cssi/SciSciGPT-SciSciNet huggingface dataset:
Sulindac suppressed beta-catenin expression in human malignant cell lines

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 3 Sulindac, a nonsteroidal anti-inflammatory drug, has been reported to be effective in suppressing tumor growth through the induction of p21WAF1/cip1 in human, animal models of colon cancer and colon cancer cells. In this study, we treated human breast cancer cell line MCF-7, lung cancer cell line A549 and colon cancer cell line SW620 with sulindac to observe the effects of sulindac in other tissue sites. In all three cell lines, proliferation was significantly inhibited by sulindac after 24 hours of treatment. The apoptosis was induced by sulindac in both lung cancer cells and colon cancer cells but the induction of apoptosis was not observed in the breast cancer cells. To further explore the role of p21WAF1 in these actions, the cell lysate was collected after the treatment of 8, 24 and 48 hours with sulindac. Protein expression was assayed by western blot. As documented previously, p21WAF1 was induced by sulindac in colon cancer cell line. However, p21 was not induced by sulindac in the breast or lung cancer cell lines. Unexpectedly, the suppression of beta-catenin, a key regulator of Wnt-pathway was seen in all the three cell lines with sulindac administration. Subsequently, cyclin D1 and cdk 4 were dramatically suppressed by sulindac. In conclusion, our data demonstrated that the efficiency of sulindac in the inhibition of cell proliferation (other than the induction of apoptosis) may be through the suppression of beta-catenin pathway in human breast and lung cancer cell lines.
MLL-Rearranged Leukemias Are Dependent On the Histone H2B Ubiquitin Ligase RNF20

Abstract Abstract 649 Histone mono-ubiquitination is a major signaling mechanism that shapes the structure and function of chromatin. Hence, factors that regulate ubiquitin attachment to histones (E2 conjugating enzymes, E3 ligases, and de-ubiquitinating enzymes) often play fundamental roles in epigenetic biological processes, including the pathophysiology of human disease. Here, we explored whether the known regulators of histone ubiquitination/deubiquitination are linked to the pathogenesis of acute myeloid leukemia, a disease often associated with aberrant chromatin signaling. To this end, an shRNA screen was performed where all histone E2s, E3s, and deubiqitinating enzymes were individually suppressed and evaluated for their role in supporting growth of acute myeloid leukemias initiated the MLL-AF9 oncogene. This analysis identified the histone H2B ubiquitin ligase RNF20 (also known as BRE1A) as essential for MLL-AF9 leukemia growth. This finding was verified in a genetically engineered mouse leukemia model (driven by MLL-AF9 together with NrasG12D) under both in vitro and in vivo conditions. In addition, human leukemia cell lines harboring MLL-rearrangements were found to be uniformly dependent on RNF20 for their proliferation. Upon inhibition of RNF20 and elimination of global H2B mono-ubiquitination, leukemia cells arrest in the G1/G0 stage of the cell-cycle without evidence of myeloid maturation. RNA-SEQ analysis identified that a suite of direct transcriptional targets of MLL-AF9 were downregulated in expression upon RNF20 inhibition, including Hoxa9, Hoxa10, Meis1, and Mef2c. While H2B mono-ubiquitination has been shown previously to promote the catalytic function of H3K4 and H3K79 methyltransferases, we find that in leukemia cells inhibition of RNF20 eradicates global H2B mono-ubiquitination without influencing global H3K4me3 and H3K79me2/me3. However, we find instead that RNF20 is selectively required to maintain local levels of H3K79 methylation in the body of MLL-AF9 target genes, such as Hoxa9. Since MLL-AF9 is known to directly recruit the H3K79 methyltransferase DOT1L to transactivate its target genes, our findings suggest a mechanism whereby targeting RNF20 interferes with the transactivation function of MLL-AF9. Moreover, we found that shRNA-based suppression of RNF20 sensitizes leukemia cells to the growth-arrest induced by the BET bromodomain inhibitor JQ1, without influencing the sensitivity to cytotoxic agents daunorubicin and etoposide. Based on these collective findings, we propose that RNF20 represents a major chromatin-based signaling pathway necessary to maintain the MLL-rearranged subtype of acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.
Structure-based voiced/usable speech detection using state space embedding

The process of speech production in the human system is very complex, possesses nonlinearities, and can only be precisely modeled in terms of nonlinear dynamics. A non-linear speech classification approach is proposed, which classifies speech based on features extracted from Takens' method of delays, a technique used to reconstruct signals into a trajectory in multidimensional state space. In this research, two types of speech detection are presented, namely, voiced and usable speech (for speaker identification purposes). The proposed approach has been able to yield a probability of error of 12% in noisy environments for voiced speech detection, and 78% correct usable speech detection by comparing the structures of embedded voiced speech frames with embedded unvoiced speech frames, and embedded usable speech frames with unusable speech. Some applications of this speech detection technique include the enhancement of speaker identification and speech recognition systems.
Multiscale modeling of silicon heterojunction solar cells

In recent years, silicon photovoltaic technologies utilizing amorphous silicon (a-Si) to form heterojunction solar cells with thin intrinsic (HIT) passivating layers have consistently demonstrated high efficiencies (>20%) including a world record efficiency of 25.6%, high fill factor's and high open circuit voltages (V OC > 700 mV). Further improvements in efficiency require a rigorous approach to better understand and improve device behavior. In this work we analyze the transport and device performance of heterojunction cells by applying a multiscale simulation methodology. Our multiscale solver consists of three primary domains, namely; the drift-diffusion (DD) domain, the ensemble Monte Carlo (EMC) and the kinetic Monte Carlo (KMC) domain. Using our multiscale methodology we investigate the role of midgap defects in the a-Si and interface defects at the crystalline silicon (c-Si) and a-Si heterointerface. Simulations indicate that recombination at the interface is a key limiting factor in device performance and contributes to the ‘S’ shaped current voltage characteristic. We have also used commercial device simulator SILVACO to investigate the role of surface potential at the heterointerface.
Temporal precedence in the identification of mediators of change: A brief comment on "Mediators of change in the child/adolescent multimodal treatment study" (Kendall et al., 2016).

Objective Comment on the issue of temporal precedence and the implications for interpreting the results of the mediation analyses in the Child/Adolescent Multimodal Treatment Study. Method Review of Kendall et al. (2016). Results Kendall et al. reported that residualized (baseline to posttreatment) change in coping efficacy, but not anxious self-talk, mediated residualized (baseline to follow-up) change in anxiety symptoms in cognitive-behavior therapy (CBT), sertraline (SRT), and CBT + SRT compared to placebo. Because the measure of anxiety symptoms included data from follow-up, it was concluded that "the gains being referred to can be viewed as 'change following treatment'" (p. 8) and, therefore, the analyses captured "true temporal precedence" (p. 3). However, the anxiety scores represented an amalgam of change occurring within and after treatment, and available data suggest much of the anxiety change occurred during the treatment, the time when the change in coping occurred. Conclusions Given the measurement timeline, a clear and unambiguous claim of demonstrating temporal precedence is not justified. Nonetheless, these results remain important for other reasons when interpreted in the context of the broad cognitive-behavioral conceptual model of anxiety that led to the selection of these mediators for examination. (PsycINFO Database Record
Why do students quit school? Implications from a dynamical modelling study

In 2012, more than three million students dropped out from high school. At this pace, we will have more than 30 million Americans without a high school degree by 2022 and relatively high dropout rates among Hispanic and African American students. We have developed and analysed a data-driven mathematical model that includes multiple interacting mechanisms and estimates of parameters using data from a specifically designed survey applied to a certain group of students of a high school in Chicago to understand the dynamics of dropouts. Our analysis suggests students9 academic achievement is directly related to the level of parental involvement more than any other factors in our study. However, if the negative peer influence (leading to lower academic grades) increases beyond a critical value, the effect of parental involvement on the dynamics of dropouts becomes negligible.
Therapeutic Angiogenesis and Vasculogenesis for Ischemic Disease

Despite significant advances in myocardial revascularization and reperfusion, coronary artery disease and subsequently myocardial infarction are the leading cause of morbidity and mortality in the United States. Thus, one of the main goals in the treatment of myocardial ischemia is the development of effective therapy for angiogenesis. The first evidence we found is the demonstration of alleviation of myocardial ischemia and increased number of collateral blood vessels in the early 1990s following intracoronary administration of basic fibroblast growth factor protein in dog. Multiple animal studies, including ours, and a small number of human studies have confirmed the concept of stimulation of collateral development by pharmacological and molecular means. This includes direct delivery of growth factors into the ischemic target tissues, or of genes that encode for synthesis of growth factors by target tissues. Both cell therapy and gene therapy have proven to be effective in promoting neovascularization in various animal models. Although cell therapy alone is proven to be beneficial, the combination of cell and gene therapy may enhance therapeutic neovascularization. Thus, clinically relevant, combined strategy could be an excellent strategy for treating patients with myocardial infarction.
Biomedical imaging using optical coherent tomography

Optical Coherence Tomography (OCT) is a new optical technique for performing non-contact, micron resolution, cross sectional tomography imaging in biological systems. The authors discuss applications of OCT to ophthalmology, general medicine, and microscopy.
System-on-Chip Photonic Integrated Circuits

Key advances which enabled the InP photonic integrated circuit (PIC) and the subsequent progression of InP PICs to fully integrated multichannel DWDM system-on-chip (SOC) PICs are described. Furthermore, the current state-of-the-art commercial multichannel SOC PICs are reviewed as well as key trends and technologies for the future of InP-based PICs in optical communications.
A Model to Integrate Health Promotion and Wellness in Physical Therapist Practice: Development and Validation

Background Globally, physical therapy professional organizations have called for physical therapists to perform lifestyle behavior management during customary care, or health-focused care, due to increasing morbidity and mortality related to noncommunicable diseases. Given the potential for health-focused care to improve health outcomes, physical therapists should integrate health promotion into their daily clinical practice. A clinical model that illustrates necessary steps to deliver health-focused care would be helpful to educate present and future physical therapists. Objective The purpose of the study was to develop and validate the Health-Focused Physical Therapy Model (HFPTM) for physical inactivity and smoking. Methods The authors used a mixed method approach. The preliminary model was informed by previous research and the investigators' shared experience in health promotion and physical therapy. An interdisciplinary group of health professionals provided input into the preliminary model by way of a World Cafe format. Eight physical therapists with health promotion and education expertise then engaged in a Delphi process to establish content validity. Results World Cafe participants indicated that: (1) physical therapists are well positioned to engage in health promotion and wellness, and (2) the model facilitates interdisciplinary collaboration and consultation. Delphi process participants reached majority consensus in 1 round. The average model content validity index (CVI) was .915 for physical inactivity and .899 for smoking. Agreement concerning the model schematic was 88% for either behavior. Investigators made few editorial changes after the Delphi process. Limitations Limitations of this study include using only 2 unhealthy lifestyle behaviors for testing, and performing the testing in a nonclinical setting. Conclusions An interdisciplinary group of health professionals believes that physical therapists should practice health-focused care and that the HFPTM is a valid model. This model could help physical therapist educators when educating physical therapist students and clinicians to practice health-focused care.
Design for Emerging Media: How MR Designers Think About Storytelling, Process, and Defining the Field

Given mixed reality’s (MR) unique status as an emerging medium that incorporates both the physical and the virtual in hybrid space, it is a particularly interesting field in which to study the design process as a whole, and interactive narrative design in particular. How prominently does story figure in MR design? What kinds of stories are being told? As MR tools become more accessible, the field is opening up to a wider variety of practitioners. However, the full breadth of methods and techniques being brought to bear in design for MR has not yet been studied. This paper presents findings from an interview study with fifteen leading MR designers, and describes the multiplicity of approaches they use. These approaches are presented as a matrix, composed of a opportunistic—deterministic spectrum (based on designs planned in advance vs. improvisation), and a storytelling—sensationalizing spectrum (based on designs aimed at narrative creation vs. development of a sensory experience).
Final adult height of patients with childhood-onset systemic lupus erythematosus: a cross sectional analysis

To compare final height to mid-parental target height among adults with childhood-onset systemic lupus erythematosus (cSLE) versus adult-onset SLE (aSLE), and to evaluate the impact of age at SLE onset on final height. Data derived from the Lupus Outcomes Study, a longitudinal cohort of adults with SLE, was used for this cross-sectional analysis (N = 728). Participants aged 18–63 years with complete height data were included (N = 566) and were classified as cSLE if age at diagnosis was 2 SD below target height. Separate analyses were conducted for females and males to account for differences in timing of the pubertal growth spurt for each sex. Participants with cSLE were, on average, 2.4 cm shorter than their target height (95% CI -4, − 0.7). The adjusted odds ratio (OR) for substantially reduced final height was 3.9 (95% CI + 2.0, + 7.2, p < 0.001) as compared to participants with aSLE. Females diagnosed between 11 and 13 years were at greatest risk for substantially reduced final height, with adjusted OR of 11.2 (95% CI + 3.4, + 36.3) as compared to participants with aSLE (p < 0.001). cSLE is associated with shorter-than-expected final height. Onset of SLE in the pubertal period, near the time of maximum linear growth, may have a particularly significant impact on final height.
“No war, no peace” in a region in flux: crisis, escalation, and possibility in the Eritrea-Ethiopia rivalry

ABSTRACTThis article examines the evolving rivalry between Eritrea and Ethiopia in light of military clashes between the two countries that occurred in June 2016. Drawing on rationalist understandings of international politics, it illustrates the calculus that sustained the rivalry for nearly 16 years. These forces, while sufficient to have maintained the situation of “no war, no peace” for a considerable period of time, gave way to a new set of dynamics that significantly eroded the fragile status quo. In that context, a slow, but perceptible shift in the regional balance power seemed to have increased the risk of another round of military conflict between Eritrea and Ethiopia. While Ethiopia’s recent selection of a new prime minister has created real possibility of a reset of Eritrea-Ethiopia relations, the underlying structural dynamics between the two countries remain volatile. For better or worse, Africa’s most intractable interstate rivalry sits at a critical juncture.
A Sustainable Design Method Acting as an Innovation Tool

Product companies generally see sustainability as a burden limiting their design process, similar to cost or safety limits. A method for sustainable design was created, attempting to turn sustainability from a burden into an innovation tool with inherent business value. The method combines creative whole-systems thinking with quantitative sustainability metrics. It facilitates innovation by the creation of visual whole-system maps that encourage more thorough and more radical brainstorming. It facilitates sustainability by using quantitative measurements, such as life-cycle assessment or point-based certification systems, to set priorities and choose final designs. The method has been anecdotally tested in classes at four universities, and many of the companies partnering with these classes have said the students provided both sustainability and feature /functionality benefits. This paper also compares the method to Lindahl’s nine recommendations for being useful to engineering designers. Thus there is at least anecdotal evidence that the design method may turn sustainability from a burden into an innovation tool. Future studies should compare the method against industry-leading innovation and green design methods.
Measurement of Photoproduction of ω 0 and ρ 0 Mesons in Hydrogen

The $t$ distribution for photoproduction of ${\ensuremath{\rho}}^{0}$ and ${\ensuremath{\omega}}^{0}$ mesons from hydrogen has been measured for incident energies between 2.9 and 4.7 GeV. A S\"oding interference model fits the ${\ensuremath{\rho}}^{0}$ data and gives $t$ distributions in agreement with ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}p$ elastic scattering and most previous ${\ensuremath{\rho}}^{0}$ experiments. The ${\ensuremath{\omega}}^{0}$ $t$ distribution changes with incident energy but in our highest-energy bin $3.7\ensuremath{\le}k\ensuremath{\le}4.7$ GeV becomes diffractive and is consistent with being equal to a constant times the ${\ensuremath{\rho}}^{0}$ $t$ distribution.
LOCAL DENSITY APPROACH TO BULK AND SURFACE CHARGE DENSITIES

As is clear from some of the other lectures given at this Institute, the current popularity of energy band theory stems from its successful application to the study of increasingly diverse problems in solid state physics. Recent new sophisticated experiments on both traditional materials and those having complex crystallographic structures have demanded, however, not only theoretical descriptions of eigenvalue phenomena but also detailed and precise wave functions with which to determine not only charge and spin densities but also the expectation values of different observable operators. Such a demanding test of the predictions of one-electron theory has the additional virtue of permitting, by their comparison with experiment, accurate determinations of the relative magnitude and importance of many-body effects in real solids. Thus, as emphasized by Norman March, there has developed considerable interest in applying the Hohenberg-Kohn-Sham (1,2) local density functional (LDF) formalism, and its recent extension as a local spin density functional (LSDF) formalism (3), to the investigation of various ground state properties of solids despite the usual difficulties of solving the associated one-particle equation characterized by a multi-center non-spherical potential.
The Role of Learning in Honey Bee Foraging

Honey bees, like all animals, are born knowing how to recognize and respond adaptively to many important stimuli. For example, an adult honey bee knows how to chew out of the cell in which it metamorphosed as a pupa, how to clean cells, how to recognize and tend larvae, how to build honey comb, how to guard the hive and attack intruders, how to recognize and remove dead bees, how to take off, fly, and land, and so on (reviewed by Gould 1982). But there are many things the lifestyle of honey bees requires them to know that are not and cannot be known in advance. The need to learn is particularly evident in the context of navigation (reviewed by Dyer & Gould 1983) and, especially, in the activity navigation primarily subserves: foraging. This paper will focus on the role of learning in foraging, and will point out the intimate association between instinct and learning in bees which results from the specialized learning programs essential for efficient foraging. The question of optimal foraging will be ignored since optimal foraging, like evolution, is essentially axiomatic rather than explanatory or testable in any non-trivial sense. Instead I will focus on mechanisms which, just as natural selection is a testable mechanism of evolution, provide an opportunity for deeper and more satisfying experimental challenge and verification.
Insulin Secretion and the Glutamine-Glutamate-Alpha-Ketoglutarate Axis

Protein-sensitive hypoglycemia in children with congenital hyperinsulinism (HI) highlights the important role of amino acids in regulation of insulin secretion. The studies of insulin secretion in three HI mouse models suggested that glutamine (Q)-glutamate (E)-alpha-ketoglutarate (αKG) axis played a key role in amino acid-stimulated insulin secretion. The mechanism of dysregulated insulin secretion in HI with a glutamate dehydrogenase (GDH) gain of function mutation is due to increased amino acid oxidation via this key axis. Loss of function mutation of Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) also cause HI, the study of SCHAD knockout mice indicated that SCHAD inhibits GDH via protein-protein interaction; HI due to SCHAD deficiency shares a similar mechanism with GDH gain of function. In contrast, loss of function mutations of ATP-dependent potassium channels are sensitive to glutamine but not to leucine-stimulated insulin secretion. 13C tracing studies in islets suggested that generation of glutamine via the reverse flux of Q-E-αKG axis during glucose oxidation is important to maintain insulin secretion stimulated by glucose. The key enzymes in the Q-E-αKG axis, including glutaminase, GDH and glutamine synthetase, serve as intracellular energy sensors to determine the sensitivity of amino acid stimulation of insulin secretion.
Technology Transfer - The Human Side of IT

Information Technology (IT) is fundamentally a people business that involves integrating technology into human processes in order to solve problems and create new capacities. These integration skills are not often taught in undergraduate computing curricula. The Galisano College of Computing and Info rmation Sciences at Rochester Institute of Technology (RIT) has been offering a course in the diffusion of innovations for several years now and considers the communication needed to diffuse an innovation core to IT’s mission. The course, called Technology Transfer, is the study of the "flow" of technology from its creation through adoption to implementation and eventual effects. Our BS in Information Techno logy has one of the few courses that address these issues directly. Many students are skeptical of the reality of organizational life and fail to understand the way that change actually occurs. The course provides a framework by which students can interpret and understand their roles as change agents in the organization. This paper provides an overview of RIT's Technology Transfer course, explains its rationale within the curriculum and its contribution to professional practice. It also discusses some of the techniques used in teaching these skills. The paper concludes with feedback on the value of the course to our graduates.
Dietary Polyphenols and Periodontitis—A Mini-Review of Literature

Periodontitis, which is a chronic infection and disease of the periodontium, is a significant global health burden and is linked to other chronic health conditions such as diabetes and cardiovascular diseases. Dietary polyphenols present in a wide variety of plant-based foods, herbs, and botanicals have been shown to exert antimicrobial, anti-inflammatory, and reduced osteoclast and alveolar bone loss activities in animal models of periodontitis. Polyphenol-containing beverages and foods especially green tea and its active catechin epigallocatechin-3-gallate, cranberries, pomegranates, and fruit and vegetable extracts have reported bacteriostatic/bactericidal activity against microbial species such as P. gingivalis and shown total bacterial burden in clinical studies. These polyphenols also exhibit anti-inflammatory and antioxidant effects, which have the potential to impact various biological mechanisms for reducing the initiation and progression of periodontitis. The main objective of this mini-review is to focus on the mechanisms of action of dietary polyphenols in improving the pathophysiology underlying chronic inflammatory diseases like periodontitis based on pre-clinical and clinical models.
Pathogenesis And Radiological Findings In Rare Case Of Salter Harris Type I Distal Tibial Fracture With Associated Osteonecrosis In The Paediatric Population.

Salter-Harris type I fractures of the distal tibia are commonly seen in paediatrics and management of such fractures follows an algorithm established in the literature. Despite this, osteonecrosis of the distal tibia can subsequently develop. Osteonecrosis or avascular necrosis is cell death that occurs secondary to trauma, metabolic disturbances, sickle cell disease, or medication side effect. It most frequently affects the femur, talus, or humerus, and rarely the tibia. Radiographs and MRI are pivotal in making a timely diagnosis in order to minimize patient discomfort. To the best of our knowledge, there has only been one previous documented case of osteonecrosis following a Salter Harris Type I distal tibial fracture. Here, we present the second such case. Keywords: Salter Harris Fracture; Osteonecrosis; Distal Tibial Fracture
A review of aortic stenosis: an anesthetic perspective

Anesthetists face many challenges in the operating room Many patients have severe comorbidities that the anesthetic plan must be tailored to In the United States aortic stenosis AS is the most common valvular disorder minus AS affects nearly two to four percent of the population over the age of Patients that are diagnosed with severe AS have a three year mortality of percent unless the valve is replaced Aortic stenosis is characterized by narrowing of the aortic valve AV causing a litany of symptoms This review will discuss the anatomy and physiology etiology pathophysiology and symptoms associated with AS Additionally anesthetic considerations for the care of a patient with AS will be reviewed
Self-heating in Inserted Oxide FINFETs

Thermal behavior of inserted oxide FinFET is studied and compared to that of conventional bulk and SOI FinFET. It is observed that thermal resistance and temperature rise in iFinFET with 3 nm thick inserted oxide is about 8% higher compared to conventional bulk FinFET. Effect of increasing inserted oxide thickness and thermal conductivity is further documented.
How long can this party last? What the rise and fall of OR/MS can teach us about the future of business analytics

Business analytics (BA) is an important organisational activity and research discipline. However, history has shown that information systems (IS)-related disciplines with promising futures do not a...
Gendered identities and German Islamophobias

The German political imaginary and reality increasingly equate the presence of Muslim ‘Others’ within and beyond national borders with the Islamization and ‘Global Islam’, deemed an existential and...
Utilizing cell penetrating peptides to enhance the potency of a thermally responsive c-Myc inhibitory polypeptide

5600 Current cancer therapy is limited by the extreme toxicity of chemotherapeutic drugs, which can cause extensive damage to non-cancerous tissues when used in doses required to eradicate cancer cells. The side effect profile and the efficacy of chemotherapeutics can be improved by two mechanisms: 1) developing drugs which are specifically toxic to the cancer cells and 2) developing methods to deliver drugs to the tumor site. In an attempt to combine these approaches, we developed a thermally responsive polypeptide inhibitor of the c-Myc oncogene. This polypeptide is based on the thermally responsive Elastin-like polypeptide (ELP). When injected systemically, ELP-fused drugs will aggregate and accumulate at the tumor site where local hyperthermia is applied. For this study, ELP was fused to a peptide which blocks c-Myc / Max dimerization (H1), thereby inhibiting transcription activation by c-Myc. In a previous study, the H1 peptide was fused to ELP and the penetratin peptide (Pen-ELP-H1), and it was shown that Pen-ELP-H1 was capable of entering MCF-7 breast cancer cells, binding and sequestering c-Myc to the cytoplasm, preventing expression of c-Myc target genes, and inhibiting cell proliferation. Here, the ELP-H1 polypeptide is fused to two different cell penetrating peptides (CPPs), the Tat peptide from HIV-1 and the Bac peptide from the antimicrobial bactenecin 7 peptide. Both CPPs improved cellular uptake relative to ELP-H1 alone, but neither produced intracellular levels equivalent to those seen with Pen-ELP-H1. However, Bac-ELP-H1 was a more potent inhibitor of MCF-7 cell proliferation than Pen-ELP-H1. Bac-ELP-H1 localized to the nucleus in a percentage of the cells, and the nuclear targeting was proportional to increases in both polypeptide concentration and time after treatment. Although more Pen-ELP-H1 entered the cell, it functioned through a mechanism of binding and sequestering newly translated c-Myc to the cytoplasm. The improved potency of Bac-ELP-H1 is likely due to its ability to deliver the H1 peptide to the nucleus, where the c-Myc / Max interaction naturally occurs. The potency of Bac-ELP-H1 was also tested against four cell lines with varying c-Myc expression levels. Bac-ELP-H1 was most potent in the cancer cell lines with high c-Myc expression, HeLa and MCF-7, and less potent in the low c-Myc expressing non-cancerous cell lines MCF-10A and WI-38. This data demonstrates that ELP can be targeted to the desired cellular compartment simply by choice of the CPP used. Also, when targeted to the nucleus by Bac, the c-Myc inhibitor was most potent in the cell lines with the highest c-Myc expression levels. The ELP-based c-Myc inhibitor employs both design strategies described above, creating a therapeutic molecule with two levels of target specificity. The polypeptide can be targeted to the tumor site using focused hyperthermia, and the polypeptide is most toxic to the cancerous cells.
Immunohistochemical staining patterns of Ki-67 and p53 in florid reactive urothelial atypia and urothelial carcinoma in situ demonstrate significant overlap.

Summary Flat urothelial lesions with atypia may pose significant diagnostic challenges. Given frequent increased proliferation rates in florid reactive urothelial atypia and limited studies on the interpretation of p53 stains in the urothelium (following current standard guidelines for correlation with P53 mutation status), we sought to further study the discriminatory value of Ki-67 and p53 for florid reactive urothelial atypia versus urothelial carcinoma in situ (CIS). Bladder specimens diagnosed as reactive urothelial atypia (n = 40) and CIS (n = 40) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, CD44, and CK20. Immunoreactivity was scored based on percent cells positive for Ki-67 and pattern of reactivity with p53 (aberrant: diffuse strong positive or negative; normal: patchy/wild type). CD44 and CK20 reactivity patterns served as adjunctive internal validation controls for reactive urothelial atypia and CIS, as previously described. In reactive urothelial atypia, Ki-67 ranged from 0% to 90% (mean, 34% ± 26) with 30 cases (75%) having >10%. In CIS, Ki-67 ranged from 5% to 95% (mean, 50% ± 25) with 17 cases (43%) having >50%. In all 40 cases (100%) of reactive urothelial atypia, p53 expression had a wild-type pattern. In CIS, aberrant p53 expression was identified in 15 cases (37%): 3 cases (7%) were p53 negative (i.e. null phenotype) and 12 cases (30%) showed strong and diffuse nuclear reactivity (in >85% of cells). The remaining 25 cases (63%) of CIS had a p53 wild-type pattern of expression. Cytoplasmic CK20 immunoreactivity in umbrella cells was seen in 34 cases (85%) of reactive urothelial atypia, and 6 cases (15%) were negative. In addition, 35 cases (88%) of reactive urothelial atypia demonstrated full-thickness CD44 expression, while 5 cases (12%) had expression confined to the basal/parabasal layers of the urothelium. Strong and diffuse CK20 positivity was present in 39 cases (98%) of CIS, and patchy positivity was detected in 1 case (2%). None of the CIS cases overexpressed CD44: 16 cases (40%) showed focal expression in the nonneoplastic basal cell layer; 24 cases (60%) demonstrated no staining. In summary, Ki-67 has poor discriminatory value for reactive urothelial atypia versus CIS and adds little to the classic CK20/CD44 immunophenotype. While p53 sensitivity for CIS is relatively low (30%) and interpretation as either wild type or negative may be challenging in a small subset of cases, strong and diffuse nuclear reactivity was 100% specific in the distinction from florid reactive urothelial atypia in this cohort.
The Stage Theory of Groups

I propose a ‘stage theory’ of groups: a group is a fusion of group-stages, where a group-stage is a plurality of individuals at a world and a time. The stage theory consists of existence conditions...
A CASE OF NOT SO BENIGN LEADLESS PACEMAKER

Leadless pacemakers have been shown to have lesser risk of complications. However, they can lead to mitral regurgitation (MR) due to iatrogenic left bundle branch block (LBBB). An 85yo man with history of atrial fibrillation (AF) diagnosed 10 years ago being treated with atenolol and warfarin; and
Genome-Wide Discovery of G-Quadruplexes in Wheat: Distribution and Putative Functional Roles.

G-quadruplexes are nucleic acid secondary structures formed by a stack of square planar G-quartets. G-quadruplexes were implicated in many biological functions including telomere maintenance, replication, transcription, and translation, in many species including humans and plants. For wheat, however, though it is one of the world’s most important staple food, no G-quadruplex studies have been reported to date. Here, we computationally identify putative G4 structures (G4s) in wheat genome for the first time and compare its distribution across the genome against five other genomes (human, maize, Arabidopsis, rice, and sorghum). We identified close to 1 million G4 motifs with a density of 76 G4s/Mb across the whole genome and 93 G4s/Mb over genic regions. Remarkably, G4s were enriched around three regions, two located on the antisense and one on the sense strand at the following positions: 1) the transcription start site (TSS) (antisense), 2) the first coding domain sequence (CDS) (antisense), and 3) the start codon (sense). Functional enrichment analysis revealed that the gene models containing G4 motifs within these peaks were associated with specific gene ontology (GO) terms, such as developmental process, localization, and cellular component organization or biogenesis. We investigated genes encoding MADS-box transcription factors and showed examples of G4 motifs within critical regulatory regions in the VRN-1 genes in wheat. Furthermore, comparison with other plants showed that monocots share a similar distribution of G4s, but Arabidopsis shows a unique G4 distribution. Our study shows for the first time the prevalence and possible functional roles of G4s in wheat.
Appreciating migration flows for health/social services planning: A case study of older adults leaving from New York to Florida

Abstract This paper utilizes the 2009/2010/2011 American Community Survey to examine spatial patterns of later-life relocation from the state of New York into Florida. Given that the first-wave of the Baby Boom generation reached the retirement age of 65 years in January 2011 and many more will continue to do so, examining the mobility/subsequent residential choices of this group is a worthwhile undertaking. This research paper is also a noteworthy contribution because it offers an interdisciplinary study of spatial statistics and population geography. Exploratory spatial analysis and multinomial regressions suggest older adults from New York leave select origins, such as Capital District, Mid-Hudson, and Lower Hudson. In addition, these older adults select preferred destinations in Florida, such as Fort Myers, Fort Pierce–Stuart, and West Palm Beach. This finding can inform planners, policy analysts, and social workers about how to best address issues related to health and community services since not all older adult migrants seeking coastal and recreational areas in Florida maintain greater wealth and better health.
An insertion unique to SARS-CoV-2 exhibits superantigenic character strengthened by recent mutations

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized condition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. These symptoms and the associated laboratory values strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic superantigens to MHCII molecules and T cell receptors (TCRs). Here, we used structure-based computational models to demonstrate that the SARS-CoV-2 spike (S) exhibits a high-affinity motif for binding TCR, interacting closely with both the α- and β-chains variable domains' complementarity-determining regions. The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in any other SARS coronavirus), which is highly similar in both sequence and structure to bacterial superantigens. Further examination revealed that this interaction between the virus and human T cells is strengthened in the context of a recently reported rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2. Furthermore, the interfacial region includes selected residues from a motif shared between the SARS viruses from the 2003 and 2019 pandemics, which has intracellular adhesion molecule (ICAM)-like character. These data suggest that the SARS-CoV-2 S may act as a superantigen to drive the development of MIS-C as well as cytokine storm in adult COVID-19 patients, with important implications for the development of therapeutic approaches.
PAX8 orchestrates an angiogenic program through interaction with SOX17

ABSTRACT Worldwide, the number of new ovarian cancer cases approaches 300,000 with more than 180,000 deaths every year. The low survival-rate reflects the limitations of current therapies and highlights the importance of identifying new therapeutic targets. Despite significant recent efforts to identify novel vulnerabilities in ovarian cancer, none have led to effective durable therapies with improvement in overall survival. PAX8, a lineage-transcription factor, whose expression is a major molecular feature of ovarian carcinomas, represents a novel therapeutic target. Herein, we have identified SOX17 as a bona fide PAX8-interacting partner and elucidated the impact of this interaction on the development of ovarian cancer. Importantly, we found that PAX8 and SOX17 regulate tumor angiogenesis in vitro and in vivo. The role of PAX8 and SOX17 in the regulation of angiogenesis reveals a novel function for these factors in regulating the tumor microenvironment and highlight this pathway as a viable therapeutic target.
Ghosts Are Our Memories : Ghosts in the Schoolyard: Racism and School Closings on Chicago’s Southside

School closures are based on an agenda to close schools in communities of color, especially African American communities. The continued disinvestment of funds and resources needed to support these ...
Housing Rent and Occupational Rank in Beijing and Shenyang, People's Republic of China

Housing reform in China is moving towards privatization or marketization of public housing. To be successful, the reform requires that policy makers allow housing rent differentials to arise and permit reform in wages parallel to reform in rent. This paper analyses the effects of occupational ranks and housing attributes on urban housing rents in Beijing and Shenyang, China. Our work focuses on the magnitude of rent discounts available to different occupational ranks.
Three-Representation Problem in Banach Spaces

We provide the proof of a previously announced result that resolves the following problem posed by A. A. Kirillov. Let T be a presentation of a group $$\mathcal {G}$$ by bounded linear operators in a Banach space G and $$E\subset G$$ be a closed invariant subspace. Then T generates in the natural way presentations $$T_1$$ in E and $$T_2$$ in $$F:=G/E$$ . What additional information is required besides $$T_1, T_2$$ to recover the presentation T? In finite-dimensional (and even in infinite dimensional Hilbert) case the solution is well known: one needs to supply a group cohomology class $$h\in H^1(\mathcal {G},Hom(F,E))$$ . The same holds in the Banach case, if the subspace E is complemented in G. However, every Banach space that is not isomorphic to a Hilbert one has non-complemented subspaces, which aggravates the problem significantly and makes it non-trivial even in the case of a trivial group action, where it boils down to what is known as the three-space problem. This explains the title we have chosen. A solution of the problem stated above has been announced by the author in 1976, but the complete proof, for non-mathematical reasons, has not been made available. This article contains the proof, as well as some related considerations of the functor $$Ext^1$$ in the category Ban of Banach spaces.
The Impact of Increasing Disease Prevalence, False Omissions, and Diagnostic Uncertainty on Coronavirus Disease 2019 (COVID-19) Test Performance.

CONTEXT.­: Coronavirus disease 2019 (COVID-19) test performance depends on predictive values in settings of increasing disease prevalence. Geospatially distributed diagnostics with minimal uncertainty facilitate efficient point-of-need strategies. OBJECTIVES.­: To use original mathematics to interpret COVID-19 test metrics; assess US Food and Drug Administration Emergency Use Authorizations and Health Canada targets; compare predictive values for multiplex, antigen, polymerase chain reaction kit, point-of-care antibody, and home tests; enhance test performance; and improve decision-making. DESIGN.­: PubMed/newsprint-generated articles documenting prevalence. Mathematica and open access software helped perform recursive calculations, graph multivariate relationships, and visualize performance by comparing predictive value geometric mean-squared patterns. RESULTS.­: Tiered sensitivity/specificity comprised: T1, 90%, 95%; T2, 95%, 97.5%; and T3, 100%, ≥99%. Tier 1 false negatives exceeded true negatives at >90.5% prevalence; false positives exceeded true positives at <5.3% prevalence. High-sensitivity/specificity tests reduced false negatives and false positives, yielding superior predictive values. Recursive testing improved predictive values. Visual logistics facilitated test comparisons. Antigen test quality fell off as prevalence increased. Multiplex severe acute respiratory syndrome (SARS)-CoV-2)*influenza A/B*respiratory syncytial virus testing performed reasonably well compared with tier 3. Tier 3 performance with a tier 2 confidence band lower limit will generate excellent performance and reliability. CONCLUSIONS.­: The overriding principle is to select the best combined performance and reliability pattern for the prevalence bracket. Some public health professionals recommend repetitive testing to compensate for low sensitivity. More logically, improved COVID-19 assays with less uncertainty conserve resources. Multiplex differentiation of COVID-19 from influenza A/B-respiratory syncytial virus represents an effective strategy if seasonal flu surges next year.
Daily-level effects of alcohol, marijuana, and simultaneous use on young adults' perceived sleep health.

Study objectives Simultaneous alcohol and marijuana (SAM) use is increasingly prevalent among young adults but has adverse health consequences. The current study examined daily-level associations between perceived sleep health and SAM use, relative to non-substance-use days and alcohol- or marijuana-only days. We also estimated linear associations between alcohol/marijuana use and perceived sleep health and explored whether effects were moderated by combined use of alcohol and marijuana. Methods A community sample of SAM-using young adults (N=409; Mage=21.61, SD=2.17; 50.9% female; 48.2% White; 48.9% college students) completed twice-daily surveys for five 14-day sampling bursts. Daily measurements assessed substance use and perceived sleep health in terms of subjective sleep quality, negative impact of sleep on functioning, and symptoms of insomnia. Results Multilevel models indicated that, relative to non-substance-use days, participants reported poorer perceived sleep health on alcohol-only days, better perceived sleep health on marijuana-only days, and mixed evidence regarding SAM use (i.e., fewer perceived symptoms of insomnia, but poorer perceived next day functioning attributed to sleep). Daily-level estimates showed increased alcohol use was associated with poorer perceived sleep health, while stronger effects from marijuana were associated with better perceived sleep health. Across all indices of sleep health, only one linear association was moderated by combined use: The adverse association between alcohol and next day functioning was weaker on days alcohol was combined with marijuana. Conclusions Findings provide additional evidence for daily-level effects of alcohol and marijuana use on perceived sleep health and address an important literature gap regarding potential adverse effects of SAM use.