cssi/SciSciGPT-SciSciNet huggingface dataset:
A comprehensive software suite for protein family construction and functional site prediction

In functionally diverse protein families, conservation in short signature regions may outperform full-length sequence comparisons for identifying proteins that belong to a subgroup within which one specific aspect of their function is conserved. The SIMBAL workflow (Sites Inferred by Metabolic Background Assertion Labeling) is a data-mining procedure for finding such signature regions. It begins by using clues from genomic context, such as co-occurrence or conserved gene neighborhoods, to build a useful training set from a large number of uncharacterized but mutually homologous proteins. When training set construction is successful, the YES partition is enriched in proteins that share function with the user's query sequence, while the NO partition is depleted. A selected query sequence is then mined for short signature regions whose closest matches overwhelmingly favor proteins from the YES partition. High-scoring signature regions typically contain key residues critical to functional specificity, so proteins with the highest sequence similarity across these regions tend to share the same function. The SIMBAL algorithm was described previously, but significant manual effort, expertise, and a supporting software infrastructure were required to prepare the requisite training sets. Here, we describe a new, distributable software suite that speeds up and simplifies the process for using SIMBAL, most notably by providing tools that automate training set construction. These tools have broad utility for comparative genomics, allowing for flexible collection of proteins or protein domains based on genomic context as well as homology, a capability that can greatly assist in protein family construction. Armed with this new software suite, SIMBAL can serve as a fast and powerful in silico alternative to direct experimentation for characterizing proteins and their functional interactions.
Testing a New Intervention With Incarcerated Women Serving Life Sentences

Purpose:Incarcerated women serving life sentences are a growing subpopulation with multiple mental health needs. However, no existing interventions have been designed for or tested with this popula...
Delay Models and Exact Timing Analysis

We consider anew the false path problem in timing verification. We argue that any solution to the false path problem inherently incorporates a delay model, and the answer is given in the context of this model. We make explicit the delay model underlying both the “floating” and “transition” sensitization computations, and give the basic assumption underying gate sensitization. We extend sensitization 88theory for the delay model underlying the ”floating mode“ computation to general (complex, possibly asymmetric) gates. This leads to the ability to compute the exact delay of a circuit under the given delay model. We give a new delay model and sensitization computation for ”transition mode“ under a bounded delay model and show that for every bounded delay model there is a natural time quantum such that on each integer-multiple bounded interval of the quantum every signal is a constant. Algorithms for exact delay computation for both floating mode and transition mode delay are given. An implementation for the floating mode model yields practical results on large benchmark circuits.
TRAIL mediated gene therapy of neuroblastoma is enhanced by simultaneous inhibition of NF-κB pathway

4593 Neuroblastoma is the most common solid extracranial neoplasm in children and is responsible for approximately 15% of all childhood cancer deaths. Despite advances in treatment modalities, prognosis for neuroblastoma remains poor, and the quality of life of the treated patients is reduced drastically, thus necessitating development of new treatment regimes. TNF-related apoptosis inducing-ligand (TRAIL) induces apoptosis in a variety of tumor types, but not in normal tissues. Moreover, animals receiving multiple doses of TRAIL lack observable histological or functional changes, which makes TRAIL a strong candidate as an anti-tumor therapeutic agent. In this study, we demonstrate that introduction of the human TRAIL gene into the human neuroblastoma cell line SKNSH using an adenoviral vector leads to the death of the tumor cells. RT-PCR analysis demonstrated that the apoptotic effect of TRAIL is mediated primarily via the TRAIL R2 receptor and, to a lesser extent, by the TRAIL R1 receptor. SKNSH cells do not express TRAIL R3 or TRAIL R4 receptors. Nuclear factor κB (NF-κB) is a transcription factor that can protect tumor cells by exerting anti-apoptotic effects. Function of the NF-κB pathway depends upon the action of a specific kinase (IKK). TRAIL-mediated cell death was enhanced when neuroblastoma cells were simultaneously infected with a dominant negative mutant of IKK, thus inhibiting activation of the NF-κB pathway and promoting apoptosis. These results suggest that concurrent inhibition of the NF-κB pathway and the induction of TRAIL-mediated apoptosis using a dual vector approach may become useful in the treatment of neuroblastoma.
Mind the Mode: Differences in Paper vs. Web-Based Survey Modes Among Women With Cancer.

Abstract Context Researchers administering surveys seek to balance data quality, sources of error, and practical concerns when selecting an administration mode. Rarely are decisions about survey administration based on the background of study participants, although socio-demographic characteristics like age, education, and race may contribute to participants' (non)responses. Objectives In this study, we describe differences in paper- and web-based surveys administered in a national cancer survivor study of women with a history of cancer to compare the ability of each survey administrative mode to provide quality, generalizable data. Methods We compared paper- and web-based survey data by socio-demographic characteristics of respondents, missing data rates, scores on primary outcome measure, and administrative costs and time using descriptive statistics, tests of mean group differences, and linear regression. Results Our findings indicate that more potentially vulnerable patients preferred paper questionnaires and that data quality, responses, and costs significantly varied by mode and participants' demographic information. We provide targeted suggestions for researchers conducting survey research to reduce survey error and increase generalizability of study results to the patient population of interest. Conclusion Researchers must carefully weigh the pros and cons of survey administration modes to ensure a representative sample and high-quality data.
Genetic biomarker for cancer immunotherapy

T cells eliminate pathogens by recognizing foreign proteins that are expressed on the cell surface (antigens). T cell activation in response to antigen occurs for a controlled period of time and is stopped by the expression of immune checkpoint proteins ( 1 ). Allison and colleagues proposed that antibody blockade of these proteins would enable prolonged T cell responses against cancer cells ( 2 ). The preclinical and clinical data that emerged using antibodies against two immune checkpoint proteins, cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death receptor-1 (PD-1), led to a paradigm shift in oncology as the treatment of some patients with these drugs led to tumor regression and durable survival for more than a decade ( 3 ). But as more patients with various types of cancer have been treated with immune checkpoint therapies, an enduring problem is to identify which patients are likely to respond. On page 409 of this issue, Le et al. ( 4 ) report the response to anti-PD-1 therapy (pembrolizumab) in 12 different tumor types, and show that patients who responded to the agent had defects in a DNA damage response pathway called mismatch repair.
IBM z14: enabling physical design in 14-nm technology for high-performance, high-reliability microprocessors

The IBM z14 design was built with the 14-nm high-performance silicon-on-insulator (SOI) technology of GLOBALFOUNDRIES. This was the first technology node after IBM transitioned from its integrated fabrication facility to operating in a fabless environment, driving significant changes to design processes and methodology. In addition to this partnership, the 14-nm technology introduced significant changes relative to previous technology nodes, including the introduction of fin-shaped field-effect transistors, the use of double patterning for the lowest back-end-of-line layers, and the introduction of middle-of-line layers to exploit contact layers for local interconnects. This combination of technical and business challenges required numerous large-scale innovations for our design, design team, and design methodologies. In this paper, we provide a survey of these innovations, including the fin-based standard cell image, deeply scaled SOI self-heating/electromigration verification, routing strategies to handle double-patterning with interlayer via awareness, fill automation to enable simultaneous design of multiple layers of hierarchy, and high-performance array design with the voltage and noise limitations of the 14-nm technology node.
“Conquering the ‘Tyrranical Commander:’” Richard Baxter on the Perils of Pride in Christian Ministry:

Pride continues to be a prevalent vice among those who serve as professional ministers and Christian leaders. English Puritan Richard Baxter (1615–1691) was attentive to this concern and wrote a gr...
Integrating metacognitive judgments and eye movements using sequential pattern mining to understand processes underlying multimedia learning

Abstract Metacomprehension is key to successful learning of complex topics when using multimedia materials. The goal of this study was to determine if eye-movement dyads could be: (1) identified by sequence mining techniques, and (2) aligned with self-reported metacognitive judgments during learning with multimedia materials that contain conceptual discrepancies designed to interfere with participants' metacomprehension. Thirty-two undergraduate students' metacognitive judgments were examined with RM-MANOVAs, and sequential pattern mining and differential sequence mining were conducted on their eye movements as they learned with complex multimedia materials. Additionally, we distinguished between event- (i.e., if participants looked at specific areas of the content) and duration-based (i.e., if participants looked at areas of interest [AOIs] for a medium or long amount of time) eye-movement dyads to assess if qualitative and quantitative differences existed in their eye-movement behaviors. For content with text and graph discrepancies, results indicated participants' metacognitive judgments were lower and less accurate, and more fixation dyads were found between the text and graph. Furthermore, specific dyads of different length (i.e., long fixations on the graph to medium fixations on the text) fixations may align with lowered and inaccurate metacognitive judgments for content with text and graph discrepancies. This study begins to address how to identify behavioral indices of metacomprehension processes during multimedia learning.
Development of a Longitudinal Behavioural Medicine Continuity Curriculum for Third Year Medical Students

Reports on Medical education consistently confirm a cluster of findings regarding primary care and Behavioural medicine: a large percentage of patients with psychosocial problems first present to primary care physicians; managed care and health economics accelerate demands and time constraints; medical students receive few opportunities to develop effective basic skills in establishing therapeutic relationships with patients and measuring progress over time. A unique opportunity occurred to test a new student training model. The course is one year long and built into the required primary care continuity clinic: one half day per week preceptorship. Key features of the curriculum include: orientation to the common behavioural issues, use of brief rating scales for screening and referral, interdisciplinary team training, preceptors teach and monitor the therapeutic process and problem based didactic skills workshops in clinical management. Evaluations include video tape analysis of skills, patient logs, use of psychological rating scales, and end of year tests using performance exams (clinical simulations). Implications for curriculum design and assessment will be discussed.
Coronary Repair and Restenosis Cellular Basis for Antisense Approaches

Coronary repair and restenosis are complex processes that likely differ from the established paradigm, which has been based on numerous observations with cultured smooth muscle cells and the response of non-coronary vascular beds to injury. Pluripotent mesenchymal ceils are present in the adventitia and may migrate into the region of underlying coronary lesions during the process of atherogenesis. The activation of these cells appears to play an important role in the development of restenosis. This includes fibroblast proliferation, their differentiation to myofibroblasts, and the synthesis of extracellular matrix proteins. Antisense oligomers against several cell cycle regulating genes inhibit cell proliferation and neointimal formation in various animal models. These compounds are pleiotropic, thus exerting their biological effects through several mechanisms. It remains to be determined whether the prevention of cell proliferation with antisense oligomers is sufficient to inhibit other important manifestations of vascular cell activation (eg, remodeling and lipid retention), which play roles in the development of coronary restenosis.
Oncolytic Herpes Simplex for Gene Therapy in Preclinical and Clinical Trials

The use of viruses to treat human malignancy is not a new concept but has only recently evolved into a clinically viable therapy. Spurred by advances in molecular biology that have allowed relatively easy manipulation of the viral genome, a number of different viruses have been evaluated and shown to have promise as anticancer agents. Of these, herpes simplex virus (HSV) has been perhaps the most intensively investigated. Several strains of replication competent oncolytic HSV have been developed, some of which have been used in clinical trials. Continuing research efforts are aimed at manipulating the viral genome to more specifically target tumor cells, to further enhance efficacy while maintaining safety, and to assess the role of oncolytic HSV in combination with chemotherapy and radiation therapy.
Watch Out for Whistleblowers

The essay, part of the Ethical Health Lawyer Series, reminds the ethical health lawyer to be prepared for whistleblowers. State and federal law's treatment of health care whistleblowers is comprehensive and complex. The essay explains how wise health lawyers can anticipate the whistleblowers in their midst and establish appropriate programs and procedures to prevent both misconduct and retaliation long before the whistleblower's story appears on CNN.
Integrity and consistency for untrusted services

A group of mutually trusting clients outsources an arbitrary computation service to a remote provider, which they do not fully trust and that may be subject to attacks. The clients do not communicate with each other and would like to verify the integrity of the stored data, the correctness of the remote computation process, and the consistency of the provider's responses. We present a novel protocol that guarantees atomic operations to all clients when the provider is correct and fork-linearizable semantics when it is faulty; this means that all clients which observe each other's operations are consistent, in the sense that their own operations, plus those operations whose effects they see, have occurred atomically in same sequence. This protocol generalizes previous approaches that provided such guarantees only for outsourced storage services.
Incidence and risk of second primary malignancy after an index potentially-human papillomavirus-associated cancer.

1593Background: Approximately 39,000 HPV-associated cancers are diagnosed annually in the US. Oncogenic HPV-infections are associated with virtually all cases of cervical, 95% of anal, 73% of oroph...
Assessing provider and racial/ethnic variation in response to the FDA antidepressant box warning.

INTRODUCTION After the 2004 FDA box warning raised concerns about increased suicidal ideation among youth taking antidepressants, antidepressant use decreased for White youth but slightly increased for Black and Latino youth. Better understanding of patient and provider factors contributing to these differences is needed to improve future risk warning dissemination. METHODS We analyzed antidepressant prescriptions for youth aged 5-17 in 2002-2006 Medicaid claims data from four states (CA, FL, NC, and NY). In multilevel models, we assessed provider- and patient-level contributions to changes in antidepressant use by race/ethnicity and compared responses to the box warning between providers with large (>2/3) and small (<1/3) proportions of minority patients. RESULTS A significant amount of variance in overall prescribing patterns (calculated by the ICC) was explained at the provider level. Significant provider-level variation was also identified in the differential effect of the box warning by racial/ethnic group. In a test of the influence of provider panel mix, we found that providers with large proportions of minority patients reduced antidepressant prescribing more slowly after the box warning than other providers. DISCUSSION This study is the first to assess provider- and patient-level variation in the impact of a health care policy change on treatment disparities. Black and Latino youth Medicaid beneficiaries were seen by largely different providers than their White counterparts, and these distinct providers were influential in driving antidepressant prescription patterns following the box warning. Concerted outreach to providers of minority beneficiaries is needed to ensure that risk warnings and clinical innovations diffuse swiftly across racial/ethnic minority groups.
Hitting America's Soft Underbelly: The Potential Threat of Deliberate Biological Attacks Against the U.S. Agricultural and Food Industry

Abstract : Agriculture1 and the food industry in general are enormously important to the social, economic, and, arguably, political stability of the United States. Although farming directly employs less than 3 percent of the American population, one in eight people works in an occupation that is directly supported by food production. Agriculture's share of produce sold overseas is more than double that of other U.S. industries, which makes the sector a major component in the U.S. balance of trade. Unfortunately, the agriculture and food industries are vulnerable to deliberate (and accidental) disruption. Critical concerns in this area include: " The concentrated and intensive nature of contemporary U.S. farming practices " The increased susceptibility of livestock to disease " A general lack of farm/food-related security and surveillance " An inefficient, passive disease-reporting system that is further hampered by a lack of trust between regulators and producers " Veterinarian training that tends not to emphasize foreign animal diseases (FADs) or large-scale husbandry" A prevailing focus on aggregate, rather than individual, livestock statistics Although vulnerability does not equate to risk, and there are few recorded instances of terrorists actually using disease against agriculture, a realistic potential for disruption exists. Indeed, what makes the vulnerabilities inherent in agriculture so worrying is that the capability requirements for exploiting those weaknesses are not significant and are certainly less considerable than those needed for a human directed bio-attack. Several factors account for this situation. First, there is a large menu of agents from which to choose, with no less than 15 "List A" pathogens identified by the Office International des Epizooties (OIE) as having the potential to severely effect agricultural populations and/or trade.
Imaging Genetics Towards a Refined Diagnosis of Schizophrenia.

Current diagnoses of schizophrenia and related psychiatric disorders are classified by phenomenological principles and clinical descriptions while ruling out other symptoms and conditions. Specific biomarkers are needed to assist the current diagnostic system. However, complicated gene and environmental factor interactions play an important role in the disease onset and induce great heterogeneity. This unclear etiology and heterogeneity raise the difficulty to induce the common biomarkers to distinguish schizophrenia from the healthy population. Simultaneously, the vast overlap in common symptoms, genetic variations and brain alterations in schizophrenia and related psychiatric disorders indicate the extension of biomarkers only achieved in schizophrenia. This complex situation compels the development of biomarkers based on research findings not only in schizophrenia but also with related disorders that includes behavior as well as imaging genetics. Imaging genetics is a unique methodology to assess the impact of genetic factors on both brain structure and function. More importantly, imaging genetics builds a bridge to understand the behavioral and clinical implications of genetics and neuroimaging. By characterizing and quantifying the brain affected in psychiatric disorders, imaging genetics is contributing to present potential biomarkers for schizophrenia and related disorders. To date, imaging genetics research includes candidate gene analysis, genome-wide association studies, polygenetic risk score analysis, and large scale collaborative studies that have made contributions to the understanding of schizophrenia with the potential to serve as biomarkers. Though limitations such as failing to capture enough genetic information and methodological arguments regarding imaging genetics itself may delay its progress, imaging genetics remains a promising as more aggregative, clustering methods and imaging genetics-compatible clinical assessments are employed in future studies.
Material Design and Surface Engineering for Bio-implants

Bio-implants are engineered medical devices developed to replace the non-functioning biological structural parts of human organisms, helping to support various functions of the biological structure of the given host. As a result, the development of bio-implants has evolved from the basis of selecting specific materials for design to the selection of materials based on specific properties. In typical implant operations, the properties that are highly sought for help the bio-implant processes undergo complete bio-integration with the biostructure. With advancements in technology and research, bio-implant materials are now also being rationally designed to help control their functionality, allowing for more optimal integration within the system as well as to optimally perform the complex functions of the system. This has been accomplished through developing surface-coating methods. With these discoveries, a transition has been seen in bio-implant operations from the selection of specific bio-inert materials for operations to the surface engineering of specific materials to help further promote bio-integration through the materials’ bio-activity. This review surveys recent developments in the field of bio-implants, material design, and surface engineering.
Evaluation of Risk Factors for Cerebrospinal Leakage in Pediatric Patients With Cerebral Palsy Treated With Intrathecal Baclofen.

BACKGROUND Insertion of an intrathecal baclofen (ITB) pump can provide significant benefits in patients with cerebral palsy (CP). However, there are little data describing the risk of complications. Specifically, there is a lack of data describing the incidence of cerebrospinal fluid (CSF) leakage and risk factors following ITB placement. The purpose of our study was to describe risk factors for developing CSF leak in pediatric patients with CP treated with ITB and to report the treatment and outcome of CSF leaks. METHODS Following institutional review board approval, 720 ITB procedures in 341 children with CP were identified retrospectively over a 15-year study period. Patients' demographic characteristics, medical comorbidities, muscle tone patterns, feeding tube status, seizure history, inpatient events, ITB-related CSF leak and headache complaints and their management, and other complications were evaluated. RESULTS Eighty-five (24.9%) patients experienced 90 CSF leak episodes over a follow-up time of 6.3±3.9 years. There were 72 episodes of headache as a result of CSF leakage in 61 (71.7%) of these 85 patients. There was a positive correlation between the risk of CSF leak and preoperative comorbidities such as epilepsy/seizure history, feeding tube, mixed type CP, and dystonic type CP. The risk of CSF leak after primary ITB administration was 5.8% (20/341), and the risk after secondary ITB procedures due to complications was 24.2% (32/132). There was no significant relationship between CSF leak and primary ITB (P=0.21), but the risk of CSF leak was positively correlated to the secondary ITB due to complications (P<0.05). CONCLUSIONS CSF leak was fairly common (25% incidence), and it correlated with epilepsy/seizure history, feeding tube, mixed type CP, and dystonic type CP. Recurrent ITB procedures were a risk factor for CSF leak. Half of these patients had self-limited symptoms that improved with conservative medical treatment, and the epidural blood patch was successful in resistant cases. Successful treatment of CSF leakage complications allows patients to continue ITB. LEVEL OF EVIDENCE Level III.
Heart Failure Management Innovation Enabled by Electronic Health Records

Patients with congestive heart failure (CHF) require complex medical management across the continuum of care. Electronic health records (EHR) are currently used for traditional tasks of documentation, reviewing and managing test results, computerized order entry, and billing. Unfortunately many clinicians view EHR as merely digitized versions of paper charts, which create additional work and cognitive burden without improving quality or efficiency of care. In fact, EHR are revolutionizing the care of chronic diseases such as CHF. This review describes how appropriate use of technologies offered by EHR can help standardize CHF care, promote adherence to evidence-based guidelines, optimize workflow efficiency, improve performance metrics, and facilitate patient engagement. This review discusses a number of tools including documentation templates, telehealth and telemedicine, health information exchange, order sets, clinical decision support, registries, and analytics. Where available, evidence of their potential utility in management of CHF is presented. Together these EHR tools can also be used to enhance quality improvement, patient management, and clinical research as part of a learning health care system model. This review describes how existing EHR tools can support patients, cardiologists, and care teams to deliver consistent, high-quality, coordinated, patient-centered, and guideline-concordant care of CHF.
A Graphic Novel: John McCloskey and Breandán Ó Conaire on the Making of An Béal Bocht

In 2012, Clo Mhaigh Eo published a graphic novel version of Myles na gCopaleen’s satirical work An Beal Bocht. Adapted from the original by Colman O Raghallaigh and edited by Breandan O Conaire, author of Myles na Gaeilge (1986), the book features the frenetic, playful, and often painfully visceral artwork of John McCloskey. Here, The Parish Review speaks with McCloskey and O Conaire about the experience.
Treatment of Multidrug Resistant Gram‐Negative Bacilli after Solid Organ Transplant: Outcomes and Complications

Background Infections caused by multidrug-resistant gram-negative bacilli (GNB) cause significant morbidity and mortality in solid organ transplant (SOT) recipients. Methods We retrospectively collected data from all SOT recipients at a single center from 1 January 2007 to 15 April 2017 treated for infections caused by multi-drug-resistant GNB. This study examined the effects of specific antibiotics on nephrotoxicity, neurotoxicity, 30-day mortality, and length of stay in the hospital and intensive care unit. Results A total of 225 infections were identified among 143 patients. Carbapenem-sensitive organisms were present in 112 (49.8%) infections and were associated with decreased 30-day mortality (OR 0.35, 95% CI 0.16-0.75). Neurotoxicity was associated with polymyxin use with an 8% increase in odds of neurotoxicity per day of exposure (P=.03). There was no relationship between nephrotoxicity and any individual antibiotic class. Increased hospital length-of-stay occurred among patients exposed to aminoglycosides (β-statistic = 0.48 (0.23); P = .04), while there was no relationship between antibiotic class and intensive care unit (ICU) length-of-stay. Mortality at 30 days occurred in 37 infections (16%). Carbapenem exposure was associated with decreased 30-day mortality (OR 0.93; 95% CI 0.90-0.98; P = .02). No other antibiotic class had a significant impact on 30-day mortality. Conclusions Carbapenems appear to be a safe and effective treatment for solid-organ transplant recipients with infections caused by carbapenem-sensitive multidrug-resistant GNB; treatment of carbapenem-resistant gram-negatives remains challenging.
Evaluation of Antibiotic Prophylaxis and Postsurgery Antibiotics for Urological Surgeries at an Academic Medical Center

Objective: The purpose of this study was to evaluate antibiotic use in patients undergoing urological procedures. Methodology: This single-center, IRB-approved, retrospective, observational study was conducted at Grady Health System. Patients were included if they underwent their first inpatient urologic procedure between April 1, 2016, and April 1, 2018. Patients were excluded if they were <18 years old, pregnant, or a prisoner. The primary outcome was percentage of overall adherence to our institutional guidelines for surgical prophylaxis as a composite of antibiotic selection, dose, preoperative timing, and postoperative duration. Secondary outcomes include individual components of the composite outcome, nephrotoxicity, Clostridium difficile infection, and discharge antibiotic prescriptions. Descriptive statistics were used. Results: Of the 100 patients evaluated, 11% achieved adherence with the primary outcome. Of the 89 patients who did not achieve composite outcome, only 8 selected the appropriate perioperative antibiotic. Overall, 30% were dosed appropriately, 47% were administered at the appropriate time with respect to time of incision, and 46% received perioperative antibiotics for no more than 24 hours. Also, 19 patients did not receive perioperative antibiotics. Overall, 14 different perioperative antibiotic regimens were utilized, despite institutional guidelines recommending 1 of 3 options. All 9 patients who developed nephrotoxicity received noncompliant perioperative prophylaxis. No patient developed Clostridium difficile infection within 30 days of surgery. Moreover, 58 patients were discharged with a prescription for at least 1 antibiotic. Conclusions: Most perioperative antibiotic prophylaxes for genitourinary surgeries are not compliant with institution guideline recommendations. Despite having institutional guidelines, there was a large variety in the antibiotic regimens that patients received. All of the patients identified as having an evaluated antibiotic-related adverse effect did not receive appropriate perioperative antibiotic prophylaxis. More than half of the patients received a prescription at discharge for at least 1 antibiotic. Funding: None Disclosures: None
Modeled vascular microenvironments: immune-endothelial cell interactions in vitro

The advancement of in vitro techniques enables a better understanding of biological processes and improves drug screening platforms. In vitro studies allow for enhanced observation of cell behavior, control over the mimicked microenvironment, and the ability to use human cells. In particular, advances in vascular microenvironment recapitulation are of interest given vasculature influence in cardiovascular vascular diseases and cancer. These investigate alterations in endothelial cell behavior and immune cell interactions with endothelial cells. Specific immune cells such as monocytes, macrophages, neutrophils, and T cells influence endothelial cell behavior by promoting or inhibiting vasculogenesis through cell-cell interaction or soluble signaling. Results from these studies showcase cell behavior in vascular diseases and in the context of tumor metastasis. In this review, we discuss examples of in vitro studies modeling immune cell-endothelial cell interactions to present methods and recent findings in the field. Schematic showcasing common methods of in vitro experimentation of endothelial-immune cell interactions, including interactions with flow, static culture, or in-direct contact.
Magnetic Properties of Materials

Modern technology would be unthinkable without magnetic materials and magnetic phenomena. Magnetic tapes or disks (for computers, video recorders, etc.) motors, generators, telephones, transformers, permanent magnets, electromagnets, loudspeakers, and magnetic strips on credit cards are only a few examples of their applications. To a certain degree, magnetism and electric phenomena can be considered to be siblings since many common mechanisms exist such as dipoles, attraction, repulsion, spontaneous or forced alignment of dipoles, field lines, field strengths, etc. Thus, the governing equations often have the same form. Actually, electrical and magnetic phenomena are linked by the famous Maxwell equations, which were mentioned already in Chapter 10.
When Judges Carve Democracies: A Primer on Court-Drawn Redistricting Plans

This essay presents guidelines for courts that undertake to draw their own redistricting plans. Although several dozen courts over the last four redistricting cycles have drawn their own plans, there is precious little in the case law or secondary sources to provide guidance. As a result, courts vary considerably in the procedures they follow and the substantive factors they take into account in their plans. This essay discusses the unique legal constraints on court-drawn plans and assesses the costs and benefits of following various procedures or substantive redistricting principles. The unique context of each case that spurs judicial involvement will often affect a plan more than will universal factors common to all such cases. However, each court that jumps into the political thicket of redistricting must make several critical decisions concerning how much deference it will give to the existing plan, whether to consider the political and incumbency-related effects of its plan, how much input the parties and the public will have in the process, and which, if any, traditional districting principles ought to apply.
Implementing community-based education : Essential elements and recommendations

Two elements are essential for implementing community-based educational programs: a vision of how community experiences fit into the training of the health professionals of the future and a local environment that will support innovation, change, and growth. Change cannot occur unless very basic assumptions regarding medical education are challenged. What is "quality education"? Can programs oriented toward tertiary and specialty care adequately provide the training that should be the core of a 3-year general training program? Do schools and programs select and train physicians to function within the microcosm of the academic center, or do they prepare physicians to manage the country's health care needs? National consensus has had little influence over local environments. Each medical school, training program, and teaching facility must reexamine its values and its culture. Each must have a vision of the physicians of the future and a commitment to train them appropriately. The role of vision and culture in creating successful programs has been clearly described. Several key elements have been found to be consistent with success, the first being vision. Four basic principles will bring the vision to fruition: (1) preserving core values while still stimulating progress; (2) emphasizing the process by which programs are created, implemented, and changed rather than the product; (3) avoiding the "tyranny of the or," learning to be inclusive with a broad vision rather than limited to an "either-or" approach; and (4) aligning the process, management, and values in working toward envisioned progress for the future. Effective leadership is essential for a group or organization to accomplish its mission, as is an organizational structure that aligns responsibility, authority, resources, and accountability.
Nonlinear Finite Element Analysis of Farm Silos

A finite element formulation for nonlinear viscoelastic analysis has been synthesized with direct application to the problem of silage-silo interaction as a typical example of farm silo analysis. The formulation is based on basic theories in continuum mechanics and employs a single integral constitutive relation for nonlinear viscoelastic materials. This nonlinear formulation has been found, through its applications, to be a more versatile and accurate scheme when compared with the conventional piecewise-linear viscoelastic finite element formulations. Among the other features of the formulation are its capability of taking prescribed load, simulating incremental construction and its convenience in incorporating the silage-silo wall interface friction mechanism. The devised formulation was applied to predict stress histories, deformations, and resulting capacities produced during sequential loading of a 24x70-ft top unloading drained silo, using materials' constitutive functions that have been previously established through triaxial creep tests on corn silage.
Charge-transfer-Anregungsenergien von Tetracyanäthylen-Molekülkomplexen phenylsubstituierter Äthylene und substituierter trans-Stilbene†‡

Der Einflus der Grose des π-Systems, der Topologie, der cis-trans-Isomerie und der Substitution von Donatoren in π,π-Molekulkomplexen wird am Beispiel der TCNE-Komplexe von 6 phenylsubstituierten Athylenen und von 9 substituierten trans-Stilbenen untersucht. Dazu werden die experimentell ermittelten ct-Anregungsenergien mit Hilfe storungstheoretischer Uberlegungen diskutiert und mit den Ergebnissen von PPP-Berechnungen der Ionisierungspotentiale der Donatoren verglichen. Die untersuchten Donatoren sind entsprechend der Zahl, Stellung und elektronischen Wirkung von Substituenten in Gruppen klassifizierbar, deren Vertreter sich durch Analogien in den ct-Spektren auszeichnen. Charge-transfer Energies of Molecular Complexes of Tetracyanoethylene with Phenylsubstituted Ethylenes and Substituted trans-Stilbenes Starting from the tetracyanoethylene (TCNE) complexes of 6 phenyl-substituted ethylenes and 9 substituted trans-stilbenes, the influence of the size of the π-system, the topology, and the substitution of donators in π,π-complexes are examined. For this aim the determined ct-excitation energies are discussed by means of terms of perturbation theory, and compared with the results of PPP-calculations for donator ionization potentials. Corresponding to the number, position and electronic effects of substituents the examined donators are classified into groups the members of which are distinguished by analogies in their ct-spectra.
Mixed metastatic lung cancer lesions in bone are inhibited by noggin overexpression and Rank:Fc administration.

Lung cancer metastases to bone produce a primarily mixed osteolytic/osteoblastic lesion. The purpose of this study was to determine if blockade of both pathways would inhibit the formation these lesions in bone. Inhibition of the osteoblastic lesion with noggin and the osteolytic lesion with RANK:Fc was a successful treatment strategy to inhibit progression of mixed lung cancer lesions in bone. Introduction: Approximately 9–30% of patients with lung cancer develop bone metastases, leading to significant morbidity and mortality. A549 is a non–small-cell lung cancer (NSCLC) line that produces a mixed metastatic lesion in bone. We sought to determine if blockade of key components in both osteolytic and osteoblastic pathways would result in a reduction of a NSCLC tumor progression in a murine model of bony metastasis. Materials and Methods: The study used a retroviral vector overexpressing noggin (RN), a specific inhibitor of BMP, and RANK:Fc, a chimeric protein that inhibits the RANK–RANKL interaction. A549 cells were transduced with RN before implantation in SCID mice. Cells were implanted in a subcutaneous model and tibial injection model. RANK:Fc was administered twice weekly at 15 mg/kg. There were five treatment groups: A549; A549 + RN; A549 + RANK:Fc; A549 + empty vector; and A549 + RN + RANK:Fc (n = 10/group). Results: In SCID mice who underwent subcutaneous A549 tumor cell injection, animals treated with A549 + RN had significantly smaller subcutaneous tumor size at 8 weeks. In an intratibial model of bony metastasis, animals injected with A549 cells developed a mixed lytic/blastic lesion with cortical destruction at 8 weeks. Treatment with RANK:Fc inhibited the formation of osteoclasts, led to a smaller tumor volume in bone, and inhibited the lytic component of the mixed lesion. Animals treated with A549 + RN had a decreased number of osteoblasts in bone lesions, smaller tumor volume, and inhibition of the blastic component of the mixed lesions. Combination treatment inhibited both the lytic and blastic components of the lesion. Conclusions: The NSCLC cell line A549 forms a mixed osteolytic/osteoblastic lesion in vivo. Noggin overexpression inhibited the formation of the osteoblastic aspect of the lesion in bone and the tumor growth in vivo. Treatment with RANK:Fc limited the formation of the lytic aspect of the mixed lesion and also inhibited the rate of in vivo tumor growth. Inhibition of both pathways is necessary to effectively inhibit the progression of mixed metastatic lesions in bone.
Mechanism of formation of concentrically laminated spherules: implication to Randall's plaque and stone formation.

We report on the formation of calcium phosphate multi-laminated spherules via a polymer-induced liquid-like precursor (PILP) process. In this non-classical crystallization route, the precipitation of liquid-like amorphous calcium phosphate (ACP) particles is promoted using anionic polypeptide additives, and these droplets coalesce to form globules that later crystallize into spherulites. During crystallization of the amorphous globules, the polymer additive, as well as the waters of hydration, is excluded ahead of the crystallization front, but some polymer becomes entrapped within diffusion-limited zones. This results in the formation of concentric laminations with layers of variable density from organic-rich inclusions. The striking resemblance of these spherules with the crystals of the Randall’s plaque and other laminated stones suggests that such biological structures may form via an amorphous precursor process as well. Given the organic-rich environment present in the urinary tract, one might expect a large amount of organic materials to become entrapped within the stratified zones of a forming stone during this type of solidification and transformation process.
Canadian Advances in Surface-Piercing Hydrofoils

The surface-piercing hydrofoil system exemplified by HMCS BRAS D'OR is a unique development which appears to combine some characteristics of other contemporary designs but, in fact, is derived from an early concept of F. W. Baldwin and Alexander Graham Bell. Essential features of this concept are compared with other surface piercing systems in a review of today's state of the art. Lessons learned from trials at sea have been incorporated in design studies of possible follow-on naval hydrofoil ships. Highlights from this continuing exploration indicate good prospects based on important advances in key areas of design for high performance with good seakeeping and cost benefits.
Bias elimination in tracking with converted position and Doppler measurements

In target tracking, it is natural to describe target motion in Cartesian coordinates. In many cases the measurements require some form of nonlinear conversion prior to use in a Cartesian coordinate tracker. There are two sources of bias that can arise as a result of this conversion. The first occurs when the conversion process introduces a bias in the expected value of the converted measurement. The second is estimation bias that occurs when the estimate of the converted measurement error covariance is correlated with the measurement noise. The conversion and estimation biases of previously proposed conversions, including the recently proposed “Decorrelated Unbiased Converted Measurement (DUCM)”, are evaluated for two forms of measurement conversion. The first is the conversion from polar to Cartesian coordinates. The second is range-rate estimation from a moving platform.
Relationships between perceived STD-related stigma, STD-related shame and STD screening among a household sample of adolescents.

CONTEXT: Important barriers to STD testing may include individuals' perceptions of STD-related stigma (negative societal attitudes toward STD infection) and expectations of STD-related shame (negative personal feelings) that would result from a positive STD test. Obtaining a clear understanding of the relationship between STD-related stigma, STD-related shame and STD testing may help inform programs and policies aimed at reducing STD transmission. METHODS: Measures derived from previously published scales were used to assess perceived STD-related stigma, anticipated STD-related shame and receipt of an STD test in the past year in an urban, household sample of 594 exually active 15–24-year-olds interviewed in 2004–2007. Logistic regression was used to examine associations between recent STD testing and perceived stigma, shame and other participant characteristics. RESULTS: Thirty-seven percent of males and 70% of females reporting having had an STD test in the past year; the largest proportions of tests (42% among males and 59% among females) had occurred in the context of a routine health care visit, not because adolescents had had disease symptoms or were concerned about exposure to infection. For both males and females, the level of STD-related stigma was negatively associated with the odds of having been tested (odds ratio, 0.5 for each). STD-related shame was not related to STD testing. CONCLUSIONS: Adolescents who view STDs as stigmatizing have a reduced likelihood of being screened, but it is unclear whether this relationship refl ects their care seeking or providers' practice of off ering STD screening at a routine health visit.