cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 634: Novel antibody-drug conjugates targeting Axl show anti-tumor activity in solid cancer xenograft models

Axl is a receptor tyrosine kinase of the TAM family, which is structurally characterized by the presence of two extracellular immunoglobulin-like domains and two fibronectin type III domains, a single-pass transmembrane region and an intracellular tyrosine kinase domain. Axl is aberrantly expressed and activated in both solid and hematological malignancies and has been associated with poor clinical prognosis in a number of cancers, including non-small cell lung cancer, breast cancer, pancreatic cancer and acute myeloid lymphoma. Functionally, Axl has been implicated in multiple pathological processes, such as tumor cell motility, adherence and migration, epithelial-to-mesenchymal transition, metastasis, angiogenesis and resistance to tyrosine kinase inhibitors. With the aim to target Axl expressing cancers, a panel of Axl-specific antibody-drug conjugates (ADC) was generated. First, high affinity human Axl antibodies were generated in HuMAb mice. Binding studies using Axl mutants, in which specific human Axl domains had been replaced with their murine analogs, demonstrated that the Axl antibody panel consisted of antibodies against different Axl extracellular domains. Second, the Axl antibodies were conjugated with the microtubule disrupting agent monomethyl auristatin E (MMAE) using the protease cleavable valine citrulline linker. Axl ADCs showed cytotoxic activity in vitro, which was dependent on target expression and on conjugation with cytotoxic payload. The anti-tumor activity of Axl ADCs was confirmed in vivo. Axl ADCs induced tumor regression in cell line derived xenograft models for lung cancer and epidermoid carcinoma. Anti-tumor activity was especially efficient in the lung cancer xenograft model, in which inhibition of tumor growth was observed upon treatment with a single dose of 0.5 mg/kg Axl ADC. In the same model, 1 mg/kg Axl ADC was sufficient to induce complete tumor regression. Importantly, Axl ADCs also showed efficient anti-tumor activity in patient-derived xenograft (PDX) models that showed heterogeneous target expression. In summary, Axl is a novel target for antibody-mediated delivery of cytotoxic agents into tumor cells. The promising results obtained in preclinical tumor models support further development of Axl-specific ADCs. Citation Format: Esther C.W. Breij, Sandra Verploegen, Andreas Lingnau, Edward N. van den Brink, Maarten Janmaat, Mischa Houtkamp, Wim K. Bleeker, David Satijn, Paul W.H.I. Parren. Novel antibody-drug conjugates targeting Axl show anti-tumor activity in solid cancer xenograft models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 634. doi:10.1158/1538-7445.AM2015-634
The complex Lorentzian Leech lattice and the bimonster

Let D be the incidence graph of the projective plane over F3. The Artin group of the graph D maps onto the bimonster and a complex hyperbolic reflection group acting on 13 dimensional complex hyperbolic space Y. The generators of the Artin group are mapped to elements of order 2 (resp. 3) in the bimonster (resp. ). Let Y ◦ ⊆ Y be the complement of the union of the fixed points of reflections in . Daniel Allcock has conjectured that the orbifold fundamental group of Y ◦ / surjects onto bimonster. In this article we study the reflection group . We show that th e Artin group of D maps to the orbifold fundamental group of Y ◦ /, thus answering a question in Allcock's article "A monstrous proposal" and taking one step towards the proof of Allcock's conjecture. The finite group Aut(D) acts on Y. We make a detailed study of the complex hyperbolic line fixed by the subgroup L3(3) ⊆ Aut(D). We define meromorphic automorphic forms on Y , invariant under , with poles along mirrors. We show that the restriction of these forms to the complex hyperbolic line fixed by L3(3) gives meromorphic modular forms of level 13.
Mulitmodal interaction for distributed interactive simulation

This paper presents an emerging application of Artificial Intelligence research to distributed interactive simulations, with the goal of reducing exercise generation time and effort, yet maximizing training effectiveness. We have developed the QuickSet prototype, a pen/voice system running on a hand-held PC, communicating via wireless LAN through an agent architecture to NRaD's LeatherNet system, a distributed interactive training simulator built for the US Marine Corps. The paper describes our novel multi modal integration strategy offering mutual compensation among modalities, as well as QuickSet's agent-based infrastructure, and provides an example of multimodal simulation setup. Finally, we discuss our applications experience and lessons learned.
The Issues, Analysis, and Interpretation of Multi-Sensor Images

Past research in computer vision has shown that image interpretation is a highly underconstrained task. Information fusion from multiple cues from the same image and from multiple views using the same modality have been marginally successful. Recently the fusion of information from different modalities of sensing has been studied to further constrain the interpretation. This paper presents an overview of approaches developed for image segmentation and analysis using multi-sensor fusion. We present examples of three systems using different modalities. These examples include a system for image segmentation and interpretation using ladar (laser radar) and thermal images, a system using registered thermal and visual images for surface heat flux analysis, and an image synthesis system that generates visual and thermal images based on the internal heat flow in objects.
Optimization study for fabrication of micro-scale stacked dielectric elastomer actuators

Fabrication of micro-scale DEAs could benefit many fields including micro-robots, micro-optical systems besides reducing the driving voltage from kV scale to possibly sub-100V range. In an earlier study, proof of concept fabrication methods for PDMS-based fiber-like micro-sized stacked dielectric elastomer actuators were introduced. This study tried to optimize the fabrication process by investigating the effect of different fabrication approaches and different design geometries on the performance of micro-sized DEAs. Micro-sized DEAs with different geometrical parameters were fabricated. Several fabrication steps were modified and the effectiveness of the new fabrication steps and parameters were investigated.
Aminolevulinic acid-mediated protoporphyrin IX and photodynamic therapy for breast cancers (Conference Presentation)

Photodynamic therapy (PDT) involves the combination of a photosensitizer and light of a specific wavelength. Upon light activation in the presence of oxygen, photosensitizer molecules generate reactive oxygen species that cause cytotoxicity by inducing oxidative stress. Aminolevulinic acid (ALA) is a pro-drug used for the diagnosis and PDT treatment of various solid tumors based on endogenous production of heme precursor protoporphyrin IX (PpIX). Although nearly all types of human cells express heme biosynthesis enzymes and produce PpIX, tumor cells are found to have more PpIX production and accumulation than normal cells, allowing for the detection and treatment of solid tumors. The objective of my research is to explore therapeutic approaches to enhance ALA-based tumor detection and therapy. We have found that high ABCG2 transporter activity in triple negative breast cancer cells (TNBC) contributed to reduced PpIX levels in cells, causing them to be more resistant towards ALA-PDT. The administration of an ABCG2 inhibitor, Ko143, was able to reverse cell resistance to ALA-PDT by enhancing PpIX mitochondrial accumulation and sensitizing cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. Furthermore, since some tyrosine kinase inhibitors (TKI) are known to block ABCG2 transporter activity, we screened a panel of tyrosine kinase inhibitors to examine its effect on enhancing PpIX fluorescence and ALA-PDT efficacy. Several TKIs including lapatinib and gefitinib showed effectiveness in increasing ALA-PpIX fluorescence in TNBC leading to increased cell death after PDT administration. These results indicate that inhibiting ABCG2 transporter using TKIs is a promising approach for targeting TNBC with ALA-based modality.
Bone and Energy Metabolism

There is an intimate relationship between fat and bone metabolism that has only recently been appreciated. Adipose depots regulate energy utilization in coordination with the liver and skeletal muscle through an intricate series of local, systemic, and neuronal mediators. Although adipose tissue is one of the largest organs in the body, its functions vary by location and origin. Adipocytes can act in an autocrine manner to regulate energy balance by sequestering triglycerides and subsequently, depending on demand, releasing fatty acids through lipolysis for energy utilization, and in some cases through uncoupling protein 1 for generating heat. Adipose tissue can also act in an endocrine or paracrine manner by releasing adipokines that modulate the function of other organs. Bone is one of those target tissues, although the skeleton can also reciprocate by releasing its own factors that modulate adipose tissue function and pancreatic islet cells production of insulin in the pancreas. The central nervous system is the final common pathway modulating these signals, both in the skeleton and in adipose tissue. Disruption in this complex regulatory circuit and its downstream tissues is manifested in a wide range of metabolic disorders, including type 2 diabetes mellitus (T2D). The aim of this chapter is to summarize our knowledge of common determinants in bone and adipose function.
Seeing below the surface: making soil processes visible to Ugandan smallholder farmers through a constructivist and experiential extension approach

Ugandan smallholder farmers need to feed a growing population, but their efforts are hampered by declining soil fertility rates. Agricultural extension can facilitate farmers’ access to new practices and technologies, yet farmers are understandably often hesitant to adopt new behaviors. New knowledge assimilation is an important component of behavior change that is often overlooked or poorly addressed by current extension efforts. We implemented a Fertility Management Education Program (FMEP) in central Uganda to investigate smallholder farmers’ existing soil knowledge and their assimilation of new scientific concepts into their knowledge framework. Qualitative data were collected through participant observation, farmer interviews, and focus groups, and coded for using a priori and emergent themes. Our exploration revealed some notable similarities between farmers’ soil knowledge and scientific concepts, particularly in regards to soil health concepts, a discovery that could facilitate communication between extension agents and farmers. However, certain scientific concepts are either unknown to farmers or discordant with existing soil knowledge; these concepts are unlikely to be assimilated by farmers without convincing and concerted extension efforts. Importantly, we found that the combination of new scientific knowledge and hands-on experimentation with novel practices gave farmers far greater confidence in implementing improved soil management practices. Our study provides evidence that extension programs should engage directly with farmers’ existing soil knowledge to develop their understanding of key biological concepts and confidence in implementing improved practices.
Mesoscopic modeling of structural self-organization of carbon nanotubes into vertically aligned networks of nanotube bundles

Abstract An effective and flexible method for the generation of computational samples for mesoscopic modeling of anisotropic networks of carbon nanotube (CNT) bundles with various degrees of CNT alignment is developed and applied for investigation of structural self-organization of nanotubes into vertically aligned CNT forests and fibers. Structural characteristics of the computational samples, such as bundle size distribution, average and maximum bundle sizes, magnitude of the Herman orientation factor, average tilt of CNT segments with respect to the direction of alignment, and average tortuosity of the nanotubes, are calculated and related to parameters of the sample preparation procedure. Good agreement between the computer-generated and experimentally-grown network structures is demonstrated, and several examples of the applications of the mesoscopic modeling for investigation of mechanical and thermal transport properties of the CNT materials are provided. The high degree of control over the structure of computational samples, provided by the sample generation procedure, enables fine-tuning of the structural characteristics of in silico generated samples to match those to particular experimental materials, as well as an efficient exploration of the multidimensional space of structural parameters aimed at optimization of mechanical and transport properties and establishing structure – property relationships for this important class of network materials.
Association Studies of Racial Disparities in Cancer Survivability

Cancer has always been and still is very prevalent in today’s society. It would be very difficult to find a person who has not been affected by some form of the disease as either diagnosed themselves or a family member or friend diagnosed. In many families, cancer may seem to be an epidemic, constantly in some form attacking. As with many diseases, advanced research, alternative treatments, and many other factors have played major roles in increasing the survival rates of patients with cancer. In this study, we analyze different types of cancer such as breast, colon rectal, and respiratory with important attributes of patients such as age, sex, tumor size, year of treatment, and year of survival. Our results show that there is disparity between White Americans and Black Americans in cancer survivability. This can assist in predicting survivability rates and treatment of future patients.
The Philadelphia story: Age, race, gender and changing travel trends

Abstract We examine changes in travel behavior in the Philadelphia region between 2000 and 2012. We use two household regional travel surveys over a decade apart, the 2000 and 2012 surveys, from the Delaware Valley Regional Planning Commission (DVRPC). Previous research, at the national scale, has highlighted changes among the Millennial cohort. We use these two regional datasets to examine the changing travel behavior among Millennials and to put these changes in context by comparing them with changes among other social groups of interest: women and minorities. We find that the travel behavior of young people did not change substantially between 2000 and 2012. Where there are changes, these pale in comparison to the changes among women and black residents. And finally, we find that the built environment factors appear to influence travel more in 2012 than in 2000. Taken together, our findings fit an overarching narrative about urban gentrification and the suburbanization of poverty, rather than a story of Millennials’ changing travel behavior.
Vasectomy: an update

Vasectomy remains an important option for contraception. Research findings have clarified many questions regarding patient selection, optimal technique, postsurgical follow-up, and risk of long-term complications. Men who receive vasectomies tend to be non-Hispanic whites, well educated, married or cohabitating, relatively affluent, and have private health insurance. The strongest predictor for wanting a vasectomy reversal is age younger than 30 years at the time of the procedure. Evidence supports the use of the no-scalpel technique to access the vasa, because it is associated with the fewest complications. The technique with the lowest failure rate is cauterization of the vasa with or without fascial interposition. The ligation techniques should be used cautiously, if at all, and only in combination with fascial interposition or cautery. A single postvasectomy semen sample at 12 weeks that shows rare, nonmotile sperm or azoospermia is acceptable to confirm sterility. No data show that vasectomy increases the risk of prostate or testicular cancer.
The Birth of the Space Age and Unmanned Missions to the Moon

After Sputnik and prior to manned flight, the Luna, and Explorer programs had taught us about the magnetic environment of the Earth with its Van Allen Radiation Belts, and shown that the moon unlike the earth had no detectable magnetic field. The Surveyor missions demonstrated that the Moon was an evolved body like Earth rather than a primitive body, so it looked as though there could be a core, in which a magnetic field might at one time have originated.
Relation of Self-Efficacy to Reported Pain and Pain Medication Usage During Labor

We studied the relationship of self-efficacy to reported labor pain and pain medication usage among 43 women. Self-efficacy ratings were judgments of confidence regarding successful completion of tasks involved in labor and delivery (e.g., doing breathing exercises) and in overcoming barriers (e.g., nonsupportive partner). Multiple regression analyses revealed that self-efficacy significantly contributed to predicting labor pain beyond other relevant variables (e.g., age, amount of menstrual pain), with barrier self-efficacy the strongest predictor. Results are discussed in the context of increasing women's confidence in overcoming barriers by incorporating relevant interventions in childbirth education.
Moving opioid misuse prevention upstream: A pilot study of community pharmacists screening for opioid misuse risk

Abstract Background Prescription opioids are known to be highly addictive, contributing to the opioid epidemic which continues to besiege victims in the United States. Pharmacists are gatekeepers straddling the prescribers of opioids and their patients; therefore they are in the ideal position to screen for opioid misuse among patients receiving opioid prescriptions and counsel them on safe use. Objectives The purpose of this study was to design the Opioid Misuse Risk Prevention Toolkit and then evaluate the utility of the toolkit by implementing it in community pharmacy practice sites. A critical element of the toolkit was the use of the Opioid Risk Tool (ORT) to screen all patients receiving opioid prescriptions for opioid use disorder. Methods Eleven pharmacists were trained in the use of the toolkit, which they implemented within their community pharmacy for all patients receiving opioid prescriptions. A triage tool was used to guide the process of screening patients for opioid use disorder, red flags (patient unknown to the pharmacy, history of early refills, requesting a particular brand, or cash paying), risk of accidental overdose, and misuse of opioids through the prescription drug monitoring program (PDMP). Pharmacist-provided services included naloxone prescribing, counseling on opioid addiction risks, partial fills of opioid prescriptions, education on medication takeback programs, and referral information for community resources for patients concerned about a substance misuse disorder. Results Twenty-six percent of individuals (n = 107) receiving opioid prescriptions were identified as at some risk of misuse and 30% at risk of an accidental overdose. Participating pharmacists preferred the value of having an objective measurement of potential of opioid misuse, to relying only on professional judgment. They also reported the value of the toolkit elements in enhancing conversations with patients. Conclusions This case report demonstrated the utility and the feasibility of screening for opioid misuse risk at the community pharmacy level.
FlowNotation: An Annotation System for Statically Enforcing Information Flow Policies in C

Programmers often need to enforce high-level policies on their cryptographic applications written in C; for instance, that private data is not sent over public channels, trusted data is not modified by untrusted functions, and that the ordering of protocol steps is maintained. These secrecy, integrity, and sequencing policies can be cumbersome to check with existing general-purpose tools. We have developed a novel means of specifying and checking these policies that allows for a much lighter-weight approach than previous tools; requiring less work from programmers. Further, we have modeled our policy annotations as an information flow type system and proved a noninterference guarantee. We embed the policy annotations in C's type system via a source-to-source translation and leverage existing C type checkers to enforce our policies, achieving high performance and scalability. We show through case studies of cryptographic libraries from both industry and recent literature that our work expresses detailed policies for large bodies of C code with little annotation burden, and finds subtle implementation bugs.
Numerical Simulation of EBIC for Analysis of Extended Defects

Electron beam induced current (EBIC) measurements and simulation are employed to better understand recombination at extended defects, such as dislocations, grain boundaries, and stacking faults. Analysis of our EBIC contrast data indicates that certain grain boundaries in mc-Si devices are comprised of a nearly uniform density of shallow and deep gap states. The effects on device performance are calculated. Recombination active stacking faults (junction shunts) exhibit high room-temperature contrast that is not described by the defect physics studied here, possibly due to formation of a Schottky barrier. The electronic properties of the latter are important for understanding potential induced degradation of the shunting type.
Entrepreneurs, Ecosystems, and Accelerators

To understand the work that accelerators are asked to do around the world, it is first necessary to understand the interplay between entrepreneurs and entrepreneurial ecosystems. When navigating the paths from promising ideas to successful companies, entrepreneurs rely on a host of individuals, organizations, and institutions to close various knowledge, network, and capital gaps. For certain entrepreneurs developing certain business ideas in certain places, the breadth and depth of the local ecosystems allow this to happen; not with absolute certainty, but with sufficient regularity to ensure a steady stream of new high-growth companies. Just think about the many white male entrepreneurs starting technology companies in Silicon Valley. For other entrepreneurs, like the founders of Togo’s first cashew processor or an Indian off-grid energy provider, these local ecosystems are much less robust. Therefore, a host of accelerators are setting up to target underserved and underestimated entrepreneurs who start impact-oriented ventures in these entrepreneurial dead spaces. We round out this chapter by using survey data collected by GALI researchers to explore this impressive global growth of accelerators. This sets the stage and provides context for the many observations that are presented throughout this book.
Assessing the use of social media in physician assistant education.

This study aims to assess physician assistant (PA) students’ experiences with social media (SM) as a part of their medical education.
AB0639 Risk of mortality in sjogren’s syndrome after 1st admission

Background The long-term prognosis of patients with SS is unclear. Population-based studies have shown conflicting evidence regarding relative mortality in SS. Objectives There is conflicting evidence regarding prognosis in patients with SS (pSS). The aim of this study was to estimate the risk factors of mortality in patients with SS through a in hospital review. Methods Through a review of databases through October 2002 till 2016, we identified cohort studies reporting relative risk (compared with standardised population), risk factors and causes of mortality in patients with SS. Results We identified 695 (83.2% females) with SS, of whom 88 patients died over a median average follow-up of 13 years. Leading causes of mortality were infections; Risk factors associated with increased mortality were advanced age at diagnosis [HR 1.045 (95% CI 1.024, 1.067], male sex [RR 2.18 (95% CI 1.45, 3.27)], associated with SLE [HR 2.448 (95% CI 1.108, 5.406)], diabetes [HR 1.986 (95% CI 1.125, 3.505)] Conclusions After first admission, the risk factor for mortality include old age, associated with SLE and diabetes. These require close follow-up. Reference [1] Baldini C, Pepe P, Quartuccio L, et al. Primary Sjogren’s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology2014;53 Acknowledgements We thanks to Kaohsiung CGMH for data support Disclosure of Interest None declared
How Communities Attracted Physicians After World War II

Since the end of World War II, the Council on Medical Service of the American Medical Association (AMA) has conducted a Physicians Placement Service to assist physicians seeking a practice location and communities seeking physicians. As part of this service, the AMA offered pamphlets that included articles and exhibits. This article features select images from one of those pamphlets.
Core Outcome Measures in Preclinical Assessment of Candidate Analgesics

All preclinical procedures for analgesic drug discovery involve two components: 1) a "pain stimulus" (the principal independent variable), which is delivered to an experimental subject with the intention of producing a pain state; and 2) a "pain behavior" (the principal dependent variable), which is measured as evidence of that pain state. Candidate analgesics are then evaluated for their effectiveness to reduce the pain behavior, and results are used to prioritize drugs for advancement to clinical testing. This review describes a taxonomy of preclinical procedures organized into an "antinociception matrix" by reference to their types of pain stimulus (noxious, inflammatory, neuropathic, disease related) and pain behavior (unconditioned, classically conditioned, operant conditioned). Particular emphasis is devoted to pain behaviors and the behavioral principals that govern their expression, pharmacological modulation, and preclinical-to-clinical translation. Strengths and weaknesses are compared and contrasted for procedures using each type of behavioral outcome measure, and the following four recommendations are offered to promote strategic use of these procedures for preclinical-to-clinical analgesic drug testing. First, attend to the degree of homology between preclinical and clinical outcome measures, and use preclinical procedures with behavioral outcome measures homologous to clinically relevant outcomes in humans. Second, use combinations of preclinical procedures with complementary strengths and weaknesses to optimize both sensitivity and selectivity of preclinical testing. Third, take advantage of failed clinical translation to identify drugs that can be back-translated preclinically as active negative controls. Finally, increase precision of procedure labels by indicating both the pain stimulus and the pain behavior in naming preclinical procedures.
Equilibrium in Coherence

The method of reflective equilibrium aims to maximize two factors in one’s beliefs: harmonious coherence, and plausibility of content.1 Analytic philosophy has long paid deference to these factors, for instance in its use of the counterexample, which attacks a principle as incoherent with the plausible (by one’s lights). A critique of this tradition has recently appeared, and it shall be my main objective here to assess its merits. An appendix will apply our results to issues of moral relativism and rationality.
New mouse model of chronic kidney disease transitioned from ischemic acute kidney injury.

Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD), which is closely associated with the severity of AKI. However, the underlying mechanisms f...
Zinc and Enzymes

Zinc metalloenzymes catalyze approximately 50 important biochemical reactions. Many of these enzymes have been isolated from more than one species, resulting in identification of over 200 catalytically active zinc metalloproteins (Galdes and Vallee, 1983).
Positive circumferential resection margins following locally advanced colon cancer surgery: Risk factors and survival impact.

Background While the prognostic implications of positive circumferential resection margins (CRM) have been established for rectal cancer, its significance in colon cancer has not been well defined. The aim of the current study was to determine national rates for positive CRM in locally advanced colon cancer, associated factors, and survival impact. Methods The National Cancer Database was queried to identify patients with stage II-III adenocarcinoma of the colon (2004-2015). Results Positive CRM was identified in 9% of stage II and 12% of stage III patients. Factors associated with negative CRM included surgery in a high-volume facility, adequate lymph-node harvest, and negative distal/proximal margins. No difference in CRM rates was observed between surgical approaches, although having a positive CRM was significantly associated with higher conversion rates. Positive CRM was associated with significantly lower overall survival on both univariate and multivariable analysis. Conclusions Positive CRM rates exceeded 10% nationally and have an adverse impact on survival. While several tumor characteristics were identified as independent risk factors, oncologic resections and surgery at high-volume centers were associated with lower rates of positive CRM. These findings emphasize the need for process improvement initiatives targeting modifiable factors, including adoption of appropriate oncologic techniques, standardized pathology reporting, and potential neoadjuvant strategies.
New frontiers in fertility preservation: a hypothesis on fertility optimization in men with hypergonadotrophic hypogonadism

Strategies exist that can mitigate the risk of causing iatrogenic infertility when men require testosterone replacement therapy (TRT). This article reviews the current medical therapies that preserve spermatogenesis when TRT is indicated. Furthermore, we highlight the re-emerging concept of hypothalamic-pituitary-gonadal (HPG) axis reset in hypergonadotrophic, hypogonadal infertile men who are planning sperm retrieval procedures. Finally, we present our hypothesis for a novel protocol to optimize hypergonadotrophic hypogonadal men before sperm extraction surgeries hormonally.
Hemophagocytic Lymphohistiocytosis and Other Culture Negative Sepsis-Like Syndromes in the ICU

There are many sepsis-like inflammatory syndromes that may be encountered by critical care practitioners. Clinically, these syndromes may imitate sepsis and are often identified after an extensive, but unrevealing evaluation for infection. In some instances, these syndromes are anticipated complications of advanced therapies for malignancy. It is vitally important to identify these disorders and treat them with specific chemotherapeutic or immunomodulating therapies. This chapter will focus on hemophagocytic lympho-histiocytosis (HLH), a rare disorder of pathologic immune system activation that presents as a sepsis-like illness in the critically ill. While treatment of HLH with chemotherapy and immunosuppression should be guided by an expert hematologist, the diagnosis is often made by the critical care medicine practitioner. We present a case illustrating the challenges of defining this syndrome in a patient with recurrent critical illness, and review the evidence underlying diagnostic and prognostic criteria for this protean syndrome. We also review several of the more common sepsis-like inflammatory syndromes that are encountered in the critical care unit along with their specific treatments.
6 – Interrupts and Alternatives

Publisher Summary The computer has to be synchronized with the fast or slow I/O device. The two main areas of concern are the amount of data that will be input or output and the type of error conditions that will arise in the I/O system. Given the varying amounts of data and different I/O error conditions, deciding the appropriate action to be taken by the microcomputer program is needed. This chapter discusses eight alternatives for solving the synchronization problem, and four software programming techniques. The programmer should select from these techniques for the best techniques that suit his or her application. The chapter provides the basic theory and many concrete examples to help the programmer make that decision, and discusses synchronization mechanisms used for slower I/O devices. There are six mechanisms used for faster devices. These are direct memory access, context switching, coprocessing, and shuttle, indirect, time-multiplexed, and video memory.
O15.6 Women’s approaches to involving others in making HIV trial enrollment decisions while pregnant in the US and malawi

Background There is a pressing need to expand the HIV prevention and treatment evidence base in pregnancy. However, research in pregnancy entails unique ethical and scientific complexities. The decision-making processes of potential trial participants in the doubly sensitive context of HIV, a highly stigmatized disease, and pregnancy, where multiple stakeholders and sociocultural practices may influence women’s preferences, are not well understood. Involvement of others in decision-making processes may vary, including who pregnant women consult and why, and the influence of consultations on decisions. Understanding women’s involvement of others in participation decisions is critical to inform practices supporting informed decision-making. Methods 140 in-depth interviews were conducted with pregnant or recently pregnant women; 70 in the U.S. and 70 in Malawi, 35 HIV-positive and 35 uninfected in each setting. Participants described whether they would involve others in enrollment decisions while pregnant for hypothetical HIV prevention or treatment research scenarios. Thematic analysis informed the analytic approach. Interviews were transcribed, translated when necessary, coded, and emergent themes identified. Results In both contexts, many women described collaborative decision-making approaches, particularly with male partners, female relatives and friends, and in the US, clinicians. Participants commonly described valuing others’ perspectives on risks and benefits and shared responsibility for the decision. Many women described sole decision-making authority, even if informing others was likely or necessary. Few women described partners having sole decisional authority. Several participants, particularly in Malawi, stated they would decide independently for fear of HIV stigma, accusations of infidelity, and relationship conflict. Conclusion Women described a variety of approaches and considerations in consulting others about HIV biomedical research enrollment while pregnant. Congress attendees will understand the importance of developing practices responsive to participants’ needs and preferences, including facilitating women’s ability to engage others in the decision-making process if she desires and supporting individual decision-making. Disclosure No significant relationships.
The Internet of Materials: A Vision for Computational Materials

Weiser inspired us by forcing us to think differently about the size and usage patterns of computers. This vision of computational materials is similarly motivated. Indeed, inspiration is critical at this time, because there are so many challenges to overcome and it will take a community to address them. Significant technical challenges and a desire to deliver meaningful value while guarding against violations of greater societal values can only happen if we are fueled by the passion of this vision.
Megalin-mediated albumin endocytosis in cultured murine mesangial cells.

Abstract Endocytosis by podocytes is gaining increased attention as a biologic means of removing large proteins such as serum albumin from the glomerular barrier. Some of this function has been attributed to the megalin/cubilin (Lrp2/Cubn) receptor complex and the albumin recycling protein FcRn (Fcgrt). However, whether other glomerular cells possess the potential to perform this same phenomenon or express these proteins remains uncharacterized. Mesangial cells are uniquely positioned in glomeruli and represent a cell type capable of performing several diverse functions. Here, the expression of megalin and FcRn in murine mesangial cells along with the megalin adaptor protein Dab-2 (Dab2) was shown for the first time. Cubilin mRNA expression was detected, but the absence of the cubilin partner amnionless (Amn) suggested that cubilin is minimally functional, if at all, in these cells. Mesangial cell endocytosis of albumin was characterized and shown to involve a receptor-mediated process. Albumin endocytosis was significantly impaired (p
Medically Assisted Reproduction and Autoimmunity

After reading this chapter, the reader will be able to understand the role and impact of autoimmunity on:
A Broad-Based Approach to Social Needs Screening in a Pediatric Primary Care Network

Abstract Objective In 2016, the American Academy of Pediatrics recommended universally screening patients for social needs, and in 2018, a quality measure for social needs screening was included in some Massachusetts Medicaid contracts. However, exact guidelines for screening were not provided. We describe the results and implications from a broad-based health-related social needs (HRSN or “social needs”) screening program within our large, pediatric primary care network. Methods We adapted items from The Health Leads toolkit to create our network's screening tool: The Health Needs Assessment (HNA). We trained staff to use the tool and provided staff with resources to assist families with their needs. All patients with a primary care physician in the network were eligible to complete an HNA. We calculated descriptive statistics and estimated the risk of identifying a social need using multivariable regression analyses. Results Between June 2018 and May 2019, 100,097 patients completed an HNA; 8% of patients identified a social need, and 33% of those patients requested assistance with the need(s). The multivariate analysis revealed an association between several patient characteristics—health insurance type, age, median household income by zip code, complex chronic conditions, race/ethnicity—and identifying a social need. Conclusions Our large, pediatric primary care network successfully instituted a broad-based HRSN screening program in response to state and national screening recommendations. We observed a low prevalence of reported social needs and a propensity to forego assistance. Additional research is needed to understand the barriers around the disclosure of social needs and requests for assistance.
Chronic Toxicity of Cobalt to Marine Organisms: Application of a Species Sensitivity Distribution Approach to Develop International Water Quality Standards

Water quality standards for cobalt (Co) have yet to be developed for the European Union or the United States. The primary objective of the present study was to produce a data set comprising marine Co toxicity data that could be used by both the European Union and the United States to determine a predicted-no-effect concentration and ambient water quality criteria, respectively. Ten marine species, ranging from algae to fish, were subjected to chronic Co toxicity tests that were designed to meet international water quality testing standards. Chronic 10% effect concentration values ranged from a low of 1.23 µg dissolved Co/L for red algae (Champia parvula) to a high of 31 800 µg dissolved Co/L for sheepshead minnow (Cyprinodon variegatus). The species sensitivity ranking for chronic marine Co exposure was as follows (from most to least sensitive): C. parvula > Neanthes arenaceodentata (polychaete) > Americamysis bahia (mysid shrimp) > Skeletonema costatum (marine diatom) > Dendraster excentricus (sand dollar) > Mytilus galloprovincialis (mussel) > Strongylocentrotus purpuratus (purple sea urchin) > Crassostrea gigas (oyster) > Dunaliella tertiolecta (marine flagellate) > C. variegatus. Chronic test results indicated that invertebrate and plant species were substantially more sensitive to Co exposure than fish. The chronic toxicity data were used to calculate a species sensitivity distribution, from which a hazardous concentration 5th percentile of 7.09 µg dissolved Co/L (95% CI 0.025-47.3 µg Co/L) was derived. Environ Toxicol Chem 2021;40:1405-1418. © 2021 SETAC.
Single-Layer Thin-Film Lithium Niobate Out-of-Plane Actuators

This work presents a novel out-of-plane actuator that is composed of a single thin-film piezoelectric layer. The devices are implemented based on a platinum-coated silicon substrate to which a lithium niobate (LN) film is bonded. The out-of-plane movement of the single-layer piezoelectric film is enabled by the unique piezoelectric properties of LN, while a relatively large movement is achieved due to the large coupling coefficients of the film combined with the optimized alignment of the actuation arms to proper LN crystalline orientation. The process flow designed for the fabrication of these devices is detailed, and the preliminary test results are presented. In situ SEM imaging was conducted to quantify the amount of displacement, which is observed to be 4µm for an applied voltage of ±25V in a 250x250 µm2 device.
Sesame Street: Beyond 50

Sesame Street characters sparked curiosity and the joy of learning in me as a young child as they have helped children around the world for over 50 years. Years later, the large body of research on...
Twist Modulates Breast Cancer Stem Cells by Transcriptional Regulation of CD24 Expression

The cancer stem cell paradigm postulates that dysregulated tissue-specific stem cells or progenitor cells are precursors for cancer biogenesis. Consequently, identifying cancer stem cells is crucial to our understanding of cancer progression and for the development of novel therapeutic agents. In this study, we demonstrate that the overexpression of Twist in breast cells can promote the generation of a breast cancer stem cell phenotype characterized by the high expression of CD44, little or no expression of CD24, and increased aldehyde dehydrogenase 1 activity, independent of the epithelial-mesenchymal transition. In addition, Twist-overexpressing cells exhibit high efflux of Hoechst 33342 and Rhodamine 123 as a result of increased expression of ABCC1 (MRP1) transporters, a property of cancer stem cells. Moreover, we show that transient expression of Twist can induce the stem cell phenotype in multiple breast cell lines and that decreasing Twist expression by short hairpin RNA in Twist-overexpressing transgenic cell lines MCF-10A/Twist and MCF-7/Twist as well as in MDA-MB-231 partially reverses the stem cell molecular signature. Importantly, we show that inoculums of only 20 cells of the Twist-overexpressing CD44 + /CD24 -/low subpopulation are capable of forming tumors in the mammary fat pad of severe combined immunodeficient mice. Finally, with respect to mechanism, we provide data to indicate that Twist transcriptionally regulates CD24 expression in breast cancer cells. Taken together, our data demonstrate the direct involvement of Twist in generating a breast cancer stem cell phenotype through down-regulation of CD24 expression and independent of an epithelial-mesenchymal transition.
Size Distribution of Membrane Proteins of Rat Liver and Their Relative Rates of Degradation

Abstract The proteins associated with various membrane fractions, including smooth and rough endoplasmic reticulum, plasma membrane, and mitochondria of rat liver, were solubilized with sodium lauryl sulfate and separated by electrophoresis on sodium lauryl sulfate acrylamide gels. Smooth and rough endoplasmic reticulum have similar electrophoretic patterns. All other fractions have characteristic patterns in which no single or predominant protein occurs. The smooth endoplasmic reticulum fraction was fractionated by use of Triton X-100, which solubilized approximately 50% of the membrane proteins. The patterns of Triton X-100-soluble and -insoluble proteins are distinctive. The relative rates of degradation of the proteins were studied by use of a double isotope technique in which 14C-leucine was administered to intact rats 4 days prior to administration of 3H-leucine. As indicated by the differences in 3H:14C ratios, there is a marked heterogeneity of turnover of proteins of both the endoplasmic reticulum and plasma membrane. There is a general correlation between the relative degradation rates of membrane proteins and the molecular size of the protein (subunit) as separated by electrophoresis in sodium lauryl sulfate acrylamide gels. This general relationship was found also for the soluble protein fraction of rat liver, whether fractionated by sodium lauryl sulfate acrylamide gels, or by Sephadex G-200 columns in the presence of sodium lauryl sulfate. A model in which membrane proteins associated and dissociate from the protein-lipid complex is favored to explain the heterogeneity of degradation, and the general correlation of size with degradation rate.
Nutrient Analysis of Iowa Grown Field Peas for Swine Feed

Introduction Field peas are a cool season legume crop. Temperate climatic conditions are the most suitable for pea growing. Higher altitudes and cool seasons can provide excellent yields in warmer climates. Most cultivated field peas belong to the same species (Pisum sativum L.), but several subspecies have been developed to meet specific agronomic, pathological, and nutritional needs of different regions.
Women and security governance in Africa

Funmi Olonisakin and Awino Oketch, Cape Town, Pambazuka Press, 2011, xii +172 pp. While the discourse of policy-makers within the international community has changed to include a greater focus on w...
Logic and Computer Design Fundamentals

Featuring a strong emphasis on the fundamentals underlying contemporary logic design using hardware description languages, synthesis, and verification, this book focuses on the ever-evolving applications of basic computer design concepts with strong connections to real-world technology. Treatment of logic design, digital system design, and computer design. Ideal for self-study by engineers and computer scientists.