Pragmatic Urbanism: South Bend\u27s West Side Main Streets

In this session we will review how in a limited resource environment master planning, road diets, matching facade grants, business assistance programs, a form-based code, and other local initiatives can be coordinated to bring about quick, visible revitalization in a low-income, slow/no growth environment. We will provide an overview of South Bend’s West Side Main Streets Revitalization Plan for Lincolnway West, Western Avenue, and adjoining neighborhoods and discuss a set of immediately implementable projects

A non-covalent peptide-based carrier for in vivo delivery of DNA mimics

The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficient delivery into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. We demonstrate that Pep-3-mediated delivery of antisense-cyclin B1-charged-PNA blocks tumour growth in vivo upon intratumoral and intravenous injection. Moreover, we show that PEGylation of Pep-3 significantly improves complex stability in vivo and consequently the efficiency of antisense cyclin B1 administered intravenously. Given the biological characteristics of these vectors, we believe that peptide-based delivery technologies hold a true promise for therapeutic applications of DNA mimics

A Characterization of Cancer Patients in Inpatient Rehabilitation Facilities: A Retrospective Cohort Study

OBJECTIVES: To identify the types of cancer patients admitted to inpatient medical rehabilitation and to describe their rehabilitation outcomes. DESIGN: Retrospective cohort study. SETTING: U.S. inpatient rehabilitation facilities (IRFs). PARTICIPANTS: Adult patients (N=27,952) with a malignant cancer diagnosis admitted to an IRF with a cancer-related impairment between October 2010 and September 2012 were identified from the Uniform Data System for Medical Rehabilitation database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic, medical, and rehabilitation characteristics for patients with various cancer tumor types were summarized using data collected from the Inpatient Rehabilitation Facility-Patient Assessment Instrument. Rehabilitation outcomes included the percentage of patients discharged to the community and acute care settings, and functional change from admission to discharge. Functional status was measured using the FIM instrument. RESULTS: Cancer patients constituted about 2.4% of the total IRF patient population. Cancer types included brain and nervous system (52.9%), digestive (12.0%), bone and joint (8.7%), blood and lymphatic (7.6%), respiratory (7.1%), and other (11.7%). Overall, 72% were discharged to a community setting, and 16.5% were discharged back to acute care. Patients with blood and lymphatic cancers had the highest frequency of discharge back to acute care (28%). On average, all cancer patient groups made significant functional gains during their IRF stay (mean FIM total change ± SD, 23.5±16.2). CONCLUSIONS: In a database representing approximately 70% of all U.S. patients in IRFs, we found that patients with a variety of cancer types are admitted to inpatient rehabilitation. Most cancer patients admitted to IRFs were discharged to a community setting and, on average, improved their function. Future research is warranted to understand the referral patterns of admission to postacute care rehabilitation and to identify factors that are associated with rehabilitation benefit in order to inform the establishment of appropriate care protocols

Efficacy of Manual Hemostasis for Percutaneous Axillary Artery Intra-Aortic Balloon Pump Removal

Background. The prevalence of peripheral vascular disease has led to the re-emergence of percutaneous axillary vascular access as a suitable alternative access site to femoral artery. We sought to investigate the efficacy and safety of manual hemostasis in the axillary artery. Methods. Data were collected from a prospective internal registry of patients who had a Maquet® (Rastatt, Germany) Mega 50 cc intra-aortic balloon pumps (IABP) placed in the axillary artery position. They were anticoagulated with weight-based intravenous heparin to maintain an activated partial thromboplastin time (aPTT) of 50-80 seconds. Anticoagulation was discontinued 2 hours prior to the device explantation. Manual compression was used to achieve the hemostasis of the axillary artery. Vascular and bleeding complications attributable to manual hemostasis were classified based on the Valve Academic Research Consortium-2 (VARC-2) and Bleeding Academic Research Consortium-2 (BARC-2) classifications, respectively. Results. 29 of 46 patients (63%) achieved axillary artery homeostasis via manual compression. The median duration of IABP implantation was 12 days (range 1-54 days). Median compression time was 20 minutes (range 5-60 minutes). There were no major vascular or bleeding complications as defined by the VARC-2 and BARC-2 criteria, respectively. Conclusion. Manual compression of the axillary artery appears to be an effective and safe method for achieving hemostasis. Large prospective randomized control trials may be needed to corroborate these findings

Fast-transient Searches in Real Time with ZTFReST: Identification of Three Optically Discovered Gamma-Ray Burst Afterglows and New Constraints on the Kilonova Rate

The most common way to discover extragalactic fast transients, which fade within a few nights in the optical, is via follow-up of gamma-ray burst and gravitational-wave triggers. However, wide-field surveys have the potential to identify rapidly fading transients independently of such external triggers. The volumetric survey speed of the Zwicky Transient Facility (ZTF) makes it sensitive to objects as faint and fast fading as kilonovae, the optical counterparts to binary neutron star mergers, out to almost 200 Mpc. We introduce an open-source software infrastructure, the ZTF REaltime Search and Triggering, ZTFReST, designed to identify kilonovae and fast transients in ZTF data. Using the ZTF alert stream combined with forced point-spread-function photometry, we have implemented automated candidate ranking based on their photometric evolution and fitting to kilonova models. Automated triggering, with a human in the loop for monitoring, of follow-up systems has also been implemented. In 13 months of science validation, we found several extragalactic fast transients independently of any external trigger, including two supernovae with post-shock cooling emission, two known afterglows with an associated gamma-ray burst (ZTF20abbiixp, ZTF20abwysqy), two known afterglows without any known gamma-ray counterpart (ZTF20aajnksq, ZTF21aaeyldq), and three new fast-declining sources (ZTF20abtxwfx, ZTF20acozryr, ZTF21aagwbjr) that are likely associated with GRB200817A, GRB201103B, and GRB210204A. However, we have not found any objects that appear to be kilonovae. We constrain the rate of GW170817-like kilonovae to R < 900 Gpc-3 yr-1 (95% confidence). A framework such as ZTFReST could become a prime tool for kilonova and fast-transient discovery with the Vera Rubin Observatory

CH−π “T-Shape” Interaction with Histidine Explains Binding of Aromatic Galactosides to Pseudomonas aeruginosa Lectin LecA

The galactose specific lectin LecA mediates biofilm formation in the opportunistic pathogen P. aeruginosa . The interaction between LecA and aromatic β-galactoside biofilm inhibitors involves an intermolecular CH-π T-shape interaction between C(ε1)-H of residue His50 in LecA and the aromatic ring of the galactoside aglycone. The generality of this interaction was tested in a diverse family of β-galactosides. LecA binding to aromatic β-galactosides (KD ∼ 8 μM) was consistently stronger than to aliphatic β-galactosides (KD ∼ 36 μM). The CH-π interaction was observed in the X-ray crystal structures of six different LecA complexes, with shorter than the van der Waals distances indicating productive binding. Related XH/cation/π-π interactions involving other residues were identified in complexes of aromatic glycosides with a variety of carbohydrate binding proteins such as concanavalin A. Exploiting such interactions might be generally useful in drug design against these targets