cssi/SciSciGPT-SciSciNet huggingface dataset:
Association of Common Carotid Artery Doppler-Determined Dicrotic Notch Velocity With the Left Ventricular Ejection Fraction

Objectives The appearance of the dicrotic notch on blood pressure tracings is associated with impaired cardiac function. Common carotid artery waveforms have similar fiduciary markers, yet they have not been related to cardiac function. We studied associations of common carotid artery dicrotic notch velocities with the left ventricular ejection fraction (LVEF) determined by echocardiography. Methods We conducted a retrospective study of 37 patients who had cardiac echocardiography and carotid Doppler evaluations within 1 day of each other. The LVEF was determined by the biplane modified Simpson rule. Doppler parameters were measured from tracings of the left common carotid artery 4 cm from the flow divider. Linear regression and stepwise multivariable linear regression models were used to evaluate any association between the LVEF and the following variables: age, sex, peak systolic velocity (PSV), end-diastolic velocity (EDV), dicrotic notch velocity, rise time (EDV to PSV), resistive index, and cardiac cycle length. Results The dicrotic notch velocity was the only variable associated with the LVEF (P = .028) in a bivariate analyses. A backward selection stepwise multivariable equation predicting the LVEF had the dicrotic notch (P = .001) and resistive index (P = .01) as significant predictors, whereas the cardiac cycle length (P = .08) and PSV (P = .08) were borderline not significant. Model goodness of fit was R(2) = 0.37 (P = .004). Conclusions Dicrotic notch velocities measured from common carotid artery Doppler waveforms are associated with the LVEF and might offer some clinical value in selected cases.
Error-event characterization on partial-response channels

Two algorithms for characterization of input error events producing specified distance at the output of certain binary-input partial-response (PR) channels are presented. Lists of error events are tabulated for PR channels of interest in digital recording.
Molecular mechanism of androgen action.

Abstract Androgens affect the growth and development of a wide variety of cell types in both males and females and produce their effects by binding to androgen receptors, which modulate the transcription of specific genes. Testosterone is the major active androgen circulating in blood, but in many tissues it is metabolized by 5α-reductase to 5α-dihydrotestosterone, which binds to and activates the androgen receptor. Androgen receptors are members of the nuclear receptor family of transcription factors, and these nuclear receptors control transcription by recruitment of a variety of co-activators and co-repressors. Mutations in the androgen receptor and 5α-reductase can affect male sexual development. 5α-Reductase is also critical for parturition and fetal survival in mice. Inhibitors of 5α-reductase are being used increasingly to treat some androgen-dependent disorders. Because androgens also suppress the growth of certain cancer cells, they might also have a role in treating prostate cancer.
Death‐Related Attitudes and Behavior among Mexican Americans: A Review

: A review of the literature on death-related attitudes and behavior of Mexican Americans is presented. Special focus is given to the 1976 study of Kalish and Reynolds which concludes that Mexican Americans are more accepting of death than Anglos and other ethnic groups. Some of the study's findings are found to suggest that the opposite may be true. An alternative interpretation of the findings is given along with suggestions for future research.
A Single-Center Experience with the NeuroPace RNS System: A Review of Techniques and Potential Problems.

Introduction The clinical results for the RNS System (NeuroPace, Mountain View, California, USA) closed-loop responsive neurostimulator for the treatment of medically intractable partial-onset seizures have been encouraging. The University of Southern California (USC) Neurorestoration Center and the Keck Hospital of USC have become the world's first institutions to implant an RNS System post U.S. Food and Drug Administration (FDA) approval. As one of the study centers, we review our experience with our group of patients who have been implanted with the RNS System. Methods A total of 40 surgeries by a single surgeon were performed on 10 patients (7 male and 3 female) with an average age of 39.2 years (24–66 years) and were followed for an average of 45 months (30–54 months). The average age at seizure onset was 14 years (birth–37 years) with an average of 4.7 (3–12) failed antiepileptic drugs. We reviewed the patients' charts for complications from the surgeries including infections requiring surgical intervention, hematomas, hardware failures, and death. Results Of the 40 surgeries, there were 10 initial implantations of the neurostimulator and leads, 24 neurostimulator replacements for expected end of neurostimulator service, 2 incision and drainage procedures (I & Ds) for soft tissue infection followed by 1 explantation and 1 reimplantation (same patient), and 2 revisions because of one lead that was damaged at the exit point between the skull and a titanium mesh and the second lead that was damaged at an acute bend over the skull (same patient). Eight of the patients had no complications and underwent an average of 2.7 neurostimulator replacements over 7 consecutive years to date. Each patient underwent routine postoperative computed tomography imaging of the brain, and none had any intracranial hematomas or misplaced leads requiring revision surgery. Finally, there were no deaths in our patient population. Conclusions Our experience with the NeuroPace RNS System over an average follow-up of 45 months suggests that the surgery and device are safe when placed by an experienced surgeon. Although there were no clinically significant hematomas or patient deaths, we did have 1 patient each with infection and lead damage at the point of exit from the skull. We compare the results of this study with other neuromodulation procedures for epilepsy to evaluate the safety and complications associated with the RNS System. Our initial experience suggests that the RNS System can be readily incorporated into an active epilepsy surgical center.
Effect of pulse width on transesophageal atrial pacing in dogs

Abstract Objective To determine the impact of stimulus pulse width (PW) on pacing threshold (PT), zone of capture (ZOC) and extraneous muscular stimulation (EMS). Study design Experimental trial in client-owned dogs. Animals Seventeen dogs, median weight 16.1 kg (interquartile range: 11.4–21.5). Methods Transesophageal atrial pacing (TAP) involved a 6 Fr pacing catheter inserted trans-orally into the esophagus to a position aboral to the heart in anesthetized dogs. The catheter was slowly withdrawn until atrial pacing was noted on an electrocardiogram. The catheter was withdrawn in 1 cm increments until TAP could not be achieved. PTs were recorded at each pacing site using PWs of 10.0, 5.0, 2.0 and 1.8 ms, always in that order. Results The overall lowest mean PTs for all dogs were 6 ± 3 mA, 9 ± 4 mA, 11 ± 5 mA and 13 ± 5 mA at PWs of 10.0, 5.0, 2.0 and 1.8 ms, respectively. A significant decrease in overall minimum PT was noted using a PW of 10.0 ms compared with either 2.0 or 1.8 ms (p = 0.043 and p = 0.001, respectively) and pacing using 5.0 ms compared with 1.8 ms (p = 0.028). A significant increase in ZOC was noted using a PW of 10.0 ms compared with PWs of 5.0, 2.0 and 1.8 ms (p = 0.0047, p = 0.0006 and p = 0.0003, respectively), using a PW of 5.0 ms compared with PWs of 2.0 and 1.8 ms (p = 0.0011 and p = 0.0003, respectively) and using a PW of 2.0 compared with one of 1.8 ms (p = 0.0084). Conclusions and clinical relevance Use of 10.0 or 5.0 ms PW to perform TAP minimized the power required to pace the atria, while a PW of 10.0 ms maximized the size of the ZOC.
Computational analysis of functional long noncoding RNAs reveals lack of peptide-coding capacity and parallels with 3′ UTRs

Recent transcriptome analyses have indicated that a large part of mammalian genomes are transcribed into long non-proteincoding RNAs (lncRNAs). However, only a very small fraction of them have been individually studied, and whether the majority of lncRNAs found in large-scale studies have a cellular role is debated. To gain insight into the sequence features and genomic architecture of the subset of lncRNAs that have been proven to be functional, we created a database containing studied lncRNAs manually culled from the literature along with a parallel database containing all annotated protein-coding human RNAs. The Functional lncRNA Database, which contains 204 lncRNAs and their splicing variants, is available at valadkhanlab.org/database. Analysis of the lncRNAs and their comparison to protein-coding transcripts revealed sequence features including paucity of introns and low GC content in lncRNAs, which could explain several biological characteristics of these transcripts, such as their nuclear localization and low expression level. The predicted ORFs in lncRNAs have poor start codon and ORF contexts, which would lead to activation of the nonsense-mediated decay pathways and thus make it unlikely for most lncRNAs to code for even short peptides. Interestingly, our analyses revealed significant similarities between the lncRNAs and the 39 untranslated regions (39 UTRs) in protein-coding RNAs in structural features and sequence composition. The presence of these intriguing parallels between the lncRNAs and 39 UTRs, which constitute the two main components of the RNA-mediated cellular regulatory system, indicates that highly similar evolutionary constraints govern the function of regulatory RNA sequences in the cell.
Growth of diamond films using an enclosed methyl-acetylene and propadiene combustion flame

Abstract Diamond growth in low-pressure combustion flames was studied using a safer, more economical substitute for acetylene: a mixture of methylacetylene, propadiene, and liquefied petroleum (MAPP gas). A burner-stabilized, low pressure, flat, premixed flame was used to deposit continuous, uniform thickness diamond films on a heated molybdenum substrate. This work identifies the dependence of film growth rate and quality on the fuel-to-oxygen ratio and the burner–substrate separation distance at two different reactor pressures of 70 and 250 Torr. A single substrate temperature of 800 °C was used to consistently produce well-faceted films. For the MAPP/O2 premixed flame, it was determined that the optimal fuel-to-oxygen ratios for diamond growth are 0.53 at 70 Torr and 0.51 at 250 Torr. Typical growth rates at these conditions were on the order of 1 μm h−1. However, growth rate and quality are very sensitive to the fuel-to-oxygen ratio, falling off rapidly in either direction from the optimal value. Increasing the ratio enhances secondary nucleation, and eventually results in graphitic and amorphous material. The growth rate is also very sensitive to the burner–substrate separation distance due to tight coupling between the transport and chemical kinetic time scales in the combustion reactor.
Myoid Gonadal Stromal Tumor with Epithelial Differentiation (? Testicular Myoepithelioma)

A 46-year-old man presented with a cytologically bland testicular tumor composed of spindle cells that showed both epitheliallike (ie, true desmosomes and tonofilamentlike structures) and myogenous differentiation (ie, thin filaments with focal densities and alpha-smooth muscle actin immunoreactivity). Tumor cells were immunoreactive for vimentin and S-100 protein but negative for cytokeratin and desmin. Peritubular myoid cells are present in the normal testis; contain subplasmalemmal micropinocytotic vesicles; show thin filaments with focal densities; and are reactive with desmin, vimentin, and alpha-smooth muscle actin. They have no desmosomes and lie outside the basement membrane of the seminiferous tubules; thus they are not true myoepithelial cells (a cell type not present in the testis). Paradoxically, the current tumor appeared to show bidirectional differentiation, mimicking both a peritubular myoid spindle cell and an epitheliallike cell (possibly similar to the granulosa cell or rete testis epithelial cell). Although the findings suggest myoepithelial differentiation, the cytogenesis of this tumor remains uncertain.
Object-Oriented Technology Education and Training: Bridging the Gap Between Academia and Industry

The benefits of object-oriented (00) technology have been widely cited in both academic and industry circles. One of the major challenges facing these audiences is 00 technology education and training. There is a shortage of software engineers who are knowledgeable and skilled in 00 technology. Universities are challenged to integrate OO concepts, analysis, design, and programming into existing curricula. Business and government organizations are challenged to retrain existing personnel in OO techniques and technology.
The Role of Fragility Assessment in Consequence-Based Engineering

Concepts of uncertainty modeling and fragility assessment in earthquake engineering and their applications in consequence-based engineering CBE of buildings in a region of low-to-moderate seismicity are presented. Efficient treatment of uncertainties in components and systems that are major contributors to building vulnerability is an essential ingredient of risk assessment and decision making. Current methodologies are reviewed first. A framework for fragility analysis then is demonstrated using an unreinforced masonry building as an example. The importance of fragility analysis in various stages of risk assessment, loss estimation, and decision making in CBE to achieve the desirable long-term objective in reduction of loss and consequence with the most efficient intervention measures is clearly indicated. Current research issues related to vulnerability assessment are identified. DOI: 10.1193/1.1979502
DESIGNING A SOIL QUALITY ASSESSMENT TOOL FOR SUSTAINABLE AGROECOSYSTEM MANAGEMENT

Sustainable agroecosystem management generally entails increased management ability and input. Decision making for sustainable management could be enhanced by tools that provide integration and synthesis of soil test results, management priorities, and environmental concerns. Science-based soil quality indices (SQIs) may provide an ecologically based approach needed for land managers to make sustainable decisions. We developed a general approach for choosing the most representative indicators from large existing data sets, combining indicators into location-specific indices of soil quality, and using this index to assess agricultural management practices. We used a poultry-litter management case study to illustrate the design and use of this SQI. Site-specific indices were created using the SQI design framework for two sites with different soil types but similar climatic regimes. At each site we compared alternative poultry-litter management practices: land application of fresh vs. composted poultry litte...
CRINOIDS FROM THE NADA MEMBER OF THE BORDEN FORMATION (LOWER MISSISSIPPIAN) IN EASTERN KENTUCKY

Thirty-four crinoid species, including four new species, are reported from the Nada Member of the Borden Formation in eastern Kentucky. The dominant crinoid group is monobathrids (18 species), but diplobathrids, disparids, cladids, and flexibles are also present. The four new species are the camerates Blairocrinus protuberatus, Uperocrinus acuminatus, and Aorocrinus nodulus, and the cladid Atelestocrinus kentuckyensis. The majority of the species in this fauna were previously known from what has traditionally been considered the ''upper part'' of the Burlington Limestone in the Mississippi River Valley and what is now recognized as the Burlington Pelmatozoan Assemblage III. The current study confirms the conclusion of Lane and DuBar (1983) that the Nada is middle Osagean in age, being deposited earlier than the well-documented Borden delta crinoid assemblages of north-central Kentucky and Indiana. The middle Osagean age of the fauna indicates a previously unrecognized unconformity between the Nada and the overlying Meramecian- age Renfro Member of the Slade Formation. In addition, this is the first well-documented middle Osagean fauna from a siliciclastic facies in North America. The dominance by camerate crinoids is enigmatic, but may be related to either a low rate of sedimentation or greater larval dispersal abilities.
Microbots on a fantastic voyage

In the 1966 film Fantastic Voyage, scientists at a U.S. laboratory shrink a submarine called Proteus and its human crew to microscopic size and then inject the vessel into an ailing scientist. Once inside, Proteus motors its way through the bloodstream and into the brain, where members of the crew don scuba gear and use a laser gun to perform delicate surgery.
Expression of cancer/testis (CT) antigens MAGE-A1, MAGE-A3, MAGE-A4, CT-7, and NY-ESO-1 in malignant gammopathies is heterogeneous and correlates with site, stage and risk status of disease

Cancer/testis (CT) antigens are expressed in several malignant tumors, but not in normal tissues except for testicular germ cells. The expression of CT antigenic proteins in malignant gammopathies has not been characterized. We examined the expression of a panel of CT antigenic proteins in 29 patients with malignant gammopathies by immunohistochemistry using the following monoclonal antibodies (mAbs): mAb MA454 to MAGE-A1, mAb M3H67 to MAGE-A3, mAb 57B to MAGE-A4, mAb CT7-33 to CT7/MAGE-C1 and mAb ES121 to NY-ESO-1. We could detect at least one CT antigen in tumors from 27 of 29 patients. The expression pattern of MAGE-A1, -A3, -A4 and NY-ESO-1 is heterogeneous in most cases, revealing staining in <25% of the tumor cells. Monoclonal antibodies CT7-33 and M3H67 show the highest incidence of immunoreactivity. Importantly, CT-7 can also be detected on the surface of some myeloma cells by flow cytometry, and in one plasmacytoma case by immunohistochemistry. Expression of CT antigens is greater in patients with stage III extramedullary plasmacytoma or high-risk myeloma relative to other cohorts. These data suggest that CT antigens may have important biological implications in malignant gammopathies and that CT-7 may be a suitable target for T cell-based and possibly antibody-mediated immunotherapy of myeloma.
Asymptotic model of clusters aggregation in media with memory

The paper deals with mathematical modeling of the aggregation of clusters in situation when the account of memory effects can be important. In the paper the non-local kinetic equation for binary aggregation in the dispersed system with memory has been submitted. The main control parameters have been defined and the asymptotic analysis of derived kinetic equation has been carried out.
The Roads We Choose

As you have undoubtedly noticed, the theme for this Annual Conference is “Follow the Road to Discovery.” In the 1979 Annual Report, which was included in the recent May issue of our membership newsletter, we were advised that “APTA Paves the Way.” It is not surprising, therefore, that when I began to prepare for this annual address to the membership, roads, pathways, and journeys came to my mind. I have always been concerned about such questions as: Where are we going? How are we getting there? Have we made the best choices? Have we picked the best roads? This afternoon, I am going to be talking to you about some of those roads, and I am going to tell you what I think about them. I am also going to propose a new road or two I believe we should begin traveling on.
The existence of inhibited lysyl oxidase and the presence of multiple forms.

Considerable difficulty in purifying tissue lysyl oxidase has been previously encountered and the cause of this difficulty has now been ascertained. For these studies, we have used blood plasma lysyl oxidase as a model system. Blood plasma has been shown to contain considerable lysyl oxidase activity. The enzyme exists in a partially or completely inhibited state. Homogeneous preparations of the enzyme from the blood have been obtained by two different methods. Method A yields one form of lysyl oxidase while Method B yields three forms of the enzyme. The methods for the purification of the enzyme and some properties of the enzyme and preliminary data on the lysyl oxidase inhibitor will be discussed.
Sweet Dreams: How Sleep and Sleep Disturbances Affect Glycemic Control in People With Diabetes: Preface.

> Sleep that knits up the ravelled sleeve of care The death of each day's life, sore labour’s bath Balm of hurt minds, great nature’s second course, Chief nourisher in life’s feast. > > —William Shakespeare, “Macbeth” One-third of our lives is spent sleeping. Nightly sleep is restorative, allowing our bodies and minds to rest and ready ourselves for a new day. For many people, sleep is often fragmented, and a full night of sound sleep is unattainable. Increasingly, people are seeking care for sleep problems, including insomnia, restless sleep, or daytime symptoms associated with disturbed sleep. Unfortunately, many people are unaware of the impact of disturbed sleep on overall health, and routine assessment of sleep disturbances should be a priority area of clinical assessment. People with diabetes are especially vulnerable to sleep disturbances such as insomnia, poor sleep quality, and sleep apnea. There is burgeoning research examining the interrelationships among sleep, altered glucose metabolism, and diabetes. Our understanding of the neurological, hormonal, and behavioral effects of altered sleep continues …
Genetic Ablation of KLHL1 Alters CaV3.2 Expression in DRG Neurons and Mechanical Pain Transmission

Pain signaling is initiated by the detection of noxious stimuli through specialized primary nociceptors located in peripheral endings in dorsal root ganglion (DRG) neurons. Low voltage activated CaV3.2 T-type calcium channels play a major role in sensory perception in these neurons; silencing their activity with antisense RNA or genetic ablation results in anti-nociceptive, anti-hyperalgesic and anti-allodynic effects1-3. These channels are regulated by a plethora of proteins, including KLHL1, a neuronal actin binding protein that stabilizes channel activity by increasing its recycling back to the plasma membrane via recycling endosome activity. We explored the role of KLHL1 and its effects on CaV3.2 and mechanical peripheral pain transmission using the KLHL1 KO mouse model. Total T-type calcium current amplitude was smaller in KO DRG neurons (12 ± 2.03 pA/pF, n=18) compared to controls (18 ± 1.89 pA/pF, n=13; p<0.05), without significant changes in voltage dependence as expected in the absence of its modulator. Western blot analysis confirmed CaV3.2 but not CaV3.1 or CaV3.3 protein was significantly decreased. Interestingly, von Frey hair tests show paw withdrawal threshold in KO mice was increased. Our data establishes KLHL1 is a calcium channel regulator in DRG neurons, providing a novel target to control peripheral pain sensation. Downregulation of CaV3.2 activity by as little as ∼30% was sufficient to alter pain perception in the KO model.
Management of multidrug resistant tuberculosis.

Drug-resistant strains of Mycobacterium tuberculosis pose a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment of tuberculosis, as well as unchecked transmission of M. tuberculosis, has resulted in alarming levels of drug-resistant tuberculosis. The World Health Organization (WHO) estimates that there were 600,000 cases of multidrug-resistant tuberculosis (MDR-TB)/rifampin-resistant (RR) tuberculosis in 2016, defined as strains that are resistant to at least isoniazid and rifampicin. Globally, WHO estimates that 4.1% of new tuberculosis cases and 19% of retreatment cases have MDR-TB. By the end of 2016, 123 countries had reported at least one case of extensively drug-resistant strains, which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. It is estimated that only 22% of all MDR-TB cases are currently receiving therapy. This article reviews the management of MDR/RR-TB and updates recommendations regarding the use of shorter course regimens and new drugs.
Abstract P6-06-01: Relationship between Vitamin D Deficiency and Breast Cancer Histology: A Retrospective Database Review

Background: Vitamin D deficiency has recently been shown to be correlated with high rates of developing breast cancer (Chen P et al, Breast Cancer Res Treat; Oct 2009). However, the association between the degree of vitamin D deficiency and specific histological subtypes of breast cancer remains unclear. Preclinical data has suggested that vitamin D plays an essential role in the terminal differentiation of breast cancer cells, and thus vitamin D deficiency would be associated with the pathogenesis of estrogen receptor negative tumors (Welsh J et al, Journal of Steroid Biochem Mol Biol; Feb 2003), in particular triple-negative tumors, which are associated with a particularly aggressive clinical course. Methods: Beginning in July 2008, the majority of newly diagnosed breast cancer patients at University of Maryland Greenebaum Cancer Center had Vitamin D 25-OH levels testedon initial presentation to the clinic. We conducted a retrospective chart review to obtain information about tumor histology and vitamin D levels in these patients. Results: We include data on 71 patients who presented with newly-diagnosed breast carcinoma or DCIS between June 2008 and December 2009. Average age at diagnosis was 57 (range 36-87), and 58% of patients were African American. Stage distribution of the cohort included; DCIS-3%, stage I-15%, stage II-41%, stage III-28%, and stage IV-10%. Overall, 80% of the patients were vitamin D deficient at diagnosis, with vitamin D levels under 30 ng/ml, and 57% had levels under 20 ng/ml. Patients with triple-negative tumors were the most likely to be vitamin D deficient at diagnosis (90%) compared to hormone receptor-positive patients (75%), and they had the lowest mean and median vitamin D levels compared to all other patients. Percentage of patients with Vitamin D deficiency Vitamin D level by histological subtype Hormone receptor-positive patients were significantly more likely to have normal vitamin D levels at diagnosis and significantly less likely to have severe deficiency (level Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-06-01.
Enhanced Electromechanical Response of Ionic Polymer Actuators by Improving Mechanical Coupling between Ions and Polymer Matrix

Poly[(vinylidene difluoride)-co-(chlorotrifluoroethylene)] (P(VDF–CTFE)) and P(VDF–CTFE)/poly(methyl methacrylate) (PMMA) cross-linked blends were exploited as ionic electroactive polymer (i-EAP) actuators with electrolyte ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate [C2mim][TfO] for the first time. Compared to the traditional i-EAPs that are based on Nafion or Aquivion (Hyflon) ionomers, i-EAP actuators made with P(VDF–CTFE) and P(VDF–CTFE)/PMMA polymers exhibited remarkably enhanced actuation strain and significantly reduced electrical capacitance. The increase in the strain–charge ratio e/C indicates that this improvement is a direct result of improved elastic coupling between the [C2mim][TfO] electrolyte and the polymer matrix. As a result, an order-of-magnitude improvement in electromechanical energy conversion efficiency is achieved for both P(VDF–CTFE) and P(VDF–CTFE)/PMMA polymer-based actuators, which makes them promising polymer matrices for i-EAP actuators.
Observations on the relationship between crystallographic orientation and biasing in apatite fission-track measurements

Analysis of extensive apatite fission-track experimental data reveals several features concerning the influence of crystallographic orientation on measurement biasing that had not been clear previously. At low levels of annealing, anisotropy in confined track lengths is most accurately depicted by an elliptical distribution, in comparison with two suggested alternatives. Quantification of length anisotropy by c -axis projection is simplified and improved, resulting in a model that better achieves its goal of removing anisotropy while preserving all other useful information. The variation of observational frequency of confined tracks with respect to orientation at low annealing levels reveals a large but heretofore-unreported biasing factor related to how an investigator interprets poorly etched tracks. The concept of an “under-etching bias” is introduced to encompass this effect, which can have consequences orders-of-magnitude greater than previously studied factors such as length and etch figure geometry. As annealing progresses, radical shifts in observational frequency with respect to angle make apparent another undocumented process: total annealing of substantial fractions of tracks oriented at high angles to the c axis. Incorporation of this loss into a previous model describing the link between confined track length and density improves the model such that its predictions are now close to the relationship observed in progressive annealing of a single population. Because under-etching biasing effects are intimately linked with orientation and extent of annealing, any future effort to develop a rigorous length calibration scheme to support thermal history modeling should take both of them explicitly into account.
Approaches of high school instrumental music educators in response to student challenges

The purpose of this multiple instrumental case study was to explore approaches of four high school instrumental music educators assuming the role of facilitative teacher in responding to challenges...
Antisense Strategies to Specifically Deplete Levels of Factors II, VII and IX in Mice To Assess Their Potential as Targets for Anticoagulation.

Abstract Numerous potential intervention points exist within coagulation pathways for development of novel anticoagulant agents. To help determine the most suitable target for the discovery of novel antithrombotic agents, we have implemented an antisense strategy to specifically deplete levels of various coagulation factors in mice. Here we report the effects of antisense oligonucleotides (ASOs) targeting factors II, VII, and IX on target RNA and protein levels in mice, as well as PT/aPTT. ISIS 401025 targeting factor II, ISIS 403102 targeting factor VII, and ISIS 402618 targeting factor IX dose-dependently suppressed their respective target transcript levels in a specific manner in primary mouse hepatocytes. Following subcutaneous administration to mice, each ASO reduced target RNA levels in liver and target protein levels in plasma in a specific and dose-dependent fashion (ED95 of approximate 25 mg/kg for each ASO). In conjunction with these effects, clotting times were also prolonged in a similar dose responsive fashion. Both PT and aPTT were increased following factor II inhibition and a PT-INR of 2.5 was achieved at 25 mg/kg, corresponding to a reduction in prothrombin transcript of 95%. As expected following factor VII ASO treatment, PT was significantly increased, while aPTT was unchanged. Conversely, following factor IX ASO treatment, aPTT was marginally but significantly prolonged, while PT was unchanged. These results demonstrate the capability of ASOs to dose-dependently and specifically modulate coagulation factor activity depletion and support the ASO approach as a novel strategy for the discovery of novel anticoagulation agents. Studies are in progress to assess relative safety and to expand the anticoagulation profile in mice for each of the factors under study.
KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage

The p53 tumor suppressor protein plays a critical role in orchestrating the genomic response to various stress signals by acting as a master transcriptional regulator. Differential gene activity is controlled by transcription factors but also dependent on the underlying chromatin structure, especially on covalent histone modifications. After screening different histone lysine methyltransferases and demethylases, we identified JMJD2B/KDM4B as a p53-inducible gene in response to DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter. JMJD2B induction attenuates the transcription of key p53 transcriptional targets including p21, PIG3 and PUMA, and this modulation is dependent on the catalytic capacity of JMJD2B. Conversely, JMJD2B silencing led to an enhancement of the DNA-damage driven induction of p21 and PIG3. These findings indicate that JMJD2B acts in an auto-regulatory loop by which p53, through JMJD2B activation, is able to influence its own transcriptional program. Functionally, exogenous expression of JMJD2B enhanced subcutaneous tumor growth of colon cancer cells in a p53-dependent manner, and genetic inhibition of JMJD2B impaired tumor growth in vivo. These studies provide new insights into the regulatory effect exerted by JMJD2B on tumor growth through the modulation of p53 target genes.
Morphological Manifestations of Ribosomal DNA Amplification during Insect Oogenesis

Genetic expression during the early stages of embryogenesis is largely under the control of the maternal genome rather than the embryo genome and appears to be a manifestation of genetic activity realized during oogenesis (reviewed by Davidson, 1976). In many organisms, ribosomes assembled during oogenesis provide the protein synthetic machinery of early embryogenesis. In such organisms, large amounts of ribosomal RNA are synthesized and accumulated during oogenesis (Harris and Forrest, 1967). In order to accomplish this, the oocytes may amplify the genes coding for ribosomal RNA (see Gall, 1969, and Tobler, 1975, for reviews).
Latino College Studentsâ€™ Perceptions of their Ethnicity as a Challenge and Resource to their Future Opportunities: A Comparative Study in Texas and California

Over 50% of all Latinos in the U.S. live in California and Texas. Educators, researchers, and policy makers are increasingly concerned with how to improve educational access and occupational mobility of Latinos in their communities. Latino youth who successfully manage to make it through the K-12 academic pipeline and gain admission into a four-year university continue to face the risk of high dropout and low graduation rates. Building upon both developmental and social identity theories, the present study examines the extent to which demographic, relational, and contextual factors and strength of ethnic identity contribute to first-year Latino college studentsâ€™ perceptions of their ethnicity as a challenge and resource to their future opportunities. This study contributes to understanding of the complexities of ethnic identity development and its impact on college adjustment, examining within-group variability of Latino college students in Texas and California. Implications of these findings and suggestions for enhancing retention and graduation rates of Latino college students in both Texas and California are discussed.
Insights into the Structural Complexity of Colloidal CdSe Nanocrystal Surfaces: Correlating the Efficiency of Nonradiative Excited-State Processes to Specific Defects.

II–VI colloidal semiconductor nanocrystals (NCs), such as CdSe NCs, are often plagued by efficient nonradiative recombination processes that severely limit their use in energy-conversion schemes. While these processes are now well-known to occur at the surface, a full understanding of the exact nature of surface defects and of their role in deactivating the excited states of NCs has yet to be established, which is partly due to challenges associated with the direct probing of the complex and dynamic surface of colloidal NCs. Here, we report a detailed study of the surface of cadmium-rich zinc-blende CdSe NCs. The surfaces of these cadmium-rich species are characterized by the presence of cadmium carboxylate complexes (CdX2) that act as Lewis acid (Z-type) ligands that passivate undercoordinated selenide surface species. The systematic displacement of CdX2 from the surface by N,N,N′,N′-tetramethylethylene-1,2-diamine (TMEDA) has been studied using a combination of 1H NMR and photoluminescence spectroscopie...
The tale of two stories: Challenges and innovations in breast cancer management.

Abstract The keynote address The Tale of Two Stories: Challenges and Innovations in Breast Cancer Management presented on March 19–20, 2017 at the celebratory Festschrift Lecture in honor of the great Dr. LaSalle Leffall's on behalf of his impact and contributions to the field of Breast cancer science and treatment as a leader, surgeon, and mentor. This presentation and follow up opinion paper in the field of Breast Disease highlights the challenges that have baffled us and the innovations that have changed and translated into outcomes and those that have not. Where do they parallel and what are the gaps?
Surface-becoming: Lyle Ashton Harris and brown jouissance

This essay analyzes Lyle Ashton Harris's large-format Polaroid, Billie #21, as a site to think about the epistemological transformations that surface thinking or thinking with the flesh enables. It...
The Claims of Bodies: Practices of Citizenship After Bhopal in Survivor Testimony and Indra Sinha's Animal's People

This essay explores political relations and practices of claim-making between Indian citizens and the state in the aftermath of the Bhopal gas explosion of 2–3 December 1984. While not discounting ...
Excavating America’s Metaphor: Race, Diaspora, and Vindicationist Archaeologies

Over more than a century, African diasporan scholars have defined identity in complex forms that aspire to resist racial essentialism yet stake consequential political claims to collective roots. Historical archaeology has painted a rich picture of the material details of African American life that also refutes black essentialism; however, archaeologists have crafted many utterly fluid African diasporan identities that sometimes fail to examine the global connections, antiracist citizen rights, and concrete cultural heritage long examined by diasporan scholars. An empirically and politically rigorous African diasporan archaeology would be significantly extended by diasporan scholarship’s vindicationist and reflective antiracist perspectives. such an archaeology could disrupt essentialist categories and outline concrete foundations for diasporan identity without lapsing into either particularism or hyperconstructivism.
Ionic gating drives correlated insulator-metal transition.

The transport of matter is central to modern condensed-matter physics. Electronic transport is vital, enabling computer communication and playing a key role in interrogating material responses. A primary classification of matter is into metals, semiconductors, and insulators, based on their electronic conductivity, and electronic considerations underpin much of the current nanomaterials revolution (1). Transport anomalies have captured the imagination of scientists, engineers, and the public, from colossal (2) and giant (3) magnetoresistance and integer (4) and fractional (5) quantum Hall effects to topological insulators (6, 7) and semimetals (8). In particular, strongly correlated electronic states offer special opportunities for manipulating transport, including superconductivity and charge-ordering transitions, and perhaps enabling practical quantum computing (9). The Mott transition holds a unique place in modern electronic transport research. The Mott state (10) is an enigma—a system that naive analysis suggests would be metallic. In a Mott insulator, nearby atoms appear to have electronic states at similar energies, suggesting easy charge flow. However, because the states are spatially localized, when an additional electron is added the energy cost is high, and the electron transfer is inhibited. This is related to “Coulomb blockade” (11) and is a type of strong electronic correlation that confers new ways of controlling electronic transport. It is now possible to envision new electronic devices (12) based on forming and disrupting the Mott insulating state, and this has been termed “Motttronics.” Beyond electronic considerations, changes of composition via ion transport are of great interest as well. The flow of ions through membranes enables fuel cells, electrochemical devices that convert fuels to electricity without combustion. Batteries also involve coupled reduction and oxidation reactions that produce voltage and current in response to electrochemical differences. State-of-the-art rechargeable batteries (13, 14) rely on ion motion (often Li) from a state that holds high-energy … [↵][1]1Email: rappe{at}sas.upenn.edu. [1]: #xref-corresp-1-1
Joachim Frank's Binding with the Ribosome

With recent technological advancements, single-particle cryogenic electron microscopy (cryo-EM) is now the technique of choice to study structure and function of biological macromolecules at near-atomic resolution. Many single-particle EM reconstruction methods necessary for these advances were pioneered by Joachim Frank, and were optimized using the ribosome as a benchmark specimen. In doing so, he made several landmark contributions to the understanding of the structure and function of ribosomes. These include the first 3D visualization of ribosome-bound transfer RNAs, the first experimentally derived structures of the primary complexes formed during the bacterial translation elongation cycle, and the critical ribosomal conformational transitions required for translation. Over the years, his laboratory studied many important functional complexes of the ribosome from both eubacterial and eukaryotic systems, including ribosomes from pathogenic organisms. This article presents a brief account of the contributions made by Joachim Frank to the ribosome field.
Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer.

Purpose: The CDK 4/6 inhibitor palbociclib rapidly and reversibly inhibits the cell cycle. The goal of this study was to exploit the cell cycle through intermittent, alternating dosing with palbociclib/paclitaxel to enhance efficacy. We determined the combination dose-limiting toxicity in patients with retinoblastoma (Rb) protein-expressing, advanced breast cancer (ABC). Experimental Design: This open-label phase I trial (NCT01320592) enrolled patients to sequential cohorts of palbociclib orally dosed intermittently between days 1 and 19 of a 28 day cycle alternating with weekly paclitaxel. Dose escalation proceeded in a standard 3 + 3 design. Ten additional patients received the combination at the recommended phase 2 dose (RP2D). Those who reached response plateau ≥6 cycles could continue on palbociclib alone on a 3 week on/1 week off schedule at one dose level above their combination dose. Results: Twenty seven patients enrolled. Although there was only 1 DLT (grade 3 ALT/AST at 125 mg), neutropenia requiring dose modification in cycle 1 resulted in an RP2D of 75 mg palbociclib/80mg/m2 paclitaxel. During cycle 1, the most common adverse event was neutropenia, occurring in 15 patients (55.6%); grade 1 or 2 nausea and peripheral neuropathy was also observed in 8 patients each (29.6%). Clinical benefit rate was 55% at the RP2D; benefit was observed across all receptor subtypes. Conclusions: Alternating sequential palbociclib/paclitaxel in patients with Rb+ ABC is feasible and safe, without evidence of additive toxicity. This represents a new application for CDK 4/6 inhibitors in Rb+ breast cancer, regardless of subtype; efficacy trials are warranted.
Expression of p15 in a spectrum of spitzoid melanocytic neoplasms

Background Accurate classification of spitzoid melanocytic lesions is difficult due to overlapping clinical and histopathologic features between Spitz nevi, atypical Spitz tumors (ASTs), and spitzoid melanomas. Expression of p16 (CDKN2A) has been used as a marker of spitzoid lesions. However, its expression may be variable. p15 is a tumor suppressor encoded by CDKN2B, loss of which has been recently shown to promote transition from nevus to melanoma. We sought to determine whether p15 is a useful immunohistochemical marker to distinguish Spitz nevi from spitzoid melanomas and to compare p15 and p16 staining in this population. Methods Immunohistochemistry for p15 and p16 was performed on Spitz nevi (n = 19), ASTs (n = 41), and spitzoid melanomas (n = 17). Immunoexpression was categorized by a four-tiered system: 0 (negative), 1+ (weak), 2+ (moderate), 3+ (strong). Results 3+/strong p15 staining was observed in 68.4% of Spitz nevi, 34.2% of ASTs, and 17.7% of spitzoid melanomas. By contrast, we observed 3+ p16 staining in roughly equivalent percentages of Spitz nevi (57.9%), ASTs (56.1%), and spitzoid melanomas (58.8%). Conclusion These data illustrate that p15 may be more useful than p16 as a biomarker to help distinguish benign from malignant spitzoid lesions.
The Process of Long-Term Suicide Bereavement: Responsibility, Familial Support, and Meaning Making

The purpose of this qualitative study was to develop understanding of the experience of long-term suicide loss survivors and begin to develop theory of the process of healing. Ten suicide loss survivors were interviewed. Our analyses identified three major categories—one harmful, one helpful, and one that helped to move from harmful to the helpful. Feelings of responsibility was the major harmful category, meaning making the helpful one, and social support the one that appeared to help move from one to the other. Suicide-related thoughts and behaviors were found to be both harmful and helpful at times. Many systemic, family, and interpersonal processes relating to suicide ideation and the perceived responsibility of suicide loss survivors were identified for intervention and future study.