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Impact of Stereochemical Replacement on Activity and Selectivity of Membrane-Active Antibacterial and Antifungal Cyclic Peptides
Get PDFHerein, we report a library of 7-mer macrocyclic peptides designed by systematically replacing one, multiple, or all L-amino acids with their D-isomers in our previously identified hit compounds. Lead peptides, 15c and 16c, showed broad-spectrum activity against bacteria (Gram-positive minimum inhibitory activity (MIC 1.5–6.2 µg/mL and Gram-negative MIC 6.2–25 µg/mL) and fungi (MIC = 3.1–25 µg/mL). Additionally, peptides 15c and 16c showed rapid kill kinetics and biofilm degradation potential against both bacteria and fungi, while resistance development was not observed. The antimicrobial effect of these macrocyclic peptides was attributed to their membranolytic action, which was confirmed by calcein dye leakage assay and scanning electron microscopy analysis. Both peptides, 15c (HC50 = 335 µg/mL) and 16c (HC50 = 310 µg/mL), exhibited significantly lower hemolytic activity compared to their parent peptide p3 (HC50 = 230 µg/mL). At 100 µg/mL, both peptides showed \u3e90% cell viability after 24 h incubation across four normal mammalian cell lines. Both peptides showed plasma stability (t1/2 ≥ 6 h), further supporting their therapeutic potential. Finally, the molecular mechanisms determining the pharmacological properties of a number of typical representatives of each series of synthesized peptides were investigated by NMR spectroscopy and computer simulations. The study revealed specific combinations of structural, dynamic, and hydrophobic parameters of these amphiphilic peptides that allow a reasonable prediction of their hemolytic activity. This Structure-Activity Relationship provides a basis for the rational design of peptides or peptidomimetics with predefined pharmacological profiles
Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf
Get PDFAfter the era of multidrug resistance (MDR) against cytotoxic chemotherapy, the development of resistance against newly developed molecularly targeted drugs also seems inevitable. While the mechanisms involved in resistance against these two categories of anticancer drugs are different, the principles are similar: inherent resistance (also known as primary resistance) is a result of heterogeneity in cancer cells where a subpopulation of the cells do not show a favorable initial response to the drug, while acquired resistance (or secondary resistance), as the name suggests, is developed after repeated treatments due to the plasticity of cancer cells. Despite the introduction of a variety of molecularly targeted drugs to clinical practice, chemotherapy is still at the forefront of the battle against cancer. In this manuscript, we review the major mechanisms involved in MDR and resistance against different categories of molecularly targeted drugs separately, and review some of the strategies studied to overcome the resistance against cancer therapy. While MDR mechanisms have been reviewed previously, the molecular mechanisms of resistance to the latest generations of anticancer drugs are rarely reviewed as a group, and the connection between the two categories of resistance is often missing in this type of publication. Our aim is to illustrate a comprehensive picture of what the landscape of cancer treatment is today with respect to resistance. While this picture seems bleak, and it is the common belief that resistance is inevitable, understanding the mechanisms involved could potentially lead to more efficient approaches to overcoming this so far unbeatable obstacle
From the Battlefield to the Archive: Tracing Testimony in Holocaust Memory
Get PDFThis thesis portfolio examines the evolving role of testimony in shaping public memory of World War II and the Holocaust. As the last generation of eyewitnesses passes, societies increasingly rely on preserved, mediated forms of testimony to understand and remember traumatic pasts. Testimony, whether handwritten, oral, visual, or digital, is not a neutral historical record but an interpretive act shaped by cultural, political, and technological forces. This portfolio argues that testimony functions as evidence and expression: it transmits trauma across generations while simultaneously reflecting the changing frameworks through which war and genocide are remembered.
The portfolio explores testimony in personal, national, and digital contexts through three essays. The first essay, Memory and Testimony of War Trauma, analyzes the wartime letters of Dr. Allen M. Boyden, a U.S. Army surgeon who served during the final year of World War II. His correspondence reveals the psychological strain of witnessing atrocity, particularly his firsthand account of the Mauthausen concentration camp\u27s liberation. These letters expose the difficulty of articulating trauma in real time and challenge institutional silence around combat stress and emotional fatigue.
The second essay, Memory and Testimony in National Reckoning, explores how Holocaust memory developed in postwar Germany. Initially marked by silence, German memory culture evolved into a complex narrative of accountability and education. The essay traces this transformation through historical shifts, scholarly debates, and a case study of the Bergen-Belsen Memorial, showing how testimony, especially across generations, has shaped national identity and public commemoration.
The third essay, Memory and Testimony in the Digital Age, focuses on how emerging technologies are reshaping Holocaust memory. Through analysis of the USC Shoah Foundation\u27s initiatives, including the Visual History Archive, Dimensions in Testimony, and The Last Goodbye, the essay interrogates how digital platforms preserve survivor voices while raising new questions about authenticity, emotional engagement, and ethical representation.
Together, the three essays argue that testimony is not merely a record of the past but a dynamic tool for remembrance. In an age of historical distance and digital innovation, testimony remains vital for confronting trauma, shaping collective memory, and ensuring that the past continues to resonate
Resisters: How Ordinary Jews Fought Persecution in Hitler’s Germany
No full textA review of Resisters: How Ordinary Jews Fought Persecution in Hitler’s Germany, by Wolf Gruner
Death, Violence, and Condemnation: The News Media Coverage of the 1981 Prisoners’ Hunger Strike in Northern Ireland in the United Kingdom and Ireland
Get PDFThe Role of Peripheral Vision in Enhancing Balance and Postual Stability: Insights from Central Vision Obstruction
No full textThis study examines the role of peripheral vision in maintaining postural stability, particularly when central vision is obstructed, using Sensory Organization Testing (SOT) with computer dynamic posturography. Ten participants (5 males, 5 females, aged 21–34 years) were tested under three conditions: full vision, full occlusion, and central vision obstruction allowing only peripheral vision access. Results revealed significantly better balance performance in the peripheral vision condition during somatosensory perturbations (Condition 4), with equilibrium scores higher than in the full vision condition (p = 0.02). Similarly, visual preference (VIS) scores, indicating reliance on visual input, were significantly elevated under peripheral vision conditions (p = 0.03). These findings highlight peripheral vision’s critical role in improving postural sway and maintaining balance when central vision is impaired, as seen in conditions such as age-related macular degeneration (AMD). While central vision is vital for daily tasks requiring focused attention, peripheral vision provides crucial environmental cues for balance and stability. This research underscores the need for targeted interventions and balance training programs to mitigate fall risks in individuals with central vision loss. Future studies will explore these effects in populations with visual impairments to enhance clinical relevance and applicability of central vision on balance
The Critical Plastocapillary Number for a Newtonian Liquid Filament Embedded into a Viscoplastic Fluid
Get PDFThe yield stress of a viscoplastic material can stabilize an embedded fluid tunnel against capillarity-induced breakup, enabling remarkable technologies such as embedded 3D printing of intricate, freeform, and small components. However, there is persistent disagreement in the published literature between the observed minimum stable diameter, min, and the theoretical plastocapillary length = 2∕, with interfacial tension and bath yield stress , leading to a prior hypothesis that the apparent surface tension is much smaller to enforce min = . Here we introduce and experimentally test a new hypothesis that the critical diameter is set by the dimensionless plastocapaillary number, = ∕2, having a non-trivial critical value different than one, ≠ 1, and therefore the prior hypothesis of adjusting to enforce = min is incorrect. We study several Newtonian inks (uncured polydimethylsiloxane (PDMS), highly refined mineral oil, silicone oil) extruded into a wide range of non-Newtonian viscoplastic bath materials (polyacrylic acid microgels, polysaccharide microgels, nanoclay gel, and micro-organogels). Across this wide parameter space, we observe a critical value of = 0.21±0.03. We explain this being less than one by analogy to other critical dimensionless groups with yield stress fluids, such as the gravitational stability of a suspended sphere or bubble, where the yield stress acts upon an effective area larger than the naïve estimate set only by embedded object diameter . These results provide a new way to understand and predict the minimum stable diameter of embedded liquid filaments, as in embedded 3D printing, as min = (2∕)
Left or Right, Loyal or Disloyal: Ideology, Partisanship, and Empire in the Construction of Interwar Japanese American Politics
Get PDFThis article examines the first cohort of Japanese American voters in California in the interwar years, in order to explore the construction of racialized parameters on Japanese American political agency. Inter-imperial competition between the United States and Japan over the future of the Pacific, along with the popular and legal linkage of race and citizenship, produced a persistent distrust of Japanese American voters. Although Japanese Americans shaped their political strategies to appease these suspicions, militarized state demands for loyalty after the attack on Pearl Harbor sharply contracted their options from a range of diverse ideologies and partisanship to a narrow political spectrum based on loyalty. The specific racialization of Asians as “perpetual foreigners” in the context of military conflict produced unique political constraints for Japanese Americans
Integrating Belowground Recovery into Tropical Forest Restoration Design and Monitoring
No full textThere is growing recognition that tropical forest restoration is key for sequestering carbon and enhancing ecosystem resilience. Soils, roots, and soil biota are central to ecosystem function and services, but belowground recovery is largely overlooked in restoration monitoring frameworks. Here, we outline current understanding of the links between above- and belowground recovery in tropical forests by examining how belowground properties before and after intervention influence recovery; by evaluating whether aboveground recovery can serve as a proxy for belowground dynamics; and by proposing a blueprint for monitoring dynamic soil physical (bulk density, aggregate stability), chemical (organic matter or carbon, pH), and biological properties (decomposition rate, macrofauna abundance) in resource-constrained projects. Although we highlight some aboveground proxies for assessing belowground recovery, a better understanding of relationships between above- and belowground indicators across diverse restoration interventions remains essential. Overall, we provide an actionable path toward integrating belowground recovery into restoration design and assessment