julilili42/papers huggingface dataset:
Assessing Target Specificity of the Small Molecule Inhibitor MARIMASTAT to Snake Venom Toxins: A Novel Application of Thermal Proteome Profiling
2024-04-27

New treatments that circumvent the pitfalls of traditional antivenom therapies are critical to address the problem of snakebite globally. Numerous snake venom toxin inhibitors have shown promising cross-species neutralization of medically significant venom toxins in vivo and in vitro. The development of high-throughput approaches for the screening of such inhibitors could accelerate their identification, testing, and implementation and thus holds exciting potential for improving the treatments and outcomes of snakebite envenomation worldwide. Energetics-based proteomic approaches, including thermal proteome profiling and proteome integral solubility alteration (PISA) assays, represent "deep proteomics" methods for high throughput, proteome-wide identification of drug targets and ligands. In the following study, we apply thermal proteome profiling and PISA methods to characterize the interactions between venom toxin proteoforms in Crotalus atrox (Western Diamondback Rattlesnake) and the snake venom metalloprotease (SVMP) inhibitor marimastat. We investigate its venom proteome-wide effects and characterize its interactions with specific SVMP proteoforms, as well as its potential targeting of non-SVMP venom toxin families. We also compare the performance of PISA thermal window and soluble supernatant with insoluble precipitate using two inhibitor concentrations, providing the first demonstration of the utility of a sensitive high-throughput PISA-based approach to assess the direct targets of small molecule inhibitors for snake venom.
Recreation in Forests
2024-04-27

Forests have been found to positively impact human health. Forests, therefore, may help mitigate health crises like the COVID-19 pandemic. However, it is still unclear which forest structures and what forest types contribute to human health and to what extent. This chapter looks at the effects of forest terpenes on human recreation. This is done by measuring the concentration and composition of terpenes together with the subjective judgement of relaxation using psychometric questionnaires in four different experimental conditions. These conditions are two forest types (a mixed forest and a coniferous forest) and two interior settings. The results show that the two forests perform better with regard to relaxation than the interior conditions. However, it is difficult to solely ascribe the relaxation effects to terpenes. The restorative quality of forests seems to profit from other factors like forest soundscape or visual appearance. From this, implications for tourism product design are deduced, which range from seasonal and weather-related recommendations to recommendations on activities and on favourable forest structures.
S1‐Guideline Sebaceous Carcinoma
2024-04-28

Summary Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir‐Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow‐up care is recommended for these potentially aggressive carcinomas.
Disentangling periodic and aperiodic resting EEG correlates of personality
2024-04-28

Previous studies of resting electroencephalography (EEG) correlates of personality traits have conflated periodic and aperiodic sources of EEG signals. Because these are associated with different underlying neural dynamics, disentangling them can avoid measurement confounds and clarify findings. In a large sample (n = 300), we investigated how disentangling these activities impacts findings related to two research programs within personality neuroscience. In Study 1 we examined associations between Extraversion and two putative markers of reward sensitivity-Left Frontal Alpha asymmetry (LFA) and Frontal-Posterior Theta (FPT). In Study 2 we used machine learning to predict personality trait scores from resting EEG. In both studies, power within each EEG frequency bin was quantified as both total power and separate contributions of periodic and aperiodic activity. In Study 1, total power LFA and FPT correlated negatively with Extraversion (r ∼ -0.14), but there was no relation when LFA and FPT were derived only from periodic activity. In Study 2, all Big Five traits could be decoded from periodic power (r ∼ 0.20), and Agreeableness could also be decoded from total power and from aperiodic indices. Taken together, these results show how separation of periodic and aperiodic activity in resting EEG may clarify findings in personality neuroscience. Disentangling these signals allows for more reliable findings relating to periodic EEG markers of personality, and highlights novel aperiodic markers to be explored in future research.
Normative Spirituality in Wahhābī Prophetology: Saʿīd b. Wahf al-Qaḥṭānī’s (d. 2018) Raḥmatan li-l-ʿĀlamīn as Reparatory Theology
2024-04-28

The Wahhābī movement within Sunni Islam—a substantial section of the larger Salafi movement—has been often depicted in both western academic studies and Muslim polemical writings negatively as devoid of spirituality, obsessed with a particular creedal understanding that drives its well-known salvific exclusivism, and with rigid legalism. This depiction is partly due to Wahhābism’s historical opposition to Sufism, the branch of Islamic knowledge and practices that has theorized, defined, and delineated Islam’s vision of the spiritual transformation taking place in the believer’s journey towards God. That opposition notwithstanding, the article argues that beyond terminological distinctions, one can locate in Wahhābī texts common Islamic themes of spiritual transformation. Primarily, such texts can be found in Wahhābī publications of the writings of 13th century Damascene Muslim scholars like Ibn Taymīya (d. 728/1328) and his most celebrated student, Ibn Qayyim al-Jawzīya (d. 751/1350). Building on that tradition, Wahhābī scholars have additionally produced texts that display core ideals of the Muslim spiritual goals. Such texts have additionally advanced the movement’s theological concerns and have driven the efforts towards “the purification” of Islamic sources from what Wahhābis deem to be heretical practices and beliefs accumulated throughout the centuries. Wahhābī prophetological texts, the article argues, serve as primary sources where both Wahhābī spiritual ideals and their sectarian reparatory agenda can be identified. The book of the late Saʿīd b. Wahf al-Qaḥṭānī (1952–2018), a well-known Saudi Wahhābī author of the second half of the twentieth century, Raḥmatan li-l-ʿĀlamīn Muḥammad Rasūl Allāh, serves as a representative text of these aims and ideals. Wahhābī spirituality, as identified in the work of al-Qaḥṭānī, has been depicted here as “normative spirituality” in order to point to its intended purpose of engendering praxis that is grounded in Islam’s well-known notion of prophetic imitatio.
Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease
2024-04-29

Importance Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). Objective To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. Design, Setting, and Participants From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD. Carriers of gene variants were assigned 3:1 to either drug or placebo. The present analysis was conducted from April to June 2023. DIAN-TU-001 spans 25 study sites in 7 countries. Biofluids and neuroimaging from carriers of DIAD gene variants in the gantenerumab, solanezumab, and placebo groups were analyzed. Interventions In 2016, initial dosing of gantenerumab, 225 mg (subcutaneously every 4 weeks) was increased every 8 weeks up to 1200 mg. In 2017, initial dosing of solanezumab, 400 mg (intravenously every 4 weeks) was increased up to 1600 mg every 4 weeks. Main Outcomes and Measures Longitudinal changes in CSF levels of neurogranin, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3–like 1 protein (YKL-40), glial fibrillary acidic protein (GFAP), neurofilament light protein (NfL), and plasma levels of GFAP and NfL. Results Of 236 eligible participants screened, 43 were excluded. A total of 142 participants (mean [SD] age, 44 [10] years; 72 female [51%]) were included in the study (gantenerumab, 52 [37%]; solanezumab, 50 [35%]; placebo, 40 [28%]). Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] β = −242.43 [48.04] pg/mL; P &amp;amp;lt; .001); reduced plasma GFAP level at year 1 (mean [SD] β = −0.02 [0.01] ng/mL; P = .02), year 2 (mean [SD] β = −0.03 [0.01] ng/mL; P = .002), and year 4 (mean [SD] β = −0.06 [0.02] ng/mL; P &amp;amp;lt; .001); and increased CSF sTREM2 level at year 2 (mean [SD] β = 1.12 [0.43] ng/mL; P = .01) and year 4 (mean [SD] β = 1.06 [0.52] ng/mL; P = .04). Solanezumab significantly increased CSF NfL (log) at year 4 (mean [SD] β = 0.14 [0.06]; P = .02). Correlation analysis for rates of change found stronger correlations between CSF markers and fluid markers with Pittsburgh compound B positron emission tomography for solanezumab and placebo. Conclusions and Relevance This randomized clinical trial supports the importance of fibrillar amyloid reduction in multiple AD-related processes of neuroinflammation and neurodegeneration in CSF and plasma in DIAD. Additional studies of antiaggregated amyloid therapies in sporadic AD and DIAD are needed to determine the utility of nonamyloid biomarkers in determining disease modification. Trial Registration ClinicalTrials.gov Identifier: NCT04623242
Microbial communities overwhelm environmental controls in explaining nitrous oxide emission in acidic soils
2024-04-29

Intensively fertilized acidic soils are global hotspots of nitrous oxide (N2O) emissions, contributing to net agronomic greenhouse gas outcomes. Identifying the key drivers of soil N2O emissions is hampered by the synergistic or antagonistic effects of multiple factors. Within a framework based on the predominant role of microbial communities producing N2O, N2O emissions are affected either by proximal regulators: temporary soil property fluctuations affect N2O production transcriptionally or by distal regulators: persistent genetic rearrangements in local microbial communities. The proximal regulators, individually or together, may spontaneously impact distal regulators. Here, we use acidic soils from tea (Camellia sinensis L.) plantations on a broader geographic scale as a model system. Based on amplicon sequencing and soil properties of 195 acidic (average pH = 5.0) soils, we determined the importance of proximal and distal regulation to N2O emissions from acidic soils. Microbial phylogenetic diversity as a distal regulator overwhelms mineral N content as a proximal regulator in explaining high N2O emissions in acidic soils. Low-abundance, diverse prokaryotic communities (e.g., Acidothermu) and more specialized denitrifying fungal communities (e.g., Fusarium) were associated with high N2O emissions. Revisiting the impact of proximal regulators on distal regulators revealed that, soil pH is the sole proximal regulator influencing the prokaryotic rare taxa that correlated with high N2O emissions. When considering proximal regulators together (here soil properties compiled as soil fertility index), the patterns of microbial diversity were independent of soil fertility. The microbial assembly was dominated by stochastic processes. Consequently, proximal regulators have a limited impact on distal regulators of N2O emissions in acidic soils. In conclusion, the framework underscored the importance of in situ microbial communities as distal regulators in explaining high N2O emissions in acidic soils.
Wagers for work: Decomposing the costs of cognitive effort
2024-04-29

Some aspects of cognition are more taxing than others. Accordingly, many people will avoid cognitively demanding tasks in favor of simpler alternatives. Which components of these tasks are costly, and how much, remains unknown. Here, we use a novel task design in which subjects request wages for completing cognitive tasks and a computational modeling procedure that decomposes their wages into the costs driving them. Using working memory as a test case, our approach revealed that gating new information into memory and protecting against interference are costly. Critically, other factors, like memory load, appeared less costly. Other key factors which may drive effort costs, such as error avoidance, had minimal influence on wage requests. Our approach is sensitive to individual differences, and could be used in psychiatric populations to understand the true underlying nature of apparent cognitive deficits.
The social life of illegality: Suspicion and surveillance against African migrants in urban India
2024-04-29

Abstract The turn of the 21st century has witnessed a rising trend of migration from the African continent to cities across India. Accompanying such flows have been racial tensions and policing spectacles, including incidents of violence, vandalism, and evictions against African migrants and their pathologization as “illegal.” These subtle yet pervasive forms of migrant policing by state and citizen actors constitute what I call the social life of “illegality” that is characterized by distinctive modes of suspicion and surveillance. Based upon ethnography conducted in an “unplanned” settlement of Delhi cohabitated by both African and Indian residents, I illuminate how caste‐race‐religion informed indexes of difference contribute to the multi‐sensorial racialization of African migrants as suspicious. In emplacing such dynamics within changing spatial economies and the moral anxieties accompanying such transitions, I further demonstrate quotidian practice of microsurveillance against African migrants as sustaining their position as rent‐paying clients who are nonetheless maintained in their racial alterity. The social life of “illegality” thus refocuses attention on the sensorial and emplaced registers that illegalize migrants, above and beyond documentation, thereby furthering a discussion on migrant “illegality” as enmeshed within racialized imaginaries, urban transformations, and alternate modes of governmentality.
Preclinical identification of acute coronary syndrome without high sensitivity troponin assays using machine learning algorithms
2024-04-29

Abstract Preclinical management of patients with acute chest pain and their identification as candidates for urgent coronary revascularization without the use of high sensitivity troponin essays remains a critical challenge in emergency medicine. We enrolled 2760 patients (average age 70 years, 58.6% male) with chest pain and suspected ACS, who were admitted to the Emergency Department of the University Hospital Tübingen, Germany, between August 2016 and October 2020. Using 26 features, eight Machine learning models (non-deep learning models) were trained with data from the preclinical rescue protocol and compared to the “TropOut” score (a modified version of the “preHEART” score which consists of history, ECG, age and cardiac risk but without troponin analysis) to predict major adverse cardiac event (MACE) and acute coronary artery occlusion (ACAO). In our study population MACE occurred in 823 (29.8%) patients and ACAO occurred in 480 patients (17.4%). Interestingly, we found that all machine learning models outperformed the “TropOut” score. The VC and the LR models showed the highest area under the receiver operating characteristic (AUROC) for predicting MACE (AUROC = 0.78) and the VC showed the highest AUROC for predicting ACAO (AUROC = 0.81). A SHapley Additive exPlanations (SHAP) analyses based on the XGB model showed that presence of ST-elevations in the electrocardiogram (ECG) were the most important features to predict both endpoints.
Qualifying System F<:: Some Terms and Conditions May Apply
2024-04-29

Type qualifiers offer a lightweight mechanism for enriching existing type systems to enforce additional, desirable, program invariants. They do so by offering a restricted but effective form of subtyping. While the theory of type qualifiers is well understood and present in many programming languages today, polymorphism over type qualifiers remains an area less well examined. We explore how such a polymorphic system could arise by constructing a calculus, System F-sub-Q, which combines the higher-rank bounded polymorphism of System F-sub with the theory of type qualifiers. We explore how the ideas used to construct System F-sub-Q can be reused in situations where type qualifiers naturally arise---in reference immutability, function colouring, and capture checking. Finally, we re-examine other qualifier systems in the literature in light of the observations presented while developing System F-sub-Q.
Deriving Dependently-Typed OOP from First Principles
2024-04-29

The expression problem describes how most types can easily be extended with new ways to produce the type or new ways to consume the type, but not both. When abstract syntax trees are defined as an algebraic data type, for example, they can easily be extended with new consumers, such as print or eval , but adding a new constructor requires the modification of all existing pattern matches. The expression problem is one way to elucidate the difference between functional or data-oriented programs (easily extendable by new consumers) and object-oriented programs (easily extendable by new producers). This difference between programs which are extensible by new producers or new consumers also exists for dependently typed programming, but with one core difference: Dependently-typed programming almost exclusively follows the functional programming model and not the object-oriented model, which leaves an interesting space in the programming language landscape unexplored. In this paper, we explore the field of dependently-typed object-oriented programming by deriving it from first principles using the principle of duality. That is, we do not extend an existing object-oriented formalism with dependent types in an ad-hoc fashion, but instead start from a familiar data-oriented language and derive its dual fragment by the systematic use of defunctionalization and refunctionalization. Our central contribution is a dependently typed calculus which contains two dual language fragments. We provide type- and semantics-preserving transformations between these two language fragments: defunctionalization and refunctionalization. We have implemented this language and these transformations and use this implementation to explain the various ways in which constructions in dependently typed programming can be explained as special instances of the general phenomenon of duality.
Draft genome sequence of Magnusiomyces sp. LA-1 isolated from a C6-C8 acid-producing bioreactor
2024-04-29

ABSTRACT Here, we report the draft genome of Magnusiomyces sp. LA-1, which was isolated from a C6-C8 carboxylic acid-producing bioreactor. The draft genome of Magnusiomyces sp. LA-1 is 19,829,165 bp in length, is divided into six contigs that comprise 6,557 CDS regions, and has a GC content of 34.5%.
Discovery of a synthetic small molecule targeting the central regulator ofSalmonellapathogenicity
2024-04-29

Abstract The enteric pathogen Salmonella enterica serovar Typhimurium relies on the activity of effector proteins to invade, replicate, and disseminate into host epithelial cells and other tissues, thereby causing disease. Secretion and injection of effector proteins into host cells is mediated by dedicated secretion systems, which hence represent major virulence determinants. Here, we report the identification of a synthetic small molecule with drug-like properties, C26, which suppresses the secretion of effector proteins, and consequently hinders bacterial invasion of eukaryotic cells. C26 binds to and inhibits HilD, the transcriptional regulator of the major secretion systems. While sharing the same binding pocket as the previously described long-chain fatty acid ligands, C26 inhibits HilD with a unique binding mode and a distinct mechanism. We provide evidence for target engagement within infected eukaryotic cells and present analogs with improved potency and suitability as scaffolds to develop anti-virulence agents against Salmonella infections in humans and animals.
Recent Trends in 3D Reconstruction of General Non‐Rigid Scenes
2024-04-30

Abstract Reconstructing models of the real world, including 3D geometry, appearance, and motion of real scenes, is essential for computer graphics and computer vision. It enables the synthesizing of photorealistic novel views, useful for the movie industry and AR/VR applications. It also facilitates the content creation necessary in computer games and AR/VR by avoiding laborious manual design processes. Further, such models are fundamental for intelligent computing systems that need to interpret real‐world scenes and actions to act and interact safely with the human world. Notably, the world surrounding us is dynamic, and reconstructing models of dynamic, non‐rigidly moving scenes is a severely underconstrained and challenging problem. This state‐of‐the‐art report (STAR) offers the reader a comprehensive summary of state‐of‐the‐art techniques with monocular and multi‐view inputs such as data from RGB and RGB‐D sensors, among others, conveying an understanding of different approaches, their potential applications, and promising further research directions. The report covers 3D reconstruction of general non‐rigid scenes and further addresses the techniques for scene decomposition, editing and controlling, and generalizable and generative modeling. More specifically, we first review the common and fundamental concepts necessary to understand and navigate the field and then discuss the state‐of‐the‐art techniques by reviewing recent approaches that use traditional and machine‐learning‐based neural representations, including a discussion on the newly enabled applications. The STAR is concluded with a discussion of the remaining limitations and open challenges.