Earlier Work Research Articles

2D Materials Kill Bacteria from Within.

Early work demonstrated that some two-dimensional (2D) materials could kill bacteria by using their sharp edges to physically rupture the bacteria envelope, which presents distinct advantages over traditional antibiotics, as bacteria are not able to evolve resistance to the former. This mechano-bactericidal mode of action, however, suffers from low antibacterial efficiency, fundamentally because of random orientation of 2D materials outside the bacteria, where the desirable "edge-to-envelope" contacts occur with low probability. Here, we demonstrate a proof-of-concept approach to significantly enhance the potency of the mechano-bactericidal activity of 2D materials. This approach is in marked contrast with previous work, as the 2D materials are designed to be in situ generated inside the bacteria from a molecularly engineered monomer in a self-assembled manner, profoundly promoting the probability of the "edge-to-envelope" contacts. The rationale in this study sheds light on a mechanically new nanostructure-enabled antibacterial strategy to combat antibiotic resistance.

The Historical Development of the Concepts Underlying the Design and Construction of Targeted Coordination Polymers/MOFs: A Personal Account.

Presented here is a personal account of how the ideas and concepts underlying the design and construction of coordination polymers/MOFs developed historically - from the earliest conjectures in the 1970's about the possibility of using pre-organized building blocks to construct targeted polymeric structures, to the initial experimental implementation of these ideas in the mid-80's and to the introduction of the name MOFs in the 90's. The early exploratory work with pre-organized building blocks described in this article paved the way for the subsequent explosion of research activity in the CP/MOF area and for the generation of an essentially unlimited range of designed coordination polymer structures promising a variety of useful properties.

The Energy Budget in the Jet of High-frequency Peaked BL Lacertae Objects

Energy equipartition and the energy budget in the jet are important issues for the radiation mechanism of blazars. Early work predominantly concentrated on flat-spectrum radio quasars and a limited number of BL Lacertae (BL Lac) objects. In this paper, we compile 348 high-frequency peaked BL Lac objects (HBLs) based on the catalog of active galactic nuclei (4LAC-DR3) from Fermi-LAT, and employ JetSet to fit the spectral energy distributions (SEDs) of these HBLs in the framework of the one-zone lepton model. We aim to determine whether the energy budget is reasonable and whether energy equipartition is satisfied in HBLs. The results of the statistical analysis suggest that: (1) SEDs of HBLs can be reproduced well by using the one-zone lepton model; however, it cannot achieve energy equalization, and the relativistic electron energy density is far greater than the magnetic field energy density, U e ≳ 100U B ; (2) the majority of HBLs are located in the t cool < t dyn region (where the horizontal coordinate represents the jet power of electrons, while the ordinate indicates the ratio of the dynamic timescale to the cooling timescale), and the jet kinetic power of HBLs is greater than the jet power of radiation; there is a very low radiation efficiency, we deduce that HBLs may have optically thin advection-dominated accretion flows; (3) logϵB of HBLs is less than zero, which indicates that the jet kinetic power of HBLs is not affected by Poynting flux; (4) the relationships U e > U Syn ∼ U B , L e ∼ L p > L B ∼ L rad, and logϵe>0.5 are established. These relations indicate that most of the energy of HBLs is stored in the population of low-energy electrons.

On the circuit model of two quantum adiabatic search algorithms

The early work of Wei et al. has shown that it is possible to do the computation in constant time for quantum search in quantum local adiabatic evolution framework if the system Hamiltonian has an extra enlarged factor proportional to the square-root of the size of the problem. Also in our prior work, we have shown that it is possible to apply a linear interpolating path in the system Hamiltonian to achieve an O(1) time complexity for a quantum global adiabatic computation. In this paper, we discuss the issues when implementing these two quantum algorithms on the quantum circuit model, and find that to our surprise, the time slices produced does not equal to the time complexity of the algorithm in each case. This is in contrast to the previous related results, because there these two quantities always coincide. When taking into account of the whole energy-level increase of the system compared with that of the usual quantum adiabatic evolutions and the corresponding time complexity simultaneously, we find that the time slices needed always consist of the two quantities multiplying together. This result is new, and may be hopeful to find application in designing quantum adiabatic algorithm for problems beyond quantum search.

Endoplasmic reticulum: Monitoring and maintaining protein and membrane homeostasis in the endoplasmic reticulum by the unfolded protein response

The endoplasmic reticulum (ER) regulates essential cellular processes, including protein folding, lipid synthesis, and calcium homeostasis. The ER homeostasis is maintained by a conserved set of signaling cascades called the Unfolded Protein Response (UPR). How the UPR senses perturbations in ER homeostasis has been the subject of active research for decades. In metazoans, the UPR consists of three ER-membrane embedded sensors: IRE1, PERK and ATF6. These sensors detect the accumulation of misfolded proteins in the ER lumen and adjust protein folding capacity according to cellular needs. Early work revealed that the ER-resident chaperone BiP binds to all three UPR sensors in higher eukaryotes and BiP binding was suggested to regulate their activity. More recent data have shown that in higher eukaryotes the interaction of the UPR sensors with a complex network of chaperones and misfolded proteins modulates their activation and deactivation dynamics. Furthermore, emerging evidence suggests that the UPR monitors ER membrane integrity beyond protein folding defects. However, the mechanistic and structural basis of UPR activation by proteotoxic and lipid bilayer stress in higher eukaryotes remains only partially understood. Here, we review the current understanding of novel protein interaction networks and the contribution of the lipid membrane environment to UPR activation.

Jellyfish detection algorithm based on multi-gradient flow feature fusion

Jellyfish detection is a challenge in the field of underwater biological identification. Although early works have solved some of the problems of jellyfish detection, there are still shortcomings. Earlier jellyfish datasets were not as extensive, necessitating heavy reliance on data augmentation. Moreover, the detection capability is limited, especially in scenarios involving jellyfish gatherings and occlusions. To overcome these limitations, we establish a high-quality dataset with more jellyfish species and propose a more robust real-time detection algorithm. Our algorithm primarily consists of a multi-gradient flow backbone and a feature fusion module GFPN. Additionally, we have designed a receptive field expansion module SPPFCSPC_G. The entire network employs the FReLU activation function, while the bounding box regression utilizes the WIOU loss function. Our methods demonstrate accuracy and run-time performance in comparison with the state-of-the-art yolo series algorithms. Results show that our algorithm achieves the highest Precision, Recall and mAP50, exceeding the baseline yolov5 by 1.1%, 4.1%, and 4.5%, and outperforming the latest yolov8 by 0.9%, 1.3%, and 2.5%. Importantly, our method effectively addresses aggregation, occlusion, and deformation issues commonly encountered in jellyfish detection.

The state of the question in early Heidegger studies

AbstractThis article surveys the state of the literature in English‐language scholarship on Heidegger's early work (1919–29). The survey falls into roughly two halves. The first is devoted to scholarship on Heidegger's intellectual development during the 1920s, focusing on four themes: Heidegger's relationship to Husserl; Heidegger's early phenomenology of religious life; Heidegger's appropriation of Aristotle; and Heidegger's retrieval of Kant's First Critique. The second half focuses on work on the early Heidegger that has arisen out of the reception of his early thought into mainstream Anglophone philosophy. It examines Hubert Dreyfus's interpretation of Heidegger, the status of “das Man” and social normativity, Heidegger's concept of death, Heidegger's conception of authenticity, and truth (with a very brief overview of further topics).

The perceived object in media-based empathy: applying Edith Stein’s concept of Wortleib

AbstractThe question of how other consciousnesses appear via media has forced us to re-think the classical phenomenological accounts of sociality. However, as the phenomenological account of empathy is very much centred around the perception of the other’s living body, it has faced challenges in discussing the empathic experience in media-based contexts, where we cannot perceive the other’s body, but something else, such as a screen or a text. In this article, I provide the concept for describing the perceived object in media-based empathy: a living textual body, based on Edith Stein’s concept of Wortleib (a living word body) referring to words as “living,” as bearers of meaning in her early work On the Problem of Empathy [Zum Problem der Einfühlung]. I divide the term Wortleib in two different cases—the empathic and non-empathic object—and thereby argue that, while the object of media-based empathic experience cannot be the other’s body, it is an empathic Wortleib, a communicative empathic object. While Stein herself discussed media-based empathy merely in paper media, I demonstrate the unique usefulness of these concepts in analysing any media-based communication and thus the timeliness of her work in this respect.

Średniowieczne cykle przedstawieniowe życia, męczeństwa i cudów św. Stanisława, Biskupa

The author has presented the state of research on the works existing in Poland as well as the ones connected with the country. Then he has compiled and discussed the same theme scenes. That compilation of cycles presenting the life and martyrdom of St. Stanislaus the Bishop and the miracles after his death shows typological similarities and differences in depicting the events recorded before and after the canonization of the Saint. Those examples do not represent any faithful imitation of some earlier work; one can only trace some similarities and concepts based on iconographie models already existing in depicting Christ and the saints.

Chinese Female Writer Zhang Yueran and Fictional Features of Her Prose

In this paper, the author analyzes the fiction of contemporary Chinese female writer Zhang Yueran (b. 1982). As a radiant and influential representative of the post-1980s generation in contemporary Chinese literature, Zhang Yueran is considered to be one of most talented and strong young writers. Post-1980s Chinese writers are known by depiction of young people’s lives in big cities with elements of magical realism, however, unlike the most Post-1980s Chinese writers, Zhang Yueran focuses more on the characters’ subjectivity and their pursuit of love (parental and romantic). Her complex characters thrive for love and happiness, but also suffer from loneliness and lack of parental attention. Zhang Yueran’s writing is visceral and almost poetic in its use of metaphor. The development of Zhang Yueran’s prose can be divided two key periods. Her early works are aesthetic psychological thrillers about unhealthy love, inspired by classical fairytales that end with a character’s death and self-destruction: while the language is beautiful and almost poetic, but there is a lack of narrative depth. In her second era, Zhang Yueran returns to realism and successfully combines style and deep narrative by contrasting scenes of cruelty and mercy. At the moment her latest novel “Cocoon” embodies all significant fictional features from the perspective of both style and narrative.

A randomized controlled trial of a brief motivational interviewing-based group intervention for emerging adults experiencing homelessness: 24-month effects on alcohol use.

Despite rates of alcohol misuse being higher among emerging adults experiencing homelessness compared to those who are stably housed, there are few brief evidence-based risk reduction programs for this population that focus on alcohol use and assess outcomes for more than 1 year. This study examines alcohol outcomes from a 24-month evaluation of AWARE, a brief motivational interviewing-based group risk reduction intervention for emerging adults experiencing homelessness. In a cluster randomized crossover trial, 18- to 25- year-olds received AWARE (n = 132) or standard care (n = 144) at one of three drop-in centers serving young people experiencing homelessness in Los Angeles County. We evaluated intervention effects on past month alcohol use, consequences, and related cognitions such as motivation to change behavior. AWARE participants showed significant reductions over 24 months in alcohol use and negative consequences from drinking and reported significant increases in their use of drinking protective strategies. Except for drinking frequency, control group participants did not show a significant change in these outcomes. Findings build on earlier work by demonstrating that AWARE is effective in reducing alcohol use and related problems among emerging adults experiencing homelessness over a 2-year period. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Perspective: Atomistic simulations of water and aqueous systems with machine learning potentials.

As the most important solvent, water has been at the center of interest since the advent of computer simulations. While early molecular dynamics and Monte Carlo simulations had to make use of simple model potentials to describe the atomic interactions, accurate abinitio molecular dynamics simulations relying on the first-principles calculation of the energies and forces have opened the way to predictive simulations of aqueous systems. Still, these simulations are very demanding, which prevents the study of complex systems and their properties. Modern machine learning potentials (MLPs) have now reached a mature state, allowing us to overcome these limitations by combining the high accuracy of electronic structure calculations with the efficiency of empirical force fields. In this Perspective, we give a concise overview about the progress made in the simulation of water and aqueous systems employing MLPs, starting from early work on free molecules and clusters via bulk liquid water to electrolyte solutions and solid-liquid interfaces.

An early Prussian Study on the Composition of Milk from 1871

Connections between the 2 scientific fields of physiology and dairy science did exist for a very long time since the 19th century. One possible explanation for this circumstance could have been the necessity for financial support, which might have played a significant role for many theoretical physiologists to conduct studies on dairy products. This study discusses a correspondence written by the physiologist R. Gscheidlen to J. A. Winter, the main editor of the German (previously Saxon) journal 'Schmidt's Yearbooks on the Entire Field of Domestic and Foreign Medicine' ("Schmids Jahrbücher der in - und ausländischen gesammten Medicin"). Gscheidlen submitted a review manuscript on the composition of milk to Winter's journal. In that work, which was published later as the first issue's very first article of the first volume (of in total 4 quarterly volumes) in 1871, Gscheidlen mainly refers to Eduard Kemmerich's studies who later became a pioneer of cattle breeding in Argentine. Therefore, studies on dairy products and on dairy science, although regularly not very significant from a theoretical and physiological point of view, obviously had concrete implications for practical purposes. Furthermore, other parts of Winter's journal, volumes 1871, indicate that Gscheidlen tried to connect these studies with his early theoretical works on physiological metabolism. These theoretical studies included experiments which already explored basic principles of the urea cycle from today's point of view. Of course, these works, which were partly carried out on animals, must have been elaborate and expensive. For that reason, it is possible to assume that early dairy science and other scientific fields in Germany around 1870, which were linked to the developing food industry, had a very significant influence on the advances in theoretical metabolism physiology.

Development and labour resistance: a class composition perspective on import-substitution industrialisation in Chile and Argentina

Research on labour and development has demonstrated the significance, both analytically and politically, of labour for understanding the political economy of development. Analyses of labour regimes highlight the central role of reorganised workplaces and changing labour processes in value chains across the global economy. Research in global labour studies illustrates the ways in which concepts and theorisations of labour struggles emanating from the Global North struggle to capture the dynamics of labour conflict in the Global South and their wider impacts. This article argues that the revival of autonomist ‘class composition’ approaches can advance a labour perspective on development by shedding light on the importance of labour’s defeats when mapping the contours of the political economy of development. This approach reveals how what E.P. Thompson called the ‘dead ends’ of labour history are essential to understanding the grounds upon which state and capital reorganise to contain workers’ demands and struggles, thereby setting new conditions for these struggles to re-emerge. Drawing on insights from the early work of Antonio Negri, the article will examine how processes of working-class composition and decomposition occurred within the trajectory of import-substitution industrialisation in Chile and Argentina, establishing new labour regimes in its early crises. The article demonstrates this through original archival research using industry journals and publications from the textile industry in Chile and metalworking industry in Argentina.

Physio-omics? Robotic development, software engineering, and machine learning for high throughput, whole animal physiology assays as a path to disease mechanism and drug discovery

Measurement and analysis of cardio-respiratory function in animal models is essential for our understanding of functional and disease mechanisms that pave the way for human therapeutics and treatments. However, physiological phenotyping in conscious animals is often an onerous process requiring significant observer time, attention, and manual effort while being susceptible to bias and variability that ultimately limits the kinds of questions that can be asked and answered. Once data is collected, comprehensive and accurate analysis is challenging as it often requires either the use of expensive commercial software(s) with limited flexibility to meet the investigator’s needs or lab developed scripts that are often arduous and require specialized skills to utilize, resulting in incremental insights. Here we present an overview of our high throughput physiology assessment and analysis pipeline for interrogating disease mechanisms and enabling drug discovery in congenital cardio-respiratory disorders such as the lethal sudden infant death syndrome (SIDS). We first developed a closed loop robotic platform for automated neonate cardio-respiratory experiments (Looper) that enables automated interventional studies (i.e. hypoxic induction or drug application) based on real-time physiological feedback during the experiment. We show that deployment of multiple Looper platforms in parallel enables an order of magnitude increase in data collection for a single observer over a single workday and is highly scalable to achieve yet greater outputs. When combined with well designed genetically engineered or other disease mouse models, large scale genetic, molecular, and cellular mechanistic insights and drug discovery become feasible through physiological screening paradigms. Next, we developed an open-sourced cardio-respiratory assessment software tool (Breathe Easy) that enables facile deep interrogation of terabytes of data in a high throughput fashion while offering extensive customization capabilities to allow for unique case by case analysis by more skilled users. Breathe Easy output offers near publication ready graphical outputs with significance markings and statistical tables for rapid presentation of results through manuscripts and web-publishing. Lastly, we will present our early work leveraging our robotic and software pipeline to build an analytical machine learning framework that can predict cardio-respiratory failure (death) with high temporal specificity (more than 10 min out) in our SIDS like assay and our efforts to utilize the trained algorithms for 1) real-time prediction, feedback, and intervention application in our SIDS like assays on the Looper platform to screen small molecules for novel therapeutics; 2) elucidating unique physiological mechanisms through comparative training in distinct SIDS models; and 3) determining the potential for these machine learning approaches to be used in human polysomnographic recordings to identify at risk infants. R01HL161142, R01HL130249. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

In or out of the groove? Mechanisms of lipid scrambling by TMEM16 proteins

Phospholipid scramblases mediate the rapid movement of lipids between membrane leaflets, a key step in establishing and maintaining membrane homeostasis of the membranes of all eukaryotic cells and their organelles. Thus, impairment of lipid scrambling can lead to a variety of pathologies. How scramblases catalyzed the transbilayer movement of lipids remains poorly understood. Despite the availability of direct structural information on three unrelated families of scramblases, the TMEM16s, the Xkrs, and ATG-9, a unifying mechanism has failed to emerge thus far. Among these, the most extensively studied and best understood are the Ca2+ activated TMEM16s, which comprise ion channels and/or scramblases. Early work supported the view that these proteins provided a hydrophilic, membrane-exposed groove through which the lipid headgroups could permeate. However, structural, and functional experiments have since challenged this mechanism, leading to the proposal that the TMEM16s distort and thin the membrane near the groove to facilitate lipid scrambling. Here, we review our understanding of the structural and mechanistic underpinnings of lipid scrambling by the TMEM16s and discuss how the different proposals account for the various experimental observations.

Differential Activation of TAS2R4 May Recover Ability to Taste Propylthiouracil for Some TAS2R38 AVI Homozygotes.

Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the TAS2R38 gene. Three SNPs form two common (AVI, PAV) and four rare haplotypes (AAI, AAV, PVI, and PAI). AVI homozygotes exhibit higher detection thresholds and lower suprathreshold bitterness for PROP compared to PAV homozygotes and heterozygotes, and these differences may influence alcohol and vegetable intake. Within a diplotype, substantial variation in suprathreshold bitterness persists, and some AVI homozygotes report moderate bitterness at high concentrations. A second receptor encoded by a gene containing a functional polymorphism may explain this. Early work has suggested that PROP might activate TAS2R4 in vitro, but later work did not replicate this. Here, we identify three TAS2R4 SNPs that result in three diplotypes-SLN/SLN, FVS/SLN, and FVS/FVS-which make up 25.1%, 44.9%, and 23.9% of our sample. These TAS2R4 haplotypes show minimal linkage disequilibrium with TAS2R38, so we examined the suprathreshold bitterness as a function of both. The participants (n = 243) rated five PROP concentrations in duplicate, interleaved with other stimuli. As expected, the TAS2R38 haplotypes explained ~29% (p < 0.0001) of the variation in the bitterness ratings, with substantial variation within the haplotypes (AVI/AVI, PAV/AVI, and PAV/PAV). Notably, the TAS2R4 diplotypes (independent of the TAS2R38 haplotypes) explained ~7-8% of the variation in the bitterness ratings (p = 0.0001). Given this, we revisited if PROP could activate heterologously expressed TAS2R4 in HEK293T cells, and calcium imaging indicated 3 mM PROP is a weak TAS2R4 agonist. In sum, our data are consistent with the second receptor hypothesis and may explain the recovery of the PROP tasting phenotype in some AVI homozygotes; further, this finding may potentially help explain the conflicting results on the TAS2R38 diplotype and food intake.

Patriarchal Dominance in English Literature

Patriarchal dominance has been a prevalent theme in English literature throughout its history. Many literary works reflect and critique the societal norms and power structures that have historically favored men over women. Patriarchal norms prescribe rigid gender roles and expectations for men and women, reinforcing stereotypes and inequalities. Women are often relegated to traditional roles as caregivers, homemakers, and subordinate members of the family, while men are expected to be the primary breadwinners and decision-makers. These gender roles perpetuate unequal power dynamics and limit women's autonomy and agency. Prominent examples include Shakespeare's plays, where gender roles and power imbalances are often central to the plot, and classic novels like Jane Austen's "Pride and Prejudice," which explores women's limited options in a patriarchal society. Over time, literature has evolved to challenge and subvert these patriarchal norms, with authors like Virginia Woolf and Charlotte Perkins Gilman addressing issues of gender inequality and women's autonomy. Feminist literature and criticism have also played a significant role in analyzing and deconstructing patriarchal themes in English literature. Patriarchal dominance, characterized by the historical and societal power imbalance that favors men over women, has been a recurring theme in English literature throughout the ages. This theme reflects and critiques the prevailing gender norms, roles, and inequalities that have persisted within different periods and cultures of English-speaking societies. From early literary works to contemporary literature, patriarchal dominance remains a complex and enduring subject of exploration.

Ferroptosis Biology.

Ferroptosis is a regulated cell death modality triggered by iron-dependent lipid peroxidation. Ferroptosis plays a causal role in the pathophysiology of various diseases, making it a promising therapeutic target. Unlike all other cell death modalities dependent on distinct signaling cues, ferroptosis occurs when cellular antioxidative defense mechanisms fail to suppress the oxidative destruction of cellular membranes, eventually leading to cell membrane rupture. Physiologically, only two such surveillance systems are known to efficiently prevent the lipid peroxidation chain reaction by reducing (phospho)lipid hydroperoxides to their corresponding alcohols or by reducing radicals in phospholipid bilayers, thus maintaining the integrity of lipid membranes. Mechanistically, these two systems are linked to the reducing capacity of glutathione peroxidase 4 (GPX4) by consuming glutathione (GSH) on the one and ferroptosis suppressor protein 1 (FSP1, formerly AIFM2) on the other hand. Notably, the importance of ferroptosis suppression in physiological contexts has been linked to a particular vulnerability of renal tissue. In fact, early work has shown that mice genetically lacking Gpx4 rapidly succumb to acute renal failure with pathohistological features of acute tubular necrosis. Promising research attempting to implicate ferroptosis in various renal disease entities, particularly those with proximal tubular involvement, has generated a wealth of knowledge with widespread potential for clinical translation. Here, we provide a brief overview of the involvement of ferroptosis in nephrology. Our goal is to introduce this expanding field for clinically versed nephrologists in the hope of spurring future efforts to prevent ferroptosis in the pathophysiological processes of the kidney.

The journey from bench to bedside - it takes a science village.

I was fortunate enough to start my career at what was the dawn of modern-day molecular biology and to apply it to an important health problem. While my early work focused on fundamental science, the desire to understand human disease better and to find practical applications for research discoveries resulted, over the following decades, in creating a stream of translational research directed specifically towards epithelial cancers. This could only have been possible through multiple collaborations. This type of team science would eventually become a hallmark of my career. With the development of higher throughput molecular techniques, the pace of research and discovery have quickened, and the concept of personalized medicine based on genomics is now coming to fruition. I hope my legacy will not just reflect my published works, but will also include the impact I have had on the development of the next generation of scientist and clinician scientists who inspired me with their dedication, knowledge and enthusiasm.