Navigating a Calculus Course During a Pandemic: A USMA Perspective

In this article we analyze publications written about different teaching modalities and evaluate how each applies to a calculus class during the on-going COVID-19 pandemic. We focus on the positives and negatives of teaching and learning in a virtual, classroom, or HyFlex environment. Although arguments could be made for each environment, especially given different institutional objectives, this work aims to explain why we eventually preferred teaching our Fall 2020 multivariable calculus course in a face-to-face classroom setting at the United States Military Academy at West Point. We also offer measures of performance to compare the current COVID-19 semester with previous semesters. The results support two major conclusions drawn from our decision to teach in-person under in a time constrained environment: learning modality matters in mathematics and this pandemic will influence student-teacher interaction for semesters to come

PPARγ agonists do not directly enhance basal or insulin-stimulated Na+ transport via the epithelial Na+ channel

Selective agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are anti-diabetic drugs that enhance cellular responsiveness to insulin. However, in some patients, fluid retention, plasma volume expansion, and edema have been observed. It is well established that insulin regulates Na(+) reabsorption via the epithelial sodium channel (ENaC) located in the distal tubule. Therefore, we hypothesized that these agonists may positively modulate insulin-stimulated ENaC activity leading to increased Na(+) reabsorption and fluid retention. Using electrophysiological techniques, dose-response curves for insulin-mediated Na(+) transport in the A6, M-1, and mpkCCD(cl4) cell lines were performed. Each line demonstrated hormone efficacy within physiological concentration ranges and, therefore, can be used to monitor clinically relevant effects of pharmacological agents which may affect electrolyte transport. Immunodetection and quantitative PCR analyses showed that each cell line expresses viable and functional PPARgamma receptors. Despite this finding, two PPARgamma agonists, pioglitazone and GW7845 did not directly enhance basal or insulin-stimulated Na(+) flux via ENaC, as shown by electrophysiological methodologies. These studies provide important results, which eliminate insulin-mediated ENaC activation as a candidate mechanism underlying the fluid retention observed with PPARgamma agonist use

Scaling factors for the in vitro-in vivo extrapolation (IV-IVE) of renal drug and xenobiotic glucuronidation clearance.

AIM: To determine the scaling factors required for inclusion of renal drug glucuronidation clearance in the prediction of total clearance via glucuronidation (CLUGT ). METHODS: Microsomal protein per gram of kidney (MPPGK) was determined for human 'mixed' kidney (n = 5) microsomes (MKM). The glucuronidation activities of deferiprone (DEF), propofol (PRO) and zidovudine (AZT) by MKM and paired cortical (KCM) and medullary (KMM) microsomes were measured, along with the UGT 1A6, 1A9 and 2B7 protein contents of each enzyme source. Unbound intrinsic clearances (CLint,u,UGT ) for PRO and morphine (MOR; 3- and 6-) glucuronidation by MKM, human liver microsomes (HLM) and recombinant UGT1A9 and 2B7 were additionally determined. Data were scaled using in vitro-in vivo extrapolation (IV-IVE) approaches to assess the influence of renal CLint,u,UGT on the prediction accuracy of the calculated CLUGT values of PRO and MOR. RESULTS: MPPGK was 9.3 ± 2.0 mg g(-1) (mean ± SD). The respective rates of DEF (UGT1A6), PRO (UGT1A9) and AZT (UGT2B7) glucuronidation by KCM were 1.4-, 5.2- and 10.5-fold higher than those for KMM. UGT 1A6, 1A9 and 2B7 were the only enzymes expressed in kidney. Consistent with the activity data, the abundance of each of these enzymes was greater in KCM than in KMM. The abundance of UGT1A9 in MKM (61.3 pmol mg(-1) ) was 2.7 fold higher than that reported for HLM. CONCLUSIONS: Scaled renal PRO glucuronidation CLint,u,UGT was double that of liver. Renal CLint,u,UGT should be accounted for in the IV-IVE of UGT1A9 and considered for UGT1A6 and 2B7 substrates

Isolation and identification of cell-specific microRNAs targeting a messenger RNA using a biotinylated anti-sense oligonucleotide capture affinity technique.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression by translational repression or messenger RNA (mRNA) degradation. Although numerous bioinformatic prediction models exist to identify miRNA-mRNA interactions, experimental validation of bona fide interactions can be difficult and laborious. Few methods can comprehensively identify miRNAs that target a single mRNA. We have developed an experimental approach to search for miRNAs targeting any mRNA using a capture affinity assay involving a biotinylated DNA anti-sense oligonucleotide. This method identifies miRNAs targeting the full length of the mRNA. The method was tested using three separate mRNA targets: alpha-1 antitrypsin (AAT) mRNA, interleukin-8 mRNA and secretory leucoprotease inhibitor mRNA. AAT mRNA-specific and total miRNAs from three different cell lines (monocytic THP-1, bronchial epithelial 16HBE14o- and liver HepG2 cells) were profiled, and validation studies revealed that AAT mRNA-specific miRNAs functionally target the AAT mRNA in a cell-specific manner, providing the first evidence of innate miRNAs selectively targeting and modulating AAT mRNA expression. Interleukin-8 and secretory leucoprotease inhibitor mRNAs and their cognate miRNAs were also successfully captured using this approach. This is a simple and an efficient method to potentially identify miRNAs targeting sequences within the full length of a given mRNA transcript

Gravity Spy: Integrating Advanced LIGO Detector Characterization, Machine Learning, and Citizen Science

(abridged for arXiv) With the first direct detection of gravitational waves, the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) has initiated a new field of astronomy by providing an alternate means of sensing the universe. The extreme sensitivity required to make such detections is achieved through exquisite isolation of all sensitive components of LIGO from non-gravitational-wave disturbances. Nonetheless, LIGO is still susceptible to a variety of instrumental and environmental sources of noise that contaminate the data. Of particular concern are noise features known as glitches, which are transient and non-Gaussian in their nature, and occur at a high enough rate so that accidental coincidence between the two LIGO detectors is non-negligible. In this paper we describe an innovative project that combines crowdsourcing with machine learning to aid in the challenging task of categorizing all of the glitches recorded by the LIGO detectors. Through the Zooniverse platform, we engage and recruit volunteers from the public to categorize images of glitches into pre-identified morphological classes and to discover new classes that appear as the detectors evolve. In addition, machine learning algorithms are used to categorize images after being trained on human-classified examples of the morphological classes. Leveraging the strengths of both classification methods, we create a combined method with the aim of improving the efficiency and accuracy of each individual classifier. The resulting classification and characterization should help LIGO scientists to identify causes of glitches and subsequently eliminate them from the data or the detector entirely, thereby improving the rate and accuracy of gravitational-wave observations. We demonstrate these methods using a small subset of data from LIGO's first observing run.Comment: 27 pages, 8 figures, 1 tabl

Outcomes of Fusions From the Cervical Spine to the Pelvis.

Study designRetrospective cohort study.ObjectiveDetermine the indications, complications, and clinical outcomes in patients requiring fusions from the cervical spine to the pelvis. Several investigators have examined fusions from the thoracic spine to the sacrum, but no similar study has been performed for cervical-to-pelvis fusions.MethodsPatients from 2003 to 2014 with an upper instrumented vertebrae (UIV) in the cervical spine (any level) and a lower instrumented vertebrae (LIV) in the sacrum or pelvis were included in the study. Those with infectious or acute trauma-related deformities were excluded. Patient demographics, medical history, diagnosis, operative procedure, and health-related quality of life measures were analyzed. Student's t test, Kruskal-Wallis test, and χ2 test were used as appropriate; significance was set at P < .05 for all tests.ResultsFifty-five patients met inclusion criteria for the study. Average follow-up was 2.8 years. Proximal junctional kyphosis was the most common indication for cervical-to-pelvis fusions (36%). The most common UIV was C2 (29%) followed by C7 (24%). There was an average 31° correction in maximum kyphosis and a 3.3 cm improvement in sagittal vertical axis. In adults, the rate of complication was 71.4%, with a major complication rate of 39.3% and reoperation rate of 53.6%. There was significant improvement in the Scoliosis Research Society (SRS-22r) score (3.0 to 3.5; P < .01).ConclusionProximal junctional kyphosis is the most common indication for patients requiring fusion to the cervical spine. Adult patients incur a significant risk of major complications and reoperations. However, significant improvement in SRS-22r outcomes are noted in these patients

Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase

Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. Although many of these enzyme families are well-characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis. Structural analysis with X-ray crystallographic diffraction data to 2.0-Å revealed that each protein subunit harbors a hot dog-fold and that the TE6 enzyme forms a hexamer with D3 symmetry. An assessment of thioesterase activity against a range of acyl-CoA substrates revealed the greatest activity against acetyl-CoA, and structure-guided mutagenesis of putative active site residues identified Asn24 and Asp39 as being essential for activity. Our structural analysis revealed that six GDP nucleotides bound the enzyme in close proximity to an intersubunit disulfide bond interactions that covalently link thioesterase domains in a double hot dog dimer. Structure-guided mutagenesis of residues within the GDP-binding pocket identified Arg93 as playing a key role in the nucleotide interaction and revealed that GDP is required for activity. All mutations were confirmed to be specific and not to have resulted from structural perturbations by X-ray crystallography. This is the first report of a bacterial GDP-regulated thioesterase and of covalent linkage of thioesterase domains through a disulfide bond, revealing structural similarities with ADP regulation in the human ACOT12 thioesterase

The Role of Entrepreneur-Venture Fit in Online Home-based Entrepreneurship: A Systematic Literature Review

Home-based businesses and their founders represent an important, but under-researched facet of entrepreneurship. Far from being small, hobby-businesses with little economic impact, home-based business make significant contribution to national economies in terms of both turnover and employment. Online home-based businesses have been recognised as an important and distinct sector of the home-based business domain, offering unique opportunity for innovation and business diversity. The paper presents a systematic literature review of extant research on online home-based entrepreneurs and their businesses. The findings of the review are structured and discussed using the theoretical lens of entrepreneur-venture fit. Use of this lens allows the study to bring coherence to previously fragmented extant studies, providing a basis for future research in this domain. The study also develops a novel model of entrepreneur-venture fit in the specific case of online home-based businesses. This allows us to suggest five positive interactions between entrepreneurial and venture characteristics. It also allows us to suggest a number of previously unidentified negative interactions, which may result in entrepreneurs becoming ‘locked-in’ and suffering multiple sources of stress