cssi/SciSciGPT-SciSciNet huggingface dataset:
Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma.

The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL). However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA). Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231) and a breast carcinoma cell line (MDA-MB-468), the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10) displayed bortezomib-resistant constitutive NF-κB activity. Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.
Quantitative Time-Lapse Fluorescence Microscopy in Single Cells

The cloning of green fluorescent protein (GFP) 15 years ago revolutionized cell biology by permitting visualization of a wide range of molecular mechanisms within living cells. Though initially used to make largely qualitative assessments of protein levels and localizations, fluorescence microscopy has since evolved to become highly quantitative and high-throughput. Computational image analysis has catalyzed this evolution, enabling rapid and automated processing of large datasets. Here, we review studies that combine time-lapse fluorescence microscopy and automated image analysis to investigate dynamic events at the single-cell level. We highlight examples where single-cell analysis provides unique mechanistic insights into cellular processes that cannot be otherwise resolved in bulk assays. Additionally, we discuss studies where quantitative microscopy facilitates the assembly of detailed 4D lineages in developing organisms. Finally, we describe recent advances in imaging technology, focusing especially on platforms that allow the simultaneous perturbation and quantitative monitoring of biological systems.
An analysis of the concept of grief

Grief is a universal response affecting every age and culture. However, this concept is surrounded by ambiguity. It is poorly understood by nurses who encounter grieving persons with increasing frequency, especially as the population ages. The ability of nurses to gain an increased understanding of grief depends on the clarification of this concept. A concept analysis is described. Antecedents, attributes, referents and intervening variables of grief are identified. In addition, model, borderline, related, invented and contrary cases are described. This analysis results in a comprehensive definition of grief which is proposed. This definition can contribute to the foundation essential to guide nursing practice with grieving persons.
Predictive duty cycle adaptation for wireless camera networks

Wireless sensor networks (WSN) typically employ dynamic duty cycle schemes to efficiently handle different patterns of communication traffic in the network. However, existing duty cycling approaches are not suitable for event-driven WSN, in particular, camera-based networks designed to track humans and objects. A characteristic feature of such networks is the spatially-correlated bursty traffic that occurs in the vicinity of potentially highly mobile objects. In this paper, we propose a concept of indirect sensing in the MAC layer of a wireless camera network and an active duty cycle adaptation scheme based on Kalman filter that continuously predicts and updates the location of the object that triggers bursty communication traffic in the network. This prediction allows the camera nodes to alter their communication protocol parameters prior to the actual increase in the communication traffic. Our simulations demonstrate that our active adaptation strategy outperforms TMAC not only in terms of energy efficiency and communication latency, but also in terms of TIBPEA, a QoS metric for event-driven WSN.
Sarcoidosis and Specific Etiologic Agents: A Continuing Enigma

Twelve cases are presented in which a diagnosis of sarcoidosis was made, but from which specific infectious agents capable of eliciting a granulomatous response were identified. The etiologic role of these agents must be seriously entertained, in spite of occasional fairly significant time intervals between the original diagnosis of sarcoidosis and the recovery of the organisms. Strict clinical and morphologic criteria for the diagnosis of sarcoidosis should be applied. These include searching for an infectious cause, which must be done in every case, by vigorously applying adequate cultural and special histologic techniques. The existence of a granulomatous disease in which initial evaluation does not uncover a specific etiologic agent compels the physician to restudy such patients periodically, since these specific agents may appear months or years later. Restudy will, in addition, provide better material for culture, since the need for it will be more greatly appreciated.
Oviductal, not oviducal.

Both etymologically and in literal meaning the term "oviductal" is overwhelmingly preferable to "oviducal."
Structural investigations of several LnVO4 compounds

Refinements of the crystallographic structures of SmVO4, EuVO4, GdVO4 and DyVO4 have been carried out by means of three dimensional single-crystal X-ray diffractometry. These orthovanadate compounds crystallize in the tetragonal space group 141/amd (Z = 4) with respective lattice constants of a = 7.2647(9), 7.2358(7), 7.2122(7), 7.1429(8) A and c = 6.384(1), 6.362(1), 6.346(2), 6.300(2) A. Anisotropic refinements of the structural data using a full-matrix least-squares program yielded final reliability (R) factors of 0.026, 0.049, 0.042 and 0.041 based on 266, 273, 261 and 220 unique reflections for Ln = Sm, Eu, Gd and Dy, respectively. The lanthamide (Ln) atoms are eight-coordinated to oxygen atoms with two unique LnO bond lengths. These non-equivalent vertices form two bisphenoidal sets. A distorted triangulated dodecahedron is produced by connecting the oxygen vertices. The orthovanadate group in each compound is a distorted tetrahedron. Important crystal data, parameters, bond lengths and angles are tabulated.
A Guide to Analyzing Message–Response Sequences and Group Interaction Patterns in Computer‐mediated Communication

This paper proposes a set of methods and a framework for evaluating, modeling, and predicting group interactions in computer‐mediated communication. The method of sequential analysis is described along with specific software tools and techniques to facilitate the analysis of message–response sequences. In addition, the Dialogic Theory and its assumptions are presented to establish a theoretical framework and guide to using sequential analysis in computer‐mediated communication research. Step‐by‐step instructions are presented to illustrate how sequential analysis can be used to measure the way latent variables (e.g., message function, response latency, communication style) and exogenous variables (e.g., gender, discourse rules, context) affect how likely a message is to elicit a response, the types of responses elicited by the message, and whether or not the elicited sequence of responses (e.g., claim → challenge → explain) mirror the processes that support group decision‐making, problem‐solving, and lear...
Mining genetic epidemiology data with Bayesian networks application to APOE gene variation and plasma lipid levels

There is a critical need for data-mining methods that can identify SNPs that predict among-individual variation in a phenotype of interest and reverse-engineer the biological network of relationships between SNPs, phenotypes, and other factors. This problem is both challenging and important in light of the large number of SNPs in many genes of interest and across the human genome. A potentially fruitful form of exploratory data analysis is the Bayesian or Belief network. A Bayesian or Belief network provides an analytic approach for identifying robust predictors of among-individual variation in a disease endpoints or risk factor levels. We have applied Belief networks to SNP variation in the human APOE gene and plasma apolipoprotein E levels from two samples: 702 African-Americans from Jackson, MS, and 854 non-Hispanic whites from Rochester, MN. Twenty variable sites in the APOE gene were genotyped in both samples. In Jackson, MS, SNPs 4036 and 4075 were identified to influence plasma apoE levels. In Rochester, MN, SNPs 3937 and 4075 were identified to influence plasma apoE levels. All three SNPs had been previously implicated in affecting measures of lipid and lipoprotein metabolism. Like all data-mining methods, Belief networks are meant to complement traditional hypothesis-driven methods of data analysis. These results document the utility of a Belief network approach for mining large scale genotype–phenotype association data.
Dynamic tracking influenced by anatomy in patellar instability

Abstract Background The current study was performed to correlate anatomical parameters related to trochlear dysplasia, tibial tuberosity position, and patella alta with in vivo patellar tracking for subjects with recurrent patellar instability. Methods Eight subjects with recurrent patellar instability that failed conservative treatment were evaluated using computational reconstruction of in vivo knee motion. Computational models were created from dynamic CT scans of the knee during extension against gravity. Shape matching techniques were utilized to position a single model of each bone (femur, patella and tibia) to represent multiple positions of knee extension. Patellar tracking was characterized by the bisect offset index (lateral shift) and lateral tilt. Anatomical parameters were characterized by the inclination of the lateral ridge of the trochlear groove, the lateral distance from the tibial tuberosity to the posterior cruciate ligament attachment (lateral TT–PCL distance), and the Caton–Deschamps index. Stepwise multivariable linear regression analysis was used to relate patellar tracking to the anatomical parameters at low ( Results At low flexion angles, both lateral trochlear inclination and lateral TT–PCL distance were significantly correlated with bisect offset index (p=0.02). Only lateral trochlear inclination was significantly correlated with lateral tilt (p Conclusion Parameters related to trochlear dysplasia and tibial tuberosity position were both related to patellar tracking, but the relationship changed with the flexion angle. Clinical relevance The anatomical parameters related to patellar tracking can be used to evaluate the risk of continued instability and guide surgical treatment.
Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana

ABSTRACTBackground: Although initially developed for medical purposes, synthetic cannabinoids have also been consumed for recreational purposes. Objective: To evaluate whether agreement with positive and negative outcome expectancies differed for synthetic cannabinoids versus botanical marijuana, and assess reported reasons for using synthetic cannabinoids. Method: Using a web-based recruitment and data collection procedure, 186 adults who had used both synthetic cannabinoids and botanical marijuana and 181 adults who had used botanical marijuana but not synthetic cannabinoids, completed measures of outcome expectancies and other relevant questionnaires. Results: A significant interaction revealed that participants who had used both synthetic cannabinoids and botanical marijuana indicated lower agreement with positive expectancies for synthetic cannabinoids, and higher agreement with positive expectancies for botanical marijuana, than did those participants who used only botanical marijuana. There was no ...
Further Bone Phosphatase Studies in Chick Perosis

Abstract PEROSIS, an anatomical deformity of the leg bones of young chicks, was first described by Hunter and Funk (1930). The condition is associated with a high intake of calcium and phosphorus, and a low intake of manganese (Hunter et al., 1931; Milby, 1934; Wilgus et al., 1936–1937; Clifcorn et al., 1938). Later, the work of Wiese et al. (1939) showed that the blood and bone phosphatase activity of perotic birds was lower than that of chicks receiving an adequate amount of manganese in their diet. As the leg bones of chicks with perosis are bent and twisted from their normal shape it was thought that there might be an abnormal distribution of the enzyme phosphatase in the bones of these chicks. In this paper we wish to report the results we have observed on the distribution of this enzyme in the leg bones of perotic and normal chicks. EXPERIMENTAL
Observation on Clinical Therapeutic Effect and Nursing Experience of Nebulization Inhalation on Pediatric Respiratory Tract Infection

Objective To explore and analyze the clinical efficacy of aerosol inhalation therapy on pediatric respiratory tract infection,and to summarize its nursing methods.Methods Totally 365 patients with pediatric respiratory tract infection hospitalized in Children's Hospital of Xi'an from January 2008 to December 2010 were retrospectively analyzed,including 191 patients with ambmxol hydrochloride atomization treatment and 174 patients with intravenous injection of ambmxol hydochloride.The therapeutic effects of the two groups were observed and compared,and the nursing methods were summarized.Results One hundred and seventy-four patients of nebulization inhalation group were cured,with the effective rate of 91.10%,and 138 patients of intravenous injection group were cured,with the effective rate of 79.31%(P0.05).Conclusions Nebulization inhalation shows very good curative effects in treating pediatric respiratory tract infection.It has the advantages of simple operation,high patient acceptance,fewer side effects,and rapid action.It is worthy to be popularized and applied.
Structural and electronic properties of the Zn0.5Cd0.5Se(100) surface

Abstract The chemical composition, atomic structure and electron affinity of Zn 0.5 Cd 0.5 Se(100) grown by molecular beam epitaxy and prepared by Se-decapping are investigated. The Se-terminated surface exhibits a (2 × 1) reconstruction which corresponds to a complete monolayer of Se dimers. The cation-terminated surface exhibits a (1 × 1) structure tentatively attributed to a vacancy structure similar to that of the c(2 × 2) Zn-terminated ZnSe surface, but randomized by the non-periodic distribution of Zn and Cd. The evolution of the electron affinity of the surface is consistent with the formation of a surface dipole induced by a cation-to-anion charge transfer which fills (empties) all anion (cation) dangling bonds. Finally, preferential desorption of Cd is observed for temperatures in excess of 370°C.
Flexural Rigidity of Various Trunnion Designs in Modular Hip Stems: A Biomechanical and Historical Analysis

There is renewed concern surrounding the potential for corrosion at the modular head-neck junction to cause early failure in modern hip implants. Although taper corrosion involves a complex interplay of many factors, previous studies have correlated decreasing flexural rigidity of the femoral trunnion with an increased likelihood of corrosion at retrieval. A multicenter retrieval analysis of 85 modular femoral stems was performed to calculate the flexural rigidity of various femoral trunnions. Stems were implanted between 1991–2012 and retrieved between 2004–2012. There were 10 different taper designs from 16 manufacturers. Digital calipers were used to measure taper geometries by two independent observers. Mean flexural rigidity was 262 Nm 2 , however there was a wide range of values among the various stems spanning nearly an order of magnitude between the most flexible (80 Nm 2 ) and most rigid (623 Nm 2 ) trunnions, which was due in part to the taper geometry and in part to the material properties of the base alloy. There was a modest but significant negative correlation between flexural rigidity of the trunnion and release date of the stem. This wide variability in flexural rigidity may predispose particular stem designs to an increased risk of corrosion at the modular head-neck taper, and may in part explain why taper corrosion is being seen with increasing frequency in modern hip arthroplasty.
Nucleobases Undergo Dynamic Rearrangements during RNA Tertiary Folding

The tertiary structure of the GTPase center (GAC) of 23S ribosomal RNA (rRNA) as seen in cocrystals is extremely compact. It is stabilized by long-range hydrogen bonds and nucleobase stacking and by a triloop that forms within its three-way junction. Its folding pathway from secondary structure to tertiary structure has not been previously observed, but it was shown to require Mg2+ ions in equilibrium experiments. The fluorescent nucleotide 2-aminopurine was substituted at selected sites within the 60-nt GAC. Fluorescence intensity changes upon addition of MgCl2 were monitored over a time-course from 1ms to 100s as the RNA folds. The folding pathway is revealed here to be hierarchical through several intermediates. Observation of the nucleobases during folding provides a new perspective on the process and the pathway, revealing the dynamics of nucleobase conformational exchange during the folding transitions.
Terahertz waveguide with a negative effective index of refraction measured using time domain techniques

We present the first experimental realization of a terahertz (THz) waveguide that exhibits a negative effective index of refraction. To demonstrate this, we designed fabricated and characterized a linear array of three-dimensional structures that consist of split ring resonators and posts. THz radiation is launched and guided in the form of surface plasmon polaritons (SPPs) along the 3D metallic structures. Using THz time-domain spectroscopy, we measure the temporal evolution of the propagating THz SPP, which yields the evidence of a negative refractive index.
Performance study of magnetic field concentration techniques on magnetoresistor/rogowski contactless current sensor

Magnetoresistor/Rogowski coil can be utilized as a wideband contactless current sensor in power electronic converters. However, the magnetic Field detected by these sensing devices varies with frequency due to skin effect. This paper presents an investigation on two Magnetic field Concentration (MCON) techniques using conductive plates and power trace. These MCONs result in a more uniform magnetic Field seen by the sensing elements over the frequency range of interest. Simulation and experimental results are presented to demonstrate the efficacy of the proposed MCONs and their impacts on performance of the sensors.
Controversies in NTOS: Is TO Decompression a Vascular, Thoracic, or Neurosurgical Procedure?

Thoracic outlet decompression is performed by a variety of surgical specialties including vascular, thoracic, neurologic, orthopedic, plastic, and general surgeons. A well-trained surgeon in any of these specialties should be able to properly care for patients with thoracic outlet syndrome, and each brings a unique perspective to this area. The specific technical skills required for thoracic outlet decompression should be mastered by anyone performing surgery for TOS, whatever their specialty is.
On the Identity of Two Supposed Faciolariid Gastropods, Fusus Mexicanus Reeve, 1848, and Peristernia Nodulosa A. Adams, 1855

On the basis of syntypes of Fusus mexicanus Reeve, 1848, this neglected species is recognized to be a junior subjective synonym of the western Atlantic muricid Calotrophon ostrearum (Conrad, 1846). Syntypes of Peristernia nodulosa A. Adams, 1855, another overlooked species, indicate that Adams' species is also not a fasciolariid but a senior synonym of Attiliosa incompta (Berry, 19 60), the type of the genus Attiliosa Emerson, 1968.
Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis

Variable drug responses depend on individual variation in the activity of drug-metabolizing enzymes, including cytochrome P450 enzymes (CYP). As the most common chronic liver disease in children and adults, nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in hepatic drug metabolism. Compared with adults, children present age-related differences in pharmacokinetics and pharmacodynamics. The purpose of this study was to determine the impact of fatty liver disease severity on the activity of a variety of CYP enzymes in children and adolescents. Healthy and nonalcoholic fatty liver disease pediatric subjects aged 12-21 years inclusive received an oral cocktail of four probe drugs: caffeine (CYP1A2, 100 mg), omeprazole (CYP2C19, 20 mg), losartan (CYP2C9, 25 mg), and midazolam (CYP3A4, 2 mg). Venous blood and urine were collected before administration and 1, 2, 4, and 6 hours after administration. Concentrations of the parent drugs and CYP-specific metabolites were quantified in plasma and urine using liquid chromatography with tandem mass spectrometry. In plasma, the decreased metabolic area under the curve (AUC) ratio, defined as the metabolite AUC to parent AUC, of omeprazole indicated significant decreases of CYP2C19 (P = 0.002) enzymatic activities in NASH adolescents, while the urine analyses did not show significant differences and were highly variable. A comparison between the present in vivo pediatric studies and a previous ex vivo study in adults indicates distinct differences in the activities of CYP1A2 and CYP2C9. These data demonstrate that pediatric NASH presents an altered pattern of CYP activity and NASH should be considered as a confounder of drug metabolism for certain CYP enzymes. These differences could lead to future investigations that may reveal unexpected variable drug responses that should be considered in pediatric dosage recommendations.
The elongation factor Spn1 is a multi-functional chromatin binding protein

The process of transcriptional elongation by RNA polymerase II (RNAPII) in a chromatin context involves a large number of crucial factors. Spn1 is a highly conserved protein encoded by an essential gene and is known to interact with RNAPII and the histone chaperone Spt6. Spn1 negatively regulates the ability of Spt6 to interact with nucleosomes, but the chromatin binding properties of Spn1 are largely unknown. Here, we demonstrate that full length Spn1 (amino acids 1-410) binds DNA, histones H3-H4, mononucleosomes and nucleosomal arrays, and has weak nucleosome assembly activity. The core domain of Spn1 (amino acids 141-305), which is necessary and sufficient in Saccharomyces cerevisiae for growth under ideal growth conditions, is unable to optimally interact with histones, nucleosomes and/or DNA and fails to assemble nucleosomes in vitro. Although competent for binding with Spt6 and RNAPII, the core domain derivative is not stably recruited to the CYC1 promoter, indicating chromatin interactions are an important aspect of normal Spn1 functions in vivo. Moreover, strong synthetic genetic interactions are observed with Spn1 mutants and deletions of histone chaperone genes. Taken together, these results indicate that Spn1 is a histone binding factor with histone chaperone functions.
Mechanisms of Output Signaling from a Circadian Oscillator

Author(s): Swan, Jeffrey A; Heisler, Joel; Dailley, Courtney; LiWang, Andy; Partch, Carrie L
Self-Healing Structures in Amorphous Computing

An Amorphous Computing medium is a highly redundant, massively parallel, asynchronous computing system. Because it makes no assumptions about any precision interconnect or precision geometrical arrangement of the parts, it is an ideal environment for exploring issues of robust design[l]. Recent work in this area has focused on demonstrating that amorphous media can be configured to generate highly complex spatial patterns. Examples of configurable patterns include Euclidean constructions, branching structures, and simple text[3]. In the spirit of robust design, we pose the following question: What happens if these prespecified patterns are later damaged by the external environment, or by defects in the computational units? Under what circumstances can the amorphous computing environment recover from such errors, and what consistency checking strategies might it employ to find them?
Formin-based control of the actin cytoskeleton during cytokinesis

Cytokinesis, the terminal event in the canonical cell cycle, physically separates daughter cells following mitosis. For cleavage to occur in many eukaryotes, a cytokinetic ring must assemble and constrict between divided genomes. Although dozens of different molecules localize to and participate within the cytokinetic ring, the core machinery comprises linear actin filaments. Accordingly, formins, which nucleate and elongate F-actin (filamentous actin) for the cytokinetic ring, are required for cytokinesis in diverse species. In the present article, we discuss specific modes of formin-based actin regulation during cell division and highlight emerging mechanisms and questions on this topic.
Developing Your Experiment

This chapter addresses several important elements in conducting experiments: design, pretesting and pilot testing, and data interpretation. Good design requires attention to variables, conditions, and manipulations. Pretesting and pilot testing help to avoid costly errors. Issues in data interpretation include power statistics and experimenter effects.
Response of Distributed Fiber Optic Temperature Sensors to High-Temperature Step Transients

Experiments were performed to test fiber optic temperature sensors under thermal conditions similar to those that would be experienced in the transient reactor test facility (TREAT) at the Idaho National Laboratory. Specifically, four single-mode optical fiber sensors were dropped into a pre-heated furnace to simulate a step temperature transient, for steps from room temperature to indicated furnace temperatures, ranging from 700 °C to 1100 °C. The four fibers were a standard SMF-28 fiber, a fiber with inscribed type-I fiber Bragg gratings (FBGs), and two fibers with inscribed type-II FBGs. The two type-II FBG fibers were different in the initial backscatter signal of the gratings; one fiber had gratings with greater backscatter reflection than the other. The type-I FBG sensor and standard SMF-28 sensor measured temperature for temperature transients with a final temperature of 700 °C. The low reflection type-II FBG sensor measured temperature transients with final temperatures up to 950 °C. The high-reflection type-II FBG sensor successfully measured temperature for short times with final temperatures up to 1050 °C. For long times at 1050 °C, there was a drift in the temperature sensing. We conclude that the high-reflection type-II FBG sensor would perform acceptably for application in the thermal environment of TREAT, or for other step temperature transients from room temperature to final temperatures up to 1000 °C.
Dysphagia in a Patient with Fahr’s Disease (P2.212)

Objective: To report dysphagia as initial symptom in a patient with Fahr’s Disease. Background: Fahr’s disease (FD) or idiopathic basal ganglia calcification (IBGC) is a rare entity characterized by calcification of the basal ganglia, cerebellum, thalamus and centrum semiovale. The most common clinical presentations include movement disorders, seizures, cognitive impairment, and psychiatric disturbances. Diagnosis is established by brain imaging, however laboratory tests should be done to exclude other causes of brain calcification. Design/Methods: A 66-year-old right-handed man with a history of migraines and obsessive-compulsive disorder (OCD) presents for second opinion regarding FD. His symptoms started 20 years ago with dysphagia followed by episodes of loss of consciousness (LOC). He has a sensation of food getting stuck before the LOC. He reports some hiccups and positional lightheadedness, but his vital signs and blood sugar levels have been stable. He had cognitive dysfunction with a Montreal cognitive assessment (MOCA) of 24/30, but no signs of parkinsonism and no focal deficits. His mother was also found to have bilateral calcifications, suggestive of FD, when she developed parkinsonism at age 35. Results: He was admitted to the hospital for investigation and had a 24-hour EEG and a transesophageal echocardiogram that were normal. MRI of the brain and CT of the Head showed multiple calcifications suggestive for FD. His first CT scan of the head was done after a transient episode of left side hemiparesis and revealed bilateral calcifications of the white matter, basal ganglia, thalamus, cerebellar hemispheres and posterior medulla. Dysautonomia testing was also found to be normal. Conclusions: FD is a rare condition and may start at different ages with a variety of presentations. Brain imaging and laboratory test are key to the evaluation, as well as family history of brain calcifications. This case describes dysphagia as the initial presentation for familial idiopathic basal ganglia calcification. Disclosure: Dr. Lima has nothing to disclose. Dr. Rodrigues has received research support from Hartford Hospital.
The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study: Protocol for a point-of-care randomized controlled trial of statin pharmacogenetics in primary care.

Abstract Background The association between the SLCO1B1 rs4149056 variant and statin-associated muscle symptoms (SAMS) is well validated, but the clinical utility of its implementation in patient care is unknown. Design The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study is a pseudo-cluster randomized controlled trial of SLCO1B1 genotyping among statin-naive primary care and women's health patients across the Veteran Affairs Boston Healthcare System. Eligible patients of enrolled primary care providers are aged 40–75 and have elevated risk of cardiovascular disease by American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Patients give consent by telephone in advance of an upcoming appointment, but they are enrolled only if and when their provider co-signs an order for SLCO1B1 testing, performed on a blood sample already collected in clinical care. Enrolled patients are randomly allocated to have their providers receive results through the electronic health record at baseline (PGx + arm) versus after 12 months (PGx- arm). The primary outcome is the change in low-density lipoprotein cholesterol (LDL-C) after one year. Secondary outcomes are concordance with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for simvastatin prescribing, concordance with ACC/AHA guidelines for statin use, and incidence of SAMS. With 408 patients, the study has >80% power to exclude a between-group LDL-C difference of 10 mg/dL (non-inferiority design) and to detect between-group differences of 15% in CPIC guideline concordance (superiority design). Conclusion The outcomes of the I-PICC Study will inform the clinical utility of preemptive SLCO1B1 testing in the routine practice of medicine, including its proposed benefits and unforeseen risks.
Single-cell sequencing defines genetic heterogeneity in pancreatic cancer precursor lesions

Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer; however, little is known about genetic heterogeneity in these lesions. The objective of this study was to characterize genetic heterogeneity in IPMNs at the single-cell level. We isolated single cells from fresh tissue from ten IPMNs, followed by whole genome amplification and targeted next-generation sequencing of pancreatic driver genes. We then determined single-cell genotypes using a novel multi-sample mutation calling algorithm. Our analyses revealed that different mutations in the same driver gene frequently occur in the same IPMN. Two IPMNs had multiple mutations in the initiating driver gene KRAS that occurred in unique tumor clones, suggesting the possibility of polyclonal origin or an unidentified initiating event preceding this critical mutation. Multiple mutations in later-occurring driver genes were also common and were frequently localized to unique tumor clones, raising the possibility of convergent evolution of these genetic events in pancreatic tumorigenesis. Single-cell sequencing of IPMNs demonstrated genetic heterogeneity with respect to early and late occurring driver gene mutations, suggesting a more complex pattern of tumor evolution than previously appreciated in these lesions. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Plastic scintillators stable for operating in wide ranges of humidity and temperature variations

Abstract To provide efficient and reproducible response to nuclear radiation, scintillating plastics should be prepared as materials of high optical transparency and homogeneity that should remain intact during the lifetime of their operation. A problem with traditionally used polyvinyltoluene (PVT) or polystyrene (PS) plastic scintillators arises from their exposure to repeated large temperature swings that cause surface and volume defects, resulting in decreased sensitivity of the detection properties. The problem can be avoided by composition modifications that enable preparation of plastics with properties that are resistant to the continuous variations in environmental conditions. This paper describes improvements in physical properties that can be achieved by the addition of crosslinkers (such as divinylbenzene, DVB) and oxygen-containing compounds or copolymers (e.g. polymethylamethacrylate, PMMA) to the traditional PVT or PS polymer matrices. Results of characterization show that the new materials can be prepared with the scintillation performance equal to that of commercial plastic scintillators, such as EJ-200.
Leucine, Palmitate, or Leucine/Palmitate Cotreatment Enhances Myotube Lipid Content and Oxidative Preference

Branched-chain amino acids (BCAA) such as leucine stimulate favorable metabolic processes involved in lean tissue preservation and skeletal muscle metabolism. However, higher levels of circulating BCAA correlate with severity of metabolic disease (including diabetes/insulin resistance), and may result from dysregulated BCAA catabolism. Past observations have demonstrated potential interaction between BCAA and dietary fat; however, much of this relationship remains underexplored. This study investigated the effect of leucine both with and without palmitate on oxidative and glycolytic metabolism, as well as indicators of BCAA catabolism using cultured skeletal muscle cells. Specifically, C2C12 myotubes were treated with or without varying concentrations of leucine both with and without palmitate for 24 h. Leucine treatment significantly elevated mRNA expression of metabolic regulators including peroxisome proliferator-activated receptor-gamma coactivator 1-alpha versus leucine with concurrent palmitate treatment. Interestingly, leucine-only, palmitate-only, and leucine with palmitate all significantly increased cellular lipid content, which translated into significantly increased oxidative capacity under substrate-limited conditions. However, upon the addition of excess substrate and carnitine, discrepancies in peak metabolic capacities between various treatments were no longer observed, suggesting leucine, palmitate, or the combination thereof causes a shift in metabolic preference from glycolytic to oxidative. These data also suggest leucine's effect on mitochondrial metabolism may result in part from increased lipid stores in addition to other previously documented pathways.
ADAPtation of Platelet Integrin αIIbβ3 to Inside-Out Activation Signals

Abstract 188 Platelets respond to excitatory agonists by binding adhesive ligands, such as fibrinogen, and by aggregating during hemostasis and thrombosis. These processes require the activation of αIIbβ3 from a low- to a high-affinity state. Activation of αIIbβ3 is mediated by inside-out signaling and ultimately by interactions of the molecular adaptors, talin and kindlin-3, with the β3 cytoplasmic domain. While certain key elements in the circuitry connecting agonist receptors and αIIbβ3 have been identified, some critical aspects of inside-out signaling remain undefined. The role of the hematopoietic adapter protein, ADAP, is a case in point. Platelets deficient in ADAP exhibit decreased αIIbβ3 activation in response to several agonists and reduced thrombus formation in vivo. How ADAP interfaces with the signaling machinery of platelets to regulate αIIbβ3 is unknown. Promotion of integrin adhesive function in lymphocytes by ADAP requires SKAP1, an ADAP-binding partner that is not expressed in platelets. While platelets express the SKAP1 homologue, SKAP2, the latter is dispensable for αIIbβ3 activation since SKAP2-null platelets are normal. We hypothesized that ADAP modulates αIIbβ3 function through interactions with talin and/or kindlin-3. Immunoprecipitation of ADAP from human or mouse platelets showed that ADAP was associated with a pool of talin and kindlin-3. To evaluate the proximity of this association in intact platelets, a proximity ligation assay was employed whereby antibody and DNA amplification techniques are combined to identify protein-protein interactions at the single cell level that occur at distances Disclosures: No relevant conflicts of interest to declare.
Supercooling preservation technology in food and biological samples: a review focused on electric and magnetic field applications

Freezing has been widely recognized as the most common process for long-term preservation of perishable foods; however, unavoidable damages associated with ice crystal formation lead to unacceptable quality losses during storage. As an alternative, supercooling preservation has a great potential to extend the shelf-life and maintain quality attributes of fresh foods without freezing damage. Investigations for the application of external electric field (EF) and magnetic field (MF) have theorized that EF and MF appear to be able to control ice nucleation by interacting with water molecules in foods and biomaterials; however, many questions remain open in terms of their roles and influences on ice nucleation with little consensus in the literature and a lack of clear understanding of the underlying mechanisms. This review is focused on understanding of ice nucleation processes and introducing the applications of EF and MF for preservation of food and biological materials.
Special Session: Physically Flexible Devices for Health and Activity Monitoring: Challenges from Design to Test

Recent developments in stretchable and flexible sensing and processing technologies enable a wide range of wearable devices. These devices can pave the way to medical applications ranging from health and activity monitoring to diagnosis and treatments of movement disorders. However, recent studies show that this potential is hindered by both adaptation challenges that affect the end users and technology challenges faced by developers. This paper first summarizes the challenges faced by wearable devices targeting health and user activity monitoring applications. Then, it reviews recent research progress towards addressing these challenges in energy harvesting, energy management, flexible system design, and test areas.
Towards global mapping of salt pans and salt playas using Landsat imagery: a case study of western United States

Monitoring salt pans is important for agricultural management in arid/semi-arid regions because salt pans can negatively affect human life, wildlife, ecology, and cause accelerated desertification,...
Analysis of Moore’s Law on Intel Processors

Moore’s law is a famous law in the field of computer hardware, stating that the number of transistors on integrated circuits doubles approximately every 2 years. In this report, we do an analysis of Moore’s law on consumer-class Intel processors to see how well Moore’s law has been doing on predicting the number of transistors of Intel processors, and whether this trend will continue in the future. We take a statistical approach by using linear regression and extrapolation. By matching actual data against the model of Moore’s law and calculating r-square, we are able to conclude that although Moore’s law has made close predictions for single-core processors, the time interval for a double in multi-core processors is actually longer than Moore’s law, thus Intel will fall behind Moore’s law in the future.
Adhesion Considerations in Safe Braking Distance Calculations

The main objective in optimizing train control is to eliminate the waste associated with the use of “worst case” assumptions to calculate Safe Braking Distances (SBD). Worst case takes the most conservative approach to the determination of train stopping distance in order to provide adequate stopping distance under virtually all conditions. This leads to stopping distances that could be far more than actually required under the circumstances at the time the train is attempting to brake. Several factors are considered in SBD; however one variable that influences a great portion of this distance is adhesion. This paper investigates adhesion to illustrate this influence on SBD and uses empirical data from Light Rail Systems with various test conditions. The interaction of the train control and other vehicle borne systems with SBD calculation will also be investigated including slip/slide control and brake assurance.Copyright © 2015 by ASME
Chapter 29. Alkaloids

Publisher Summary This chapter presents an overview of developments in the field of alkaloids during the period 1967—1968. The single major advance of this period was the greater understanding of the biosynthesis of the indolealkaloids. The monoterpenoid origin for the nontryptamine portion, already demonstrated with the incorporation of radio-labeled mevalonate and geraniol (I) pyrophosphate. The biosynthesis of the Ipecac alkaloids involved geraniol and loganin for the nontyramine derived portion a manner similar to the indole alkaloids. Lycopodine from Lycopodium flabelliforme was found to incorporate label from lycine-2- 14 C and -6- 14 C and to fit an origin from two isopelletierine units, a scheme at variance with a polyacetate origin. The X-ray determined structure of batrachotoxinin A, the more stable water addition product of pseudobatrachotoxin and one of a number of cardiotoxic substances from the Colombian arrow poison frog, Phyllobates aurotaenia , was reported. It represented a novel steroid structure containing an N -methylethanolamine unit. Another new type of steroid alkaloid represented by veramine, veralkamine, and veralinin was obtained from Veratrum album subsp. lobelianum. The structures were established by physical and chemical methods including X-ray analysis of veralkamine hydroiodide.
Echocardiography and Cardiopulmonary Bypass

Echocardiography has become indispensable to modern cardiac surgery, particularly since the introduction of transesophageal echocardiography (TEE) approximately 20 years ago. With TEE, an ultrasound transducer attached to a flexible scope (Fig. 1) is positioned in the esophagus or the stomach posterior to the heart. Because it does not interfere with the surgical field, produces high-resolution images of the heart and great vessels, and with Doppler echocardiography demonstrates and measures blood flow, all in real time, TEE has found many uses during heart surgery, as both a diagnostic tool and a monitor of cardiac function. This chapter explores ways in which echocardiography can be of use in patients undergoing cardiopulmonary bypass (CPB). It will begin by considering how echocardiography can be used to prevent complications of CPB by identifying risk factors before cannulation, discuss using TEE to insert and position cannula, and finish up by covering the topic of intracardiac air.
Chapter 6 The role of gap junctional intercellular communication in neoplasia

Summary Gap junctions consist of clusters of channels embedded in the plasma membranes of adjacent cells that directly link the two cell interiors and that permit the cell-to-cell exchange of small ( The proposed roles of GJIC include tissue homeostasis, electrical synapsing, coordination of cellular responses to hormones, regulation of embryonic development, and regulation of cellular growth and phenotypic expression. This latter function is especially relevant to understanding dysregulated growth in the neoplastic cell. Growth regulatory factors may be exchanged between cells via gap junctions. A reduction in gap junction formation and function is commonly observed in neoplastic cells and in cells treated with certain nongenotoxic, growth-enhancing carcinogens. The inhibition of GJIC is thought to isolate cells from the growth regulatory influences of their neighbors and to facilitate dysrgulated growth. The restoration of GJIC in neoplastic cells has been achieved genetically by connexin gene transfection and pharmacologically by treatment with vitamins, hormones, and other agents. This enhancement has resulted in reduced neoplastic cell growth and tumorigenicity in experimental animals. Such results suggest that the stimulation of GJIC should be pursued as a potential antineoplastic approach.
Update on the pharmacologic treatment of hypertension in pediatrics.

J Clin Hypertens (Greenwich). 2012; 14:383–387. ©2012 Wiley Periodicals, Inc. The past decade of investigation into the pharmacologic treatment of hypertension in children has been rewarding. The studies have shown that blood pressure medications effectively reduce blood pressure in children with hypertension and that these agents are generally well tolerated with few treatment-related adverse effects. While we have advanced our capacity to make rational therapeutic decisions, future efforts must be directed towards comparing the effectiveness of the different classes of antihypertensive agents and studies evaluating the impact of antihypertensive agents on outcome.
Nuclear Fraction of Bacillus subtilis as a Template for Ribonucleic Acid Synthesis

A “nuclear fraction” prepared from Bacillus subtilis was a more efficient template than purified deoxyribonucleic acid for the synthesis of ribonucleic acid by exogenously added ribonucleic acid polymerase isolated from B. subtilis. The initial rate of synthesis with the nuclear fraction was higher and synthesis continued for several hours, yielding an amount of ribonucleic acid greater than the amount of deoxyribonucleic acid used as the template. The product was heterogenous in size, with a large portion exceeding 23S. When purified deoxyribonucleic acid was the template, a more limited synthesis was observed with a predominantly 7S product. However, the ribonucleic acids produced in vitro from these templates were very similar to each other and to in vivo synthesized ribonucleic acid as determined by the competition of ribonucleic acid from whole cells in the annealing of in vitro synthesized ribonucleic acids to deoxyribonucleic acid. Treatment of the nuclear fraction with heat (60 C for 15 min) or trypsin reduced the capacity of the nuclear fraction to synthesize ribonucleic acid to the level observed with purified deoxyribonucleic acid.