On a singular variety associated to a polynomial mapping

In the paper "Geometry of polynomial mapping at infinity via intersection homology" the second and third authors associated to a given polynomial mapping F : \C^2 \to \C^2 with nonvanishing jacobian a variety whose homology or intersection homology describes the geometry of singularities at infinity of the mapping. We generalize this result.Comment: 1 figur

The Effect of N-Terminal Cyclization on the Function of the HIV Entry Inhibitor 5P12-RANTES.

Despite effective treatment for those living with Human Immunodeficiency Virus (HIV), there are still two million new infections each year. Protein-based HIV entry inhibitors, being highly effective and specific, could be used to protect people from initial infection. One of the most promising of these for clinical use is 5P12-RANTES, a variant of the chemokine RANTES/CCL5. The N-terminal amino acid of 5P12-RANTES is glutamine (Gln; called Q0), a residue that is prone to spontaneous cyclization when at the N-terminus of a protein. It is not known how this cyclization affects the potency of the inhibitor or whether cyclization is necessary for the function of the protein, although the N-terminal region of RANTES has been shown to be critical for receptor interactions, with even small changes having a large effect. We have studied the kinetics of cyclization of 5P12-RANTES as well as N-terminal variations of the protein that either produce an identical cyclized terminus (Glu0) or that cannot similarly cyclize (Asn0, Phe0, Ile0, and Leu0). We find that the half life for N-terminal cyclization of Gln is roughly 20 h at pH 7.3 at 37 °C. However, our results show that cyclization is not necessary for the potency of this protein and that several replacement terminal amino acids produce nearly-equally potent HIV inhibitors while remaining CC chemokine receptor 5 (CCR5) antagonists. This work has ramifications for the production of active 5P12-RANTES for use in the clinic, while also opening the possibility of developing other inhibitors by varying the N-terminus of the protein

Machine Learning for Integrating Data in Biology and Medicine: Principles, Practice, and Opportunities

New technologies have enabled the investigation of biology and human health at an unprecedented scale and in multiple dimensions. These dimensions include a myriad of properties describing genome, epigenome, transcriptome, microbiome, phenotype, and lifestyle. No single data type, however, can capture the complexity of all the factors relevant to understanding a phenomenon such as a disease. Integrative methods that combine data from multiple technologies have thus emerged as critical statistical and computational approaches. The key challenge in developing such approaches is the identification of effective models to provide a comprehensive and relevant systems view. An ideal method can answer a biological or medical question, identifying important features and predicting outcomes, by harnessing heterogeneous data across several dimensions of biological variation. In this Review, we describe the principles of data integration and discuss current methods and available implementations. We provide examples of successful data integration in biology and medicine. Finally, we discuss current challenges in biomedical integrative methods and our perspective on the future development of the field

Adipocytes, aldosterone and obesity-related hypertension

Understanding the mechanisms linking obesity with hypertension is important in the current obesity epidemic as it may improve therapeutic interventions. Plasma aldosterone levels are positively correlated with body mass index and weight loss in obese patients is reported to be accompanied by decreased aldosterone levels. This suggests a relationship between adipose tissue and the production/secretion of aldosterone. Aldosterone is synthesized principally by the adrenal glands, but its production may be regulated by many factors, including factors secreted by adipocytes. In addition, studies have reported local synthesis of aldosterone in extra-adrenal tissues, including adipose tissue. Experimental studies have highlighted a role for adipocyte-secreted aldosterone in the pathogenesis of obesity-related cardiovascular complications via the mineralocorticoid receptor. This review focuses on how aldosterone secretion may be influenced by adipose tissue and the importance of these mechanisms in the context of obesity-related hypertension

Organizational Behavior Meets Marketing: Increasing Productivity with Art in the Workplace

Edward Lisi and Ngoc Nguyen's poster on the productivity effects of art in the workplace

Illicit drug use and cerebral microbleeds in stroke and transient ischemic attack patients

Background: Cerebral microbleeds (CMB) signal cerebral small vessel disease and are associated with ischemic stroke (IS) incidence, recurrence, and complications. While illicit drug use (IDU) is associated with cerebral small vessel disease, the association between CMB and IDU is understudied. We sought to delineate differences in vascular risk factors between IDU and CMB and determine the effect of this relationship on outcomes in IS/transient ischemic attack (TIA) patients. Methods: We included 2001 consecutive IS and TIA patients (years 2009-2018) with a readable T2*gradient-echo MRI sequence. CMB rating followed standardized guidelines and CMB were grouped topographically into lobar, deep or infratentorial. IDU data (history and/or urine toxicology) was available for 1746 patients. The adverse composite outcome included pneumonia, urinary tract infection, deep venous thrombosis or death during hospitalization. Good functional outcome was defined as modified Rankin scale score < 3 and ambulatory on discharge. Univariate analysis was used to assess vascular risk factors and multivariable logistic regression was used to characterize the IDU/CMB relationship on outcomes. Results: We observed IDU in 13.8 % (n=241), and CMB in 32.9% (n=575, 53.8% lobar, 27.3% deep and 18.8% infratentorial). Patients with IDU and at least one CMB were older (53.6±10.5 vs. 56.9±11.5, p=0.04), had a lower BMI (28.1±5.9 vs. 26.6±4.4, p=0.04), and were more likely to have had a previous IS/TIA (25.1% vs. 41.9%, p=0.01). IDU trended higher for those with severe CMB (10+) compared with those without CMB and 1-9 CMB (25% [n=9] vs 14.3% [n=1171] and 12.1% [n=65] respectively; p=0.07) without individual drug deviations from this pattern. Adverse and good functional outcomes were observed in 177 and 905 total patients, respectively. No significant interaction was observed between IDU and CMB with either adverse or functional composite outcomes. Conclusion: IDU prevalence was high in our urban study population, and showed a borderline association with increasing CMB burden. Patients with CMB and IDU history were older and more likely to have had a previous IS/TIA. Further studies are required to clarify the clinical consequences related to the relationship between IDU and CMB.Author Disclosures: B. Petrie: None. H. Lau: None. F. Cajiga-Pena: None. S. Abbas: None. B. Finn: None. K. Dam: None. A. Cervantes-Arslanian: None. T.N. Nguyen: None. H. Aparicio: None. D. Greer: None. J.R. Romero: Speakers' Bureau; Modest; Received speaker honoraria from Ferrer Group