cssi/SciSciGPT-SciSciNet huggingface dataset:
Moving students through steps of mathematical knowing: An account of the practice of an elementary mathematics teacher in transition

Abstract We present an account of a sixth-grade teacher's practice as she responds to the challenges of current reform initiatives. We analyzed classroom observations and interviews to understand how the teacher, Ivy, teaches and thinks about teaching mathematics to her students. For Ivy, mathematical meaning is available in particular experiences. She creates these experiences for her students by leading them through a predetermined sequence of steps of mathematical knowing. This account contributed to our postulation of a perspective on mathematics learning that we refer to as perception-based, in which the goal of instruction is to create opportunities for students to perceive, first hand, mathematics that exists as part of an external reality. We examine implications of this account of Ivy's practice for mathematics teacher development.
Nonlinear and time-resolved optical study of the 112-type iron-based superconductor parent Ca 1 − x La x FeAs 2 across its structural phase transition

The newly discovered 112-type ferropnictide superconductors contain chains of As atoms that break the tetragonal symmetry between the ɑ and b axes. This feature eliminates the need for uniaxial strain that is usually required to stabilize large single domains in the electronic nematic state that exists in the vicinity of magnetic order in the iron-based superconductors. We report detailed structural symmetry measurements of 112-type Ca_(0.73)La_(0.27)FeAs_2 using rotational anisotropy optical second-harmonic generation. This technique is complementary to diffraction experiments and enables a precise determination of the point-group symmetry of a crystal. By combining our measurements with density functional theory calculations, we uncover a strong optical second-harmonic response of bulk electric dipole origin from the Fe and Ca 3d-derived states that enables us to assign C_2 as the crystallographic point group. This makes the 112-type materials high-temperature superconductors without a center of inversion, allowing for the possible mixing of singlet and triplet Cooper pairs in the superconducting state. We also perform pump-probe transient reflectivity experiments that reveal a 4.6-THz phonon mode associated with the out-of-plane motion of As atoms in the FeAs layers. We do not observe any suppression of the optical second-harmonic response or shift in the phonon frequency upon cooling through the reported monoclinic-to-triclinic transition at 58 K. This allows us to identify C_1 as the low-temperature crystallographic point group but suggests that structural changes induced by long-range magnetic order are subtle and do not significantly affect electronic states near the Fermi level.
Kinetics of Testosterone Induced-Cholesterol Synthesis in Rat Ventral Prostate

SummaryThe absolute cholesterol content and rate of cholesterol synthesis was compared in rat ventral prostates obtained from adult normal and castrated rats. Cholesterol content and synthesis reduces to about 8–12% in the ventral prostate of castrated animals as compared to normal rats. Daily testosterone injections to castrated rats elicits a sharp increase in cholesterol content which correlates with an increase in prostate weight. The rate of cholesterol synthesis per microgram of prostatic DNA increases steeply 2 days after testosterone administration and then goes down and reaches a steady state after 5 days.
Hybrid Breakdown and Cellular-DNA Content in a Contact Zone between Two Species of Pocket Gophers (Geomys)

DNA content and coefficients of variation surrounding mean values were examined in 35 individuals from a contact zone between Geomys bursarius major and G. knoxjonesi in New Mexico. Three classes of individuals (parental types and hybrids) from the contact zone were compared to reference samples from outside the contact zone. No significant differences were found in either DNA content or in individual coefficients of variation among any of the five classes examined. Comparison of data from Peromyscus leucopus and pocket gophers documents that hybrid breakdown in cellular-DNA content is not correlated with magnitude of chromosomal, allozymic, and mitochondrial-DNA, or ribosomal-DNA differentiation that distinguishes parental types. Mechanisms that maintain the integrity of the respective gene pools of G. b. major and G. knoxjonesi are not associated with differences in mean DNA content or with variation in quantity of DNA among cells of an individual.
First Row Transition Metal(II) Thiocyanate Complexes, and Formation of 1-, 2-, and 3-Dimensional Extended Network Structures of M(NCS)2(Solvent)2 (M = Cr, Mn, Co) Composition

The reaction of first row transition MII ions with KSCN in various solvents form tetrahedral (NMe4)2[MII(NCS)4] (M = Fe, Co), octahedral trans-MII(NCS)2(Sol)4 (M = Fe, V, Ni; Sol = MeCN, THF), and K4[MII(NCS)6] (M = V, Ni). The reaction of M(NCS)2(OCMe2)2 (M = Cr, Mn) in MeCN and [Co(NCMe)6](BF4)2 and KSCN in acetone and after diffusion of diethyl ether form M(NCS)2(Sol)2 that structurally differ as they form one-dimensional (1-D) (M = Co; Sol = THF), two-dimensional (2-D) (M = Mn; Sol = MeCN), and three-dimensional (3-D) (M = Cr; Sol = MeCN) extended structures. 1-D Co(NCS)2(THF)2 has trans-THFs, while the acetonitriles have a cis geometry for 2- and 3-D M(NCS)2(NCMe)2 (M = Cr, Mn). 2-D Mn(NCS)2(NCMe)2 is best described as MnII(μN,N-NCS)(μN,S-NCS)(NCMe)2 [= Mn2(μN,N-NCS)2(μN,S-NCS)2(NCMe)4] with the latter μN,S-NCS providing the 2-D connectivity. In addition, the reaction of Fe(NCS)2(OCMe2)2 and 7,7,8,8-tetracyanoquino-p-dimethane (TCNQ) forms 2-D structured FeII(NCS)2TCNQ. The magnetic behavior of 1-D C...
Thermal Degradation of Piperazine/4-Hydroxy-1-methylpiperidine for CO2 Capture

The thermal degradation of aqueous piperazine (PZ)/4-hydroxy-1-methylpiperidine (HMPD) for CO2 capture was rigorously evaluated and compared to that of PZ/n-methyldiethanolamine (MDEA). The degradation mechanism for PZ/HMPD was investigated by performing measurements under various conditions and identifying degradation products. The “arm switching” reaction between PZ and HMPD to produce methylpiperazine (MPZ) and hydroxypiperidine (HPD) is the major degradation pathway. A second-order rate model consistent with proposed degradation pathways accurately models the initial degradation rate. The significantly greater stability of PZ/HMPD compared to that of PZ/MDEA is due to the remarkable thermal stability of its immediate degradation product, the smaller initial degradation rate of PZ/HMPD, and the greater thermal stability of HMPD compared to that of MDEA. The potential environmental issues caused by the volatility of one minor degradation product, 1,4-dimethylpiperazine (1,4 DMPZ), need to be addressed f...
Management Information Systems Education from A Systemic Viewpoint

As a proponent of systems thinking and as an MIS educator, I am interested in assuring that systems thinking is (and remains) incorporated into MIS education, not nominally but truly in spirit. This paper reviews some of the highlights of the history of MIS education, with a view toward the identification and preservation of its systemic spirit.
A survey of 215 non-hemophilic patients with inhibitors to Factor VIII.

Information was obtained by questionnaire about 215 nonhemophilic patients who developed inhibitors against factor VIII (antihemophilic factor). The majority of the patients were over 50 years of age, and approximately equal numbers of males and females were reported. Rheumatoid arthritis was present in 8% of the cases, 7% occurred during pregnancy or the post-partum period, and in several there was an association with allergy to penicillin, asthma, “auto-immune” diseases, or malignancy. In 46% of cases, no underlying disorders were identified. Major bleeding was observed in 87 % of patients, and in 22%, death was attributed either directly or indirectly to the presence of the inhibitor. In 11 of 31 patients receiving no therapy other than supportive transfusions of blood or factor VIII concentrate, the inhibitor disappeared after being present for an average duration of 14 months. Corticosteriods were thought to be effective in abolishing the inhibitor in 22 of 45 patients in whom these were the only drugs administered. Twenty-eight patients received azathioprine as well as corticosteriods; in 19, the inhibitor declined or disappeared during treatment. Finally, 80 patients were treated with cyclophosphamide; in 37 there was a favorable outcome. Inhibitors in children and post-partum patients were more likely to disappear spontaneously or with steroid therapy, whereas those in patients with rheumatoid arthritis or other “autoimmune” disorders required treatment with alkylating agents. However, before any specific therapy can be recommended for this disorder, prospective trials of potential therapeutic agents should be conducted in selected subgroups.
Catalysis Science of NOx Selective Catalytic Reduction With Ammonia Over Cu-SSZ-13 and Cu-SAPO-34

Abstract Copper-exchanged, small-pore chabazite (CHA) zeolites were commercialized in 2009 for the selective catalytic reduction (SCR) of NOx compounds with ammonia, as an emissions control strategy in diesel automotive exhaust aftertreatment. Here, we review the fundamental scientific advances that have since been made in the molecular-level understanding of the active sites and mechanisms responsible for NOx SCR with NH3 on Cu-CHA catalysts. A large body of experimental and theoretical characterization has identified that these “single-site” catalysts contain Cu sites of different local coordinations and structures, influenced by synthetic and environmental factors. The speciation of isolated Cu ions is inextricably linked to the support composition and the conditions of exposure. We make new and unifying connections among the seemingly disparate findings of experimental investigations of Cu-CHA catalysts that differ in origin and treatment history, using ex situ and in situ characterizations, and operando characterization during catalysis. We discuss theory-based studies, in conjunction with multiple experimental spectroscopic methods performed on model Cu-CHA catalysts, that provide precise molecular assignments across a wide range of catalysts and conditions. We highlight how molecular-level descriptions of the active sites and mechanisms can provide insight into the chemical factors that influence practical SCR performance and behavior, including the onset of low-temperature NOx conversion, and the critical role of NH3 solvation of Cu active sites for low-temperature activity. Finally, we describe how the fundamental heterogeneous catalysis science approaches used to interrogate Cu-CHA catalysts used for NOx SCR with NH3 can be used to elucidate the molecular-level details of chemistry that occurs on other single-site catalysts.
Intrapancreatic Splenule in a Pancreas Allograft: Case Report.

A 16-year-old white man was involved in a motor vehicle collision and suffered head, chest, and abdominal trauma. Despite initial resuscitative efforts, he progressed to brain death and was designated to be an organ donor by his family. He had no earlier medical or surgical history and no high-risk behaviors. Blood work revealed normal creatinine, liver function tests, lipase, and amylase. Viral serologies were negative except for cytomegalovirus IgG and Epstein-Barr virus nucleic acid. Imaging revealed a right kidney contusion, a manubrial fracture, and fractures of right first rib and bilateral scapulae. No other abdominal trauma was identified, specifically to the pancreas, duodenum, or spleen. Our transplant center accepted the pancreas from this donor. During back-table inspection of the pancreas, a 1.5 × 1.5 cm dark purple rubbery mass was identified within the parenchyma of the pancreas in the tail. An incisional biopsy of the lesion was sent for frozen section, which yielded a mixed inflammatory infiltrate consisting of neutrophils and lymphocytes and an overlying fibrous capsule. The diagnosis of lymphoma or another neoplasm could not be definitely ruled out. Owing to uncertainty in diagnosis, the entire lesion was excised along with the distal pancreas with the use of a linear stapler. The staple line was oversewn with running 4-0 polypropylene suture, and the pancreas was transplanted. After surgery, the pancreas allograft functioned well with a small pancreatic leak, which had resolved by the first postoperative outpatient visit.
Cystic metastatic lymph nodes in malignant melanoma: a case report

Melanoma is a rare type of skin cancer with a high mortality rate. Local invasion and metastatic spread are primarily responsible for the morbidity and mortality of melanoma. While metastatic lesions vary from cystic to solid, cystic metastases can be challenging to diagnose. Up to date, there are only a few published studies that describe cystic metastases in melanoma and other conditions such as lymphoma, squamous cell carcinoma and thyroid papillary carcinoma. We describe a case of cystic metastatic axillary lymph nodes in a patient with subungual acral lentiginous melanoma and the challenges to reaching an accurate diagnosis.
Nicotine content and physical properties of large cigars and cigarillos in the united states

Introduction Cigars are combusted tobacco products consisting of filler, binder, and wrapper, which are derived from tobacco. Despite the abundance of literature on the composition of traditional combusted cigarettes, research is limited on the physical and chemical properties of cigars. Therefore, research on cigar properties may be useful to better understand their health impact. Methods In this study, twenty large cigar and cigarillo products were characterized for physical properties (ie, weight, length, and diameter), filler nicotine content, and tobacco pH. Tobacco pH was used to calculate free nicotine content, free nicotine concentration, and percent free nicotine for all cigars using the Henderson-Hasselbach equation. An additional analysis was performed on a second batch of two large cigar and two cigarillo brands to determine within-brand consistency. All analyses were performed in triplicate. Results The initial analysis of the twenty cigars showed that cigars exhibited wide variation in product size and nicotine content, although tobacco pH was similar across cigars. Furthermore, in the two large cigar and cigarillo brands analyzed a second time, there was considerable within-brand variance in nicotine content and concentration between the first and second analyses. Conclusions While only a small sample of commercially-available cigars was analyzed, our data suggest there is wide variability in nicotine content and some physical properties in the domestic cigar market. The data may help to inform potential future regulatory decisions related to these products. Implications This study reveals some of the challenges to experimental cigar research and illustrates the need to characterize cigar products (eg, nicotine and tobacco content) before use in clinical studies. Additional studies and characterization of the physical and chemical properties of cigars may be useful to further understand these products' toxicity, abuse potential, and public health impact.
Comparison of Proportional and On/Off Solar Collector Loop Control Strategies Using a Dynamic Collector Model

Common control strategies used to regulate the flow of liquid through flat-plate solar collectors are discussed and evaluated using a dynamic collector model. Performance of all strategies is compared using different set points, flow rates, insolation levels and patterns (clear and cloudy days), and ambient temperature conditions. The unique characteristic of the dynamic collector model is that it includes effects of collector capacitance. In general, capacitance has a minimal effect on long term collector performance; however, short term temperature response and the energy =storage capability of collector capacitance are shown to play significant roles in comparing on/off and proportional controllers. Inclusion of these effects has produced considerably more realistic simulations than any generated by steady-state models. Simulations indicate relative advantages and disadvantages of both types of controllers, conditions under which each performs better, and the importance of pump cycling and controller set points on total energy collection. Results show that the turn-on set point is not always a critical factor in energy collection since collectors store energy while they warm up and during cycling; and, that proportional flow controllers provide improved energy collection only during periods of interrupted or very low insolation when the maximum possible energy collection is rela=more » tively low. Although proportional controllers initiate flow ·at lower insolation levels than on/off controllers, proportional controllers produce lower flow rates and higher average collector temperatures resulting in slightly lower instantaneous collection efficiencies.« less
Ex-Vivo Regulatory T Cells Isolated from Patients with Amyotrophic Lateral Sclerosis Are Dysfunctional (S20.006)

Objective: To determine whether regulatory T cells (Tregs) from patients with amyotrophic lateral sclerosis (ALS) lack the ability to suppress the proliferation of effector T cells (Teffs) and whether such inability is mediated by an epigenetic mechanism. Background: In ALS mice, Tregs are neuroprotective and slow disease progression. Concomitantly, data from ALS patients suggested that Tregs influence disease progression rates, and that early reduced FoxP3 expression levels were predictive of future rapid progression and attenuated survival. Design/Methods: Lymphocytes were isolated from the blood of 27 patients with confirmed ALS and 17 healthy control volunteers. Treg suppression assays were then performed. Methylation assays of the Treg-specific demethylated region (TSDR) were performed on Treg DNA, followed by bi-sulphite treatment, PCR amplification, and sequencing. Results: ALS Tregs did not effectively suppress the proliferation of Teffs compared with control Tregs; ALS and control Teffs expanded to a similar extent. The more impaired or rapidly-progressing the ALS patient, the greater the Treg dysfunction. This dysfunction was a property of the ALS Tregs since suppression of ALS Teffs by control Tregs was not compromised. Epigenetically, the percent methylation of the TSDR was greater in ALS Tregs compared with control Tregs. More importantly, when ALS Tregs that had decreased suppressive function were expanded in-vitro using IL-2 and rapamycin, the suppressive abilities of these ALS Tregs were restored to that of control Tregs. Conclusions: Freshly isolated ex-vivo ALS Tregs are functionally less suppressive than similarly isolated control Tregs. Epigenetically, the reduced suppressive abilities of rapidly- progressing patients’ Tregs may be due to increased methylation of the TSDR. Since the dysfunction is reversible, the in-vivo loss of suppression may be mediated by serum factors. Thus, autologous passive transfer of in-vitro expanded Tregs may offer a novel cellular therapy for some ALS patients, thereby slowing disease progression. Disclosure: Dr. Beers has received research support from Glaxo Smith Kline. Dr. Zhao has received research support from GlaxoSmithKline. Dr. Thonhoff has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Alsuliman has nothing to disclose. Dr. Shpall has nothing to disclose. Dr. Rezvani has nothing to disclose. Dr. Appel has received research support from Neuraltus, Inc., and GlaxoSmithKline.
Home Monitoring Heart Failure Care Does Not Improve Patient Outcomes Looking Beyond Telephone-Based Disease Management

Despite considerable advances in evidence-based medical therapy, heart failure continues to contribute a substantial burden of morbidity, mortality, and economic cost to the American healthcare system. After an admission for heart failure management, nearly 25% of patients are readmitted within 30 days, and by 6 months, this proportion reaches nearly 50%.1,2 Medicare payments for unplanned hospital readmissions totaling more than $17 billion account for nearly 15% to 20% of total Medicare expenditure on acute hospital care.3 Accordingly, in 2009, the US Center of Medicare and Medicaid Services began public reporting of all-cause readmission rates after heart failure hospitalization, and last year, the Patient Protection and Affordable Care Act (PPACA)4 was signed into law, establishing financial incentives for hospitals to reduce cardiovascular readmissions. These trends underscore the growing fiscal and medical imperative to develop better strategies to improve care delivery to heart failure patients and reduce rehospitalization rates. Response by Konstam on p 836 Because nearly one half to two thirds of these readmissions appear to be triggered by potentially remediable factors, including poor discharge planning, nonadherence to recommendations regarding diet and medical treatment, inadequate follow-up, poor social supports, and delays in seeking medical attention,5–7 there is increasing interest in restructuring the care of ambulatory heart failure patients to reduce fragmentation, enhance patient self-efficacy, and improve cost-effectiveness, quality, and clinical outcomes while smoothing the transition from hospital to home. Initiatives focused on these goals are broadly categorized as “disease management programs ” and are increasingly endorsed by congressional initiatives to overhaul the U.S. healthcare system, as exemplified by their inclusion as part of the essential health benefits enshrined in section 1302 of the PPACA.4 Although heart failure disease management programs vary widely in their specific content and focus, most provide for some …
BCH for Solid-State-Drives

Given that the NAND Flash memory is not a very reliable medium, it follows that a Solid State Disk needs some help to achieve a reliability suitable for computing applications: the Error Correction Code (ECC).
Some Examples of Crinkles

Many physical problems can be phrased as the problem of minimizing some energy functional E[f] over a given class of admissible functions f. It can happen that there is a minimizing sequence fn that approaches a limit f but f does not minimize E, either because f is not in the admissible class or because E is not lower semicontinuous. In the examples that I discuss here, this happens because the derivatives # are highly discontinuous and do not approach f’ in the limit. I call such sequences crinkles, and call the limiting function f the carrier of the crinkle. Young [1] has written a book on the subject; he calls such sequences generalized curves. In control theory the same sort of thing is also called a chattering state.
Metaphor, Music and Humor: A Reconstruction of the Literature

Robert Frost said, All thinking …is metaphorical. Poetry is simply made of metaphor. 1 So also is philosophy—and science. The first annotated metaphor bibliography contained nearly all of the previous writing on metaphor.2 This was followed by two more bibliographies.3 The literature on metaphor has exploded in the last twenty years. What is to be shown here is that and how metaphor is relevant to art.
A Low-Noise, Rapid Microelectrode

Ion-selective microelectrodes (/u-ISE) using an ion-selective liquid ion–exchanger membrane have very high resistances because of their very sgall tip diameter (0.5 – 1.0 /um). The value of the resistance ranges from 109 Ω to 1011 Ω (2, 8, 10) depending on the tip size and the type of ion exchanger. This imposes the requirement of a very high input impedance and a very small leakage current on the measuring electrometer.
CHAPTER 17 – Imaging dendritic cells: a primer

Dendritic cells (DCs) can be identified according to many different phenotypic characteristics, related both to their tissue of origin and stage of differentiation. Different populations can be fluorescently immunolabeled using antibodies to one or more molecules expressed by the cells. Fluorescence microscopy can be used to examine the specific locations of different populations of endogenous DCs within sections of various tissues, tonsil, and their interactions with other types of cells within the tissue. Electron microscopy (EM) is useful for freshly sorted or isolated dendritic cells or cultured dendritic cells. DCs have unique ultrastructural characteristics that set them apart from other mesenchymal cells, including leukocytes such as monocytes, T, and B cells. DCs are often best identified from other leukocytes using surface topology afforded by scanning electron microscopy (SEM). This technique allows the visualization of the membrane “veils” or “dendrites,” which readily distinguish DCs from other cell types.
Theoretical study of electron-impact excitation of N 2 +

We report the results of an ab initio treatment of electron-impact excitation cross sections for the process ${\mathit{e}}^{\mathrm{\ensuremath{-}}}$+${\mathrm{N}}_{2}^{+}$(X${\mathrm{}}^{2}$${\mathrm{\ensuremath{\Sigma}}}_{\mathit{g}}^{+}$)\ensuremath{\rightarrow}${\mathit{e}}^{\mathrm{\ensuremath{-}}}$+${\mathrm{N}}_{2}^{+}$(B${\mathrm{}}^{2}$${\mathrm{\ensuremath{\Sigma}}}_{\mathit{u}}^{+}$) from 5.0 to 40 eV. The dynamically important low-order partial wave components of the scattering amplitude were obtained from multistate close-coupling calculations with correlated target wave functions. The calculations were carried out using a modification of the complex Kohn variational method. The higher-order partial-wave components, which are essential for computing converged cross sections for optically allowed transitions such as this, were efficiently evaluated by an asymptotic Coulomb-Born approximation. Of the widely differing sets of experimental cross sections reported for this process, our calculations are in excellent agreement with the most recent measurements.
Abstract 2694: Receptor-interacting protein kinase 2 promotes prostate cancer progression by activating the MAX:MYC pathway

Background: Prostate Cancer (PCa) is the most common non-skin cancer among American man. Currently, major challenges in the clinical management of PCa include 1) a lack of biomarkers that can reliably distinguish aggressive from indolent PCa and 2) a shortage of therapeutic strategies that can prevent or suppress the progression of PCa into aggressive PCa. Methods: Label-free quantitative proteomics was performed on three widely used PCa cell lines with different levels of aggressiveness (i.e., LNCaP, DU145 and PC3). Upstream regulator analysis and network modeling were conducted to identify candidate key promoters of PCa aggressiveness. The levels of gene amplification, mRNA expression, and protein expression of a key candidate promoter, receptor-interacting protein kinase 2 (RIPK2), were compared by analyzing publicly accessible PCa genomic and transcriptomic datasets and by immunohistochemistry (IHC) staining of PCa tissue microarrays (TMA). Cell proliferation and invasion assays were performed to compare PC3 cells with or without CRISPR/Cas9 knock-out of RIPK2. Quantitative proteomics and bioinformatics analysis were conducted to identify the underlying mechanisms, followed by validation via western blotting, quantitative real-time PCR (qRT-PCR) and in vitro functional assays. Results: Quantitative proteomics analysis of the three PCa cell lines identified over 6,500 proteins, among which 341 are significantly (adjusted p-value Conclusion: Taken together, our data elucidate that RIPK29s amplification and overexpression in PCa cells may activate the MAX:MYC-EIF2 signaling axis and thus in turn promote PCa cell proliferation and invasion. The aberrant activation of the RIPK2-MAX:MYC-EIF2 pathway may serve as a valuable biomarker and novel drug target of PCa progression. Citation Format: Yiwu Yan, Bo Zhou, Xiaopu Yuan, Michael E. Doche, Zhaoxuan Ma, Colm Morrissey, Arkadiusz Gertych, Sungyong You, Beatrice Knudsen, Michael R. Freeman, Wei Yang. Receptor-interacting protein kinase 2 promotes prostate cancer progression by activating the MAX:MYC pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2694.
Abstract A176: Overcoming CD8 T-cell suppression in the tumor microenvironment

CD8 T-cell-mediated antitumor immunity is required for the control and elimination of tumors. However, tumors are able to overcome immune response resulting in immunosuppression, tumor growth, and metastatic spread. CD8 T-cells are controlled through a homeostatic network of positive and negative feedback loops. These negative signals are exploited by the tumor and associated suppressive cell populations in the tumor microenvironment. Immunotherapies targeted to receptors that control these negative signals, termed immune checkpoint inhibitors, have provided robust and durable responses to a number of cancers. Unfortunately, only a subset of patients will respond to current immunotherapies. This is due to the accruement of suppressive and inhibitory mechanisms employed by the tumor and its microenvironment. These include expression of inhibitory ligands, release of immune-suppressive factors, and the recruitment of suppressive cell populations. Furthermore, the administration of immune checkpoint inhibitors can enhance tumor acquisition of a more suppressive phenotype, diminishing immune responses through additional inhibitory pathways. We therefore propose that further CD8 T-cell-intrinsic negative regulators most likely exist, which can be targeted to improve antitumor responses. Here, we have used functional genomic approaches to identify pathways that can be targeted to advance anti-tumor responses, either in combination with anti-PD-1 or to overcome suppressive mechanisms employed by the tumor microenvironment. Using both in vivo and in vitro assays, we have identified both a novel target that provides an enhancement to CD8 T-cell effector function when in combination with PD-1 checkpoint blockade, and CD8 T-cell-intrinsic pathways that are modulated by the presence of suppressive cells associated with the tumor microenvironment. Citation Format: Adam N.R Cartwright, Peng Jiang, Assieh Saadatpour, Guo-Cheng Yuan, Shirley X. Liu, Kai W. Wucherpfennig. Overcoming CD8 T-cell suppression in the tumor microenvironment [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A176.
Nuclear Energy: A Second Round of Questions.

Ambrosia Lake region in New Mexico contains the world's largest known uranium reserve, but how many Ambrosia Lakes will be needed to meet projected demands?Is there enough uranium ore in the United States to fuel the light water reactor, and does success hinge on the untried breeder? The government should halt or reduce the present program until the answers are better known
Push, pull, rerun: television reruns and streaming media.

In scholarly and industry analyses of television’s expansion into online distribution, few have accounted for the specific negotiations required when old television content streams on new media. Th...
Comparing the kinetics of the hydrolysis of by-product from channel catfish (Ictalurus punctatus)fillet processing by eight proteases

Abstract Channel catfish farming is the most important warm water aquaculture in the United States and is very important to the rural economy. This study's objective was to investigate the kinetics of the enzymatic hydrolysis of catfish by-product. Channel catfish (Ictalurus punctatus) by-products (heads and frames) were collected from local catfish processing plant. Papain, ficin, bromelain, neutrase, alcalase, protamex, novo-proD and thermolysin were used for hydrolysis. Proteolytic activities of those proteases were examined at different hydrolysis temperature, proteases cost for reaching certain degree of hydrolysis was predicted. Degree of hydrolysis (DH) of the hydrolysates and hydrolysis kinetics were studied. Emulsifying and foaming property and stability of selected hydrolysates were evaluated. Results indicated that thermolysin had the highest activity (8.2 × 108 Azocoll U/g and 5.6 × 106 Azocasein U/g) at 70 °C. The highest DH of the hydrolysates were observed in 120 min with the concentration of 80 AzU/g for all enzymes. Ficin (80 AzU/g) was the most efficient in hydrolyzing the by-product (DH reaching 71%) in 120 min at 30 °C. The hydrolysis curves fit the Peleg model well with R2 higher than 0.91. This study provides important engineering information for choosing proteases and processing conditions for optimization of efficiency, yield and economy.
Role of DNA-PKcs/topoisomerase I interaction in the cellular sensitivity to S-phase-induced DNA damaging agents.

5779 Topoisomerase I (Top1) is a nuclear enzyme involved in the removal of torsional constraints associated with DNA replication and transcription. It cleaves the DNA on one strand and forms covalent top1-DNA cleavage complexes which are the target of top1 inhibitors such as camptothecins (CPT) and its analogs which are widely used in the treatment of human cancers. Cleavage complexes are not toxic per se but their conversion into irreversible DNA double-strand breaks (DSBs) lead to cell death. They result from the blockage of advancing replication forks by stabilized cleavage complexes. The precise mechanism of repair of Top1-mediated DSBs is not known, but probably involves various pathways including Homologous Recombination (HR) and Non-Homologous End-Joining (NHEJ). Previous studies have shown that M059J and CHO-V3 NHEJ-deficient cells were more sensitive than their NHEJ-proficient counterparts, MO59K and V3-F18. Because these cells lack DNA-PKcs (which associates to Ku70 and Ku86 to form DNA-PK), this effect was attributed to a defect in repair. Here, we show that CHO cells expressing a kinase dead-domain DNA-PKcs (V3-KA4) were not hypersensitive to CPT. This demonstrates for the first time that the absence of DNA-PKcs, but not the inhibition of its kinase activity, is responsible for the hypersensitivity of MO59J and V3 cells to CPT. Since Top1 was reported to interact with DNA-PKcs, we studied whether DNA-PKcs/Top1 interaction could be involved in the regulation of the cellular response to CPT. We show that Top1 interacts predominantly with the free form of DNA-PKcs in HeLa cells. This interaction was dramatically reduced when cells were treated by CPT and pre-treatment with the replication inhibitor aphidicolin could prevent the dissociation of Top1 from DNA-PKcs. Moreover, DNA-PK inhibits DNA relaxation and DNA cleavage catalyzed by purified Top1 in vitro. This inhibition depends on the presence of the N-terminus of Top1 since no effect was observed when the 70 kDa N-terminal truncated Top1 was used. Interestingly, we found that in untreated cells, absence of DNA-PKcs resulted in a higher amount of Top1-DNA cleavage complexes, as well as a higher DNA damage signalling as indicated by the increase in DSB formation, apoptosis levels, or p21 expression. We also show that in S-phase, the absence of DNA-PKcs could also sensitize cells to ionizing radiations. Altogether, our data shed light on a new potential role for DNA-PKcs, independent of its kinase activity and of NHEJ, where its interaction with Top1 regulates the cellular sensitivity to Top1 poisons and other DNA-damaging agents in S-phase.
Precision medicine and actionable alterations in lung cancer: A single institution experience.

Objectives Oncology has become more reliant on new testing methods and a greater use of electronic medical records, which provide a plethora of information available to physicians and researchers. However, to take advantage of vital clinical and research data for precision medicine, we must initially make an effort to create an infrastructure for the collection, storage, and utilization of this information with uniquely designed disease-specific registries that could support the collection of a large number of patients. Materials and methods In this study, we perform an in-depth analysis of a series of lung adenocarcinoma patients (n = 415) with genomic and clinical data in a recently created thoracic patient registry. Results Of the 415 patients with lung adenocarcinoma, 59% (n = 245) were female; the median age was 64 (range, 22–92) years with a median OS of 33.29 months (95% CI, 29.77–39.48). The most common actionable alterations were identified in EGFR (n = 177/415 [42.7%]), ALK (n = 28/377 [7.4%]), and BRAF V600E (n = 7/288 [2.4%]). There was also a discernible difference in survival for 222 patients, who had an actionable alteration, with a median OS of 39.8 months as compared to 193 wild-type patients with a median OS of 26.0 months (P<0.001). We identified an unprecedented number of actionable alterations [53.5% (222/415)], including distinct individual alteration rates, as compared with 15.0% and 22.3% in TCGA and GENIE respectively. Conclusion The use of patient registries, focused genomic panels and the appropriate use of clinical guidelines in community and academic settings may influence cohort selection for clinical trials and improve survival outcomes.
Chapter 24 – The Vitamins

Publisher Summary The goals of this chapter are to outline selected functions of vitamins and to develop concepts and principles relative to vitamins that may aid in clinical assessment. Vitamins represent a diverse array of molecules, which have equally diverse functional roles in an array of organisms and species. However, there are many common themes and similarities that have practical significance. Differences in requirements among species are usually due to unique pathways for production, degradation, or disposal. Ascorbic acid and niacin are examples of vitamins that cannot be synthesized by some animals and, therefore, are trace vitamins. Similarly, there is a dietary requirement for vitamin D in cats and dogs, but the requirement is conditional for most other species. Taurine is an example of a nutrient where continual enteric degradation and loss results in a nutritional need. With respect to functions, vitamins evolved to serve unique and complex roles as cofactors, as signaling agents in cells, as regulators of gene expression, and as redox and free-radical quenching agents. As is the case for any substance that is essential to a given function, all vitamins at some point in development can be viewed as limiting nutrients, the absence of which results in specific deficiency signs and symptoms.
New Insights on the Mobility of Viral and Host Non-Coding RNAs Reveal Extracellular Vesicles as Intriguing Candidate Antiviral Targets

Intercellular communication occurring by cell-to-cell contacts and via secreted messengers trafficked through extracellular vehicles is critical for regulating biological functions of multicellular organisms. Recent research has revealed that non-coding RNAs can be found in extracellular vesicles consistent with a functional importance of these molecular vehicles in virus propagation and suggesting that these essential membrane-bound bodies can be highjacked by viruses to promote disease pathogenesis. Newly emerging evidence that coronaviruses generate non-coding RNAs and use extracellular vesicles to facilitate viral pathogenicity may have important implications for the development of effective strategies to combat COVID-19, a disease caused by infection with the novel coronavirus, SARS-CoV-2. This article provides a short overview of our current understanding of the interactions between non-coding RNAs and extracellular vesicles and highlights recent research which supports these interactions as potential therapeutic targets in the development of novel antiviral therapies.
Bioinspired Shape-Changing Soft Robots for Underwater Locomotion: Actuation and Optimization for Crawling and Swimming

Many existing rigid underwater robots use propellers to create thrust. These traditional robots are widely used because they are capable of moving large payloads at high speeds through open water. However, the movement patterns exhibited by soft underwater organisms suggest that there are alternative locomotion methods that robots can use to be more efficient, less disruptive to the environment, and to navigate confined spaces more easily than current rigid robots. Biological strategies that have survived through the evolutionary process can be used as inspiration to create robust locomotion of robots using soft materials. This chapter reviews how soft, underwater organisms change their shapes to enhance motion, catalogues how researchers have used soft active materials to mimic these abilities, and discusses how recent work uses optimization to produce more effective underwater robotic locomotion. We categorize underwater locomotion into crawling and swimming, where crawling uses contact with a solid substrate for moving through the fluid, and swimming relies purely on hydrodynamic forces for propulsion. We summarize the main categories of actuators for soft robotics with a focus on how these actuators can be used to create shape-changing mechanisms. By further categorizing the state-of-the-art in bioinspired robotic locomotion for different types of crawling and swimming motions, we identify future avenues for research. We also detail how optimization can be used to design robot components and behaviors, and to explore how active online optimization of design parameters can improve robot performance. The biological inspirations and engineering applications described in this chapter form the basis for the design of soft underwater robots that locomote effectively by creating favorable interactions with fluid environments.
Shared Consciousness and the Emergence of Mind

The need to share experience represents a core component of human biological and psychological, ranging from mother–infant attachment to core aspects of consciousness, including the capacity to differentiate internal from external stimuli, language acquisition and symbolic reasoning, and the development of functional social relationships. Nondisclosure, on the other hand, represents another essential domain of interpersonal functioning, and is intrinsic to self-differentiation, development of autonomy, and adherence to social norms. Nondisclosure takes many forms and occurs in different settings for different reasons.
In Search of Missing Risk Factors: Hedge Fund Return Replication with ETFs

Fully spanning the space of potential risk factors with tradable liquid portfolios is paramount in the context of a risk-based factor model. We develop a factor selection methodology of spanning the space of hedge fund risk factors with all available exchange traded funds (ETFs). We demonstrate the efficacy of the methodology with out-of-sample hedge fund return replication, and find that the replication accuracy increases with the number of ETFs available. This is consistent with our interpretation of ETF returns as proxies to alternative risk factors driving hedge fund returns. We further consider portfolios of “cloneable” and “non-cloneable” hedge funds, defined as top and bottom in-sample R2 matches. We find superior risk-adjusted performance for “non-cloneable” funds, while “cloneable” funds fail to deliver significantly positive risk-adjusted performance. Our methodology provides value in both identifying skilled managers of “non-cloneable” hedge funds, as well as successfully replicating out-of-sample returns that are due to alternative risk exposures of “cloneable” hedge funds, thus providing a transparent and liquid alternative to investors who may find these return patterns attractive.
What is the force of forced migration? Diagnosis and critique of a conceptual relativization

Theorizing of forced migration and refugees has been paralyzed by excessive reliance on migration theory. This article suggests the need to transfer conceptualizations of forced migration to sociological theories of violence. To that end, a preliminary step is argued to be indispensable: the affirmation of the force factor as a vital concept for meaningful theorization of refugee phenomena. Conceptual and empirical reasons are offered to resurrect the force factor’s centrality. First, I suggest the need to resolve the conceptual residuality of “forced migration” in sociological theory, proposing manageable terminology for the task at hand. Second, I sketch conceptual and empirical reasons that the force factor is a viable and urgent candidate for our theoretical toolkit. Finally, I assess in depth the shortcomings of three prominent relativization conditions: (1) unwitting severity; (2) processual dilution; and (3) political-economic indeterminacy. By overcoming onerous relativization habits, we open horizons for coercion-centric theoretical insights on forced migration.
Interferons and potential consequences for sars-cov-2 infection

RATIONALE: Severe acute respiratory syndrome 2 (SARS-CoV-2) and resulting coronavirus disease 2019 (COVID-19) have been associated with several symptoms including fever, chills, cough, fatigue, loss of taste or smell, sore throat, and congestion. Moderate cases may require hospitalization and severe cases have resulted in death. Interferons (IFNs) are a class of immune molecules typically involved in the anti-viral response. Their role in SARS-CoV-2 infection is controversial as IFNs may increase angiotensin-converting enzyme 2 (ACE2) expression, the receptor for SARS-CoV-2, yet also enhance viral clearance. IFN-α2 stimulation increases gene expression of Interleukin-6 (IL-6), a cytokine that activates STAT proteins and is associated with poor hospital outcomes in COVID-19 patients. Meanwhile, surfactant protein A (SP-A), an immunomodulatory respiratory protein, is known from our work to bind to cytokine receptors such as IL-13α1 and IL-13 ligand (Francisco et al, JI 2020). Therefore, we hypothesized that SP-A binds to ACE2 and IL-6, making it a possible novel regulator of SARS-CoV-2 infection that potentially impacts disease severity.Methods: Normal human bronchial epithelial cells (NHBE) and asthmatic diseased bronchial human epithelial cells (DHBE) were cultured at air liquid interface for 2 weeks and stimulated with increasing doses of IFN-α2 (0.1, 1, and 10 ng/ml) for 48 hours. RT-PCR was performed and gene expression for ACE2 and IL-6 was assessed by normalizing to PPIA. Binding assays were performed using a 96-well, immunosorbent assay coated with either IL-6, IL-6Rα, GP130, ACE2, IFN-α2 or the negative control, EGFR and incubated with increasing concentrations of full-length SP-A (0-5000 ng/ml) and a SPA-HRP conjugated antibody. In separate experiments, western blotting was used to detect levels of total and phosphorylated STAT-1 in primary asthmatic bronchial epithelial cells treated for 30 minutes with IL-6 (10 ng/ml) in the presence and absence of SP-A2 (20 ug/ml) peptide.Results: Stimulation with 10 ng/ml IFN-α2 significantly increased ACE2 and IL-6 gene expression in NHBE and DHBE cells (p<.05). Full length SP-A was found to bind ACE2, both IL-6 receptors (IL-6Rα and GP-130), and to a lesser extent, IL-6 cytokine. SP-A did not bind to IFN-α2 or EGFR. Asthmatic primary human lung epithelial cells treated with IL-6 resulted in phosphorylation of STAT-1, and pre-treatment with SP-A2 peptides reduced this activation by approximately 45%.Conclusion: While IFNs may play a role in viral clearance, our data suggest potential dysregulation of mechanisms affecting the response to SARS-CoV-2. SP-A may be protective based upon its effects on ACE2 and IL-6.