cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulatory roles of high-density and low-density lipoproteins in cellular proliferation and secretion of progesterone and insulin-like growth factor I by enriched cultures of bovine small and large luteal cells

We tested the hypotheses that bovine high-density (HDL) and low-density (LDL) lipoproteins differentially influence cellular proliferation and progesterone and IGF-I production by bovine small and large luteal cells. Unit gravity sedimentation was used to produce enriched cultures of small (> 95% pure) and large (75 to 90% pure) luteal cells from corpora lutea (CL) on d 4 and 10 of the estrous cycle. Addition of LDL, HDL, or both resulted in the maintenance of higher (P < .05) numbers of 3beta-hydroxysteroid dehydrogenase (HSD)-positive small and large cells in culture and produced a marked proliferation of 3beta-HSD-negative small luteal cells compared to control medium. Low-density lipoprotein and HDL each stimulated greater (P < .01) progesterone secretion in enriched large cell cultures on both days of the cycle, and by small luteal cells on d 10, compared to the control. Together, LDL and HDL maximized this response. Lipoproteins markedly stimulated (P < .01) the secretion of IGF-I by bovine large luteal cells, and secretion was greater (P < .05) by cells from d 10 CL compared to d 4 CL. Results suggest that the actions of lipoproteins in bovine luteal cells extend beyond their widely recognized roles in steroidogenesis and include remarkable effects on cellular proliferation and IGF-I secretion. Type of lipoprotein (LDL vs HDL) did not have differential effects on any of the variables measured.
Effects of clofibrate on plasma lipids and high-density lipoprotein levels in renal allograft recipients.

Thirteen successfully transplanted renal patients with normal and elevated plasma lipids were treated as out-patients for two-month intervals with placebo and clofibrate (2 g/day) and whole plasma and lipoprotein triglyceride and cholesterol concentrations were measured. With clofibrate treatment, plasma triglyceride (194 +/- 11 to 157 +/- 10 mg/100 ml; P less than .01) and cholesterol (242 +/- 8 to 212 +/- 8 mg/100 ml; P less than .002) concentrations both decreased significantly despite the continued administration of stable immunosuppressive doses of prednisolone. While the absolute changes in cholesterol in the low and high-density lipoprotein classes varied considerably following clofibrate administration, the ratio of cholesterol in the low and high-density lipoproteins fell from 3.8 to 3.3. This theoretically beneficial anti-atherogenic effect was significant (P less than .01) in male allograft recipients only. These findings indicate that clofibrate treatment favorably influences the cardiovascular risk posed by both qualitative and quantitative disturbances in lipoprotein transport following successful renal allografting.
Exfoliative Cytology and GI Cancer

In combination with x-ray and other procedures, this relatively simple technique raises diagnostic accuracy in gastric cancer to near perfection, and its false-positive rate is close to zero. These advantages argue for a much wider use of exfoliative cytology of the G I tract than is currently being made. Paramedical personnel can readily be trained to perform the procedure and interpret the results.
Distribution and Pharmacokinetics

Publisher Summary For a pesticide to elicit toxicity, it must be transferred from the external site of exposure to the target site and achieve a sufficiently high concentration in the target organ to understand how nontarget species' exposure to a pesticide may result in toxicity, one must first understand how the pesticide enters, moves about in, and is eliminated from the body. Pharmacokinetics, the study of the absorption, distribution, metabolism, and elimination of chemicals, utilizes mathematical models to describe the time course of the chemical in the body. This chapter provides a general discussion of distribution and pharmacokinetics. Pharmacokinetic models typically describe the change in blood (or plasma) concentration of the chemical with time. There are two basic approaches to characterizing the pharmacokinetics of a chemical in the body: compartmental and noncompartmental. Compartmental pharmacokinetic models represent the body as discrete compartments with mathematical descriptions of the movement of chemical between compartments, including the processes of absorption and elimination. Noncompartmental models use statistical moment theory for analysis of plasma concentration–time data. Noncompartmental, compartmental, and physiological models are considered, including the quantitative methodology for utilizing these models.
Synthesis, evaluation, and CoMFA study of fluoroquinophenoxazine derivatives as bacterial topoisomerase IA inhibitors.

New antibacterial agents with novel target and mechanism of action are urgently needed to combat problematic bacterial infections and mounting antibiotic resistances. Topoisomerase IA represents an attractive and underexplored antibacterial target, as such, there is a growing interest in developing selective and potent topoisomerase I inhibitors for antibacterial therapy. Based on our initial biological screening, fluoroquinophenoxazine 1 was discovered as a low micromolar inhibitor against E. coli topoisomerase IA. In the literature, fluoroquinophenoxazine analogs have been investigated as antibacterial and anticancer agents, however, their topoisomerase I inhibition was relatively underexplored and there is little structure-activity relationship (SAR) available. The good topoisomerase I inhibitory activity of 1 and the lack of SAR prompted us to design and synthesize a series of fluoroquinophenoxazine analogs to systematically evaluate the SAR and to probe the structural elements of the fluoroquinophenoxazine core toward topoisomerase I enzyme target recognition. In this study, a series of fluoroquinophenoxazine analogs was designed, synthesized, and evaluated as topoisomerase I inhibitors and antibacterial agents. Target-based assays revealed that the fluoroquinophenoxazine derivatives with 9-NH2 and/or 6-substituted amine functionalities generally exhibited good to excellent inhibitory activities against topoisomerase I with IC50s ranging from 0.24 to 3.9 μM. Notably, 11a bearing the 6-methylpiperazinyl and 9-amino motifs was identified as one of the most potent topoisomerase I inhibitors (IC50 = 0.48 μM), and showed broad spectrum antibacterial activity (MICs = 0.78-7.6 μM) against all the bacteria strains tested. Compound 11g with the 6-bipiperidinyl lipophilic side chain exhibited the most potent antituberculosis activity (MIC = 2.5 μM, SI = 9.8). In addition, CoMFA analysis was performed to investigate the 3D-QSAR of this class of fluoroquinophenoxazine derivatives. The constructed CoMFA model produced reasonable statistics (q2 = 0.688 and r2 = 0.806). The predictive power of the developed model was obtained using a test set of 7 compounds, giving a predictive correlation coefficient r2pred of 0.767. Collectively, these promising data demonstrated that fluoroquinophenoxazine derivatives have the potential to be developed as a new chemotype of potent topoisomerase IA inhibitors with antibacterial therapeutic potential.
Notes on Child Labor and Education: A Personal Statement

It is a matter of concern that in today’s prosperous world, there are 168 million children who work as laborers, deprived of not just the joys of childhood but also of the education that is essential for decent life as an adult. As the world advances in terms of information technology and in other ways, literacy becomes more important than ever before. Child labor and the deprivation of education persisted for so long partly because of the naive belief that markets, left free, would correct these ills. In reality, we need well-crafted interventions. But, this essay argues, the argument is more complex than appears at first sight. A blunt, legalistic intervention, as often proposed, can curtail child labor but only by exacerbating child poverty. The problem has to be tackled through a cocktail of interventions that involve government, civil society and the private sector. Unless this urgent problem of our times is attended to, we are likely to see rising inequality, deprivation and conflict.
Leaching and retention of dissolved metals in particulate loaded pervious concrete columns.

This study examined metal leaching and retention in pervious concrete with or without embedded particulate matter. Particulate matter was collected from an adjacent parking lot and from a nearby parking garage as examples of weathered and un-weathered particulate matter. Particle size distributions were similar, but metal content was 3-35-fold higher and organic matter content was 3-fold higher in the parking garage particulate matter compared to the parking lot particulate matter. Replicate columns were established with either no particulate added as the control, or 20 g of parking lot or parking garage particulate matter. Synthetic rainwater was passed through the columns at variable rainfall intensity or fixed intensity to assess leaching. Metals were leached at higher concentrations from the parking garage particulate amended column, but from all columns less than 1% of the metal mass leached. Rainfall intensity did not have a large effect on leached metal concentrations, only varying effluent by about 2-fold. Synthetic stormwater with elevated dissolved Cu, Zn, Cd and Pb concentrations was passed through the same columns and metal removal efficiencies were on the order of 85-95%, 30-95%, 60-90%, and 95+% for each metal, respectively. After loading the column with a year's worth of stormwater metal exposure, removal efficiencies in the no particulate and parking lot particulate amended columns decreased, while parking garage particulate amended columns performed similarly with a small drop in Cu and Pb removal efficiencies. Generally, columns with no particulate and parking lot particulate amendments performed similarly, suggesting the pervious concrete is responsible for the majority of the initial metal retention. The parking garage particulate amended columns retained more metals from stormwater, perhaps due to an increase in pH that promoted surface precipitation as hydroxides or carbonate species on the pervious concrete, or due to complexation in the higher concentrations of organic matter and iron oxides in the particulate matter. Overall, metal retention was aided by the presence of organic matter in the particulate matter, but the pervious concrete itself was more important than particulates for metal retention. A strategy to increase metal retention and removal from the environment could involve amending pervious concrete with mixtures of well-defined sorbents to enhance metal retention.
Brief cognitive behavioral intervention for children and adolescents with persistent post-concussive symptoms: A pilot study.

ABSTRACTThis study aims to evaluate the efficacy of a brief cognitive behavioral intervention program for children and adolescents experiencing persistent post-concussion symptoms. A total of 31 patients aged 10 to 18 years participated in the intervention. The median time since injury at treatment onset was 95 days though the range was large (23–720 days). Treatment was on average four sessions in duration. Sessions included concussion education, activity scheduling, sleep hygiene relaxation training, and cognitive restructuring. Outcomes were measured using symptom reports on the Sports Concussion Assessment Tool – Third Edition (SCAT-3) and parent-reported quality of life on the Pediatric Quality of Life Inventory (PedsQL). Mixed-effects models revealed that symptom reports did not decrease prior to the initiation of this treatment, though significant symptom improvement occurred following treatment. Quality of life scores significantly improved across domains, with the largest gains made in the emotio...
Femoropopliteal artery chronic total occlusion intervention

Femoropopliteal (FP) artery endovascular intervention procedures are one of the most common lower extremity peripheral artery interventions (PAI) worldwide. Chronic total occlusions are highly prevalent in this vascular bed and comprise nearly 40–50% of lesions treated [1]. Intervention on FP CTO lesions is technically more challenging, is an independent predictor of procedure failure, and is associated with higher complication rates compared with non-FP CTO procedures [2]. Therefore, a systematic and step-by-step approach to such lesions, along with familiarity with various PAI tools and their attributes, is crucial to successful PAI interventional practice. In this chapter we will review a step-by-step approach to FP CTO. Given the high likelihood of tackling such lesions in clinical practice, the ability to treat FP CTO is nearly obligatory for an endovascular specialist treating patients with peripheral artery disease (PAD).
Associations Between β-Peripapillary Atrophy and Reticular Pseudodrusen in Early Age-Related Macular Degeneration

Purpose Choroidal thinning has been associated with reticular pseudodrusen (RPD) and β-peripapillary atrophy (β-PPA), which have been linked to normal-tension glaucoma (NTG). This analysis sought to determine whether RPD are independently associated with β-PPA in early AMD patients. Secondary outcomes included the association of RPD and preexisting diagnosis of glaucoma, cup-to-disc ratio (CDR), subfoveal choroidal thickness (SFCT), and IOP. Methods This prospective cross-sectional study examined 78 age- and sex-matched early AMD patients: 43 RPD patients (63 eyes) and 35 non-RPD patients (64 eyes). Exclusion criteria included advanced AMD, high myopia, and vitreoretinal conditions/surgery. RPD and non-RPD groups were identified by confocal scanning laser ophthalmoscopy. β-PPA as well as CDR were graded on digital, nonstereoscopic fundus photos. SFCT was measured on spectral-domain optical coherence tomography for 69 patients (35 RPD and 34 non-RPD). IOP and glaucoma diagnosis were extracted from charts. Results β-PPA had a greater prevalence in RPD than non-RPD (44% vs. 19%, P = 0.002); however, this relationship was not significant when SFCT was added to the model (P = 0.150). A preexisting diagnosis of glaucoma (P = 0.156), CDR (P = 0.176), and IOP (P = 0.98) was not different between groups. Conclusions RPD in early AMD are associated with presence of β-PPA, but choroidal thickness is a confounder in this relationship. Because β-PPA is a common finding in NTG, focusing on a potential shared pathway between RPD and NTG could improve the understanding of pathophysiology and expand therapies for each condition.
Examining Collaboration in Teacher Preparation and Clinical Practice

ABSTRACTCollaboration among educators is a vital component for teachers’ success working with diverse students. Teacher preparation programs, however, have not sufficiently included experiences in which teacher candidates can learn about professional collaboration in preparation for clinical and professional experiences. In this article, the authors describe the experiences from two pairs of teacher candidates—one pair who completed a cotaught teacher preparation course focused on collaboration, and the other pair who did not. The authors used interviews, observations, and content analysis of candidate artifacts to examine these experiences within the framework of symbolic interactionism. Findings suggest differences between these pairs of teacher candidates related to how they understood and managed collaborative situations. Implications for teacher preparation and clinical practice are included.
The late Quaternary bird community of New Providence, Bahamas

ABSTRACT Avian fossils give us a unique opportunity to assess changes through time in species diversity and distributions. We report a previously unstudied collection of ∼500 bird fossils from Banana Hole, New Providence Island, Commonwealth of The Bahamas. Based on comparisons with fossil sites of known age on Abaco, the species composition of the Banana Hole fossils suggests a late Pleistocene rather than Holocene age for the site, although this remains uncertain because of the inability to date the fossils radiometrically. The specimens represent 49 species (45 resident, 4 migratory), 25 of which had not been recorded before as fossils from Banana Hole. Among the 45 resident species, 4 are extinct and 17 others are extirpated from New Providence. Combining our data with those previously compiled from Banana Hole, 52 resident species of birds now are known from this site, among which 6 (12%) are extinct (a hawk [Buteo quadratus], eagle [Titanohierax gloveralleni], caracara [Caracara creightoni], barn-ow...
Properties of Materials

The selection of materials for plasma-interactive components in a magnetic confinement fusion device is a complex process that usually involves numerous trade-offs. In general, the selection criteria are heavily weighted according to specific design objectives or constraints, and it is difficult to make broad statements regarding the properties of “good” versus “bad” materials. Accordingly, no attempt is made in this chapter to describe a set of properties for an optimum material, but rather, the purpose here is to review some important fundamental properties that can be used to guide the selection or development of materials for a specific first-surface application.
Diagnosing and Managing the Adnexal Mass

Age is an important consideration in the management of a patient with an adnexal mass. For the following discussion, I have divided patients into three age groups: birth to 20 years, 20 to 40 years, and over 40 years. Occurrence during pregnancy is considered separately, later in the chapter.
The medical-legal aspects of compartment syndrome.

Background: Management of compartment syndrome in the modern era involves not only avoiding the sequelae of a missed diagnosis but also minimizing the risk of a malpractice claim. Little information is available on the legal aspects of compartment syndrome. Methods: Twenty-three years of records on closed malpractice claims involving compartment syndrome were reviewed. The data were abstracted from medical records and were analyzed to determine the factors associated with a successful defense. Results: Nineteen closed claims, involving sixteen patients and encompassing a total liability of $3.8 million, were found in the data for malpractice claims closed between 1980 and 2003. Ten claims were resolved in favor of the physician. The average time to closure was 5.5 years. All three claims that went to trial resulted in a verdict for the physician. Evidence of poor physician-patient communication was found in six cases, all of which resulted in an indemnity payment (p < 0.01). Increasing time from the onset of symptoms to the fasciotomy was linearly associated with an increased indemnity payment (p < 0.05). A fasciotomy performed within eight hours after the first presentation of symptoms was uniformly associated with a successful defense. Conclusions: While malpractice claims involving compartment syndrome were uncommon, they resulted in a high rate and amount of indemnity payments. Early fasciotomy not only improves patient outcome but is also associated with decreased indemnity risk.
Psychosocial Issues Confronting Young Women with Breast Cancer

The current paper reviews the literature regarding psychosocial issues confronting young women with breast cancer. The findings indicate that younger women with breast cancer experience a lower quality of life after cancer compared to older women. In part, this lower quality of life results from the effects of medical treatment. The effects of surgery and removal of the breast result in more negative feelings regarding body image, particularly for young women. With systemic treatment, many younger women experience the sudden onset of menopause, with the attendant symptoms of hot flashes, decreased sexual desire, and vaginal dryness. These physical effects along with a variety of relationship issues contribute to a high level of sexual concerns for young women. From a psychosocial perspective, breast cancer affects both females and their male partners. Both partners experience psychological distress including depression and anxiety. Within the relationship, emotional support from the partner is important in women's adjustment. In terms of psychosocial interventions for breast cancer, findings suggest that the most frequently employed interventions, which treat the woman without her partner, are not optimal. Initial findings provide encouraging evidence that couple-based psychosocial interventions for women and their partners might be of particular assistance to both partners.
Location of the intermolecular crosslinking sites in collagen.

Collagen is stabilized by intermolecular crosslinks which occur following the enzymatic conversion of the e-amino groups of selected lysyl and hydroxylysyl residues to the aldehydes, allysine and hydroxyallysine. These aldehydes combine specifically with other allysine or hydroxyallysine residues and/or the side chains of lysine, hydroxylysine or histidine to produce characteristic crosslinks composed of two, three, or four amino acid components. These crosslinks may be converted to more complex compounds by reaction with other amino acids. The newly discovered crosslink, hydroxyaldol-histidine, appears to arise by condensation of one residue each of allysine, hydroxyallysine, and histidine. It was found in a peptide from a tryptic digest of insoluble calf skin collagen which contains three constituent chains, one arising from a region of αl-CB5 and one from αl-CB6. Data obtained in this laboratory, from peptides which were originally isolated from an extensive proteolytic digest of reconstituted calf skin collagen are consistent with a crosslink between the hydroxylysine at residue 927 in αl-CB6 and the allysine at residue 9N in αl-CB(0,1). This is supported by other investigators who have isolated an analogous crosslinked peptide from CNBr digests. The amino acid sequence of a peptide derived from limited alkaline hydrolysis of insoluble calf bone collagen indicates the presence of the crosslink S,o’-dihydroxylysinonorleucine at residue 671 in αl-CB7. It is apparent, on both theoretical and experimental bases, that many more cross-linked peptides occur; detailed studies should elucidatethe three-dimensional structure of the collagen fibril.
Prevalence of documented alcohol and opioid use disorder diagnoses and treatments in a regional primary care practice-based research network.

Abstract Background Most people with alcohol or opioid use disorders (AUD or OUD) are not diagnosed or treated for these conditions in primary care. This study takes a critical step toward quantifying service gaps and directing improvement efforts for AUD and OUD by using electronic health record (EHR) data from diverse primary care organizations to quantify the extent to which AUD and OUD are underdiagnosed and undertreated in primary care practices. Methods We extracted and integrated diagnosis, medication, and behavioral health visit data from the EHRs of 21 primary care clinics within four independent healthcare organizations representing community health centers and rural hospital-associated clinics in the Pacific Northwest United States. Rates of documented AUD and OUD diagnoses, pharmacological treatments, and behavioral health visits were evaluated over a two-year period (2015–2016). Results Out of 47,502 adult primary care patients, 1476 (3.1%) had documented AUD; of these, 115 (7.8%) had orders for AUD medications and 271 (18.4%) had at least one documented visit with a non-physician behavioral health specialist. Only 402 (0.8%) patients had documented OUD, and of these, 107 (26.6%) received OUD medications and 119 (29.6%) had at least one documented visit with a non-physician behavioral health specialist. Rates of AUD diagnosis and AUD and OUD medications were higher in clinics that had co-located non-physician behavioral health specialists. Conclusions AUD and OUD are underdiagnosed and undertreated within a sample of independent primary care organizations serving mostly rural patients. Primary care organizations likely need service models, technologies, and workforces, including non-physician behavioral health specialists, to improve capacities to diagnose and treat AUD and OUD.
Developmental change in partition dependent resource allocation behavior.

Partition dependence, the tendency to distribute choices differently based on the way options are grouped, has important implications for decision making. This phenomenon, observed in adults across a variety of contexts such as allocating resources or making selections from a menu of items, can bias decision makers toward some choices and away from others. Only one study to date (Reichelson, Zax, Patalano, & Barth, Quarterly Journal of Experimental Psychology, 72, 1029–1036, 2019) has investigated the developmental trajectory of this phenomenon. In the current study we investigate children’s and adults’ susceptibility to partitioning effects in a child-friendly resource allocation task. In Experiment 1 (N = 80), adults distributed 12 food tokens to animals at the zoo. Based on previous findings that older children show weaker partition dependence in this task, we predicted that adults might exhibit reduced partition dependent behavior: they showed none. In Experiment 2 (N = 272), we used a less transparent task with only five food tokens, predicting that both adults and children (ages 3–10 years) would show partition dependence. Children, but not adults, made partition dependent resource allocations, with younger children exhibiting greater effects than older children. These experiments provide further evidence that children’s decisions, like adults’ (in other tasks), are influenced by the arbitrary partitioning of the available options. This work supports previous findings that younger children may be more susceptible to these effects, and maps developmental change in partition dependent behavior from early childhood to adulthood on this child-friendly partition dependence task.
COVID-19 fatalities, latitude, sunlight, and vitamin D.

Abstract Background Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. Methods Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the “worldometer” web site, a correlation analysis was done between death rates and a country's latitude. Results A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r = .40 p Discussion This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. Conclusion Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.
Nearly Free Sustainable Electric and Thermal Power for Desalination

The plummeting reserves and increasing demand of freshwater resources are responsible for a global water crisis. The process of desalination offers a solution to meet the growing water demands. However, the process of desalination is energy-intensive and has a large carbon footprint. Photovoltaic based DC power when coupled with desalination can achieve tremendous energy savings and cost reduction with negligible carbon emissions.
Euglycemic Diabetic Ketoacidosis Precipitated by SGLT-2 Inhibitor Use, Pericarditis, and Fasting: A Case Report.

Author(s): Mendelsohn, Rebecca A.; Taveras, Anabelle N.; Mazer, Benjamin A.; Clayton, Lisa M. | Abstract: Introduction: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Less prevalent is euglycemic DKA (eDKA)—DKA with serum glucose less than 200 mg/dL; however, it is increasing in frequency with the introduction of sodium glucose cotransporter 2 (SGLT-2) inhibitors for treatment of type 2 diabetes.Case Report: We report a case of SGLT-2 inhibitor-associated eDKA presenting with concurrent acute pericarditis.Discussion: Our case suggests that the cause of eDKA can be multifactorial when decreased oral intake occurs in the setting of an acute cause of physiologic stress.Conclusion: Prompt recognition of eDKA in the emergency department may allow earlier diagnosis and treatment directed at one or more of its underlying causes.
Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: a meta-analysis of individual data from three independent samples of US postmenopausal women.

Recent animal and small clinical studies have suggested depression is related to altered lipid and amino acid profiles. However, this has not been examined in a population-based sample, particularly in women. We identified multiple metabolites associated with depression as potential candidates from prior studies. Cross-sectional data from three independent samples of postmenopausal women were analyzed, including women from the Women’s Health Initiative-Observational Study (WHI-OS, n = 926), the WHI-Hormone Trials (WHI-HT; n = 1,325), and the Nurses’ Health Study II Mind-Body Study (NHSII-MBS; n = 218). Positive depression status was defined as having any of the following: elevated depressive symptoms, antidepressant use, or depression history. Plasma metabolites were measured using liquid chromatography-tandem mass spectrometry (21 phosphatidylcholines (PCs), 7 lysophosphatidylethanolamines, 5 ceramides, 3 branched chain amino acids, and 9 neurotransmitters). Associations between depression status and metabolites were evaluated using multivariable linear regression; results were pooled by random-effects meta-analysis with multiple testing adjustment using the false discovery rate (FDR). Prevalence rates of positive depression status were 24.4% (WHI-OS), 25.7% (WHI-HT), and 44.7% (NHSII-MBS). After multivariable adjustment, positive depression status was associated with higher levels of glutamate and PC 36 : 1/38 : 3, and lower levels of tryptophan and GABA-to-glutamate and GABA-to-glutamine ratio (FDR-p < 0.05). Positive associations with LPE 18 : 0/18 : 1 and inverse associations with valine and serotonin were also observed, although these associations did not survive FDR adjustment. Associations of positive depression status with several candidate metabolites including PC 36 : 1/38 : 3 and amino acids involved in neurotransmission suggest potential depression-related metabolic alterations in postmenopausal women, with possible implications for later chronic disease.
Complement Regulates the Procoagulant Effects of HIT Immune Complexes

Heparin induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by ultra-large immune complexes (ULICs) containing IgG antibodies bound to multivalent complexes of platelet factor 4 (PF4) and heparin (H). HIT ULICs activate cellular FcγIIA receptors that initiate diverse cellular effector functions including neutrophil degranulation and monocyte expression of tissue factor (TF). Previous studies have shown that HIT ULICs also potently activate complement through the classical pathway (Cines et al., 1980). Whether complement activation contributes to FcγRIIA-dependent prothrombotic pathways has not been addressed in detail. In studies that follow, we describe: 1) robust complement activation by HIT ULICs in plasma and whole blood (WB), 2) cell-surface deposition of complement and IgG triggered by HIT ULICs, 3) complement-dependent neutrophil degranulation and monocyte TF expression, 4) efficacy of proximal, but not terminal, pathway inhibition in regulating monocyte TF expression, and 5) deposition of complement in thrombi formed in “HIT mice” that generate ULICs containing KKO, a HIT-like monoclonal antibody (Arepally et al., 2000). Consistent with prior studies showing involvement of the classical pathway in HIT (Cines et al., 1980), we observed that binding of C1q induced marked enlargement of HIT ULICs in buffer assessed by dynamic light scattering as well as in plasma using confocal microscopy (data not shown). To assess complement activation by HIT ULICs, we incubated WB and plasma with PF4 (25 µg/mL) ± heparin (1 U/mL) in the presence of KKO (or isotype, “ISO”; 50 µg/mL) or HIT IgG (or control IgG, “CON”; 500 µg/mL) and measured C3c with a capture immunoassay as previously described (Khandelwal et al., 2018). KKO (Figure 1A) or HIT ULICs (n=3; HIT1-3, Figure 1B), showed robust generation of C3c in the presence of PF4/heparin, but not antigens alone or with control IgG (ISO/CON). Complement activation by HIT ULICs leads to downstream generation of C5a and formation of sC5b-9 (data not shown). Pre-incubation of plasma or WB with a variety of classical pathway inhibitors, including a C1r inhibitor derived from Borrelia burgdorferi (BBK 32), C1 esterase inhibitor (Berinert, CSL Behring) and anti-C1q antibody (α-C1q Ab; Annexon Biosciences) inhibited C3c generation by KKO ULICs (p Download : Download high-res image (432KB) Download : Download full-size image Disclosures Arepally: Novartis: Consultancy; Alexion: Other; Annexon Biosciences: Consultancy, Other; Veralox Therapeutics: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Biokit: Consultancy, Patents & Royalties; Apotex: Consultancy, Research Funding.
Image-based data on strain fields of microstructures with porosity defects.

The present article provides a compilation of microstructures and respective strain fields expressed by them during elastic loading. These microstructures were synthesized in Abaqus Standard software and their strain fields were modelled using Abaqus based static implicit analysis. The Python Development Environment (PDE) in Abaqus was used. These microstructures were subjected to uniform displacement boundary condition to obtain strain fields in the plane-strain mode. The purpose of the generating this data was to test the efficacy of convolutional neural networks (CNNs) in predicting strain fields. This raw data consisting of microstructure and their strain fields was converted to images using MATLAB as two dimensional arrays with each pixel denoting value to be used as input for training the CNN. This processed data in the form of images can be potentially used in deep learning or data science methodologies to perform finite element simulations.
THE POROUS BOUNDARY: COMPARING LATE POSTCLASSIC–EARLY COLONIAL MAYA PROJECTILE TECHNOLOGIES ACROSS PETEN AND BELIZE

This study examines the intersection of political, cultural, and linguistic differences in the archaeological study of boundaries. The Late Postclassic and Early Colonial periods (a.d. 1350–1525) in the Maya lowlands are known for political instability and the formulation of new identities, especially in the northern region of the Peten Lakes District (Guatemala) to the greater Rio Hondo drainage (Belize). This article approaches the theoretical formulations of archaeological borders from the perspective of lithic technology, focusing on small projectile points recovered from numerous sites in the subregion. Analysis of data suggests differences in resource acquisition, material preference, and production during a time of historically fluid interaction and occasional conflict in the Peten-Belize area. Such information adds to our understandings of political frontiers of Late Postclassic polities from a social and economic perspective that is often ignored.
Selecting the Optimal CAR-T for the Treatment of B-Cell Malignancies

Chimeric antigen receptor T-cell (CAR-T) therapy is a form of adoptive cellular therapy that has revolutionized the treatment landscape in hematologic malignancies, especially B-cell lymphomas. In this review, we will discuss some of the landmark data behind these therapies and then lay out our approach to utilizing this new therapy. CD19-directed CAR-Ts are the most common type currently used in treatment of relapsed B-cell lymphoid neoplasms. There are currently three FDA-approved products: axicabtagene ciluecel and tisagenlecleucel for the treatment of relapsed/refractory large B-cell lymphoma and pediatric B-cell acute lymphocytic leukemia (tisagenlecleucel only) and brexucabtagene autoleucel for the treatment of relapsed/refractory mantle cell lymphoma. These therapies are associated with distinctive acute toxicities such as cytokine release syndrome and neurotoxicity and chronic toxicities such as cytopenias and hypogammaglobulinemia. CAR-T therapy provides significant potential in the treatment of relapsed B-cell lymphomas despite current limitations. Several novel CAR cell designs are currently being studied in clinical trials which include tandem CAR-Ts, allogeneic CAR-Ts, and CAR-NK cells.
Indigenous-Driven Sustainability Initiatives in Mountainous Regions: The Shuar in the Tropical Andes of Ecuador

Land use change in tropical places with variable topography followed an elevation-sensitive pattern during the last 3 decades of the 20th century. Deforestation, driven by farmers, was concentrated in accessible, lowland settings, while sustainability initiatives, promoted by natural scientists, occurred in remote, upland settings. This lowland deforestation–upland sustainability pattern persists, but the drivers of sustainability initiatives have recently changed with the emergence of organizations of rain-forest–dwelling indigenous peoples that promote upland sustainability. This article describes and, by means of a case study, explains this shift in sustainability dynamics. Indigenous groups have gained more control over the lands they inhabit, and their populations have increased. With these changes, indigenous peoples' organizations have assumed pivotal roles in upland sustainability initiatives. The history of indigenous control over sustainability efforts where the Andes meet the Amazon in southeastern Ecuador, an area inhabited by the Shuar, illustrates this pattern of change.
Temperature and strain-rate dependence of the elevated temperature ductility of Inconel 718 prepared by selective laser melting

Abstract The elevated temperature tensile properties of SLM IN718 were measured as a function of strain rate and test temperature to better understand the time-dependent and thermal aspects of environmental sensitivity. SLM and wrought materials were solution treated, aged, and tested over the range of 550–750 °C and 10−3 to 10−6 s−1. The SLM material tested across all conditions had inferior strength and ductility compared to wrought material of the same heat treatment because of environmental sensitivity in the form of dynamic embrittlement. SLM samples show evidence of brittle intergranular fracture, crack growth, and oxidized NbC particles on the fracture surface, which all contribute to the observed poor ductility. These features, and subsequent embrittlement, are intensified with decreasing strain rate and increasing temperature. Higher strain rates and lower temperatures are shown to improve the ductility in SLM IN718 but despite this recovery it remains susceptible to environmental attack even in the extreme cases of the current study. The prevalence of NbC at grain boundaries in the SLM material is the principal source of dynamic embrittlement and environmental sensitivity.
Identification of Ligands to Manganese and Calcium in Photosystem II by Site-Directed Mutagenesis

The Mn and Ca ions in Photosystem II are believed to be located at the interface between the intrinsic and extrinsic polypeptides of the PSII core. The recent identification of YZ [1,2] and YD [3,4] as Tyr-161 and Tyr-160 of the D1 and D2 polypeptides, respectively, suggests that many of the ligands to Mn and Ca are likely to be contributed by the D1 and D2 polypeptides. From considerations of Mn coordination chemistry[5,6], and from recent EPR [7] and electron spin echo [8] measurements with 15N, the Mn ions are believed to be coordinated primarily by carboxyl residues. Carboxyl residues are also likely ligands for Ca. There are 27 carboxyl residues in the lumenally-exposed regions of the mature forms of the D1 and D2 polypeptides. Several models for Mn and Ca ligation have been advanced incorporating a number of these residues [9,10]. However, there appears to be no compelling reason for selecting any particular residue over any other; unlike the previous situation with YZ and YD, there is no apparent C2 symmetry between the D1 and D2 polypeptides in this region.
Female with Fabry Disease Unknowingly Donates Affected Kidney to Sister: A Call for Pre-transplant Genetic Testing.

Fabry disease, an X-linked lysosomal storage disorder, is caused by the deficiency of the alpha-galactosidase A enzyme and the progressive accumulation of globotriaosylceramide in vascular endothelial cells. The multi-systemic manifestations of Fabry disease include cardiac, gastrointestinal, renal, and neuropathic complications. Renal dysfunction and ultimately end-stage renal disease occurs in classically affected males and in about 10–15% of female heterozygotes from classically affected families as a result of progressive glycosphingolipid accumulation. We report a case in which a female with a de novo GLA mutation donated a kidney to her sister prior to the diagnosis of symptomatic Fabry disease. The transplant recipient has progressed to graft failure and has been relisted for transplant. This case report demonstrates the need to screen potential kidney transplant donors and recipients for Fabry disease.
Hostile Environmental Jolts, Transaction Set and New Business Development

In this exploratory study, we examine empirically the effects of environmental jolts on the evolution of the set of relationships that entrepreneurs have with their customers and suppliers (which we call the transaction set). We believe that understanding how turbulence in the environment affects the ability of entrepreneurs to hold on to their existing relationships or to add new relationships is fundamental to understanding the evolution and growth of an organization from a start-up to a stable, wealth-creating enterprise in the long-run.Using longitudinal data spanning 7 to 10 years from five start-up firms, we investigate three questions on the connection between environmental jolts and changes in the transaction set of the firm. First, do environmental jolts during the early life of the firm induce significant reductions in the set of relationships of a new, small firm? Second, are entrepreneurs able to add new relationships in greater numbers than the exit of old relationships following a jolt? And, third, do start-ups enjoy a “honeymoon” period when environmental jolts do not induce significant reductions in the set of relationships after a jolt?Our study yielded several findings that may be of interest to entrepreneurs, academics, and incubator managers. First, environmental jolts have a significant impact on the exits of relationships from the transaction set of a new, small firm, but not necessarily on the entry of new relationships into the set. Thus, although liabilities of newness and small size seem to affect the ability of entrepreneurs to hold on to their existing relationships during environmental jolts, these jolts do not seem to affect the entrepreneur's ability to add ties, at least in the very early life of the firm. Second, the level of reduction after environmental jolts seems to be less severe during the early life and greatest during the adolescent period. Further, entries of new relationships decrease with each succeeding jolt.
Cyclic polysilanes : VIII. The crystal structure of 1,2,3,4-tetra-tert-butyl-tetramethylcyclotetrasilane

Abstract The crystal structure of [Si(CH3)(t-C4H9)]4 has been determined by single crystal X-ray diffraction. The crystals are tetragonal, P42/n; a = b = 13.069(4), c = 7.880(2) A, Z = 2. The structure was determined using 745 independent data and refined with anisotropic least-squares to a final unweighted R-value of 3.5%. Each tetrameric molecule was found to be arranged about a 4 axis, with the independent crystallographic unit comprising one silicon atom, one methyl and one tert-butyl group. The four-membered ring of silicon atoms is nonplanar with an unusually large dihedral angle of 36.8°. The principal mean bond lengths are SiSi 2.377(1), SiC(methyl) 1.893(4), SiC(tert-butyl) 1.918(3) A, and the SiSiSi bond angle is 86.99°. The SiSi bond length is somewhat longer than in other polysilanes.
Patterns in Student Assignment to Elementary School Classrooms

In an effort to better understand aggregate patterns in the way elementary school students are assigned to classes, we conduct a careful analysis of observed classroom assignment outcomes in the 5 th grade in North Carolina elementary schools. First, we model the probability that a pair of students are classmates as a function of the characteristics of that pair of students. This novel methodological technique enables us to directly observe the degree to which actual assignment patterns differ from what might be expected under random assignment for a wide variety of student characteristics. Second, we analyze patterns in classroom assignment and discuss the implications of these patterns. We show that classroom assignments tend to deviate from random assignment in a way that tends to group similar students and that these deviations tend to be greatly magnified in Magnet schools. Importantly, we find evidence that administrators sort students based on attributes not normally observable by researchers. These findings have important implications for researchers using value-added modeling (VAM) techniques. Finally, we find that classroom assignment patterns are generally stable across the racial, income, and geographic characteristics of schools.
Nuclear and Cytoplasmic Glycosylation

abstract O-GlcNAcylation is a form of cytoplasmic and nuclear glycosylation that is found on many diverse proteins of the cell including RNA polymerase II and its associated transcription factors, cytoskeletal proteins, nucleoporins, viral proteins, heat shock proteins, tumor suppressors, and oncogenes. It involves the attachment of a single, unmodified N -acetylglucosaminyl residue O-glycosidically linked to the hydroxyl groups of serine and threonine moieties of proteins. It is a highly abundant and dynamic form of posttranslational modification that appears to modulate function in a manner similar to phosphorylation. All O -GlcNAc-containing proteins are phosphoproteins that are involved in the formation of multimeric complexes, suggesting that O -GlcNAc may play a role in mediating protein-protein interactions. O -GlcNAc sites resemble phosphorylation sites and in many cases the two modifications are mutually exclusive; therefore, O-GlcNAcylation may act as an antagonist of phosphorylation and help to mediate many essential functions of the cell.