cssi/SciSciGPT-SciSciNet huggingface dataset:
Therapeutic potential of an anti-angiogenic multimodal biomimetic peptide in hepatocellular carcinoma

// Mustafa A. Barbhuiya 1, * , Adam C. Mirando 2, * , Brian W. Simons 3 , Ghali Lemtiri-Chlieh 1 , Jordan J. Green 2 , Aleksander S. Popel 2 , Niranjan B. Pandey 2 and Phuoc T. Tran 1, 3 1 Department of Radiation Oncology and Molecular and Radiation Sciences, Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins School of Medicine, Baltimore, MD, USA 2 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Centre and Department of Urology, The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA * These authors have contributed equally to this work Correspondence to: Phuoc T. Tran, email: tranp@jhmi.edu , tranpt21@sbcglobal.net Niranjan B. Pandey, email: npandey4@jhmi.edu , npandey@asclepix.com Aleksander S. Popel, email: apopel@jhu.edu Keywords: hepatocellular carcinoma; angiogenesis; c-Met; HGF; IGF1R Received: April 07, 2017 Accepted: August 26, 2017 Published: September 21, 2017 ABSTRACT Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Due to inadequate screening methods and the common coexistence of limited functional liver reserves, curative treatment options are limited. Liver transplantation is the only curative treatment modality for early HCC. There are multidisciplinary treatment options like ablative treatments, radiation and systemic therapy available for more advanced patients or those that are inoperable. Treatment resistance and progression is inevitable for these HCC patients. Newer therapeutics need to be explored for better management of HCC. HCC is a hypervascular tumor and many pro-angiogenic proteins are found significantly overexpressed in HCC. Here we explored the therapeutic potential of the anti-angiogenic, anti-lymphangiogenic, and directly anti-tumorigenic biomimetic collagen IV-derived peptide developed by our group. Human HCC cell lines HuH7, Hep3b and HepG2 showed significant disruption of cell adhesion and migration upon treatment with the peptide. Consistent with previously described multimodal inhibitory properties, the peptide was found to inhibit both c-Met and IGF1R signaling in HepG2 cells and blocked HepG2 conditioned media stimulation of microvascular endothelial cell (MEC) tube formation. Furthermore, the peptide treatment of mouse HepG2 tumor xenografts significantly inhibited growth relative to untreated controls. The peptide was also found to improve the survival of autochthonous Myc-induced HCC in a transgenic mouse model. Mechanistically, we found that the peptide treatment reduced microvascular density in the autochthonous liver tumors with increased apoptosis. This study shows the promising therapeutic potential of our biomimetic peptide in the treatment of HCC.
Epigenetic Biomarkers in Cancer Epidemiology

Cancer remains a significant global public health issue, with 17.5 million incident cancer cases and 8.7 million cancer deaths in 2015. Although traditional epidemiology methods have significantly improved understanding of etiologic and prognostic risk factors for cancer, leading to targeted interventions, improvements in our understanding of cancer biology and genomics have ushered in a new era of epidemiologic studies integrating molecular biomarkers. Cancer biomarkers have led to improvements in the validity of risk-assessment measures and early detection strategies, and provide insights into disease progression and prognosis, all of which have been useful in targeted, personalized cancer therapies. Epigenetic modification holds significant promise as cancer biomarkers as they can be used to evaluate specific, reversible changes in genes relevant for disease, and can be used to monitor critical events in tumorigenesis. There are challenges in the use of cancer biomarkers, including availability and quality of biospecimen, cost, and logistical challenges with analysis, and for epigenetic biomarkers specifically, more work is needed to fully characterize the range of epigenetic changes in humans. Progress has been made in addressing some of these limitations in recent years, and the ongoing collaborations between basic scientists, geneticists, and population scientists incorporating the use of epigenetic biomarkers into cancer research have significant potential to translate into actionable strategies to reduce the burden of cancer.
Blunt cerebrovascular injury in children: Underreported or underrecognized? A multicenter ATOMAC study

BACKGROUNDBlunt cerebrovascular injury (BCVI) has been well described in the adult trauma literature. The risk factors, proper screening, and treatment options are well known. In pediatric trauma, there has been very little research performed regarding this injury. We hypothesize that the incidence
Pericallosal aneurysm coiling with a “hubbed” 167 cm 0.013″ headway duo via a transradial approach

Abstract Cerebral aneurysms in patients with extreme proximal tortuosity may contraindicate endovascular therapy as a result of both the approach and an inability to navigate a coil-compatible microcatheter into the aneurysm due to microcatheter length. We present a 72 year-old male with multiple medical comorbidities admitted with a grade 3, ruptured pericallosal aneurysm. Aortoiliac disease contraindicated a transfemoral approach and thus a 6 French 105 cm guide catheter was advanced through a 6 French short radial sheath into a bovine left common carotid artery. After straightening proximal access anatomy with an Amplatz wire to allow advancement of the guide catheter into the internal carotid artery, a 167 cm 0.013 in. headway duo was advanced through a 5 French Sofia through the guide catheter and “hubbed” to enter the aneurysm. The aneurysm was then successfully coil embolized with 4 Target Ultrasoft coils. This case illustrates the utility of a 167 cm microcatheter for coil embolization of a pericallosal aneurysm with significant proximal tortuosity via a transradial approach. Despite its 0.013 in. inner diameter and length, common Target coils were compatible and deployed without incident.
H-2-linked genes determine the level of the primary in vitro anti-Mls response.

The level of cell proliferation and interleukin-2 (IL-2) production observed in an anti-Mls mixed lymphocyte reaction between spleen cells from H-2 compatible, Mls incompatible mouse strains is determined by the H-2 haplotype of the mouse combination. Thus, while AKR (H-2k) spleen cells stimulated strong M1sa responses in H-2k responder cells, AKR H-2b spleen cells stimulated no or negligible M1sa responses in responder cells from H-2bmouse strains. This effect was observed at the levels of IL-2 production and cell proliferation. The magnitude of the response observed using F1 (H-2k/H-2b) responder cells was found to be a function of stimulator rather than responder cells. The poor stimulatory capacity of AKRH-2bspleen cells was also shown not to be due to the loss of the stimulatory Mlsaallele during the construction of the congenic strain from AKR and C57BL/6 parental strains. Using stimulator cells from a second series of congenic mice, we found H-2b(strain DLLP) again to represent a poorly Mlsa stimulatory H-2 haplotype. In addition, H-2q (DBA/1) cells displayed very poor Mlsa stimulatory potential while H-2d (D1.C) cells were efficient Mlsa stimulators. Again the effect was shown to be at the level of the stimulator cells. In toto, our findings indicate that the H-2kand H-2dhaplotypes encode strong Mlsa stimulatory potential while the H-2band H-2qhaplotypes determine poor Mlsa stimulatory potential in primary in vitro responses, measured as cell proliferation and IL-2 production.
Electrospinning and its influence on the structure of polymeric nanofibers

Abstract: Electrospinning is a process of creating solid continuous fibers of material with diameter in the micro- to nanometer range by using electric fields. Electrospinning has attracted increased attention in the past few years in a broad range of biomedical and industrial applications due to the ease of forming fibers with a wide range of properties. This chapter discusses the basic electrospinning technique and the factors that influence the process and the resulting nanofibers. Information on the creation of various types of nanofibers (such as hollow, helical, porous, flat, aligned, non-woven and conductive) has also been provided. The section on fiber structure describes some of the unique features of electrospun fibers. The chapter ends with a description of the impact of structure on the properties of fibers (such as mechanical, thermal, transport and surface).
Patient information handouts: taking care of yourself--a self-help guide for patients with cancer.

PURPOSE/OBJECTIVES To present a series of informational cards designed to alert patients to undesirable side effects of cancer treatments, serious complications of cancer, possible oncologic emergencies, and symptoms of cancer metastasis. DATA SOURCES Published articles, clinical experience, consultation with oncologists and oncology nurses, National Cancer Institute and American Cancer Society publications. DATA SYNTHESIS Individualized informational cards were developed and compiled into an easily identifiable University of Wisconsin Comprehensive Cancer Center folder for distribution to patients and families. CONCLUSIONS Most patients and families are receptive to and appreciative of the information provided on the cards. Staff members can use the cards to encourage patients to ask questions and to aid interactions with patients. IMPLICATIONS FOR NURSING PRACTICE Receiving concise, easily understood information helps patients become aware of potential cancer-related problems and encourages them to take appropriate actions before a crisis occurs. This is especially important in today's healthcare system, where patients increasingly are treated on an outpatient basis and where most patients' untoward symptoms will occur when the patient is out of the hospital.
Effect of the support systems' compliance on total hip modular taper seating stability.

Assembly of a femoral head onto the stem remains non-standardized. The literature shows altering mechanical conditions during seating affects taper strength and lower assembly load may increase fre...
The Influence of Temporal Frame on Guilt and Shame Appeals

This work examines guilt and shame appeals through the lens of construal level theory in health messaging. An experiment was conducted to examine the interplay between emotional appeal and temporal...
First clinical application of low cost portable OCT system (Conference Presentation)

Optical coherence tomography (OCT) is currently recognized as the gold standard for identifying retinal structural abnormalities in ophthalmology. However, its availability is often limited to large eye centers and research labs due to its high cost and lack of portability. We present a low-cost, portable spectral-domain OCT system with a total cost of materials under $6,000. Compared to current commercial systems, our design offers 50% size reduction and over 80% cost reduction. Image acquisition interface is incorporated and displayed onto a mounted 7-inch touchscreen. Human retinal imaging is demonstrated, and performance is compared with a commercial OCT system. Based on contrast-to-noise ratio analysis, the low-cost OCT demonstrates comparable imaging capabilities.
A small network simulator for learning routing fundamentals

In this Innovative Practice Full Paper, we present a novel network simulator designed specifically for beginner students (at undergraduate or graduate level) learning the fundamental principles of data communications at the data link and network layers. The simulator can also be used to strengthen programming skills. Simulation is one of the main tools in computer network engineering, both in education and in industry. One of its benefits in education is that it allows every student the freedom to explore, implement and analyze different networks, without requiring the use of physical laboratory infrastructure. This hands-on approach usually complements and supports a lecture course that covers networking theory. Many available network simulators, however, are oriented towards research and industry applications and their complexity can make them difficult to use for beginner students. Furthermore, they do not readily expose the layer-2 and layer-3 algorithms that perform some of the fundamental network functions, and it can be difficult for students to study and modify them. In contrast, the proposed network simulator is tailored to teaching fundamental networking algorithms and network analysis. Some interesting features of the simulator are its very small size and its capability to simulate data flow on arbitrary graphs. The simulator is designed so that students can easily modify it to add to its functionality; it is also fully documented and released under an open-source license.
Electronic structure of the new high-Tc superconductors Tl2Ba2CuO6, Tl2Ba2Cu2O8, Tl2Ba2Ca2Cu3O10, and Tl2BaCa3Cu4O12.

We discuss the electronic structure of the first four members of the high-${T}_{c}$ superconductor family ${\mathrm{Tl}}_{2}{\mathrm{Ba}}_{2}{\mathrm{Ca}}_{L\ensuremath{-}1}{\mathrm{Cu}}_{L}{\mathrm{O}}_{4+2L}$, where $L$ is the number of Cu${\mathrm{O}}_{2}$ layers. Using a simplified BCS-type model, we relate ${T}_{c}$ to $L$ using the partial density of states of the Cu${\mathrm{O}}_{2}$ layers as the physical link. According to our model, the pure phase of ${\mathrm{Tl}}_{2}$${\mathrm{Ba}}_{2}$${\mathrm{Ca}}_{3}$ ${\mathrm{Cu}}_{4}$${\mathrm{O}}_{12}$ ($L=4$) would have a value of ${T}_{c}$ in the range 135 to 165 K.
Inclusion of pathological gambling in DSM-III, its classification as a disorder of impulse control, and the role of Robert Custer

The inclusion of pathological gambling (PG) in DSM-III was a watershed event for the field of gambling studies. Although research is lacking into the circumstances, both the literature and popular ...
The Immigrant Paradox Among the UK’s Adolescents: Data from the LSYPE 2004–2010 Project

The literature on the acculturation of the UK’s ethnic minority youth by generation status is limited. This gap in knowledge base brings to question whether we see different adaption patterns among adolescents from different ethnic groups over time. I examined the sociocultural adaptation of the UK’s ethnic minority youth by comparing first-generation youth to their second plus generation counterparts. By doing so, I establish baseline measures of sociocultural adaptation for first-generation youth for this cohort. I compared 13–15-year-old adolescents on the sociocultural scales of risky behavior (7 items), feelings about school (11 items), mental health (12 items), relational family efficacy (4 items), and bully victimization (5 items), as well as on achievement gains by key stage 3 (9th grade). I used the first Longitudinal Study of Young People in England 2004–2010 database to make these analyses by modeling generation effects, ethnicity effects, and generation × ethnicity interaction effects (Bangladeshi, n = 743; Black African, n = 716; Black Caribbean, n = 990; Indian, n = 1019; Pakistani, n = 963; White immigrant, n = 232). Analyses included multivariate linear regression and hierarchical linear regression when appropriate. My findings demonstrated an immigrant paradox on achievement gains for four of the ethnic groups but an immigrant disadvantage on mental health for White immigrants. I discuss my findings within the contexts of segmented assimilation theory, protective factors, and supports that schools and communities can provide.
CT-based multi-organ segmentation using a 3D self-attention U-net network for pancreatic radiotherapy

Purpose Segmentation of organs-at-risk (OARs) is a weak link in radiotherapeutic treatment planning process because the manual contouring action is labor-intensive and time-consuming. This work aimed to develop a deep learning-based method for rapid and accurate pancreatic multi-organ segmentation that can expedite the treatment planning process. Methods We retrospectively investigated one hundred patients with computed tomography (CT) simulation scanned and contours delineated. Eight OARs including large bowel, small bowel, duodenum, left kidney, right kidney, liver, spinal cord and stomach were the target organs to be segmented. The proposed three-dimensional (3D) deep attention U-Net is featured with a deep attention strategy to effectively differentiate multiple organs. Performance of the proposed method was evaluated using six metrics, including Dice similarity coefficient (DSC), sensitivity, specificity, Hausdorff distance 95% (HD95), mean surface distance (MSD) and residual mean square distance (RMSD). Results The contours generated by the proposed method closely resemble the ground-truth manual contours, as evidenced by encouraging quantitative results in terms of DSC, sensitivity, specificity, HD95, MSD and RMSD. For DSC, mean values of 0.91 ± 0.03, 0.89 ± 0.06, 0.86 ± 0.06, 0.95 ± 0.02, 0.95 ± 0.02, 0.96 ± 0.01, 0.87 ± 0.05 and 0.93 ± 0.03 were achieved for large bowel, small bowel, duodenum, left kidney, right kidney, liver, spinal cord and stomach, respectively. Conclusions The proposed method could significantly expedite the treatment planning process by rapidly segmenting multiple OARs. The method could potentially be used in pancreatic adaptive radiotherapy to increase dose delivery accuracy and minimize gastrointestinal toxicity.
Perovskite-filled membranes for flexible and large-area direct-conversion X-ray detector arrays

The soft nature of metal halide perovskites makes them potentially applicable as flexible X-ray detectors. Here we report a structure of perovskite-filled membranes (PFMs) for highly sensitive, flexible and large-area X-ray detectors. PFMs with areas up to 400 cm2 are formed by infiltrating saturated perovskite solution through porous polymer membranes followed by hot lamination. The good connectivity and crystallization of perovskite crystals in the membranes enable a large mobility–lifetime product. The sensitivity of the X-ray detectors under a field of 0.05 V µm−1 reaches 8,696 ± 228 µC Gyair−1 cm−2 and shows no degradation after storage for over six months and exposure to a dose of 376.8 Gyair, equivalent to 1.88 million chest X-ray scans. The flexible PFMs can be bent at radii down to 2 mm without losing performance. The stand-alone detector array is curved and put inside metal pipes for the detection of material defects with imaging quality superior to flat-panel detectors. Perovskite-filled-membranes enable flexible, sensitive and large-area X-ray detectors. The structures are made by infiltrating perovskite solution into porous polymer membranes.
Stakeholders, Risk from Mercury, and the Savannah River Site: Iterative and Inclusive Solutions to Deal with Risk from Fish Consumption

Many states issue consumption advisories to provide information, mainly to anglers, on the risk from eating fish from contaminated water bodies. The Savannah River passes between South Carolina and Georgia, yet, in 1999, the state-issued consumption advisories for self-caught fish were not in agreement. This chapter examines a stakeholder-driven process that involved state and federal regulators, wildlife biologists, Center for Disease Control, Department of Energy (DOE), fishers themselves, and others to reduce risk for people eating self-caught fish from the river adjacent to the Savannah River Site (a DOE facility). The process included problem formulation, stakeholder identification, identification of the scientific data needed to answer the key questions, development of studies to address these questions, refinement based on stakeholder collaboration, and then development of a mechanism to advise potentially affected persons of the risk. In sum, data on fishing behavior, consumption patterns and mercury levels in fish indicated that people who ate fish frequently were at risk from excess mercury exposure from eating some fish, and an information brochure embraced by the several regulatory agencies and jurisdictions was developed that specifically addressed these issues for people fishing in the Savannah River. This solution sidestepped competing jurisdictional issues between the two states and allowed all parties to create a Fish Fact Sheet brochure that could be distributed annually to those fishing along the Savannah River.
Persistent dysesthesias in involuted infantile hemangiomas: An uncommon complication in a common condition.

Background/objectives Infantile hemangiomas (IHs) are common benign vascular tumors of infancy. IHs tend to grow in the first few months of life and then gradually involute over years, often leaving fibrofatty residua or textural changes in their place. Classically, these lesions are painless throughout their entire natural history; however, we now report on seven patients with involuted IH with intermittent but persistent sensory symptoms. Methods This is a multicenter case series in which members of the Birthmarks Focused Study Group of the Pediatric Dermatology Research Alliance (PeDRA) and the Hemangioma Investigator Group contributed patients with IH and dysesthesias from their clinical practices. Charts were then reviewed to document clinical details. Results Seven patients were included, presenting at an average age of 14.6 years (range 3-48 years) for complaints related to discomfort in the region of involuted IH. The majority (6/7) reported pain or tenderness to the area. One patient reported pruritus. All patients reported intermittent symptoms. The length of symptoms ranged between 4 months and 5 years. Treatment was attempted in 5/7 patients. Ice, oral propranolol, topical capsaicin, and intralesional triamcinolone partially improved symptoms. Conclusions Persistent cutaneous dysesthesias were present in seven patients, in most cases many years after completion of involution. Further research is needed to fully elucidate the pathophysiology and optimal treatments for this IH complication.
A deep learning model for burn depth classification using ultrasound imaging

Identification of burn depth with sufficient accuracy is a challenging problem. This paper presents a deep convolutional neural network to classify burn depth based on altered tissue morphology of burned skin manifested as texture patterns in the ultrasound images. The network first learns a low-dimensional manifold of the unburned skin images using an encoder-decoder architecture that reconstructs it from ultrasound images of burned skin. The encoder is then re-trained to classify burn depths. The encoder-decoder network is trained using a dataset comprised of B-mode ultrasound images of unburned and burned ex vivo porcine skin samples. The classifier is developed using B-mode images of burned in situ skin samples obtained from freshly euthanized postmortem pigs. The performance metrics obtained from 20-fold cross-validation show that the model can identify deep-partial thickness burns, which is the most difficult to diagnose clinically, with 99% accuracy, 98% sensitivity, and 100% specificity. The diagnostic accuracy of the classifier is further illustrated by the high area under the curve values of 0.99 and 0.95, respectively, for the receiver operating characteristic and precision-recall curves. A post hoc explanation indicates that the classifier activates the discriminative textural features in the B-mode images for burn classification. The proposed model has the potential for clinical utility in assisting the clinical assessment of burn depths using a widely available clinical imaging device.
Sinoatrial Reentrant Tachycardia: Inappropriate Sinus Tachycardia

The rare and unusual findings in sinoatrial reentrant tachycardia and inappropriate sinus tachycardia are outlined. This electrophysiologic characters and management are briefly discussed.
Endotoxin-induced tolerance to toxic manifestations of Candida albicans.

Hasenclever, H. F. (National Institutes of Health, Bethesda, Md.) and William O. Mitchell. Endotoxin-induced tolerance to toxic manifestations of Candida albicans. J. Bacteriol. 85:1088–1093. 1963.—Mice exposed to 425 r total body irradiation failed to become tolerant to Candida albicans toxicity after injection with lipopolysaccharide. Mice injected with lipopolysaccharide and then X-rayed did not demonstrate the tolerant state. An injection of thorium dioxide in mice that had previously received tolerance-inducing amounts of lipopolysaccharide rendered them as susceptible to acute C. albicans toxicity as control mice. A bimodal manifestation of tolerance was noted. Groups of mice given single injections of lipopolysaccharide at 6 or 1 days before challenge demonstrated high levels of tolerance, whereas the tolerance in mice given a single dose at 3 days was negligible. The bimodal effect was not observed in tolerant mice challenged with lipopolysaccharide. Injections of viable or nonviable pathogenic fungi known to produce tolerance to the toxicity of C. albicans in recipient mice did not produce tolerance to lipopolysaccharide. Serum from mice injected with lipopolysaccharide showed in vitro inhibitory activity for C. albicans.
Identification of two cardiac glycosides as Na(+)-pump inhibitors in rat urine and diet.

Abstract Endogenous Na(+)-pump specific inhibitors are present in the plasma, urine, and tissues of humans and animals. To date, the source of these inhibitors has not been rigorously defined. In the present study, large amounts of several Na(+)-pump specific inhibitors have been demonstrated to exist in the urine of rats raised on a regular chow diet and tap water. All of the inhibitor levels have been found to increase 1.5-8-fold by the surgical preparation of reduced renal mass (RRM) and one-kidney, one-clip (IK, IC) hypertension. These urinary inhibitors, however, except for the ouabain-like inhibitor which eluted from a high performance liquid chromatography C18 column at the same retention time as [3H]ouabain, disappeared within a week after switching the diet from regular diet (number 5001, PMI Feeds, Inc.) to pure synthetic diet (number 5755). The urinary level of the ouabain-like inhibitor decreased to only one-half of the level in the control rat raised on a regular diet. Two of these inhibitors were purified from both urine and diet by a combination of Amberlite XAD-2 adsorption chromatography, reverse phase low pressure liquid chromatography, and several high performance liquid chromatographies. Reverse phase high performance liquid chromatography, liquid secondary ion and gas-liquid mass spectrometries, and proton nuclear magnetic resonance spectroscopy identified these inhibitors as a stereoisomer of convalloside, probably neoconvalloside, and a mono-rhamnoside of periplogenin or its stereoisomer. These cardiac glycosides exhibited inhibitory potencies comparable to ouabain against ouabain-displacement from Na+,K(+)-ATPase and against 86Rb uptake into human erythrocytes, and they also exhibited cross-reactivity to anti-ouabain antibodies and anti-digoxin antibodies. These results clearly demonstrate that the principal source of most of the inhibitors in rat urine is the diet. The results suggest that the ouabain-like inhibitor may be derived from an endogenous origin.
Collaborative Integration of Speech and 3D Gesture for Map-Based Applications

QuickSet [6] is a multimodal system that gives users the capability to create and control map-based collaborative interactive simulations by supporting the simultaneous input from speech and pen gestures. In this paper, we report on the augmentation of the graphical pen input enabling the drawings to be formed by 3D hand movements. While pen and mouse can still be used for ink generation drawing can also occur with natural human pointing. To that extent, we use the hand to define a line in space, and consider its possible intersection point with a virtual paper that needs to be determined by the operator as a limited plane surface in the three dimensional space at the begin of the interaction session. The entire system can be seen as a collaborative body-centered alternative to the traditional mouse-, pen-, or keyboard-based multimodal graphical programs. Its potential applications include battlefield or crisis management, tele-medicine and other types of collaborative decision-making during which users can also be mobile.
CD4+ T-Cell Responses to Aspergillus fumigatus

This chapter reviews recent advances in understanding Aspergillus fumigatus-specific CD4+ T-cell activation and differentiation. Repeated exposure to fungal antigens is inconsequential in most individuals, due primarily to the rapid induction of antimicrobial defenses by innate immune cells of the airways. In some susceptible individuals, however, a variety of allergic responses to A. fumigatus, including allergic rhinitis, allergic sinusitis, and allergic asthma, can ensue. It has been documented that antigen presentation by pulmonary dendritic cells (DCs) primes Th2-biased CD4+ T-cell responses. One of the most studied mechanisms of pathogen recognition employed by DCs and other innate cells is through the family of Toll-like receptors (TLRs). Although studies of endogenous, polyclonal CD4+ T-cell responses to A. fumigatus have provided valuable information regarding the general kinetics of CD4+ T-cell activation and have demonstrated the contribution of CD4+ T cells in immunity to this fungal pathogen, they have not provided a full picture of CD4+ T-cell responses to A. fumigatus. Priming of CD4+ T cells by activated DCs presenting their cognate antigen results in vigorous T-cell proliferation and expansion of antigen-specific clones that can mediate protection against infection. Although the role of Th17 CD4+ T-cell responses in infection is just starting to be elucidated, it seems that Th17 CD4+ T-cell responses may be particularly important in immunity to fungi. The studies summarized in this chapter provide extensive experimental data demonstrating the participation of adaptive immune responses, in particular by CD4+ T lymphocytes, in antifungal immunity.
Design of complex systems: issues and challenges

Several techniques currently exist to design complex systems. The most common technique used is to divide complex systems into smaller modules (or subsystems), build the modules separately, and later integrate them. Depending on the user requirements and domain-specific and system-specific characteristics, the division is based on factors such as functionality, geographical locations (within the system), and inter-component interactions. Resulting modules have well-defined interfaces. An interface is an abstraction through which the internal details of a module are hidden from other modules. Understanding and tracking the relationships between modules is very important. This paper presents various factors that have to be considered during division of systems. Reuse is the most popular method used to build the modules. Reuse is the process of building systems from existing systems rather than building them from scratch. This concept utilizes general methods and experience of the domain life cycle from earlier product developments, which results in improved productivity, quality and efficiency, while minimizing man-hours, cost, and complexity. Abstraction, selection, customization, and integration are the four steps of this approach (Krueger, 1992). Among these, integration is the most complicated step. Fewer the modules to integrate, easier the integration, but smaller is the chance of reusability. On the other hand, smaller modules result in efficient reuse, but complex integration process. Thus, there is a tradeoff between reusability and integration. Using examples from various domains such as software engineering and health management systems, this paper discusses the concepts mentioned.
BDNF-mediated signal transduction is modulated by GSK3β and mood stabilizing agents

Brain-derived neurotrophic factor (BDNF) is a major neurotrophin in the brain and abnormal regulation of BDNF may contribute to the pathophysiology of mood disorders. In the present study, we examined if alterations in the activity of glycogen synthase kinase-3-beta (GSK3beta) or treatment with mood stabilizers modulated BDNF-mediated signal transduction pathways in differentiated human neuroblastoma SH-SY5Y cells. BDNF increased the phosphorylation of the forkhead transcription factor FKHRL1 through activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, and the phosphorylation of the cyclic AMP response element binding protein (CREB) through activation of extracellular signal-regulated kinase1/2 (ERK1/2). BDNF also increased serine(9) -phosphorylation of GSK3beta, which inhibits GSK3beta activity. Overexpression of GSK3beta did not affect BDNF-induced phosphorylation of Akt, ERK1/2, or FKHRL1, but abolished CREB phosphorylation induced by BDNF. This inhibition of BDNF-induced CREB phosphorylation in GSK3beta-overexpressing SH-SY5Y cells was blocked by treatment with lithium. In contrast to lithium, sodium valproate and lamotrigine did not affect BDNF-mediated signaling, whereas carbamazepine induced a rapid and prolonged phosphorylation of ERK1/2 and CREB in the absence or the presence of BDNF. Therefore, increased GSK3beta selectively attenuates BDNF-induced CREB phosphorylation, and lithium and carbamazepine can facilitate activation of CREB.
Instabilities and Information in Biological Self-Organization

Two classes of self-organizing systems have received much attention, the statistically unstable systems that spontaneously generate new dynamical modes and information-dependent systems in which nonstatistical constraints harness the dynamics. Theories of statistically unstable systems are described in the language of physics and physical chemistry, and they depend strongly on the fundamental laws of nature and only weakly on the initial conditions. By contrast, the information-dependent systems are described largely by special initial conditions and constraints, and they depend only weakly, if at all, on the fundamental laws. This results in statistically unstable theories being described by rate-dependent equations, while the information-dependent systems are described by rate-independent (nonintegrable) constraints. It is argued that an adequate theory of biological self-organization requires that these two complementary modes of description be functionally related, since the key process in morphogenesis is the harnessing of cellular dynamics by the informational constraints of the gene. This could arise if the triggering role of fluctuations could be displaced by informational constraints in the control of the dynamical behavior. However, the spontaneous replacement of chance fluctuations by deterministic informational codes is itself a serious problem of self-organization. At present the only approach requires complementary modes of description for the molecular informational constraints and for the macroscopic dynamical behavior that they harness.
Encrypting virtual memory

In modern operating systems, cryptographic file systems can protect confidential data from unauthorized access. However, once an authorized process has accessed data from a cryptographic file system, the data can appear as plaintext in the unprotected virtual memory backing store, even after system shutdown. The solution described in this paper uses swap encryption for processes in possession of confidential data. Volatile encryption keys are chosen randomly, and remain valid only for short time periods. Invalid encryption keys are deleted, effectively erasing all data that was encrypted with them. The swap encryption system has been implemented for the UVM [7] virtual memory system and its performance is acceptable.
EVIDENCE THAT ASCHOFF BODIES OF RHEUMATIC MYOCARDITIS DEVELOP FROM INJURED MYOFIBERS

Comparative studies on the histopathogenesis of experimentally induced lesions of myocardial Aschoff body type in rabbits and of many myocardial Aschoff bodies from several active rheumatic fever patients have revealed the following: Almost invariably these experimental lesions and very frequently the myocardial Aschoff bodies studied in their early stages have been shown to originate in and evolve from lesions of heart muscle fibers. The mono-, multi-, and non-nuciested cell masses, most characteristic of myocardial disease of the rheumatic type, appear to be damaged muscle fibers their fragments, and syncytial cell masses of probable muscular origin that proliferate from beneath the sarcolemma and in the tracks of damaged muscle fibers in reaction to that damage. In addition to destructive changes in cardiac muscle fibers an attempt at myofiber regeneration may occur in some myocardial Aschoff bodies. The most distinguishing histologic feature of the myocardial Aschoff bodies in rheumatic heart disease are the peculiar lesions of muscle fibers. Therefore, it is proposed that they be designated as myofiber Aschoff bodies in order to indicate their origin more accurately. The results of these investigations contrast with the widely accepted theory that all myocardial Aschoff bodies originate as injured interstitial collagen, and that, as they evolve, they consist of damaged interstitial collagen intermingled with cells of non-myogenic derivation that proliferated in response to that collagen injury. These studies, furthermore, provide evidence that experimental homologues of rheumatic myocardial Aschoff bodies have been induced in a very few among many rabbits subjected to reposted focal infections with group A streptococci of different serological types. Hence, they support the concept that the myocardial Aschoff bodies of rheumatic fever are induced by repeated infections with group A streptococci of several different serological types; even though only a certain few among the many patients so infected develop these lesions.
The Origami Exercise: Exposing Students to Training Effectiveness and Assessment

Training is an important Human Resource Management (HRM) function. Training not only provides employees with knowledge and skills to more effectively perform their jobs, it can directly contribute to the bottom line. Training programs must deliver important skills and the assessment of their effectiveness is essential. In this experiential exercise, students are trained, act as trainers of other students, and participate in the assessment of training effectiveness. The exercise provides feedback to student trainers on communication skills. It also allows students to see different types of information collected from a variety of training assessments. Analyses of class-generated data are also provided.
Locus coeruleus activity in vitro: intrinsic regulation by a calcium- dependent potassium conductance but not alpha 2-adrenoceptors

Locus coeruleus neurons recorded intracellularly in rat brainstem slices exhibited spontaneous activity and a marked afterhyperpolarization following a burst of spikes. This afterhyperpolarization was associated with an increase in membrane conductance and resulted in a marked postactivation inhibition of spontaneous activity. Since the reversal potential of the afterhyperpolarization was found to be virtually identical when recorded with KCl or potassium acetate-filled electrodes and shifted in the hyperpolarizing and depolarizing direction with decreases and increases in extracellular potassium concentrations, respectively, the afterhyperpolarization seen following a burst of spikes in this cell group appears to be mediated by an increase in potassium conductance. The afterhyperpolarization and postactivation inhibition were markedly attenuated by reducing calcium influx by either omitting extracellular calcium in the bathing medium or blocking calcium channels with manganese or cadmium. Thus, the afterhyperpolarization and the resulting postactivation inhibition appear to be largely mediated by the activation of a calcium-dependent potassium conductance. Previous reports in vivo have suggested that activation of alpha 2-adrenoceptors by norepinephrine release from recurrent axons or dendrites may mediate self-inhibition in the locus coeruleus. In this study, we examined the effect of blocking alpha 2-adrenoceptors on the afterhyperpolarization and postactivation inhibition. Administration of the alpha 2- adrenoceptor antagonist piperoxane failed to produce any changes in either of these parameters, suggesting that at least in vitro the afterhyperpolarization and postactivation inhibition seen in locus coeruleus neurons do not result from the activation of alpha 2- adrenoceptors.
Chree analysis of pressure-temperature-corrected cosmic-ray burst frequencies

By Chree’s method of superposed epochs, recurrence phenomena (1) and relations to other variables (4) had been found in the frequency of occurrence of small cosmic-ray bursts in a heavily shielded chamber at 1 646 meters altitude and 49° N geomagnetic latitude. The recurrences at intervals of about 27 days have been found to persist after correction of the burst data for variations in barometric pressure and atmospheric temperature by application of the very large coefficients,-4.58 ±0.22 percent/mm Hg and -2.53 ±0.10 percent/°C, determined recently (6). A defense of the Chree method of analysis is included.
α2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons

Abstract Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium channels are one likely target for such modulation. We used the whole-cell patch-clamp technique to study noradrenergic modulation of barium currents in acutely dissociated pyramidal neurons from rat sensorimotor cortex. Extracellular application of specific agonists and antagonists revealed that norepinephrine (NE) reduced Ca 2+ current. A major component of this modulation was due to activation of α 2 receptors. Activation of α 2 -adrenergic receptors resulted in a fast, voltage-dependent pathway involving G i /G o G-proteins. This pathway targeted N- and P-type calcium channels The α 2 modulation was partially reversed by repeated action potential waveforms (APWs). N- and P-type channels have been implicated in synaptic transmission and activation of afterhyperpolarizations in these cells. Our findings suggest that NE can regulate these cellular processes by mechanisms sensitive to spike activity.
Nuclear Magnetic Resonance in Phase Stud: LiCl-CrCl 3

THERE is evidence for reaction between mixtures of pure anhydrous LiCl and CrCl3 when they are fused at between 500° and 700° C, and the resultant melts are cooled. An equation can be written This evidence consisted of the destruction of the characteristic purple, insoluble layer crystals of CrCl3 and the formation of a pink salt soluble in water. Reaction 1 is written in analogy to the reactions believed to occur in the NaCl–CrCl3 and the KCl–CrCl3 systems with fusion and cooling. Cook1 has reported the formation of Na3CrCl6 and K3CrCl6 in these systems. Such reactions can be regarded as depolymerizing reactions without change in either the covalence or oxidation state of the central metal atoms.
Molecular dynamics simulations of highly charged green fluorescent proteins

A recent experimental study showed that green fluorescent proteins (GFPs) that have been mutated to have ultra-high positive or negative net charges, retain their native structure and fluorescent properties while gaining resistance to aggregation under denaturing conditions. These proteins also provide an ideal test case for studying the effects of surface charge on protein structure and dynamics. Classical molecular dynamics (MD) simulations have been performed on the near-neutral wildtype GFP and mutants with net charges of −29 and +35. The resulting trajectories were analysed to quantify differences in structure and dynamics between the three GFPs. This analysis shows that all three proteins are stable over the MD trajectory, with the near-neutral wild type GFP exhibiting somewhat more flexibility than the positive or negative GFP mutants, as measured by the order parameter and changes in ϕ–ψ angles. There are more dramatic differences in the properties of the water and counter ions surrounding the pro...
Using Videotape to Evaluate Medical Students' Physical Examination Skills

A videotaped evaluation methodology was used to assess second year medical students' physical examination skills. Students were assigned to groups of three where each student in the group served as the physician, the patient, and the camera person until all students had been videotaped performing an examination. Each group of three students reviewed the videotapes and evaluated their own as well as their peers' performance using criterion-based checklists. Faculty and staff members also reviewed the tapes and evaluated the examinations using the same evaluation checklists as the students. This videotaping evaluation methodology provides several benefits: (1) patients are not required, thus increasing flexibility in scheduling and evaluation opportunities; (2) technical staff can monitor and run the videotaping sessions; and (3) faculty can review the videotapes in their off hours rather than trying to observe the examinations during a busy day. Additionally, the peer and self-assessments based upon checkl...
Making Connections: Using Skill Theory to Recognize How Students Build and Rebuild Understanding.

In this companion to Marc Schwartz and Kurt Fischer's article, Patricia King and JoNes VanHecke describe how student affairs educators can help students become sophisticated thinkers.
Evolutionary appearance of mononucleotide repeats in the coding sequences of four genes in primates

The replication instability of homopolymeric nucleotide runs is associated with several human diseases and has linked with colorectal cancers (Shibata et al. 1994). Little is known, however, about the evolutionary pattern of these sequences. The aim of this study was to analyse the long homopolymeric nucleotide runs that are unstable regions subject to replication errors, present in the coding sequence of four genes, TGFBRII, BAX, MSH6 andMLH3, in six nonhuman primates encompassing 55 million years of evolution, and in humans. The results show that the (A)10 of TGFBRII and the (G)8 of BAX are already present in the ancestral ring-tailed lemur. The (C)8 of MSH6 appears during the orangutan–gorilla divergence and the (A)9 ofMLH3 coexists with a putative precursor of the homopolymeric nucleotide runs until the rhesus macaque–orangutan divergence. Variations between clones of the homopolymeric nucleotide runs in each species are probably somatic changes due to slipped mispairing. They are not observed with homopolymeric nucleotide runs of less than eight nucleotides and, with runs of eight nucleotides or more, there is a tendency toward an increase in the sequence variations with the length of the run.
The hyperstoichiometric ZrMn1 + xFe1 + y−H2 system I: Hydrogen storage characteristics

Abstract The ZrMn1 + xFe1 + y−H2 systems with x,y = 0.11-0.53 and x + y ⩽ 0.64 were studied as a function of composition, temperature (0–200 °C) and hydrogen dissociation pressure (0.01–50 atm). The hyperstoichiometric manganese and iron appear to substitute at the zirconium sites with a net effect of raising the vapor pressure of their hydrides to 500–1500 times that of ZrMn2 hydride. The ZrMn1.27Fe1.58 alloy does not absorb measurable quantities of hydrogen, presumably because of the very high vapor pressure of its hypothetical hydride. The hydrides of ZrMn1.22Fe1.11 and ZrMn1.11Fe1.22 alloys have dissociation pressures in the range of 1–2 atm at room temperature. The hydrogen capacities of these alloys are quite high, e.g. about 185 cm3 g−1. Enthalpies and entropies of dehydrogenation, obtained from a van't Hoff plot of ln pH2versus 1/T, are very low, being 9.8–13.4 kJ (mol H2)−1 and 42–53 J (mol H2)−1 K−1 respectively. The kinetics of hydrogen absorption and desorption are extremely fast.