cssi/SciSciGPT-SciSciNet huggingface dataset:
Retinoic acid regulates clonal growth and differentiation of cultured limbal and peripheral corneal epithelium.

Purpose To determine if vitamin A could be one of the factors in serum responsible for the previously observed effect of 20% fetal bovine serum on stimulating clonal growth of an additional subpopulation in limbal cultures, possibly stem cells, but inhibiting that of transient amplifying cells in peripheral corneal cultures. Methods A reported serum-free clonal growth assay was used. The mitogenic response was measured by colony-forming efficiency (CFE), colony size, and BrdU labeling index; the differentiation was assessed by colony morphology, AE-5 monoclonal antibody staining, and cornified envelope formation. Results HPLC analyses revealed that added retinoic acid (RA) was rapidly taken up by cultured cells. As compared to the control without RA, low concentrations of RA (10(-9) M to 10(-7) M) stimulated the CFE of limbal cultures but did not change that of peripheral corneal cultures. Furthermore, 10(-8) M RA induced the emergence of two new types of colonies, one of which was almost exclusively present in limbal cultures, and allowed continuous clonal growth of some colonies in late limbal cultures. RA also dose dependently reduced colony size and BrdU labeling index in both limbal and peripheral corneal cultures. RA in concentrations above 10(-8) M stimulated normal differentiation of both limbal and peripheral corneal epithelial cells, as evidenced by increased AE-5 staining, but inhibited the formation of cornified envelopes, an index for abnormal, squamous metaplasia, in late cultures. Conclusion These results suggest that RA has a differential dose-dependent effect on subpopulations of corneal and limbal epithelial cells. Although RA stimulates the conversion of limbal stem cells to transient amplifying cells, it inhibits the amplification of corneal and limbal transient amplifying cells and prevents abnormal terminal differentiation. These data further support the role of vitamin A as a physiological modulator of proliferation and differentiation of the ocular surface epithelium.
Light-Driven Translocation of Signaling Proteins in Vertebrate Photoreceptors

Sustained illumination causes massive translocation of at least three signal transduction proteins (transducin, arrestin, and recoverin) into and out of the outer segment compartment of rod and cone photoreceptors. This phenomenon is thought to contribute to photoreceptor adaptation to diurnal changes in ambient light intensity and likely to photoreceptor neuroprotection from the adverse effects of bright light illumination.
Of floods and droughts: The uneven politics of stormwater in Los Angeles

Abstract Stormwater is a complex political and geographical problem. It is at once bound to land-use decisions, tied to geographical features such as lakes and rivers, and capable of flowing across different political boundaries and jurisdictions. In this paper, I empirically focus on how disparate understandings of stormwater are forged through different institutional arrangements and the ways multiple actors interact across scales of governance in Los Angeles. The results indicate four discourses influence decisions on urban stormwater management and are articulated through different forms of knowledge and power in environmental governance. The discourses diverge over contrasting perspectives on infrastructural interventions, the role of economic approaches, and the need for new institutions and rules. I suggest that disagreement may not deter integration and collaboration across different scales of governance, but without addressing conflict over key discursive claims about how stormwater governance should proceed, broadly accepted outcomes may remain elusive. With current trends in environmental governance moving towards hybrid forms that bring together groups that transcend traditional organizational structures, this paper reveals how more sustainable outcomes are being devised through current configurations of knowledge and power.
U.S.-Chinese trade : interface and lawfare

This chapter offers a perspective on the legal aspects of U.S.-China trade relations, focusing on how the rise of China has challenged U.S. perspectives and principles. There are serious issues raised by the interface between China’s state-controlled economy and the U.S. privately-controlled economy. The existing WTO legal rules are not well-designed to manage these issues, resulting in increasing U.S. dissatisfaction. The Chinese economic and governmental structure is different from that of the U.S., and is not fully suited to the WTO free trade regime due to the extent of state control of the economy. In order to provide a level playing field for U.S. and Chinese enterprises, it will be necessary to develop new disciplines of transparency and neutrality in order to ensure that market-opening agreements are not nullified or impaired.
Costs of Preventable Childhood Illness: The Price We Pay for Pollution

A growing body of scientific literature implicates toxic exposures in childhood illnesses and developmental disorders. When these illnesses and disabilities result from environmental factors under human control, they can and should be prevented. This report documents monetary costs associated with five major areas of health problems in children that have been linked to preventable environmental exposures: cancer, asthma, lead poisoning, neurobehavioral disorders, and birth defects. We review incidence and prevalence estimates for these disorders, as well as estimates of the associated monetary costs. We apply the concept of the "environmentally attributable fraction" (EAF) of an illness, where EAF is the estimated percentage of cases of an illness that result from an environmental exposure. Preventable childhood illnesses and disabilities attributable to environmental factors are associated with large monetary costs. Our estimate of direct and indirect costs ranges from $1.1 to $1.6 billion annually in Massachusetts. Of course, there is no dollar measure of the full practical and emotional burden borne by these children, their families, and the communities in which they live.
Active monitoring in non-invasive breast cancer: insight gained from a large national database

The objective was to evaluate women diagnosed with ductal carcinoma in situ (DCIS) preoperatively and elucidate factors, including time from biopsy to excision, associated with invasive disease found on final pathology (underestimation). The National Cancer Database was queried for women with preoperative DCIS receiving lumpectomy/mastectomy from 1998 to 2012 and investigated for factors associated with underestimation (invasive disease in the breast/nodes on excision). One hundred fifty-six thousand five hundred thirty-five women met inclusion criteria and 10.8% had underestimation of disease. 9.1% had invasive disease in the breast alone, 0.4% had nodal disease despite only DCIS in the breast, and 1.4% had both invasive disease in the breast and the axillary nodes. The adjusted risk of underestimation of invasive disease increased steadily with more time from biopsy to surgery (p < 0.001), as did the adjusted risk nodal disease (p < 0.001). Several presurgical findings can predict for occult-invasive breast cancer including time from diagnosis to definitive surgery.
Geographic and Socially Embedded B2C and B2B E-Commerce

The term electronic commerce (e-commerce) provides visions of anonymous online transactions with companies like Amazon or Buy.com, where personal contact need not exist and locations of purchasers and sellers are irrelevant. Much business to consumer (B2C) e-commerce occurs this way, and the approach was prevalent among firms in the ‘dot.com’ era, e.g., Verticalnet and biz2biz.com. Such visions reflect the dominant perception of the role of e-commerce in economic exchange prior to the widespread failure of dot.com firms in 2000 and 2001. That is, e-commerce enables firms to access new markets, replace outmoded or inefficient supply chains and distribution channels, and achieve substantial growth in customer reach (Wigand and Benjamin 1995; Cairncross 1997; Choi et al. 1997). These perceived opportunities stem from maintained assumptions held at that time. (2003b) describes the primitive beliefs that shaped corporate e-commerce practice and strategy: a) Geography is irrelevant. Electronic exchange costs are the same regardless of distance (Cairncross 1997). Indeed, unless a Web site explicitly identifies the geographical location of the firm, the physical address remains unknown to most users. An implication for economic exchange is that purchasers and sellers are not required to be geographically close. The Internet had reduced transaction costs for transacting with geographically distant partners to the extent that distant sellers are competitive with local sellers (Bakos 1997, 1998). b) Internet transactions are substitutes for transactions formerly conducted in person or through other forms of direct communication. Enhanced graphics and multimedia enable highly complex products to be sold through this medium. Customization and personalized features substitute for the activity of sales personnel who formerly interacted directly with customers (Rayport and Sviokla 1995). Modern logistics and transport systems ensure rapid fulfillment of online orders, hence the essential elements needed to effectively automate transactions are present, and enable on-line transactions that are perfect substitutes for physical transactions (Choi et al. 1997). c) E-commerce orientated firms experience network effects. Hence, firms that accumulate a substantial customer base will achieve a sustainable competitive advantage (Choi et al. 1997; Shapiro and Varian 1999; Kaplan and Sawhney 2000; Afuah and Tucci 2001). The presence of a network effect translates into increased customer marginal utility the greater is Web site patronage. Such effects are thought crucial for sites that provide intermediary services, e.g., brokerage. To improve market liquidity such sites must attract a critical mass, or minimum efficient scale, of customers. The more customers attracted to a market, the greater the probability a customer has of finding a desired match.1
Ecology of belowground biological control: Entomopathogenic nematode interactions with soil biota

Abstract Entomopathogenic nematodes (EPNs) have potential to control many soil-dwelling insect pests but have been limited in their usage, partly by their unpredictable field performance. Numerous abiotic and biotic factors are thought to contribute to this poor predictability, but the exact impacts and relative importance of these factors in affecting EPN performance in the field are not well understood. Previous studies have highlighted diverse interactions between EPNs and other members of the soil community, from plants and fungi to arthropods and annelids. These interactions may help or hinder EPNs in a variety of ways. However, current research has yet to determine how many of these interactions influence EPN performance under field conditions, specifically, if they contribute to the variability limiting EPN efficacy and wide-scale adoption. Here we outline current knowledge of these interactions as well as challenges and avenues for future research, such as greater integration of EPN research with soil animal and rhizosphere ecology, that will better elucidate the potential, limitations, and proper use of EPNs in pest management.
A Comparison of Least-to-Most Prompts and Progressive Time Delay on the Disruptive Behavior of Students with Autism

We compared the effects of two instructional strategies on the frequency of errors and episodes of disruptive behavior of 4 students with autism. In Phase I, easy and difficult tasks were presented to determine whether the tasks were associated with differential rates of disruptive behavior. Phase II compared the effects of a least-to-most prompting procedure (LTM) to a progressive time delay procedure (PTD) on errors and disruptive behavior when difficult tasks were presented. Observers sequentially recorded instructor instructions, response prompts, prompts for appropriate sitting, and feedback statements; and student disruptive, correct, error, and no responses during 1:1 sessions. Results showed PTD produced fewer errors than LTM for all 4 students, and lower rates of disruptive behavior for 2 students. When PTD was implemented as the final phase with 2 of the students, rates of disruptive behavior associated with the task previously taught with LTM immediately decreased. Conditional probability statements indicated that disruptive behavior occurred infrequently with all 4 students when effective response prompts were used.
Comfortable Elegance—Taking Cues from History

This project explores how historical fashion can inform lounge-wear options that are both comfortable and elegant. The project draws on references from the 1910s and 1920s, and explores the use of silk crepe for a design that is functional and aesthetically pleasing.
Early Fever after Haploidentical Bone Marrow Transplantation Correlates with Class II HLA-Mismatching and Myeloablation but Not Outcomes.

Abstract Noninfectious fevers are common early after T cell–replete HLA haploidentical (haplo) peripheral blood transplants and have been associated with cytokine release syndrome and overall mortality. However, less is known regarding the incidence and associations of early fever after bone marrow transplantation (BMT) with post-transplant cyclophosphamide (PTCy). We hypothesized that early fever would be associated with myeloablative conditioning (MAC), because of its relative increase in tissue damage augmenting antigen presentation and class II HLA-mismatching because of recognition of antigen-presenting cells by CD4+ T cells. In 672 recipients of MAC HLA-matched related donor (MRD) (n = 183), MAC HLA-matched unrelated donor (MUD) (n = 115), MAC haplo (n = 79), or nonmyeloablative (NMA) haplo (n = 295) T cell–replete BMT with PTCy, we retrospectively analyzed early noninfectious fever defined as temperature of ≥38.3°C once or ≥38.0°C twice or more on days 1 to 6. Fever occurred in 13% after MAC MRD, 23% after MAC MUD, 44% after NMA haplo, and 84% after MAC haplo BMT (P
Community College Student Affairs and Student Success

A few years ago, I delivered an invited lecture, “Old Wine in New Bottles: Student Affairs Leadership Challenges” where I grounded my remarks about contemporary challenges in the context of histori...
Surgical implantation of the synthetic sling (the 6-point fixation technique and weight-adjusted spacing nomogram): technique and results.

The pubovaginal sling may be used to correct symptomatic Type I, II, and III female stress urinary incontinence.4 Autologous, synthetic, and cadaver allografts have been utilized as the supporting material.5,13,16,23,24 The most feared complication of pubovaginal slings is urethral obstruction; intractable de novo urge incontinence is a close second. Literature reports that the current incidence of urethral obstruction ranges from 5 to 10%, even in the hands of the most experienced surgeons.3-5,13,14,16,23,24 Complications unique to synthetic slings include urethral erosion, vaginal granulation tissue formation, and sling infection.
Characteristics of inbred progenies from morphologically unstable Sorghum plants

Progenies from 68 self-pollinated panicles of 10 somatically unstable sorghum-sudangrass hybrid sectors were grown. Data are presented for 25 progenies from three representative unstable plants. Highly uniform progenies were obtained from most panicles. Results indicate chromosome assortment was not always at random. Major distinctions between panicle progenies suggested that: (a) sorghum-like and sudangrass-like genomes functioned as units; (b) gene transfer and association were non-random further indicating that somatic chromosome substitution or somatic translocations, or other gross changes, may have occurred; and (c) other deviating behaviors implied genetic segregation.
Quantifying electrical interactions between cardiomyocytes and other cells in micropatterned cell pairs.

Micropatterning is a powerful technique to control cell shape and position on a culture substrate. In this chapter, we describe the method to reproducibly create large numbers of micropatterned heterotypic cell pairs with defined size, shape, and length of cell–cell contact. These cell pairs can be utilized in patch clamp recordings to quantify electrical interactions between cardiomyocytes and non-cardiomyocytes.
The Chemotactic Response in Bacteria

Es ist eine grose Freude fur mich, vor einem Auditorium der Gesellschaft fur Biologische Chemie zu sprechen. Jeder Biochemiker der Welt wird geehrt sein, das Land zu besuchen, in dem Fischer, Warburg, Buchner, Meyerhof und viele andere legendare Personlichkeiten der Biochemie ihre Laboratorien hatten. Und es ist insbesondere stimulierend, da die gegenwartigen Beitrage Deutschlands zur Biochemie diese gute, feine Tradition fortsetzen.
Clinical Dialogue and Communication

We spend much of our waking time communicating with others, by speaking, writing, and through “body language.” Communication is a little like sex. It is a normal function and most of us think we are good at it and some are, but many aren’t. Superior clinical communication is a learned skill. Speaking with patients, families, and colleagues calls for a studied blend of selective curiosity, quiet intensity, and the ability to attend to what is not being said.
Efficacy of intraarticular corticosteroid hip injections for osteoarthritis and subsequent surgery

Our study aimed to determine the duration of pain relief from intraarticular hip corticosteroid injections and identify patient predictive factors on injection response. We also sought to determine the subsequent rate of hip surgery and whether severity of hip osteoarthritis or injection response correlated with the decision to undergo surgery. All intraarticular hip steroid injections performed for osteoarthritis under fluoroscopic guidance at a single institution between January 2010 to December 2012 were retrospectively reviewed. Response was divided into three groups: no relief, immediate (≤ 2 weeks of pain relief), and continued (> 2 weeks of pain relief). Presence of hip surgery for osteoarthritis performed within 2 years following injection was obtained. Correlation between patient characteristics with injection outcome and hip surgery was analyzed. Of 78 patients, a total of 82 injections were analyzed. For injections, 19.5% (16/82) showed no response, 47.6% (39/82) showed immediate response, and 32.9% (27/82) showed continued response. There was no significant correlation between injection outcome with age, Tonnis grade, BMI, or duration of symptoms. In total, 48.7% had hip surgery within 2 years after initial injection. There was a significant association between Tonnis grade and surgery, with higher Tonnis grades correlating with decision to undergo surgery (p = 0.002). Gender, age, BMI, duration of symptoms, and radiographic severity of disease do not predict injection response. Due to high surgical rates and poor response, intraarticular hip steroid injections may be less effective in the long term, and surgical management may be considered earlier.
Impact of Crack Sealant on Pavement Skid Resistance

Crack sealing is often a cost-effective preventive maintenance strategy for prolonging pavement service life when applied to pavements in relatively good condition. Crack sealing is generally ineff...
Landslide inventory and main geomorphological features affecting slope stability in the Picentino river basin (Campania, southern Italy)

The landslide inventory of the Picentino basin was realized at 1:25,000, with focus on main geomorphological features affecting slope stability. It is based on different sets of air-photos (scales ...
Freezing-of-Gait Detection Using Wearable Sensor Technology and Possibilistic K-Nearest-Neighbor Algorithm

Freezing of Gait (FoG) is an episodic motor disturbance in Parkinson disease (PD) that causes patients to be unable to initiate or maintain their locomotion. Prior work that used simple and easy-to-learn algorithms based on a singular feature and rule-based classifiers are not sufficient to learn variations in patient walking styles and freezing patterns. Efforts to use machine-learning algorithms suffer from challenges caused by imbalanced datasets. Here, we propose a new approach for FoG detection using a wide set of online calculable features and an instance-based and non-parametric Possibilistic K-Nearest-Neighbor (KNN) classifier. The issue of imbalanced datasets is addressed using the Self-Organizing-Map (SOM) algorithm.
Home-Based Physical Therapy with an Interactive Computer Vision System

In this paper, we present ExerciseCheck. ExerciseCheck is an interactive computer vision system that is sufficiently modular to work with different sources of human pose estimates, i.e., estimates from deep or traditional models that interpret RGB or RGB-D camera input. In a pilot study, we first compare the pose estimates produced by four deep models based on RGB input with those of the MS Kinect based on RGB-D data. The results indicate a performance gap that required us to choose the MS Kinect when we tested ExerciseCheck with Parkinson's disease patients in their homes. ExerciseCheck is capable of customizing exercises, capturing exercise information, evaluating patient performance, providing therapeutic feedback to the patient and the therapist, checking the progress of the user over the course of the physical therapy, and supporting the patient throughout this period. We conclude that ExerciseCheck is a user-friendly computer vision application that can assist patients by providing motivation and guidance to en-sure correct execution of the required exercises. Our re-sults also suggest that while there has been considerable progress in the field of pose estimation using deep learning, current deep learning models are not fully ready to replace RGB-D sensors, especially when the exercises involved are complex, and the patient population being accounted for has to be carefully tracked for its "active range of motion."
DQA: Scalable, Automated and Interactive Data Quality Advisor

Fueled with growth in the fields of Internet of Things (IoT) and Big Data, data has become one of the most valuable assets in today’s world. While we are leveraging this data for analyzing complex systems using machine learning and deep learning, a considerable amount of time and effort is spent on addressing data quality issues. If undetected, data quality issues can cause large deviations in the analysis, misleading data scientists. To ease the effort of identifying and addressing data quality challenges, we introduce DQA, a scalable, automated and interactive data quality advisor. In this paper, we describe the DQA framework, provide detailed description of its components and the benefits of integrating it in a data science process. We propose a programmatic approach for implementing the data quality framework which automatically generates dynamic executable graphs for performing data validations fine-tuned for a given dataset. We discuss the use of DQA to build a library of validation checks common to many applications. We provide insight into how DQA addresses many persistence and usability issues which currently make data cleaning a laborious task for data scientists. Finally, we provide a case study of how DQA is implemented in a realworld system and describe the benefits realized.
Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets

The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.
Functional Analysis of Distinct Populations of Subthalamic Nucleus Neurons on Parkinson Disease and OCD-like Behaviors in Mice

The Subthalamic Nucleus (STN) is a component of the basal ganglia and plays a key role to control movement and limbic-associative functions. STN modulation with Deep Brain Stimulation (DBS) improves the symptoms of Parkinson Disease (PD) and Obsessive-Compulsive Disorder (OCD) patients. However, DBS does not allow for cell-type specific modulation of the STN. While extensive work has focused on understanding STN functionality, the understanding of its cellular components is limited. Here, we first performed an anatomical characterization of molecular markers for specific STN neurons. These studies revealed that most STN neurons express Pitx2, and that different overlapping subsets express Gabrr3, Ndnf or Nos1. Next, we used neuronal modulatory tools to demonstrate their roles in regulating locomotor and limbic functions in mice. Specifically, we showed that optogenetic photoactivation of STN neurons in Pitx2-Cre mice or of the Gabrr3- expressing subpopulation induces locomotor changes, and improves locomotion in a PD mouse model. Additionally, photoactivation of Pitx2 and Gabrr3 cells induced repetitive grooming, a phenotype associated with OCD. Repeated stimulation prompted a persistent increase in grooming that could be reversed by fluoxetine treatment, a first-line drug therapy for OCD. Conversely, repeated inhibition of STNGabrr3 neurons suppressed grooming in Sapap3-KO mice, a model for OCD. Finally, circuit and functional mapping of STNGabrr3 neurons showed that these effects are mediated via projections to the globus pallidus/entopeduncular nucleus and substantia nigra reticulata. Altogether, these data identify Gabrr3 neurons as a key population in mediating the beneficial effects of STN modulation thus providing a new molecular handle for PD and OCD drug discovery.
The Story of the Silent Killer : A History of Hypertension: Its Discovery, Diagnosis, Treatment, and Debates.

Hypertension is the leading risk factor for death and disability-adjusted life-years lost globally. Despite this tremendous impact on health, blood pressure measurement and treatment are relatively new to medical practice, with widespread measurement beginning just over 100 years ago. How, in such a short time, did blood pressure become such an integral measurement in medical practice that it is now considered one of the vital signs? Key revelations through Stephen Hales and his horse experiment, Riva-Rocci’s modern blood pressure cuff, Korotkoff sounds, and President Roosevelt’s death set the stage for discovery. Landmark trials such as the VA Cooperative studies of the 1960s through the recent Systolic Blood Pressure Intervention Trial and Prevention with Mediterranean Diet trials provide the foundation for modern clinical practice. An understanding of the history of hypertension can directly affect current clinical practice and offers unique insights into how the medical community has approached the management of one of the deadliest medical conditions in history.
Smartphone-Based Pavement Roughness Estimation Using Deep Learning with Entity Embedding

The commonly used index for measuring pavement roughness is the International Roughness index (IRI). Traditional method for collecting road surface information is expensive and as such researchers ...
Heteroskedastic Price Forecasting for Food Security Management in Developing Countries

Price forecasting systems are of considerable importance to food security management by governments' and non-governmental organizations. Sparse data availability in low-income economies, however, generally necessitates reliance on reduced form forecasting methods. Relatively recent innovations in heteroscedasticity-consistent time series techniques offer price forecasting tools that are feasible given available data and analysis technologies in low-income economies. Moreover, extended GARCH models exhibit superior out-of-sample forecast accuracy using monthly food price data from Madagascar. These techniques also permit cost reduction in food security operations by more precise estimation of the risk of hitting a critical price level.
Kiobel's 'Touch and Concern' Test in the Eleventh Circuit (and Elsewhere) and a New Paradigm for the Extraterritorial Application of U.S. Law.

The U.S. Supreme Court's jurisprudence on extraterritoriality suffers from a deep incoherence, namely what is meant by extraterritorial application of federal law. Most often the Court gravitates to the law of the place of allegedly illegal conduct, but in other contexts has considered the residence and citizenship of the parties, the effect on U.S. citizens, and other factors. The difficulties with the Supreme Court's approach were on full display in the Supreme Court's 2013 decision in Kiobel v. Royal Dutch Petroleum Co. That case considered the application of the Alien Tort Statute, a federal law that been in place since the late 18th Century. The Court seemed to hold that at least some of the illegal conduct must take place in the U.S., but then held that the presumption against extraterritorial application of the statute could be overcome if the matter were to "touch and concern" the U.S. with "sufficient force." Lower courts have been predictably confused in attempting to apply this test, as well as in attempting to make sense out of the spate of Supreme Court decisions on extraterritoriality since 2010. This article argues that the Supreme Court's approach leads to under-enforcement of U.S. law and proposes a test that would generally allow application of U.S. law in cases in which an essential part of the conduct took place in the U.S. (even if some conduct is foreign) or to the extent that effects are felt by U.S. citizens in the U.S.
Abstract 1648: Checkpoint molecule profiling in tumor cell lines and immune cell lines for application in immuno-oncology drug screening

The development of cancer immunotherapies has emerged as an exciting new method in treating cancer. Inhibition of immune checkpoint is one of the most promising approaches to unleash the potential of the anti-tumor immune response. Immune checkpoint blockades are monoclonal antibodies that bind to checkpoint molecules on the surface of immune and tumor cells. Tumor cells utilize immune checkpoints to suppress immune response and increase survival. There are several established and novel checkpoint molecules being studied to create cancer immune therapeutics. PD-1 (Programmable Death-1) is one of the most studied of these checkpoint molecules and is the basis for several FDA approved therapeutics on the market. Although immune checkpoint blockades have exhibited anti-tumor effects in multiple cancer types, there are still challenges to overcome such as resistance and low response rate. In addition, clinical studies have shown that the efficacy of these treatments vary depending on cancer type. There is a need for comprehensive data on the expression levels of checkpoint molecules based on cancer type, which can be utilized to guide specific treatment plans and combinations. ATCC provides the scientific community a vast portfolio of human tumor and immune cell lines. In this study, we profiled a cross-section of those cell lines with a number of established and novel checkpoint molecules. FACS analysis was used to evaluate expression level of the checkpoint markers including, but not limited to, PD-1, CTLA4, LAG-3, TIGIT, and VISTA. HLA typing was also performed on those cell lines. With this profiling data, we further tested the responses of the cell lines to several on-the-market immunotherapy biologics, such as Pembrolizumab (anti-PD1), Nivolumab (anti-PD1), and Ipilimumab (anti-CTLA4). In our physiological relevant checkpoint assay system, an activated human CD4+ T-cell line and primary CD8+ T-cells were co-cultured with target cell lines with the addition of a serial dilution of checkpoint blockade treatment. We were able to demonstrate T-cell proliferation and increased cytokine expression based on immunotherapy antibody treatment. In summary, this study presents a comprehensive checkpoint molecule profiling data set of T cells lines and tumor cell lines derived from various cancer types that can be used to develop custom assays, as required. The combination of established cell lines and primary T cells offers a unique and effective approach in checkpoint assay development, which provides a valuable tool for studying checkpoint molecule interactions and screening biologics as cancer immunotherapy treatments. Citation Format: Brian Della Fera, Haiyun Liu, Fang Tian. Checkpoint molecule profiling in tumor cell lines and immune cell lines for application in immuno-oncology drug screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1648.
Grading Arson

Criminalizing arson is both easy and hard. On the substantive merits, the conduct of damaging property by fire uncontroversially warrants criminal sanction. Indeed, punishment for such conduct is overdetermined, as the conduct threatens multiple harms of concern to the criminal law: both damage to property and injury to people. Yet the same multiplicity of harms or threats that makes it easy to criminalize “arson” (in the sense of deciding to proscribe the underlying behavior) also makes it hard to criminalize “arson” (in the sense of formulating the offense(s) that will address that behavior). This article asks whether adopting one or more arson offenses is the best way for criminal law to address the conduct in question, or whether that conduct is more properly conceptualized, criminalized, and punished as multiple distinct offenses.
Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition

Summary Targeting protein quality control (PQC) pathways using proteasome or p97/VCP inhibition can effectively treat blood tumors. However, in solid tumors, only p97/VCP inhibitors are effective. To probe this difference in efficacy, we tracked HCT116 colon cancer cells using temporal proteomics to define the cellular and molecular responses to proteasome and p97 inhibition. Proteins involved in general PQC pathways were similarly upregulated by both treatments, suggesting that the proteotoxic stress caused by inhibitors does not explain the differential therapeutic effectiveness. Unexpectedly, proteins specifically dysregulated by two p97 inhibitors are involved in cell cycle control. Indeed, eleven cell cycle proteins were downregulated by p97 inhibition but not by proteasome inhibition. Western blot analysis validated the degradation of cyclin D1 and Securin, which depends on proteasome but not on p97. Differing regulation of cell cycle proteins by p97 and the proteasome may, therefore, explain the therapeutic efficacy of p97 inhibitors in colon cancer.
Tracer Studies of Sediment Transport Processes

Particles of various diameters and specific gravities were coated with fluorescent dyes and used as tracers to study the transport and dispersion of sand-size particles for the flat-bed condition in the Rio Grande conveyance channel and for a dune-bed condition in the Atrisco Feeder Canal, NM. Particle velocities for the dune bed depended on size but were only weakly dependent on specific gravity. Particle velocities for the flat bed depended on size and specific gravity, and were several orders of magnitude greater than the particle velocities for the dune bed. Lateral mixing of the tracers from a point source was considerably greater for the dune bed than for the flat bed. Vertical mixing of the tracers for the flat bed was limited to the thin layer of material moving near the bed surface, with essentially no penetration into the bed. Vertical mixing for the dune bed occurred to a depth approximately equal to the heights of the dunes.
Online Collaboration and Social Networking

This chapter informs how collaborative learning as an instructional strategy can support students in the learning process. Readers are introduced to collaborative learning in online environments and shown how these collaborative environments can further support what they do in their own classes (face-to-face or online). Numerous examples of collaborative tools, social media, course management systems (CMS), and collaborative development environments are defined and explained. Finally, each of the collaborative learning environments is accompanied by a scenario giving a concrete example of how the technology might be used in the classroom.
Of Virtues and Values: Sympathy, Empathy, and Agonistic Respect in Recent Democratic Theory

Recently, political scientists and political theorists have delved into a rich and rapidly growing literature in cognitive neuroscience that examines the interrelation between reason and emotion, cognition and affect. A number of political theorists, inspired by this literature, have begun mapping the affective virtues and values needed to sustain just, legitimate, and other-regarding political decisions. Breaking with dominant rationalist theories, these works construct normative conceptions of the ideal affective-cognitive dispositions required for democratic citizenship. Here, I critically examine three such conceptions: based on sympathy, empathy, and “agonistic respect” respectively. I argue that significant points of convergence exist but presently risk being overlooked, potentially to the peril of shared practical goals such as democratic legitimacy and concern for the Other. Nevertheless, I claim that agonistic pluralism remains the most promising of these articulations in two critical respects. First, an agonistic democratic orientation remains the most viable democratic vehicle for engaging the perspectives of those we deem to be dogmatic, intolerant, and unreasonable. Second, the virtues espoused by agonism offer promise in engaging nascent and emergent political identities, and opening democratic spaces to previously marginalized and hitherto silenced claims of injustice and oppression. Despite this, existing proponents of agonism do a disservice to these goals by speaking a dense, esoteric language that blurs the practical imperatives of such an orientation. I conclude by initiating a call for agonistic pluralism to move in the direction of a more tangible “public philosophy.”
Molecular analysis of plasmid DNA repair within ultraviolet-irradiated Escherichia coli. I. T4 endonuclease V-initiated excision repair.

The process by which DNA-interactive proteins locate specific sequences or target sites on cellular DNA within Escherichia coli is a poorly understood phenomenon. In this study, we present the first direct in vivo analysis of the interaction of a DNA repair enzyme, T4 endonuclease V, and its substrate, pyrimidine dimer-containing plasmid DNA, within UV-irradiated E. coli. A pyrimidine dimer represents a small target site within large domains of DNA. There are two possible paradigms by which endonuclease V could locate these small target sites: a processive mechanism in which the enzyme scans DNA for dimer sites or a distributive process in which dimers are located by random three-dimensional diffusion. In order to discriminate between these two possibilities in E. coli, an in vivo DNA repair assay was developed to study the kinetics of plasmid DNA repair and the dimer frequency (i.e. the number of dimer sites on a given plasmid molecule) in plasmid DNA as a function of time during repair. Our results demonstrate that the overall process of plasmid DNA repair initiated by T4 endonuclease V (expressed from a recombinant plasmid within repair-deficient E. coli) occurs by a processive mechanism. Furthermore, by reducing the temperature of the repair incubation,more » the endonuclease V-catalyzed incision step has been effectively decoupled from the subsequent steps including repair patch synthesis, ligation, and supercoiling. By this manipulation, it was determined that the overall processive mechanism is composed of two phases: a rapid processive endonuclease V-catalyzed incision reaction, followed by a slower processive mechanism, the ultimate product of which is the dimer-free supercoiled plasmid molecule.« less
Metabolic inhibition of mammalian uridine diphosphate galactose 4-epimerase in cell cultures and in tumor cells.

Abstract The metabolism of galactose compounds, especially that of uridine diphosphate d-galactose, has been studied in intact as well as in broken L cells and HeLa cells. It has been shown that the incorporation of d-galactose 1-phosphate into UDP-galactose is rate-limiting in broken cell preparations, whereas the enzymatic 4-epimerization takes place at an appreciable rate. The latter reaction is strongly inhibited by reduced diphosphopyridine nucleotide, especially at a pH close to 7. In intact L cells and HeLa cells, UDP-galactose 4-epimerase is rate-limiting. The intracellular epimerase activity constitutes only about 0.1% of that found under optimal conditions in broken cells. Addition of galactose to these cells brings about a block between the general carbon pool of metabolites and the UDP-hexose pool. This is borne out by the fact that administration to intact L cells or to HeLa cells of 14C-galactose and 12C-glucose in equimolar amounts brings about incorporation by 14C into UDP-hexose without detectable dilution of nonradioactive glucose. This blockage of the UDP-hexose pool from the general metabolic pool as well as the blockage of UDP-galactose 4-epimerase may have biological implications, some of which are briefly discussed.
Max Weber's remarks on Islam: The Protestant Ethic among Muslim puritans

Abstract This article takes a look at Max Weber's remarks on Islam compared with Calvinism with reference to the doctrine of predestination, the quest for salvation, inner-worldly asceticism and the concept of rationalization. The comparison shows that Weber regarded Islam as the polar opposite of the Protestant ethic, particularly in its Calvinist variant. The article then shifts its focus to Indonesian Islam in order to demonstrate that ‘Islam’ and ‘Muslim’ are not univocal but multivocal. Indeed, Indonesian Islam contrasts sharply with Weber's portrait of Islam in the Middle East. Finally, the article examines the extent to which the rise of Muslim puritans within the early Islamic reformist movement in the Muhammadiyah of Indonesia resembles ascetic Protestantism, particularly Calvinism.
Narrow-Band k-Distribution Database for Atomic Radiation in Hypersonic Nonequilibrium Flows

Full-spectrum k-distribution (FSK) and multi-group FSK approaches make it possible to evaluate radiative fluxes at a fraction of the cost needed for line-by-line calculations. However, the required k-distributions need to be assembled from accurate absorption coefficient data for each flow condition, which is computationally expensive. An accurate and compact narrow-band k-distribution database has been developed for the most important species encountered in hypersonic nonequilibrium flow. The database allows users to calculate desired full-spectrum k-distributions through look-up and interpolation. Strategies for k-distribution data generation are outlined. The accuracy of the database is tested by comparing narrow-band mean absorption coefficients and narrow-band emissivities with those obtained from line-by-line calculations. Application of the database to construct full-spectrum k-distributions accurately and efficiently is discussed, and results from a number of heat transfer calculations and cpu-time studies are presented.Copyright © 2009 by ASME
Genetic labeling of both the axons of transduced, glutamatergic neurons in rat postrhinal cortex and their postsynaptic neurons in other neocortical areas by Herpes Simplex Virus vectors that coexpress an axon-targeted β-galactosidase and wheat germ agglutinin from a vesicular glutamate transporter-1 promoter

Neuronal circuits comprise the foundation for neuronal physiology and synaptic plasticity, and thus for consequent behaviors and learning, but our knowledge of neocortical circuits is incomplete. Mapping neocortical circuits is a challenging problem because these circuits contain large numbers of neurons, a high density of synapses, and numerous classes and subclasses of neurons that form many different types of synapses. Expression of specific genetic tracers in small numbers of specific subclasses of neocortical neurons has the potential to map neocortical circuits. Suitable genetic tracers have been established in neurons in subcortical areas, but application to neocortical circuits has been limited. Enabling this approach, Herpes Simplex Virus (HSV-1) plasmid (amplicon) vectors can transduce small numbers of neurons in a specific neocortical area. Further, expression of a particular genetic tracer can be restricted to specific subclasses of neurons; in particular, the vesicular glutamate transporter-1 (VGLUT1) promoter supports expression in VGLUT1-containing glutamatergic neurons in rat postrhinal (POR) cortex. Here, we show that expression of an axon-targeted β-galactosidase (β-gal) from such vectors supports mapping specific commissural and associative projections of the transduced neurons in POR cortex. Further, coexpression of wheat germ agglutinin (WGA) and an axon-targeted β-gal supports mapping both specific projections of the transduced neurons and identifying specific postsynaptic neurons for the transduced neurons. The neocortical circuit mapping capabilities developed here may support mapping specific neocortical circuits that have critical roles in cognitive learning.
Monsanto: partnering for sustainable agriculture

Monsanto is driven by a global commitment to sustainable agricultural production. This commitment includes bringing technologies to farmers that improve their lives by helping them be more productive while using fewer resources--leading to a reduced overall effect on the environment. By using this commitment to drive our actions, we believe we are creating a positive impact on our world. But, we cannot do this alone. That's why, in addition to developing our own products, we also partner and collaborate with others to develop technologies for farmers. We also license our biotech traits and germplasm to other seed companies, giving farmers the opportunity to purchase seed technologies in the brands they choose. External technology collaborations are a key to our promise of delivering innovative new products in the future. At Monsanto, we are focused on developing collaborative alliances that product lasting benefits for our farmer customers and all involved [1].
MathPlayer: web-based math accessibility

MathPlayer is a plug-in to Microsoft's Internet Explorer (IE) that renders MathML[11] visually. It also contains a number of features that make mathematical expressions accessible to people with print-disabilities. MathPlayer integrates with many screen readers including JAWS and Window-Eyes. MathPlayer also works with a number of TextHELP!'s learning disabilities products.
Case study research methods for firm and market research

Case studies are a useful analytical tool for researching firms and industries in transition, so as to gain insights that may not be found in historical time series. However, it is incumbent on researchers to show process rigor in using this tool for theory-building and theory-testing. The article makes prescriptions for case study research design and execution. © 1998 John Wiley & Sons, Inc.