Wavelength-Orthogonal Stiffening of Hydrogel Networks with Visible Light

Herein, we introduce the wavelength-orthogonal crosslinking of hydrogel networks using two red-shifted chromophores, i.e. acrylpyerene (AP, λ$_{activation}$=410–490 nm) and styrylpyrido[2,3-b]pyrazine (SPP, λ$_{activation}$=400–550 nm), able to undergo [2+2] photocycloaddition in the visible-light regime. The photoreactivity of the SPP moiety is pH-dependent, whereby an acidic environment inhibits the cycloaddition. By employing a spiropyran-based photoacid generator with suitable absorption wavelength, we are able to restrict the activation wavelength of the SPP moiety to the green light region (λ$_{activation}$=520–550 nm), enabling wavelength-orthogonal activation of the AP group. Our wavelength-orthogonal photochemical system was successfully applied in the design of hydrogels whose stiffness can be tuned independently by either green or blue light

Ugi multicomponent reaction to prepare peptide–peptoid hybrid structures with diverse chemical functionalities

Monodisperse sequenced peptides and peptoids present unique nano-structures based on their self-assembled secondary and tertiary structures. However, the generation of peptide and peptoid hybrid oligomers in a sequence-defined manner via Ugi multicomponent reaction has not yet been studied. Herein, we report a synthetic strategy that enables both the modification of peptides as well as the generation of sequence-defined peptide–peptoid hybrid structures. Our synthetic methodology rests on the fusion of solid phase peptide synthesis with Ugi multicomponent reactions. We evidence that a diversity of chemical functionalities can be inserted into peptides or used in the design of peptide–peptoid hybrids exploiting a wide functional array including amines, carboxylic acids, hydrocarbons, carbohydrates as well as polymers, introducing a sequence-defined synthetic platform technology for precision peptoid hybrids

Zero Frequency Current Noise for the Double Tunnel Junction Coulomb Blockade

We compute the zero frequency current noise numerically and in several limits analytically for the coulomb blockade problem consisting of two tunnel junctions connected in series. At low temperatures over a wide range of voltages, capacitances, and resistances it is shown that the noise measures the variance in the number of electrons in the region between the two tunnel junctions. The average current, on the other hand, only measures the mean number of electrons. Thus, the noise provides additional information about transport in these devices which is not available from measuring the current alone.Comment: 33 pages, 10 figure

Patient-Reported Barriers to Adherence Among ACEI/ARB Users from a Motivational Interviewing Telephonic Intervention

Purpose: Hypertension is a common comorbidity among type 2 diabetes mellitus (T2DM) patients, which increases the risk of cardiovascular diseases. Despite the proven benefit of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in this population, poor medication adherence is prevalent, resulting in higher complications and mortality rate. Motivational interviewing (MoI) has demonstrated effectiveness in improving medication adherence and identifying barriers. This study aimed to assess and identify patient-reported barriers to adherence to ACEI/ARB from an MoI telephonic intervention conducted by student pharmacist interns. Patients and Methods: This retrospective study was conducted within an MoI intervention customized by past ACEI/ARB adherence trajectories for nonadherent patients with T2DM and hypertension enrolled in a Medicare Advantage Plan. Adherence barriers were extracted from the interviewers’ notes by two independent researchers. Descriptive analysis was performed to summarize the overall frequency of barriers as well as across trajectory groups, identified from the initial and follow-up calls. Results: In total, 247 patients received the initial MoI call from which 41% did not communicate any barrier for ACEI/ARB use despite having low adherence. About 59% of the patients reported at least one barrier during the initial call. The most common barriers included forgetfulness, discontinuation by physicians, side effects, multiple comorbidities, polypharmacy, lack of knowledge about disease/medication, and cost issues. The follow-up calls helped with uncovering at least one new barrier for 28 patients who previously communicated a different issue with their medication during the first call. Additionally, 18 patients with initial denial for having any barrier to adherence reported at least one barrier throughout the follow-up calls. Conclusion: This study summarized patient-reported barriers to ACEI/ARB adherence from an MoI telephonic intervention performed among nonadherent patients. Identifying specific barriers for patients may help to further design tailored interventions that address the barriers and improve adherence

Pathways of Resistance to Thymineless Death in Escherichia coli and the Function of UvrD

Thymineless death (TLD) is the rapid loss of viability in bacterial, yeast, and human cells starved of thymine. TLD is the mode of action of common anticancer drugs and some antibiotics. TLD in Escherichia coli is accompanied by blocked replication and chromosomal DNA loss and recent work identified activities of recombination protein RecA and the SOS DNA-damage response as causes of TLD. Here, we examine the basis of hypersensitivity to thymine deprivation (hyper-TLD) in mutants that lack the UvrD helicase, which opposes RecA action and participates in some DNA repair mechanisms, RecBCD exonuclease, which degrades double-stranded linear DNA and works with RecA in double-strand-break repair and SOS induction, and RuvABC Holliday-junction resolvase. We report that hyper-TLD in ∆uvrD cells is partly RecA dependent and cannot be attributed to accumulation of intermediates in mismatch repair or nucleotide-excision repair. These data imply that both its known role in opposing RecA and an additional as-yet-unknown function of UvrD promote TLD resistance. The hyper-TLD of ∆ruvABC cells requires RecA but not RecQ or RecJ. The hyper-TLD of recB cells requires neither RecA nor RecQ, implying that neither recombination nor SOS induction causes hyper-TLD in recB cells, and RecQ is not the sole source of double-strand ends (DSEs) during TLD, as previously proposed; models are suggested. These results define pathways by which cells resist TLD and suggest strategies for combating TLD resistance during chemotherapies

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin