cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel educational approach for medical students: improved retention rates using interactive medical software compared with traditional lecture-based format.

Background Mannequin and computer-based simulators are useful for the practice of patient management, physical procedures, and competency. However, they are ineffective in teaching clinical medicine. StepStone Interactive Medical Software (SS) is a web-based medical learning modality that provides the user with a highly focused set of evaluative and interventional tasks to treat memorable virtual patients in a visual case-based format. Objective To determine whether the SS learning modality is superior to traditional lecture format in medical student learning and retention. Methods After Institutional Review Board (IRB) approval was obtained and the consents were signed, 30 third-year medical students were assigned randomly to 2 groups of 15 students each: The control group received two 30-minute PowerPoint lectures (Microsoft Corporation, Redmond, Washington) about torsades de pointes (TdP) and pulseless electrical activity (PEA), and the SS group was given 1 hour to review 2 SS cases teaching TdP and PEA. A preintervention test was given to assess their baseline knowledge. An immediate postintervention test was given to both groups. Twenty-two days later, a long-term retention test was administered. The results were analyzed using a Student t test for continuous variables. Results The mean scores for the preintervention test in the control and SS groups were 44.9 ± 3% and 44.1 ± 2%, respectively (p = 0.41). The mean scores for the postintervention test in the control and SS groups were 61.7 ± 2% and 86.7 ± 2%, respectively (p Conclusions The SS learning modality demonstrated a significant improvement in student learning retention compared to traditional didactic lecture format. SS is an effective web-based medical education tool.
Computer-based synthetic data to assess the tree delineation algorithm from airborne LiDAR survey

Small Footprint LiDAR (Light Detection And Ranging) has been proposed as an effective tool for measuring detailed biophysical characteristics of forests over broad spatial scales. However, by itself LiDAR yields only a sample of the true 3D structure of a forest. In order to extract useful forestry relevant information, this data must be interpreted using mathematical models and computer algorithms that infer or estimate specific forest metrics. For these outputs to be useful, algorithms must be validated and/or calibrated using a sub-sample of `known' metrics measured using more detailed, reliable methods such as field sampling. In this paper we describe a novel method for delineating and deriving metrics of individual trees from LiDAR data based on watershed segmentation. Because of the costs involved with collecting both LiDAR data and field samples for validation, we use synthetic LiDAR data to validate and assess the accuracy of our algorithm. This synthetic LiDAR data is generated using a simple geometric model of Loblolly pine (Pinus taeda) trees and a simulation of LiDAR sampling. Our results suggest that point densities greater than 2 and preferably greater than 4 points per m2 are necessary to obtain accurate forest inventory data from Loblolly pine stands. However the results also demonstrate that the detection errors (i.e. the accuracy and biases of the algorithm) are intrinsically related to the structural characteristics of the forest being measured. We argue that experiments with synthetic data are directly useful to forest managers to guide the design of operational forest inventory studies. In addition, we argue that the development of LiDAR simulation models and experiments with the data they generate represents a fundamental and useful approach to designing, improving and exploring the accuracy and efficiency of LiDAR algorithms.
Phylogenetic relationships of Palaeogene ziphodont eusuchians and the status of Pristichampsus Gervais, 1853

Eusuchians with deep snouts and labiolingually compressed teeth are known from the Palaeogene of Laurasia. These are usually referred to Pristichampsinae, but the type species, Pristichampsus rollinati, is based on insufficiently diagnostic material and should be treated as a nomen dubium. At least two Lutetian species formerly referred to Pristichampsus can be recognised – Boverisuchus magnifrons in Germany and possibly elsewhere in Europe, and Boverisuchus vorax, new combination, in western North America. Material from the middle Eocene of Italy and Texas may represent distinct species. A phylogenetic analysis confirms their close relationship and also supports a relationship with two Asian forms – early Eocene Planocrania datangensis and Palaeocene Planocrania hengdongensis. The name Planocraniidae Li 1976 is applied to this group. A distinctive quadrate with a prominent dorsal peak between medial and lateral hemicondyles is known only in Boverisuchus, and although the teeth of Planocrania are flattened, they are not serrated. Planocraniids maintain a phylogenetic position as the sister group to Crocodyloidea+Alligatoroidea, but this part of the tree is unstable and discovery of older, more primitive planocraniids will help resolve conflicts on the phylogenetic relationships of extant crocodylian lineages.
Surface activity of sodium salts of alpha-sulfo fatty esters: The air-water interface

Adsorption at the air-water interface of sodium hexyl α-sulfopelargonate, sodium heptyl α-sulfopelargonate, sodium methyl α-sulfomyristate, and sodium methyl α-sulfopalmitate has been investigated.
The influence of photon attenuation on tumor-to-background and signal-to-noise ratios for SPECT imaging

Expanding on the work of Nuyts et. al [1], Bai et. al. [2], and Bai and Shao [3], who all studied the effects of attenuation and attenuation correction on tumor-to-background ratios and signal detection, we have derived a general expression for the tumor-to-background ratio (TBR) for SPECT attenuated data that have been reconstructed with a linear, non-iterative reconstruction operator O. A special case of this is when O represents discrete filtered back-projection (FBP). The TBR of the reconstructed, uncorrected attenuated data (TBRno-Ac) can be written as a weighted sum of the TBR of the FBP- reconstructed unattenuated data (TBRFBP) and the TBR of the FBP-reconstructed "difference" projection data (TBRdiff). We evaluated the expression for TBRno-Ac for a variety of objects and attenuation conditions. The ideal observer signal-to-noise ratio (SNRideai) was also computed in projection space, in order to obtain an upper bound on signal detectability for a signal- known-exactly/background-known-exactly (SKE/BKE) detection task. The results generally show that SNRideal is lower for tumors located deeper within the attenuating medium and increases for tumors nearer the edge of the object. In addition, larger values for the uniform attenuation coefficient mu lead to lower values for SNRideal. The TBR for FBP-reconstructed, uncorrected attenuated data can both under- and over-estimate the true TBR, depending on several properties of the attenuating medium, including the shape of the attenuator, the uniformity of the attenuator, and the degree to which the data are attenuated.
Sediment-generated noise and bed stress in a tidal channel

[1] Tidally driven currents and bed stresses can result in noise generated by moving sediments. At a site in Admiralty Inlet, Puget Sound, Washington State (USA), peak bed stresses exceed 20 Pa. Significant increases in noise levels are attributed to mobilized sediments at frequencies from 4–30 kHz with more modest increases noted from 1–4 kHz. Sediment-generated noise during strong currents masks background noise from other sources, including vessel traffic. Inversions of the acoustic spectra for equivalent grain sizes are consistent with qualitative data of the seabed composition. Bed stress calculations using log layer, Reynolds stress, and inertial dissipation techniques generally agree well and are used to estimate the shear stresses at which noise levels increase for different grain sizes. Regressions of the acoustic intensity versus near-bed hydrodynamic power demonstrate that noise levels are highly predictable above a critical threshold despite the scatter introduced by the localized nature of mobilization events.
The Discovery of the 27-nm Norwalk Virus: An Historic Perspective

In 1972, a 27-nm virus-like particle was discovered by use of immune electron microscopy (IEM) in an infectious stool filtrate derived from an outbreak of gastroenteritis in an elementary school in Norwalk, Ohio. IEM enabled the direct visualization of antigen-antibody interaction, as the particles were aggregated and coated by specific antibodies. This allowed the recognition and identification of a 27-nm virus-like particle that did not have a distinctive morphology, was low-titered, and was among the smallest viruses known. Serum antibody responses to the 27-nm particle were demonstrated in key individuals infected under natural or experimental conditions; this and other evidence suggested that this virus-like particle was the etiologic agent of the Norwalk gastroenteritis outbreak. The fastidious 27-nm Norwalk virus is now considered to be the prototype strain of a group of noncultivatable viruses that are important etiologic agents of epidemic gastroenteritis in adults and older children.
Skeletal muscle weakness due to deficiency of CuZn-superoxide dismutase is associated with loss of functional innervation

An association between oxidative stress and muscle atrophy and weakness in vivo is supported by elevated oxidative damage and accelerated loss of muscle mass and force with aging in CuZn-superoxide dismutase-deficient (Sod1(-/-)) mice. The purpose was to determine the basis for low specific force (N/cm(2)) of gastrocnemius muscles in Sod1(-/-) mice and establish the extent to which structural and functional changes in muscles of Sod1(-/-) mice resemble those associated with normal aging. We tested the hypothesis that muscle weakness in Sod1(-/-) mice is due to functionally denervated fibers by comparing forces during nerve and direct muscle stimulation. No differences were observed for wild-type mice at any age in the forces generated in response to nerve and muscle stimulation. Nerve- and muscle-stimulated forces were also not different for 4-wk-old Sod1(-/-) mice, whereas, for 8- and 20-mo-old mice, forces during muscle stimulation were 16 and 30% greater, respectively, than those obtained using nerve stimulation. In addition to functional evidence of denervation with aging, fiber number was not different for Sod1(-/-) and wild-type mice at 4 wk, but 50% lower for Sod1(-/-) mice by 20 mo, and denervated motor end plates were prevalent in Sod1(-/-) mice at both 8 and 20 mo and in WT mice by 28 mo. The data suggest ongoing denervation in muscles of Sod1(-/-) mice that results in fiber loss and muscle atrophy. Moreover, the findings support using Sod1(-/-) mice to explore mechanistic links between oxidative stress and the progression of deficits in muscle structure and function.
The role of chemical interactions and epitaxy during nucleation of organic crystals on crystalline substrates

A tandem strategy to control polymorphism through epitaxial relationships with crystalline substrates reveals the importance of chemical interactions at the nucleation surface compared with the periodic surface potential associated with epitaxy.
TRPV1-antagonist AMG9810 promotes mouse skin tumorigenesis through EGFR/Akt signaling

In addition to capsaicin, a transient receptor potential channel vanilloid subfamily 1 (TRPV1) agonist, two kinds of antagonists against this receptor are used as therapeutic drugs for pain relief. Indeed, a number of small molecule TRPV1 antagonists are currently undergoing Phase I/II clinical trials to determine their effect on relieving chronic inflammatory pain and migraine headache pain. However, we previously reported that the absence of TRPV1 in mice results in a striking increase in skin carcinogenesis, suggesting that chronic blockade of TRPV1 might increase the risk of tumor development. In this study, we found that a typical TRPV1 antagonist, AMG9810, promotes mouse skin tumor development. The topical application of AMG9810 resulted in a significant increase in the expression level of the epidermal growth factor receptor (EGFR) and its downstream Akt/mammalian target of rapamycin (mTOR)-signaling pathway. This increase was not only observed in AMG9810-treated tumor tissue but was also found in skin tissue treated with AMG9810. In telomerase-immortalized primary human keratinocytes, AMG9810 promoted proliferation that was mediated through the EGFR/Akt/mTOR-signaling pathway. In summary, our data suggest that the TRPV1 antagonist, AMG9810, promotes mouse skin tumorigenesis mediated through EGFR/Akt/mTOR signaling. Thus, the application of this compound for pain relief might increase the risk of skin cancer.
Regulation of Arabidopsis flower development.

Plant development is governed by intrinsic and environmen- tal factors that regulate the identity and activity of meristems, organized tissues of pluripotent "stem" cells, that together de- termine plant form and architecture. However, little is known about how these factors act at the molecular leve1 to affect meristem identity and function. Genetic studies in Arabidop- sis and other plant species such as snapdragon, petunia, and maize have revealed a hierarchy of regulatory genes that func- tion together to promote the formation of the floral meristem and to regulate floral organogenesis. Mutations in these genes result in dramatic defects in flower development that can af- fect both meristem identity and organ development. Table 1 lists the Arabidopsis genes that are known to control meristem and organ identity and their snapdragon equivalents. One class of regulatory genes, the homeotic organ identity genes, have provided important insights into the genetic and molecular mechanisms that govern floral organ identity and development (Bowman et al., 1991; Coen and Meyerowitz, 1991; Coen and Carpenter, 1993, this issue; van der Krol and Chua, 1993, this issue). In Arabidopsis, these genes include
MRI and implanted medical devices: basic interactions with an emphasis on heating

There are three principal magnetic fields in magnetic resonance imaging (MRI) that may interact with medical implants. The static field will induce force and torque on ferromagnetic objects. The pulsed gradients are of audio frequency and the implant may concentrate the induced currents, with a potential for nerve stimulation or electrical inference. The currents induced in the body by the radio frequency (RF) field may also be concentrated by an implant, resulting in potentially dangerous heating of surrounding tissues. This paper presents basic information about MRI interactions with implants with an emphasis on RF-induced heating of leads used for deep brain stimulation (DBS). The temperature rise at the electrodes was measured in vitro as a function of the overall length of a DBS lead at an RF frequency of 64 MHz. The maximal temperature rise occurred for an overall length of 41 cm. The method of moments was used to calculate the current induced in the lead. From the induced currents, the RF power deposition near the electrodes was calculated and the heat equation was used to model the temperature rise. The calculated temperature rises as a function of lead length were in good agreement with the measured values.
Meningioma: Urokinase Plasminogen Activator

Meningiomas, which arise from the meninges, are by far the most frequently occurring intracranial primary tumors in adults. Histopathological and clinical variants of meningiomas offer new challenges in diagnosis, pathology and treatment modalities. Moreover, recurrence of the more aggressive tumors demand the development of novel, targeted therapeutic strategies. Significant progress has been made in recent years in delineating the molecular mechanisms involved in meningioma formation, growth, and malignant progression. However, many questions remain unanswered. A different approach to the molecular genetics of meningiomas is to examine some aspects of carcinogenesis that are not necessarily specific to meningiomas. To that end, current literature demonstrates that the expression and cleavage of urokinase plasminogen activator (uPA) plays an important role in the tumorigenicity of brain tumors, and high endogenous levels of uPA are associated with advanced metastatic/invasive cancers. Extracellular matrix (ECM) degradation has been implicated as a key step in this process and is mediated by different classes of proteinases among which the uPA system plays a central role. In addition to its role in tumor propagation by binding to uPAR, uPA promotes proteolysis of plasminogen and activates matrix metalloproteinases (MMPs) and transduces signals affecting chemotactic, adhesive and mitgoenic properties of cancer cells. Recent studies have revealed that the targeted silencing of uPA and its receptor uPAR impedes the aggressive characteristics of gliomas and meningiomas. In the present article, we review the salient features of pericellular proteases (with a focus on the uPA system), the possible signaling mechanisms involved, and the therapeutic usefulness of uPA knockdown in the management of meningiomas.
Codesign-extended applications

We challenge the widespread assumption that an embedded system's functionality can be captured in a single specification and then partitioned among software and custom hardware processors. The specification of some functions in software is very different from the specification of the same function in hardware - too different to conceive of automatically deriving one from the other. We illustrate this concept using a digital camera example. We introduce the idea of codesign-extended applications to deal with the situation, wherein critical functions are written in multiple versions, and integrated such that simple compiler/synthesis flags instantiate a particular version along with the necessary control and communication behavior. By capturing a specification as a codesign-extended application, a designer enables smooth migration among platforms with increasing amounts of on-chip configurable logic.
Secretion of Glycosylated Pro–B-Type Natriuretic Peptide from Normal Cardiomyocytes

BACKGROUND: B-type natriuretic peptide (BNP), a key cardiac hormone in cardiorenal homeostasis, is produced as a 108 amino acid prohormone, proBNP1-108, which is converted to a biologically active peptide BNP1-32 and an inactive N-terminal (NT)-proBNP1-76. The widely accepted model is that the normal heart releases a proteolytically processed BNP1-32 and NT-proBNP, whereas the diseased heart secretes high amounts of unprocessed/glycosylated proBNP1-108 or inappropriately processed BNPs. In contrast, circulating proBNP1-108 has recently been identified in healthy individuals, indicating that the normal heart also secretes unprocessed proBNP1-108. However, the mechanism of proBNP1-108 secretion from the normal heart remains elusive. Our goal was to determine the molecular mechanisms underlying proBNP1-108 intracellular trafficking and secretion from the normal heart. METHODS: We expressed preproBNP in cardiomyocytes, and determined the subcellular localization and dominant intracellular and extracellular forms of BNP. RESULTS: Intracellular immunoreactive BNPs were first accumulated in the Golgi apparatus, and then distributed throughout the cytoplasm as secretory vesicles. The predominant intracellular form of BNP was nonglycosylated proBNP1-108, rather than BNP1-32. Glycosylated proBNP1-108, but not nonglycosylated proBNP1-108, was detected as the major extracellular form in the culture supernatants of preproBNP-expressing cell lines and primary human cardiomyocytes. Ablation of O -glycosylation of proBNP1-108 at T71 residue, near the convertase recognition site, reduced the extracellular proBNP1-108 and increased extracellular BNP1-32. CONCLUSIONS: Intracellular proBNP trafficking occurs through a conventional Golgi–endoplasmic reticulum pathway. Glycosylation of proBNP1-108 controls the stability and processing of extracellular proBNP1-108. Our data establish a new BNP secretion model in which the normal cardiac cells secrete glycosylated proBNP1-108.
Pediatric Antidepressant Use After The Black-Box Warning

In 2004 the Food and Drug Administration (FDA) required a black-box warning on antidepressants that describes a possible suicide risk in children. An analysis of the events, evidence, and FDA actions reveals information asymmetries that affect various players’ ability to identify and act on risks. Antidepressant use declined sharply overall, not just among children, and the FDA’s emphasis on the proven efficacy of fluoxetine (generic Prozac) did not prompt dramatic shifts in prescribing. We conclude that risk communication strategies need to be refined, to ensure intended results.
Role of definitive radiation therapy in carcinoma of unknown primary in the abdomen and pelvis.

Objectives Carcinoma of unknown primary (CUP) in the abdomen and pelvis is a heterogeneous group of cancers with no standard treatment. Considered by many to be incurable, these patients are often treated with chemotherapy alone. In this study, we determined the effectiveness of radiation therapy in combination with chemotherapy in patients with CUP in the abdomen and pelvis. Patients and Methods Medical records were reviewed for 37 patients with CUP treated with radiation therapy for disease located in the soft tissues and/or nodal basins of the abdomen and pelvis at the University of Texas M.D. Anderson Cancer between 2002 and 2009. All patients underwent chemotherapy, either before or concurrent with radiation therapy. Patients were selected for radiation therapy on the basis of histologic type, disease extent, and prior therapy response. Twenty patients underwent definitive radiation therapy (defined as radiation therapy targeting all known disease sites with at least 45 Gy) and 17 patients underwent palliative radiation therapy. Only 6 patients had surgical resection of their disease. Patient and treatment characteristics were extracted and the endpoints of local disease control, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity incidence were analyzed. Results The 2-year PFS and OS rates for the entire cohort were 32% and 57%, respectively. However, in patients treated with definitive radiation therapy, the rates were 48% and 76%, and 7 patients lived more than 3 years after treatment with no evidence of disease progression. Nevertheless, radiation-associated toxicity was significant in this cohort, as 40% experienced Grade 2 or higher late toxicities. Conclusions The use of definitive radiation therapy should be considered in selected patients with CUP in the soft tissues or nodal basins of the abdomen and pelvis.
Physical Education in the War and in the Peace

(1943). Physical Education in the War and in the Peace. The Journal of Health and Physical Education: Vol. 14, No. 2, pp. 74-126.
Experimental Endocarditis Due to Pseudomonas aeruginosa. I. Description of a Model

Rabbits with sterile, right ventricular cardiac vegetationss were challenged with Staphylococcus aureus and serum-susceptible or -resistant isolates of Pseudomonas aeruginosa. None of the rabbits challenged with serum-susceptible P. aeruginosa died or had greater than 10(2) colony-forming units (cfu)/g cultured from vegetations two weeks later. In contrast, 78% of animals challenged with serum-resistant P. aeruginosa died within three weeks, and 74% sacrificed at three days had organisms cultured from vegetations. All of the animals challenged with S. aureus died, and all had greater than 10(8) cfu of P. aeruginosa/g in vegetation tissue at three days. There was a significantly greater number of organisms (P less than 0.001) in the vegetations of animals dying of S. aureus infection than in those of animals with P. aeruginosa endocarditis (mean, 10(9.6) vs. 10(7.5) cfu/g, respectively). Left-sided endocarditis was produced in 100% of rabbits injected with serum-resistant P. aeruginosa. These models could be used for studies of the pathogenesis and therapy of P. aeruginosa endocarditis.
The baton dialyzer.

Macromolecular solutions (such as radioactive materials, sterile solutions, infectious materials) requiring special handling precautions for dialysis may be safely and easily handled using a baton-shaped dialysis device.
Abstract LB-153: PDE4D as a new prostate cancer drug target

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC We have been conducting a two-species screen for prostate cancer oncogenes that are suitable for use as new prostate cancer drug targets. The initial screen utilized transposon-based somatic mutagenesis in mice to induce prostate tumors and molecularly tag candidate oncogenes. This approach identified several candidate prostate cancer genes including known oncogenes such as Nras and Braf as well as new candidate oncogenes including Pde4d. A secondary screen used human prostate tissue microarrays (TMAs) to validate the relevance of new candidate oncogenes for understanding human prostate cancer. Automated quantitative analysis of PDE4D protein expression on the human TMAs confirmed its over-expression in human prostate cancer patients. The Pde4d mRNA is alternatively spliced to encode a family of related PDE4D enzymes. These enzymes share a common catalytic domain that gives all of the enzymes cAMP-specific 3′,5′-cyclic phosphodiesterase activity. Protein domains outside the catalytic domain allow for differential protein regulation and sub-cellular localization of different PDE4D isoforms. Several small molecules have been identified that are highly selective inhibitors of PDE4D activity including cilomilast and NVP-ABE171. In vitro testing of these small molecules has shown that they inhibit the growth of some but not all commonly used prostate cancer cell lines. Growth-inhibition was associated with down-regulation of the MEK-ERK and Shh signaling pathways. Current studies are investigating the molecular mechanisms associated with differential sensitivity/resistance to PDE4D inhibition as well as the potential use of PDE4D inhibitors as anti-prostate cancer drugs in vivo. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-153.
Architectural and Micro-Architectural Techniques for Software Controlled Microprocessor Soft-Error Mitigation

A MIPS 4Kc compliant embedded microprocessor core design that incorporates architectural features for software controlled radiation upset recovery is presented. The design uses fault tolerance techniques, i.e., error detection and instruction restart, implemented at the micro-architectural level, with architectural level changes, i.e., new instructions, for error recovery. Fine-grained, self-correcting triple mode redundant circuits protect key architectural state, in addition to dual mode redundancy in the instruction execution pipelines, cache subsystems, and error detection and correction in the register file. The design is implemented in a commercial low standby power 90-nm bulk low standby power CMOS process and the prototype operates at up to 336 MHz.
Prefrontal Regulation of Neuronal Activity in the Ventral Tegmental Area

Growing evidence indicates that midbrain dopamine (DA) cells integrate reward expectancy-related information from the prefrontal cortex to properly compute errors in reward prediction. Here we investigated how 2 major prefrontal subregions, the orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC), contributed to DAergic prediction errors while rats performed a delay discounting task on a T-maze. Most putative DA cells in the task showed phasic responses to salient cues that predicted delayed rewards, but not to the actual rewards. After temporary inactivation of the OFC, putative DA cells exhibited strikingly reduced phasic responses to reward-predicting cues but increased responses to rewards. In contrast, mPFC inactivation significantly elevated DA responses to both predictive cues and rewards. In addition, OFC, but not mPFC, inactivation disrupted the activity of putative non-DA cells that encoded expected reward values during waiting periods. These results suggest that the 2 prefrontal subregions differentially regulate DAergic prediction errors and the OFC conveys value signals to midbrain dopamine systems.
The Cell Surface Receptor CD44: NMR-Based Characterization of Putative Ligands

The cell surface receptor CD44 is a glycoprotein belonging to the hyaluronan-binding proteins, termed hyaladherins. CD44 is expressed in a wide variety of isoforms in many cells and, in particular, is present on the surface of malignant cells where it is involved in the onset and progression of cancer. In a first attempt to identify novel CD44-binding agents, we first characterized, with NMR spectroscopic techniques, several agents that were reported to bind to human CD44 (hCD44). To our surprise, however, none of these putative CD44-binding agents, including a peptide that is in phase 2 clinical trials (A6 peptide) and a recently reported fragment hit, were found to interact significantly with recombinant hCD44(21-178). Nonetheless, we further report that a fragment-screening campaign, with solution NMR spectroscopy as the detection method, identified a viable fragment hit that bound in a potentially functional pocket on the surface of CD44, opposite to the hyaluronic acid binding site. We hypothesize that this pocket could be indirectly associated with the cellular and in vivo activity of the A6 peptide, which would provide a novel framework for the possible development of therapeutically viable CD44 antagonists.
Clinical Analysis of Cerebral Hemorrhage in Xing’an League from 2008 to 2009

Objective: To investigate the epidemiological characteristics of cerebral hemorrhage in Xing’an league,and to provide a theoretical basis for targeted prevention and control of cerebral hemorrhage in this area.Methods: New cases of cerebral hemorrhage in Xing’an league form April 2008 to March 2009 were monitored and their distribution were analyzed.Results: Form April 2008 to March 2009,the new case number of cerebral hemorrhage were 423 patients,in which male patients were 258 cases,the peak age of onset was 51～60 years old.The peak incidence of cerebral hemorrhage was on January 1,the peak season was October 1 to April 1 of next year.Conclusion: Through this clinical monitoring,the epidemiological characteristics of cerebral hemorrhage in Xing’an league were primarily understood,which can provide a theoretical basis for targeted prevention and control cerebral hemorrhage of this area in the future.
Abstract PL04-03: Evidence for increased muscle breakdown associated with early pancreatic cancer

Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression had not been studied. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from pancreatic cancer cases and matched controls from four prospective cohort studies. We found that elevated plasma levels of branched chain amino acids (BCAAs) are associated with a greater than 2–fold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years prior to diagnosis when occult disease is likely present. Utilizing genetically engineered mouse models of PDAC, we have confirmed that these elevations represent a marker of early, sub-clinical disease. Furthermore, using these model systems, we demonstrate that the increase in plasma BCAAs reflects a breakdown of tissue protein that accompanies early stage disease. Together, these findings suggest that altered whole body amino acid metabolism is an early event in development of PDAC, and that elevations in BCAAs can be seen in patients years before their pancreatic cancer diagnosis. Citation Format: Matthew G. Vander Heiden. Evidence for increased muscle breakdown associated with early pancreatic cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL04-03.
Bimodal MRI/fluorescence imaging contrast agent targeting human prostate cancer

57 Objectives We aimed to develop novel site-specific nanoparticles targeting the BB2 receptors overexpressed in aggressive prostate cancers. Methods Water soluble ultra-small superparamagnetic iron oxide (USPIO) nanoparticles with a core size of 5 nm were prepared via glucose and casein coating reactions. Cy7.5 was conjugated to K-8AOC-QWAVGHLMNH2 at a molar ratio of 1:1 followed by the conjugation with the COOH groups on USPIO. The Cy7.5-BBN was purified using RP-HPLC and characterized by mass spectroscopy. The USPIO-Cy7.5-BBN nanoparticles were purified via 100 KDa membrane filtration and characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) and Fourier transform infrared (FTIR) spectroscopy. MRI r2 relaxivity was measured at 7T. In vitro binding affinity was performed in PC-3 cells. In vivo T2 MRI contrast enhancement in PC-3 tumors was evaluated after tail vein injections of nanoparticles in mice at a dose of 87 µg Fe/mouse on 7T MRI. In vivo near infrared fluorescence (NIRF) imaging was performed using IVIS-Spectrum. Mice were assigned to three groups: targeting group were injected with USPIO-Cy7.5-BBN, blocking group were pre-injected with 50 µg unlabeled BBN[1-14] before the injection of USPIO-Cy7.5-BBN, and control group were injected with USPIO-Dylit800. Results USPIO-Cy7.5-BBN has a core diameter of 5.1±0.5 nm and a hydrodynamic diameter of 15.4±3.6 nm. The r2 relaxivity was 70.2±2.5 s-1mM-1 at 7T. In vivo MRI contrast enhancement ratio of tumor to muscle was significantly increased in the uptake group at 4hr (31.1±3.4%) and 24hr (25.7±2.1%) post injection compared to the blocking group (4hr: 15.3±2.0% and 24hr: 2.8±6.8%). In vivo and ex vivo NIRF imaging showed a significantly increased fluorescence on the tumors in the uptake group compared to the blocking group. Conclusions We synthesized a bimodal USPIO-Cy7.5-BBN nanoparticle with a small core size and high relaxivity. In vitro and in vivo data showed high affinity and specificity to the BB2r expressed by PC-3 cells.
Coverage and Connectivity for Regular Deployments

Up till now, we have considered WSN to have a large number of randomly deployed SNs, primarily useful for defense applications and natural disasters. But, they can be utilized using a regular topology pattern if the area is accessible and SNs can be placed at any point within the area.
Probability of Undiagnosed Obstructive Sleep Apnea Does Not Correlate With Adverse Pulmonary Events nor Length of Stay in Hip and Knee Arthroplasty Using Intrathecal Opioid.

Abstract Background Recent emphasis on bundled payments and outcomes tracking has increased the focus on preoperative optimization in patients undergoing elective lower extremity arthroplasty. Since patients with obstructive sleep apnea (OSA) have an increased risk of adverse perioperative pulmonary events, screening for undiagnosed OSA is sometimes included as part of preoperative risk assessment. However, there are limited data regarding quantification of OSA risk in lower extremity arthroplasty patients, and little is known about the utility of quantitative OSA screening and the risk of pulmonary complications in hip and knee arthroplasty patients who receive intrathecal morphine anesthetic. Methods A retrospective review of 990 patients at a tertiary care, urban academic medical center who underwent lower extremity arthroplasty with a multimodal pain regimen including intrathecal morphine anesthesia, comparing the rate of pulmonary complications and length of stay between patients previously diagnosed with OSA and those identified as low, moderate, and high risk of undiagnosed OSA established by screening with the STOP-BANG questionnaire in the preoperative setting. Results Using logistic regression and adjusting for age, gender, and body mass index, the results suggested the rate of complications was not different across the sleep apnea risk groups (P = .4024). In addition, linear regression suggested length of stay did not differ significantly by sleep apnea risk group (P = .2823). Conclusion In patients receiving intrathecal morphine as part of a multimodal pain regimen undergoing hip or knee arthroplasty, neither risk of adverse pulmonary events nor length of stay appeared to correlate with preoperative risk of undiagnosed OSA.
Zebrafish Pancreas Development and Regeneration: Fishing for Diabetes Therapies

The zebrafish pancreas shares its basic organization and cell types with the mammalian pancreas. In addition, the developmental pathways that lead to the establishment of the pancreatic islets of Langherhans are generally conserved from fish to mammals. Zebrafish provides a powerful tool to probe the mechanisms controlling establishment of the pancreatic endocrine cell types from early embryonic progenitor cells, as well as the regeneration of endocrine cells after damage. This knowledge is, in turn, applicable to refining protocols to generate renewable sources of human pancreatic islet cells that are critical for regulation of blood sugar levels. Here, we review how previous and ongoing studies in zebrafish and beyond are influencing the understanding of molecular mechanisms underlying various forms of diabetes and efforts to develop cell-based approaches to cure this increasingly widespread disease.
Targeted therapies for renal cell carcinoma

The management of patients with metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. Nephrectomy remains an important intervention for localized RCC but systemic therapy is the mainstay of treatment for patients who relapse after surgery or who have metastatic RCC. Before 2005, medical therapies for RCC were limited to cytokine therapies, which are very toxic and benefit only a small percentage of patients. In 2017, therapeutic agents now include kinase and immune checkpoint inhibitors. Contemporary research with these agents is now focusing on combinatorial and perioperative therapy. The field is now faced with the evolving challenge of how to select the best therapy for each patient during their natural history of disease, which has created a strong interest in modern sequencing and molecular approaches to identify biomarkers to personalize treatments. New therapeutic agents and approaches are associated with different toxicities and financial burdens, which require consideration of value by measuring clinical benefit, toxicity, and the cost of each drug with an organized framework. In this Review, we discuss the mechanisms underlying RCC and how improved molecular understanding helped the development of therapies, as well as biomarkers of response to treatment. We also discuss the value of these agents and their impact on personalization of therapy and drug development for RCC.
Extraction of circuit transfer functions with SuTra analyses

Finding node admittance and voltage gain transfer functions with SuTra (Suspendance and Trajectance) analyses are introduced in this paper. All other transfer functions are obtained when the two fundamental node admittance and voltage gain transfer functions are calculated. The numerator of the node admittance is obtained by Suspendance analysis and the numerator of the voltage gain is obtained by Trajectance analysis. The denominator of both transfer functions are obtained by Suspendance analysis when the input node of the circuit is shorted to ground. To calculate Suspendance, passive components are shorted at a time and their admittances are multiplied by the Suspendance of the remaining circuit which will be calculated recursively. Components shorted earlier are then removed from the circuit in following steps of Suspendance calculation. All results are added together to get the overall Suspendance. To calculate Trajectance, all paths that connect the input and output nodes through sequential passive components and dependent active sources are determined. Segments of these paths are shorted to ground and the Suspendance of the remaining circuit is calculated. The admittance contributions of each path is multiplied by its corresponding Suspendance and all results are added together to calculate Trajectance. A four-node two-stage BJT amplifier is analyzed and characterized in this paper. Results fully match with those obtained from Spice simulation verifying the effectiveness of the Suspendance and Trajectance analyses.
Analytic trails: supporting provenance, collaboration, and reuse for visual data analysis by business users

In this paper, we discuss the use of analytic trails to support the needs of business users when conducting visual data analysis, focusing particularly on the aspects of analytic provenance, asynchronous collaboration, and reuse of analyses. We present a prototype implementation of analytic trail technology as part of Smarter Decisions - a web-based visual analytic tool, with the goal of helping business users derive insights from structured and unstructured data. To understand the value and shortcomings of trails in supporting visual analytic tasks in business environments, we performed a user study with 21 participants. While the majority of participants found trails to be useful for capturing and understanding the provenance of an analysis, they viewed trails as more valuable for personal use rather than for communicating the analytic process to other people as part of a collaboration. Study results also indicate that rich search mechanisms for easily finding relevant trails (or portions of a trail) is critical to the successful adaptation and reuse of existing saved trails.
Editorial 2: “Meaning” and the Welby—Peirce Correspondence

This second editorial of this book is on the importance of the correspondence between Charles Sanders Peirce and Lady Victoria Welby—their letters show many aspects of an evolving philosophical insight that centers (in hindsight) around the issue of meaning. The two letters, which are introduced here, form as it were an autobiography of Peircean philosophy, its semiotic dimensions and considerations why Peirce could not entirely go with Lady Welby in forwarding significs included. Whoever wants to reflect on the difference between the two, should read these letters and consider their arguments. It interests how Peirce takes all the trouble to explain his triad of Firstness, Secondness and Thirdness, and what his own skepticism in view of that triad means. For legal semiotics, the issue is of great interest in so far as the power of expressiveness inherent in legal language is considered in vicinity to De Haan, the first legal semiotician.
Injuries of the colon

I T has been shown many times that surgica1 diseases of the ahmentary tract are far Iess common in negroes than in white people. RaciaI characteristics may pIay a part in this difference, but diet is an important factor. IndividuaIs Iike the East Indians who subsist on so-caIIed “natura1” foods escape aImost entireIy such Iesions as peptic uIcer, gaII-bIadder disease, appendicitis and carcinoma of the digestive system. Such foods are those which are grown in the community where they are consumed with IittIe deIay, and are subjected to but IittIe packing, shipping and storing. On the other hand these diseases occur with marked and increasing frequency in a popuIation whose foods are poIished, pickIed, frozen, thawed, steriIized and canned, and then transported to distant pIaces where they may remain a Iong time before being used. The negro of our Southern states Iives on food somewhat simiIar to that of the East Indians, and a survey of ten years ago made in AtIanta demonstrated that these diseases were four times as common in the white as in the coIored race. More recentIy, as the city-dweIIing negro takes on the habits and nourishment of his white neighbor, he has become more subject to the aflictions of the Caucasian. Now these surgica1 diseases of the aIimentary tract are beIieved to be onIy twice as common in white patients as in coIored. Such is the record of carcinoma of the coIon. During the eight-year period, IgsI-1938, among approximateIy the same number of admissions to the Grady (municipal) HospitaI, of AtIanta, there GEORGIA
Conditions DataHandling in the Multithreaded ATLAS Framework

In preparation for Run 3 of the LHC, the ATLAS experiment is migrating its offline software to use a multithreaded framework, which will allow multiple events to be processed simultaneously. This implies that the handling of non-event, time-dependent (conditions) data, such as calibrations and geometry, must also be extended to allow for multiple versions of such data to exist simultaneously. This has now been implemented as part of the new ATLAS framework. The detector geometry is included in this scheme by having sets of time-dependent displacements on top of a static base geometry.
Maximum-Likelihood Event Parameter Estimation from Digital Waveform Capture

A preclinical Single Photon Emission Computed Tomography (SPECT) system design is presented, that will be used in rabbit myocardial perfusion and related cardiac studies. The system includes digital-waveform capture of all PMT signals, which allows for optimal maximum-likelihood estimation in the gamma-ray event parameter estimation and tomographic reconstruction processes. In a typical gamma ray camera, only the integrated signal of a gamma ray event is recorded. Here, because the entire waveform is recorded, it is possible to incorporate information from the waveform shape into the maximum-likelihood estimation. A likelihood model for incorporating waveforms in estimating event parameters (x, y, z, energy, and time) is explored. The detector, a full-size clinical SPECT camera with 61 PMTs, was retrofitted with an array of active buffers that tap into raw low-level signals before they reach the Anger-logic network. Methods for system calibration and integration are discussed, along with predictions and measurements of system performance.
An Integrated Forward-View 2-Axis Mems Scanner for Compact 3D Lidar

This paper reports an integrated forward-view 2-axis MEMS scanner that enables ultrasmall 3D LiDAR for applications in micro-air vehicles (MAV). A new design of a pair of vertically-oriented 2-axis scanning MEMS scanner is proposed and fabricated using an innovative fabrication process. Such MEMS scanners are integrated on a silicon optical bench and bent vertically to the substrate, thus forward scan is realized without any beam-folding mirrors. The mirror plate is $\mathbf{0.7\ mm}\times \mathbf{0.7}$ mm. The measured optical scan range reaches 17° in both axes at only 4.5 V. The measured resonance frequency of the angular scanning mode is 2.2 kHz. Good optical alignment for LiDAR scanners can be achieved without extra alignment efforts. This MEMS mirror allows a forward-view LiDAR scanner to be monolithically integrated and aligned on a single chip.