cssi/SciSciGPT-SciSciNet huggingface dataset:
The effect of implant macro-thread design on implant stability in the early post-operative period: a randomized, controlled pilot study.

Introduction Available literature suggests there is a transient drop in implant stability from approximately week 0 to week 3–4 as a result of peri-implant bone remodeling as it transitions from a primary, mechanical stability to a secondary, biological stability. Research investigating the influence of macro-thread design on this process is scant. Aim The specific aim of this study was to evaluate the role of macro-thread design on implant stability in the early post-operative healing period using resonance frequency analysis (RFA). Material and methods Seven patients, each missing at least two posterior teeth in the same arch, were included in the study. Three patients qualified for four implants resulting in a total of 10 matched pairs. All sites were healed (>6 months), non-grafted sites with sufficient bone to place implants. Each site in a matched pair was randomly assigned to receive either a control (Megagen EZ Plus Internal; EZ) or test (Megagen AnyRidge; AR) implant. The test implant incorporates a novel thread design with a wide thread depth and increased thread pitch. RFA was used to determine implant stability quotient (ISQ) values for each implant at the time of placement and weekly for the first 8 weeks. Results Implants consistently achieved a relatively high insertion torque (30–45 N/cm) and high initial ISQ value (79.8 ± 1.49). Baseline ISQ values for test (AR; 79.55 ± 1.61) and control (EZ; 80.05 ± 1.37) implants were similar. A general pattern of stability from baseline through all eight follow-up evaluations was observed for the test implants. A pattern of decreasing ISQ values was observed for the control implants across the early follow-up evaluations up to week four, where the value plateaued. There was a statistically significant main effect due to implant type (P < 0.01) and a statistically significant interaction between implant type and time (P < 0.01), indicating that the test and control implants performed differently at certain time points. Conclusions Within the limitations of this study, macro-thread design appears to play a role in implant stability in the early post-operative healing period as assessed by RFA. These findings may have important implications related to immediate or early loading protocols.
Balancing Difficulty of Performance Targets: Theory and Evidence

We examine how firms balance the relative importance of financial and nonfinancial performance measures in their annual bonus plans. We present a theoretical model showing that managerial allocation of effort is a function of both relative incentive weights and the difficulty of performance targets. We find that relative incentive weight and target difficulty can be either complements or substitutes in motivating effort depending on the extent to which managers have alternative employment opportunities. We use survey data on the choice of performance targets in 1,217 companies to test the predictions of our model. Consistent with the model, we find that when firms are greatly concerned about managerial retention, relative incentive weights are negatively associated with perceived target difficulty. Conversely, when retention concerns are low, relative incentive weights are positively associated with target difficulty. Combined, our study extends prior work by highlighting the importance of balancing target difficulty when designing performance measurement systems.
Comparison of exosomal microRNAs secreted by 786-O clear cell renal carcinoma cells and HK-2 proximal tubule-derived cells in culture identifies microRNA-205 as a potential biomarker of clear cell renal carcinoma

Previous reports have indicated that the abundance of specific microRNAs (miRNA) contained within the exosome/microvesicle compartment of patient biofluids may be useful in diagnosing specific types of cancer. In the present study, the 786-O cell line, which is derived from a clear cell renal cell carcinoma (ccRCC), was used as an in vitro ccRCC tumor model and the human renal proximal tubule cell line HK-2 was used as its normal renal tissue control to investigate the similarities of exosomal content of selected ccRCC miRNA biomarkers in the supernatant with the content of those markers in the cells themselves. A PCR array identified miRNA biomarkers of solid RCC tumors (miR-210, MiR-34a, miR-155-5p and miR-150-5p) that were increased by 2-8 fold in 786-O exosomes compared with the control. These were subsequently chosen for further investigation using TaqMan RT-qPCR in addition to miR-15a and miR-205, which were selected based on prior interest as RCC biomarkers. MiR-15a, -34a, -210 and -155 levels were significantly lower in exosomes when compared with that in whole cells but did not differ between the HK-2 and 786-O cells in either the cytoplasmic, exosome or exosome-free supernatant fractions. By contrast, cytoplasmic miR-150 and miR-205 exhibited significant differences in concentration between the two cell lines. In addition, the cytoplasmic content of miR-150 and miR-205 was mirrored in the exosomal content of these miRNAs. Furthermore, the difference in exosomal miR-205 content was statistically significant. The present study indicated that measurements of the exosomal content of miR-205 and possibly miR-150, but not those of the other examined miRNAs, are proportional to their respective contents in the cells that secreted them. These findings suggest that in vitro RCC systems may be useful in identifying miRNAs with sufficiently high levels of exportation into exosomes; and with sufficiently different expression levels between tumor and normal cells to serve as ccRCC biomarkers in vivo.
Towards Achieving Accountability, Auditability and Trust in Cloud Computing

The lack of confidence in entrusting sensitive information to cloud computing service providers (CSPs) is one of the primary obstacles to widespread adoption of cloud computing, as reported by a number of surveys. From the CSPs’ perspective, their long-term return-on-investment in cloud infrastructure hinges on overcoming this obstacle. Encryption and privacy protection techniques only solve part of this problem: in addition, research is needed to increase the accountability and auditability of CSPs. However, achieving cloud accountability is a complex challenge; as we now have to consider large-scale virtual and physical distributed server environments to achieve (1) real-time tracing of source and duplicate file locations, (2) logging of a file’s life cycle, and (3) logging of content modification and access history. This position paper considers related research challenges and lays a foundation towards addressing these via three main abstraction layers of cloud accountability and a Cloud Accountability Life Cycle.
Editorial: Software engineering challenges of the Net generation

The theme of the 2008 IEEE Conference on Software Engineering Education and Training (CSEE&T'08) was ''Educating the Net Generation of Software Engineers.'' The theme acknowledged the vital role that Internet technologies and applications play in the society and the importance of properly educating and training the ''Net'' generation of software engineers. The Net generation characterizes the current students who may have never known life without the Internet. Their early and ubiquitous exposure to technology has defined their styles, their modes of communication, their learning preferences, their social choices, and their entertainment preferences. Additionally, the realities of the software industry for which the Net generation need to prepare have shifted from that of the foundational beliefs and practices of many software engineering educators. Thus the educators need to become familiar with the Net era's teaching and training challenges, to investigate the peculiarities of educating and training Net software engineers, and to identify the necessary ingredients for success and for improving our teaching practices and course delivery methodologies. In addition, Gartner (http://www.gartner.com) has projected the world market for open source software to grow to $35B before the end of this decade. How do we need to change our curriculum to prepare students to develop open source software? The number of security attacks on software is growing exponentially each year. How do we teach students to build security into their software and to implement software consistent with privacy policies? Increasingly, software development teams are geographically distributed as teams are disbursed throughout the globe and as telecommuting is on the rise. Are students learning about communication and coordination practices for working in these distributed teams? As educators, how do we adjust our teaching to meet the personal preferences and technical challenges of the net generation of software engineers? These and similar open issues were addressed at the CSEE&T '08 in a number of keynotes, technical and experience papers, presentations, and workshops. A number of these were selected and further extended for the current issue of the Journal of Systems and Software. A summary of each article is provided below.
Analysis of Classical Biological Control Programs

As noted in Chapter 8, p. 128 or more pest insects and weeds have been completely or substantially controlled by imported natural enemies (Table 9.1). Some of these have been of minor or localized status, while others have been species of continental distribution and great economic importance. In certain cases success was attained with but modest effort, while in others success came only after elaborate preparation, dogged perseverance over many years, and great expense. Among the pest insects, by far the greatest number of successes have been scored against homopterous species, particularly diaspine and lecaniine scales. Some researchers have suggested that scale insects are particularly amenable to biological control because, being sessile during much of their life cycle, they cannot escape or avert natural enemies, and the colonies once found are vulnerable to maximum exploitation. But others point out that scale insects are particularly common pests of horticultural crops such as citrus, and that the considerable success against them may simply reflect the greater emphasis placed on biological control of such orchard pests. There is probably some validity to each contention, but this is perhaps irrelevant, for striking successes have also been scored against species of Coleoptera, Lepidoptera, Diptera, and Hymenoptera in a variety of situations. This is evidence enough that the chances for successful biological control exist across a wide spectrum of the major pest groups.
Violence Risk Assessment

Violence risk assessments can be difficult to grasp for many, especially in the context of a changing environment regarding how to evaluate different types of violence. Many psychometric tools, including scales and questionnaires, have been and continue to be utilized for the purposes of assessing violence toward self or others. These sorts of means provide a sense of confidence that, without clinical experience, can be easily misrepresented and misinterpreted. It is extremely important to rely on a robust clinical acumen and wide range of patient encounters, as well as availing ourselves of all the resources possible, including legal and clinical collateral sources of information and from those close to the person in question before resting on the results of a single data point. In the case to follow, a child in school needed to be evaluated as to the risk he posed toward classmates, and it is important to mention the exhaustive amount of research and reviewing of relevant documents that went into the opinion rendered. As the breadth of those included in the forensic mental health field widens, it is paramount to maintain an expertise in the clinical evaluation first and foremost, before utilizing generalizable research tools when formulating our opinions. The tests are indicators that have to be validated clinically. The purpose of a measuring device (questionnaires/testing) is to provide data for decision-making. In other words, the results of a scored test should supplement a clinical evaluation and never the other way around. I would also like to highlight that when assessing for violence risk whether appearing to be physical or sexual, we may find ourselves more quickly to err on the side of caution, especially when the stakes are high, that is, the safety of individuals is a concern. Risk is the probability that something undesirable happens. On the same token, it is important to always remember that we are not asked to predict whether an event will take place – our ability to “fortune-tell” is, although sometimes wished, outside of our professional scope. To that end, we will only be able to ascertain whether or not a pattern of behaviors will fit a model that comes with the individual in question. To assess this, we must understand how an individual’s personality fits in with their social structures and support systems, their motivations, the presence of a psychiatric disorder, and so on. The most important modifiable risk factor is mental illness. Assessing risk is a process, not an event. When risk factors compound, the risk increases. Our job is to assess for the presence of risk factors, not for the prediction of its occurrence.
CENTERS FOR DISEASE CONTROL AND PREVENTION’S HEALTHY BRAIN INITIATIVE: A PUBLIC HEALTH APPROACH TO COGNITIVE HEALTH

Cognitive health, a crucial component of healthy aging, is a recently recognized public health issue. CDC, through its Healthy Brain Initiative, is working to advance cognitive aging as a vital, integral component of public health practice, in an effort to keep older Americans healthy and independent as long as possible. The Healthy Brain Initiative creates and supports partnerships, collects and reports data, increases awareness of cognitive aging, through utilization of its flagship publication, The Healthy Brain Initiative: The Public Health Road Map for State and National Partnerships, 2018–2023. The Road Map outlines 25-items within its Action Agenda that identify how state and local public health agencies and their partners can promote brain health, address cognitive impairment for persons living in the community, and address the needs of caregivers to persons with a cognitive impairment. Because dementia, including Alzheimer’s disease, doesn’t have a cure, identifying and reducing risks are the best public health approaches for maintaining health and independence. The session will emphasize activities of partners implementing Road Map action items: The Alzheimer’s Association, a national organization providing assistance to state public health agencies; activities of CDC’s Healthy Brain Research Network which is a thematic network of the CDC Prevention Research Centers Program; and The Balm in Gilead’s efforts to increase awareness of cognition-related issues in African-American healthcare professionals and faith-based organizations; American College of Preventive Medicine will highlighted a new collaborative continuing education module for physicians; and the discussant will describe the HBI from a historical perspective and impact.
CHAPTER 238 – Regulation of the NADPH Oxidase by Rac GTPase

Phagocytic leukocytes play critical roles in the innate immune response to pathogens. An important component of this response is the ability of leukocytes to generate reactive oxygen species (ROS) via a membrane-associated NADPH oxidase. This multicomponent enzyme utilizes electrons derived from intracellular NADPH to generate superoxide anion, which subsequently dismutates to H2O2 and other ROS that are used for host defense. The NADPH oxidase of phagocytic leukocytes was the first identified, and remains one of the best-characterized, Rho GTPaseregulated systems. Historically, the involvement of a GTP binding protein in the NADPH oxidase regulation was suspected when guanine nucleotide analogs such as GTPƔS and Gpp(NH) p were found to enhance superoxide production in cell-free assays. A requirement for a prenylated cytosolic component suggested the involvement of a small GTPase. Subsequently, it was simultaneously shown that either Racl or Rac2 GTPase was required for oxidase activity in the cell-free system, with Rac2 being the predominantly active isoform in human neutrophils. Several additional lines of evidence have established that Rac is an integral and required component of the NADPH oxidase. Rac antisense oligonucleotide inhibited superoxide production in Epstein-Barr virus (EBV)-transformed B lymphocytes. In neutrophils of bcr-null transgenic mice, Rac activity was increased due to the loss of a GTPase-activating protein, Bcr, and superoxide production was concomitantly increased, suggesting that not only is Rac activation required, but that it may be rate-limiting for oxidase activity. Finally, the generation of Rac2-null mice led to the demonstration that rac2 -I- neutrophils had significantly reduced or absent superoxide production in response to various stimuli.
The Price of Bread: Regulating the Market in the Dutch Republic

A prime contemporary concern - how to maintain fair market relations - is addressed through this study of the regulation of bread prices. This was the single most important economic reality of Europe's daily life in the early modern period. Jan de Vries uses the Dutch Republic as a case study of how the market functioned and how the regulatory system evolved and acted. The ways in which consumer behaviour adapted to these structures, and the state interacted with producers and consumers in the pursuit of its own interests, had major implications for the measurement of living standards in this period. The long-term consequences of the Dutch state's interventions reveal how capitalist economies, far from being the outcome of unfettered market economics, are inextricably linked with regulatory fiscal regimes. The humble loaf serves as a prism through which to explore major developments in early modern European society and how public market regulation affected private economic life.
Mixed-Effects Models

We have covered a variety of statistical models in this book, but all have shared a common feature: The criterion and error term were treated as random variables, but all of the predictors were assumed to be fixed. In this chapter, we will consider models that include a broader mixture of fixed and random variables. For obvious reasons, these models are called mixed-effects models or mixed models.
Pharmacogenetics of therapeutics

Abstract Genetic biomarkers that can change a drug pharmacokinetics and pharmacology; absorption, distribution, metabolism, and excretion; drug-target engagement and reaction of a human body to a drug effect and, hence, an overall drug efficacy and/or toxicity; and the laboratory tools to evaluate those genes are called pharmacogenetics and pharmacogenomics (PGx). The concept has been known since the ancient time but with the advancement in molecular technologies, the approach has been heavily investigated and considered in drug development and patient standard of care. Some genetic variants can change exposure of two individuals from the same drug dose taken by the same route of administration by up to 600-fold. This chapter will summarize more than 70 PGx biomarkers (or biomarker panels) that have been listed on more than 360 drug labels for different purposes. Examples from each category of PGx biomarkers will be handled in more details, including prevalence of different polymorphic forms in different ethnic populations.
Readability and Understandability Analysis of Online Materials Related to Abdominal Aortic Aneurysm Repair

Background:Patients commonly use online materials as a source of health information. Since poor health literacy has been shown to correlate with negative outcomes, it is recommended that patient-di...
The effect of methadone on the hypothalamic pituitary gonadal axis and sexual function: A systematic review

Abstract Background Opioid abuse is a public health crisis. As opioid misuse worsens, efforts are being made to increase access to medication-assisted treatments. Methadone is a medication-assisted treatment used to treat opioid dependence and chronic pain. While methadone is beneficial in the treatment of opiate abuse and chronic pain, side effects of the medication include hormonal and sexual function changes. The purpose of this report is to review the effects of methadone on the hypothalamic pituitary gonadal axis hormones and sexual functioning in males and females. Methods A search of PubMed was conducted using pre-defined criteria, resulting in the evaluation of 295 articles. A total of 72 articles, including 52 human studies and 20 animal studies, met the selection criteria and were reviewed. The included studies examined the effects of methadone on the hypothalamic pituitary gonadal axis and/or sexual function. Results There was evidence of methadone-induced hormonal changes, disruptions in the hypothalamic pituitary gonadal axis, and sexual dysfunction, although there was some variability in the results of the reviewed studies. Differences in methadone dose and length of exposure to treatment appears to influence the variability in the results. Much of the literature examines the effects of methadone in males, with very limited research examining the effects in females. Conclusions Despite its effectiveness for opiate abuse and chronic pain treatment, methadone has disruptive effects on the hypothalamic pituitary gonadal axis and sexual function. Further research is warranted to better define potential methadone-induced endocrine consequences and to further examine the effects of methadone in females.
Staphylococcus aureus toxin suppresses antigen-specific T cell responses

Staphylococcus aureus remains a leading cause of human infection. These infections frequently recur when the skin is a primary site of infection, especially in infants and children. In contrast, invasive staphylococcal disease is less commonly associated with reinfection, suggesting that tissue-specific mechanisms govern the development of immunity. Knowledge of how S. aureus manipulates protective immunity has been hampered by a lack of antigen-specific models to interrogate the T cell response. Using a chicken egg OVA-expressing S. aureus strain to analyze OVA-specific T cell responses, we demonstrated that primary skin infection was associated with impaired development of T cell memory. Conversely, invasive infection induced antigen-specific memory and protected against reinfection. This defect in adaptive immunity following skin infection was associated with a loss of DCs, attributable to S. aureus α-toxin (Hla) expression. Gene- and immunization-based approaches to protect against Hla during skin infection restored the T cell response. Within the human population, exposure to α-toxin through skin infection may modulate the establishment of T cell-mediated immunity, adversely affecting long-term protection. These studies prompt consideration that vaccination targeting S. aureus may be most effective if delivered prior to initial contact with the organism.
Comparing synchronous and asynchronous online discussions for students with disabilities: The impact of social presence

Abstract The affordances of online learning have the potential to improve learning outcomes for students with disabilities by allowing customization and flexibility to meet individual needs. However, there are significant executive function and language processing demands that may be particularly challenging for this population. With that in mind, interventions guided by social presence theory may increase students' ability to engage in online settings. This study implemented a computer mediated, blended classroom setting in order to assess students’ understanding of statistics concepts following synchronous and asynchronous online, video-based discussion sessions. Social presence theory predicts that the immediacy of synchronous interactions should improve social presence, thereby increasing student engagement and performance. Data was collected from 105 students with high-incidence disabilities using a mixed methods experimental design with a within subjects quantitative component. Our findings indicate that while students with disabilities expressed preference for synchronous discussions, including self-reported greater engagement and self-reported improved comprehension, their performance on assessments of conceptual understanding was slightly better following asynchronous discussions. Implications for these disparities between preference and performance are discussed.
Fractography of silicon nitride based ceramics to guide process improvements

Abstract Fractography is an important tool to understand and identify the cause of the failure in materials. This understanding can be used to make changes in raw materials selection and processing to increase the strength of brittle materials. This study reports the fracture behavior of hot-pressed silicon nitride based ceramics, with focus on dominant flaw identification with respect to material and process parameters. Silicon nitride is an important material for structural applications which require high strength and wear resistance, such as bearings, nozzles, and cutting tools. Silicon nitride with a target base composition of Si6-zAlzOzN8-z (z = 0.5), along with varying boron dopant levels, was explored in this work. Detailed fractographic analyses revealed that the majority of fracture origins were internal flaws due to the foreign impurities introduced at various stages of processing. All materials were found to have reasonably high strength (800−1100 MPa). Strength was inversely proportional to the square root of the flaw size, however no correlation was found between measured flexural strength and fracture origin types. Mirror constants calculated from fracture mirror measurements ranged between 5.8 and 9.8 MPa.m1/2.
Efficacy of immune checkpoint inhibitors (ICIs) in rare histological variants of bladder cancer.

502Background: ICIs are effective agents in metastatic urothelial carcinoma in both platinum-refractory and frontline settings. Responses in patients (pts) with non-urothelial histological variants...
Family Processes and Mental Health among Children and Caregivers in a Family Strengthening Program

Oppositional defiant disorder (ODD) is a common mental health concern and is particularly prevalent among children living in poverty-impacted communities. A family strengthening/parent management training (PMT)-based multiple family group (MFG) program entitled, the 4 Rs and 2 Ss for Strengthening Families, focuses on the following family process variables: rules, responsibilities, relationships, respectful communication, social support, and stress. While evidence supports effectiveness of this treatment program, less is known about the specific relationship between the family process variables and mental health outcomes of children and caregivers. The current study examined these relationships among a sample of 287 caregiver/child dyads who participated in a NIMH-funded Type II hybrid effectiveness-implementation study in New York City. Data were analyzed using SPSS 27 and Mplus 8. Results indicated that two of the six family process variables related to one or more child and caregiver mental health outcome. Caregiver stress significantly related to child inattention (b = 0.034, SE = 0.01, p < 0.001), child ODD (b = 0.053, SE = 0.02, p < 0.01), and caregiver depression (b = 0.049, SE = 0.02, p < 0.01). Family rules significantly related to caregiver depression (b = 0.228, SE = 0.11, p < 0.05) over time. Findings point towards the substantial role of caregiver stress in child and caregiver mental health, in addition to the impact of inconsistent discipline with difficulty establishing rules on caregiver depression. Examinations of treatment components in relation to improvements in child and caregiver mental health can guide practitioners towards utilizing models that result in positive therapeutic outcomes and/or making adaptations with added content that has been shown to be effective.
Salt Marsh Plant Community Structure Influences Success of Avicennia germinans During Poleward Encroachment.

Along the Florida coast, decreasing freeze events are promoting the range shift of the mangrove species Avicennia germinans northward into temperate salt marsh wetlands. Although plant species’ ranges are tightly linked with their climatic tolerances, there is considerable variability in the magnitude by which biotic factors like competition and facilitation may also influence range shifts. Changes in mangrove and marsh plant abundance can alter both the above and belowground environment, which may in turn influence ecosystem services typically associated with these systems such as storm surge abatement and carbon storage. Therefore, it is key to understand (1) how the above and belowground environment of established salt marshes influences establishment of mangroves, and (2) how above and belowground environments shift in response to mangrove encroachment. Using a semi-natural mangrove planting experiment, we investigated the impact of four distinct marsh plant community structures (Batis maritima, Spartina alterniflora, mixture of B. maritima and S. alterniflora, mudflat) on mangrove survivorship and decomposition rate. In mixed marsh plots, mangrove survivorship was 42 % higher compared to survivorship in mudflat plots, and decomposition rate was 47 % greater in mixed marsh plots compared to mudflat. However, percent cover of vegetation differed across treatments, and was highest in mixed marsh plots. High survivorship in mixed marsh plots is likely due to increased protection from physical stressors by the dense aboveground cover, and belowground plant root-driven effects such as nutrient availability and oxygen delivery. Our findings suggest that above and below ground differences in salt marsh plant community structure can have an impact on the survival of encroaching mangroves, which may have implications for predicting future mangrove encroachment and improving mangrove restoration techniques.
Segregation engineering of grain boundaries of a metastable Fe-Mn-Co-Cr-Si high entropy alloy with laser-powder bed fusion additive manufacturing

Abstract Laser-powder bed fusion (L-PBF) additive manufacturing offers unprecedented microstructural fine-tuning capabilities. Naturally, benefitting from such capability requires alloys that are amenable to microstructural heterogeneity and hierarchy (MHH) and that exhibit a low hot-cracking susceptibility (HCS). However, columnar growth, which is characterized by capillary effects and poor strain accommodation capabilities, is prevalent in L-PBF and increases the HCS of the processed alloys. Further, while solute segregation is prominent in cellular and dendritic growth modes during L-PBF, the effects of solute segregation on the alloy HCS and L-PBF processing window remain widely unexplored. Here, we demonstrate that solute segregation affects columnar growth, grain coalescence behavior during solidification, MHH and mechanical properties of a metastable Fe40Mn20Co20Cr15Si5 (at.%) high entropy alloy (CS-HEA) doped with 0.5 wt.% B4C (termed CS-BC). A theoretical framework is proposed, which reveals that a boundary-strengthening segregant may reduce the alloy HCS during L-PBF. In as-built CS-BC, boron, a boundary strengthener, segregated to the solidification cell boundaries, whereas carbon remained in the solid solution. The as-built CS-BC exhibited suppressed columnar growth, more random texture, smaller cell size and higher strength as compared to the as-built CS-HEA. Further, a wide crack-free L-PBF processing window of CS-BC allowed fine-tuning of its MHH and thus the mechanical properties. Upon annealing, as carbon-containing precipitates formed, CS-BC exhibited a metastable microstructure and transformation induced plasticity effect, which led to high synergistic strength-ductility. These findings will foster design of alloys that facilitate application-specific manufacture with L-PBF and thus, an extended outreach of L-PBF for structural applications.
Acquisition of Portal Venous Circulating Tumor Cells From Patients With Pancreaticobiliary Cancers by Endoscopic Ultrasound

Background & Aims Tumor cells circulate in low numbers in peripheral blood; their detection is used predominantly in metastatic disease. We evaluated the feasibility and safety of sampling portal venous blood via endoscopic ultrasound (EUS) to count portal venous circulating tumor cells (CTCs), compared with paired peripheral CTCs, in patients with pancreaticobiliary cancers (PBCs). Methods In a single-center cohort study, we evaluated 18 patients with suspected PBCs. Under EUS guidance, a 19-gauge EUS fine needle was advanced transhepatically into the portal vein and as many as four 7.5-mL aliquots of blood were aspirated. Paired peripheral blood samples were obtained. Epithelial-derived CTCs were sorted magnetically based on expression of epithelial cell adhesion molecules; only those with a proper morphology and found to be CD45 negative and positive for cytokeratins 8, 18, and/or 19 and 4′,6-diamidino-2-phenylindole were considered to be CTCs. For 5 samples, CTCs also were isolated by flow cytometry and based on CD45 depletion. ImageStream was used to determine the relative protein levels of P16, SMAD4, and P53. DNA was extracted from CTCs for sequencing of select KRAS codons. Results There were no complications from portal vein blood acquisition. We detected CTCs in portal vein samples from all 18 patients (100%) vs peripheral blood samples from only 4 patients (22.2%). Patients with confirmed PBCs had a mean of 118.4 ± 36.8 CTCs/7.5 mL portal vein blood, compared with a mean of 0.8 ± 0.4 CTCs/7.5 mL peripheral blood (P Conclusions It is feasible and safe to collect portal venous blood from patients undergoing EUS. We identified CTCs in all portal vein blood samples from patients with PBCs, but less than 25% of peripheral blood samples. Portal vein CTCs can be used for molecular characterization of PBCs and share features of metastatic tissue. This technique might be used to study the pathogenesis and progression of PBCs, as well as a diagnostic or prognostic tool to stratify risk of cancer recurrence or developing metastases.
Role of Interleukin‐13 in Cancer, Pulmonary Fibrosis, and Other TH2‐Type Diseases

Interleukin (IL)-13 plays a major role in various inflammatory diseases including cancer, asthma, and allergy. It mediates a variety of different effects on various cell types including B cells, monocytes, natural killer cells, endothelial cells, and fibroblasts. IL-13 binds to two primary receptor chains IL-13Ralpha1 and IL-13Ralpha2. The IL-13Ralpha2 but not IL-13Ralpha1 chain binds IL-13 with high affinity and is overexpressed in a variety of human cancer cells derived from glioma, squamous cell carcinoma of head and neck, and AIDS-associated Kaposi's sarcoma. We have also demonstrated that IL-13Ralpha2 expression is greatly increased in lung cells when mice were challenged intranasally with bleomycin or Aspergillus fumigatus. In addition, IL-13Ralpha2 increased in surgical lung biopsies from patients with usual interstitial pneumonia, nonspecific interstitial pneumonia, and respiratory bronchiolitic interstitial pneumonia of unknown origin. Based on various studies, it is concluded that IL-13Ralpha2-expressing cells are involved in various pulmonary pathological conditions. In contrast, normal tissues such as brain, lung, endothelial cells, and head and neck tissues express IL-13Ralpha1 chain, but show only marginal expression of IL-13Ralpha2 chain. Thus, IL-13Ralpha2 chain may serve as a novel biomarker for diseased cells such as cancer or fibrosis and a target for receptor-directed therapeutic agents. To target IL-13R, a recombinant fusion protein composed of IL-13 and a derivative of Pseudomonas exotoxin (PE) has been produced. This cytotoxin termed as IL-13PE38QQR or IL-13PE38, or IL-13PE is highly and specifically cytotoxic to a variety of human tumor cell lines. In preclinical models of human glioblastoma, head and neck and AIDS-associated Kaposi's cancer, IL-13PE has been found to have significant antitumor activity at a tolerated dose. Several phase I clinical trials have been completed in patients with recurrent malignant glioma. Recently a phase III clinical trial (PRECISE) in patients with recurrent malignant glioma has been completed recruiting a total of 294 patients. IL-13PE cytotoxin has also shown a significant therapeutic effect in preclinical bleomycin or A. fumigatus or Schistosoma mansoni-induced pulmonary pathology including granulomatous fibrosis in mouse models. A clinical study in these diseases has yet to be initiated.
Morphologic changes in skeletal muscle induced by serotonin treatment: a light- and electron-microscope study.

Abstract Normal, adult mice were injected daily with either one or 10 μg/gm body weight serotonin creatinine sulfate (5-hydroxytryptamine) for periods of three or nine weeks. After three weeks, the most obvious histologic changes were central rowing of nuclei and infrequent fibers with basophilic sarcoplasm. Other fibers, undergoing degenerative changes, had fragmenting sarcoplams with a distinctive loss of striations and staining; leucocytes and phagocytes infiltrated these areas. Electron micrographs showed increased numbers of interfibrillar and subsarcolemmal mitochondria which were enlarged and pleomorphic as compared to control muscle. Although most of the sarcomeres were apparently normal at this time, the Z-lines were indistinct in many fibers from serotonin-treated mice. After nine weeks of treatment with serotonin, these morphologic alterations were exaggerated. Skeletal muscle from the axial musculature and the gracilis and gastrocnemius muscles had numerous regenerating fibers with deeply basophilic sarcoplasm and rows of centrally-arranged, spherical nuclei containing large chromatophilic masses and basophilic nucleoli. Electron micrographs of these muscles showed extensive myofibrillar fragmentation and disorientation with remnants of Z-lines and pleomorphic mitochondria scattered throughout the sarcoplasm.
Aproximación histórica a la Psicología de la educación

Se senala en el presente articulo la complementariedad con otro sobre la misma materia y que trato de la educacion en U.S.A. Aqui se trata de la psicologia de la educacion y de las reflexiones previas a su aparicion, sus comienzos, su desarrollo y su estado actual; se presenta un breve esquema de dicha materia en otros paises fuera del area norteamericana.
Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin

Some strains of Staphylococcus aureus bind collagen with a high degree of specificity and affinity. This interaction can represent a mechanism of substrate adhesion and may be an important step in the pathogenesis of osteomyelitis and infectious arthritis. We now report on the cloning, sequencing, and expression of a gene name cna, encoding a S. aureus collagen adhesin. The cna gene was isolated from a lambda GT11 S. aureus genomic library and encodes an 1185 amino acid polypeptide. The deduced amino acid sequence reveals several structural characteristics similar to previously described Gram-positive bacterial cell surface proteins. Antibodies raised against the native collagen adhesin from S. aureus recognize the recombinant collagen adhesin. Collagen binding activity can be detected in a lysate obtained from Escherichia coli cells, which harbor the cloned cna gene on an expression plasmid. Collagen-binding proteins can be detected in the lysate when analyzed by a Western blot type assay in which the membrane-transferred proteins are probed with radioactively labeled collagen. Finally, the bacterial lysate containing the recombinant adhesin can effectively inhibit the binding of soluble collagen to cells of S. aureus.
Targeted genetic manipulations of neuronal subtypes using promoter-specific combinatorial AAVs in wild-type animals

Techniques to genetically manipulate the activity of defined neuronal subpopulations have been useful in elucidating function, however applicability to translational research beyond transgenic mice is limited. Subtype targeted transgene expression can be achieved using specific promoters, but often currently available promoters are either too large to package into many vectors, in particular adeno-associated virus (AAV), or do not drive expression at levels sufficient to alter behavior. To permit neuron subtype specific gene expression in wildtype animals, we developed a combinatorial AAV targeting system that drives, in combination, subtype specific Cre-recombinase expression with a strong but non-specific Cre-conditional transgene. Using this system we demonstrate that the tyrosine hydroxylase promoter (TH-Cre-AAV) restricted expression of channelrhodopsin-2 (EF1α-DIO-ChR2-EYFP-AAV) to the rat ventral tegmental area (VTA), or an activating DREADD (hSyn-DIO-hM3Dq-mCherry-AAV) to the rat locus coeruleus (LC). High expression levels were achieved in both regions. Immunohistochemistry (IHC) showed the majority of ChR2+ neurons (>93%) colocalized with TH in the VTA, and optical stimulation evoked striatal dopamine release. Activation of TH neurons in the LC produced sustained EEG and behavioral arousal. TH-specific hM3Dq expression in the LC was further compared with: (1) a Cre construct driven by a strong but non-specific promoter (non-targeting); and (2) a retrogradely-transported WGA-Cre delivery mechanism (targeting a specific projection). IHC revealed that the area of c-fos activation after CNO treatment in the LC and peri-LC neurons appeared proportional to the resulting increase in wakefulness (non-targeted > targeted > ACC to LC projection restricted). Our dual AAV targeting system effectively overcomes the large size and weak activity barrier prevalent with many subtype specific promoters by functionally separating subtype specificity from promoter strength.
Endocytic Active Zones: Hot Spots for Endocytosis in Vertebrate Neuromuscular Terminals

We have used a sensitive activity-dependent probe, sulforhodamine 101 (SR101), to view endocytic events within snake motor nerve terminals. After very brief neural stimulation at reduced temperature, SR101 is visualized exclusively at punctate sites located just inside the presynaptic membrane of each terminal bouton. The number of sites (∼26 sites/bouton) and their location (in register with postsynaptic folds) are similar to the number and location of active zones in snake motor terminals, suggesting a spatial association between exocytosis and endocytosis under these stimulus conditions. With more prolonged stimulation, larger SR101-containing structures appear at the bouton margins. Thus endocytosis occurs initially at distinct sites, which we call “endocytic active zones,” whereas further stimulation recruits a second endocytic paradigm.
The Scale of Experience

Specific cells in the hippocampus allow the rat brain to track spatial location at different scales.
Methane Oxidation at Metal Oxide Surfaces

The presence of large reserves of natural gas, located mainly in remote regions, has prompted extensive research on the partial oxidation of methane. Research on catalytic oxidation has been directed mainly toward the development of processes which will produce either oxygenates (methanol and formaldehyde) or coupling products (ethane and ethylene). The latter approach has been somewhat more successful and will be the subject of this paper.
Breaking the Binary: Using Kohlberg and Lesko to Examine Adolescence in Asher’s Thirteen Reasons Why

This article uses Kohlberg’s cognitive-developmental model of adolescent stages of moral growth (developmental) to examine Jay Asher’s Thirteen Reasons Why and how character development might affect adolescent and adult readers’ understandings of adolescence (social construction). It argues that young adult books like Asher’s reduce the adolescent experience to a series of decisions made by overly exuberant and hormone-ridden brains, and that, therefore, they are ineffective, and even irresponsible, in portraying adolescent life. YA novels make incredible contributions to the cultural construction of adolescent, and examining those contributions is a crucial part of understanding why adolescents hold their current position in society and how that position is constructed.
CONSTITUENTS OF THE HYDROCARBON FRACTION OF BEEF BRAINS.

Abstract A hydrocarbon fraction previously detected in acetone concentrates of beef brains has been found to contain squalene. In addition, a homologous series of saturated, branched hydrocarbons ranging in size from approximately C 10 to C 30 was indicated by gas chromatography and other criteria. The possibility of paraffin hydrocarbons being present was indicated also. The presence of squalane was strongly indicated among these hydrocarbons, although more rigorous proof will be necessary to establish its identity with certainty.
Conditionally averaged vorticity field and turbulence modeling

The conditionally averaged vorticity (CAV) field with fixed vorticity in a point is obtained from a direct numerical simulation of isotropic turbulence. The characteristic attenuation scale for the twisting and hyperboloidal CAV components is found to be of order ten times greater than the Kolmogorov microscale. A simple analytical model qualitatively agrees with the obtained CAV. For turbulent free-surface flows, the twisting part of CAV is expected to connect to the free surface. An alternative type of subgrid-scale modeling of turbulence, based on CAV, is suggested for the large-eddy simulations. \textcopyright{} 1996 The American Physical Society.
Growth Linkages and Urban Development in Niger

. It is increasingly recognized that the assumption that the supply of tradable output is perfectly elastic, which underlies many regional economic models (esp. economic base models), does not hold in many developing countries. When the supply of tradable output (primarily agricultural products) and, in many cases, non-tradable output is inelastic, the resulting income multipliers will be substantially reduced. Recent calls for the promotion of market towns and smaller urban centers have not fully considered the impact of supply in elasticities on the capacity of such measures to stimulate broad-based development. This study uses data collected from firms in several market-town systems in Niger to examine the probable consequences. The paper argues that such policies are unlikely to be effective in countries like Niger where the vulnerability of the rural economy has severely limited the elasticity of the supply response, especially for agriculture and nonfarm production by small-scale producers.
Quasi-elastic processes in the 28Si+40Ca reaction at 225 MeV.

Elastic, inelastic, and single-nucleon transfer data are reported for $^{28}$Si${+\mathrm{}}^{40}$Ca at ${E}_{\mathrm{lab}=225}$ MeV. Standard optical model and distorted-wave Born approximation analyses of the elastic and inelastic scattering angular distributions have been performed resulting in good descriptions of the data. In the inelastic scattering analysis, the nuclear deformation lengths were found to be consistent with the Coulomb deformation lengths obtained from electron scattering. The data for one-nucleon transfers were analyzed using the distorted-wave Born approximation with the optical potential fitted to the elastic scattering and the spectroscopic factors taken from light-ion studies. With the exception of small shifts in angle, the distorted-wave Born approximation correctly predicts the shapes of the angular distributions and the relative intensities of transitions to different states populated in the same reaction. The magnitudes of the single-particle transfer cross sections are reproduced to within a factor of 1.5. However, the distorted-wave Born approximation fails to predict the nearly 40% difference in the magnitudes of the cross sections observed for the ${(}^{28}$Si, $^{27}\mathrm{Si}$) and ${(}^{28}$Si, $^{27}\mathrm{Al}$) reactions, which populate mirror states.