during the SIP (Session Initiation Protocol) handshaking phase. This information may help the investigator either to corroborate or to contradict an investigative hypothesis.
Fire detection and temperature retrieval using EO-1 Hyperion data over selected Alaskan boreal forest fires

Abstract Infrared imaging spectrometers are used to map and characterize wildland fire based on their sensitivity to fire-emitted thermal radiation and ability to resolve spectral emission or absorption features. There is a general paucity of research on the use of space-borne imaging spectroscopy to study active fires in the North American boreal forest. We used hyperspectral data acquired by the Hyperion sensor on the EO-1 satellite over three wildfires in Alaska's boreal forest to evaluate three fire detection methods: a metric to detect an emission feature from potassium emitted by biomass burning; a continuum-interpolated band ratio (CIBR) that measures the depth of a carbon dioxide absorption line at 2010 nm; and the Hyperspectral Fire Detection Index (HFDI), which is a normalized difference index based on spectral radiance in the short-wave infrared range. We found that a modified version of the HFDI produces a well-defined map of the active fire areas. The CO2 CIBR, though affected by sensor noise and smoke, contributes a slight improvement to the fire detection performance when combined with HFDI-type indices. In contrast, detecting a fire signal from potassium emission was not reliably possible in a practically useful way. We furthermore retrieved fire temperatures by modeling the at-sensor radiance as a linear mixture of two emitted and two reflected spectral radiance endmembers. High-temperature fire areas (the high-intensity fire front, modeled at 800–900 K) and low-temperature combustion (residual fire at 500–600 K), were mapped. High-temperature burning areas as small as half a percent of a Hyperion pixel (approx. 5 m2) were detectable. These techniques are of potential interest for fire characterization in the boreal areas of the circumpolar North using current and future satellite-borne imaging spectrometers.
Informativeness of Performance Measures in the Presence of Reporting Discretion

Accounting performance measures are the end products of a series of unobservable managerial product decisions, unobservable noise, and accounting choices. This paper develops conditions under which...
Periconceptional folic acid and risk for neural tube defects among higher risk pregnancies

Background Women with a previous neural tube defect (NTD)-affected pregnancy are recommended to consume 4,000 μg daily folic acid (FA) for prevention (10 times the general-population recommendation). Protection from doses between 400 and 4,000 μg for this and other higher risk groups is unclear. Methods In the case-control Slone Birth Defects Study (1988-2015), we examined the associations between periconceptional FA doses and NTDs among four higher risk groups: NTD family history, periconceptional antiepileptic drug exposure (AED), pregestational diabetes, and prepregnancy obesity. Mothers completed standardized interviews about pregnancy events and exposures. FA categorizations were based on (a) supplements only and (b) supplements and diet ("total folate"). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) (adjusted for age and study center) using logistic regression. Results Cases and controls included: 45 and 119 with family history, 25 and 108 with AED exposure, 12 and 63 with pregestational diabetes, 111 and 1,243 with obesity. Daily FA supplementation was associated with lower NTD risk compared to no supplementation (adjusted ORs were 0.33 [95% CI 0.13, 0.76] for family history, 0.31 [0.09, 0.95] for AED exposure, 0.25 [0.04, 1.05] for pregestational diabetes, 0.65 [0.40, 1.04] for obesity). Though estimates were imprecise, as total folate increased stronger point estimates were observed, notably among family history. No mothers with a prior NTD-affected pregnancy supplemented with 4,000 μg. Conclusions Our findings reinforce that all women of childbearing potential should consume at least 400 μg FA/day to protect against NTDs. Higher risk groups may benefit from higher doses.
The Photisterion in Late Antiquity: Reconsidering Terminology for Sites and Rites of Initiation

What is a photisterion? Translators usually render the Greek word phōtistērion (site of illumination) as ‘baptistery’ (site of immersion in water). This article reopens the study of phōtistēria, arguing that being ‘immersed’ or ‘illuminated’ evokes different senses of the concomitant meaning of the sites and rites of initiation. It situates late ancient phōtistēria from epigraphic and literary sources in their theological and liturgical contexts. The evidence from Galilee, Syria, Jordan and Cyprus corroborates the idea that many Christians of late antiquity preferred ‘illumination’ to express the composite rite of initiation in a phōtistērion, within which ‘baptism’ was one part.
PHARMACY: The clinical pharmacist on a pediatric unit

(1969). PHARMACY: The clinical pharmacist on a pediatric unit. Hospital Topics: Vol. 47, No. 11, pp. 81-89.
Toward the Goal of Human Heart Regeneration

Heart regeneration, a relatively new field of biology, is one of the most active and controversial areas of biomedical research. The potential impact of successful human heart regeneration therapeutics cannot be overstated, given the magnitude and prognosis of heart failure. However, the regenerative process is highly complex, and premature claims of successful heart regeneration have both fueled interest and created controversy. The field as a whole is now in the process of course correction, and a clearer picture is beginning to emerge. Despite the challenges, fundamental principles in developmental biology have provided a framework for hypothesis-driven approaches toward the ultimate goal of adult heart regeneration and repair. In this review, we discuss the current state of the field and outline the potential paths forward toward regenerating the human myocardium.
Polysulfide entrapment and retardation in gel electrolyte Li–S batteries: experiments and modeling

Gelling the electrolyte in lithium–sulfur (Li–S) batteries provides advantages in terms of safety and mitigating polysulfide shuttling leading to reduced side reactions and dendrite growth on the anode side. In the current study, organic and ceramic crosslinkers have been used to improve the entrapment of polysulfides and prevent them from shuttling to the anode side. However, the performance of gel electrolytes is still far from being on par with liquid electrolytes in terms of raw capacity. The discharge curves exhibit an extended first plateau for gel electrolyte batteries compared to liquid electrolytes, showing that polysulfides are better trapped in the gel system. Yet, in the conversion of soluble polysulfides into insoluble polysulfides, the second plateau was delayed. Qualitative and quantitative analysis of the polysulfide diffusion in the liquid electrolyte and gel electrolyte systems were also conducted to predict the relative diffusivity ratio between the liquid electrolyte and gel electrolyte for simulation. To probe what happens at the end of the discharge, where the mass transport in the gel electrolyte appears to be slow, a modified discharge procedure was used where the cell is first paused after discharge and then discharged a second time before recharging normally. Coin cell tests for two gel electrolytes in addition to liquid electrolyte show up to 7% capacity recovery after the pause, which indicates that the diffusion of species during the pause is responsible for the failure recovery. Additionally, the recovery is higher for gel electrolytes compared to liquid, for higher C-rates, and for longer pause times. To better understand this behavior, a Li–S numerical model with mass transport limited reactions was used to examine the polysulfide diffusion coefficients expected in different electrolyte systems. The model is able to reproduce the trends seen in experiments and yields a higher recovery for smaller Li2S4 diffusion coefficients, suggesting that insufficient Li2S4 mass transport is responsible for failure at the end of discharge. By identifying the effect that gel electrolytes have on the state of the battery during discharge using both experimental and simulation methods, this work is a step towards leveraging the advantages of gel electrolytes and mitigating their weaknesses.
Potential low powered smart window coating using a stoichiometrically downgraded vanadium oxide thin film structure

With a metal to insulator transition (MIT) temperature of ∼68 °C to 70 °C, which is close to room temperature (RT), vanadium oxide (VO2) has piqued interest in research communities for several applications, such as Mott-transistors and smart windows. This unique characteristic and multi-faceted application of VO2 makes it ideal for several fields, from consumer electronics to defense applications. However, despite this advantage over several other materials, VO2 has some serious shortcomings. In this paper, we attempt to address these issues, such as higher than RT transition temperature, metastability of the material, and its need for a separate heater layer to trigger the MIT, by using a stoichiometrically downgraded multi-layered structure that can both demonstrate the MIT property and serve as an embedded heater layer. This eliminates the need to use a system with a different material such as aluminum-doped zinc oxide. By using the multi-layered structure, we were able to achieve a transition temperature of ∼48 °C, which is ∼22 °C lower than the transition temperature of bulk VO2 films. We also noted a reduction of over 50% in transmission in the infra-red region by application of less than 15 V, as well as an enhancement of ∼10% in the visible region transmission beyond the MIT temperature, which demonstrates the potential of this structure to be used as an energy-efficient smart window device.
Paravalvular Leak Assessment: Challenges in Assessing Severity and Interventional Approaches

With increasing use of prosthetic valves to treat degenerative valvular heart disease (VHD) in an aging population, the incidence and adverse consequences of paravalvular leaks (PVL) are better recognized. The present work aims to provide a cohesive review of the available literature in order to better guide the evaluation and management of PVL. Despite gains in operator experience and design innovation, significant PVL remains a significant complication that may present with congestive heart failure and/or hemolytic anemia. To date, clear consensus or guidelines on the evaluation and management of PVL remain lacking. Although the evolution of transcatheter valve therapies has had a tremendous impact on the management of patients with VHD, the limitations and complications of such techniques, including PVL, present further challenges. Incidence of PVL, graded as moderate or greater, ranges from 4 to 7.4% in surgical and transcatheter valve replacements, respectively. Improved imaging modalities and the advent of novel surgical and percutaneous therapies have undoubtedly yielded a better understanding of PVL including its anatomical location, mechanism, severity, and treatment options. Echocardiography, used in conjunction with cardiac computed tomography and cardiac magnetic resonance, provides essential details for diagnosis and management of PVL. Transcatheter intervention has become a favored approach in lieu of surgical intervention in select patients after previous surgical or percutaneous valve replacement. PVL treatment with vascular plugs, balloon post-dilation, and the valve-in-valve methods have shown technical success with promising clinical outcomes in appropriately selected patients.
Prognostic factors and survival of patients undergoing surgical intervention for breast cancer bone metastases.

Introduction Bone is the most common distant site of breast cancer metastasis. Skeletal lesions can cause significant morbidity due to pain, pathologic fracture, and electrolyte abnormalities. Current treatment for patients with bone metastases (BoM) from breast cancer is highly personalized and often involves a multidisciplinary approach with chemotherapy, hormone therapy, bone-targeted antiresorptive agents, radiation therapy, and surgery. We have retrospectively collected clinical data from a series of patients with bone metastases to evaluate the clinical characteristics, prognostic factors, and survival patterns of patients with breast cancer BoM receiving standard multimodal therapy. Methods A consecutive series of 167 patients with breast cancer BoM treated at a single institution between August 2013 and March 2020 were identified. Clinical information was obtained from the medical record and survival analyses were performed to evaluate patient outcomes and identify prognostic factors. Results Thirty-seven patients (22%) presented with de novo BoM - bone metastases at the time of breast cancer diagnosis - and were 2.6 times more likely to die within the study period than those with asynchronous BoM (HR = 2.62, p = <0.0001). Patients who received bone-targeted medical therapy were 61% less likely to die after BoM diagnosis than those who did not (HR = 0.39, p = 0.001). Operative stabilization of BoM was more frequently employed in patients with lytic (p = 0.02) or mixed (p = 0.02) tumors than it was for those with blastic lesions. Patients treated with surgery had a lower overall bone metastasis survival than those treated without (p < 0.03). Discussion These findings reflect the current patterns in metastatic breast cancer treatment and associated outcomes. In a series of 167 consecutive patients, we demonstrate the natural history of breast cancer with BoM being treated with modern multimodal therapy. Understanding these treatment patterns and prognostic factors enhances the provider's ability to counsel patients and direct appropriate treatments.
Population structure of a worldwide Phytophthora palmivora collection suggests lack of host specificity and reduced genetic diversity in South American and Caribbean.

Phytophthora palmivora (Butler) is a highly destructive plant pathogen that infects tropical hosts worldwide - many are economically important crops. Despite the broad host range and the wide distribution, the pathogen has displayed considerable variation in morphological characters, including virulence. However, the genetic variability at the global level was still unclear, preventing understanding of the center of origin and the potential disease transmission pathway(s). Here, we mapped the genetic variation of P. palmivora using isolates representing four regions, 15 countries, and 14 host species. We designed a large set of simple sequence repeats (SSRs) markers from the P. palmivora genome and picked 17 selectively neutral ones to screen 98 P. palmivora isolates. We found that P. palmivora populations from our collection generally did not cluster according to the host. Some isolates from North America were distinct from all other populations. Isolates from South America and the Caribbean clustered and appeared to share ancestry with isolates from Asia. Populations from North America and Asia were the most genetically diverse, but the South American and Caribbean populations exhibited similar reduced genetic diversity. The isolates collected in various plantations in Colombia didn't show host or geographic specificity. Our study sheds some light on understanding this pathogen, although the determination for the hypothesized source of origin, spread, and evolution would need further sampling. The genomic resources developed in this study would facilitate future studies on P. palmivora diagnostics and management.
Sub-diffraction-limit optofluidic scanning microscopy

Optofluidic microscopes use fluids’ properties as an additional degree of freedom for optical detection and microfluidics to perform simple and low-cost object manipulation. In particular, several devices have been optimized for fluorescencebased imaging. These are usually based on the adaptation of established microscopy tools to the microfluidic system with different levels of integration. However, these systems can rarely resolve sub-micron details, posing a limit to the structures that can be studied. An exception is represented by systems developed for particle detection, which are capable to quantify protein expression and analyze small molecules even at nanoscale resolution. However, in this case high resolution requires a low emitter density and it cannot be used to visualize densely packed structures such as membranes and organelles. Hence, we have developed a system for sub-diffraction-limited optofluidic scanning microscopy (OSM) that uses the optofluidics paradigm to extract the inherent super-resolution information of a confocal system. OSM uses the optofluidic flow scanning scheme and a multifocal illumination pattern to obtain resolution doubling with minimal system complexity. In addition, it does not require any mechanical part for the scanning, so that it can be readily adapted to different levels of integration from commercial microscopes to on-chip configurations. This makes our system the most viable configuration for super-resolution optofluidics, being both suitable for continuous flow scanning and compatible with on-chip configurations through the adoption of integrated optics.
The Roots of Rough Justice: Origins of American Lynching – By Michael J. Pfeifer

Only in the last twenty years have scholars begun to historicize lynching, overcoming a strong tendency to view every act of murderous racial violence as part of an unchanging sociological reality....
Purification of a specific repressor of ferritin mRNA translation from rabbit liver.

Abstract The synthesis of ferritin is regulated at the translation level in coordination with iron availability. Under conditions of low iron, translation of ferritin mRNA is repressed and the majority of ferritin mRNA is non-polysomal. Upon an increase in iron, translation of ferritin mRNA is derepressed resulting in as much as a 50-100-fold increase in the rate of ferritin synthesis. This regulation is mediated at least in part by a specific translational repressor which binds to a conserved sequence, the iron responsive element, located in the 5'-untranslated region of ferritin mRNA. In this communication we report the purification of such a repressor from rabbit liver. This repressor, which we call the "ferritin repressor protein," has an apparent molecular mass of 90 kDa when analyzed by gel filtration chromatography. It inhibits translation of ferritin mRNA in a highly specific fashion when added to a wheat germ lysate programmed with liver poly(A+) mRNA. In addition, it binds specifically to sequences contained within the first 92 nucleotides of ferritin mRNA, most likely the iron responsive element. Analysis of highly purified repressor by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that it is composed primarily of a single polypeptide of approximately 90 kDa. Elution of this 90-kDa polypeptide from a sodium dodecyl sulfate gel followed by renaturation and analysis for repressor activity shows that it both binds to the 5'-untranslated region of ferritin mRNA and represses its translation in vitro.
Expression of connexin 43 (Cx43) is critical for normal hematopoiesis.

Gap junctions are intercellular channels, formed by individual structural units known as connexins (Cx), that allow the intercellular exchange of various messenger molecules. The finding that numbers of Cx43-type gap junctions in bone marrow are elevated during establishment and regeneration of the hematopoietic system has led to the hypothesis that expression of Cx43 is critical during the initiation of blood cell formation. To test this hypothesis, lymphoid and myeloid development were examined in mice with a targeted disruption of the gene encoding Cx43. Because Cx43−/− mice die perinatally, initial analyses were performed on Cx43−/−, Cx43+/−, and Cx43+/+ embryos and newborns. The data indicate that lack of Cx43 expression during embryogenesis compromises the terminal stages of primary T and B lymphopoiesis. Cx43−/− embryos and neonates had a reduced frequency of CD4+ and T-cell receptor-expressing thymocytes and surface IgM+cells compared to their Cx43+/+ littermates. Surprisingly, Cx43+/− embryos/neonates also showed defects in B- and T-cell development similar to those observed in Cx43−/− littermates, but their hematopoietic system was normal at 4 weeks of age. However, the regeneration of lymphoid and myeloid cells was severely impaired in the Cx43+/− mice after cytoablative treatment. Taken together, these data indicate that loss of a single Cx43 allele can affect blood cell formation. Finally, the results of reciprocal bone marrow transplants between Cx43+/+ and Cx43+/− mice and examination of hematopoietic progenitors and stromal cells in vitro indicates that the primary effects of Cx43 are mediated through its expression in the hematopoietic microenvironment.
Language and Communication in Non-Alzheimer's Dementias

Disturbances in language and communication are prominent symptoms in dementia. Many dementing illnesses lead to aphasia, others primarily impair verbal fluency or result in motor speech disturbances such as dysarthria. This chapter discusses language and communication disturbances that occur in non-Alzheimer's dementias, including related abnormalities in cognition, aspects of neuropathology, and neuroimaging. The language deficits in vascular dementia (VaD), frontotemporal dementia (FTD) (e.g., Pick's disease), Huntington's disease (HD), progressive supranuclear palsy (PSP), Creutzfeldt-Jakob disease (CJD), and primary progessive aphasia (PPA) are included. Implications for future research are also noted.
Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis.

Abstract Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease, was shown previously to cleave SREBP-1 and SREBP-2 in vitro at an aspartic acid between the basic helix-loop-helix leucine zipper domain and the first trans-membrane domain, liberating a transcriptionally active fragment. Here, we show that CPP32 exists in an inactive 32 kDa form in Chinese hamster ovary (CHO) cells. When apoptosis was induced with the protein kinase inhibitor staurosporine, CPP32 was cleaved to subunits of 20 and 10 kDa to form the active protease. Under these conditions membrane-bound SREBP-1 and SREBP-2 were both cleaved, and the transcriptionally active N-terminal fragments were found in nuclear extracts. Similar results were obtained in human U937 cells induced to undergo apoptosis by anti-Fas and etoposide. The apoptosis-induced cleavage of SREBPs was not suppressed by sterols, indicating that apoptosis-induced cleavage and sterol-regulated cleavage are mediated by different proteases. CHO cells expressing a mutant SREBP-2 with an Asp--> Ala mutation at the CPP32 cleavage site showed sterol-regulated cleavage but no apoptosis-induced cleavage. These data are consistent with the emerging concept that CPP32 is a central mediator in apoptosis. They also indicate that SREBPs, like poly (ADP) ribose polymerase, are cleaved by CPP32 during programmed cell death.
Scaffolding knowledge integration through designing multimedia case studies of engineering design

The paper describes our experiences teaching a freshman design course ME39C using multimedia case studies of engineering design, multimedia tools, and the Internet. Students, in mixed-ability groups, learn design process and practice through reviewing engineering cases on CD-ROM and using software tools to develop a multimedia case of their own. The curriculum, although having theoretical bases in education research, is highly governed by practical concerns such as rapidly changing technologies, different background experiences of students, and the grading of open-ended work. The course is also driven by new developments in technology and the changing demands of students. In three years, a five person seminar course has evolved into a laboratory of thirty, changing the nature of learning, teaching style, and quality of student work in both positive and negative ways. We describe this course as it progressed from an experimental course to an institutionalized one. Our experiences confirm our belief that curricula should be designed to promote scaffolded knowledge integration by encouraging students to become more independent learners while capitalizing on collaboration and social aspects of learning. Moreover, curricula should be continuously refined and updated to meet the needs of students and reflect advances in technological development toward better preparation in engineering.
Granular element method for three-dimensional discrete element calculations

This paper endows the recently-proposed granular element method (GEM) with the ability to perform 3D discrete element calculations. By using non-uniform rational B-Splines to accurately represent complex grain geometries, we proposed an alternative approach to clustering-based and polyhedra-based discrete element methods whereby the need for complicated and ad hoc approaches to construct 3D grain geometries is entirely bypassed. We demonstrate the ability of GEM in capturing arbitrary-shaped 3D grains with great ease, flexibility, and without excessive geometric information. Furthermore, the applicability of GEM is enhanced by its tight integration with existing non-uniform rational B-Splines modeling tools and ability to provide a seamless transition from binary images of real grain shapes (e.g., from 3D X-ray CT) to modeling and discrete mechanics computations.
Red Blood Cell Responses To Pulsed Laser Irradiation

Laser parameters have recently been optimized to specifically destroy cutaneous blood vessels and at the same time, spare injury to adjacent epidermal and dermal structures such as collagen. When these parameters have been used in clinical treatmeng, it has been observed that electron-lucent spherules of 600-800 A diameter have consistently been present in these irradiated red blood cells (RBC) producing de-st'ruction of abnormal port wine stain blood vessels. It has been postulated that these changes were due to oxygen released during laser irradiation with the implication that the oxygenated status of the blood affected. the clinical outcome. This study demonstrates that this clinically related RBC morphology is independent of the oxygenated status of the blood. Microspectrophotometric measurements of absorbance across individual RBC of laser irradiated oxygenated and deoxygenated erythrocytes as well as those rapidly heated to temperatures greater than 100°C confirm that these electron-lucent structures are due to a phase change occurring in the RBC and not to oxygen release.
Physical Activity among Certified Health Education Specialists

Abstract This study examined the self-reported physical activity behavior of a randomly selected sample of certified health education specialists (CHESs) in the United States. A cross-sectional descriptive study was conducted. The independent variables were gender, race, exercise physiology course experience, exercise prescription course experience, and education. The dependent variables were total physical activity (TPA) and total physical activity excluding household activities, stair climbing, and lawn work (PA excluding HSL). Stratified random sampling was used to select 1,000 CHESs who received the Aerobics Center Longitudinal Study Physical Activity Questionnaire through the U.S. mail. A total of 540 (54%) surveys were returned. Household activities (91.8%), stair climbing (84.8%), and walking (73.0%) were the most frequently reported physical activities. There were no statistically significant differences in TPA among or between the various groups. Significant differences in PA excluding HSL were f...
Specific Biosynthesis of an Envelope Protein of Escherichia coli

A UNIQUE structural protein in the envelope of Escherichia coli, of molecular weight about 7,500 and covalently attached to the peptidoglycan, was found by Braun et al.1–4, who reported that its amino-acid sequence lacks histidine, proline, glycine, cysteine, phenylalanine and tryptophan4. Recently we found that this lipoprotein exists in the E. coli envelope fraction not only in the bound form found by Braun et al.1–3 but also in a free form, not covalently attached to the peptidoglycan5. This form accounts for about two-thirds of the lipoprotein and serves as a precursor of the bound form5. We describe here an in vivo situation in which only this lipoprotein is biosynthesized. Using these conditions, we have investigated the biosynthetic mechanism of this envelope protein.