cssi/SciSciGPT-SciSciNet huggingface dataset:
Expression of X-Linked Inhibitor of Apoptosis Protein in Reactive Lymphoid Tissues, Non-Hodgkin’s Lymphomas, and Hodgkin’s Disease.

X-linked inhibitor of apoptosis protein (XIAP) is an important regulator of apoptosis which binds to and inhibits caspases-3, -7 and -9, blocking the caspase 9-mediated apoptosis pathway. This pathway is activated by p53 and DNA damage and may be an important determinant of responsiveness to chemotherapy. Apoptosis also plays a major role in the regulation of follicle center B-cell proliferation and BCL2-mediated inhibition of apoptosis is a key factor in B-cell lymphomagenesis. In this study we examined the expression of XIAP in 65 reactive and neoplastic lymphoid proliferations utilizing a monoclonal antibody to XIAP (#610763 BD Biosciences, San Jose, CA) and immunohistochemistry with avidin-biotin-complex immunoperoxidase technique on formalin-fixed, paraffin-embedded sections. In reactive lymph nodes and tonsils, expression of XIAP was limited to large noncleaved cells in follicle centers (5 of 6 cases). XIAP was absent in plasmacytoma (3 cases) and small lymphocytic lymphoma/chronic lymphocytic leukemia (1 case). XIAP was expressed in follicular lymphoma, predominantly in large noncleaved cells (6 of 9 cases) and in diffuse large B cell lymphoma (11 of 16 cases), including cases of T-cell/histiocyte-rich diffuse large B cell lymphoma (2 cases), primary mediastinal large B cell lymphoma (1 case), and posttransplantation diffuse large B cell lymphoma (1 case). XIAP was consistently expressed in Burkitt and Burkitt-like lymphoma (3 of 3 cases) and anaplastic large cell lymphoma (3 of 3 cases) and in one case of adult T cell leukemia/lymphoma. XIAP was variably expressed in marginal-zone B cell lymphoma, predominantly in large blasts (2 of 4 cases) and in mantle cell lymphoma (2 of 3 cases). XIAP was not detected in peripheral T cell lymphoma, unspecified (1 case), extranodal NK/T cell lymphoma, nasal type (1 case), precursor B cell lymphoblastic leukemia (1 case), or granulocytic sarcoma (1 case). XIAP was consistently expressed in the Reed-Sternberg and mononuclear Reed-Sternberg-variant cells of classical Hodgkin disease (9 of 9 cases) and the L+H Reed-Sternberg-variant cells of nodular lymphocyte predominance Hodgkin disease (3 of 3 cases). XIAP is expressed across a broad range of lymphoproliferative disorders, including classical and nodular lymphocyte predominance Hodgkin disease, diffuse large B cell lymphoma, follicular lymphoma, Burkitt lymphoma, marginal-zone and mantle cell lymphoma, and anaplastic large cell lymphoma. XIAP appears to be selectively expressed in the proliferating elements of these lymphomas. The possible prognostic and therapeutic significance of XIAP expression needs to be determined.
Content Analysis of Cyber Insurance Policies: How do carriers write policies and price cyber risk?

Data breaches and security incidents have become commonplace, with thousands occurring each year and some costing hundreds of millions of dollars. Consequently, the market for insuring against these losses (aka cyber insurance) has grown rapidly in the past decade. However, very little is known about these policies and the mechanisms behind the risk assessments. While there exists much theoretical literature about cyber insurance, very little practical information is publicly available. For example, what losses are actually covered by cyber insurance policies, and what are the exclusions? What factors are used to compute the premiums, and how do existing underwriting approaches reflect the technical rate of risk? In this research, we collect and analyze over 100 cyber insurance policies filed with state insurance commissioners. By analyzing these policies, we provide the first-ever analysis of the underwriting process for cyber insurance and uncover how insurance companies understand and price cyber risks.
On the mechanism of methanol conversion to hydrocarbons over HZSM-5

Abstract Studies of methanol conversion over HZSM-5 using 13 C-labeled methanol in the presence of various olefins and aromatics revealed the importance of desorption limitation of reaction intermediates, as evidenced by extensive multiple labeling of polymethylbenzenes produced from unlabeled toluene. These studies also indicated that most of the ethylene produced from methanol is not a primary C 1 coupling product, but rather a secondary product derived from methyl attack on C 3 + olefins, as evidenced by the predominant formation of singly labeled ethylene. A classical carbenium ion mechanism incorporating these findings is presented for the conversion of methanol to hydrocarbons over HZSM-5.
Regulated in Development and DNA Damage Response 1 Deficiency Impairs Autophagy and Mitochondrial Biogenesis in Articular Cartilage and Increases the Severity of Experimental Osteoarthritis

Objective Regulated in development and DNA damage response 1 (REDD1) is an endogenous inhibitor of mechanistic target of rapamycin (mTOR) that regulates cellular stress responses. REDD1 expression is decreased in aged and osteoarthritic (OA) cartilage, and it regulates mTOR signaling and autophagy in articular chondrocytes in vitro. This study was undertaken to investigate the effects of REDD1 deletion in vivo using a mouse model of experimental OA. Methods OA severity was histologically assessed in 4-month-old wild-type and REDD1−/− mice subjected to surgical destabilization of the medial meniscus (DMM). Chondrocyte autophagy, apoptosis, mitochondrial content, and expression of mitochondrial biogenesis markers were determined in cartilage and cultured chondrocytes from wild-type and REDD1−/− mice. Results REDD1 deficiency increased the severity of changes in cartilage, menisci, subchondral bone, and synovium in the DMM model of OA. Chondrocyte death was increased in the cartilage of REDD1−/− mice and in cultured REDD1−/− mouse chondrocytes under oxidative stress conditions. Expression of key autophagy markers (microtubule-associated protein 1A/1B light chain 3 and autophagy protein 5) was markedly reduced in cartilage from REDD1−/− mice and in cultured human and mouse chondrocytes with REDD1 depletion. Mitochondrial content, ATP levels, and expression of the mitochondrial biogenesis markers peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α) and transcription factor A, mitochondrial (TFAM) were also decreased in REDD1-deficient chondrocytes. REDD1 was required for AMP-activated protein kinase–induced PGC-1α in chondrocytes. Conclusion Our findings suggest that REDD1 is a key mediator of cartilage homeostasis through regulation of autophagy and mitochondrial biogenesis and that REDD1 deficiency exacerbates the severity of injury-induced OA.
Positively worded subscale score of the Perceived Stress Scale is associated with cognitive domain function.

Objectives: To examine the cross-sectional associations of the separate subscales of the Perceived Stress Scale (PSS) and tests measuring cognitive domains in older adults. Methods: 897 adults over the age of 70 free of amnestic mild cognitive impairment and dementia and enrolled in the Einstein Aging Study made up the study sample. The PSS-14 was used to measure stress. Three cognitive domains (language, episodic memory, and frontal-executive) had previously been found using principle component analysis. Linear regression analyses were used to determine the relationship between the PSS subscales and cognitive domain function. Results: The study sample had a mean age of 79.1 years and 62.8% were female. Bivariate correlations show that the PSS-14 positively worded subscale of the PSS (PSS-PW) was significantly associated with all three cognitive domains (language: r = -0.15, p Conclusion: Worse PSS-PW scores are associated with reduced cognitive function in the executive, memory, and language domains in nondemented older adults. The PSS-PW subscale correlated better with cognitive function than the overall PSS-14. Future research should evaluate the temporality of the association and if stress reduction therapies improve cognitive performance.
Insulin-like growth factor-I regulates pro-B cell differentiation

Progression of B-lymphocyte development in the bone marrow of postnatal mammals is marked by progressive rearrangement and expression of immunoglobulin (Ig) heavy- and light-chain genes. Following productive VHDJH gene rearrangement in the Ig heavy-chain gene complex, mu-heavy chain is the first Ig gene product expressed in cells committed to the B-lymphoid differentiation pathway. Interleukin (IL)-7 has been shown to stimulate proliferation of pre-B cells following c mu expression and this proliferative stimulus is potentiated by kit ligand (KL). However, it appears that neither of these cytokines contributes to differentiation of pro-B cells or initiation of expression of Ig gene products. We previously demonstrated that differentiation of pro-B cells and expression of mu-heavy chain is stimulated by either bone marrow stromal cell line S17 or cell-free supernatants from that line. This biological activity was attributed to molecules with an apparent M(r) of less than 10 Kd and approximately 40 to 60 Kd. We now report that this biological activity resides with stromal cell-derived insulin- like growth factor-I (IGF-I). Recombinant IGF-I stimulated the expression of cytoplasmic mu-heavy chain in short-term bone marrow cultures and this stimulus was abrogated in the presence of anti-IGF-I antibody. We also demonstrate that either anti-IGF-I antibody or pretreatment of S17 cells with antisense oligonucleotide for IGF-I abrogated the pro-B cell differentiation activity of S17 stromal cell supernatants. Although IGF-I did not directly stimulate proliferation of B-lineage cells, like KL, it potentiated the proliferative stimulus provided by IL-7. Taken together, these data strongly suggest that IGF- I produced by bone marrow stromal cells in the hematopoietic microenvironment plays a key role in regulating primary B lymphopoiesis.
Unexpected Functions of Granulocyte-Macrophage Colony Stimulating Factor

Cytokines are small glycoproteins which play critical roles in hematopoiesis, immunity, and inflammation1. Two major themes underlying current understanding of cytokine biology are the redundancy and pleiotropy of cytokine functions. Numerous in vitro systems suggest that many cytokines demonstrate overlapping activities, and that any individual cytokine demonstrates multiple activities. These findings, considered together with the complex circuitry of cytokine expression in vivo, render problematic delineating the central and distinctive properties of any given molecule. The limited understanding of cytokine physiology in turn has hindered the most effective application of these proteins to the treatment of clinically important human disorders, including cancer, bone marrow failure, autoimmunity, and infectious disease.
The Bereitschafts Potential (BP) and the Conscious Will/Intention to Act

The discovery of the BP by Kornhuber and Deecke (1965) opened the way for further analyses of the volitional process, and it made possible my studies of the conscious will to act in relation to neural events in the brain.
Customer Service and Relationships

Whether a company sells brilliant technological gadgets or is a simple retailer, customer service should be a key strategy focus. Without customers, a company has no sales, no profits and serves no purpose. Failure to focus on customer service is a hallmark of underperforming companies. It’s not enough for a company to proclaim it is customer focused, it must be focused on the wants and needs of its customers every day.
Comparison of Surface Permanent Magnet Axial and Radial Flux Coaxial Magnetic Gears

This paper provides a thorough, parametric comparison of axial and radial flux coaxial magnetic gears with surface-mounted permanent magnets. While both topologies share similar operating principles and can achieve comparable shear stresses, they exhibit different scaling trends with respect to key design parameters. Both topologies’ volumetric torque densities (VTDs) increase with the outer radius, but the axial flux topology's VTD increases with the radius at a much faster rate than the radial flux topology's VTD. Another difference between the topologies involves their cross-sectional scaling parameters. The stack length axially scales radial flux gear cross sections, and, as it increases, the impact of end-effects decreases, which improves the performance. For axial flux gears, the radii ratio scales the cross section's radial width between different radii. This fundamentally changes optimal parameter values and design performance tradeoffs. Finally, axial flux rotors experience significant axial forces, but the radial forces on radial flux rotors can be balanced out. Based on these trends, radial flux gears are superior to axial flux gears for most applications; however, axial flux gears have a significant advantage when a large radius and a small axial length are permissible or when mechanical power needs to be transmitted across a flat barrier.
Experimental study of growth on exit surface of various transmissive materials at 351 nm and 1053 nm

High-energy laser systems are limited by the onset and subsequent growth of damage on constituent optics. This has been extensively studied for optics comprised of fused silica, but less so for other common optical materials. There are very few materials as well characterized as fused silica and, in this work, we explore the growth characteristics of other widely used optical materials with a range of physical parameters, namely sapphire, potassium dihydrogen phosphate, calcium fluoride, and compare them to fused silica. Since current understanding is that material fracture must be present before the fluences used in ns laser systems might cause a surface flaw to grow, we have chosen to study flaws on the exit surfaces created with a Vickers indenter. A range of indenter forces were selected that would produce flaw sizes typical of those that have been seen in laser created damage. Samples with arrays of indents were tested in the in the Optical Science Laser (OSL), a master oscillator power amplifier system, with a front-end pulse shaping capability able to deliver relevant fluences with a large area beam. Samples were tested in vacuum at 351 nm and at atmosphere at 1053 nm with a single shot fired every 45 minutes exposing multiple sites simultaneously. High resolution images of each flaw were taken after every shot to document changes. Additional tests at 1064 nm were conducted of individual sites at a 60 Hz rep rate in the Gigashot Optical Laser Damage (GOLD) system. The probability of growth at 3ω at 5.5 J/cm2 is near 100% for both calcium fluoride and fused silica about 50% for the other materials. The growth rates at 3ω at from 5 to 8 J/cm2 are comparable for all but potassium dihydrogen phosphate which are better than five times lower. At 1ω all the materials had about a factor of five increase in the threshold for growth.
The prominence of e-cigarettes is a symptom of decades of failure to tackle smoking properly

There is a danger that debate around e-cigarettes drowns out the work needed to implement the full range of tobacco control measures
Characteristics of Urban Inpatient Smokers With and Without Chronic Pain: Foundations for Targeted Cessation Programs.

Background Cigarette smoking and chronic pain are prevalent, comorbid conditions with significant consequences for individuals and society. Despite overlap between smoking and chronic pain, and pain's role as a potential barrier to quitting, there are no validated interventions targeted for smokers with chronic pains (SWCPs). Objective To compare characteristics of urban inpatient smokers with and without chronic pain to inform the development of SWCP-targeted cessation interventions. Methods This study reports partial results from a randomized comparative effectiveness trial of two smoking cessation interventions (NCT01363245). Participants were enrolled at two safety net hospitals in New York, NY in 2011-2014. Data were collected from the electronic health record and an interviewer-administered survey. Participants were considered to have chronic pain if they affirmed having "long-lasting, persistent, or chronic pain in the last six months" on survey. Results Among smokers assessed for pain (n = 1093), the prevalence of chronic pain was 44%. SWCPs were more likely to report depressive symptoms and to have a history of psychiatric diagnosis (nonsubstance related) than smokers without pain. Severe problems with mobility and with performing usual activities were more common in SWCPs. No significant difference was observed in sex, race, education, nicotine dependence level, confidence in quit ability, or history of substance misuse. Conclusions/Importance: Chronic pain in smokers admitted to safety net hospitals is prevalent and associated with hindered mobility, history of psychiatric diagnosis, and prescription opioid use. Urban safety net hospitals are an appropriate setting in which to pilot SWCP-targeted cessation programs, which should be designed with consideration for patients' psychiatric history and mobility status.
Epidemiological analysis of viral hepatitis in Pinggu District of Beijing City in 2012

[Objective]To understand the epidemiological characteristics and epidemic tendency of viral hepatitis,and provide scientific evidence for its control and prevention.[Methods]Epidemiological analysis was adopted.[Results]Of 297 reported cases,201 were male(67.68%) and 96 female(32.32%),The ratio of male to female was 2.09 ∶ 1;the difference was significant(χ2= 35.93,P 0.01);The morbidity in 55-60 years age group was highest(120.55 /100 000).Constituent ratio of hepatitis type showed HBV accounted for 84.85%.Farmers were the majority with the rate of 47.47%.[Conclusion]The incidence of hepatitis has fallen greatly among 15 years old group shows that the effect after inoculation of Hepatitis A B Vaccine is satisfied.It is necessary to strengthen hepatitis B vaccination and publicity among young farmers in future.Adult hepatitis B immunization and supplementary immunization are urgent problem which should be solved in hepatitis B control.
Inner-cladding-doped optical fiber for high-power radiation balancing (Conference Presentation)

Currently heat management is a big hurdle for power-scaling of high-power fiber lasers and amplifiers. Different methods have been developed over the years to mitigate the heat generation in high-power lasers and amplifiers; radiation balancing is a new method that leverages the radiative cooling for heat mitigation. In this study, the effects of different design parameters on the operation of a doped-double-cladding (DC) fiber laser and amplifier for radiation balancing are investigated. The results show that the value of the internal quantum efficiency for an effective heat mitigation by radiation balancing is not required to be very close to unity. Conversely, it is shown that in high-power operation, even small values of background absorption can be detrimental to radiation balancing. It is argued that both the background absorption and the small dopant area of the doped-DC fibers are big hurdles in achieving an effective heat mitigation by radiation balancing in high power operation. In order to address this issue, we suggest to dope the inner cladding of the DC fiber such that at the pump wavelength, the inner cladding cools down by optical refrigeration. Due to the geometry of the fiber, the temperature is uniformly homogenized across the fiber and the effective fiber temperature decreases, allowing Yb-doped DC fiber lasers and amplifiers to operate at Kilo-Watt levels in radiation balanced mode.
Women’s empowerment and nutrition status: The case of iron deficiency in India

Abstract In this paper we study the relationship between women’s empowerment in agriculture and their iron deficiency status in Maharashtra, India. This is the first time the Women’s Empowerment in Agriculture Index (WEAI) has been used in association with explicit measurement of medical biomarkers for women’s iron deficiency status. Using primary data for 960 women we find that the log odds of a poor iron status in women decline as women’s empowerment levels in agriculture improve. Further, this decline is seen in the presence of multiple dietary diversity measures (dietary diversity score, share of rice and wheat in the diet, total iron intake and iron intake from iron-rich food groups – all for 24-h and 30-day recalls) suggesting that in addition to dietary pathways women’s empowerment can play a role in addressing micronutrient deficiencies like those of iron in a vulnerable sub-group of the population. It also reinforces the need to move away from the ‘staple grain fundamentalism’ that has characterized agricultural policy in India, towards more nutrition-sensitive food systems.
Glucose Metabolic Reprogramming and Cell Proliferation Arrest in Colorectal Micropapillary Carcinoma.

Background Micropapillary carcinoma (MPC) has been reported as an aggressive variant of colorectal carcinoma (CRC) associated with frequent lymphovascular invasion and poor outcome. Altered glycogen metabolism by metabolic reprogramming plays a critical role for cancer cell growth and survival. We aimed to investigate glucose metabolic reprogramming in colorectal MPC. Methods Immmunostains for Ki-67 and glucose transporter 1 (GLUT1) were performed on 10 colorectal MPCs. Real-time PCR analysis of expressions of GLUT1 and glycogen metabolizing enzymes: glycogen synthase (GYS1) and glycogen phosphorylase (PYGL) was performed on cultured monolayer and three-dimensional (3D) spheroid HCT116 colon cancer cells. Results GLUT1 was strongly expressed in MPC as compared to adjacent conventional glandular component, and was also significantly increased expression in 3D spheroids. Upregulation of GYS1 and PYGL was markedly increased in 3D spheroids. The proliferation rate (Ki-67) of MPC was significantly lower compared to conventional glandular component. The 3D spheroids showed increased cell cycle arrest. Our results demonstrate altered glycogen metabolism in colorectal MPC. Conclusion The reprogramming of glycogen metabolism in MPC provides a source of energy contributing to tumor cell survival in a low proliferation state. Targeting glucose-regulated metabolism may warrant consideration as possible MPC therapies.
Colonialism, Legal Borrowing, and Disruption in Africa

Disruptive and other technologies have spread throughout Africa in recent years. Many see the digital economy as a potential new path that might enable leapfrogging that narrows economic and technological gaps between Africa and the rest of the world. Today, more than half a century after the end of colonialism, far too many remain poor in Africa. High rates of economic growth in the early years of the new millennium have decreased, while the population in many African countries is set to double between now and 2050. Unemployment and underemployment are pervasive in many African countries today.
Imaging : new electronic tool for clinicians.

The Imaging system captures clinical images, scanned documents, electrocardiogram (EKG) waveforms, and radiology images. Image and text data are provided in an integrated manner that facilitates the clinician's and nurses task of correlating the data and making patient care decisions in a timely and accurate way. It serves five important purposes: documents findings, makes images accessible to clinicians and nurses within the hospital, assists in conference decision making and education, aids in follow-up treatment of patients and facilitates telemedicine. The captured images are extremely helpful in follow-up care. The images are real time; so waiting time is decreased and patient care decisions are sooner. With the Image system, the process flow has completely changed. There is no longer a waiting time for x-ray's or EKG's to be brought to the units for the physicians or nurses to review, they can now access and view these reports from the computer at their work stations.
Sucker Rod Pump

Sucker rod pump, rod pump, reciprocating pump or pump jack is different names of an oldest and most widely used artificial lift method for oil wells. There is a high percentage of oil wells in North America and other areas in the world that are vertical and produce less than 10 barrels of oil per day. These wells are called stripper wells and are commonly lifted with sucker rod pumps.
Synchrotron x-ray tomography for non-destructive metrology of micro-orifices in automotive fuel injectors (Conference Presentation)

X-ray Computed Tomography has gained popularity as a metrology technique for components with detailed internal features. However achieving micron-scale resolution using X-ray CT is challenging. Synchrotron X-ray sources are highly collimated and brilliant, allowing high resolution tomography in metallic components. The X-ray Fuel Spray research at Argonne National Lab is aimed at utilizing synchrotron X-ray diagnostics for providing insights into automotive fuel injection. We present a case study of micro-CT for automotive fuel injectors, with orifices smaller than 100 micrometers. These orifices are imaged with 1 micrometer voxel size with minimal resolvable features of 2 micrometer. Tomographic analysis on large datasets must preserve resolution while being computationally efficient, which is facilitated by deep learning techniques for segmentation developed in-house. The accuracy of segmentation is evaluated using synthetic data. As results, we show high-quality iso-surface extraction and measurements of orifice features for 7 identical fuel injectors, indicating the extent of manufacturing variability. The capabilities developed in our team have potential applicability in the field of metal additive manufacturing, specifically for millimeter-sized components with micron-scale features.
NB-UVB phototherapy in the treatment of anti-PD-1 inhibitor induced psoriasis: A case report

Abstract Immune-mediated cutaneous reactions are a frequent occurrence in cancer patients treated with immune checkpoint inhibitors. A small subset of these adverse events are psoriasiform reactions. To date, there is no high-level evidence supporting the most appropriate management of this often debilitating dermatologic side effect. In many cases where topical therapy is ineffective, oral steroids are often prescribed which may lead to poorer outcomes in cancer patients. In this case report and review, we describe the clinical courses of two patients with anti-PD-1 inhibitor induced psoriasiform reactions who were treated with narrow band UVB phototherapy. We review the rationale, advantages, and disadvantages of this underutilized treatment as a therapeutic option to spare cancer patients from systemic immunosuppressive agents.
A phase field computational procedure for electromigration with specified contact angle and diffusional anisotropy

Electromigration in electrical interconnects with high current density causes voids to form and grow near the cathode. These voids can possibly grow large enough to cause open circuit failure. The simulation of electromigration void nucleation and growth is challenging because of the complex interaction of electrical, thermal and mechanical fields that lead to the observed voids. In this paper, a phase-field approach is developed to study void growth due to electromigration taking into account diffusional anisotropy and specified contact angle. Consideration of anisotropy and contact angle is critical in applications including electronic assemblies that most commonly use Sn-based solder interconnects. In such systems, Sn exhibits significant anisotropy in its self-diffusivity, which assumes importance in small solder joints that are known to contain only a few grains. Furthermore, the contact angle at the void-bonding pad-solder triple junction is known to influence the void size and shape. To the best of the authors’ knowledge, only anisotropy in surface diffusivity has been considered in phase-field electromigration literature, whereas the contact angle at a triple junction has not been considered. The developed phase-field model incorporates effects of both contact angle and anisotropy in self-diffusivity. The model is used to simulate systems with different contact angles and dominant directions of diffusion. It is observed that diffusional anisotropy plays a more dominant role in failure, while the contact angle dictates evolution of the shape of voids.
Abstract 2891: Targeting breast cancer stem cells with anti-EMP2 immunotoxins delivering granzyme b

Despite new therapies, breast cancer remains one of the leading causes of cancer-related death in women worldwide. Part of the issue remains the inability of these therapies to target cancer stem cells (CSCs). These cells show unique resistance to chemotherapy and have enhanced capacity for self-renewal. Recently, our group has shown that Epithelial membrane protein-2, or EMP2, is expressed on CSCs defined by increased aldehyde dehydrogenase activity (ALDH+). Clinical data supports the role of EMP2 in advanced breast cancer as increased expression of the protein is observed in metastatic lesions compared to primary tumors and its expression is enhanced in chemotherapy resistant tumors. In parallel, EMP2 expression correlated with enhanced mammosphere formation, an accepted surrogate for cells with enriched stem cell capacity. We have recently developed a novel IgG1 monoclonal antibody to EMP2, which has been shown to reduce tumor load. As the antibody-antigen complex rapidly internalizes, we hypothesized that its anti-tumor effects could be enhanced through the creation of a fusion protein. Granzyme B (GrB) is a serine protease that plays a critical role in the body9s defense against viral infection and tumor development by initiating the apoptotic cascade via both caspase-dependent and -independent mechanisms. We developed novel fusion proteins composed of the anti-EMP2 backbone as the targeting moiety and granzyme B as the cytotoxic payload. Our initial design comprised of the active GrB fused to the IgG heavy chain (Fc) domain containing 2 single-chain antibodies against EMP2, a format that results in a longer plasma retention time. This new construct showed high and specific affinity for EMP2 (10−10M) using both flow cytometry and ELISA based formats. Moreover, treatment with these agents induced cell death to EMP2 positive cells, including those characterized by high ALDEFLUOR activity. Preclinical assessment of the anti-EMP2 immunotoxins showed no acute toxicity and acceptable plasma retention. Preliminary results using a 4T1 model system produced a significant reduction in tumor burden. Our results suggest that continued development of these agents may be successful at targeting advanced disease. Research supported, in part, by NCI R21 CA234642 and the Clayton Foundation for Research. Citation Format: Khalid A. Mohamedali, Kok Su-yin, Lawrence H. Cheung, Naina Dhawan, Michael G. Rosenblum, Madhuri Wadehra. Targeting breast cancer stem cells with anti-EMP2 immunotoxins delivering granzyme b [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2891.
Topology-Optimized Multilayered Metaoptics

Compact metasurface devices herald an exciting revolution in optics technology. Their design complexity and functionality has been restricted to intuitive by-hand designs for single-layered devices. This study proposes a large-scale approach known as topology optimization, applied to multiple, closely spaced device layers, which greatly expands the scope and functionality of metadevices. In particular, the authors demonstrate angular phase control, the ability to encode arbitrary information using different angles of incidence, which enables $e.g.$ the design of a one-piece, aberration-corrected metalens, and of an angle-convergent metalens.
Mining mutation contexts across the cancer genome to map tumor site of origin

The vast preponderance of somatic mutations in a typical cancer are either extremely rare or have never been previously recorded in available databases that track somatic mutations. These constitute a hidden genome that contrasts the relatively small number of mutations that occur frequently, the properties of which have been studied in depth. Here we demonstrate that this hidden genome contains much more accurate information than common mutations for the purpose of identifying the site of origin of primary cancers in settings where this is unknown. We accomplish this using a projection-based statistical method that achieves a highly effective signal condensation, by leveraging DNA sequence and epigenetic contexts using a set of meta-features that embody the mutation contexts of rare variants throughout the genome.
An Approximation of 2-D Inverse Scattering Problems From a Convex Optimization Perspective

We present a two-step strategy to solve an inverse scattering problem in 2-D geometry. The first step approximates the inverse scattering as a convex optimization problem and provides an estimation of the total field inside the domain under investigation without a priori knowledge or tuning parameters. In the second step, the previously estimated total field is used to reconstruct the unknown contrast permittivity, which is represented by a superposition of level-1 Haar wavelet transform basis functions. Subject to l₁-norm constraints of the wavelet coefficients, a least absolute shrinkage and selection operator (LASSO) problem that searches for the global minimum of the l₂-norm residual is exploited by accounting for the sparsity of the wavelet-based permittivity representation. Numerical results are presented to assess the effectiveness of the proposed formulation against objects with relatively small electric size. Finally, the approach is validated against experimental data.
Neonatal arrhythmias in Turner syndrome: a case report and review of the literature.

Background While left-sided congenital heart defects have been well described in females with Turner syndrome (45, X), the literature is scarce regarding arrhythmias in this patient population. Case summary A full-term neonate referred to cardiology was found to have a non-apex forming left ventricle and partial anomalous pulmonary venous return. During the echocardiogram, she developed atrial flutter, followed by orthodromic reentrant supraventricular tachycardia (SVT). She was started on propranolol and eventually switched to sotalol due to breakthrough SVT. A genetics evaluation revealed Turner syndrome with complete monosomy X (45, X). The patient is now 18 months old and has not had any further arrhythmias. Discussion We present a rare case of atrial flutter followed by supraventricular tachycardia in a neonate with Turner syndrome and left-sided heart defects. This case highlights the importance of early and precise investigation of cardiac abnormalities in neonatal patients, especially among females with Turner syndrome given their relatively higher risk of cardiovascular disease compared to the general population.
Proton pump inhibitors and gastric cancer: a population-based cohort study.

We read with great interest the recent article by Seo et al regarding the association of proton pump inhibitors (PPI) and gastric cancer.1 We want to congratulate the authors for their exemplary work as the prevalence of PPI in current clinical practice cannot be overstated. After reviewing the article, we have some comments to share with you. As mentioned in the Methods section and also in figure 1, the target cohort was defined as ‘new PPI users’ who were prescribed PPI for more than 30 consecutive days. Although we understood that the subjects underwent 365 days of continuous observation to be classified as new PPI users, we are curious to know if the remote history of PPI use (>365 days ago) was taken into consideration before enrolment into the target cohort. The authors have defined index date as the first day of a new …
Evaluation of a novel process for selecting advanced pharmacy practice experiences.

Abstract Introduction Matching an increasing number of pharmacy students with a limited number of advanced pharmacy practice experience (APPE) sites has become challenging for pharmacy schools. Selective tiered optimization (STO), a process for matching students with competitive APPE electives, was implemented by The University of Mississippi School of Pharmacy (UMSOP) in 2015 to address these concerns. This pilot study sought to evaluate student and preceptor satisfaction with the process. Methods Electronic surveys were sent to students enrolled in APPEs and individuals who precepted APPE students at the UMSOP from 2016 to 2019. The surveys were designed to gauge satisfaction with STO's process, goals, utility, and fairness. Results There were 63 responses from 149 preceptors (42% response rate) and 70 respondents from 314 students (22% response rate). Overall, both students and preceptors expressed satisfaction and found value in participating in STO. Both groups indicated that the benefit they received from participating in STO outweighed the extra effort required. Preceptors indicated that students who participated in STO were of higher quality and more focused, hardworking, and interested than those who did not participate. Conclusions Respondents were satisfied with the STO process and experience. The process was perceived by preceptors to be fair for all students and worthwhile for its participants. Our results also demonstrated that this process is effective for easing the competitive APPE selection process. Schools and colleges of pharmacy should consider utilizing this process to alleviate applicable challenges with APPE selection.
World View, Ideology and Tactical Programs

There is a phrase in the Lotus Sutra that reads Nange nan’nyu, which supposedly means, “The Lotus Sutra is ‘difficult to understand’, and the gate of enlightenment is ‘difficult to enter.’”1 For the non-Gakkai-educated person to attempt to give even a reasonably accurate interpretation of the basic Gakkai beliefs, many of which stem from the Lotus Sutra, is a most difficult proposition. The writer once read a response by a Gakkai leader to a Western-educated person investigating Soka Gakkai. The leader said that since the investigator was trained in Western ways of thinking, it would be impossible for him to understand the Lotus Sutra and basic Nichiren beliefs without dedicated study. Toda is also quoted as saying to a believer: Mr. Iwamori, don’t worry. Because we cannot completely believe in what Nichiren Daishonin teaches us, we are Bompu, average common mortals. But if we Bompu continue earnestly in the faith, we will not fail to attain Buddhahood. There is no doubt. When we devote ourselves to faith, practice and study, with strong belief in the Gohonzon, we will no more be in the troubled state of Bompu … In science, without making research and experiment, you cannot understand the philosophy and achievements of Einstein.2
Superconductors: Current limits to wire technology

High-temperature superconductors could be a boon to the power industry, carrying large currents with virtually no energy loss. Unfortunately, these brittle materials are difficult to make into wires, so in practice they are powdered and encased in silver strips, and drawn out to align the powder crystallites. But the current capacity of these tapes is still severely limited. That is probably due to misalignment of the crystallites, according to new magnet-optical imaging studies. So for commercial applications, slightly different processing strategies may be needed — or an entirely different type of tape.
Purification and characterization of constituent androstenedione 15α-hydroxylase (Cytochrome P45015αAD) from mouse liver: Sex- and tissue-dependent expression

Abstract Hepatic microsomal androstenedione 15α-hydroxylase (i.e. cytochrome P450 15αAD ) was purified from female CD-1 mice. Protein purification was monitored in eluates from Fractogel, DEAE-Sephacel, and hydroxylapatite columns at heme absorbing 417 nm, by cytochrome P450 content, reactivity to monoclonal antibody against female-specific rat cytochrome P450 2C12, and androstenedione 15α-hydroxylase activity. The catalytic activity for androgens of the purified cytochrome P450 15αAD , exhibiting a high degree of regioselectivity and stereospecificity, was restricted to the 7α- and 15α-hydroxylation of androstenedione, representing, respectively, >5% and >93% of the total metabolites. Polyclonal antibodies against cytochrome P450 15αAD exhibited a concentration-dependent and very selective inhibition of hepatic microsomal androstenedione 7α and 15α-hydroxylation and a 60% inhibition of benzphetamine demethylation, the latter drug appearing to be a much more effective substrate than androgens. Cytochrome P450 15αAD accounted for about 3% of the total P450 in female mouse liver microsomes. The apparent subunit molecular weight of P450 15αAD was 53,000, and the protein appeared as a single band on sodium dodecyl sulfate-polyacrylamide gels. The isoform was intensely expressed in both liver and lung of CD-1 female mice and was female-predominant in the livers of five or eight strains examined; it was sex-independent in the remaining three strains. Amino-terminal sequence analysis indicates that cytochrome P450 15αAD is a member of the murine cytochrome P450 2c subfamily.
FINITE ELEMENT MODELING OF HYBRID III HEAD-NECK COMPLEX

A three-dimensional finite element model of the Hybrid III dummy head- neck complex was created to simulate the Amended Part 572 Head-Neck Pendulum Compliance Test, of the Code of Federal Regulations. The model consisted of a rigid head and five circular aluminium disks joined together by butyl elastomer rubber. Contact surfaces were defined to allow the anterior neck to separate upon an application of extension moments. Two mounting positions, one for flexion and the other one for extension, were used to simulate the head-neck calibration tests. An explicit finite element code PAM-CRASH was utilized to simulate the model dynamic responses. Simulation results were compared to experimental data obtained from First Technology Safety Systems Inc. Model predictions agreed well in both flexion and extension. This model can be used to study the head-neck biomechanics of the existing dummy as well as in the development of new dummies. For the covering abstract see IRRD 864472.
Beyond inpatient and outpatient care: alternative model for hypertension management

Hypertension is a major contributor to worldwide cardiovascular mortality, however, only one-third of patients with hypertension have their blood pressure treated to guideline recommended levels. To improve hypertension control, there may need to be a fundamental shift in care delivery, one that is population-based and simultaneously addresses patient, provider and system barriers. One potential approach is home-based disease management, based on the triad of home monitoring, team care, and patient self-care. Although there may be challenges to achieving the vision of home-based disease management, there are tremendous potential benefits of such an approach for reducing the global burden of cardiovascular disease.
Lining Up to Avoid Bias

Algorithms that align DNA sequences can introduce bias and uncertainty into evolutionary analyses.
Disparate regulation of IGF-1 in primary osteoblasts isolated from MAPK phosphatase-1 knockout mice involves AKT/ β-catenin pathway (802.18)

The role of MAPKs in osteogenesis and in Parathyroid hormone (PTH) signaling has been shown in vitro and in vivo previously. However, the role of MAPK phosphatase-1 (MKP-1) in bone formation remains unclear. We observed age dependent sexual dimorphism in bone phenotype of MKP-1 knock out (KO) mice showing osteopenia in females and osteopetrosis in males. We investigate the involvement of MKP-1 on b-catenin, a key mediator of the canonical Wnt signaling pathway and an important regulator of bone forming cells, the osteoblasts. Signal transduction through b-catenin requires inhibition of GSK-3b which is also inhibited via phosphorylation by AKT upon insulin-like growth factor-1 (IGF-1) signaling. Real-time PCR analysis of primary calvarial osteoblasts revealed significant down-regulation of IGF-1 mRNA expression in osteoblasts isolated from MKP-1 KO female mice in contrast to KO osteoblasts from males. Inhibition of P-ERK and P-p38 with pharmacological inhibitors showed disparate regulation of IGF-1 express...
Replacement lipomatosis of the kidney: sonographic features.

Replacement renal sinus lipomatosis (RRSL) is an uncommon disorder characterized by renal sinus fat proliferation resulting from renal parenchymal atrophy, inflammation, or calculous disease. We present the sonographic features of RRSL secondary to nephrolithiasis in a 75-year-old man. The patient was successfully treated with lithotripsy. Several entities can resemble the appearance of RRSL, including malakoplakia, fat-containing tumors, and xanthogranulomatous pyelonephritis (XGP). Sonography and a high index of suspicion are helpful in making a diagnosis of RRSL.
Partisan Bias, Political Information and Spatial Voting in the 2008 Presidential Election

This article provides direct estimates of the parameters of spatial utility models of voting using data from the 2008 presidential election. By measuring citizens’ views on issues for which candidates' stances are known, I estimate voter ideology on the same scale as candidate positions. Using these estimates, I demonstrate that policy exerts a strong influence on vote choice for most voters. While independents appear to cast their ballots in accordance with the assumptions of unbiased spatial voting, partisans are strongly biased toward their party’s nominee by spatial standards. At lower levels of political information, voters are influenced primarily by their party identification, with policy views having little impact on vote choice. More highly informed citizens, by contrast, show strong relationships between policy views and vote choice. As information levels increase, the spatial biases exhibited by partisan voters decreases, but even among the most informed citizens, significant partisan biases re...